Description: Heart rate variability (HRV) is a common measure of the autonomic modulation of the heart. To ensure accuracy, various external factors known to affect HRV such as medication use and concurrent illnesses are frequently controlled during measurement. Despite extensive recognition of the importance of such confounds, the influence of ostensibly innocuous daily activities such as drinking and eating have received remarkably little attention in comparison. Water consumption provokes a powerful pressor stimulus that is buffered by changes in cardiovagal outflow yet it is sporadically controlled during experimentation. This paper examines the dose-dependent magnitude of the effect of water on HRV, the loss of HRV during a common attentional task after water consumption, and the typical scenario of water and mixed meal ingestion. Water affects HRV in a dose-dependent manner, and exaggerates attentionally- mediated HRV reduction. This effect is antagonised by simultaneous mixed meal consumption, which strongly increases cardiac sympathetic activity. Water consumption during or previous to HRV measurement should be carefully controlled, if possible. Considering the diverse nature of experimental protocols and populations, we suggest a hierarchy of methods to control for water consumption in HRV research.


text:
import React from 'react';
import ReactDOM from 'react-dom';
import fetch from 'isomorphic-fetch';
import 'babel-polyfill';  // 为generator 使用
import {BootstrapTable, TableHeaderColumn} from 'react-bootstrap-table';

export default class Data extends React.Component {
    constructor(props) {
        super(props);
    }

    render() {
        // var data = this.props.data || [];
        const cellEdit = {
            mode: 'dbclick',
            defaultSortName: 'name',
            defaultSortOrder: 'asc',

        };

        const selectRow = {
            mode: 'checkbox',
            columnWidth: '60px',
            onSelect: this.handleRowSelect
            //selectRow={ selectRow }
        };
        return (
            <BootstrapTable
             data={this.props.data}
             remote={true}
             pagination = {true}
             fetchInfo={ { dataTotalSize: this.props.totalDataSize } }
             options={ { sizePerPage: this.props.sizePerPage,
                                  onPageChange: this.props.onPageChange,
                                  sizePerPageList: [ 5, 10 ],
                                  page: this.props.currentPage,
                                  onSizePerPageList: this.props.onSizePerPageList } }
             selectRow={selectRow}
             tableContainerClass='my-custom-class'
             search hover striped>
               <TableHeaderColumn isKey dataField='id'> ID</TableHeaderColumn>
               <TableHeaderColumn dataField='name' dataSort={ true }> Name</TableHeaderColumn>
               <TableHeaderColumn dataField='assigned_user_id'>sales</TableHeaderColumn>
               <TableHeaderColumn dataField='_acl'>acl</TableHeaderColumn>
               <TableHeaderColumn dataField='sales_stage'>sales_stage</TableHeaderColumn>
               <TableHeaderColumn dataField='date_closed' editable={{ type:'date'}}>date_closed</TableHeaderColumn>
               <TableHeaderColumn dataField='sales_stage'>sales_stage</TableHeaderColumn>
               <TableHeaderColumn dataField='worst_case'>worst_case</TableHeaderColumn>
            </BootstrapTable>
        );
    }
}

