cssi/SciSciGPT-SciSciNet huggingface dataset:
Aortic valve replacement for the asymptomatic patient with aortic regurgitation: a new piece of the strategic puzzle.

For patients with hemodynamically severe aortic regurgitation (AR), the primary remedial therapy is surgical aortic valve replacement (AVR). Timing of surgery, however, is a moving target. Techniques and prosthetic devices continually improve, justifying AVR progressively earlier in the natural history of the disease. Indeed, there is currently a general consensus that surgery for AR is appropriate when congestive symptoms first appear, even if they are mild.1 This philosophy represents a distinct departure from the accepted standard of a generation ago, when the symptomatic indication for AVR was New York Heart Association functional class III. For asymptomatic patients, AVR remains controversial, except when left ventricular (LV) systolic performance is subnormal at rest as judged from ejection fraction (EF, or the parallel echocardiographic measure of fractional shortening [FS]). This standard was first suggested by Henry et al,2,3⇓ who began a prospective echocardiographic and clinical assessment of patients with AR in 1972. Henry et al tested two hypotheses: first, that outcome after AVR is dependent on LV systolic performance, and second, that progression to symptoms is predictable when performance is subnormal in asymptomatic patients. See p 2687 The patients of Henry et al underwent AVR only when symptoms developed.2 If, by that time, FS at rest was subnormal, long-term postoperative survival averaged approximately 45% at 4 years after operation, compared with 90% if FS was normal pre-AVR. Although the point estimates were confounded in some of their 49 patients by concomitant mild aortic stenosis or by coronary artery bypass grafting, the importance of LV performance in predicting outcome was clear, as was the sharp outcome dichotomization associated with normal versus subnormal LV performance. The data of Henry et al soon were supported by those of Cunha et al,4 Forman, et al,5 and Greves et al.6 In …
Recapitulation of short RNA-directed translational gene silencing in vitro

microRNAs (miRNAs) are a large class of endogenous short RNAs that repress gene expression. Many miRNAs are conserved throughout evolution, and dysregulation of miRNA pathways has been correlated with an increasing number of human diseases. In animals, miRNAs typically bind to the 3' untranslated region (3'UTR) of target mRNAs with imperfect sequence complementarity and repress translation. Despite their importance in regulating biological processes in numerous organisms, the mechanisms of miRNA function are largely unknown. Here, we report in vitro reactions for miRNA-directed translational gene silencing. These reactions faithfully recapitulate known in vivo hallmarks of mammalian miRNA function, including a requirement for a 5' phosphate and perfect complementarity to the mRNA target in the 5' seed region. Translational gene silencing by miRNAs in vitro requires target mRNAs to possess a 7-methyl G cap and a polyA tail, whereas increasing polyA tail length alone can increase miRNA silencing activity.
Mutation and expression analysis in medulloblastoma yields prognostic variants and a putative mechanism of disease for i17q tumors

Current consensus identifies four molecular subtypes of medulloblastoma (MB): WNT, sonic hedgehog (SHH), and groups “3/C” and “4/D”. Group 4 is not well characterized, but harbors the most frequently observed chromosomal abnormality in MB, i17q, whose presence may confer a worse outcome. Recent publications have identified mutations in chromatin remodeling genes that may be overrepresented in this group, suggesting a biological role for these genes in i17q. This work seeks to explore the pathology that underlies i17q in MB. Specifically, we examine the prognostic significance of the previously-identified gene mutations in an independent set of MBs as well as to examine biological relevance of these genes and related pathways by gene expression profiling. The previously-implicated p53 signaling pathway is also examined as a putative driver of i17q tumor oncogenesis. The data show gene mutations associated with i17q tumors in previous studies (KMD6A, ZMYM3, MLL3 and GPS2) were correlated with significantly worse outcomes despite not being specific to i17q in this set. Expression of these genes did not appear to underlie the biology of the molecular variants. TP53 expression was significantly reduced in i17q/ group 4 tumors; this could not be accounted for by dosage effects alone. Expression of regulators and mediators of p53 signaling were significantly altered in i17q tumors. Our findings support that chromatin remodeling gene mutations are associated with significantly worse outcomes in MB but cannot explain outcomes or pathogenesis of i17q tumors. However, expression analyses of the p53 signaling pathway shows alterations in i17q tumors that cannot be explained by dosage effects and is strongly suggestive of an oncogenic role.
Alkane desaturation by concerted double hydrogen atom transfer to benzyne

