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Identification of biomarkers for the fruiting body formation in Myxococcus xanthus (2014)
Wolfram Lorenzen
Myxobacteria are on order of Gram-negative, soil dwelling bacteria that feature an impressive number of properties: they can glide on solid surfaces by using two different motility motors, subsist by preying on other microorganisms, are often producers of multiple natural products, and upon adverse environmental conditions, they are able to form multicellular structures called "fruiting bodies". The process, in which these macroscopically visible structures arise from independent single cells, has been the predominant subject of myxobacterial research for many decades. More precisely, researchers have strived for the discovery of genes, proteins and small molecules that act as signals, receivers or modulators of this complex process. In this regard, the species Myxococcus xanthus has evolved into the model organism due to its relatively simple and reliable handling in a laboratory environment. The research underlying this thesis focused on the identification and biosynthesis of lipids that may act as intercellular signaling molecules during the course of fruiting body formation of the myxobacterium Myxococcus xanthus as part of the "E-signal" system. In general, lipids containing branched-chain fatty acids with an uneven number of carbon atoms were found to be important players in this particular process. Nevertheless, their exact roles remain largely unknown as of this day. The first publication that is part of this thesis deals with an aspect that even strengthened the importance of role of iso-branched compounds in myxobacteria: myxobacterial metabolism is able to transform precursors of iso-lipids to isoprenoids. It addresses the question whether isoprenoids in general are important for fruiting body formation. Phenotypic analysis of mutants impaired in the biosynthesis of the central isoprenoid precursor 3-hydroxymethylglutaryl-Coenzyme A (3-HMG-CoA) from acetate and/or branched chain keto acids and their genetic and metabolic complementation clearly showed that isoprenoids are essential for fruiting body formation and confirmed that leucine derived isovalerate is an important source for isoprenoid precursors in myxobacteria. The second, and by far and away most tedious and sophisticated study, addressed the question as to how myxobacteria form fatty acid derived iso-branched ether lipids and to what extent they are important for fruiting body formation and sporulation. In a previous study, those unusual lipids were identified as specific biomarkers for myxobacterial development. No biochemical pathways to ether lipids specific for prokaryotes were known by then. In this study, a putative candidate gene that may be in involved in ether lipid biosynthesis was investigated. A combination of gene disruption and complementation experiments, phenotypic analysis and monitoring of ether lipid formation by means of GC-MS demonstrated its involvement in myxobacterial ether lipid biosynthesis and the importance of these lipids for the developmental process. Heterologous expression and biochemical testing of this gene together with in-silico sequence analysis and docking experiments confirmed the functions of its predicted domains. The discussion section provides an additional suggestion on how the ether bond formation is performed. Furthermore and most importantly, iso-branched ether lipids were found to be essential for sporulation but not for fruiting body formation. In summary, one or several molecules derived from an iso-branched alkylglycerol seem to play a role during sporulation in M. xanthus and a multidomain enzyme unique for myxobacteria is involved in their biosynthesis. The last manuscript addresses the complexity of lipid metabolism in myxobacteria. Prior to this work, there was limited knowledge about the exact composition of the myxobacterial lipidome and no method was available to monitor putative changes in the myxobacterial lipidome down to the single molecular species for studying lipid biosynthesis or regulation. An ultra-performance liquid chromatography coupled with mass spectrometry based method with electrospray ionization (UPLC-ESI-MS) utilizing standard equipment and a water/acetonitrile/isopropanol based eluent system proved to be geared for the construction of lipid profiles for wild type and mutant cells of M. xanthus and to show their differences. Fragmentation spectra based structure elucidation of lipid molecular species resulted in the identification of 99 molecular species comprising glycerophosphoethanolamines, glycerophosphoglycerols, glycerolipids, ceramides and ceramide phosphoinositols. The latter have never been described for any prokaryotes before. Three dimensional plots were created from the relative intensity differences of the single molecular ion species between the different samples to provide an efficient and versatile visualization of the data and enable the researcher to quickly detect differences.
Unnatural amino acids as novel probes for ultrafast 2D-IR spectroscopy of proteins : towards real-time investigation of biomolecular dynamics and vibrational energy flow (2014)
Henrike Müller-Werkmeister
Ultrafast protein dynamics are of great interest for understanding the molecular basis of biochemical function. One method to study structural changes with highest time-resolution starting in the femtosecond regime is 2D-IR spectroscopy. However its application to investigate protein dynamics both with high temporal and spatial resolution is currently limited to few biological systems with intrinsic chromophores. Spectral congestion, the contribution of many similar oscillators to the same signals, makes it difficult to draw conclusions about local structural dynamics in most other proteins. The aim of this thesis is to extend the application of 2D-IR spectroscopy to a wider range of proteins by introducing unnatural amino acids (UAAs) with azide or nitrile groups as site-specific vibrational probes, which absorb in the free spectral window between 1800 to 3000 cm-1 by using methods from chemical biology. In a comparative experimental study using FTIR and 2D-IR spectroscopy of single amino acids azidohomoalanine (Aha), a methionine analogue, was identified as preferred label. To demonstrate the application potential of UAAs as site-specific probes, Aha was then incorporated into different positions in a small globular protein. By using both FTIR and ultrafast 2D-IR it was shown, that indeed the local microenvironment as well as conformational fluctuations on picosecond timescale could be monitored with high spatial information. The azide moiety shows a shift of its absorption frequency depending on the polarity of its surrounding. Using this approach, different subensembles for the protein conformations with more polar and less polar environment around the vibrational probe can be distinguished. A second major application of site-specific labels is the study of vibrational energy transfer processes (VET), predicted to be relevant for allosteric communication in protein domains such as the PDZ domain. VET can be tracked with high spatial resolution using time-resolved IR spectroscopy by exciting a localized vibrational mode and probing separate modes in a two-colour 2D-IR experiment. To extend this kind of experiment to proteins, a specific donor-acceptor pair of two UAAs was introduced. It uses an azulene moiety as donor that can be excited in the visible range but deposits the excess energy by internal conversion into the vibrational modes of the ground state. In small peptides this VET pair was applied successfully, showing a distance-dependent energy transfer induced signal for VET through covalent bonds. These findings bare great promise for the direct observation of vibrational energy flow in proteins in real-time. Overall this thesis is the basis for extending the usability of 2D-IR spectroscopy to study structural dynamics in a wide range of proteins systems both with high temporal and spatial resolution.
Evolutionary genetics of bears and red foxes over phylogenetic and phylogeographic time scales (2014)
Verena Esther Kutschera
Climatic fluctuations during the Pleistocene (2.6-0.01 million years) have played an important role during evolution of many species. Cyclic range contractions and expansions had demographic consequences within species, provided environmental conditions for population divergence and speciation and enabled secondary contact and interspecific hybridization. These and other evolutionary processes have left genetic signatures in the genomes of affected organisms. Comprehensive and unbiased estimates of evolutionary processes can be obtained using genetic markers from different parts of the genome and by integrating population genetic and phylogenetic concepts. Suitable for studies on evolutionary processes and patterns over different evolutionary time scales are bears (Ursidae) and foxes (Vulpes), which occupy a wide range of habitats and evolved during the past few millions of years. In my thesis, I therefore used bears and red foxes as study species to investigate the genetic variation within and between species and to obtain estimates of evolutionary relationships and divergence times of populations and species that I interpreted in a climatic context. Further, I investigated population genetic processes during the evolution of bears. My thesis includes three publications and one submitted manuscript, spanning different evolutionary time scales - from evolutionary relationships and processes among species (phylogenetic time scales, Publications I & II), among populations and closely related species in a geographical context (phylogeographic time scales, Publications II & III), to ongoing processes within species (population genetic time scales, Publication IV). In Publication I (Kutschera et al. 2014, Mol Biol Evol 31(8):2004-2017), I studied bears at several nuclear markers from several individuals per species, complemented with markers from the Y chromosome. Using approaches based on a population genetic concept (coalescent theory) I obtained a species tree with divergence time estimates. Further, I studied two evolutionary processes in bears, interspecific gene flow and incomplete lineage sorting (ILS). This study contributed to the growing evidence that population genetic processes can be relevant on time scales up to several millions of years. In Publication II (Hailer, Kutschera et al. 2012, Science 336(6079):344-347), we complemented previous mitochondrial (mt) DNA-based inference of the evolutionary history of polar and brown bears with nuclear DNA. Coalescence-based species tree analyses of multiple nuclear markers from several individuals per species placed polar bears as sister lineage to brown bears and their divergence time to about 600 thousand years ago (ka). This contrasted previous mtDNA-based inference. We explained this discrepancy between mtDNA and nuclear DNA with interspecific gene flow between polar and brown bears. In Publication III (Kutschera et al. 2013, BMC Evol Biol 13:114), I studied range-wide phylogeographic events and their timing in red foxes. A synthesis of newly generated and published mtDNA sequences was analyzed using a coalescence-based approach with multiple fossil calibration points. Thereby, I validated the identity and geographic distribution of several red fox lineages and showed that red foxes colonized North America and Japan several times independently during the late Pleistocene (126-11 ka) and around the last glacial maximum (26.5-19 ka). In a comparison of my results from red foxes to brown bears and grey wolves, I identified similar phylogeographic patterns. In Publication IV (Kutschera et al., submitted to Biol Conserv), I found similar levels of genetic variability in vagrant polar bears that had reached Iceland compared to established subpopulations from across the range. Based on climate projections reported by the Intergovernmental Panel on Climate Change in 2014, polar bear habitat will markedly decline and become increasingly fragmented within the next decades. Dispersal will play an important role by connecting isolated subpopulations, thereby maintaining genetic diversity levels. My results indicate that vagrants could stabilize genetic variability when immigrating into established subpopulations. In conclusion, my thesis provided a deeper understanding of evolutionary genetic processes and patterns and their timing in bears and red foxes in a climatic context, which can have conservation implications. Further, I showed that processes like ILS and interspecific gene flow can be relevant over different time scales and are important aspects of evolutionary history. Thereby, my thesis contributed to the knowledge on the evolutionary history of several carnivore species and on evolutionary processes acting within and between closely related species.
