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"Fatal Flaws" Shows Assisted Suicide is About Despair, Not Terminal Illness
Posted On: Friday, July 27th, 2018
In June, the Euthanasia Prevention Coalition and DunnMedia & Entertainment released Fatal Flaws: Legalizing Assisted Death, a full-length documentary examining the long-term consequences of legal assisted suicide. Kevin Dunn, the filmmaker, travelled to the Netherlands, Belgium, the U.S., and Canada to interview patients and physicians who have been affected by these laws, both assisted suicide advocates and those who oppose them. The film is chilling. It reveals how assisted suicide, once legalized, can transform a culture and alter the way it treats those who are suffering.
The concern that Dunn expresses throughout the film is how these laws have gradually expanded in Europe from the terminally ill, to the chronically ill, to the mentally ill, and finally to those who are simply "tired of life." He fears the same loosening of assisted suicide laws—especially of eligibility requirements—will happen in the U.S. and Canada, too. Of course, what's happening overseas cannot necessarily predict the future in North America. But Dunn clearly believes we should take note.
Psychiatric patients "not treatable"?
The 80-minute film features several testimonies from patients and their families who have been affected by assisted suicide laws. Featured interviews include a young disabled woman who was pressured to end her own life due to treatable medical complications, a daughter whose elderly mother was euthanized without family consent, and an elected representative whose husband was pressured to "get out of the way" when he became critically ill.
But the most disturbing moment is when viewers meet Aurelia Brouwers, a 29-year-old woman from the Netherlands. "I'm very interested in euthanasia," she says. Physically, Aurelia is healthy; her reason for wanting euthanasia is an ongoing struggle with "severe psychiatric problems." People like her—people in profound mental anguish—are "not treatable anymore," she tells Dunn. In her opinion, their suffering ought to make them candidates for lethal drugs.
When Dunn asked Aurelia what she would do if a cure for her suffering was discovered the next day, she replied, "I don't believe there is any cure for me left." "So, no hope?" asked Dunn. "No, I don't believe there is any," she answered.
Dunn fights back tears as he reflects on the encounter: "I have to ask, who has failed her?"
Dunn kept in touch with Aurelia and says he pleaded with her to change her mind. Above all, he wanted her to know, "there is always hope, that the world is a better place with her in it." But tragically, Aurelia followed through on her death wish. She killed herself with lethal drugs on January 26, 2018, assisted by a doctor from the End-of-Life Clinic in the Netherlands.
The worst suffering is existential, not physical
Aurelia's story is a tragedy. It is also a crucial part of the story that Dunn is trying to tell. Aurelia's conviction that she is beyond rescue rips wide open the real issue behind assisted suicide and euthanasia: existential despair.
Research consistently indicates that physical suffering is not the reason people choose assisted suicide. That choice comes primarily from fear: fear of being a burden on loved ones, of "losing dignity," of being dependent on others. Underpinning all these fears is a loss of hope that life, even with suffering, even with disability, is still worth fighting for. Patients who choose assisted suicide no longer believe there is hope for them—which is exactly what Aurelia falsely believed when she ended her life.
The worst suffering is not physical; it is existential. When we give people access to legal assisted suicide, we communicate to them that it is good to give in to despair, that they are better off dead than alive.
Where does it end?
For more than a decade, Oregon was the only state in the U.S. with assisted suicide on the books. Since then, there appears to have been something like a domino-effect, with six other states and Washington D.C. following suit in rapid-fire succession. Compassion & Choices and its affiliates have had a hand in passing every one of these laws and now they are pushing for the legalization of assisted suicide in Minnesota. They cloak their agenda in the language of compassion, arguing that assisted suicide (or, as they insist on calling it, "medical aid-in-dying") relieves unbearable suffering.
But the truly unbearable suffering is that of despair and purposelessness. Experiencing these things is normal for people facing serious illness and death, but the proper response is love, support, and compassion, not quick-and-easy death on demand. In Minnesota, no one should die thinking that the world will be better off without them, that it is better for them to die than to live. We are known for excellence in health care and are working to make palliative care better and more available to Minnesotans. Assisted suicide is a false compassion; it sends the wrong message to those struggling to hope.
Join the coalition against assisted suicide in Minnesota:
« As I See It: The AMA grapples with issue of physician assisted suicide [TELEGRAPH.COM] Chronically ill man releases audio of hospital staff offering assisted death [CTV NEWS] »


Purpose: The Goals of the North American Skull Base Society are to promote dissemination of information about diseases involving the skull base, including the anatomy, physiology, pathology, and clinical management, in order to facilitate coordinated excellence in the delivery of care to patients, and to promote advancement of the scientific basis for treatment of patients with skull base disorders.
Content Areas: The content areas focus on the development, validation and dissemination of basic scientific information and clinical application of evidence-based approaches useful to specialists in the care of diseases of the skull base, and to provide broader distribution of this information among the various scientific disciplines caring for patients with skull base diseases. We encourage the application of these advances and encourage efforts to stimulate further interest in skull base diseases.
Target Audience: Our participants are physicians with sub-specialty interest in the diseases of the skull base, particularly neurosurgeons, otolaryngologists, head and neck surgeons, and plastic surgeons, as well as ophthalmologists, radiologists, pathologists, rehabilitation specialists, medical and radiation oncologists, and others with interest in diseases involving the cranial base. Physicians within the North American continent are particularly targeted, but the Society is also open to participation from qualified international members from around the world.
Types of Activities: The primary activity for the NASBS is its Annual Meeting. This meeting is held annually, either in the late winter or early spring, at locations chosen by the executive leadership for access, facilities and the ability to support the educational program. In addition, a Practical Course in Skull Base Anatomy and Surgery has been a prominent addition to the educational mission since 1995. This Practical Course, which now includes both Traditional and Endoscopic Surgical techniques, now takes place every summer.
Effectively disseminate evidence-based scientific advances and relate them to new and evolving standards of care.
Create opportunities for members and others to share aggregate outcomes data as one of the measures for effective educational interventions and also as a source of identification of professional practice gaps for future planning.
Highlight emerging outcomes data in skull base pathology and science.


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Q: How to fix 'ClassNotFoundError' when loading classes from a folder outside the classpath I'm writing a module system that loads modules with additional functionality to my Spigot plugin. When I try to load a class dynamically from my modules, I get a ClassNotFoundException.
I am using a classloader to load the jar file of my modules, which are stored in a seperate folder also called "modules". I have looked for several tutorials regarding classloaders, and as far as I am aware I am doing nothing wrong in this bit of code.
Here's my code:
        File modulesFolder = new File(instance.getDataFolder(), "modules/");
        if (!modulesFolder.exists())
            modulesFolder.mkdirs();

        System.out.println("scanning modules folder...");
        for (File f:modulesFolder.listFiles()) {
            if (f.isFile() && f.getName().endsWith(".jar")) {
                String moduleName = LCStringUtils.trimString(f.getName(), ".jar");
                Class<?> moduleClass = null;
                try {
                    ClassLoader loader = URLClassLoader.newInstance(
                            new URL[] {f.toURI().toURL()},
                            getClass().getClassLoader()
                        );

                    moduleClass = Class.forName("net.libercraft." + moduleName.toLowerCase() + "." + moduleName, true, loader);
                } catch (ClassNotFoundException | MalformedURLException e) {
                    e.printStackTrace();
                }
                if (moduleClass == null || !Module.class.isAssignableFrom(moduleClass))
                    continue;
                System.out.println(moduleClass.getName());
            }
        }

I'm quite sure that the class should be there. The code is able to load the name of the file, which it needs to get the classpath. And as you can see in the file structure for the LiberEffects.jar, it does also contain a class called LiberEffects. I have placed this jar file in the modules folder, but when it tries to load the net.libercraft.libereffects.LiberEffects class it throws the error.
File structure:
https://i.imgur.com/EvHBt10.png

A: ¿Have you tried putting the entire path of the directory instead of "modules/"? For example C:\Users\userName\Documents\NetBeansProjects\Erste_projeckt\modules.

redpajama_set_name: RedPajamaStackExchange


 Map And Contact Information For The Franklin Suite Hotel Fort McMurray.
For bookings and information for Vantage Inn & Suites, as well as six sister properties; Clearwater Suite Hotel, Franklin Studio Suites, Merit Hotel & Suites, Nomad Hotel & Suites, Clearwater Residence Hotel–Timberlea and Radisson Fort McMurray.
Head west toward Route 69. Turn right onto Route 69. Turn right onto Route 63N/Sakitawaw Trail. Turn right onto King St. Turn left to stay on King St. Turn left onto Franklin Ave.
Exit Morrison Street, Turn left at light onto Franklin Boulevard, hotel is located 2 blocks further North just past Richard Street.


text:
  Vulvoz est
       un village
       localisé dans le département de Jura en Franche-Comté. Elle totalisait 17 habitants en 2008.

Si vous envisagez de emmenager à Vulvoz, vous pourrez aisément trouver une maison à vendre.

Le parc d'habitations, à Vulvoz, était réparti en 2011 en un appartements et 21 maisons soit
 un marché plutôt équilibré.