The removal of two vicinal hydrogen atoms from an alkane to produce an alkene is a challenge for synthetic chemists. In nature, desaturases and acetylenases are adept at achieving this essential oxidative functionalization reaction, for example during the biosynthesis of unsaturated fatty acids, eicosanoids, gibberellins and carotenoids. Alkane-to-alkene conversion almost always involves one or more chemical intermediates in a multistep reaction pathway; these may be either isolable species (such as alcohols or alkyl halides) or reactive intermediates (such as carbocations, alkyl radicals, or σ-alkyl-metal species). Here we report a desaturation reaction of simple, unactivated alkanes that is mechanistically unique. We show that benzynes are capable of the concerted removal of two vicinal hydrogen atoms from a hydrocarbon. The discovery of this exothermic, net redox process was enabled by the simple thermal generation of reactive benzyne intermediates through the hexadehydro-Diels-Alder cycloisomerization reaction of triyne substrates. We are not aware of any single-step, bimolecular reaction in which two hydrogen atoms are simultaneously transferred from a saturated alkane. Computational studies indicate a preferred geometry with eclipsed vicinal C-H bonds in the alkane donor.
Gastrointestinal bleed after left ventricular assist device implantation: incidence, management, and prevention.

Background: Continuous-flow left ventricular assist devices (CF-LVADs) have become the standard of care for patients with end-stage heart failure (HF). While these devices have improved durability compared to earlier generation left ventricular assist devices (LVADs), increased frequency in some complications has been seen, including gastrointestinal bleeding (GIB), pump thrombosis and hemolysis. We discuss the incidence, management and prevention of GIB after CF-LVAD implantation. Methods: We reviewed the current literature available on the incidence, management and prevention of GIB after CF-LVAD implantation with a focus on our experience at the University of Minnesota, with data on nearly 300 patients who received a CF-LVAD from 2005 to 2013. Results: The incidence of GIB after CF-LVAD varies between 18-40% in numerous studies. At the University of Minnesota, out of 233 patients who underwent HeartMate II (HMII) implantation between 2005-2013, 60 GIB episodes occurred in 51 patients (22%), with an event rate of 0.17 gastrointestinal bleeds/patient-year of support. The etiology of GIB appears to be multifactorial. The main factors which have been identified include the need for chronic anticoagulation, acquired von Willebrand syndrome, platelet dysfunction and increased incidence of arteriovenous malformations due to chronic low pulse pressure. When managing an LVAD patient with GIB, a multi-disciplinary approach is needed. The main goals of treatment are evaluating the location and severity of the bleed, holding anti-coagulants and resuscitation to maintain stable hemodynamics. Conclusions: GIB is a complication with considerable morbidity. Future efforts to further understand the etiology of GIB and optimize anti-coagulation are needed to improve outcomes following CF-LVAD implantation.
Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity

Recent studies have demonstrated the presence of the (pro)renin receptor (PRR) in the glomerular mesangium and the subendothelial layer of the renal arteries. We hypothesized that diabetes upregulates PRR expression through enhanced angiotensin subtype 1 (AT1) receptor-NADPH oxidase cascade activity. Using real-time polymerase chain reaction, Western blot analysis and immunostaining, we studied renal localization of the PRR in the streptozotocin-induced diabetic rat model and in response to 1 week of treatment with the AT1 receptor blocker valsartan (10 mg kg(-1) day(-1)), the angiotensin AT2 receptor blocker PD123319 (0.5 mg kg(-1) day(-1)) or the NADPH oxidase inhibitor diphenylene iodonium (DPI; 0.5 mg kg(-1) day(-1)) 6 weeks post-induction of diabetes. Both PRR mRNA and protein were expressed constitutively in the kidneys of normal rat renal cortex and medulla, mainly in glomerular mesangium, proximal, distal and collecting tubules. Compared with normal rats (100%), diabetic rats demonstrated an increase in renal PRR mRNA (184%), protein (228%) and immunostaining. Valsartan and DPI prevented the increase in the PRR mRNA (106 and 126%, respectively), protein (97 and 140%, respectively) and immunostaining that was seen in the kidneys of diabetic rats. The AT2 blocker PD123319 did not have significant effects on PRR mRNA (157%) or protein expression (200%) in the kidneys of diabetic rats. These results demonstrate that the PRR is constitutively expressed in renal glomeruli and tubules. Expression of the PRR is upregulated in diabetes via enhancement of AT1 receptor-NADPH oxidase activity.
A tiered aquatic life unit bioassessment model for Gulf of Mexico coastal streams