Fast pulse shape analysis for AGATA (2014)
Tobias Habermann
High resolution gamma spectroscopy with sophisticated detector arrays significantly contributes to nuclear structure physics. The Advanced Gamma Tracking Array (AGATA) combines gamma tracking and pulse shape analysis to achieve an efficiency and quality of the spectra that could not be reached with spectrometers of the previous generation. Tracking of the photons interacting in the detector requires a precise knowledge of the individual interaction positions. The task of the pulse shape analysis is to provide a position resolution of better than $5mm$ FWHM, a value that could not be achieved by segmentation of the detector alone. As the signals induced on the electrodes of the detectors depends on the position of interaction, the charge pulses can be used to infer the interaction position. To be able to handle high rates, algorithms that are used have to be optimized to be able to process the data in real-time. Pulse shape analysis is the most involved part of the real-time processing and requires further improvement. This work is dealing with optimizations and improvements of pulse shape analysis algorithms. The Grid Search algorithm localizes the interaction position by comparing the measured pulse shape with precomputed shapes in a database to find the best fit. Two linear filters based on orthogonal transformations have been compared and it could be concluded that the one based on a singular value decomposition of the pulse shapes works best. It speeds up the pulse shape analysis by a factor of roughly $2-3$ (depending on how it is combined with the other modifications). Further, a new method to exclude most signals from the database as best fit has been developed based on the principle of lateration. Most interaction positions can be excluded by means of a fast check and for single interactions on average only $34.8\%$ of all signals from the database have to be compared to the measured one. The overhead introduced by the method is negligible and the reduced number of comparisons almost direclty translates into increased efficiency of the algorithm. A similar method could also be applied for double interactions. Two or more interactions taking place in the same segment require special treatment as the measured signals cannot be directly compared to signals from the database. A new method to calculate the figure of merit that quantifies the fit in case of a double interaction has been introduced. Compared to the unmodified algorithm the new method finds the best fit for double interactions roughly two orders of magnitude faster. Actually, the time required to localize double interactions is almost the same as for single interactions. Apart from optimizing the algorithm, also the achievable position resolution was investigated. It strongly varies inside the volume of the detector and it crucially depends on the shape of all signals in the database and the amplitude of the noise present in the measured signals. As a first step towards a precise analytic expression for the position resolution, an estimate for the probability to find the correct position has been derived.
Chopping and transport of high-intensity ion beams (2014)
Christoph Wiesner
In this thesis, a novel 257 kHz chopper device was numerically developed, technically designed and experimentally commissioned; a 4-solenoid, low-energy ion beam transport line was numerically investigated, installed and experimentally commissioned; and a novel massless beam-separation system was numerically developed. The chopper combines a pulsed electric field with a static magnetic field in an ExB or Wien-filter type field configuration. Chopped beam pulses with a 257 kHz repetition rate and rise times of 110 ns were experimentally achieved using a 14 keV helium beam. Due to the achieved results, the complete LEBT line for the future Frankfurt Neutron Source FRANZ is ready to deliver a dc or a pulsed beam. At the same time, the LEBT section represents an attractive test stand for the study of low-energy ion beams. It combines magnetic lenses, which allow space-charge compensated beam transport, and a chopper system capable of producing short beam pulses in the hundred nanosecond range. Since these beam pulses are transported onwards, their longitudinal and transverse properties can be analyzed. The pulse duration and time of flight are well below the rise time for the space-charge compensation through residual gas ionization. This opens the possibility for dedicated investigations of the transport of short, low-energy beam pulses including longitudinal and transverse space-charge effects and of relevant issues like the dynamics of space-charge compensation and electron effects in short pulses.
Open heavy flavor and other hard probes in ultra-relativistic heavy-ion collisions (2014)
Jan Uphoff
In this thesis hard probes are studied in the partonic transport model BAMPS (Boltzmann Approach to MultiParton Scatterings). Employing Monte Carlo techniques, this model describes the 3+1 dimensional evolution of the quark gluon plasma phase in ultra-relativistic heavy-ion collisions by propagating all particles in space and time and carrying out their collisions according to the Boltzmann equation. Since hard probes are produced in hard processes with a large momentum transfer, the value of the running coupling is small and their interactions should be describable within perturbative QCD (pQCD). This work focuses on open heavy flavor, but also addresses the suppression of light parton jets, in particular to highlight differences due to the mass. For light partons, radiative processes are the dominant contribution to their energy loss. For heavy quarks, we show that also binary interactions with a running coupling and an improved Debye screening matched to hard-thermal-loop calculations play an important role. Furthermore, the impact of the mass in radiative interactions, prominently named the dead cone effect, and the interplay with the Landau-Pomeranchuk-Migdal (LPM) effect are studied in great detail. Since the transport model BAMPS has access to all medium properties and the space time information of heavy quarks, it is the ideal tool to study the dissociation and regeneration of J/psi mesons, which is also investigated in this thesis.
The phylogeny of the genus Gazella and the phylogeography and population genetics of arabian species (2014)
Hannes Lerp
Biodiversity is caused by a fundamental evolutionary process: speciation. When species can spread into new habitats and are allowed to colonize new ecological niches, speciation can become accelerated and is then called radiation. This can happen, e.g., when formerly separated land masses become connected. A prime example of such a scenario is the Arabian Peninsula that connects Africa and Asia since the Oligocene (approx. 30 Ma ago). Since then, the peninsula promoted several faunal exchanges between both continents. The mammalian genus Gazella is an excellent candidate for investigating this faunal exchange. Species are distributed on both, the African and Asian continent as well as on the Arabian Peninsula that is located in between. The aim of my thesis was to cast new light on the evolution and speciation of the genus and, furthermore, to evaluate the currently problematic taxonomy to infer suggestions for improved conservation actions for threatened gazelle species. Therefore, I investigated the taxon Gazella genetically and identified factors that promoted the speciation of this diverse genus. I assessed intraspecific genetic variability for species that inhabited the Arabian Peninsula to infer the past demography of those species and to estimate the history of species divergence and past population parameters. In the first part of my thesis I inferred a mitochondrial phylogeny based on cytochrome b gene sequences using samples of all nine extant species of Gazella and also of closely related taxa (chapter 2). Besides the monophyly of the genus Gazella two reciprocally monophyletic clades were detected that evolved in allopatry: one predominantly African and one predominantly Asian clade. Within both clades species pairs could be inferred with species being ecologically adapted to different habitats: one species is a desert-dweller (probably the ancestral character state combination), while the other one is adapted to rather mountainous and humid habitats. These adaptations also correlate with the behavior of the species with the mountainous forms being sedentary, territorial and living in small groups and the desert forms being migratory, non-territorial and living in larger herds. The second part of my thesis focuses on the Arabian gazelle species. In a study about G. subgutturosa I could show that the Arabian form G. marica (sand gazelle)—previously recognized as a subspecies of G. subgutturosa—is genetically distinct from the nominate form (chapter 3). Moreover, a phylogenetic tree based on cytochrome b gene sequences revealed a polyphyly of G. subgutturosa and G. marica with sand gazelles being more closely related to G. leptoceros and G. cuvieri of North Africa. Consequently, I suggested the restoration to full species level for G. marica corroborating earlier conservation practices of breeding both taxa separately in captivity. In case of G. dorcas such a genetic differentiation could not be detected (chapter 4). Despite the large distribution range from Mali in the west to Saudi Arabia in the east only low genetic variation was detectable in mitochondrial sequence data. Statistically parsimony network analyses revealed pronounced haplotype sharing across regions. Using a coalescence approach I observed a steep population decline that started about 25,000 years ago and which is still ongoing. The decline could be correlated with human hunting activities in the Sahara. Hence, hunting of G. dorcas (already in ancient times) had a much larger impact on gazelle populations than previously thought and even led to the extinction of the Arabian form of G. dorcas. In chapter 5 of my thesis I provided a rigorous test to genetically distinguish between the potential species G. gazella and G. arabica. Previously recognized as a single species mitochondrial sequence analyses provided first hints for the separation of both taxa. But without the investigation of nuclear loci the observed pattern could also be the result of male biased dispersal combined with female philopatry. Therefore, I amplified mitochondrial sequence markers and nuclear microsatellite loci for both taxa and found support for the earlier view of two separate species. No signs of recurrent gene flow could be detected between neighboring populations of G. arabica and G. gazella. The split of both species could be estimated one million years ago and the recommendation of breeding both taxa separately in captivity for conservation purposes is fully justified. Several populations of G. arabica suffer from a severe decline. In chapter 6 I asked whether the population occurring on the Farasan archipelago—being at stable individual numbers for decades—may serve as potential source for future reintroduction on the Arabian mainland, although the gazelles show a reduced body size. Analyzing the genetic differentiation of Farasan gazelles, a genetic cluster could be inferred being endemic to the archipelago. However, only approx. 70% of Farasan individuals were assigned to this specific cluster, while the others showed at least intermediate or even complete assignment to the mainland cluster. This indicates ongoing introgression that is probably mediated by human translocations of gazelles from and onto the islands. Considering the uniform dwarfism of Farasan gazelles, reasons for the smaller body size might be direct consequences of resource limitations, i.e., phenotypic plasticity. If the population decline on the mainland will hold on Farasan gazelles could serve as stocks for future reintroductions.