redpajama_set_name: RedPajamaGithub


text:
Jung, Y., Klein, O.J., Wang, H. & Evans, C.L. Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT. Sci Rep 6, 27017 (2016).Abstract
Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.
Chen, S.-H., Forrester, W. & Lahav, G. Schedule-dependent interaction between anticancer treatments. Science 351, 6278, 1204-8 (2016).Abstract
The oncogene MDMX is overexpressed in many cancers, leading to suppression of the tumor suppressor p53. Inhibitors of the oncogene product MDMX therefore might help reactivate p53 and enhance the efficacy of DNA-damaging drugs. However, we currently lack a quantitative understanding of how MDMX inhibition affects the p53 signaling pathway and cell sensitivity to DNA damage. Live cell imaging showed that MDMX depletion triggered two distinct phases of p53 accumulation in single cells: an initial postmitotic pulse, followed by low-amplitude oscillations. The response to DNA damage was sharply different in these two phases; in the first phase, MDMX depletion was synergistic with DNA damage in causing cell death, whereas in the second phase, depletion of MDMX inhibited cell death. Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.
Kang, C. & Elledge, S.J. How autophagy both activates and inhibits cellular senescence. Autophagy 12, 5, 898-9 (2016).Abstract
Autophagy and cellular senescence are stress responses essential for homeostasis. While recent studies indicate a genetic relationship between autophagy and senescence, whether autophagy acts positively or negatively on senescence is still subject to debate. Although autophagy was originally recognized as a nonspecific lysosomal degradation pathway (general autophagy), increasing evidence supports a selective form of autophagy that mediates the degradation of specific targets (selective autophagy). Our recent study revealed distinctive roles of selective autophagy and general autophagy in the regulation of senescence, at least in part resolving apparently contradictory reports regarding the relationship between these 2 important homeostatic stress responses.
Drier, Y., et al. An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet 48, 3, 265-72 (2016).Abstract
Translocation events are frequent in cancer and may create chimeric fusions or 'regulatory rearrangements' that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps highlight distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in alternate ACC lineages.
German, N.J., et al. PHD3 Loss in Cancer Enables Metabolic Reliance on Fatty Acid Oxidation via Deactivation of ACC2. Mol Cell 63, 6, 1006-20 (2016).Abstract
While much research has examined the use of glucose and glutamine by tumor cells, many cancers instead prefer to metabolize fats. Despite the pervasiveness of this phenotype, knowledge of pathways that drive fatty acid oxidation (FAO) in cancer is limited. Prolyl hydroxylase domain proteins hydroxylate substrate proline residues and have been linked to fuel switching. Here, we reveal that PHD3 rapidly triggers repression of FAO in response to nutrient abundance via hydroxylation of acetyl-coA carboxylase 2 (ACC2). We find that PHD3 expression is strongly decreased in subsets of cancer including acute myeloid leukemia (AML) and is linked to a reliance on fat catabolism regardless of external nutrient cues. Overexpressing PHD3 limits FAO via regulation of ACC2 and consequently impedes leukemia cell proliferation. Thus, loss of PHD3 enables greater utilization of fatty acids but may also serve as a metabolic and therapeutic liability by indicating cancer cell susceptibility to FAO inhibition.
Kim, J., et al. Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nat Genet 48, 6, 600-6 (2016).Abstract
Alterations in DNA repair pathways are common in tumors and can result in characteristic mutational signatures; however, a specific mutational signature associated with somatic alterations in the nucleotide- excision repair (NER) pathway has not yet been identified. Here we examine the mutational processes operating in urothelial cancer, a tumor type in which the core NER gene ERCC2 is significantly mutated. Analysis of three independent urothelial tumor cohorts demonstrates a strong association between somatic ERCC2 mutations and the activity of a mutational signature characterized by a broad spectrum of base changes. In addition, we note an association between the activity of this signature and smoking that is independent of ERCC2 mutation status, providing genomic evidence of tobacco-related mutagenesis in urothelial cancer. Together, these analyses identify an NER-related mutational signature and highlight the related roles of DNA damage and subsequent DNA repair in shaping tumor mutational landscape.
Sage, P.T., et al. Suppression by TFR cells leads to durable and selective inhibition of B cell effector function. Nat Immunol (2016).Abstract
Follicular regulatory T cells (TFR cells) inhibit follicular helper T cell (TFH cell)-mediated antibody production. The mechanisms by which TFR cells exert their key immunoregulatory functions are largely unknown. Here we found that TFR cells induced a distinct suppressive state in TFH cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by TFR cells was durable and persisted even in the absence of TFR cells. This durable suppression was due in part to epigenetic changes. The cytokine IL-21 was able to overcome TFR cell-mediated suppression and inhibited TFR cells and stimulated B cells. By determining mechanisms of TFR cell-mediated suppression, we have identified methods for modulating the function of TFR cells and antibody production.
Xu, D., et al. USP14 regulates autophagy by suppressing K63 ubiquitination of Beclin 1. Genes Dev 30, 15, 1718-30 (2016).Abstract
The ubiquitin-proteasome system (UPS) and autophagy are two major intracellular degradative mechanisms that mediate the turnover of complementary repertoires of intracellular proteomes. Simultaneously activating both UPS and autophagy might provide a powerful strategy for the clearance of misfolded proteins. However, it is not clear whether UPS and autophagy can be controlled by a common regulatory mechanism. K48 deubiquitination by USP14 is known to inhibit UPS. Here we show that USP14 regulates autophagy by negatively controlling K63 ubiquitination of Beclin 1. Furthermore, we show that activation of USP14 by Akt-mediated phosphorylation provides a mechanism for Akt to negatively regulate autophagy by promoting K63 deubiquitination. Our study suggests that Akt-regulated USP14 activity modulates both proteasomal degradation and autophagy through controlling K48 and K63 ubiquitination, respectively. Therefore, regulation of USP14 provides a mechanism for Akt to control both proteasomal and autophagic degradation. We propose that inhibition of USP14 may provide a strategy to promote both UPS and autophagy for developing novel therapeutics targeting neurodegenerative diseases.
Sykes, D.B., et al. Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia. Cell 167, 1, 171-186.e15 (2016).Abstract
While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a powerful treatment strategy. We leveraged the observation that the majority of AML, despite their genetically heterogeneity, share in the expression of HoxA9, a gene normally downregulated during myeloid differentiation. Using a conditional HoxA9 model system, we performed a high-throughput phenotypic screen and defined compounds that overcame differentiation blockade. Target identification led to the unanticipated discovery that inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) enables myeloid differentiation in human and mouse AML models. In vivo, DHODH inhibitors reduced leukemic cell burden, decreased levels of leukemia-initiating cells, and improved survival. These data demonstrate the role of DHODH as a metabolic regulator of differentiation and point to its inhibition as a strategy for overcoming differentiation blockade in AML.
Martin, J.D., Fukumura, D., Duda, D.G., Boucher, Y. & Jain, R.K. Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity. Cold Spring Harb Perspect Med (2016).Abstract
Solid tumors consist of cancer cells and stromal cells, including resident and transiting immune cells-all ensconced in an extracellular matrix (ECM)-nourished by blood vessels and drained by lymphatic vessels. The microenvironment constituents are abnormal and heterogeneous in morphology, phenotype, and physiology. Such irregularities include an inefficient tumor vascular network comprised of leaky and compressed vessels, which impair blood flow and oxygen delivery. Low oxygenation in certain tumor regions-or focal hypoxia-is a mediator of cancer progression, metastasis, immunosuppression, and treatment resistance. Thus, repairing an abnormal and heterogeneous microenvironment-and hypoxia in particular-can significantly improve treatments of solid tumors. Here, we summarize two strategies to reengineer the tumor microenvironment (TME)-vessel normalization and decompression-that can alleviate hypoxia. In addition, we discuss how these two strategies alone and in combination with each other-or other therapeutic strategies-may overcome the challenges posed by cancer heterogeneity.
Marusyk, A., et al. Spatial proximity to fibroblasts impacts molecular features and therapeutic sensitivity of breast cancer cells influencing clinical outcomes. Cancer Res (2016).Abstract
Using a 3D co-culture model, we identified significant sub-type-specific changes in gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAFs). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that fibroblasts strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold. Fibroblasts from normal breast tissues and stromal cultures of brain metastases of breast cancer had similar effects as CAFs. Using synthetic lethality approaches, we identified molecular pathways whose inhibition sensitizes HER2+ breast cancer cells to lapatinib both in vitro and in vivo including JAK2/STAT3 and hyaluronic acid. Neoadjuvant lapatinib therapy in HER2+ breast tumors lead to a significant increase of phospho-STAT3+ cancer cells and a decrease in the spatial proximity of proliferating (Ki67+) cells to CAFs impacting therapeutic responses. Our studies identify CAF-induced physiologically and clinically relevant changes in cancer cells and offer novel approaches for overcoming microenvironment-mediated therapeutic resistance.
Vyas, S., Zaganjor, E. & Haigis, M.C. Mitochondria and Cancer. Cell 166, 3, 555-66 (2016).Abstract
Mitochondria are bioenergetic, biosynthetic, and signaling organelles that are integral in stress sensing to allow for cellular adaptation to the environment. Therefore, it is not surprising that mitochondria are important mediators of tumorigenesis, as this process requires flexibility to adapt to cellular and environmental alterations in addition to cancer treatments. Multiple aspects of mitochondrial biology beyond bioenergetics support transformation, including mitochondrial biogenesis and turnover, fission and fusion dynamics, cell death susceptibility, oxidative stress regulation, metabolism, and signaling. Thus, understanding mechanisms of mitochondrial function during tumorigenesis will be critical for the next generation of cancer therapeutics.
Lien, E.C., et al. Glutathione biosynthesis is a metabolic vulnerability in PI(3)K/Akt-driven breast cancer. Nat Cell Biol (2016).Abstract
Cancer cells often select for mutations that enhance signalling through pathways that promote anabolic metabolism. Although the PI(3)K/Akt signalling pathway, which is frequently dysregulated in breast cancer, is a well-established regulator of central glucose metabolism and aerobic glycolysis, its regulation of other metabolic processes required for tumour growth is not well defined. Here we report that in mammary epithelial cells, oncogenic PI(3)K/Akt stimulates glutathione (GSH) biosynthesis by stabilizing and activating NRF2 to upregulate the GSH biosynthetic genes. Increased NRF2 stability is dependent on the Akt-mediated accumulation of p21(Cip1/WAF1) and GSK-3β inhibition. Consistently, in human breast tumours, upregulation of NRF2 targets is associated with PI(3)K pathway mutation status and oncogenic Akt activation. Elevated GSH biosynthesis is required for PI(3)K/Akt-driven resistance to oxidative stress, initiation of tumour spheroids, and anchorage-independent growth. Furthermore, inhibition of GSH biosynthesis with buthionine sulfoximine synergizes with cisplatin to selectively induce tumour regression in PI(3)K pathway mutant breast cancer cells, both in vitro and in vivo. Our findings provide insight into GSH biosynthesis as a metabolic vulnerability associated with PI(3)K pathway mutant breast cancers.
Hata, A.N., et al. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med (2016).Abstract
Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of pre-existing EGFR(T790M)-positive clones or via genetic evolution of initially EGFR(T790M)-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR(T790M); treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic.
Flavahan, W.A., et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529, 7584, 110-4 (2016).Abstract
Gain-of-function IDH mutations are initiating events that define major clinical and prognostic classes of gliomas. Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglutarate, which interferes with iron-dependent hydroxylases, including the TET family of 5'-methylcytosine hydroxylases. TET enzymes catalyse a key step in the removal of DNA methylation. IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP), although the functional importance of this altered epigenetic state remains unclear. Here we show that human IDH mutant gliomas exhibit hypermethylation at cohesin and CCCTC-binding factor (CTCF)-binding sites, compromising binding of this methylation-sensitive insulator protein. Reduced CTCF binding is associated with loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to interact aberrantly with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with a demethylating agent partially restores insulator function and downregulates PDGFRA. Conversely, CRISPR-mediated disruption of the CTCF motif in IDH wild-type gliomaspheres upregulates PDGFRA and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.
Shu, S., et al. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature (2016).Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance.
Dey-Guha, I., et al. A mechanism for asymmetric cell division resulting in proliferative asynchronicity. Mol Cancer Res 13, 2, 223-30 (2015).Abstract
UNLABELLED: All cancers contain an admixture of rapidly and slowly proliferating cancer cells. This proliferative heterogeneity complicates the diagnosis and treatment of patients with cancer because slow proliferators are hard to eradicate, can be difficult to detect, and may cause disease relapse sometimes years after apparently curative treatment. While clonal selection theory explains the presence and evolution of rapid proliferators within cancer cell populations, the circumstances and molecular details of how slow proliferators are produced is not well understood. Here, a β1-integrin/FAK/mTORC2/AKT1-associated signaling pathway is discovered that can be triggered for rapidly proliferating cancer cells to undergo asymmetric cell division and produce slowly proliferating AKT1(low) daughter cells. In addition, evidence indicates that the proliferative output of this signaling cascade involves a proteasome-dependent degradation process mediated by the E3 ubiquitin ligase TTC3. These findings reveal that proliferative heterogeneity within cancer cell populations, in part, is produced through a targetable signaling mechanism, with potential implications for understanding cancer progression, dormancy, and therapeutic resistance. IMPLICATIONS: These findings provide a deeper understanding of the proliferative heterogeneity that exists in the tumor environment and highlight the importance of designing future therapies against multiple proliferative contexts. VISUAL OVERVIEW: A proposed mechanism for producing slowly proliferating cancer cells. http://mcr.aacrjournals.org/content/early/2015/01/09/1541-7786.MCR-14-04....
Yeh, A.C. & Ramaswamy, S. Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?. Cancer Res 75, 23, 5014-22 (2015).Abstract
Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance.
Fallahi-Sichani, M., et al. Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis. Mol Syst Biol 11, 3, 797 (2015).Abstract
Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAF(V) (600E) melanoma. Adaptive responses to RAF/MEK inhibition occur on a timescale of hours to days, involve homeostatic responses that reactivate MAP kinase signaling and compensatory mitogenic pathways, and attenuate the anti-tumor effects of RAF/MEK inhibitors. We profile adaptive responses across a panel of melanoma cell lines using multiplex biochemical measurement, single-cell assays, and statistical modeling and show that adaptation involves at least six signaling cascades that act to reduce drug potency (IC50) and maximal effect (i.e., Emax ≪ 1). Among these cascades, we identify a role for JNK/c-Jun signaling in vemurafenib adaptation and show that RAF and JNK inhibitors synergize in cell killing. This arises because JNK inhibition prevents a subset of cells in a cycling population from becoming quiescent upon vemurafenib treatment, thereby reducing drug Emax. Our findings demonstrate the breadth and diversity of adaptive responses to RAF/MEK inhibition and a means to identify which steps in a signaling cascade are most predictive of phenotypic response.
Kang, C., et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 349, 6255, aaa5612 (2015).Abstract
Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence is the senescence-associated secretory phenotype (SASP), a pro-inflammatory response linked to tumor promotion and aging. We have identified the transcription factor GATA4 as a senescence and SASP regulator. GATA4 is stabilized in cells undergoing senescence and is required for the SASP. Normally, GATA4 is degraded by p62-mediated selective autophagy, but this regulation is suppressed during senescence, thereby stabilizing GATA4. GATA4 in turn activates the transcription factor NF-κB to initiate the SASP and facilitate senescence. GATA4 activation depends on the DNA damage response regulators ATM and ATR, but not on p53 or p16(INK4a). GATA4 accumulates in multiple tissues, including the aging brain, and could contribute to aging and its associated inflammation.

redpajama_set_name: RedPajamaCommonCrawl


Find out more about our study rooms and how you can access them. In addition to over 60,000 objects on display in the Museum, the V&A also has a number of study rooms, both on and off-site, where it is possible to view over 2 million objects from the Reference Collections and to conduct private research.... In a large living room, even after filling out a main seating arrangement, there will likely be an odd corner that remains unfilled. If you put as much effort into this corner as into the "main" seating area, it may well become your favorite hangout spot.
Arranging furniture in a 12-by-16 foot living room follows the same process as furniture arrangement in a room of any size. It is accomplished by following a few design guidelines and using furniture appropriate to the size of the room.... Before arranging the living room, you need to decide which functional units (groups) should be included, depending on the habits and needs of each individual family.
7/09/2012 · How to create an ideal study space for the student in your home. -- Pin this video on Pinterest: http://goo.gl/6kPbp -- Get the product list on Menards.com:... Finding a quiet place to concentrate is of the highest importance for those who work or study from home. But more than that – it needs to be well equipped for the task, capable of containing the books or computer accessories necessary for productivity.
Room Arranging Learn how to arrange living room furniture with these easy tips and savvy layouts. Whether your room is long and narrow or small and square, we have smart ideas for furniture arrangements that are versatile and will make the most of your space.
In a large living room, even after filling out a main seating arrangement, there will likely be an odd corner that remains unfilled. If you put as much effort into this corner as into the "main" seating area, it may well become your favorite hangout spot.