À coté de Vulvoz sont localisées les communes de
Coyrière localisée à 4 km, 61 habitants,
Rogna située à 3 km, 207 habitants,
Vaux-lès-Saint-Claude à 5 km, 703 habitants,
Choux à 2 km, 144 habitants,
Coiserette à 3 km, 44 habitants,
Les Bouchoux localisée à 4 km, 321 habitants,
 entre autres. De plus, Vulvoz est située à seulement douze km de Oyonnax.

redpajama_set_name: RedPajamaGithub


text:
Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation
Wenqiang Yu1 na1,
Vasudeva Ginjala1 na1,
Vinod Pant1 na1,
Igor Chernukhin2 na1,
Joanne Whitehead1 na1,
France Docquier2,
Dawn Farrar2,
Gholamreza Tavoosidana1,
Rituparna Mukhopadhyay1,
Chandrasekhar Kanduri1,
Mitsuo Oshimura3,
Andrew P Feinberg4,
Victor Lobanenkov5,
Elena Klenova2 &
Rolf Ohlsson1
Nature Genetics volume 36, pages1105–1110(2004)Cite this article
Chromatin insulators demarcate expression domains by blocking the cis effects of enhancers or silencers in a position-dependent manner1,2. We show that the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation. Chromatin immunoprecipitation analysis showed that a poly(ADP-ribosyl)ation mark, which exclusively segregates with the maternal allele of the insulator domain in the H19 imprinting control region, requires the bases that are essential for interaction with CTCF3. Chromatin immunoprecipitation–on–chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. An insulator trap assay showed that the insulator function of most of these CTCF target sites is sensitive to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase activity. We suggest that poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions.
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Poly(ADP-ribosyl)ation is traditionally associated with DNA repair and apoptosis4, but this view may be too limited5,6. For example, one of the poly(ADP-ribose) (PAR) polymerases, PARP-1, is associated both with formation of heterochromatin and with regions of high transcriptional activity in fruit flies7. To explore a potential correlation between poly(ADP-ribosyl)ation and expression domains in the mouse, we analyzed the allelic distribution of poly(ADP-ribosyl)ated protein complexes on the chromatin insulator at the H19 imprinting control region (ICR), which partitions expression domains in a parent of origin–specific manner8. We analyzed chromatin-immunoprecipitated DNA of fetal liver of M. musculus domesticus × M. musculus musculus intraspecific hybrid crosses by a PCR assay, which exploited a polymorphic BsmAI restriction site at the second CTCF target site9. Only the maternally inherited allele was specifically captured using a specific antibody that detects polymers containing ten or more ADP-ribose units (Fig. 1a).
Figure 1: A PAR mark of the H19 ICR is allele-specific and depends on intact CTCF target sites.
(a) ChIP analysis of formaldehyde-crosslinked DNA (derived from fetal liver of intraspecific hybrid crosses of M. m. domesticus (D) and M. m. musculus (M)). The PCR primers spanned a polymorphic BsmAI site (specific for the M. m. musculus allele). (b) ChIP analysis of primary cultures of fetuses derived from reciprocal crosses between the 142* (with three of the four CTCF target sites point-mutated at the H19 ICR) and SD7 strains10. The PCR primers covered CTCF target site 2, as above. (c) JEG-3 cells transfected with mutated and wild-type H19 ICRs, mixed in equimolar amounts. The representation of wild-type and mutant CTCF target sites in both CTCF and poly(ADP-ribosyl)ation-specific ChIP DNA was examined by PCR at site 3 and exploited the mutant-specific EcoRV restriction site10. All crosses are listed with the mother's strain first and the father's strain second.
As the chromatin insulator protein CTCF is the only factor known to interact preferentially with the maternal H19 ICR allele in vivo3, we examined the interaction between poly(ADP-ribosyl)ated proteins and the H19 ICR with point-mutated CTCF target sites10. We carried out chromatin immunoprecipitation (ChIP) analysis of primary mouse fibroblast cultures, with the mutation inherited maternally or paternally, followed by PCR of the H19 ICR. The H19 ICR was associated with a poly(ADP-ribosyl)ation mark only if the wild-type allele was inherited maternally (Fig. 1b). Although this result suggested that the poly(ADP-ribosyl)ation mark of the maternal H19 ICR allele requires functional CTCF target sites, we could not rule out indirect effects from de novo methylation3. We therefore mixed equimolar amounts of plasmids containing the wild-type H19 ICR and plasmids containing the H19 ICR with mutations of CTCF target sites and transfected JEG-3 cells with the mixture. ChIP assays on the protein-DNA complexes of the transfected plasmids showed that antibodies to CTCF and to PAR captured only the wild-type allele (Fig. 1c). As there is no de novo methylation of the episomal H19 ICR under these conditions (data not shown), poly(ADP-ribosyl)ated proteins associate to the H19 ICR exclusively through the CTCF target sites.
We explored the possibility that the poly(ADP-ribosyl)ated protein was identical to CTCF using in vitro poly(ADP-ribosyl)ating recombinant baculovirus CTCF (bvCTCF). After immunopurification, a substantial proportion of the total CTCF fraction was specifically retained (Fig. 2a). A modified western-blot protocol allowed us to resolve the default (130 kDa) and poly(ADP-ribosyl)ated (180 kDa) versions of bvCTCF (Fig. 2b). To confirm that CTCF is similarly poly(ADP-ribosyl)ated in vivo, we analyzed immunoprecipitated CTCF from several different sources (including MCF-7 breast cancer cells; Fig. 2e) by western blotting of nuclear extracts immunoprecipitated with a polyclonal antibody to CTCF. After immunoprecipitation with antibodies to CTCF and to PAR, we detected a 180-kDa band (Fig. 2c). We conclude that the poly(ADP-ribosyl)ated form of CTCF does exist in vivo and that it can be generated from recombinant CTCF by in vitro poly(ADP-ribosyl)ation.
Figure 2: CTCF is poly(ADP-ribosyl)ated.
(a) CTCF can be poly(ADP-ribosyl)ated in vitro. The bvCTCF protein was poly(ADP-ribosyl)ated in vitro and subjected to affinity chromatography on a matrix with the immobilized antibodies to PAR. MW, molecular weight; PIS, preimmune serum. (b) Western-blot analysis of nonpoly(ADP-ribosyl)ated and poly(ADP-ribosyl)ated bvCTCF after optimization of the western-blotting conditions. MW, molecular weight. (c) Western-blot analysis of nonpoly(ADP-ribosyl)ated and poly(ADP-ribosyl)ated CTCF of the human breast cancer cell line MCF-7 after optimization of the western-blotting conditions. MW, molecular weight. (d) Mobility shift analysis shows that the affinity-purified, in vitro poly(ADP-ribosyl)ated CTCF retains its DNA binding capacity. The yCTCF lane depicts an EMSA analysis using Pichia recombinant CTCF. (e) The N-terminal domain of CTCF is a preferred target for poly(ADP-ribosyl)ation in vitro. Arrow indicates the position of the poly(ADP-ribosyl)ated N-terminal domain of CTCF. C, C-terminal domain; N, N-terminal domain; Zn, Zinc finger domain.
To examine whether the poly(ADP-ribosyl)ated CTCF was able to interact with the H19 ICR, we used recombinant in vitro poly(ADP-ribosyl)ated and immunopurified bvCTCF (Fig. 2a) in mobility shift assays. Poly(ADP-ribosyl)ation of CTCF did not markedly interfere with its interaction with one of the CTCF target sites in the H19 ICR (Fig. 2d). Although we cannot rule out altered binding affinity of the poly(ADP-ribosyl)ated CTCF to its target sites, the mobility shift result is in contrast with previous reports on the ablation of DNA binding caused by the poly(ADP-ribosyl)ation of transcription factors such as YY1 (ref. 5). This difference might be due to the localization of key poly(ADP-ribosyl)ation sites, as the N-terminal portion, but not the 11-zinc-finger domain, of CTCF is the preferred in vitro target for PARP-1 (Fig. 2e).
We examined the generality of the link between CTCF and poly(ADP-ribosyl)ation using two approaches. First, a western-blot analysis of mouse neonatal tissues showed that the proportion of 180-kDa CTCF relative to 130-kDa CTCF varied in a tissue-specific manner (Fig. 3a). Notably, the 180-kDa poly(ADP-ribosyl)ated CTCF was abundant in heart and muscle but scarce in neonatal liver and brain, suggestive of tissue-specific differences in the turnover of the poly(ADP-ribosyl)ation mark. Because the poly(ADP-ribosyl)ation mark might, in some instances, not relate to the pool of CTCF but be a specific feature of the DNA-bound CTCF complexes, we used a second strategy: ChIP on chip analysis, exploiting CTCF target site library microarrays. Figure 3b shows the hybridization images and Figure 3c shows a scatter plot analysis comparing the hybridization signals clone by clone. This analysis indicated that 78% of the CTCF target sites of the mouse liver library were immunoprecipitated by the antibodies to PAR and to CTCF.
Figure 3: Extensive overlap in the patterns of poly(ADP-ribosyl)ation marks and CTCF occupancy.
(a) A western-blot analysis of total representation of nonpoly(ADP-ribosyl)ated (130 kDa) and poly(ADP-ribosyl)ated CTCF (180 kDa) in various mouse neonatal tissues. MW, molecular weight. (b,c) ChIP probes, derived from neonatal liver and enriched in sequences interacting in vivo with CTCF or poly(ADP-ribosyl)ated proteins, were hybridized to microarrays of a library of CTCF target sites. (b) A selection of relevant array images of ChIP on chip hybridizations. (c) A scatter-plot analysis (in log2 scale) comparing the PAR and CTCF hybridization signals from these images. Control ChIP samples, obtained by using normal serum, showed no detectable signal in either instance (data not shown).
Whereas the data in Figure 3a suggest that only a fraction of CTCF is poly(ADP-ribosyl)ated before its association to target sites in some tissues, the data in Figure 3b,c show that there is a strong correlation between CTCF occupancy and the presence of a poly(ADP-ribosyl)ation mark. The exceptions to this rule could be due to the fact that PAR marks involving fewer than ten units are not detected by the antibody to PAR. Taken together, the results indicate that a mechanism underlying the formation or the extension of the PAR mark exists at some individual sites only after the CTCF-DNA complex has been formed. This possibility is supported by the observation that CTCF target sites can be relocated to the nucleoli, which are enriched in PARP-1, through a CTCF-nucleophosmin interaction11. Therefore, the tethering of CTCF target sites to the nucleolus might be essential for de novo poly(ADP-ribosyl)ation of CTCF and its insulator function.