Formation of PGE 2 in the tumor microenvironment and its impact on tumorigenesis (2014)
Weixiao Sha
Tumor development usually follows predictable paths where tumor cells acquire common characteristics and features known as the hallmarks of cancer. Recently, additional characteristics have been added to these hallmarks since solid tumors are composed of a very heterogeneous population of transformed, formerly normal tissue cells and stromal cells, e.g. immune cells and fibroblasts. Compelling evidence suggests that stromal cells and tumor cells maintain a symbiotic relationship to build up the tumor microenvironment and to fuel tumor growth. In cancer therapies, common features of tumors such as unrestricted cell growth, suppression of immunological responses, and the ability to form new blood vessels (angiogenesis) have emerged as the main targets of interest. The lipid mediator prostaglandin E2 (PGE2) is known to promote all these features and thus, is connected to cancer progression in general. Its synthesis is triggered in response to stress factors or during inflammation. Inducible PGE2 production relies on the enzymes cyclooxygenase 2 (COX-2) and microsomal prostanglandin E synthase 1 (mPGES-1), which are simultaneously expressed in response to a variety of different stimuli and are functionally coupled. Inhibition of COX-2 with non-steroidal antiinflammatory drugs (NSAIDs) for cancer treatment is, however, limited by cardiovascular risks, since selective COX-2 inhibition disrupts the prostacyclin/thromboxane balance. Therefore targeting mPGES-1 downstream of COX-2 for PGE2 inhibition was evaluated in this work in different steps of carcinogenesis. Knockdown of mPGES-1 in DU145 prostate cancer cells revealed that the mPGES-1 status did not affect growth of monolayer tumor cells, but significantly impaired 3D growth of multi-cellular tumor spheroids (MCTS). Spheroid formation induced COX-2 in DU145 and other prostate cancer spheroids. High levels of PGE2 were detected in supernatants of DU145 MCTS as opposed to monolayer DU145 cells. Pharmacological inhibition of COX-2 and mPGES-1 confirmed the pivotal role of PGE2 for DU145 MCTS growth. Besides promoting spheroid growth, MCTS-derived PGE2 also inhibited cytotoxic T lymphocyte (CTL) activation. When investigating the mechanisms of COX-2 induction during spheroid formation, the typical tumor microenvironmental factors such as glucose deprivation, hypoxia or tumor cell apoptosis failed to enhance COX-2. Interestingly, when interfering with apoptosis in DU145 spheroids, the pan-caspase inhibitor Z-VAD-FMK triggered a Summary 12 shift towards necrosis, thus enhancing COX-2 expression. Coculturing viable DU145 monolayer cells with isolated heat-shocked-treated necrotic DU145 cells, but not with necrotic cell supernatants, induced COX-2 and PGE2, confirming the impact of necrosis for MCTS growth and CTL inhibition. As mentioned, in vivo tumors are very heterogenous mixtures of tumor cells and stromal cells e.g. immune cells. Hence, the interaction of the immune system with tumors was investigated in further experiments. When coculturing MCF-7 breast cancer spheroids with human peripheral blood mononuclear cells (PBMCs), only low levels of PGE2 were detected, since MCF-7 cells did not upregulate COX-2 during spheroid formation and did not induce PGE2 production by PBMCs. Under inflammatory conditions, by adding the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) to cocultures, PGE2 production was triggered, spheroid sizes were reduced, and numbers of high levels of granzyme B expressing (GrBhi) CTLs were increased, while CD80 expression by tumor-associated phagocytes was also elevated. Inhibition of CD80 but not CD86 diminished numbers of GrBhi CTLs and attenuated spheroid lysis. To determine the role of ctivation-induced PGE2 production, use of the COX-2 inhibitor celecoxib and the experimental mPGES-1 inhibitor C3 further increased CD80 expression. Addition of PGE2, the prostaglandin E2 (EP2) receptor agonist butaprost, and the phosphodiesterase 4 (PDE4) inhibitor rolipram reduced LPS/C3-triggered CD80 expression, confirming the impact of COX- 2/mPGES-1-derived PGE2 on shaping phagocyte phenotypes in an EP2/cAMP-dependent manner. In a spontaneous breast cancer model (MMTV-PyMT), mPGES-1-deficiency significantly delayed tumor growth in mice, confirming an overall protumorigenic role of mPGES-1 in breast cancer development in vivo. However in tumors of mPGES-1-/- mice, tumor-infiltrating phagocytes expressed low levels of CD80 similar to their wildtype counterparts. These data suggest that the immunosuppressive microenvironment does not allow for immunostimulatory effects by mPGES-1 inhibition without an activating stimulus. Evidences in this study recommend the application of mPGES-1 inhibitors for treating cancer diseases, since mPGES-1 promotes tumor growth in multiple steps of carcinogenesis, ranging from well-characterized effects of tumor cell growth to immune suppression of CTL activity and phagocyte polarization. Regarding the latter, blunting PGE2 during immune activation may limit the tumor-favoring features of inflammation and improve the efficiency of TLR4 based immune therapies.
Reprogramming of tumor cells : signaling events and phenotypes (2014)
Chul Min Yang
Cancer is a disease characterized by uncontrolled cell growth and the capacity to disseminate to distant organs. The properties of cancers are caused by genetic and epigenetic alterations when compared to their normal counterparts. Genetic mutations occur in oncogenes and tumor suppressor genes and are the initial drivers of cellular transformation (Lengauer et al., 1998; Vogelstein and Kinzler, 2004). In addition, epigenetic alterations, which influence the expression of oncogenes and tumor suppressor genes independently from sequence alterations, are also involved in the transformation process (Esteller and Herman, 2001; Sharma et al., 2010). Genetic alterations and epigenetic regulatory signals cooperate in tumor etiology. Glioblastoma multiforme (GBM) is a frequent and aggressive malignant brain tumor in humans. The median survival of GBM patients is about 15 months after diagnosis. Like in other cancers, genetic and epigenetic alterations can be detected in GBM. Genetic alterations in GBM affect cell growth, apoptosis, angiogenesis, and invasion; however, epigenetic alterations in GBM also affect the expression of oncogenes or tumor suppresser genes that increase tumor malignancy (Nagarajan and Costello, 2009). Reprogramming is a cellular process in which somatic cells can be induced to assume the properties of less differentiated stem cells. This process can be mediated through epigenetic modifications of the genome of somatic cells by the action of four defined transcription factors (Oct4, Sox2, Klf4 and Myc) or by the action of the miR 302/367 cluster (Anokye-Danso et al., 2011; Takahashi and Yamanaka, 2006; Takahashi et al., 2007) and result in the generation of induced pluripotent stem cells (iPS cells). Reprogramming of somatic cells by the miR 302/367 cluster can generate nontumorigenic iPS cells through the inhibition of the epithelial to mesenchymal transition (EMT), cell cycle regulatory genes and epigenetic modifiers (Lin and Ying, 2013).
Energy- and cost-efficient Lattice-QCD computations using graphics processing units (2014)
Quarks and gluons are the building blocks of all hadronic matter, like protons and neutrons. Their interaction is described by Quantum Chromodynamics (QCD), a theory under test by large scale experiments like the Large Hadron Collider (LHC) at CERN and in the future at the Facility for Antiproton and Ion Research (FAIR) at GSI. However, perturbative methods can only be applied to QCD for high energies. Studies from first principles are possible via a discretization onto an Euclidean space-time grid. This discretization of QCD is called Lattice QCD (LQCD) and is the only ab-initio option outside of the high-energy regime. LQCD is extremely compute and memory intensive. In particular, it is by definition always bandwidth limited. Thus—despite the complexity of LQCD applications—it led to the development of several specialized compute platforms and influenced the development of others. However, in recent years General-Purpose computation on Graphics Processing Units (GPGPU) came up as a new means for parallel computing. Contrary to machines traditionally used for LQCD, graphics processing units (GPUs) are a massmarket product. This promises advantages in both the pace at which higher-performing hardware becomes available and its price. CL2QCD is an OpenCL based implementation of LQCD using Wilson fermions that was developed within this thesis. It operates on GPUs by all major vendors as well as on central processing units (CPUs). On the AMD Radeon HD 7970 it provides the fastest double-precision D= kernel for a single GPU, achieving 120GFLOPS. D=—the most compute intensive kernel in LQCD simulations—is commonly used to compare LQCD platforms. This performance is enabled by an in-depth analysis of optimization techniques for bandwidth-limited codes on GPUs. Further, analysis of the communication between GPU and CPU, as well as between multiple GPUs, enables high-performance Krylov space solvers and linear scaling to multiple GPUs within a single system. LQCD calculations require a sampling of the phase space. The hybrid Monte Carlo (HMC) algorithm performs this. For this task, a single AMD Radeon HD 7970 GPU provides four times the performance of two AMD Opteron 6220 running an optimized reference code. The same advantage is achieved in terms of energy-efficiency. In terms of normalized total cost of acquisition (TCA), GPU-based clusters match conventional large-scale LQCD systems. Contrary to those, however, they can be scaled up from a single node. Examples of large GPU-based systems are LOEWE-CSC and SANAM. On both, CL2QCD has already been used in production for LQCD studies.