In the first meeting this year, Duke destroyed VT 100-65 in a lopsided affair at Duke. Last night, the Virginia Tech Men's Basketball Team knocked off the #7-ranked Duke Blue Devils in Blacksburg - a rather significant upset for a team that was predicted to finish next-to-last in the ACC. . In fact, the Hokies are currently tied for 4th place in the conference with two other teams!


Bible study is foundational for our spiritual health. Unfortunately, too many Christians are either satisfied with a surface knowledge of scripture or think that since they have discovered the correct doctrinal positions on key issues they have arrived. This is hurtful to the individual and to the cause of Christ. As disciples of Christ we need to trust that whatever God revealed, he intended for us to know. When God revealed Isaiah, Zechariah, and Chronicles, he expected us to diligently seek to understand these books.
We cannot be content with mainly "scriptural facts" lest we miss out on the beauty of the mind of God. Paul said that the Holy Spirit had revealed "the deep things of God" (1 Cor. 2:10). Before marrying, couples spend hours upon hours talking, asking questions, and learning about one another. Women especially want to know what is really going on in their husband's mind. It should be our overriding passion to be with the Lord. So, do we truly know him? Are we excited to discover all we can about our spiritual husband? And if we are not searching the deep things of his mind and learning how wonderful he is, how will we motivate those around us to also pursue the Lord?
Bible study, like marriage was designed to be enjoyed. If we are not enjoying it, we are just not doing it right. It is evident that most Christians would love to know God and his word more thoroughly. So what is the problem? Below are seven typical mistakes Christians make that keep them from a more enjoyable Bible study experience.
Not investing the appropriate amount of time into study. The purpose of study is to draw closer to God and develop an intimate, meaningful relationship with him. "Knowledge" is a means to the goal, but knowledge itself is not the goal. Christians are too often studying as if they are "cramming" for a test. What is our problem? We are too busy. Am I right? Christians at the very least should be scheduling two hours per week of uninterrupted, in-depth study, besides daily Bible reading. After all, without God's word we will starve to death.
Just reading. I've known people who boasted about how many times they have read through the Bible. Of course, we never want to discourage reading the Bible, but as one person said, "It is not how many times you have gone through the Bible that is important, but how many times the Bible has gone through you." Further, when we are "just reading" it is too easy to forget what we have read. The pencil is one of the best eyes we have. Joseph Gettys said, "You should stress to all of your pupils the importance of working on paper, for what is written on paper releases the mind to fasten its attention on something more" (Teaching Pupils How to Study the Bible). Keep a journal next to your Bible and write down your discoveries. Use colored pencils to mark the text – underline, circle, and shade what you find interesting. If you don't want to mark in your Bible, at least print the text from your computer leaving a margin to make notes.
Not looking for the message of the text or understanding how the original recipients heard the message. When the prophets, Jesus, or the apostles are speaking to Jews, are you "thinking Jewish?" When the first words uttered by John the Baptist were, "The one who comes after me…will baptize you with the Holy Spirit…" our first thought should be, "What did first century Jews know about the Holy Spirit from the Old Testament, and therefore how were they hearing John?" Until we know what the original hearer understood, we cannot draw conclusions or make applications.
Not getting the big picture. Could you summarize the message of Ephesians in a sentence? How about Philippians or the gospel John? Christians typically focus on the details of a text without having a grasp of the bigger message. In other words, when the Galatians received their letter from Paul, did they begin a 13-week detailed exposition of the letter? Or did they first just read the letter? A study of any book of the Bible should always begin with a quick reading while jotting down brief observations that help you discover the author's reason for writing. By getting a feel of the road you are about to travel, you will be more likely to keep your discoveries in context and find the Holy Spirit's method of revelation.
Being enamored with justifying doctrinal positions. Christians who study primarily to prove themselves right or prove others wrong will invariably draw erroneous conclusions and take passages out of context. Our first objective must be to know what God is actually revealing. The word is a sharp sword designed to "penetrate the thoughts and intents of our heart" (Heb. 4:12). If my study does not first draw blood on me, I have not studied properly.
Quickly fleeing to a commentary to learn about a text instead of enjoying and meditating on the text itself. Again, we must remember our goal. We study God's word in order to get to know God, not just to know facts. God's mind is enjoyable; it feeds our soul and delights our heart. Commentaries are typically cold and surgical and can hinder our own abilities to discover. Commentaries are good if used as you would a friend off whom you bounce your conclusions.
Neglecting parts of the Bible that seem to be too difficult to understand. For most people, the Old Testament, and especially the prophets, is the main area of neglect. Paul's reminder to Timothy is helpful when he says, "How that from childhood you have been acquainted with the sacred writings, which are able to make you wise for salvation through faith in Christ Jesus" (2 Tim. 3:15). The Old Testament is the key to understanding Jesus. It also gives us a clear description of God's purpose for his people and the character of the Messiah's disciples.
Enjoying Bible study and using our study time effectively is imperative. If we do not study efficiently so that God stirs our soul, we will not enjoy our study. And if we do not enjoy our study, we will likely stop studying and growing closer to the Lord.


text:
Noord-Sleen (voorheen: Noordsleen, Drents: Noord-Slien) is een dorp in de Nederlandse provincie Drenthe, gemeente Coevorden.

Geschiedenis
Noord-Sleen ligt ten noorden van het dorp Sleen, dat vroeger ook wel Zuid-Sleen werd genoemd. Noord-Sleen en Sleen zijn in de vroege middeleeuwen ontstaan door splitsing van een oude nederzetting die ongeveer halverwege de huidige dorpen lag. 'Zuid-Sleen' heeft zich later ontwikkeld tot het hoofddorp van de gemeente Sleen, die op 1 januari 1998 opging in de gemeente Coevorden. Noord-Sleen werd voor het eerst genoemd in 1365 als van Nortslene.

Uit bodemvondsten kon worden afgeleid dat er nabij het huidige Noord-Sleen al in de prehistorie een nederzetting was. Daarvan getuigen ook de hunebedden (D50 en D51) aan de Hunebedweg. In 2015 werden tijdens voorbereidingen voor de bouw van een nieuwe boerderij overblijfselen ontdekt van bewoning uit de laatste bronstijd en begin ijzertijd. Paalgaten van een aantal spiekerboerderijen werden blootgelegd aan de Zweeloërstraat. Dit bevestigde het vermoeden dat er al meer dan 3000 jaar bewoning plaatsvindt in dit gebied.

Bezienswaardigheden

Noord-Sleen is een langgerekt esdorp met nog veel Saksische boerderijen. Bezienswaardig zijn verder de molen Albertdina, een grondzeiler uit 1906.

De marke van Noord-Sleen kenmerkt zich door essen. Hier zijn twee hunebedden te vinden. In het bos ligt het hunebed de Papeloze Kerk, verwijzend naar de hagenpreken die hier tijdens de Reformatie op de heide werden gehouden. Ten noorden van Noord-Sleen ligt de uitgestrekte, 1600 ha grote Boswachterij Sleenerzand (Staatsbosbeheer). Het meest noordelijke punt was de zevenmarkensteen ten noorden van De Kiel. De bossen zijn, zoals de naam al doet vermoeden, aangeplant op een groot heide- en stuifzandgebied. Op enkele kleine heideveldjes na is hier niets meer van over.

Aan de zuidkant van het bos staat een monument voor de omgekomen bemanningsleden van een Brits vliegtuig dat daar op 14 mei 1943 in het toen nog jonge bos is neergestort. Aan de zuidoostkant van het bos, vlak bij het dorp Noord-Sleen, ligt recreatieplas de Kibbelkoele.

Voorzieningen
In het dorp zijn een basisschool, een café-restaurant, enkele winkels, een openluchtzwembad en twee minicampings. Noord-Sleen is bereikbaar over de weg via de provinciale wegen N376 en N381.

Externe link
 Dorpsbelangen Noord-Sleen

Brinkdorp
Coevorden
Plaats in Drenthe

redpajama_set_name: RedPajamaWikipedia


Bring your Water Bottles to UNI!!
College Policy Debate Forums > TOURNAMENTS > DECEMBER > Northern Iowa > Bring your Water Bottles to UNI!!
In an effort to be green, healthy, and cost efficient, we will have a large water dispenser at the tournament this weekend. In efforts to cut down on trash and save money, we would encourage folks to bring a reusable water bottle to the tournament. This water will be available the entire weekend (in addition to pop at meals). Thank you for your assistance!


New Zealand's state-backed Ultrafast Broadband (UFB) fibre network added more than 60,000 new connections last quarter, taking the total number of subscribers to just under 669,000.
The rollout of the network, which is being led by wholesale operator Chorus under contract with the government, is now 76.3% complete.
This represents nearly half of the roughly 1.4 million New Zealand households and businesses in the current UFB coverage area, according to the latest report into the government's UFB program.
The report from the New Zealand Ministry of Broadcasting, Communications and Digital Media found that the UFB project is on track to meet its target of making the network available to 87% of the population across around 390 cities and towns by the end of 2022.
The government's concurrent Rural Broadband Initiative Phase 2, as well as the Mobile Blackspot Fund, is also helping to improve the nation's broadband infrastructure.
Under the two programs, over 70,000 rural households and businesses are expected to receive new or improved broadband, while around 1000 km of state highway and over 100 tourism attractions are expected to receive nationwide mobile coverage.
During phase 1 of the program, 154 new towers were built, while over 111,000 copper lines and 387 existing towers have been upgraded.