To investigate this possibility, we used an insulator trap assay to examine a functional link between poly(ADP-ribosyl)ation and CTCF-dependent chromatin insulator function. This assay12 depends on the ability of the candidate sequence to protect the toxin-A gene from the SV40 enhancer in an episomal context. We transfected JEG-3 cells with the plasmid mixture ligated with or without the H19 ICR and scored the number of surviving colonies, which is directly proportional to insulator strength. Under these conditions, there is no detectable integration of the episomal constructs into the genome9,13,14,15. Figure 4a outlines the toxin vectors used. H19 ICR insulator function is sensitive to 3-aminobenzamide (3-ABA), a general inhibitor of PAR polymerases, as the numbers (Fig. 4b) and sizes (data not shown) of colonies surviving treatment with 3-ABA were substantially reduced in cells without the H19 ICR in the insulator position of the toxin-A vector. We ruled out the possibility that double selection by hygromycin and 3-ABA adversely affected the survival of the cells: in the absence of the toxin-A reporter gene, there was no marked difference in cell survival after treatment with hygromycin versus hygromycin and 3-ABA (Fig. 4b). Figure 4c documents the efficiency of the 3-ABA treatment, which rapidly eliminated the PAR content of H19 ICR chromatin, whereas CTCF association remained intact.
Figure 4: The insulator trap assay and 3-ABA sensitivity of chromatin insulator functions.
(a) Schematic maps of the different pREPtox vectors. (b) The number of surviving cell clones in the presence or absence of 3-ABA. (c) Inhibition of PAR polymerases directly affects the PAR content of the H19 ICR. The specific representation of H19 ICR sequences in each of the ChIP samples was determined by real-time PCR analysis. Two independent experiments are shown. SC, serum control. (d) A scatter-plot analysis of insulator strength in the presence or absence of 3-ABA, as determined from the microarray analysis. (e) A standard deviation analysis indicating that lower-strength insulators have a higher deviation from average than higher-strength insulators. (f) Poly(ADP-ribosyl)ation and the imprinted state. IGF2 expression levels were analyzed by RNase protection of RNA isolated from mouse-human cell hybrids, untreated (control) or treated with 3-ABA. (g) ChIP assays indicate that the activation of the maternal IGF2 allele in M11PA9 cells was paralleled by a strong reduction in the poly(ADP-ribosyl)ation mark of the H19 ICR of human origin. MWS, molecular weight standard.
We inserted the entire amplified CTCF target site library into the insulator position of the pREPtoxA vector, between the toxin-A promoter and the SV40 enhancer. We used amplification primers with XhoI and KpnI restriction sites to prevent the generation of vectors with multiple inserts. After transfecting cells with the ligation mixture and selecting with hygromycin for three weeks, we scored for surviving cell colonies, as described above. Treatment with 3-ABA reduced the number of surviving colonies by >70% (Fig. 4b). This result could indicate, by analogy to the effect on the H19 ICR, that there is a gradual and similar loss of insulator function for all the insulator segments. Alternatively, the effect might be specific for some insulators.
To discriminate between these possibilities, we amplified the insulator DNA segments by flanking primers from DNA of pooled surviving cell clones and then hybridized it to the CTCF target site library microarray. We visualized the resulting patterns by comparing the hybridization signal ratios of samples treated with 3-ABA versus those of untreated samples (Fig. 4d). The lower the insulator index ratio is, the more sensitive the insulator is to 3-ABA. The hybridization signal in the control insulator trap assay, which is a direct correlate of insulator strength12, served as an internal reference. The scatter-plot analysis indicated that most of the insulator sequences were sensitive to 3-ABA (Fig. 4d). By plotting the standard deviation of the insulator index of binned data points across the control insulator axis, we visualized the high variation in 3-ABA sensitivity of weak insulators relative to strong insulators (Fig. 4e). This trend suggests that the 3-ABA sensitivity of the insulator property is common to all CTCF target sites.
As the endogenous insulator of the maternal H19 ICR allele insulates the upstream Igf2 from downstream enhancers, we examined the effect of 3-ABA treatment on allelic IGF2 expression patterns using mouse cells carrying human chromosome 11 of maternal or paternal origin16. RNase protection analysis showed that the repressed status of the maternal IGF2 allele was lost in cells treated with 3-ABA (Fig. 4f). This result was paralleled by a reduction of the poly(ADP-ribosyl)ation mark at the H19 ICR (Fig. 4g), strengthening the link between a poly(ADP-ribosyl)ation-dependent chromatin insulator and the repression of the maternal IGF2 allele.
We conclude that there is a genome-wide and potentially context-dependent link between CTCF, poly(ADP-ribosyl)ation and chromatin insulator function. Although there is no report published on epigenetic lesions in mice with a targeted deletion of Adprt (encoding PARP-1), a short form of PARP-1 is constitutively expressed in Adprt−/− cells and enzymatically active in a DNA damage–independent manner17. Moreover, the known PAR polymerase gene family encoding 3-ABA-sensitive polymerases is continuously expanding, suggesting that there is a certain degree of redundancy of constitutively expressed PAR polymerase enzymatic functions5. The polymerases do not constitute the whole picture, however, as poly(ADP-ribosyl)ation marks are rapidly turning over18. The macro domain of histone macroH2A, which covers only the inactive X chromosome19, has been proposed to enzymatically degrade PAR20. Accordingly, one function of macroH2A might be to erase chromatin insulator functions to facilitate the spreading of silencing along the chromatin fiber during X-chromosome inactivation. These considerations offer new perspectives also in cancer, as an unscheduled change in the dynamic equilibrium of constitutive PAR marks might lead to loss of CTCF-dependent chromatin insulator functions, with ensuing pathological lesions in expression domains and networks.
Mice.
We used M. m. musculus (CZECH II, Jackson Laboratories) and M. m. domesticus (NMRI strain) mice to create intraspecific F1 hybrid M. m. domesticus × M. m. musculus or M. m. musculus × M. m. domesticus conceptuses (where the mother's strain is given first and the father's strain second). We crossed the 142* strain with three of the four CTCF target sites mutated in a 129/SvJ background10 with the recombinant SD7 strain (gift from W. Reik; Babraham Institute, Cambridge, UK)21. We collected fetal livers at 16.5 d post coitum and neonatal tissues from 2-d-old conceptuses. All animal experiments were approved by the local ethical committee at Uppsala.
Cell cultures and transfections.
We established primary cultures of fetuses (e13; 142* × SD7 or SD7 × 142* crosses) and propagated them in Dulbecco's modified Eagle medium (Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (Gibco) and glutamax. We maintained the JEG-3 cell line as described22. We added 3-ABA (Sigma) to the culture medium 28 h after transfection at a final concentration of 8 mM. We collected the cells after 14 h of exposure to 3-ABA. We maintained the M11PA9 maternal and P11PA9 paternal cell lines16 in Dulbecco's modified Eagle medium (Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (Gibco) and Blasticidin S (CAYLA). We treated the maternal and paternal cell lines with 8 mM of 3-ABA for 48 h. We collected total RNA using the Qiagen RNA extraction kit. We carried out transfections using the FuGene 6 transfection reagent (Roche) with equimolar amounts of the plasmid DNAs (5 μg for the basal promoter constructs) and 0.5 μg of control plasmid (pREP9-RFP).
Chromatin immunopurification assay.
We collected cells and crosslinked them with formaldehyde as described3. We immunopurified the DNA-protein complexes using antibody to PAR polymer (Trevigen) and protein A 4 Fast Flow Sepharose beads (Amersham Biosciences) and then amplified the immunopurified DNA from mouse fetal liver by PCR using BsmAI forward and reverse primers (sequences available on request). The PCR conditions were 95 °C for 5 min; six cycles of 94 °C for 1 min, 57 °C for 1 min and 72 °C for 1 min; 24 cycles of 94 °C for 30 s, 57 °C for 30 s and 72 °C for 30 s; and 72 °C for 3 min. We amplified the immunopurified DNA from the mutated or wild-type H19 ICR allele by PCR using S2-Par forward primer and Meth-Dn reverse primer (sequences available on request). One of the primers was labeled with P32-γ-ATP (Amersham Biosciences). The PCR conditions were 95 °C for 5 min; 25 cycles of 94 °C for 30 s, 54 °C for 40 s and 72 °C for 40 s; and 72 °C for 5 min. We visualized the PCR products on a 6% acrylamide gel and analyzed them with a Fuji-FLA 3000 Phosphorimager or exposed them on Kodak BioMax-MS X-ray film.
Real-time PCR analysis of ChIP samples.
We transfected JEG-3 cells with the pB-GFP plasmid, treated some of them with 8 mM of 3-ABA after transfection and left others untreated. We carried out ChIP with antibodies to PAR (Trevigen) and to CTCF (Upstate Biotechnologies). We diluted DNA samples to 10 ng μl−1 and carried out real-time PCR analysis using an ABI PRISM-7700 cycler (Applied Biosystems), Taqman Gold Universal Master mix (Perkin-Elmer) and TmanS1-For– and TmanS1-Rev– primers (sequences available on request). PCR conditions were 95 °C for 10 min followed by 40 cycles at 95 °C for 15 s and 60 °C for 1 min.
Analysis of IGF2 expression and poly(ADP-ribosyl)ation mark.
We extracted RNA from the mouse-human hybrid M11PA9 and P11PA9 cell lines and analyzed it by RNase protection using the Ambion RPA III kit. We cut a 558-bp HinfI-PstI human IGF2 cDNA insert23 with XhoI and used it as the template to generate an IGF2 antisense riboprobe (145 bases; SP6 polymerase)24. We carried out the ChIP assay of M11PA9 cells treated with 3-ABA using an antibody to PAR as described above. We analyzed the region 2 human H19 ICR, propagated in mouse cells, by PCR amplification as described25.
Recombinant CTCF and poly(ADP-ribosyl)ation.
We analyzed CTCF expression in the baculovirus system and expression of the N-terminal, zinc finger and C-terminal domains of CTCF in a bacterial system as previously described26. We prepared Pichia recombinant CTCF, a gift from A Vostrov and W. Quitschke (Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, New York, USA), as described27. The bvCTCF protein and the three CTCF domains were poly(ADP-ribosyl)ated using a published protocol28 with modifications. We incubated ∼50 pM of protein in 200 μl of a reaction buffer containing 50 mM Tris-HEPES buffer (pH 8.0), 0.15 mM KCl, 10 mM MgCl2, 10 mM 2-mercaptoethanol, 200 μM βNAD+, 200 ng of calf thymus DNA pretreated with DNase I and 500 ng of bovine PAR polymerase (Alexis Biochemicals) for 1 h at 30 °C. We purified the poly(ADP-ribosyl)ated CTCF protein using a matrix with immobilized antibodies to PAR. We mixed 50 μl of antibody to PAR–sepharose conjugate with a bvCTCF protein sample diluted to 0.5 ml with immunoprecipitation buffer (50 mM Tris-HEPES buffer (pH 8.0), 0.15 M NaCl, 2 mM EDTA and 0.1% Triton X-100) and incubated the mixture for 3 h at 4 °C on a rotating platform. After washing, we eluted the protein with 0.1 M NaH2PO4 (pH 4.0), 20 mM 2-mercaptoethanol and 7 M urea and renatured it by dialysis against 10 mM HEPES buffer–KOH (pH 7.0), 0.3 M KCl and 10 mM 2-mercaptoethanol containing 10% glycerol.