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Purcellville Farmers Market
Saturday, Jan 7, 2023 at 10:00 a.m.
250 South Nursery Avenue
purcellvillefarmersmarket.com
Season: Winter and Spring
December 2022 - March 2023
Saturdays,10AM - 1PM
Location: 250 South Nursery Avenue
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2 Massive Companies That Have Doubled Their Sales in 5 Years
David Jagielski, The Motley Fool
Two examples of massive companies that are worth more than $100 billion and that have still managed to double their sales over the past five years are Bristol Myers Squibb (NYSE: BMY) and Amazon (NASDAQ: AMZN). Pharmaceutical giant Bristol Myers Squibb has a market cap of more than $160 billion and a portfolio of blockbuster drugs that generate more than $1 billion in annual revenue. Bristol Myers also has a strong pipeline of potential treatments for more than 35 diseases.
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It's hard to be an older female artist. Look at the sexist snark thrown at Madonna
As a longtime fan, I've come to see that whatever she's being criticized for, that's what she's asking us to examine
Want to Buy a Home In 2023? 10 Cities to Consider
Image source: Getty Images I'm sure a lot of people would love to forget about the state of the housing market in 2022, but unfortunately, we've probably still got a ways to go before things significantly improve from high prices and high mortgage rates.
IBM Grows Free Cash Flow but Will Likely Miss 2024 Goal
Following the spinoff of its managed infrastructure services business, which removed around $19 billion of less-than-desirable revenue from the income statement, International Business Machines (NYSE: IBM) is a leaner and more focused company. Hybrid cloud, artificial intelligence, high-margin software, and consulting are the businesses that will drive revenue and profit growth in the coming years. Total revenue was up 6% adjusted for currency, with over 70% of that revenue coming from software and consulting.
Dame Esther Rantzen has said she is remaining "optimistic" after revealing she has been diagnosed with lung cancer.
Life Time Miami Marathon and Half Marathon off-and-running right now. Stay tuned for winners
The Life Time Miami Marathon and Half Marathon participants took off down Biscayne Boulevard at 6 a.m. Sunday and will be racing for hours.
PARIS, January 29, 2023--Regulatory News: TotalEnergies (Paris:TTE) (LSE:TTE) (NYSE:TTE) and Eni have completed the transfer to QatarEnergy of a 30% interest in exploration Blocks 4 and 9 off the coast of Lebanon.
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Professor Amirouche joined UIC after completing his doctorate at the University of Cincinnati in 1984. Sine then, he has gained national recognition for research in mechanical systems dynamics. Today, he is widely recognized for his work with flexible multi-body systems. His research concepts and inventions give drivers a solution to fatigue and chronic back pain, and aid doctors and patients in total knee replacement surgery and faster recovery.
Amirouche has also used his work to minimize traffic congestion. In 2002, UIC and the University of California at Berkeley were awarded $300,000 to investigate dedicated routes for automated vehicles, a solution for clearing Chicago's congested roads. Amirouche conducted UIC's portion of the yearlong study, including running an automated bus circulator system to serve the Chicago loop and examining freight interchanges using automated trucks to transfer containers between connections.
Professor Amirouche is the author of four books and has recently contracted with McGraw-Hill to write a fifth, "Fundamentals of Biomechanics," to be published in 2007. He also has written more than 50 articles in peer-reviewed journals and submitted more than 120 technical conference papers. Amirouche serves as contributor to McGraw-Hill's most popular dynamics book on the market, "Vector Mechanics for Engineers: Dynamics," and serves onteh Golf Digest Scientific Advisory Board, where he evaluates the design of golf clubs and balls from several manufacturers.
In addition to his work at UIC, Amirouche recently founded his own company, Ortho Sensing Technology. Years of research in orthopedic biomechanics and his work with the College of Medicine orthopedics department have proven to be a successful combination for Amirouche. In 2004, his company received more than $500,000 from Depuy Orthopedics, a Johnson & Johnson Division, to develop a wireless total knee repair device for balancing of the soft tissue during arthroplasty.


Technology in classrooms isn't anything new.
But the way our teachers are using it is.
Everyone learns at different speeds, and in different ways. Some students are visual learners. Others learn better by listening. Some thrive in groups, while others prefer working alone. Parents and teachers know there's no one-size-fits-all approach to teaching and learning. Technology tools allow students to work at their own speed, provide different ways to learn the same concepts, and give students the power to collaborate and share.
As a parent, you want to be in the loop. You want to know how your child is doing, and what you can do to help them succeed. You want to connect with your child's teacher, know which resources to use if your child needs help with homework, and provide additional learning tools at home. From e-mail and text messages to dashboards, homework portals, e-books and learning apps, technology provides the information and support parents want.
Teaching. Lesson planning. Grading. Tracking student progress. Connecting with parents. Teachers face a daily balancing act to make the most of a precious resource: time. Technology empowers teachers with tools to learn, manage, and instruct. Whether it's a means for improving a lesson or streamlining countless hours of paperwork, teachers deserve access to the tools of today that make their job easier, reduce administrative burdens, and give them more time for planning, teaching, and connecting with students.
Making sure schedules allow students to take the classes they need to graduate. Hiring great teachers for every classroom. Making tough choices on budgets. School leaders make decisions every day that impact teaching and learning. Technology helps them reduce time spent on paperwork, identify and solve problems, and improve communications with teachers and parents. That way, everyone can spend more time focusing on what really matters—each child's education.
Every day, educators are using technology to engage students, involve parents, and enable great teaching in their classroom. At home, parents are using technology to support their children and stay in the loop. We know technology can't solve every problem, but it can support teachers, engage students, and empower parents.
The Smarter Schools Project was launched to highlight the exciting ways that schools and families are using technology to meet their needs. In the process, we hope to spark a conversation among parents, educators, and innovators about their hopes, concerns and goals for technology in education.
Teachers and students are already doing amazing things in the classroom with technology. From providing new ways of learning, to creating more opportunities for communication and collaboration, teachers and students are using digital tools in inspiring ways.


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Fifa have handed Nigeria and Ghana stern warnings to fix their issues or they risk being hit with suspensions.
The tussle for power in the Nigeria Football Federation is still ongoing with Chris Giwa and Amaju Pinnick factions yet to settle their differences – a consequence which led to the delay in resumption of the Nigeria Professional Football League.
According to Fifa, Pinnick is the legitimate head of the NFF following his triumph in the election held on 30 September 2014, hence, Giwa must staff off before August 20, 2018.
However, Nigeria U20 women who have progressed to the last eight of the U20 Women's World Cup will be allowed to carry on provided they make the semi-final.
"Two decisions of the Bureau of the Fifa Council in relation to undue influence in the affairs of the Nigeria Football Federation and the Ghana Football Association have been notified on 13 August 2018," read a statement from Fifa.
"In line with art. 16 par. 1 of the Fifa Statutes, the Bureau of the Fifa Council decided that if by Monday, 20 August 2018, at 12:00 (CET), the Nigeria Football Federation (NFF) offices are not handed back to the legitimate NFF executive committee under President Amaju Melvin Pinnick, who was duly elected on 30 September 2014, the NFF will be suspended with immediate effect for contravening art. 14 par. 1 i) and art. 19, as well as art. 14 par. 1 a) of the Fifa Statutes. The suspension would be lifted only once the NFF, under President Amaju Melvin Pinnick and General Secretary Mohammed Sanusi, confirms that it has been given back effective control of the NFF and its offices.


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1981 International 14 Team Races and World Championships
Almost three months ago, I wrote about the three major championships I sailed thirty years ago in August/September 1981. I wrote three posts about the 1981 International Canoe Championships that took place in August of that year but, again, in a bout of procrastination, I have yet to mention the other two championships.
In mid September, 1981, on consecutive weeks, I raced in both, the International 14 Team Races and, the International 14 Worlds out of Annapolis. I teamed with Bill Moss on his Kirby IV.
For many years leading up to 1981, the International 14 class had considered the Team Racing Championship as the defacto World Championship (oddly enough there was no perpetual trophy) but, by 1981, changes were afoot. The class had held it's first World Championship in Alamitos Bay, California in 1979. The 1981 Worlds was to be the second World Championship for the class and there was a strong movement to move the class towards amalgamating the rule with the Australian 14 class.
However, in 1981, the International Team Racing Championship was still THE prestigious event in the class, even though it was basically a three country, English speaking affair (the U.S having a West Coast and East Coast team to make it a four team round robin with England and Canada). The East Coast had never won the International Team Racing Championship but in 1981, with the event in home town Annapolis and having the reigning 1979 World Champion, John Gallagher, the East Coast team looked poised to compete for the top spot.
And we did eventually win the Team Racing Championship, but it was a difficult road as every one of us on the East Coast Team had a race where we totally screwed the pooch; for me it was one of the races against the West Coast where I tried to sneak inside at a mark without an overlap and got shut out by Baird Bardason. Extremely mad at my stupidity, I withdrew and crossed my fingers that we could pull this race out with only three boats....and we did. It seemed race after race, one of us would step up to save the team's bacon. It was an extremely hard fought series against the Canadians, there were a couple of protests that went our way but, in the end, we prevailed. The first and only East Coast team to win the International Team Race series.