A story of a regular girl who is trying to make big in her life. She is a little less focussed when it comes to her job. A supportive father, a nagging mother, a few good friends, a reliable colleague, a picture perfect boyfriend and a sarcastic boss, Kajal, the protagonist of the book, her life was similar to the life of any regular girl. She works for an ad-agency where she has to deal with clients from every field and ensure that they keep grinning from ear to ear. There comes a time, when Kajal realises that she is not giving her 100% towards her job and thats when things begin to fall in place in her life.
"You Never Know When You'll Get Lucky" is an unputdownable, witty and fast paced read, which instantly falls in the my kind of book category. The characters are very real and you would feel that you have seen them in your life too.
Love makes you do weird things and when it comes to dating, things get a lot more weird. By the end of the 3rd chapter, Priya Narendra was successful in grabbing my interest, which is a good thing. It took me around 3.5 hours to finish this 230 page book.
The book is a complete entertainer, with a no non-sense plot. You might feel that you can predict the plot, but it takes you by surprise towards the end. I loved the way, the title of the book has been connected with the story, but I would not like to get into the plot, because it might reveal everything. Pick this book if you are going for a small journey and have got nothing to do. I promise you, it won't bore you.


text:
A Searchlight Soul
Posted on July 26, 2017 by jcschildbach
Chester Bennington completed suicide by hanging on Chris Cornell's birthday, just over a month after Chris Cornell completed suicide by hanging on the 37th anniversary of Ian Curtis' suicide by hanging.
For those unfamiliar, Bennington was best known as the lead singer of Linkin Park; Chris Cornell was best known as the lead singer of Soundgarden; and Ian Curtis was best known as lead singer of Joy Division.
Now, Linkin Park's music makes me want to grind my teeth, spit, and curse—and not in a good way. And I never got into Joy Division beyond owning a 'greatest hits' collection for a few years as an undergrad. I am, however, a big fan of Soundgarden, as well as another of Cornell's bands, Audioslave—not such a big fan that I ever made it to a concert. But, living in Seattle, I would see members of the band at other bands' shows around town in the way back of the early 90s.
How would I know? Cornell from 'Fell on Black Days.'
I have no idea if Cornell's suicide was related to Curtis' beyond coincidence. But Bennington's was directly connected to Cornell's. They were friends, and, from what I understand, Bennington took Cornell's death particularly hard. Both Cornell and Bennington had struggled with addiction and mental health issues during their lives.
But the takeaway shouldn't only be that a life marbled with addiction and mental health issues leads to suicide. That makes it too easy for people to distance themselves from suicide, its causes, and our potential susceptibility to its draw.
In the wake of a loved one's death, thoughts of suicide can arise or increase, and suicide attempts climb.
In the wake of a loved one's death from suicide, those thoughts and those attempts climb significantly higher.
There are those who have criticized Curtis', Cornell's, and Bennington's suicides by pointing out that they had achieved success, or had spouses, friends, children…all of which should have somehow prevented them from committing suicide, much less having thoughts of such.
That's a natural impulse—to want to point out why we never would have killed ourselves in similar circumstances. But it's also false comfort.
Just try to imagine finding yourself in a space where money, success, and a loving family can be discounted as not providing enough impetus to go on living. Imagine finding yourself in a space where you actually feel the people who care about you most will be better off without you. Imagine being so deep into that thought process that you can't find your way out—that it seems completely logical—that suicide actually seems like the only rational decision.
I could get into explanations of survivor guilt, or what grief can do to people, or the impact of knowing that a friend reached the conclusion that suicide was an appropriate response to the world around them–a world that you were part of.
But I'd rather you think on how declaring yourself immune to something, insisting you are completely separate from some problem, is the first step to blocking your understanding of that problem…or worse, blocking your compassion toward others affected by that problem. You can feel for the families and friends of those who complete suicide without feeling the need to condemn the dead. That condemnation does nothing to help the grieving, or anybody else, least of all you.
This entry was posted in Depression, Mental Health, Suicide, Uncategorized and tagged Addiction, Chester Bennington, Chris Cornell, Depression, Ian Curtis, Joy Division, Linkin Park, Mental Health, Music, Soundgarden, Suicide, Suicide Prevention by jcschildbach. Bookmark the permalink.
3 thoughts on "A Searchlight Soul"
Robert Matthew Goldstein on July 27, 2017 at 12:13 said:
Thank you for this post. We live in a Nation that seems to be in deep denial about the seriousness of mental Illness and its lethal outcomes. We do this at our peril.
from Respect the Blankie
jcschildbach on July 27, 2017 at 12:31 said:
Thanks for the re-blog and other sharing! Much appreciated!


text:
https://apnews.com/article/coronavirus-pandemic-business-europe-romania-european-union-587e7987187bd17cf251549c366252ce
Romania hits record infections, deaths amid vaccination lag
By STEPHEN McGRATHOctober 19, 2021 GMT
Paramedics bring an elderly patient to the emergency room, turned into a CODIV-19 unit due the high number of cases, at the Bagdasar-Arseni hospital in Bucharest, Romania, Tuesday, Oct. 12, 2021. Romania reported on Tuesday nearly 17,000 new COVID-19 infections and 442 deaths, the highest number of coronavirus infections and deaths in a day since the pandemic started, as the nation's health care system struggles to cope with an acute surge of new cases.(AP Photo/Andreea Alexandru)
BUCHAREST, Romania (AP) — Romania on Tuesday hit daily records in both coronavirus infections and deaths as the country grapples with an acute virus surge amid alarmingly low vaccination uptake.
Romania confirmed a record high of 18,863 new COVID-19 infections and 574 deaths in one day. It was the first time the European Union nation of 19 million surpassed 500 deaths in a single day.
Romania has the second-lowest vaccination rate in the EU behind Bulgaria — with just 34% adults fully inoculated against COVID-19, compared to the bloc average of 74%. That is stretching the country's ailing health care system to maximum capacity: more than 1,800 coronavirus patients are now in intensive care.
Romanian President Klaus Iohannis called the situation a "national drama of terrible proportions" and urged Romanians to get vaccinated.
He told in a press conference Tuesday that the "lack of concrete action on the part of the authorities is alarming" and said he has convened a meeting with government officials Wednesday to "establish clear, restrictive measures."
"There are 574 hearts of Romanians that stopped beating because they lost the fight with this deadly virus," Iohannis said. "People who, just a few weeks ago, enjoyed life, dreamed and made plans for the future — (and) now leave behind the tears and despair of those who mourn their death."
In response to the unfolding disaster, the World Health Organisation said Tuesday it will send a senior expert to Romania to help strengthen the country's pandemic response and it will facilitate the provision of 34,000 rapid COVID-19 diagnostic tests and 200 oxygen concentrators to treat virus patients.
"An urgent priority is to boost vaccination among vulnerable groups, reduce the risk of hospitalization and death, and relieve pressure on the health system," Dr. Heather Papowitz, the WHO expert, said in a statement.
Last week, as Romania's health care system struggled to cope with the onslaught of COVID-19 patients, several dozen patients were sent to Hungary to receive intensive care treatment and Italy sent 5,200 doses of monoclonal antibodies.
Romania has so far confirmed more than 1.4 million COVID-19 infections and the deaths of 42,616 COVID-19 patients.
Follow all AP stories on the coronavirus pandemic at https://apnews.com/hub/coronavirus-pandemic.


DPD Courier may release funds to the Seller after the Inspection Period has ended. The Inspection Period is agreed upon by both parties and commences once the Buyer confirms receipt of vehicle or merchandise.
Funds are released to the Seller the same or next business day after successful completion of a transaction and upon verification by DPD Courier.


2. Offering a complete solution for non woven fabric products needs, our rich collection of pp spunbond nonwoven fabric is widely popular in international arena. Our given Non Woven Fabric is precisely designed in accordance with the quality standards by using excellent quality material.
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S&R Garage Hard Lemon Tea is a refreshing hard drink with a taste of lemon tea. It is pleasant to the taste and is perfectly refreshing in the summer heat.
Made of malt, glucose-fructose syrup, barley, hop and water. Contains acidity regulators citric acid and ascorbic acid, the "Lemon Tea" flavor, acacia extract, natural caramel color.


In this Artifact Art piece, a cowboy and horse scene is depicted on a Kitchen Cleaver alongside a genuine horseshoe. Both are mounted on a rough Redwood board. Add a small piece of the Old West to your kitchen!
The Cleaver was an important implement used by all Chuckwagon cooks in the Old West. In fact, the cook (or "cookie" as they were often referred to), was often second in command right behind the "trailboss" on a cattle drive.
The old horseshoe in this piece came from the John Wayne Ranch in Stanfield, Arizona -- not far from our home in Casa Grande, Arizona. This fact gives an added authenticity to the piece.


Watch the new video "Midnight Champion" from Icelandic electronic alt-rockers Legend below. It's a dark affair shot in their home country.
- It's basically about how we create killers with our prejudice and abuse. The main character is a broken dark soul - Midnight Champion - out for revenge against mankind and becomes a martyr, frontman Krummi tells Revolver.
Legend's second album with the same title is set for release on October 13 on Artoffact.