The tiered aquatic life unit (TALU) model allows quick and efficient bioassessment with goals that are based on practical, systematic sampling of commonly measured stream variables. A six-tier hybrid TALU model was developed as a proof of concept study for streams in six level IV ecoregions in the north-central Gulf of Mexico coastal plain. The model used in-stream habitat variables, land use, surveys of the unionid mussels, number of intolerant fish species and fish diversity in streams varying from 2nd through 6th order. The model classification identified sites considered a priori either as impaired or best available and minimised Type I (mistakenly concluding impairment) and Type II (failing to detect impairment) errors. The model also detected transitional sites, thereby illustrating incremental degradation or recovery, in contrast to previous monitoring tools focused on pass/fail approaches. Because the model classifies transitional sites and is easily modified to fit other ecoregions, it offers a useful foundation for resource managers to monitor the health of coastal plain rivers.
Nuclear cardiology. I. Radionuclide angiographic assessment of left ventricular contraction: uses, limitations and future directions.

Radionuclide angiography has been increasingly utilized to evaluate left ventricular function in a wide variety of disease states. Comparison with contrast ventriculography has shown that radionuclide angiography is an accurate means of determining global ejection fraction. Moreover, studies have shown that this technique is of particular value in detecting the presence and severity of regional asynergy as, for example, in the delineation of a discrete aneurysm versus global asynergy as the cause of congestive heart failure. The relative ease of repetitive examinations permits evaluation of left ventricular function under different conditions. Thus, radionuclide angiography is being increasingly used as a prognostic and therapeutic guide. In addition, it can be used during an acute intervention—for example, with administration of nitroglycerin to detect reversible asynergy or, as recently demonstrated by several groups, during exercise as a relatively sensitive and specific means to detect coronary heart disease.
Molecular characterization of the tdc operon of Escherichia coli K-12.

The nucleotide sequence of a 2-kilobase DNA fragment of the tdc region of Escherichia coli K-12, previously cloned in this laboratory, revealed two open reading frames, tdcC and ORFX, downstream from the tdcB gene (formerly designated tdc) encoding biodegradative threonine dehydratase. A 24-base-pair sequence separated tdcC from the dehydratase coding region, and an untranslated region of 60 nucleotides, which contains a recognizable -10 consensus sequence, was found between tdcC and ORFX. The deduced amino acid sequence of tdcC showed it to be a large hydrophobic polypeptide of 431 amino acid residues, whereas ORFX coded for a small 135-residue polypeptide lacking glutamine and tryptophan. A computer-assisted sequence analysis revealed no similarity among the tdcB, tdcC, and ORFX polypeptides, and a search of the GenBank database failed to detect similarity with any other known proteins. The tdc genes and ORFX showed similar codon usage and, in analogy with other bacterial genes, showed codon usage typical for genes expressed at an intermediate level. Transcriptional analysis with S1 nuclease indicated two distinct transcription start sites upstream of the tdcB gene in regions previously identified as promoterlike elements P1 and P2. Interestingly, expression of tdcB and tdcC, but not ORFX, was contingent upon the presence of P1. These results taken together tend to suggest that the biodegradative threonine dehydratase is the second gene in a polycistronic transcription unit constituting a novel operon (tdcABC) in E. coli implicated in anaerobic threonine metabolism. Images
Interplay of Cytokines and Adjuvants in the Regulation of Mucosal and Systemic HIV-Specific CTL

We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and GM-CSF when administered together with the HIV peptide PCLUS3–18IIIB and cholera toxin (CT) in the induction of CTL activity and protection against mucosal viral transmission. Further, we examine the efficacy of mutant Escherichia coli labile toxin, LT(R192G), as a less toxic adjuvant than CT. LT(R192G) was as effective as or more effective than CT at inducing a mucosal CTL response. Moreover, LT(R192G) was as effective without IL-12 as CT was when combined with IL-12, and the response elicited by LT(R192G) with the vaccine was not further enhanced by the addition of IL-12. GM-CSF synergized with LT(R192G) without exogenous IL-12. Therefore, LT(R192G) may induce a more favorable cytokine response by not inhibiting IL-12 production. In particular, less IL-4 is made after LT(R192G) than CT immunization, and the response is less susceptible to anti-IL-12 inhibition. Thus, the choice of mucosal adjuvant affects the cytokine environment, and the mucosal response and protection can be enhanced by manipulating the cytokine environment with synergistic cytokine combinations incorporated in the vaccine.
Nanosecond polarization-resolved laser-induced breakdown spectroscopy