Mug shot of the 1981 East Coast International 14 Team after one of the races......
From Left to Right; Chris Price, Eric Arens, Bill Moss, Tom Price, Paul Weiss, John Gallagher, David Gallagher, Rod Mincher
The World Championship the next week started with three days of a hard 20-25 mph Northwester blow. It wasn't if you were going to capsize, it was when you were going to capsize. I remember a hard reach right on the edge of control when the rudder stalled out and stayed stalled. The rudder was turned, there was a nice rooster tail but no control. "Hang on!", I yelled at Bill, "No rudder!" right before the 14 headed up and rolled over. The breeze moderated toward the end of the week.... Bill and I had a couple of good races to finish mid teens which wasn't too different from where I ended up at the International Canoe Worlds a month earlier.
Below is a photo from Annapolis rag, "The Evening Capitol". Crew were on the English team; Alan Fitzgerald and Nick Burgin.
From an email from English team member, Andy Fitzgerald.....
"Yes it's me and my crew Nick Burgin (who went on to sail a FD successfully with Roger Yeoman before pulling out before the Seoul Olympics, to be replaced by another 14 sailor Neil Mcdonald of round the world fame)........It was still in my mind the windiest race ever - we all hid in the lee of the supertanker and the race really started there. My introduction to the cut and thrust of team racing, not to mention the Canadians who were getting on top of their game."
John Evans, member of the English team, added this comment which I've dragged over to the main post.
"Yes, indeed , it was a memorable event in 1981 - as we not only had 25+knots wind for one days racing in the Worlds, but also an Annapolis "Buster" with hail, rain and thunder one evening - it stopped the Naval Academy Band from practising, which was a relief! I won the windy day race, and did quite well overall.....Bob and Peggy Reeves hosted us. Andy Fitzgerald raced with a guy called Nick Burgin...my crew was called Pete Barr, who knew all Baird Bardason daughters really well!"
Alan Laflin emailed his recollections;
"Eric A and I have owned 2 14s together since the 97 Worlds and raced it in the Totally Dinghy regatta in September. We're both 72 (me next week) and we won the Century Cup in England in 2008. First non Brits and the oldest combined age ever. The 1981 picture in front of the Naval Academy was just after we won the first race of the Worlds and went downhill after that. I think we were 2nd in the US Nationals part of the Regatta."
Eric Arens emailed this clarification about the photo below;
"The picture is left to right reversed as you can see in the Naval Academy. I forget the photographer's name, but he lived in Annapolis; and he reversed the picture so that it would fit on the fold-out cover of Sailing World's predecessor magazine.
Your note on the team races is very good in stating that each of us really messed up at some time or other. I got disqualified before the start of one race when I was on port tack. I still do not know how little room a boat tacking to port has to give a starboard tacker so that the starboard tacker cannot change course and bear down on the port tacker."
And Mark Adams added a comment which I've dragged over to the main post;
"I think the b/w picture is indeed of Andy Fitzgerald from the UK. I used to run into him in England on business and we would always talk about the windy day of the Worlds. We managed to make it 3 miles or so downwind in 30, then hung out in the lee of an anchored tanker while the RC set the course. We both agreed that it was the windiest day of racing we'd ever had in a dinghy. And I'm from San Francisco and he's from windy ole England. Oh and the photographer's name who took that pic of me and Chris, Alan and Jim was Bob Dollard if I recall correctly."
On the picture below, West Coasties, Alan Laflin and crew Jim Anderson (foreground) with Mark Adams and Chris Benedict (3rd in the Worlds) to weather, beating back to SSA after the days races. Photo from Sailing World.
And this article from "The Evening Capitol" fills out who made it to podium finishes.......
The following email is about some of the shenanigans that took place at the informal Team Race party. I missed the good bits because of a very pregnant wife. (I've tried to keep the players somewhat anonymous.)
"The relay race on the big lawn at Tom Price's house that resulted in Ed.... from Canada and me having to run against each other because the Canadians kept the $1 entry fee from each country and wouldn't pay up to the East Coast when we (East Coast) had won. Since the course included chugging a beer and stripping down to nothing at the far end of the lawn before returning, the opportunity was realized and taken to remove my clothes. Anyway, in the confusion we did not get the money. But justice was served, although years later. About the year 2000 I was at an airport in British Columbia getting ready to get onto a helicopter to go to a lodge in the mountains to back county ski for a week when I heard a call "Eric......" I looked over and saw Ed.... and immediately said "You owe me $10." He bought a round of drinks at the lodge, but the rest of the East Coast never did get rewarded for winning."
Labels: 1981, International 14
Music Whenever: Quelqu'un and Lorenzo "Lay Lady Lay"
I like this cover of the Bob Dylan tune. Never heard of the duo though.
And I like the weirdness; the trailer park, the bikes and the band jam emerging from the coverlet.
(The NSFW cover photo has nothing to do with the video, just a simple hook to let our animal desires move that finger over the mouse to click the play button.)
LayLadyLay from Patrice De Bruyne on Vimeo.
Laser Heavy Air Slalom
I tweak on the "The Kirby Sailboat formerly known as The Laser" class every so often, but you can't knock the world class quality of these dinghy sailors. The Laser Slalom was a big deal in the 70's but stopped as a competition after about five years. I remember 30 years ago, they set a Laser Slalom up in Annapolis.... there was some breeze and my attempts to master the close set marks, particularly gybing, was very ragged to say the least.
Thankfully someone resurrected the Laser Heavy Air Slalom this year in San Francisco and this great video captures some of the highlights and lowlights (like the almost total submarining about 39 seconds into the video).
Laser Heavy Air Slalom from Tj Stacy on Vimeo.
Labels: Blasting, Laser, Oh Sh#%t, Oops
Header Photo: 2010 Cooper River Fall
Classic Moths on the hard with "The Kirby Sailboat formerly known as the Laser" fleet racing in the background.
Labels: Header Photo
Racing on the Gorge
A neat compendium of video shorts of dinghy and foiler racing on the Columbia Gorge. (There's even an old fart handling the Laser downwind with aplomb.)
Sail the Gorge! from Bill Symes on Vimeo.
And going back in the Earwigoagin archives are two videos of the insane Laser Long Distance Race in the Gorge. Click over here and over here .
Labels: Blasting, Foilers, Intercollegiate Sailing, Laser, Olympic Classes, Other sailing dinghies
Skate Sail in Saskatchewan
Holy Moly Batman, someone already has ice in North America.! But not much wind!
Slow-time Skate Sail from Village Rainbows on Vimeo.
Labels: Ice boat
Why a Classic Moth is Better than a Laser
Upon writing a post about Cooper River 2011, I was reminded that I had yet to write a post that I had intended for last year. The post was supposed to be in response to an incident at Cooper River 2010 (as I have mentioned before, this blog is all about timeliness!).
Last year at Cooper River, just before launching my Classic Moth for the day, I was rounding the corner of the clubhouse when I overheard a conversation between two Laser sailors. Both of them were looking over at our congregation of Classic Moths when one of them said;
"I understand why someone would sail a foiler Moth, but I can't understand why someone would sail one of these", as he nodded his head toward our fleet.
I didn't respond, just smiled to myself and kept going. It wasn't the time or place, I had to get ready for the day on the water. But the gauntlet had been thrown down. It just takes me a while to pick it up.
Tillerman has merrily gone down this path before with several posts on "Reasons why such-and-such class is better", the Sunfish/Laser being a target in his post Ten Reasons Why Sunfish are better than Lasers , and then with the Force Five/Laser with Seven Reasons Why Force Fives are Better than Lasers . (Tillerman even had a tongue-in-cheek, self flagellation post, Seven Reasons to Hate Laser Sailors, but that isn't germane to this post.)
I can come up with five strong reasons why I persist in sailing the Classic Moth and not return to the Laser Borg (though you will find me every once in a while racing a Laser.)
Classic Moths are so much Lighter
Every time I sail a Laser I dread carrying an enormously heavy Board Bag to the boat, wrestling an enormously heavy mast with sail attached into the mast tube, heaving a heavy Laser hull onto a dolly, and staggering backwards up the inclined float with the Laser on dolly. Admittedly this may be my age talking but, in reality, I have the Classic Moth to compare it too. The Classic Moth minimum hull weight is 75 lbs (34 kg), though most of my Classic Moths have weighed closer to 90 lbs (41 kg). This is still 40 lbs (18 kg) lighter than a Laser! My heavier Classic Moth aluminum mast weighs 10 lbs - 4.5kg ( (carbon masts are even less). I think a Laser mast is 18 lbs (8kg). My blades, which are wood, nothing special, feel to be 1/2 the weight of a Lasers. All this lightness of a Classic Moth makes the off the water chores of rigging and moving and loading boats that much more enjoyable than a Laser. And on the water, that lightness of the Classic Moth plays into reason #3 below.
My Classic Moth fits Me
The Laser has a flat deck, great for production but very uncomfortable for hiking. The Laser has a very raked rudder which develops a lot of helm fast with any bit of heel. The Laser now has "improved sail controls" but the cleats are still forward of the daggerboard, which is a long way to reach. The Laser has a marginal bailer which, upwind, still leaves the cockpit full of water in a breeze. With the Classic Moth, I can change all this.... or not. If I don't like a flat deck, I can build a different one, or if I like a flat deck, I can build a flat deck. And so on down the line. For the most part, in a Classic Moth, if I don't like it, I can change it. And fitting the boat to me makes it more enjoyable to sail.