Notice, of course, that illegal substances or weapons, or what have you do not have to be found for an arrest and conviction to be made. A secret compartment, by itself, is intent. The bill reads: "Proof that a conveyance contains a hidden compartment as defined in this section shall be prima facie evidence that the conveyance was used intended for use in and for the business of unlawfully manufacturing, dispensing, or distributing controlled substances." You, dear reader, may think the passage of such a wrong-headed, idiotic law is next to impossible. However, the great state of Ohio already has such a law on the books. In 2013. Norman Gurley was stopped by Ohio state troopers, who noticed some wires in his vehicle and in turn discovered the car had a secret compartment. No drugs were found, but he was arrested and charged with violating Ohio's law against secret compartments.
You, dear reader, may think the passage of such a wrong-headed, idiotic law is next to impossible. However, the great state of Ohio already has such a law on the books. In 2013. Norman Gurley was stopped by Ohio state troopers, who noticed some wires in his vehicle and in turn discovered the car had a secret compartment. No drugs were found, but he was arrested and charged with violating Ohio's law against secret compartments. Policing For Profit The Massachusetts bill H. 1266 mentioned above has the full-throated support of the Massachusetts state police despite being criticized for violating due process and property rights. As written, the law will allow police to keep any vehicle they seize. According to the Institute for Justice, Massachusetts (along with North Dakota) has the worst civil asset forfeiture laws in the country. And that is saying something. Law enforcement need only have probable cause (like justifying a search warrant) that a person's property or money is connected to a crime in order to seize it.
The Massachusetts bill H. 1266 mentioned above has the full-throated support of the Massachusetts state police despite being criticized for violating due process and property rights. As written, the law will allow police to keep any vehicle they seize.
According to the Institute for Justice, Massachusetts (along with North Dakota) has the worst civil asset forfeiture laws in the country. And that is saying something. Law enforcement need only have probable cause (like justifying a search warrant) that a person's property or money is connected to a crime in order to seize it.
The state of Massachusetts doesn't have to prove a citizen's guilt to keep the property. It's up to the citizen to prove innocence for the return of the property. And under Massachusetts law, police get to keep 100 percent of what is seized. This is huge financial incentive to claim anyone they pull over and search is connected to the drug trade—especially if that person has any possessions of value.
Police in Massachusetts already confiscate over $9 million a year from forfeitures.
And that's not all. Massachusetts law enforcement participates in the Department of Justice's equitable sharing program—earning the state a ranking by Institute for Justice of 46th nationally. This compounds the problems with the state's forfeiture laws. Law enforcement agencies received $63.5 million in equitable sharing proceeds between 2000 and 2013, or $4.5 million per calendar year.
Samuel Adams and the Sons of Liberty, who threw 342 chests of tea into Boston Harbor to protest the oppressive British government, are rolling over in their graves.


text:
Q: Авторизация в Steam на Delphi Добрый день, есть желание из своей программы, написанной на Delphi, авторизоваться в Steam.
Посмотрев исходники программы Steam Desktop Authenticator, пришел к выводу, что нам нужно сделать 2 POST-запроса к серверу Steam, первый вернет нам модуль и экспоненту открытого ключа RSA, которым мы должны зашифровать свой пароль и отправить его во втором запросе. Решил попробовать реализовать это с помощью функций Microsoft CryptoAPI: Next Generation.
Набросал функцию, которая на входе получает 3 строки: пароль от Стима, открытые модуль и экспоненту в виде строк, состоящих из шестнадцатеричных символов (их нам присылает сервер). На выходе должны получить пароль, зашифрованный открытым ключом по алгоритму RSA и закодированный в BASE64.

    unit uRSA;

    interface
    uses WinAPI.Windows, System.SysUtils, VCL.Dialogs, System.NetEncoding;

    //БЛОБ открытого ключа RSA, описание структуры есть на MSDN
    type TPublicKeyBLOB = packed record
    Magic: ULONG;
    BitLength: ULONG;
    cbPublicExp: ULONG;
    cbModulus: ULONG;
    cbPrime1: ULONG;
    cbPrime2: ULONG;
    exponent: array[0..2] of byte;
    modulus: array[0..255] of byte;
    end;
    pPublicKeyBLOB = ^TPublicKeyBLOB;

    //прототипы функций из библиотеки BCRYPT.DLL
    TBCryptOpenAlgorithmProvider = function (phAlgorithm: pHandle; pszAlgId: LPCWSTR;
    pszImplementation: LPCWSTR; dwFlags: DWORD): ULONG; stdcall;
    //--
    TBCryptImportKeyPair = function (hAlgorithm: THandle; hImportKey: THandle; pszBlobType: LPCWSTR;
    phKey: pHandle; pbInput: pPublicKeyBLOB; cbInput: ULONG; dwFlags: ULONG): ULONG; stdcall;
    //--
    TBCryptEncrypt = function (hKey: THandle; pbInput: PUCHAR; cbInput: ULONG; pPaddingInfo: POINTER;
    pbIV: PUCHAR; cbIV: ULONG; pbOutput: PUCHAR; cbOutput: ULONG; pcbResult: PULONG; dwFlags: ULONG): ULONG; stdcall;
    //--
    TBCryptCloseAlgorithmProvider = function (hAlgorithm: THandle; dwFlags: ULONG): ULONG; stdcall;

    //сама функция шифрования
    type TRSA = class
    public
    function RSA_Encrypt(DataStr: string; modulusStr: string; exponentStr:   string): string;
    end;

    const
    BCRYPT_RSAPUBLIC_MAGIC = $31415352;  // RSA1
    BCRYPT_PAD_PKCS1 = $00000002;

    implementation

    function HexToByte(Str: string): Byte;
    begin
    result :=  Byte(StrToInt('$' + (Str)));
    end;

    function TRsa.RSA_Encrypt(DataStr: string; modulusStr: string; exponentStr: string): string;
    var
    PublicKeyBLOB: TPublicKeyBlob;
    i: word;
    status: ULONG;
    hLib: THandle;
    hAlg: THandle;
    hKey: tHandle;
    Password: TBytes;
    EncryptedPassword: TBytes;
    EncryptedSize: ULONG;
    BCryptOpenAlgorithmProvider: TBCryptOpenAlgorithmProvider;
    BCryptImportKeyPair: TBCryptImportKeyPair;
    BCryptEncrypt: TBCryptEncrypt;
    BCryptCloseAlgorithmProvider: TBCryptCloseAlgorithmProvider;
    begin
    //преобразовываем входные данные в массив байтов;
    Password := TEncoding.ASCII.GetBytes(DataStr);
    hLib := LoadLibrary('BCRYPT.DLL');
    //загрузка функций из библиотеки
    //функция инициализации провайдера
    @BCryptOpenAlgorithmProvider := GetProcAddress(hLib, 'BCryptOpenAlgorithmProvider');
    //функция импорта ключа
    @BCryptImportKeyPair := GetProcAddress(hLib, 'BCryptImportKeyPair');
    //функция шифрования
    @BCryptEncrypt := GetProcAddress(hLib, 'BCryptEncrypt');
    //функция освобождения провайдера
    @BCryptCloseAlgorithmProvider := GetProcAddress(hLib, 'BCryptCloseAlgorithmProvider');
    //собираем ключ
    with PublicKeyBLOB do
    begin
    Magic := BCRYPT_RSAPUBLIC_MAGIC;  // RSA1;
    BitLength := SizeOf(Modulus)*8;//размер модуля в битах
    cbPublicExp := SizeOf(Exponent);//размер экспоненты в байтах
    cbModulus := SizeOf(Modulus);//размер модуля в байтах
    //(необязательно) проверим, что в переданных параметрах - четное количество символов
    if (length(exponentstr) mod 2)  0 then
    exponentstr := '0' + exponentstr;
    if (length(modulusstr) mod 2)  0 then
    modulusstr := '0' + modulusstr;
    for i := Low(exponent) to High(exponent) do
    exponent[i] := HexToByte(copy(exponentstr,i*2+1,2));
    for i := Low(modulus) to High(modulus) do
    modulus[i] := HexToByte(copy(modulusstr,i*2+1,2));
    end;
    //инициализация провайдера
    status := BCryptOpenAlgorithmProvider(@halg,'RSA',nil,0);
    //импорт ключа
    status := BCryptImportKeyPair(hAlg,0,'RSAPUBLICBLOB', @hKey, @PublicKeyBLOB,
    SizeOf(PublicKeyBLOB),0);
    //шифрование сообщения. Первый проход - получаем размер выходного буфера, второй - шифруем текст
    status := BCryptEncrypt(hKey, @Password[0], Length(Password), nil, nil, 0, nil, 0, @EncryptedSize, BCRYPT_PAD_PKCS1);
    SetLength(EncryptedPassword,EncryptedSize);
    status := BCryptEncrypt(hKey, @Password[0], Length(Password), nil, nil, 0, @EncryptedPassword[0], Length(EncryptedPassword), @EncryptedSize, BCRYPT_PAD_PKCS1);
    //кодируем зашифрованное сообщение в Base64
    Result := TNetEncoding.Base64.EncodeBytesToString(EncryptedPassword);
    //освобождаем память
    status := BCryptCloseAlgorithmProvider(hAlg,0);
    FreeLibrary(hLib);
    end;

    end.

Вроде бы все успешно отрабатывает, но, когда делаю POST-запрос с зашифрованным паролем к серверу STEAM - получаю в ответ:
    {"success":false,"requires_twofactor":false,
   "message":"The account name or password that you have entered is incorrect.",
   "clear_password_field":true,"captcha_needed":false,"captcha_gid":-1}

На вход функции подаются строки в виде

   "publickey_mod":"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",
   "publickey_exp":"010001"

Буду очень признателен, если кто-нибудь укажет на ошибку или даст совет: как в Delphi можно зашифровать сообщение, имея экспоненту и модуль открытого ключа RSA.