Western-blot analysis.
We prepared extracts from tissues as follows. We solubilized frozen tissue sections in lysis buffer (20 mM Tris buffered with HEPES buffer (pH 8.0), 2 mM EDTA, 0.5 M NaCl, 0.5% sodium deoxycholate, 0.5 % Triton X-100, 0.25 M sucrose, 50 mM 2-ME and a cocktail of inhibitors; Roche) at approximately 5 mg of tissue per ml buffer and homogenized them. We then incubated the extracts on ice for 20 min, filtered them to remove unresolved tissue particles, centrifuged them at 14,000 r.p.m. at 4 °C, collected the supernatants, mixed them with SDS-loading buffer (1/1, vol/vol), heated them for 5 min at 95 °C and resolved them in SDS-PAGE. We optimized the conditions to resolve poly(ADP-ribosyl)ated and nonpoly(ADP-ribosyl)ated forms of CTCF as follows. We resolved the samples in 6.5% SDS-PAGE and then subjected the gel to treatment for 15 min in an SDS running buffer with 1% methanol before blotting to improve the transfer of the poly(ADP-ribosyl)ated form of CTCF. We electroblotted the gels onto Immobilon P polyvinylidene difluoride filters (Millipore), probed membranes with the primary antibodies (at 1:1,000 dilution for the antibody to PAR 10H (Trevigen/Chemicon) and 1:1,000 dilution for the polyclonal antibody to CTCF (Abcam)) and then incubated the samples with the secondary antibodies to mouse and to rabbit, respectively. We developed the membranes with the ECL kit (Amersham Biosciences).
Band-shift assay.
We end-labeled a 120-bp fragment containing the fourth CTCF site in the H19 ICR29 using T4-PNK (New England Biolabs) and 32P-γ-ATP (Amersham Biosciences). We carried out the band-shift assay, using full-length bvCTCF and affinity-purified poly(ADP-ribosyl)ated bvCTCF, as described30.
ChIP on chip hybridization analysis.
We amplified the ChIP DNA specimens by a two-step PCR method12. We prepared the probe using CyScribe Post-Labelling kit (Cy Dye Post-labelling Reactive Dye Pack, Amersham Biosciences). We pooled probes and precipitated them with 100 μg of Cot-1 DNA (Clontech). We dissolved the labeled DNA in water and hybridization solution (GlassHyb Hybridization solution, Clontech), denatured it and incubated it at 45 °C for 2 h. We hybridized and washed microarrays in accordance with the GlassHyb Hybridization Solution kit User Manual (Clontech). We scanned the slides using a Scanarray 4000 and analyzed them with Quantarray version 3.0 (Packard Biosciences). Local background and signals from negative controls were subtracted.
Insulator trap assay.
The pREPtoxA vector contains a multiple cloning site flanked by two reporter genes12. We scored the Diphtheria toxin-A gene for insulator and silencer properties and the hygromycin gene only for silencing activity. We used the multiple cloning site to insert the entire CTCF library with aid of primers Xho1-T7, Kpn1-Sp6, Kpn1-T7 and Xho1-Sp6 (sequences available on request). We transfected the JEG-3 cell line with the entire ligation mixture and then selected clones against hygromycin (150 μg ml−1) for 2–3 weeks. We prepared genomic DNA from the surviving clones using the Wizard Genomic DNA Purification kit (Promega). We amplified the inserts by PCR using the above primers, labeled them and hybridized them to the CTCF target site library microarray as above.
Bell, A.C., West, A.G. & Felsenfeld, G. Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science 291, 447–450 (2001).
Ohlsson, R., Renkawitz, R. & Lobanenkov, V. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 17, 520–527 (2001).
Kanduri, C. et al. Functional interaction of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr. Biol. 10, 853–856 (2000).
Ziegler, M. & Oei, S.L. A cellular switch: poly(ADP-ribosy)lation stimulates DNA repair and silences transcription. Bioessays 23, 543–548 (2001).
Smith, S. The world according to PARP. Trends Biochem. Sci. 26, 174–179 (2001).
Kraus, W. & Lis, J. PARP goes transcription. Cell 113, 677–683 (2003).
Tulin, A., Stewart, D. & Spradling, A. The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development. Genes Dev. 16, 2108–2119 (2002).
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Kanduri, C. et al. The 5′-flank of the murine H19 gene in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication. Curr. Biol. 10, 449–457 (2000).
Pant, V. et al. The nucleotides responsible for the direct physical contact between the chromatin insulator protein CTCF and the H19 imprinting control region manifest parent of origin-specific long-distance insulation and methylation-free domains. Genes Dev. 17, 586–590 (2003).
Yusufzai, T., Tagami, H., Nakatani, Y. & Felsenfeld, G. CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol. Cell 13, 291–298 (2004).
Mukhopadhyay, R. et al. The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genomewide. Genome Res. 14, 1594–1602 (2004).
Holmgren, C. et al. CpG methylation regulates the Igf2/H19 insulator. Curr. Biol. 11, 1128–1130 (2001).
Kanduri, C., Kanduri, M., Thakur, N., Pfeifer, S. & Ohlsson, R. The kinetics of deregulation of expression by de novo methylation of the H19 imprinting control region in cancer cells. Cancer Res. 62, 4545–4548 (2002).
Kanduri, C. et al. A differentially methylated imprinting control region within the Kcnq1 locus harbours a methylation-sensitive chromatin insulator. J. Biol. Chem. 277, 18106–18110 (2002).
Horike, S. et al. Targeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith-Wiedemann syndrome. Hum. Mol. Genet. 9, 2075–2083 (2000).
Sallmann, F.R., Vodenicharov, M.D., Wang, Z.Q. & Poirier, G.G. Characterization of sPARP-1. An alternative product of PARP-1 gene with poly(ADP-ribose) polymerase activity independent of DNA strand breaks. J. Biol. Chem. 275, 15504–15511 (2000).
Davidovic, L., Vodenicharov, M., Affar, E. & Poirier, G. Importance of poly(ADP-ribose) glucohydrolase in the control of poly(ADP-ribose) metabolism. Exp. Cell Res. 268, 7–13 (2001).
Constanzi, C. & Pehrson, J. Histone macroH2A1 is concentrated in the inactive X chromosome in female mammals. Nature 393, 599–601 (1998).
Allen, M., Buckle, A., Cordell, S., Lowe, J. & Bycroft, M. The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A. J. Mol. Biol. 330, 503–511 (2003).
Dean, W. et al. Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with abberant phenotypes. Development 125, 2273–2282 (1998).
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Ohlsson, R., Holmgren, L., Glaser, A., Szpecht, A. & Pfeifer-Ohlsson, S. Insulin-like growth factor 2 and short-range stimulatory loops in control of human placental growth. EMBO J. 8, 1993–1999 (1989).
Li, Y.-M. et al. The H19 transcript is associated with polysomes and may regulate IGF2 expression in trans. J. Biol. Chem. 273, 28247–28252 (1998).
Lynch, C., Tycko, B., Bestor, T. & Walsh, C. Reactivation of a silenced H19 gene in human rhabdomyosarcoma by demethylation of DNA but not histone hyperacetylation. Mol. Cancer. 1, 2 (2002).
Chernukhin, I. et al. Physical and functional interaction between two pluripotent proteins the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF. J. Biol. Chem. 275, 29915–29921 (2000).
Quitschke, W.W., Taheny, M.J., Fochtmann, L.J. & Vostrov, A.A. Differential effect of zinc finger deletions on the binding of CTCF to the promoter of the amyloid precursor protein gene. Nucleic Acids Res. 28, 3370–3378 (2000).
Miranda, E., Dantzer, F., O'Farrell, M., de Murcia, G. & de Murcia, J. Characterisation of a gain-of-function mutant of poly(ADP-ribose) polymerase. Biochem. Biophys. Res. Commun. 212, 317–325 (1995).
Kanduri, M. et al. Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region. Mol. Cell. Biol. 22, 3339–3344 (2002).
Klenova, E. et al. CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms. Mol. Cell. Biol. 13, 7612–7624 (1993).
We thank A. Mattsson for expert technical assistance, H. Smith and M. O'Farrell for help with the in vitro poly(ADP-ribosyl)ation assay, S. Shamsuddin for providing the domains of CTCF expressed in bacterial system, P. Hassa for helpful comments, A. Vostrov and W. Quitschke for the recombinant CTCF from Pichia and A. Isaksson and the Wallenberg microarray platform at the Rudbeck Laboratory for their assistance. This work was supported by the Swedish Science Research Council (V.R., R.O.), the Swedish Cancer Research Foundation (C.F., R.O.), the Swedish Pediatric Cancer Foundation (B.C.F., R.O.), the Lundberg Foundation (R.O.), the Wallenberg Foundation (R.O.), the Juvenile Diabetes Research Foundation International (R.O.), the Breast Cancer Campaign (F.D., E.K.), PhD Studentship from the University of Essex (D.F.), Research Promotion Fund from the University of Essex (I.C., F.D., E.K.) and the Association for International Cancer Research (I.C., E.K.).
Wenqiang Yu, Vasudeva Ginjala, Vinod Pant, Igor Chernukhin and Joanne Whitehead: These authors contributed equally to this work.
Department of Development & Genetics, Evolution Biology Centre, Uppsala University, Norbyvägen 18A, Uppsala, S-752 36, Sweden
Wenqiang Yu, Vasudeva Ginjala, Vinod Pant, Joanne Whitehead, Gholamreza Tavoosidana, Rituparna Mukhopadhyay, Chandrasekhar Kanduri & Rolf Ohlsson
Department of Biological Sciences, Central Campus, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, Essex, UK
Igor Chernukhin, France Docquier, Dawn Farrar & Elena Klenova
Department of Molecular and Cellular Biology, Tottori University, Tottori, Japan
Mitsuo Oshimura
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA
Andrew P Feinberg
Molecular Pathology Section, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA
Victor Lobanenkov
Wenqiang Yu
Vasudeva Ginjala
Vinod Pant
Igor Chernukhin
Joanne Whitehead
France Docquier
Dawn Farrar
Gholamreza Tavoosidana
Rituparna Mukhopadhyay
Chandrasekhar Kanduri
Elena Klenova
Rolf Ohlsson
Correspondence to Rolf Ohlsson.
The authors declare no competing financial interests.
Yu, W., Ginjala, V., Pant, V. et al. Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation. Nat Genet 36, 1105–1110 (2004). https://doi.org/10.1038/ng1426
Issue Date: 01 October 2004
DOI: https://doi.org/10.1038/ng1426
Regulation of 3D chromatin organization by CTCF
Jian-Feng Xiang
& Victor G Corces
Current Opinion in Genetics & Development (2021)
Role of PARP-catalyzed ADP-ribosylation in the Crosstalk Between DNA Strand Breaks and Epigenetic Regulation
Haser H. Sutcu
, Elie Matta
& Alexander A. Ishchenko
Journal of Molecular Biology (2020)
Many facades of CTCF unified by its coding for three-dimensional genome architecture
Qiang Wu
, Peifeng Liu
& Leyang Wang
Journal of Genetics and Genomics (2020)
CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention
Elena M. Pugacheva
, Naoki Kubo
, Dmitri Loukinov
, Md Tajmul
, Sungyun Kang
, Alexander L. Kovalchuk
, Alexander V. Strunnikov
, Gabriel E. Zentner
, Bing Ren
& Victor V. Lobanenkov
Proceedings of the National Academy of Sciences (2020)
PARPs and ADP-ribosylation in RNA biology: from RNA expression and processing to protein translation and proteostasis
Dae-Seok Kim
, Sridevi Challa
, Aarin Jones
& W. Lee Kraus
Genes & Development (2020)
Nature Genetics | News & Views
Shifting insulator boundaries
Sangkyun Jeong
& Karl Pfeifer
Primers & PrimeViews
Nature Genetics ISSN 1546-1718 (online)