The Classic Moth is more fun to sail
Anytime I get into a Laser, it feels like an aircraft carrier compared to a Classic Moth. The Classic Moth, with it's shorter length and lighter weight is just more lively on the water. I have a rudder which is tuned to be very balanced so it has a great feel upwind. Offwind, with it's lighter weight, the Classic Moth lights up in a breeze. There is no doubt that the Laser is considerably faster than the Classic Moth (except maybe in drifting conditions) but I just enjoy sailing the Classic Moth more. A friend of mine said there were two types of sailboat racers; those that were more interested in hard core racing, the intensity and the competition,and those that were more interested in racing boats that have certain appealing characteristics. Throughout my sailing career, I've straddled those two groups but, as I have aged, my interests have slid over from the hard-core racing into "I race in this class because I appreciate how it sails".
Classic Moths are Cheaper
My Maser I picked up for $500 (no rig) and I have another hull in my collection I picked up for $350. Complete Classic Moths with National Championship speed have been had for under $1000. Used Classic Moths going for more than $3000 are unheard of (but if you want to build your own, you'll probably spend around $3000 when all is said and done). Granted we have no professional builder, so it's a little harder to take your check book out and purchase one, but a little leg work will usually find some Classic Moth that will fit your bill.
The Classic Moth People
You stay with a class because you fit in with the people. The Classic Moth is diverse, the people are diverse. And laid back. Because I did the Laser thing in my twenties and I don't need that kind of intensity year round in my sailboat racing. I get tired of talking about that left shift I missed at the weather mark to drop me behind 25 Lasers. I've been missing those shifts for many years and I just as soon talk about that Vintage 1940's Moth you've restored or that Savannah Wedge design you pulled out of retirement, or your trip to Sweden, or tell me about the latest A-cat developments.
Here's John Z's [Gen II Mistral Mothman] reasons why a Classic Moth is better than a Laser:
"I sail both a Laser and a Mistral Classic Moth and racing the Classic Moth is definitely more fun, mainly because Moths are much lighter so they accelerate more. When you're sailing you feel acceleration more than you feel velocity (F=ma). Classic Moths leap frog down the reach legs so we sail triangles a lot.
"Moths also have more controllable rigs. In 20+ knots I can flatten out the Moth sail, put the traveler down and keep blasting along. In a Laser, Radial included, I'm struggling - at 140 lbs.
"I still enjoy the Laser because we sail all summer at my club on Tuesday nights with 15+ boats on the line every week. We only race Moths five or six times a year and it takes some driving (NJ, NC, FL, MD).
"If you like to putter on boats and don't mind driving you should definitely consider the "more fun" boat ...
Click here to have a look at the various designs of Classic Moth - including some you can build!
Photos of some of my Classic Moths:
My Gen II Energizer (mod Stockholm Sprite -plywood) showing some blue masking tape remaining post-painting.
My Gen II Tweezer (strip planked - own design).
My Gen I Maser (Laser cut-down to fit Classic Moth rule).
Why is a Laser faster than a Classic Moth?
Posted by Tweezerman at 11:42 AM 3 comments
Labels: Blogmeister, Classic Moth, Laser, Tillerman
Music Whenever: John Mellencamp "Pink Houses"
Another great tune I file under the genre "Americana" rock.
There's a black man with a black cat
Livin' in a black neighborhood
He's got an interstate runnin' through his front yard
You know he thinks that he's got it so good
And there's a woman in the kitchen
Cleanin' up the evenin' slop
And he looks at her and says
"Hey darlin', I can remember when you could stop a clock"
Oh, but ain't that America for you and me
Ain't that America somethin' to see baby
Ain't that America home of the free
Little pink houses for you and me
There's a young man in a t-shirt
Listenin' to a rockin' rollin' station
He's got greasy hair, greasy smile
He says, "Lord this must be my destination"
'Cause they told me when I was younger
"Boy you're gonna be President"
But just like everything else those old crazy dreams
Just kinda came and went
Well there's people and more people
What do they know know know
Go to work in some high rise
And vacation down at the Gulf of Mexico, ooh yeah
And there's winners and there's losers
But they ain't no big deal
'Cause the simple man baby pays for the thrills, the bills
The pills that kill
Labels: Americana, Music for Fridays
Cooper River Fall 2011
The more astute among those of you who still read my drivel after all these years; you may have noticed that I haven't been sailing my Classic Moth that much...... and you're right! I last raced my Maser in June and neither my Maser or any of my project Classic Moths have been dipped in water since.... that is until last weekend. My job as a sailmaker for the US Naval Academy went away in July, it was a temporary assignment after all, and I, in trying to navigate what is indeed a difficult job market, I haven't been able to wrap my head around racing my Classic Moths. There have been other distractions as well; a wedding and other temporary work. Well, last weekend I bundled my trusty Maser onto the trailer and made the trip up to Philadelphia with my Mothboater travel mate, John Z. The river provided a nice 5-7 knot, typically fluky breeze, the temps were close to 60 F, the sun was out, not a cloud in the sky, a gorgeous afternoon. We raced 6 short races, I finished 3rd out of 5 and had a blast. After the racing, as is the custom, the Mid-Atlantic Mothboaters spent time sampling weird and wonderful beers, orchestrated by Mike and Barbara Parsons. We had the Dogfish Pangea, a spicy beer with a strong orange taste, Fegleys Imperial Pumpkin, my review of which has been relegated to my Pumpkin Beer post , Samuel Smith Winter Ale with a typical English maltiness and my cheaper but still tasty, Farmhouse Ale Stout. A picture from left to right; George, who is the author of the blog Mid-Atlantic Musings, Mike, a friend of Mike's who only likes watered down lite beer but we still let him join the party, Barbara, who brought out the Imperial Pumpkin Ale, and the blogmeister, still sporting his zinc oxide sun screen. (John Z is behind the camera.) One of the neat things about Cooper River is that it has the feeling of being in a quiet suburban setting but you can see the skyline of Philadelphia poking out above the treeline. Here is the skyline behind the massive rowing center building on Cooper River. In my dotage, I pick my fall days I want to go sailing and you couldn't pick one better than this.
Labels: Beer, Blogmeister, Classic Moth, River sailing
Music Whenever: Tribute "While My Guitar Gently Weeps"
From Wikipedia :
In 2004, George Harrison was inducted posthumously into the Rock and Roll Hall of Fame as a solo artist. "While My Guitar Gently Weeps" was played in tribute by Tom Petty and the Heartbreakers Tom Petty, Jeff Lynne, Steve Winwood, Steve Ferrone, Marc Mann, and Dhani Harrison, along with fellow inductee Prince.
Actually this serves two purposes; it allows me to cleverly connect this following music video into the current mess in the Laser class.
In the mid 90's, Prince decided to change his name into a symbol that couldn't be printed. Everyone had to refer to him awkwardly as "the artist formerly known as Prince".
As Tillerman notes, in 2011, Bruce Kirby decided to rename his Laser design to "The Kirby Sailboat". Now everyone should refer to Tillerman's favorite sailboat (again awkwardly) as "the Kirby Sailboat formerly known as the Laser".
Anyway, great music video, particularly when "the artist formerly known as Prince" does his solo at the end.
Update: Baydog has kindly posted another version of "While My Guitar Gently Weeps" (as well as some Bob Dylan) over here . Also, in the comments, Tillerman suggests going to YouTube and watching a live version with George and Eric Clapton done during a 1992 Japanese concert.
Kids and Parents and Sailing
A few years ago, Nick Hayes published a book "Saving Sailing; full of suggestions to grow the sport. Tillerman wrote a post about his thoughts on the book over here . One of the suggestions Nick made was that parents should actually go sailing with their kids rather than dropping them off at the club to be herded around the water by some college aged instructors. I think there is some merit in Nick's suggestion, though I am not one that can be held up as an example; I was much more into my singlehanded sailing as my kids were growing up and not so much into taking them out. Understandably my kids went off and found other activities they enjoyed more.
Here are three very different videos with parents/adults sailing with their kid(s).
The first one has a young tyke, somewhat overwhelmed, bombing along close to the water with his parents in a Hobe Tri-Foiler.
Salim goes sailing August 2011 from AaronDavis on Vimeo.
The second video has mom crewing for her two kids, one steering and one tending the jib on an older wooden catamaran (by the look of the crossbeams it may very well be an old Prout Shearwater, but I'm guessing this is Australia so it may be some home grown design). The video ends with what looks like Dad and maybe an older son, double trapezing on a modern skiff type vessel.
Sailing at the richmond river sailing club and rowing sunday 6/11/2011. from Callum on Vimeo.
And for Baydog, who has written about his family sailing on an E-scow , here is a kid steering an E-scow. By his grin from ear to ear, an experience he'll remember the rest of his life. (And plenty of grins and laughter from the old farts too!)
I've got to add this one from a fellow blogger. My2Fish, blogger about Sunfish sailing, music, and Michigan State football , points to his video of sunset sailing on his Sunfish with his oldest son. Beautiful colors in this video.
sunfish sailing with my son from my2fish on Vimeo.
Labels: catamarans, Parents and Kids, Scow
Music Whenever: Bon Iver "Holocene"
Another recommendation from Robyn.
Supposedly Bon Iver fell in love with the beauty of Iceland and I have never seen a better music video in capturing stunning natural wonders. Combine this with Bon Iver's haunting acoustic sound to create something special.