It is shown that the continuum emission produced in the ablation of an Al target with nanosecond laser pulses is much more strongly polarized than the discrete line emission. This effect may be utilized to improve the resolution of the laser-induced breakdown spectroscopy spectrum by using a polarizer to filter out the continuum background. The effects of laser fluence and focal position are also reported. It is further shown that the lifetime of the emission closely tracks the intensity spectrum.
Fusion Between Southeastern United States Argentine Ant Colonies and Its Effect on Colony Size and Productivity

The ecological success of invasive ants has been linked to their ability to form expansive supercolonies. In the Argentine ant, Linepithema humile (Mayr), increased productivity and com- petitive ability of introduced supercolonies in several places, e.g., California and southern Europe, has been linked to high population densities that could have been attained via fusion of nonaggressive and genetically similar nests. Recently, we have found that introduced L. humile colonies in the south- eastern United States, which have higher levels of intraspeciÞc aggression and genetic diversity than those in California and southern Europe, sometimes also fuse; yet it is unclear what the longer term consequences of such colony fusion might be. In this study, we examined whether fusion of these southeastern United States L. humile colonies results in larger colonies by recording colony size and productivity in pairs that fused and in pairs that did not fuse. After 6 mo, colonies that fused produced 47% more workers and had twice as many queens as colony pairs that did not fuse. Also, fused colonies had an overall per capita colony productivity (number of brood and workers produced per queen and per worker) comparable to that of nonfused pairs and unpaired controls. Furthermore, all queens contributed to worker pupae production in fused colonies. Thus, fusion of initially aggressive south- eastern United States L. humile colonies results in colonies with higher worker number without decreasing per capita productivity. Moreover, offspring contribution by all queens in fused colonies may alter colony genotypic composition resulting in reduced intraspeciÞc aggression that in turn promotes further fusion. This process may be relevant to the establishment of incipient colonies in areas where multiple introductions have occurred.
Considerations in Placement of Right Internal Jugular Cannulas

Abstract This case report describes a patient who had paroxysmal ventricular bigeminy of an unrecognized etiology. After 24 hours of observation, it was noted that the patient's head position correlated with the bigeminy. A single-lumen infusion catheter, which had been placed through an internal jugular cannula, was transduced and demonstrated a ventricular pressure waveform. This catheter was removed and the ectopy resolved. The factors associated with this arrhythmia are discussed.
The application of the 2-amino-4-pyrimidones to supramolecular synthesis

Abstract A strategy for preparation of two dimensional layered compounds is introduced. This strategy explores the possibility of using the 2-amino-4( H )-pyrimidone ring system as a host for dicarboxylic acids guests. This strategy is successful for the orientation of adipic acid into a two dimensional β-network with a molecular repeat distance of 6.5 A.
Summary of MTS coastal zone monitoring conference Friday, June 30, 1995 The Scripps Institution of Oceanography, La Jolla, Calif

This second annual environmental technology workshop was sponsored by the marine technology society, the Scripps Institution of Oceanography, and the Universidad Autonoma de Baja California. The ocean and its inhabitants do not recognize national boundaries, and to be successful, coastal monitoring programs for the California and Baja California coast by necessity should be bi-national. One of the goals of this workshop was to increase communication among members of the marine technology community who are concerned with the marine environment. Communication and interaction between the marine environmental community and members of the corporate, industrial, and scientific research communities prove beneficial in the effort to reduce coastal pollution and to create lasting solutions to environmental problems. This workshop served as a platform or launch-site from which scientific expertise, marine technology, industry, and community concern are able to join forces and share ideas in an effort to safeguard the coastal environment.
Efficiency of microlens arrays for projection LCD