redpajama_set_name: RedPajamaCommonCrawl


text:
A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis
Ravindran, Vinod, Scott, D. L. and Choy, Ernest Ho Sing 2008. A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis. Annals of the Rheumatic Diseases 67 (6) , pp. 855-859. 10.1136/ard.2007.072652
Official URL: http://dx.doi.org/10.1136/ard.2007.072652
Objective: Treatments for psoriatic arthritis (PsA) range from high-cost agents such as tumour necrosis factor (TNF) inhibitors evaluated in large randomised control trials (RCTs) and low-cost disease-modifying anti-rheumatic drugs (DMARDs) studied in less detail. We compared their efficacy and toxicity in a systematic review. Methods: We searched Medline, PubMed and EmBase (1966–2006) for RCTs in PsA. We included RCTs that were randomised, placebo-controlled, in English, involved current treatments and only enrolled PsA patients. Efficacy was assessed by the numbers of patients withdrawn for lack of effect; toxicity by withdrawals for adverse events. RCTs were compared using risk ratios (RR) with 95% confidence intervals (CI). Results: We identified 32 potentially relevant RCTs; 14 were excluded because they involved unused agents, were unblinded, were not placebo-controlled and enrolled patients with other diseases. 18 studies were included in the meta-analysis assessing DMARD monotherapy (11), DMARD combinations (one), TNF inhibitors (five) and alefacept (one). Treatment was more effective than placebo (RR = 0.35; 95% CI 0.25, 0.49) but caused more toxicity (RR = 2.33; 95% CI 1.61, 3.37). There was evidence that gold, sulfasalazine, leflunomide and TNF inhibitors were effective; gold and TNF inhibitors showed the largest effect sizes; TNF inhibitors had the best efficacy/toxicity ratio (number needed to harm/number needed to treat = 0.25); tolerability was least with gold and leflunomide. Conclusions: Efficacy/toxicity ratios were highest with TNF inhibitors followed by leflunomide, gold and sulfasalazine. Gold, though effective, has excessive toxicity and sulfasalazine, though of low toxicity, was also relatively ineffective.
Systems Immunity Research Institute (SIURI)
R Medicine > RC Internal medicine
R Medicine > RM Therapeutics. Pharmacology
BMJ Publishing Group


It was August, four years ago, when I first knew.
Something's going to raise itself up from the dark soon, something's going to get pulled out of the ground, something's going to be liberated…something. is going. to die.
I could almost smell it, but I couldn't see it. Some elusive thing was pulling on me from the inside. And it hurt.
It was a tangled thread, a muffled song, a caged blackbird that only sings at night.
THIS THING needed to be brought out into the light of day, so I made the decision to HUNT IT DOWN.
Flaming arrow in hand, and equipped with night vision, I danced in the dark with the wounds of my marriage, my creativity, my body, my home, my community.
But still, this thing remained. And I couldn't quite locate it, so I did what I always do when Mystery presents herself.
A third Winter came, since that August hunch. And I shut myself into a hermitage.
I stayed on the land for close to an entire month, without setting foot in a car, or any place other than my homestead.
I broke bread with chosen family. I prayed. I listened. I cooked. I baked. I grieved. I walked with wild coyotes. I wept on my knees in the snow, again and again.
And, it's taken me more than half a year to STAND UP again because, THIS.
…A shimmering golden thread that MUST be woven into the fabric of a movement. A song that I'm learning to hear ~ the sweetest melody of the most incomprehensible beauty, sung by a bird who's taking broken wings to flight.
THIS, I care about almost more than anything in the world.
THIS is a purpose, a promise, a thing to live for.
A holy realization. A revolution.
Maybe you're thinking, 'of course'.
Until this changes, I promise. I will TAKE A STAND.
With shaking knees, I'LL STAND AND SING above the grave of the thing that I could smell decaying, August, four years ago.
It was my own silence waiting to die.
I want you to know that I AM HERE.
I HAVE A VOICE, and I will use it for good.
And so, #40DaysofFemalePower is Born.
Bearing witness. Thankyou for including me.
as I lie here awake at 2:08 AM thinking to myself …. no one should be left with their own thoughts alone at night.
I read this short essay now thinking everyone should be forced to feel their own thoughts alone at night in the dark while the coyotes circle the house hungry and waiting.
day 40. how many days is a lifetime? maybe a lifetime comes down to one monumental moment when you wake to realize this shall be no more as you find your voice and take back your joy realizing you aren't afraid of anything any more .
I want us to reframe the languaging of our uprising.
I see the importance of focusing on "The Feminine", not on the female gender.
That which is creative, nurturing, caring, cyclic, inclusive, softer, circular… for the greater good…. that force that will heal the gender-based atrocities and injustices perpetrated by men against women and against our mother planet… that is feminine and that is what matters.
Feminine power matters. And that power, that perspective, must come from all our hearts, not just women. That force MUST rise in every heart in order for us all to survive what we have done to each other and our planet.
And women must take responsibility for our part in empowering the patriarchy. It would be a mistake to think that the solution for our time is gender-based.
I believe that what we are feeling is the uprising of the feminine in the cosmos, in the sentient planetary mother, in nature, in all of us. This is the thing to be dedicated to. This is the stand I take.
I say SHE IS rising!
I am standing with you in THIS. I too have just spent a month in silence on retreat in South Africa and felt the presence of the land speaking to me so strongly. I am not sure what is going to emerge in my life, but I have declared that I AM WILLING. I have also declared that I will be part of STOPPING THE VIOLENCE that is so endemic on our earth – again I don't know how yet. I will also use my voice for THIS.
Welcome Beauty. Unsure as to how I was lucky enough to be blessed with this deep , honest, magical post, but it mirrors my lifelong work/play of co-creating Woman/Earth honoring ritual circles. How inspiring, how affirming to witness the steady spiraling spread of this empowered Woman-consciousness. Carry on!
Thank you for sharing this always powerful realization, to germinate again and again in our bodies and our souls. I am with you.
More than fantastic. I hear you speaking from so deep, knowing, through you, to earth. Powerful. And yes!!!
Wow. Perfect. Powerful. Thank you.
I too feel this way, sister. But how do we make this change? To awaken women's power, to bring back the respect and honor for all women.
Wow! Awesome! thank you for doing the work. I witness you. I'm with you. Well maybe behind you… I'm doing the work, slowly, to find my voice.
My spirit quickened as I read, yes I feel you, I stand up with you For Woman Matter dearly.
Thank you, I am here, I am here standing with you and for us all.
Thank you , miles de gracias India por estas hermosas palabras y este re inicio.


Solar powered lights can be installed anywhere, where a traditional, grid-bound installation would be to time-consuming or simply impossible due to local conditions.
High reliability and little maintenance efforts make an efficient operation possible.
The solar powered lighting solution from DewiTec is completely solar powered, reducing installation time and costs. Removing reliance on grid-power allows the system to be portable and quickly deployed.
Accepted for use globally, the 2.4GHz wireless network allows users to directly control the operation of lights from a hand-held controller. Control light intensities, switch between visual or Infra-Red (IR), or turn the operational mode of the entire system ON or OFF.
The helipad perimeter lights available at DeWiTec are the only solar-powered helipad lights to comply with the photometric performance and height requirements of ICAO Annex 14 international standards.
Using clean, pollution-free energy from the sun to power the lights offers an eco-friendly and cost effective lighting solution. Because these aviation lights are run using solar power there are zero carbon dioxide emissions!
There are zero electricity costs associated with running a solar airfield lighting system because the electricity used to power the lights is produced by solar panels using the energy from the sun. Depending on the type of operation and the cost of electricity, this can add up to hundreds of thousands of dollars in savings over the life of the system.
The Solar Powered aviation lights use energy efficient LEDs as their light source which have a working life up to 100,000 hours. This long life, combined with the advanced batteries and self-contained power supply mean that the entire system is virtually maintenance free. The user-replaceable batteries last up to five years, meaning the only scheduled maintenance for most operators would be battery replacement at the five year mark.


text:
Q: integral identity relating to tan(x) How can I prove the integral identity below?

$$
\int_0^{\pi/12}\ln \Big(\cot x \tan^2(3x)\Big)dx=\int_0^{\pi/12}\ln \Big(\tan x\Big(\frac{3-\tan^2x}{1-3\tan^2x}\Big)^2\Big)dx=0
$$

where we employed the fact that $\tan(3x)=\tan x\frac{3-\tan^2x}{1-3\tan^2x}$.