BON IVER "Holocene" from nabil elderkin on Vimeo.
Header Photo; 1888 Topsail Cutter "Elf"
I wrote a post in June about the Elf Classic Yacht Race, a cross-the-Chesapeake Bay Classic Yacht Race. This is the restored 'Elf', off Annapolis Harbor, waiting for her skipper to row out so she can get underway in the race.
Labels: Annapolis, Classic Sailboats, Header Photo, Keelers, Traditional Sailing Craft
Volvo Ocean Race: 2011 Edition
The around the world Volvo Ocean Race starts tomorrow. I think those Volvo guys are absolutely nuts, right up there with those crazies that jump off mountains in those flying squirrel suits and then zoom feet from the rock face. I would be hard pressed to name another endurance event that is as long and draining as the Volvo Ocean Race. American Kenny Read hits the nail on the head with this interview.............
Labels: Keelers, VOR 2011-12
1981 International 14 Team Races and World Champio...
Music Whenever: Tribute "While My Guitar Gently We...


Basic operations in food engineering, packaging, conversion, and separation operations.
04The student will be able to solve material and energy balances in the systems involved in the typical processes of food engineering.
The evaluation is done through daily monitoring and participation in class, with the resolution of the problems, this represents 20% of the final grade.


Coverage by Bhat Dittakavi of Variance.AI on "AI Deep Learning" by Jerric Lyns John, CEO of a Nucarbn at T-HUB on 7th March.
Speaker Jerric from Bangalore, with his trademark pony tail and business acumen mixed with occasional swear words, let his love for AI speak.
His best quote for the evening: "Only when you imagine a promise land, you will eventually make it there. Being futuristic is the key." He has a wearable startuo called Nucarbn.
They are coming up with a wearable device similar to fitbit but it has ability to track your emotion and understand and the human inside you.
At some point the network wakes up! Singularity.
The driving force in everyone's life is emotion.
Fear is negative and the joy on the other side is positive. These are two extremes. We could only capture few emotions and not all.
Emotions lead to actions. At times, we think with our emotions.
Next revolution is quantification of emotion, not just steps.
-Directly linked to motion. Neural projections.
-Hands sweat when you are nervous.
Enable AI to target you as a person. Custom AI. Tailored AI to understand you from you. Your activity that you do affects your heart and your skin. More beats, more heat. Less beat, less heat.
-Emotionless. Body is at peace.
Fitbit is goal driven and is disconnected with your current emotion.
Apple Watch is going down. Wearable devices are becoming fad. It is more about understanding the person now. Enable a system that understand the person.
2020: When 5G enabled network is out there with latency of 1ms. Connectivity is no issue. There would be billions of devices. Hope to see system controlled IoTs. Most of these IoTs are controlled manually.
See home automation systems. They are lying wasted after initial excitement. Automation without understanding the person is going to go down. We track emotion. We can't improvise the person's life otherwise.
In wearable device industry, only first two months create excitement. Later on readings remain the same as they see the same readings and hence stop seeing value in the device. This is not core value. No life improvisation and hence wearable device dusts the shelves.
Integrating home control and personal fitness. This is our goal.
Most of the wearable devives understand your sleep pattern. But their advice is no good.
How long do you interact with a chatbot? What if you have a wearable that adjusts room temperature based on your body temperature right after your return from morning jog.
We are releasing a fully connected wearable device in 4 months. We use bio-impedence systems.
We use kind of wireless charging. No batteries.
AIBRAINDUMP.COM session in Bangalore is coming on March 24th at midnight. Join us. We bring Valley guys there on skype. We are bringing some of the best Startups there. Join us.
We have a public initiative. In AI, we have NLU focus beyond what capabilities we have today. It is about making human dialogue systems more natural. When you have multiple rounds of discussions, what kind of action items we can do?
Anafora and diactic ambiguities that we are solving. We try to understand the temporal flow.
NLP is all about accuracy. We modified it with specific domains that we concentrate. We do lots of pre processing and post processing both in syntax and semantics. Not just syntax.
Jerric) Design thinking and user experience for users is cut from PC mobile to wearable to our case of zero interaction design. Don't ask the person to do it, let us do it by ourselves.
Accuracy matters most for medical devices. FDA approval on Wearable clothing is easily possible.
Q) You are into personal assistance that doesnt get you bored. Right?
Q) I work in Kavitha Vemuri lab at IIIT and we have many devices. Value is one thing and how you interpret is one thing.
Jerric) Sleep tracking can't be understood by the device we have. Club the sleep data with brain waves that are linked with sleep pattern. This is how we are getting things cross checked.
First feed of data comes and we learn. Then we take conversational feedback from the user. Then we apply probabilities.
We use different streams of the data for self training the machine.
Lab to reality, percentage of accuracy goes haywire. Deep learning with the time series and waveforms can extract more data. We can see the difference between standing and sitting.
You enable the system to work. Before we used sygmoid functions. Now we don't know. My co-founder is asking systems with memory in it.
How do you provide user holistically proper experience?
It takes two days to understand your habits. Understanding the person helps us to improve the life.
Our friend has a policy in his company to read at least 8 research papers. By now all the interns are able to read every day 8 research papers. Now they are doing great job.
When we do, we keep it updated. We are getting insights we never had.
We do normal classification earlier and we are doing deep learning now.
Q) Do we track gender relevant emotions?
This one we are targeting now is for the ones with white collar jobs. They are early adapters and ok to go through the pains.
Q) Lab data versus field data?
Lab data is controlled. We recalibrate the field data.
Q) What kinds of emotions?


Let's talk about the issues around proprietary software and closed ecosystems. Using them keeps your embedded devices enclosed. However, some may come to think there is no better option out there, especially when they've seen how other people have tried to break the proprietary bond but failed. Yes, looking at you Munich! Meanwhile the world continues to innovate at stellar speeds, and you constantly play a game of catch up.
Time was obviously not on Munich's side, but that's no reason to go backwards. Perhaps it's helpful to think of open source software like a cute puppy: it needs a lot of attentionbut if trained properly it can grow into an amazing friend. Sure, open source has no license tied to it, but if we leave it alone in the woods, it will require more grooming down the road, or in the case of the Munich project, a conversion of 9000+ machines back to Windows.
This equates to a great deal of work for every development team, open source savvy or not. An easy solution would be to turn to the experts. They will give you the peace of mind that comes with support and maintenance for your software, but also protection from other legal liabilities, as well as the elimination of lengthy certification processes.
If your developer team is up to the task of building in functionality and they still want to get their hands dirty, they should do that, but just that. Concentrate on productivity, on features that actually make a difference, instead of recreating the wheel and watching maintenance costs soar over time. When faced with the build vs. buy decision, let experts like Wind River help you evaluate the options to consider in fully understand what it takes to maintain a roll-your-own solution down the road. For years, Wind River has been working with countless customers, and helping them bring their devices to the market while staying on schedule and avoiding unpredictable soaring costs. Wind River Linux receives constant attention and care, with regular fixes and updates delivered safely through an automatic electronic delivery system that is easy to use. Also, when dealing with the unexpected, hot fixes are available instantly, within 24 hours. For example, this is what we've done with the recent OpenSSL Heartbleed and Bash Shell Shock vulnerabilities.
Essentially, Wind River can help keep the "puppy" well fed, perfectly groomed, and immunized against all threats. So, will your project flourish with proprietary software or are you interested in unlocking the open source advantage?


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text:
Selling Austerity With Chutzpah
Federal Opinion
By Deborah Meier — October 25, 2012 3 min read
Deborah Meier is a teacher, author, and founder of successful small schools in New York City and Boston.
Editor's note: See addendum added by Deborah Meier after this was first published.
Dear Pedro,
Their ability to sell austerity to white males, whose jobs are disappearing and social usefulness is being undermined, is a tribute to the "good" education the 1 percent got from their privileged schools. But it's also a damning statement about what was happening in the schools the rest of us went to, let's say, the bottom 80 percent. Why didn't we learn to defend our self-interests? So when I argue that we all need schools that prepare the ruling class ("the people") to rule, I can't get nostalgic about the "good old days." They weren't good for us. We need what they got.
Alas, the rich learned to be individualistic, to celebrate their own self-interests without any qualms, and—this is where it hurts—to join together, to pool their resources to overwhelm the rest of us when there was an opening for such ruthlessness. They may even have had liberal-minded teachers (I would guess so), but they set their own course differently.
And they even learned the best trick of all, to make the 80 to 99 percent think that they were undeserving, while those in the 1 percent were being unfairly criticized! They led us to think it was "reasonable" to tax income that was earned—by the sweat of our brow—while "unearned" income went scot-free. With enough tax lawyers in the family maybe we could have figured out how to turn our wages into "unearned" income? Too many, not too few, of us have been sympathetic to the whining grievances against President Barack Obama for making a few mildly critical statements about their greed (while their allies in the Republican party were throwing crude schoolyard taunts at Obama—about his very legitimacy as an American!). Some Americans learned chutzpah in school and from their families. It's time for the rest of us to go to schools that teach us chutzpah too.
"Is It Still OK To Be Rich in America?" appears prominently on the cover of the Sept. 24 Fortune magazine. According to the author, the rich kids are feeling excluded and afraid to display their wealth, their mansions, their many cars, etc., etc. Fortunately for the rich, since most of us still can't quite get our hands around the difference between millions and billions and trillions, we have a hard time following the budget debates (we were too busy trying to make sense of algebra to ever grasp what the difference is between 10 squared and 10 to the 10th power).