The properties relevant to the use of a microlens array in a projection LCD device are examined and discussed. In particular, the effect of the lens geometry, shape, focal length, cover glass thickness, and beam spread angle, are related to the optical performance as measured by the improvement in light transmission through the LCD. Experimental data suggest that the performance of a lens array with hexagonal cross-section and a focal length of 0.7 mm can lead to an 80% increase in the light through-put. >
The exponentially weighted moving average

The Shewhart and CUSUM control chart techniques have found wide application in the manufacturing industries. However, workpiece quality has also been greatly enhanced by rapid and precise individual item measurements and by improvements in automatic dynamic machine control. One consequence is a growing similarity in the control problems faced by the workpiece quality control engineer and his compatriot in the continuous process industries. The purpose of this paper is to exposit a control chart technique that may be of value to both manufacturing and continuous process quality control engineers: the exponentially weighted moving average (EWMA) control chart. The EWMA has its origins in the early work of econometricians, and although its use in quality control has been recognized, it remains a largely neglected tool. The EWMA chart is easy to plot, easy to interpret, and its control limits are easy to obtain. Further, the EWMA leads naturally to an empirical dynamic control equation.
Life as a numerator: Putting the person in personal genomics.

While the science of human genomics is often focused on odds and probability, most of us do not experience risk that way. I am a carrier of a mutation in ABCC6, as is my husband. Rather than experiencing the odds we would have children with the autosomal recessive condition pseudoxanthoma elasticum (25% each pregnancy) as an abstraction, our reality is having two of two children affected by PXE: our experience is 100%. Twice. PXE affects 1 in 50,000 people. Our kids are the numerators. In 1994, when PXE was discovered in our then-very-young children, we felt not only overwhelmed by the prospect of taking care of them and anxious about the uncertainty of their futures, but isolated by the rare nature of their condition. Genetics? We didn't want to talk about it then and even if we did, we didn't have anyone with whom we could talk about it. Today? Not so much. We—and thousands of others in similar circumstances—are bombarded with information from sequencing centers, clinics, research studies, and direct-to-consumer sites. And, spam fatigue notwithstanding, that's mostly to the good. Genetic disease is a long-tail problem that can only be solved if crowdsourcing rises to the occasion, that is, if families like mine and others contributing to and discussed in this issue are not alone. Precision medicine, biomedical research, and human health writ large all stand to benefit if the masses get involved. Indeed, I would argue that crowdsourcing is our only hope. Here I describe ways in which this is already happening and a vision for a future where it is standard practice.
The Use of an Unmanned Aerial Vehicle to Locate Alligator Nests

Abstract Coastal marshes of Louisiana provide nesting habitat for Alligator mississippiensis (American Alligator). Helicopters are typically used to locate Alligator nests in remote interior marshes. We tested the use of an unmanned aerial vehicle (UAV) to detect Alligator nests on Rockefeller Wildlife Refuge in Grand Chenier, LA. Three brief flights with a combined search time of approximately 25 minutes and 9 seconds were conducted in a single afternoon, covering 28.2 ha. While in the field, we observed 6 Alligator nests with the UAV, and later review of video imagery recorded allowed us to detect an additional 6 Alligator nests. The use of UAVs may be a useful tool for detecting Alligator nests.
A permanent rat gastric fistula.

SummaryA simple technic for preparation of a chronic rumenal fistula in the rat using a specially designed Pavlov's type of cannula is described.
Abstract 5390: Chemical disruption of Wnt protein fatty acylation as an anti-cancer therapeutic strategy.

The secreted Wnt signaling molecules are associated with a broad range of cancers and represent high priority therapeutic targets. Recently identified small molecules that disrupt Wnt biosynthesis by disabling the extracellular acyltransferase Porcupine (Porcn) form the basis of a novel targeted anti-cancer therapeutic strategy. Porcn is a founding member of a sixteen gene family known as Membrane-Bound O-Acyltransferases (MBOATs) that likely control the production of a broad range of disease-relevant signaling molecules. A deeper understanding of the chemical-protein interaction that confers Porcn inhibitors with selectivity would facilitate the engineering of improved Porcn inhibitors and molecules with activity against other MBOAT family members. Using synthetic fatty acyl analogues that allow direct labeling of Wnt proteins and chemical inhibitors of fatty acid metabolic enzymes, we have uncovered that Porcn utilizes a monounsaturated 16-carbon fatty acid as a substrate. Chemical disruption of stearoyl-CoA desturase (SCD) that converts palmitate to palmitoleate blocks Wnt protein production and activity thus revealing another potential chemical strategy for inhibiting Wnt-dependent cancerous growth. The inability of several other Porcn family members with known protein substrates to utilize palmitoleate may account for the selectivity of Porcn classes of inhibitors. Our study expands the number of drug targets to include those enzymes that control the production of secreted signaling molecules and reveals a direct influence of cellular metabolic status on coordinated and cancerous cell growth regulation. Citation Format: Rubina Tuladhar, Lawrence Lum. Chemical disruption of Wnt protein fatty acylation as an anti-cancer therapeutic strategy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5390. doi:10.1158/1538-7445.AM2013-5390
Unraveling K-12 Standard Alignment: Report on a New Attempt