A: Use the identity:
$$\int_0^a f(x)dx=\int_0^a f(a-x)dx$$
And then try to add them.
$$I=\int_0^{\pi/12}\ln(\cot x)+2\int_0^{\pi/12}\ln(\tan 3x)\\=\int_0^{\pi/12}\ln(\cot x)+2\int_0^{\pi/12}\ln(\tan (3(\pi/12-x)))\\=\int_0^{\pi/12}\ln(\cot x)+2\int_0^{\pi/12}\ln(\tan (\pi/4-3x))$$


text:
The Blue Bird's Palace
Written by Orianne Lallemand and Illustrated by Carole Henaff
Inspired by the Russian storytelling tradition, this contemporary fairy tale about a relatable heroine's inner transformation from materialism to gratefulness will captivate readers of all ages. The relevant message, hardcover format and stunning full color illustrations will make this a cherished gift during the holidays and throughout the year.
Classic Fairy Tales Activity Guide for Pk-2
This activity guide supports classic fairy tales for grades PK-2.
Classic Fairy Tales Activity Guide for 3-5
This activity guide supports classic fairy tales for grades 3-5.
Daniel Tiger's Neighborhood: You're Still You!
Written by Maggie Testa and Illustrated by Jason Fruchter
Lots of Daniel's friends look different today: Prince Wednesday isn't wearing his glasses, Teacher...
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Written and Illustrated by Rachel Renee Russell
Life is looking up for Nikki Maxwell, especially since her crush, Brandon, asked her to be his lab...
The Three Little Pigs
Written and Illustrated by Marie-Louise Gay
Marie Louise Gay's wacky take on the classic tale of the Three Little Pigs brings new life to this...
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Written by Chris Paul and Illustrated by Frank Morrison
Everybody told Chris that he was too small to play basketball. But he ignored them all...because he...
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Let's go walking down our street. Friends and neighbors here to greet. There are oh so many folks to...
The Fox and the Falling Leaves
Written by Julia Rawlinson and Illustrated by Tiphanie Beeke
In a first encounter with the changing seasons, a young fox is worried when his favorite tree drops...
Max the Brave
Written by Ed Vere
Max is a fearless kitten. Max is a brave kitten. Max is a kitten who chases mice. There's only one...
Written by Margaret Wise Brown and Illustrated by Clement Hurd
This short, simple story—considered a classic-- helps children put closure on their day and go to...
The August 5
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Fourteen-year-old Tommy Shore lives a life of privilege: he has the finest clothing, food, and...
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Will Mr. Fish find perfect gifts for everyone on his list? Will he finish his shopping in time? Swim...
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Trisha is very excited to start school, but is dismayed to find learning to read so challenging. She...


Donpaul McAllister is an American song-writer, guitar player and vocalist. His richly textured musical layers are distinctive in a style pulling from multiple genres and coming together in a blend of emotion and a stark visual component developed through thoughtful lyrics and delicate vocal delivery.
structure that can carry emotion and atmosphere; this is what art is to me.


Internal Revenue Commissioner John Koskinen on Tuesday declined to appear at a House Judiciary Committee hearing planned a week ago to investigate his "misconduct" in allegedly withholding information from Congress on the long-simmering charges that the agency is biased against conservatives.
That posture angered Republicans on the Judiciary panel, prompting Chairman Rep. Bob Goodlatte, R-Va., after some debate, to rule against including Koskinen's prepared defense in the hearing record.
Conyers accused the majority of representing only a small group, citing objections to impeachment proceedings from House Speaker Paul Ryan, R-Wis.; former Speaker John Boehner, R-Ohio; Ways and Means member Rep. Charles Boustany, R-La.; and Sen. Orrin Hatch, R-Utah, chairman of the Finance Committee. "The claim is not that we disagree with his decisions, or that we question the speed and completeness with which his agency provided answers—but that he knowingly and intentionally supplied us with false information," Conyers said.
Panel Democrats clashed with Rep. Darrell Issa, R-Calif., over whether the hearing was an investigation of the evidence of misconduct, or an "impeachment inquiry," in Issa's phrase. Koskinen has "delivered a self-serving statement and refused to be here for our impeachment inquiry," said Issa, likening the commissioner's tactic to that of former IRS official Lois Lerner, who appeared before Issa's Oversight panel, proclaimed her innocence and pleaded the Fifth Amendment.
"Would we ordinarily accept such a statement?" Issa asked, saying he would agree to putting Koskinen's letter in the record only if it was made clear the commissioner was invited, failed to appear and delivered a "self-serving statement." In the end, the statement was not included, though Goodlatte did permit a written defense of Koskinen submitted by Rep. Elijah Cummings, D-Md., ranking member of the House Oversight and Government Reform panel.
The hearing then proceeded with videos and testimony against Koskinen from witnesses who are members of the panel: Rep. Jason Chaffetz, R-Utah., and Ron DeSantis, R-Fla.
The hearing came the same day the IRS saw its budget targeted for a $236 million cut in the fiscal 2017 Financial Services spending bill unveiled by the House Appropriations Committee. The administration had requested an increase of $1 billion. The bill "holds the agency's budget to below the 2008 level, but provides sufficient resources to perform its core duties," the committee said in a statement.
"The IRS has been plagued in recent years by the inappropriate actions of its employees and political leadership, resulting in the waste of taxpayer dollars and in unjust treatment and targeting of certain ideological groups," the appropriators added, itemizing a list of provisions aimed at trimming bonuses and preventing regulations that might appear to target groups for ideological reasons.


text:
Rural/CountrySide
Living the Village Life in Italy
Is the fate of many unique, virtually abandoned villages in the unknown corner of Abruzzo sealed? Not if Swedish-Italian millionaire Daniele Kihlgren can help it. In 1999, a solitary motorbike trip proved to be a revelation for this modern-day idealist. By chance, he stumbled upon the almost-deserted hilltop village of Santo Stefano di Sessanio in the Gran Sasso and Monti della Laga National Park in the Apennines. He was struck speechless, not only by the outstanding beauty of the setting, but also because almost everything was untouched. "Time seemed to have stood perfectly still – no concrete buildings, no factories, no tourist infrastructure like the Swiss chalets you find in so many Abruzzese towns," says Kihlgren. It wasn't long before he returned to Santo Stefano – not only with his motorbike, but also with a plan to save this village from extinction. Kihlgren, in his mid-forties, has been described as a maverick, a millionaire with enormous willpower. And where there's a will, there's a way. Kihlgren bought a house in Santo Stefano and soon many more. Next step was signing a deal with the local authorities to leave Santo Stefano in its original condition – in other words, an embargo on building new houses and a ban on the use of concrete. In exchange, Kihlgren would spend a substantial sum, up to €4.5 million – a mix of his own and borrowed money – on breathing new life into the village and giving it a second chance. "This has nothing to do with renovation," Kihlgren insists. "It's about restoration – restoring honour. I had a unique opportunity to save one of the last authentic places in Italy from the grip of cement." In 2004, five years after Kihlgren first wandered through Santo Stefano, the village was ready for its second life. Kihlgren received help from some big names, including the renowned British architect David Chipperfield, who also supports the concept of 'conservative restoration', or restoring while maintaining original features. The result of the first project here in Santo Stefano di Sessanio is Sextantio Albergo Diffuso. A fairly recent concept in the hotel business, an albergo diffuso is a 'hotel' scattered throughout a town in different houses. Guests are assimilated into the village and feel part of the community. Kihlgren's Sextantio originally had 32 houses, but some have been sold to foreigners. Buying a completely restored house from Kihlgren costs about €1200 to €1500 (from $1470) per square metres. The rest serve as hotel rooms with a central reception area, hotel manager and staff.The rooms usually come with a kitchenette, a table and chairs, a fireplace – Spartan luxury.
"We try to retain everything that refers back to village life," says Kihlgren. "Only local materials are used, and old furniture and artefacts were sourced in the area. Modern technology, such as under-floor heating and light switches, is discreetly hidden. We also conducted research with the National Museum of Abruzzo and talked to the elderly residents of Santo Stefano to discover how people used to live and what materials they used. Even beter, after a couple of days staying here, you feel connected with the place. Probably just how Kihlgren felt the moment he decided to save a part of Italian heritage.
Santo Stefano di Sessanio is 150 kilometres (a 1.5-hour drive) from Rome and 100 kilometres from the Adriatic coast and the city of Pescara. The best way to explore the region is by car. Sextantio Albergo Diffuso has 27 rooms dotted throughout several buildings, ranging from double rooms to suites, which are twice as large.
A Classic Room with breakfast for two starts at a bargain €160 ($196) per night in low season. While the setting is perfect, there's definitely room for improvement on the hospitality side.
Source: Classe Touriste
Posted by: Vipul Kapoor // Culture, From Around the World, Romantic, Rural/CountrySide // apennines, culture, heritage, history, hotel review, italy, santo stefano di sessanio, unique hotel, village life // January 13, 2015
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THU > org > IMM > Biomechatronics > News
We will attend the "Symposium für Biomechanik & Orthopädie" on April 28th 2022 at the company ZwickRoell with an own contribution from the filed "Biomechanics".(https://www.zwickroell.com/de/news-events/messen-veranstaltungen/zwickroell-biomechanik-symposium/)
We will attend the 21. ITG/GMA- Fachtagung Sensoren und Messsysteme 2022 on May 10th-11th 2022 with own contributions from the field "SensAI".
(https://www.ama-science.org/ama-conferences/21-itggma-fachtagung-sensoren-und-messsysteme-2022/itg-sensoren-und-messsysteme-2022/)
We will attend the international trade show and world congress OT World 2022 on May 10th-13th 2022 with an own booth. Find us in hall 1/floor 0.
(https://www.ot-world.com)
On October 29, 2021, Eugen Dötzel successfully defended his dissertation at the Medical Faculty of the University of Ulm with the title: A clinical study to investigate the biomechanics of forefoot amputees when wearing an individually adapted carbon prosthesis and a (Standard) silicone prosthesis.


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KSK Energy ties up $3.6 bn for power project
1 min read . Updated: 20 Sep 2010, 11:30 AM IST Reuters
KSK Energy VenturesShandong Electric Power ConstructionKSK MahanadiHome
Mumbai: The Indian unit of London-based KSK Power Ventur Plc said on Monday it had tied up $3.6 billion in loans and equity for a 3,600 megawatt thermal power project in India.
Shares in KSK Energy Ventures Ltd, which has started civil work on the complex in the state of Chhattisgarh, rose as much as 6.7% on the news.
The company has appointed Chinese firm Shandong Electric Power Construction Corp. to design and build the project called KSK Mahanadi, while Indian companies such as Punj Lloyd and Petron Engineering Construction have been offered sub-contracts.
Twenty-seven banks and institutions have offered $2.88 billion in loans, while state-run finance firm IFCI Ltd has agreed to invest $56 million for a 7.72% stake in the project, the company said in a statement.
KSK Mahanadi has signed a bulk power transmission agreement with Power Grid Corp. of India. The company did not say when the project would be completed.
The KSK Group, founded by two finance professionals S. Kishore and K.A. Sastry, has four operational power plants in India with a combined capacity of 279 megawatt, while work on going on three plants aggregating to 4,183 megawatt.
At 10:57 a.m., shares of KSK Energy were trading up 5.1% at Rs181.5, while the main BSE index was up 0.9%.