The word got around that people like me are living off a too-generous pension and Social Security. We have become the objects of envious rage from those whose union jobs disappeared or whose pensions have gone the way of bankruptcy. (Note: The rise of the black middle class is largely due to the fact that they had a good shot at public employment while being shut out of the more lucrative private sector.) "Why not me, too?" has turned into "Why them?"
The magazine In These Times has a great piece this week by Peter Frase and Bhaskar Sunkara on why this might be just the right time for expanding, not shrinking, the welfare state.
It was fun to read after my two days at a conference in Brussels sponsored by Education International—a coalition of teachers' unions from around the world. It echoed what I was hearing over there: the way the "austerity movement" has crippled education, above all in the so-called "developing" nations. Not to mention crippling, literally, the health and welfare of the world's children. We heard from economists and labor leaders about the steps that must be taken to build an anti-austerity future. There is no shortage of resources—plain, ordinary wealth—but it has been trickling upward and out of our hands at a rapid pace in the past 20 to 30 years. Meanwhile, millions and billions have been redistributed to rich people whose work serves no social purpose at all and who have no intention of sharing any of it because ... they worked hard for it. Unlike you and me. (Yes, definitely, read Ayn Rand.)
More on Belgium—including Belgian waffles—later.
ADDENDUM, ADDED AT 2:20 P.M. BY DEBORAH MEIER: As I reread what I wrote, it tells me something about what last Wednesday was like for me—a bad day! Of course, some businessmen do some social good. And I think unearned income is taxed at a lower rate, not quite scot-free. But what got lost was important and the direction I'd like us to move into: what schools need to be like—even if it doesn't close the scoring gap—to give the have-nots the knowledge and skill and disposition to be a powerful force in democracy both locally and nationally. I got side-tracked into a rant!
The opinions expressed in Bridging Differences are strictly those of the author(s) and do not reflect the opinions or endorsement of Editorial Projects in Education, or any of its publications.
Teachers from Seattle Public Schools picket outside Roosevelt High School on what was supposed to be the first day of classes, Wednesday, Sept. 7, 2022, in Seattle. The first day of classes at Seattle Public Schools was cancelled and teachers are on strike over issues that include pay, mental health support, and staffing ratios for special education and multilingual students.
Jason Redmond/AP
Federal What's Behind the Push for a $60K Base Teacher Salary
Libby Stanford, January 26, 2023


School security measure passes the Colorado Senate in late night reversal - Denverite, the Denver site!
A budget amendment sets aside $35 million for school resource officers and building upgrades to improve security.
Apr. 04, 2018, 8:10 p.m.
The Colorado Senate joined the House in adopting a budget amendment Wednesday that sets aside $35 million for school resource officers and building upgrades to improve security. The late night vote came after the initial version of the amendment failed on something close to a party line vote.
Our school safety plan – putting $35 million towards school resource officers in Colorado schools – just passed on a bipartisan 20 to 15 vote.
There are some complicated political dynamics in play with this budget allocation, but the reversal in the Senate makes it much more likely that a large, security-focused allocation will be included in the final budget. A separate bill would be necessary to describe the uses of the money and the distribution process.
The House version of the amendment passed with the support of Republicans and some Democrats and draws money from the general fund. The Senate version draws from the state education and public schools funds.
"Clearly safety has been a priority in both chambers," said state Rep. Millie Hamner, a Dillon Democrat who chairs the Joint Budget Committee, which will have to reconcile the House and Senate versions of the budget. This is a much larger addition to the state's $28.9 billion budget than most of the amendments under consideration in either chamber.
Some Democrats, particularly members of the African-American and Latino caucuses, opposed this amendment because they worry about adding more law enforcement presence to schools. Community groups have also mobilized to oppose this idea. Democrats proposed that schools be able to apply for grants for counselors and school psychologists, conflict resolution training, and other uses that focus on less tangible aspects of school safety, along with school resource officers and building upgrades.
Neville's son, state Rep. Patrick Neville, is a survivor of the Columbine shooting. As House minority leader, the younger Neville made a passionate case for spending more money on school security last week. He called it a "less political" solution than his preferred answer, more armed adults in schools.
But as the debate on the Senate floor showed, school security is very political, and Republicans and Democrats arrived at their positions from very different worldviews and life experiences.
State Sen. Angela Williams, a Denver Democrat, said she feared more police in schools would lead more children into the school-to-prison pipeline and reminded her colleagues of an infamous video from South Carolina that showed an officer dragging a girl from her chair and throwing her to the ground.
"Students, especially youth of color, are being arrested for misbehavior that used to be handled by school administrators and counselors," she said.
The other co-sponsor, state Sen. John Cooke, a Republican from Weld County and the former sheriff there, said he had never seen a school-to-prison pipeline.
"(Police) are there to protect our children, not to send them to prison," he said.
State Sen. Rhonda Fields, an Aurora Democrat, said $35 million could be better used in other ways.
Senate Majority Leader Chris Holbert, a Parker Republican, said he wanted to offer "perspective." The money is not that much, once it's spread around, but it might mean the next school shooter gets confronted by an armed, trained person.


September 2013, Dominic will attend the 8th NIZO Conference in Papendal, the Netherlands.
Milk Proteins by Enzyme Immobilized on Polyester".
September 2013, Huazhen attended 13th Oxford School on Neutron Scattering.
Oxford School on Neutron Scattering covers the theory and practice of neutron diffraction and spectroscopy with Lectures and tutorials given by international experts.
June-July 2013, Jason visited Helmut Schmidt University in Hamburg, Germany.
Jason's visit was funded by 2013-2014 Group of Eight Australia – Germany Joint Research Co-operation Scheme. His visit was part of the research project "Advanced biocatalysis for biomolecule production at high pressure".
December 2012, Jason was awarded New Horizons Joint PhD Scholarship.
May 2012, Dominic was awarded AINSE Postgraduate Research Awards.Supported by the PRA, Dominic will carry out research project "Interfacial properties of stimuli-responsive peptide biosurfactants and their interaction with chemical surfactants for advanced foaming control".
July 2012, Dominic, Jason and Jingxiong attended Australian Protein Production Symposium in Brisbane.
The biannual Australian Protein Production Symposium gathers world experts in the field of recombinant protein production. Dominic and Jason were partially supported by EMBL Australia Student Sponsorship to attend the Symposium.


To bring people back security to their digital lives!
For the challenge is: today's society relies on applications and technologies that simplify our current life in many ways, e.g. online banking, online shopping and e-government applications. Trust in such technologies opens the door, however, to identity thieves, making access possible to personal data and misuse of it. Law enforcement authorities call identity theft "the world's fastest growing crime today". Also at the official Data Protection Authority' identity theft is the most often mentioned topics on the telephone hotline.


text:
Owsley striving to provide 50 families with Christmas gifts; free meal event set for Friday
By Katie Pickens
November 30, 2020 | 12:10 am
Updated November 30, 2020 | 12:28 pm
Photo by Katie Pickens
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One Owensboro resident has worked consistently over the last several months to provide for his community in light of the pandemic. Travis Owsley, founder of Beverly's Hearty Slice, is now working to provide Christmas gifts for 50 families this holiday season.
Owsley and a team of supporters most recently secured and distributed 145 Thanksgiving meals to families in need.
Owsley's efforts in supporting local families has allowed him to secure the funding and legal necessities to turn Beverly's Hearty Slice — named in honor of his late mother who was known for her generosity in feeding her neighbors — into an official nonprofit organization.
On Dec. 18, Owsley will be holding the first annual Beverly's Hearty Slice Christmas event, where he will distribute stockings filled with Christmas presents and gift cards to 50 families in need. The event will take place from 5:30-7 p.m. at Kendall Perkins Park.
Already, Owsley and his team of volunteers have received several significant donations that have gotten them closer to their goal.
On Dec. 4, Owsley will be offering free pizza, soft drinks and packaged desserts to the community. The event will be held at Kendall Perkins Park but hosted by The Party Space Place, located at 5010 Wildcat Way. All of the food was made available through donations from Pepsi, Little Debbie Snack Cakes and members of the community.
"It's crazy," Owsley said of the growing support his organization has received. "From August to now — it's unbelievable."
Other businesses and agencies — such as Ernie Davis & Sons Mechanical and the Sheila K. Foundation — have chipped in $1,000 and $500, respectively, to go toward Owsley's Christmas events.
"People have purchased Walmart gift cards for us, too," he said. "I'm hoping to provide $35-$40 gift cards to each of the 50 families. With COVID, it's causing a depression, financially, for so many people right now."
At both events, residents will be served on a first-come, first-serve basis. Prior to the Christmas gift event, Owsley said he will be accepting additional donations in the form of toys, coats and pants with hopes that he can help as many people as possible.
Anyone and everyone from the community is welcome to participate in either event, he added.
Owsley, who serves as the administrative supervisor at St. Joseph Peace Mission, said plans for turning Beverly's Hearty Slice into its own nonprofit organization are already well underway.
"I've got someone helping me start it. We have the [funding we need in place] and an attorney who's been [handling the legalities]," Owsley said. "All of my board members will be strong, independent women, just like my mom."
Home » Features » Community » Owsley striving to provide 50 families with Christmas gifts; free meal event set for Friday
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