A: Проблема была в некорректной работе
//кодируем зашифрованное сообщение в Base64
Result := TNetEncoding.Base64.EncodeBytesToString(EncryptedPassword);

Эта функция не убирает переносы строки, так что придется получившийся результат обработать дополнительно:
//кодируем зашифрованное сообщение в Base64
Result := TNetEncoding.Base64.EncodeBytesToString(EncryptedPassword);
//удалим переносы строки
Result := StringReplace(Result, #13#10, '',[rfReplaceAll]);

Либо же можно использовать аналогичную функцию из пакета Indy, которая работает верно:
uses IdCoderMIME, idcoder, idglobal;
...
function MyFunc(): string;
var
Temp: TIdBytes;
begin
...
Result := TIdEncoderMIME.EncodeBytes(Temp);
end;

Рабочий код :
unit uRSA;

interface
uses WinAPI.Windows, System.SysUtils, VCL.Dialogs, System.NetEncoding;

//БЛОБ открытого ключа RSA, описание структуры есть на MSDN
type TPublicKeyBLOB = packed record
Magic: ULONG;
BitLength: ULONG;
cbPublicExp: ULONG;
cbModulus: ULONG;
cbPrime1: ULONG;
cbPrime2: ULONG;
exponent: array[0..2] of byte;
modulus: array[0..255] of byte;
end;
pPublicKeyBLOB = ^TPublicKeyBLOB;

//прототипы функций из библиотеки BCRYPT.DLL
TBCryptOpenAlgorithmProvider = function (phAlgorithm: pHandle; pszAlgId: LPCWSTR;
pszImplementation: LPCWSTR; dwFlags: DWORD): ULONG; stdcall;
//--
TBCryptImportKeyPair = function (hAlgorithm: THandle; hImportKey: THandle; pszBlobType: LPCWSTR;
phKey: pHandle; pbInput: pPublicKeyBLOB; cbInput: ULONG; dwFlags: ULONG): ULONG; stdcall;
//--
TBCryptEncrypt = function (hKey: THandle; pbInput: PUCHAR; cbInput: ULONG; pPaddingInfo: POINTER;
pbIV: PUCHAR; cbIV: ULONG; pbOutput: PUCHAR; cbOutput: ULONG; pcbResult: PULONG; dwFlags: ULONG): ULONG; stdcall;
//--
TBCryptCloseAlgorithmProvider = function (hAlgorithm: THandle; dwFlags: ULONG): ULONG; stdcall;

//сама функция шифрования
type TRSA = class
public
function Encrypt(DataStr: string; modulusStr: string; exponentStr:   string): string;
end;

const
BCRYPT_RSAPUBLIC_MAGIC = $31415352;  // RSA1
BCRYPT_PAD_PKCS1 = $00000002;
BCRYPT_RSA_ALGORITHM = 'RSA';
BCRYPT_RSAPUBLIC_BLOB = 'RSAPUBLICBLOB';

implementation

function HexToByte(Str: string): Byte;
begin
result :=  Byte(StrToInt('$' + (Str)));
end;

function TRsa.Encrypt(DataStr: string; modulusStr: string; exponentStr: string): string;
var
PublicKeyBLOB: TPublicKeyBlob;
i: word;
status: ULONG;
hLib: THandle;
hAlg: THandle;
hKey: tHandle;
Password: TBytes;
EncryptedPassword: TBytes;
EncryptedSize: ULONG;
BCryptOpenAlgorithmProvider: TBCryptOpenAlgorithmProvider;
BCryptImportKeyPair: TBCryptImportKeyPair;
BCryptEncrypt: TBCryptEncrypt;
BCryptCloseAlgorithmProvider: TBCryptCloseAlgorithmProvider;
begin
//преобразовываем входные данные в массив байтов;
Password := TEncoding.ASCII.GetBytes(DataStr);
hLib := LoadLibrary('BCRYPT.DLL');
if hLib < 32 then
begin
 ShowMessage('Error while loading BCRYPT.DLL!');
 exit;
end;
//загрузка функций из библиотеки
//функция инициализации провайдера
@BCryptOpenAlgorithmProvider := GetProcAddress(hLib, 'BCryptOpenAlgorithmProvider');
//функция импорта ключа
@BCryptImportKeyPair := GetProcAddress(hLib, 'BCryptImportKeyPair');
//функция шифрования
@BCryptEncrypt := GetProcAddress(hLib, 'BCryptEncrypt');
//функция освобождения провайдера
@BCryptCloseAlgorithmProvider := GetProcAddress(hLib, 'BCryptCloseAlgorithmProvider');
//собираем ключ
with PublicKeyBLOB do
begin
Magic := BCRYPT_RSAPUBLIC_MAGIC;  // RSA1;
BitLength := SizeOf(Modulus)*8;//размер модуля в битах
cbPublicExp := SizeOf(Exponent);//размер экспоненты в байтах
cbModulus := SizeOf(Modulus);//размер модуля в байтах
//(необязательно) проверим, что в переданных параметрах - четное количество символов
if (length(exponentstr) mod 2) <> 0 then
exponentstr := '0' + exponentstr;
if (length(modulusstr) mod 2) <> 0 then
modulusstr := '0' + modulusstr;
for i := Low(exponent) to High(exponent) do
exponent[i] := HexToByte(copy(exponentstr,i*2+1,2));
for i := Low(modulus) to High(modulus) do
modulus[i] := HexToByte(copy(modulusstr,i*2+1,2));
end;
//инициализация провайдера
status := BCryptOpenAlgorithmProvider(@halg,BCRYPT_RSA_ALGORITHM,nil,0);
if status <> 0 then
begin
ShowMessage('BCryptOpenAlgorithmProvider error, status: ' + IntToStr(status)  + ', ' + SysErrorMessage(GetLastError()));
exit;
end;
//импорт ключа
status := BCryptImportKeyPair(hAlg,0,BCRYPT_RSAPUBLIC_BLOB, @hKey, @PublicKeyBLOB, SizeOf(PublicKeyBLOB),0);
if status <> 0 then
begin
ShowMessage('BCryptImportKeyPair error, status: ' + IntToStr(status) + ', ' + SysErrorMessage(GetLastError()));
exit;
end;
//шифрование сообщения. Первый проход - получаем размер выходного буфера, второй - шифруем текст
status := BCryptEncrypt(hKey, @Password[0], Length(Password), nil, nil, 0, nil, 0, @EncryptedSize, BCRYPT_PAD_PKCS1);
if status <> 0 then
begin
ShowMessage('BCryptEncrypt error 1, status: ' + IntToStr(status) + ', ' + SysErrorMessage(GetLastError()));
exit;
end;
SetLength(EncryptedPassword,EncryptedSize);
status := BCryptEncrypt(hKey, @Password[0], Length(Password), nil, nil, 0, @EncryptedPassword[0], Length(EncryptedPassword), @EncryptedSize, BCRYPT_PAD_PKCS1);
if status <> 0 then
begin
ShowMessage('BCryptEncrypt error 2, status: ' + IntToStr(status) + ', ' + SysErrorMessage(GetLastError()));
exit;
end;
//освобождаем занятые ресурсы
status := BCryptCloseAlgorithmProvider(hAlg,0);
if status <> 0 then
begin
ShowMessage('BCryptCloseAlgorithmProvider error, status: ' + IntToStr(status) + SysErrorMessage(GetLastError()));
exit;
end;
//кодируем зашифрованное сообщение в Base64
Result := TNetEncoding.Base64.EncodeBytesToString(EncryptedPassword);
//удалим переносы строки
Result := StringReplace(Result, #13#10, '',[rfReplaceAll]);
//выгружаем библиотеку
FreeLibrary(hLib);
end;

end.

На вход функции подаются строки в виде:

"publickey_mod":"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",
  "publickey_exp":"010001"

redpajama_set_name: RedPajamaStackExchange


text:
Q: Trying to simulate sand pixels using raycasts I'm trying to simulate sand particles with a prefab gameobject, there's a script inside it that checks if the ground raycast has a collision detection, and if it has, it moves either to the left or to the right. It half works but the sand gameobjects stack in 5-6 blocks horizontally, here's my script:
ps: I know alot of raycasts uses alot of performance, but i'll do this way for now, when I learn more about this, i'll use unity tiles. I'm also using a simple OnMouseButtonDown to spawn the sand gameobjects into the scene, each sand gameobject has a collider so the raycasts can work properly. sorry if there's any english mistake
    using UnityEngine;

public class sandSimulation : MonoBehaviour
{
    int speedY = 1;
    int speedX = 1;
    [SerializeField] Transform ground, corner1, corner2, side1, side2;
    [SerializeField] LayerMask layer, solid;
    //public Rigidbody2D rb;
    bool goingDown;
    void FixedUpdate()
    {
        // rb.MovePosition(transform.position + new Vector3(0,-speedY,0) * 1);
        Debug.DrawLine(transform.position, ground.position, Color.red);
        Debug.DrawLine(transform.position, corner1.position, Color.red);
        Debug.DrawLine(transform.position, corner2.position, Color.red);
        Debug.DrawLine(side1.position, side2.position, Color.red);

        RaycastHit2D hitSolidDown = Physics2D.Linecast(transform.position, ground.position, solid);
        RaycastHit2D hitGround = Physics2D.Linecast(transform.position, ground.position, layer);
        RaycastHit2D hitCorner1 = Physics2D.Linecast(transform.position, corner2.position, layer);
        RaycastHit2D hitCorner2 = Physics2D.Linecast(transform.position, corner1.position, layer);
        RaycastHit2D hitSide1 = Physics2D.Linecast(transform.position, corner1.position, layer);
        RaycastHit2D hitSide2 = Physics2D.Linecast(transform.position, corner2.position, layer);

        if (hitSolidDown.collider == null)
        {
            if(transform.position != transform.position)
            {
                goingDown = true;
            }
            if (hitGround.collider == null)
            {
                //rb.MovePosition(transform.position + new Vector3(0, -speedY, 0) * 1);
                transform.Translate(new Vector2(0, -speedY));
                goingDown = true;
            }
            else if(hitGround.collider != null)
            {
                goingDown = false;
            }

            if (!goingDown)
            {
                if (hitCorner1.collider == null)
                {
                    //rb.MovePosition(transform.position + new Vector3(-speedX, 0, 0) * 1);
                    transform.Translate(new Vector2(-speedX, 0));
                    Debug.Log("Moved");
                }
                else if (hitCorner2.collider == null)
                {
                    //rb.MovePosition(transform.position + new Vector3(speedX, 0, 0) * 1);
                    transform.Translate(new Vector2(speedX, 0));
                    Debug.Log("Moved");
                }

                if(hitCorner1.collider != null && hitGround.collider != null && hitSide1.collider == null)
                {
                    transform.Translate(new Vector2(speedX, -speedY));
                }
                if (hitCorner2.collider != null && hitGround.collider != null && hitSide2.collider == null)
                {
                    transform.Translate(new Vector2(-speedX, -speedY));
                }
            }
            if(hitCorner1.collider != null || hitCorner2.collider != null)
            {
                Debug.Log("bug?");
            }
        }
    }
}

Screenshot here
Here is a gif showing whats happening
I got it working better and updated my code a little, but sometimes the sand drops just enters eachother and they still have a chance to stack.