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Groovemeister
Date and Time : 10 October 2019, 9pm to 11:55pmAdd to Calendar 10/10/2019 21:00 10/10/2019 23:55 Asia/Kolkata Groovemeister Must check for Details and on Event day before visiting :
https://www.delhievents.com/2019/10/music-groovemeister-piano-man-gurugram.html The Piano Man, 32nd avenue, Sector 15 Part 2, Gurugram, Haryana 122002DD/MM/YYYY
Entry : by Tickets priced at Rs. 199, Rs. 299, Available at :
Online : BookMyShow
Offline : at the venue before the show if not sold out
Tele-Booking : 011-41315181
Venue : The Piano Man, 32nd avenue, Sector 15 Part 2, Gurugram, Haryana 122002
Venue Info : thepianoman.in | Map | Nearest Metro Station - 'IFFCO Chowk(Yellow Line)'
Event Description : MUSIC : Groovemeister
Groovemeister is a quintet from Bangalore, India.
They love to tell stories through the use of modern sounds laced with influences from contemporary jazz, blues, funk and soul. The ultimate purpose of this unit is to groove, to communicate at an abstract level beyond the realms of language, thought and gesture.
Through their compositions and collective improvisation they strive to evoke emotions and visions of the stories that they conjure up.
Vijayganesh Panchanadhan : Guitar
Vijay can often be seen twisting and jumping while playing. His playing is an expression of the joy that music brings to him. Vijay is a student of world music and constantly tries to incorporate harmonic and rhythmic concepts from across the globe in his playing. His influences are diverse and include artists like Phish, John Scofield, Steely Dan, as well as Carnatic and African styles.
Legsang Sherpa : Guitar
Legsang Sherpa's calm aura hides a musician with a command over his instrument. His playing draws from the vast reservoir of ideas that he has acquired through diligent practice of his craft. His melodies and harmonic language display the nuances of the Jazz and Blues idioms delivered with deftness of a classically trained guitarist. His influences range from Led Zeppelin, Lynyrd Skynyrd to Charlie Hunter, Pat Metheny and many others.
Siddharth Suresh : Piano/Keyboards
Siddharth Suresh has an inimitable style on the keys with an immovable groove and an ever-evolving harmonic language. His playing ebbs and flows with ease as is required by the music. He is inspired and influenced by a wide palette of music from Classical, Rock to Jazz.
Arjun Ramdas : Bass
Arjun Ramdas is the vital cog in this groove outfit. His playing has the magic that breathes life into the song. He is an ardent student of the music and a fearless improviser who constantly pushes his personal and the band's boundaries
Wesley Newton : Drums
Wesley is the pocket-machine and the foundation this outfit is built upon. The source of his music is his heart and his playing is a reflection of his personality. His musical influences range from African-American Gospel Music to R&B/Soul and Jazz.
• Being invited to play at ThePianoManJazzClub, Delhi.
• Playing alongside The Amyt Dutta Project at The Bflat Bar, Bangalore.
• Inaugurating the Groovemeister DIYSeries at Artville Cafe, Bangalore.
• Being invited to play at The Sofar Sounds, Bangalore.
Music : www.facebook.com/pg/groovemeisterindia/videos
Related Links : Music | Nightlife
Groovemeister Reviewed by DelhiEvents on Thursday, October 10, 2019 Rating: 5


Contents: Introduction -- Program management -- DoE initiatives -- SBIR and STTR awards at DoE -- Quantitative outcomes -- Participation of women and minorities -- Insights from case studies and survey responses -- Findings and recommendations -- Appendixes -- Appendix A: Overview of methodological approaches, data sources, and survey tools -- Appendix B: Major changes to the SBIR and STTR programs resulting from the 2011 SBIR Reauthorization Act, P.L. 112-81, December 2011 -- Appendix C: National Academies of Sciences, Engineering, and Medicine 2014 SBIR/STTR survey -- Appendix D: List of research institutions involved in surveyed DoE SBIR/STTR awards -- Appendix E: Case studies -- Appendix F: Annex to Chapter 5: extended 2014 survey data -- Appendix G: Glossary -- Appendix H: Bibliography.Includes bibliographical references (pages 396-417).Summary: "The Small Business Innovation Research (SBIR) program is one of the largest examples of U.S. public-private partnerships, and was established in 1982 to encourage small businesses to develop new processes and products and to provide quality research in support of the U.S. government's many missions. The Small Business Technology Transfer (STTR) Program was created in 1992 by the Small Business Research and Development Enhancement Act to expand joint venture opportunities for small businesses and nonprofit research institutions by requiring small business recipients to collaborate formally with a research institution. The U.S. Congress tasked the National Research Council with undertaking a comprehensive study of how the SBIR and STTR programs have stimulated technological innovation and used small businesses to meet federal research and development needs, and with recommending further improvements to the programs. In the first round of this study, an ad hoc committee prepared a series of reports from 2004 to 2009 on the SBIR and STTR programs at the five agencies responsible for 96 percent of the programs' operations -- including the Department of Energy (DoE). Building on the outcomes from the first round, this second round presents the committee's second review of the DoE SBIR program's operations. Public-private partnerships like SBIR and STTR are particularly important since today's knowledge economy is driven in large part by the nation's capacity to innovate. One of the defining features of the U.S. economy is a high level of entrepreneurial activity. Entrepreneurs in the United States see opportunities and are willing and able to assume risk to bring new welfare-enhancing, wealth-generating technologies to the market. Yet, although discoveries in areas such as genomics, bioinformatics, and nanotechnology present new opportunities, converting these discoveries into innovations for the market involves substantial challenges. The American capacity for innovation can be strengthened by addressing the challenges faced by entrepreneurs"--Publisher's description.


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FERCtastic: What MLP and Midstream Investors Should Know about the FERC
10/15/19 | Stacey Morris
    
Midstream investors should have some familiarity with the FERC given its oversight of interstate pipeline rates, LNG export projects, and interstate natural gas pipeline projects.
FERC is tasked with making sure rates on interstate pipelines are just and reasonable.
FERC has been criticized for delays in approving LNG export facilities but has made progress in improving its processes.
While a regulatory body may seem like a dry topic, midstream investors should have a basic understanding of the Federal Energy Regulatory Commission (FERC), as its oversight powers and policies can have implications for midstream assets. FERC is tasked with regulating interstate pipelines, including rates, and overseeing the siting and construction of liquefied natural gas (LNG) export facilities. FERC is an independent agency, which has up to five commissioners appointed by the President to serve five-year terms. (Currently, two commissioner seats are open, with James Danly recently nominated to fill one commissioner vacancy pending Senate approval.)
For investors, FERC became tantamount to a four-letter word in March 2018 when the Commission announced a policy revision intra-day that sent MLP equities spiraling. To say the announcement could have been better handled is an understatement. The implications of the March 2018 announcement have largely played out with greater clarity provided in the finalized rule issued in July 2018. In short, the result was not nearly as bad as initially feared. However, investors have long memories, especially when money is lost, and many maintain a negative perception of the FERC as a potential risk to MLPs and midstream. Today, we provide a brief overview of the FERC's regulation of pipelines – where the commission has jurisdiction and how they regulate rates – and discuss FERC's role in approving LNG export facilities.
FERC regulates interstate pipelines.
If a pipeline crosses state lines, it is subject to FERC regulation, with some variances depending on what the pipeline transports. FERC evaluates applications for building and operating interstate natural gas pipelines under Section 7 of the Natural Gas Act (read more). In order to build an interstate natural gas pipeline, companies must go through a multi-step process that includes notifying and soliciting feedback from stakeholders, applying for a certificate of public convenience and necessity from the FERC, and conducting environmental studies (read more). In April 2018, FERC announced a notice of inquiry to receive feedback on its policies surrounding its review of natural gas pipeline projects, but no action has been taken since then.
FERC regulates interstate liquids pipelines under the Interstate Commerce Act, which refers to common carriers transporting oil by pipeline between different states. Oil here encompasses crude oil, refined products, and natural gas liquids, which we will refer to collectively as liquids for ease. FERC is tasked with making sure shippers receive equal service and equal access to liquids pipelines. Unlike natural gas pipelines, FERC does not approve the construction (or abandonment) of liquids pipelines.
What does FERC not regulate when it comes to pipelines? For both liquids and natural gas pipelines, FERC has no oversight of pipeline safety, which falls to the Pipeline and Hazardous Materials Safety Administration (PHMSA). Additionally, pipelines that do not cross state lines are regulated by the relevant state. For example, pipelines in Texas are regulated by the Railroad Commission of Texas.
How are pipeline rates regulated?
The Office of Energy Market Regulation (OEMR) within the FERC reviews filings from natural gas and liquids pipelines to make sure rates and terms of service are just and reasonable and not unduly discriminatory or preferential. FERC is supposed to ensure that pipeline operators receive a reasonable fee for their services and reasonable returns – an important point to keep in mind for those who view the FERC negatively following the March 2018 announcement. Though the same body regulates rates for both gas and liquids pipelines, the approach for tariffs differs.
Natural Gas Pipelines – According to the Natural Gas Act, FERC is tasked with ensuring that rates on natural gas pipelines are just and reasonable. The Natural Gas Policy Act of 1978 authorized FERC to regulate intrastate natural gas pipelines that operate in or support interstate commerce. These intrastate pipelines must have an approved tariff on record with the FERC, but the rate can be based on different methodologies as filed with the appropriate state regulatory agency (read more). Rates must be "fair and equitable." Interstate natural gas pipelines may charge cost-of-service, market, or negotiated rates.
A natural gas pipeline can apply to increase its rates in a Section 4 rate case, but the pipeline must prove that the new rate is just and reasonable. Once the filing has been submitted, the pipeline and its customer(s) may agree to settle a new negotiated rate, or the case could be heard by an Administrative Law Judge. If a rate is considered to be too high, FERC can require a prospective rate change under Section 5 but must prove that rates are no longer just and reasonable. FERC can initiate a rate investigation on its own or in response to a shipper complaint. As an example, FERC initiated a rate investigation of two gas pipelines in 2017, with one earning an estimated return on equity above 20% and the other earning an estimated return just shy of 20%.
Liquids Pipelines – Most interstate liquids pipelines adjust their rates based on FERC's Oil Pipeline Index, which sets a maximum for annual rate increases based on the Producer Price Index for Finished Goods plus an adjustment (currently PPI-FG + 1.23%). The index is reviewed every five years, with the current methodology applicable through July 2021. While most liquids pipelines use the index, rates can be based on cost of service, market rates, or negotiated rates.
FERC making progress on improvements to LNG export project reviews.
FERC's review process for LNG export facilities has been criticized due to delays. FERC approves the siting and construction of LNG export facilities under Section 3 of the Natural Gas Act, reviewing the environmental impacts, safety, and engineering of facilities. In August 2018, FERC provided environmental schedules for twelve LNG facilities and announced streamlining efforts for reviewing LNG applications, which were expected to reduce reviews by 9-12 months in some cases. At the time, FERC announced other steps to improve the application process including partnering with the PHMSA for input on safety and the hiring of outside contractors to assist with reviews.
In February 2019, FERC approved Venture Global's Calcasieu Pass LNG export facility – its first LNG export project approval in over two years. Subsequently, additional LNG projects have been approved this year, including Tellurian's (TELL) Driftwood LNG and Sempra Energy's (SRE) Port Arthur LNG project (read our latest piece on LNG exports for more detail). In July 2019, FERC announced a new LNG division within its Office of Energy Projects and a new satellite office in Houston for eight staff members, complementing the twenty LNG-focused employees based in Washington, D.C. With the US expected to become the largest exporter of LNG in 2024 according to the International Energy Agency, FERC's approval process has weighty implications for US LNG exports, and the Commission has clearly made an effort to improve its processes. For more information on LNG projects, FERC's website includes details on the status of projects, whether they've been approved, approved but not built, or have merely been proposed.
An article about the FERC may seem like the ideal reading material to ease into a Sunday afternoon nap. However, FERC's oversight of interstate pipeline rates, LNG export projects, and interstate natural gas pipeline projects means that FERC can have some bearing on midstream revenues (depending on the pipeline and rate mechanism) and project timelines. For that reason, it's helpful to have a working knowledge of the FERC.
Other insights recommended for you
2020 Midstream Outlook Video
Seasons Greetings: Energy Seasonality and Midstream
Midstream Macro
Midstream Energy Battle: What Subgroup Has Performed Best in 2019?
Investment Considerations