We present the results of an experiment which indicate that automated alignment of electronic learning objects to educational standards may be more feasible than previously implied. We highlight some important deficiencies in existing alignment systems and formulate suggestions for improved future ones. We consider how the changing substance of newer educational standards, a multi-faceted view of standard alignment, and a more nuanced view of the ‘alignment’ concept may bring the long-sought goal of automated standard alignment closer. We explore how lexical similarity of documents, a World+Method representation of semantics, and network-based analysis can yield promising results. We furthermore investigate the nature of false positives to better understand how validity of match is evaluated so as to better focus future alignment system development.
Topographic factors in distribution of homonymous group Ia-afferent input to cat medial gastrocnemius motoneurons

Experiments were performed to determine whether the topographic relationships between muscle spindles and their surrounding extrafusal fibers are preserved in the pattern of homonymous, monosynaptic connections from Ia-afferents to motoneurons. The medial gastrocnemius (MG) muscle of adult cats was chosen as a model system because previous studies have shown that its muscle nerve divides into several branches, each of which innervates a distinct muscle compartment (20, 27, 28, 38), and that the Ia-afferent fibers innervating muscle spindles within a compartment are found in the same nerve branch (27, 28). Thus, we could make intracellular recordings from MG motoneurons, determine which intramuscular compartment they innervated, and then compare the synaptic input they received from Ia-afferents innervating the same compartment with that which they received from Ia-afferents innervating different compartments. Our results indicate that homonymous Ia-afferent input is "topographically weighted" within the MG motor nucleus such that afferents innervating a given intramuscular compartment exert relatively greater synaptic effects in motoneurons that project to the same compartment than in other homonymous motoneurons. The degree of topographic weighting was quite variable in the different experiments but appeared more prominently in experiments in which a high proportion of the motoneurons studied were characterized by high-rheobase values and low input resistances. This suggests that topographic factors may exert more influence on the distribution of Ia-afferent input to large motoneurons than to small motoneurons. In the DISCUSSION, the extent of topographic weighting within the homonymous motoneuron pool is compared with weighting across synergist motoneuron pools, and alternative models of topographic weighting are proposed and evaluated.
Problems about justification

Theological attempts to justify Christian beliefs by appealing to inner experience, foundations, or epistemic dependence all face daunting problems. The arguments which suggest these difficulties are in part philosophical, both in the obvious sense that they have been proposed mainly by philosophers, and in the more important sense that they trade on assumptions which one does not have to hold distinctively Christian beliefs to accept. The logical links between these three theses are loose enough that it would be possible to accept any one of them without accepting the other two. I group them together not only because modern theology has tended to do so, but also for my own purposes: these three theses seem to me alike unsalvageable. That a theological claim faces philosophical problems does not, to be sure, necessarily require abandoning it. If central Christian beliefs require the thesis, then ways will have to be found to defend it. Later chapters will argue that this is not the case with any of the present theses, mainly by trying to show that a plausible theological account of epistemic justification may be developed which forgoes any appeal to them, and which makes constructive use of the philosophical arguments which suggest that they are beyond rescue. The belief-dependence of inner experience Emotion and intention In theology, justificatory appeals to inner experience tend to turn on a claim about the relation between these experiences and the beliefs which express or describe them. For the interiorist the relevant experiences, while in some sense pre-linguistic or “wordless,” give rise to beliefs and sentences which publicly express and communicate the experiences.
Cell therapy for patients with acute myocardial infarction: ACCRUEd evidence to date.