You are here: Home / Cash Flow Business / What Determines a Mortgage Note's Value?
How is the credit on the people who are paying on the mortgage note? Obviously the higher the credit scores the better. That said, many people carry back a note because the buyer could not qualify for a bank loan to begin with. Credit is just one piece of the puzzle and poorer credit can be offset by positive factors in other categories.
This is a big one. How much does the buyer owe vs. how much is the property worth? Most note buyers are going to want to see at least 10% equity in a property. That does not mean they are going to pay up to 90% of the value of the property for a note, it just means a note buyer wants to see some sort of financial reason the buyers would not just walk away and leave equity on the table. 10% is about the minimum, 20%+ is a lot better.
Although down payment will directly affect equity, it is another factor. It shows how much the buyer made a financial commitment right out of the gate.
How long has the buyer made payments? If they have only been in the property for 2-3 months, they are not very committed at this point. There is no payment history or track record to show that they will continue to make payments. However, if they have been making payments for two to five years – you now have a very good case of showing a strong payment history.
The terms include interest rate, payment amount, frequency, and the date for when payments are due in full. A higher interest rate on the promissory note is more attractive to an investor, provided the buyer can afford the payments. If there is a balloon payment a Funder will want to know the buyer can reasonably refinance when the time comes, especially if the note is short term.
Some investors are very concerned with the location and type of property. Judicial vs. Non-Judicial states. Favorable schools. Specific demographics. Although these may not specifically aid in the note payments being made on time, it may affect what happens if the Funder has to take back the real estate and resell it.
The best part about the note business is that the above parameters often intertwine and offset each other. A note that has poor down payment can be offset by a longer amount of seasoning. Poor credit can be offset by a larger amount of equity.
In the end, each investor sets their own "rules" to determine the fair market value of a note. Pay attention to these items when creating the deal and you might just get top dollar should you ever want to sell payments.
Looking for a great resource? Check out the 2012 Directory of Note Buyers and 21 Secrets to Selling Mortgage Notes!


Lincoln Hills Construction - Why choose Lincoln Hills Construction?
Why choose Lincoln Hills Construction?
Our goal is to ensure our work is high in quality, executed in a safe manner and completed on time. We provide our clients with a project that is clearly communicated in writing and in accordance with the CSLB regulations. Our clients understand that we will never cut corners, cheapen our materials or provide sub-par workmanship. Our work is guaranteed. Always. There is no "sales pitch", no hidden costs and all contracts will be in writing. I personally meet with every client and am involved in EVERY STEP of the project. We also perform custom projects, commercial TI, work with designers and welcome non-traditional projects for clients that want to expand their creativity. Our references speak for themselves.
Quality: We strive to continually exceed our clients' expectations by maintaining strict quality controls. We are one of the few contractors that warranty & guarantee our workmanship. We ensure the completion of our work in a timely manner and at a reasonable cost.
Protection: Every effort is taken to keep dust, debris and work area traffic to a minimum. We use sheeting to minimize work area contaminants and work efficiently. We also carry the required licenses & insurances to give our clients' peace of mind.
Marc Boisvert has been in the construction industry for over 30 years. He started in his teens as an apprentice and worked his way up, learning various parts of the industry. His specialties are carpentry and tile. He takes pride in his quality craftsmanship and maintaining a good relationship with his clients. He looks forward to custom projects and challenges.
Marc also has an impressive reputation in the community as a soccer coach, president of the youth soccer league and community volunteer. He also enjoys spending time with his three boys and wife, Shannon, and playing on a men's league soccer team.