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Cryptonews News 'Market-led' Currencies Can Live Alongside Digital Euro - ECB Board Member
Sead Fadilpašić
@sead-fadilpasic
'Market-led' Currencies Can Live Alongside Digital Euro - ECB Board Member
While global regulators are warning about the risks of cryptocurrencies and private money initiatives such as Facebook's Libra, a member of the Executive Board of the European Central Bank (ECB) made a somewhat surprising statement in support of "market-led initiatives."
Fabio Panetta. Source: ecb.int
In a recent blog post, Fabio Panetta emphasized that the ECB is looking into "possible future avenues by assessing the case for issuing a "digital euro"." He added that there is a high-level task force exploring both the benefits and the disadvantages of introducing a digital currency that intermediaries or possibly citizens could eventually use via electronic devices for every-day spending.
"However, our analysis of the opportunities and challenges of central bank digital currencies – which will consider the experience of the COVID-19 crisis – should not discourage or crowd out market-led initiatives aimed at introducing private electronic means of payment with similar features in terms of user needs," he stressed.
Panetta also served as Senior Deputy Governor of the Bank of Italy before joining the Executive Board at the ECB. Coincidentally, a recent survey showed that Italians are among the biggest crypto believers in Europe.
Meanwhile, the statement is placed in the context of the growing demand for efficient, safe, easy-to-use, and low-cost electronic payment solutions amidst the ongoing coronavirus pandemic and lockdowns across Europe and the world - which might be here to stay for a while. Regular consumers need to be able to get money, as well as send it to their families and friends, or use it to purchase products online. Such payment systems are also necessary to "quickly mobilize the resources made available to support small companies, self-employed workers and social institutions," Panetta said.
But he also pointed out that this is not a novel approach for the ECB, stating that the bank had been stressing the need for Europe to "supply fundamental services such as electronic payments autonomously, in order to strengthen its sovereignty in the global economy," even before the pandemic. An eventual digital euro is one potential path towards making this happen, which, as said, is still being looked into. But in the meantime, Panetta said that the goal of the Eurosystem's retail payment strategy is "to foster pan-European market solutions" for instant payments at both the point-of-sale and online payments.
Meanwhile, last week, the Dutch National Bank (DNB) admitted that some parts of Bitcoin's underlying technology could be used in creating a new type of currency. DNB stressed that "the Netherlands provides a suitable testing ground for such an experiment," and is "ready to play a leading role."
Learn more: Can CBDC Help Recover From Coronavirus Recession And Lead To Bitcoin?
Cash demand
Another point the ECB Executive Board Member touched upon is people hoarding cash in the time of crisis. There was a spike in demand for cash once the pandemic started spreading across the continent, which the weekly increase in the value of banknotes in circulation almost reaching the historical peak of EUR 19 billion (USD 20.65 billion) mid-March. The increase reflects higher spending in supermarkets and shops, as well as "people's impulse to hoard cash during a crisis," which is not a new phenomenon. Already in early April, cash demand returned to normal levels, while several countries reported below-expected cash withdrawals for the time of year, which is partly due to the lockdown, explained Panetta.
As to how the ECB is dealing with this, he said that "the Eurosystem – the ECB and the 19 euro area national central banks (NCBs) – plans the activities related to the cash supply chain (production, storage, distribution and re-circulation) well in advance," thus being "well-prepared to ensure the continued availability of banknotes in crisis times." The NCBs have large stocks of cash, including a strategic contingency stock to cope with unexpected developments, and these stocks are continuously monitored, he adds. Nonetheless, given the major barriers the lockdowns pose, the ECB is adapting their processes "on an ongoing basis to ensure that the banknotes supply chain remains intact," such as intensifying the virtual contacts between the ECB as coordinator and the NCBs, as well as at national level, between the NCBs and external partners (e.g. cash-in-transit companies and banks).
As reported, the "central bank of central banks" - the Bank for International Settlements (BIS) - and multiple analysts think that the fear of the coronavirus transmission via cash and banking cards may shorten the road to CBDCs. Both the BIS and the ECB through their respective research found that coronaviruses can survive more easily on a stainless steel surface and can be transferred more easily from plastic compared to cotton banknotes. "Overall, banknotes do not represent a particularly significant risk of infection compared with other kinds of surface that people come into contact with in daily life," said the ECB, noting that their research into this continues.
Learn more: This Is How G20 Might Keep Crypto And Stablecoins at Bay
European Central Bank Cryptocurrency Digital fiat CBDC


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Blackhawks notes: Desperate playoff chase hinges on Corey Crawford
By Jason Lieser Mar 9, 2019, 1:29pm CST
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The Blackhawks are depending on Corey Crawford to lead them to the playoffs. | Jonathan Daniel/Getty Images
DALLAS — Even though Corey Crawford still is working his way back to peak form after a long absence, there's no one Blackhawks coach Jeremy Colliton trusts more in net for a big game.
The Hawks need a furious finish to have a chance in the wild-card race and believe Crawford has progressed in his first two weeks back from a concussion.
"His track record speaks for itself," Colliton said of the two-time Stanley Cup winner. "If we're going to go on a run here, he's going to be the guy. I think he's feeling better every day. I thought he looked really good in practice."
It was expected that Crawford would need a few games to get going, but the Hawks can't afford a prolonged transition at this point. He had an .865 save percentage and allowed 13 goals in his first three starts, two of which were victories.
Crawford stopped 26 of 27 shots Saturday in the Hawks' 2-1 victory against the Stars in his best performance since returning. He saved the game by breaking up a two-on-one rush with 3:31 left by slapping the puck away.
Colliton has little choice but to count on Crawford. Cam Ward, who started 27 games, is out at least another week because of a knee injury. Ward had a .908 save percentage in his last 10 games.
The Hawks recalled rookie Collin Delia from Rockford on Tuesday to be Crawford's backup. He has had an encouraging season overall but allowed 13 goals and had an .831 save percentage in three starts — he was pulled eight minutes into one of those — before being sent down last month.
Ample firepower not enough
The Hawks have issues, but offense isn't one of them. They were No. 8 in the NHL in scoring heading into the game against the Stars and had three of the league's top 26 goal-scorers.
Patrick Kane (40), Alex DeBrincat (37) and Jonathan Toews (29) are having potentially the best seasons of their careers, and their 106 goals make them the highest-scoring trio in the league. The Lightning are next at 104 from Nikita Kucherov, Brayden Point and Steven Stamkos.
The Hawks also have the league's top foursome with Brandon Saad chipping in 21.
• Blackhawks deliver defensive gem, keep playoff hopes alive in 2-1 win over Stars
• Brendan Perlini finds new perspective during frustrating season
"We know we're gonna score goals; we're not worried about that," Colliton said. "But when you go on the ice, let's make sure that we're ready to defend, ready to compete, because we can create offense out of that.
"That's one thing our team really does well is create offense out of transition, so we want our guys to go on the ice with the mindset that, 'We're ready to defend,' and if we do that, then we're gonna be harder to beat."
The Hawks were last in the league with 3.78 goals allowed and 11.3 high-danger scoring chances against per game. They were second-worst with an average of 35 shots on goal allowed.
Caggiula out
Winger Drake Caggiula, who had been playing on the top line, remains in the concussion protocol and missed his fourth consecutive game. He did not travel to Dallas.
Caggiula suffered a concussion when Ducks winger Rickard Rakell smashed him face-first into the boards Feb. 27. Rakell was ejected, but a league spokesperson said the play was reviewed, and the NHL decided against a fine or suspension.
Next Up In Blackhawks
Seth Jones' return boosts Blackhawks with games against Wild, Avalanche looming
Blackhawks will have an Olympian after all in goalie prospect Drew Commesso
Blackhawks' February schedule updated, with 7 games rescheduled
As NHL plans to cease asymptomatic testing, Blackhawks' COVID-19 issues subside
Blackhawks notebook: Marc-Andre Fleury's stellar January keeps getting better
Defenseman Seth Jones' absence finally catches up to Blackhawks in loss to Kraken