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text:
Prosecuting Hate
Q & A with Oscar Garcia, San Diego Deputy District Attorney, Hate Crimes Unit
Editor's Note: Oscar Garcia has been a prosecutor for 24 years, and for the last three years, he's specialized in hate crime cases in San Diego County. His team prosecutes on average 15 to 20 cases every year. NIOT.org spoke with Garcia about California's hate crime law, the challenges in doing this work, and the role law enforcement can play in helping improve underreporting of hate crimes, as well as hate crime prevention.
NIOT.org: Who is protected under the California hate crime statutes?
Oscar Garcia: I like to refer to hate crimes more as crimes of bias, because that focuses in on what as a prosecutor I need to prove to a jury. I need to prove that the offender was substantially motivated by a bias against a particular group. In California, the protected categories are race, ethnicity, nationality, sexual orientation, gender, religion and disability, which can be both a physical, and/or a mental disability.
NIOT.org: How do you respond to the belief that all crimes involve hate and that hate crime laws are redundant?
Oscar Garcia: I hear that a lot, even at the judiciary level. One judge told me in open court on the record that he really didn't agree with the hate crimes statute or that we should be punishing people for what they're thinking. It's important to understand why California passed this legislation in the first place. Victims of bias crimes tend to take twice as long to recover on an emotional level, because it's a very personal attack upon them -- be it because of their skin color, sexual orientation, or religion. These crimes are message crimes, not just to that one victim. We really have an entire community that's victimized when one person of a certain group is targeted because of who they are.
I analogize hate crime enhancements to the fact that we have additional penalties when someone is seriously injured [in an assault.] We call it serious bodily injury and you can get up to three more years prison time. In the case of a hate crime, it may be even more significant for the victim because the physical wound may heal, but the mental injury takes a lot longer to recover from, and sometimes victims of hate crimes never do recover.
NIOT.org: Do hate crime enhancements, whether they involve extra prison time or a fine, make a difference?
Oscar Garcia: I think they do make a difference, even if ultimately we don't get a judge to give that extra penalty. Every opportunity we have when a hate crime occurs, I want to get the message out to would-be hate crime offenders that we're going to fervently prosecute these cases, that we treat them differently and that they are looking at a more severe penalty -- sometimes up to double the penalty if it's a group attack. The hardcore white supremacists are probably going to continue to commit these crimes of opportunity. But for those who are maybe on the fence, who are the wannabes, and especially the juvenile offenders, hopefully we can reach them.
NIOT.org: Are there situations in which bias is clearly involved, but the law doesn't allow your office to act?
Oscar Garcia: We live in a country where we value the first amendment, so when someone says a slur, that doesn't mean it's a hate crime, and we do not file hate crime charges every time somebody says a slur. (Though I will also point out that the first amendment was never intended to protect hateful speech.) Even if it's a fight and someone yells a slur, that alone may very well not result in hate crime charges. It is something we'll look at, and it's a red flag, depending on the totality of the circumstances. Sometimes the absence of a motive is enough and we'll base hate crime charges on the fact that there isn't any other reasonable explanation why an attack happened. We had one case where a perpetrator took off his tank top, displayed a swastika [tattoo], and no words were said before he sucker punched an African-American male in a bar. The victim hit his head on the concrete and was brain damaged for life. We filed hate crime charges after looking at the evidence, including white supremacist paraphernalia we found at his house. So we have to look at the totality of the circumstances.
Still, we do encourage people to report slurs and encourage the police to take reports, because we see some people who feel empowered that they can't get arrested just for saying a slur. And then it leads to vandalism or violence.
NIOT.org: Describe some of the challenges you face in your work prosecuting hate crimes.
Oscar Garcia: Most experts agree there's a lot of underreporting of hate crimes both in California, as well as nationally. From the victim's perspective, sometimes they may be very fearful because of retaliation. So one of the challenges is trying to get the victims to cooperate. Another is identifying the perpetrators because attacks are often committed by groups and occur at night, and victims often have a difficult time identifying the perpetrators. So for every reported incident in which we're able to identify a suspect, we have at least maybe 10 times as many where the victims are unable to identify their attacker. And unfortunately in these instances, the case goes unsolved. The apprehension rate of perpetrators for my own local county averages out to about 10 – 15 percent. In comparison, for other crimes, perpetrators are typically apprehended in at least 50 percent of cases. Then, even when we are able to identify perpetrators, it's challenging to try these cases in front of twelve jurors, members of the community, to get them to understand why these cases are so important to prosecute and treat differently. It's the only time where the prosecution is required to prove motive for the crime. Every other crime, including murder, the prosecutor is not required to prove motive.
NIOT.org: What role can law enforcement play in helping victims feel less frightened and more supported?
Here in San Diego we have mandatory education for police officers. I teach, with a police detective specializing in hate crimes and a representative from the Anti-Defamation League, new recruits at the police academy. We try to educate them about what hate crimes are about, how they can better investigate them and the ramifications to the entire community. We talk about how these crimes deteriorate an entire community and why there may be additional penalties for these crimes. We're also trying to make it so that recruits are also tested on this, as they are required to do in many other classes at academy.
I think across the nation we should make bias crime training and testing mandatory of police officers. It's important that officers are sensitive to what hate crime victims experience and why a victim may not want to cooperate with the police. Maybe a victim comes from a country where they don't trust the police. Or here in our country, in the South in the 1960s, we had groups like the Ku Klux Klan infiltrating police forces, and older generations remember this history. So there's still a lot of distrust towards the police that we need to overcome.
In other cases, sometimes the victims don't think to highlight to the police when they're interviewed, "oh, yeah, by the way they yelled out these slurs to me." They may not see the significance of it until we question why did this happen or see some red flags, and then we go out and re-interview the witnesses. So a lot of it is education – education of our police, but also the greater community.
As part of what I do here, I also chair the San Diego Regional Hate Crimes Coalition, which brings together law enforcement agencies in San Diego County with community- based organizations to educate and respond to hate crimes. We also run separate intelligence committee meetings bi-monthly for just law enforcement, where we talk about ongoing cases and strategize and look at trends.
In addition, we hold trainings and also organize a yearly contest called Unity in Action at the local schools, rewarding students for their efforts emulating anti bias and tolerance. We want to highlight when youth are doing something very positive to try to combat hate crimes. One year we tied the contest in with an annual video contest organized by the San Diego County Office of Education. We helped get a new competition category created for videos promoting the message of tolerance and anti-bias, and the winner of it that year won one of the highest awards for the entire program.
NIOT.org: With San Diego so close to the U.S.-Mexico border, have you seen a rise in anti-immigrant organizing and hate crimes against Latino immigrants?
Oscar Garcia: We've had problems with the San Diego Minutemen, which has been identified by the Southern Poverty Law Center as a nativist group with confrontational tactics. These types of groups have spread out throughout the nation especially along the border cities, but we seem to have some of the most active groups coming out here trying to act like vigilantes. They claim they're doing it merely to exercise their political first amendment rights of wanting those that are here illegally out of the country. But organizations like Southern Poverty Law Center have documented some very hardcore white supremacist group members infiltrating the San Diego Minutemen in the past. And this group does cause a lot of problems here with law enforcement, which have to monitor their demonstrations at day labor sites. The Minutemen are out there sometimes intimidating both the persons trying to get work and those hiring laborers.
We've [prosecuted] some hate crimes targeting Latino immigrants. But unfortunately we've had more cases where we've had unidentified perpetrators. As is consistent with a lot of these cases, identification of the perpetrator can be a big issue.
NIOT.org: What drew you to do this work?
Oscar Garcia: What drew me to prosecution in the first place was I had a family member, my father, who was brutally murdered when I was child. That drew me to prosecution and police work, and to work towards helping crime victims, especially victims of violent crimes.
I've been a prosecutor for about twenty-four years now, and worked gang cases for a number of years. This current position prosecuting hate crimes is a very close cousin to the gang cases I would prosecute. Not always, but oftentimes the attacks in hate crimes are committed by groups. And unfortunately some of those groups are taking on a lot more behaviors of the traditional gangs and that's a concern to us -- that they are becoming more organized. So much so we're starting to look at prosecuting more of these cases also under the gang statutes, which carries even more significant penalties.
The mental trauma, in addition to the physical trauma, that victims of hate crimes and their families are left to endure, and the fact that these victims can be anybody, also draws me to work hate crime cases. In other crimes, a lot of times you see victims think back to the trauma, for example being robbed at an ATM, and they tell themselves, "I won't go to that ATM late at night anymore." But victims of hate crimes don't do anything to make themselves more vulnerable, and we see these attacks even happen in broad daylight or in a public setting. It's just they unfortunately crossed paths with someone who's prone to commit these crimes.
Local Lessons:
Law Enforcement in the Fight Against Hate
NIOT:
oscar garcia
bias crime
hate crime enhancement
prosecuting hate crime
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text:
Home / Book / The Thought War: Japanese Imperial Propaganda
The Thought War: Japanese Imperial Propaganda
by Barak Kushner
The Thought War: Japanese Imperial Propaganda quantity
"A major contribution both to the study of Japan and propaganda in the twentieth century. Barak Kushner meticulously and convincingly reveals the full scope of what was assumed to not have existed; namely an organized, multifaceted, and disturbingly resilient system of Japanese propaganda. Based on an impressive array of primary sources, many only recently uncovered, The Thought War provides a fascinating assessment of the complex and often contradictory processes of Japanese propaganda in an imperial context." —Michael Baskett, professor of film studies, University of Kansas
"Barak Kushner has written a first-rate study of propaganda in Japan during the Second World War. In a work of painstaking research, he takes his readers into the heart of wartime Japan, building a compelling argument that Japanese propaganda was sophisticated and effective in rallying the population and, after the war, seamlessly redirecting it to aid the transformation of Imperial Japan into the post-war democracy of today. The Thought War is a superbly competent piece of research that floods light into a place where only generalization, supposition, and stereotype had existed before." —Nicholas J. Cull, University of Southern California, editor, Propaganda and Mass Persuasion: A Historical Encyclopedia, 1500–present
"The Thought War is a unique and remarkable study. Barak Kushner reveals that Japanese propaganda during World War II was astonishingly sophisticated, diverse, and effective. What's more, the methods, messages, and makers of wartime propaganda proved just as successful at shaping public opinion in the wake of Japan's defeat as they earlier had been in mobilizing the nation for war. Kushner's insights on Japan's path from empire, through war, and into postwar reconstruction are provocative, compelling, and thoroughly convincing." —William M. Tsutsui, chair of the Department of Asian Studies, University of Kansas
The Thought War is the first book in English to examine the full extent of Japan's wartime propaganda. Based on a wide range of archival material and sources in Japanese, Chinese, and English, it explores the propaganda programs of the Japanese government from 1931 to 1945, demonstrating the true scope of imperial propaganda and its pervasive influence, an influence that is still felt today. Contrary to popular postwar rhetoric, it was not emperor worship or military authoritarianism that led an entire nation to war. Rather, it was the creation of a powerful image of Japan as the leader of modern Asia and the belief that the Japanese could and would guide Asia to a new, glorious period of reform that appealed to imperial subjects.
Kushner analyzes the role of the police and military in defining socially acceptable belief and behavior by using their influence to root out malcontents. His research is the first of its kind to treat propaganda as a profession in wartime Japan. He shows that the leadership was not confined to the crude tools of sloganeering and government-sponsored demonstrations but was able instead to appropriate the expertise of the nation's advertising firms to "sell" the image of Japan as Asia's leader and modernizer. In his exploration of the propaganda war in popular culture and the entertainment industry, Kushner discloses how entertainers sought to bolster their careers by adopting as their own pro-war messages that then filtered down into society and took hold. Japanese propaganda frequently conflicted with Chinese and American visions of empire, and Kushner reveals the reactions of these two nations to Japan's efforts and the meaning of their responses.
Barak Kushner, Author


text:
Home News Press Release
NPF Party will do everything to bring peace and for the welfare of the Naga people
Kohima, September 22: NPF Secretary General and MP Rajya Sabha, K.G Kenye asserted that NPF party will do everything to bring peace in the state and work for the welfare of the Naga people though some expelled and suspended members are creating some chaotic situation from outside the parameter of the party Constitution.
Addressing media persons at the NPF Central office on Thursday, Kenye said the party has done everything to bring peace in the state citing the instances where 12 elected members from Democratic Party, the forerunner of the NPF, resigned enmasse from the assembly after ceasefire agreement was signed between the GoI and federal Nagaland on September 6, 1964.
He also said that the regional party has made "peace" priority for the state and during all these years, the party has passed a resolution more than 50 times and said the party shall stand by it till honorable and acceptable solution was achieved.
"The party has sacrificed and refrained from participating in the 1998 General Elections heeding the call of Naga Hoho who desired peace and not election and also maintained the party for five years without single MLA in the legislative assembly," Kenye said.
He also said that if NPF party which has been the bridge between the Naga people and the Government of India for more than half a century, were to be dismantled, it would be a colossal loss to the people of the state and that no will be able to build the damaged bridge under any circumstance.
Reacting sharply against the statement made by MP Lok Sabha Neiphiu Rio who claimed that the party Constitution has been changed at the whims and fancies of the present leadership, Kenye said the Constitution amendment was done on July 13, 2015 after Central Executive Council of the party endorsed the amendments and authorized its president Dr. Shurhozelie to do the needful and that the members themselves voted in favour of the amendments.
"The president did not by-pass the CEC and so the allegation is baseless and unfounded," he said.
On the allegation that extra constitutional power was exercised by the president, Kenye clarified that under the 7th amendment Article V it mentioned about the powers and functions of the president and in the new constitution, 8th amendment, nothing was changed from 7th amendment under the "Powers and Function of the President".
On registering the dispute with ECI, Kenye said during the 2015 issue, ECI registered the case as "dispute case" within three days but during the present crisis which has been going on for more than two months now, ECI has not registered the case though the rebel group has asked the ECI to register as dispute case on August 27.
Therefore, Kenye said, there was no need to panic as ECI will determine if the party has violated its Constitution and will intimate the party if they register any complaints.
The MP was apprehensive that like in 2015, even this time the rebel might be intending to suggest ECI to freeze the party symbol, but exuded confidence that ECI will not act as such.
On the ultimatum served to NPF president Kenye reiterated that there was no provision in the constitution to impeach the president neither there was any law that empowers the legislators to "impeach" the party president.
However, he clarified, the President of the party, like all party functionaries, was liable to face disciplinary action to the extent of being expelled if the Disciplinary Action Committee finds him indulging in anti-party activities.
He said the NPF Legislature Wing, like any other subordinate Wings of the party, does not even have the power or competence to elect party functionaries even in village level, thereby he said the question of the President stepping down through the demand of the legislators does not arise.
The MP maintained that NPF was not a power monger and affirmed to stand by its principles and manifesto.
On whip issue, Kenye said the idea of having whip was to impose party principles and to ensure that legislators do not go out of the party constitution and said whip was an "appointed post" by the party.
He pointed out that legislators are not authorized persons to elect the Whip for the political party they belong to.
This Press Release was sent by NPF Bureau, who can be contacted at npfpressbureau(at)rediffmail(dot)com.
Ceasefire Agreement
Disciplinary Action Committee
Election Commission of Indi
K.G Kenye
naga hoho
Neiphiu Rio
NPF party
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