Bone marrow (BM)–derived cell therapy for the damaged heart has now been under investigation for almost 2 decades. Right from the outset, both in vitro and in animal models of cardiac damage, early studies using BM-derived cells showed incredible promise and reported numerous broadly positive findings, driving enthusiasm for the clinical translation of this approach. To mention just a few of those early studies, findings from the late 1990s included the successful differentiation of BM stromal cells into cardiomyocyte-like cells1; increased angiogenesis and the formation of cardiomyocyte-like cells in vivo when BM-derived cells were injected into the scarred left ventricular (LV) wall2; and the identification that the BM is a reservoir for circulating endothelial progenitor cells that contribute to new vessel formation in the adult.3 Then, in 2001, it was reported that the intravenous administration of human CD34+ BM-derived cells into immune-deficient rats after acute myocardial infarction (MI) led to the proliferation of pre-existing vasculature and de novo new blood vessel formation in the infarct bed, which contributed to the salvage of viable myocardium and dramatic improvements in LV ejection fraction (LVEF).4 Concurrently, others reported that a specific fraction of BM cells that expressed c-kit, but not hematopoietic markers, could give rise not only to new vessels but also to cardiomyocytes5 and that the mobilization of BM cells using specific factors in the post-MI period leads to the homing of these cells to the MI region, reduced infarct size, and improved survival in an animal model.6 Article, see p 1346 With these and other remarkable preclinical studies appearing in rapid succession, clinician scientists were swift to begin investigating BM-derived cells to ameliorate cardiovascular disease in humans.7 Indeed, still in 2001, what we think to be the first human report of …
Medicare D Subsidies and Racial Disparities in Persistence and Adherence With Hormonal Therapy

Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially reduce racial and ethnic disparities.
High-performance 1.5 μm GalnNAsSb lasers grown on GaAs

Substantially reduced threshold current density and improved efficiency in long-wavelength (>1.4 µm) GaAs-based lasers are reported. A 20×1220 µm as-cleaved device showed a room temperature continuous-wave threshold current density of 580 A/cm2, external efficiency of 53%, and 200 mW peak output power at 1.5 µm. The pulsed threshold current density was 450 A/cm2 with 1145 mW peak output power.
Surface-Plasmon-Mediated Gradient Force Enhancement and Mechanical State Transitions of Graphene Sheets

Graphene, a two-dimensional material possessing extraordinary properties in electronics as well as mechanics, provides a great platform for various optoelectronic and optomechanical devices. Here, we theoretically study the optical gradient force arising from the coupling of surface plasmon modes on parallel graphene sheets, which can be several orders stronger than that between regular dielectric waveguides. Furthermore, with an energy functional optimization model, possible force-induced deformation of graphene sheets is calculated. We show that the significantly enhanced optical gradient force may lead to mechanical state transitions of graphene sheets, which are accompanied by abrupt changes in reflection and transmission spectra of the system. Our demonstrations illustrate the potential for broader graphene-related applications such as force sensors and actuators.
Varicella seroprevalence in the U.S.: data from the National Health and Nutrition Examination Survey, 1999-2004.

Objective.We estimated the varicella seroprevalence among the U.S. population aged 6–49 years based on retested National Health and Nutrition Examination Survey (NHANES) specimens collected between...
A thermal analysis study of ascorbic acid and its pharmaceutical formulations

In a previous publication, the thermogravimetric (TG) analysis of ascorbic acid was considered. Simultaneously with the production of the TG data, time-temperature plots were also generated on the work station which allowed the process to be classified as exothermic or endothermic and identified the energy change with the reaction sequence. This aspect is investigated in the present study. To maximize the energy change, the model mixtures were assessed at a mass ratio of 1∶1. The analytical implications of this approach are explored. To avoid complications in this kind of analysis, the present study is restricted to the behavior of binary systems heat treated in nitrogen.
Kingdom Without End? The Inevitable Expansion of Religious Sovereignty Claims

In a society that is increasingly polarized on the basis of religion and politics, there is perhaps no greater manifestation of that polarization than the claim to a realm entirely separate from, and independent of, the sovereignty of the civil state. Claims of religious institutions seeking autonomy with respect to their internal affairs sometimes include such sovereignty claims. Though institutional autonomy for religious organizations may be intended as a way of protecting civil rights, it also entails difficulties that are not easily resolved — not least among them their natural and nearly inevitable tendency to expand. This Essay considers the ever-expanding nature of religious sovereignty claims, tracing a trajectory of increasing breadth through a series of recent Supreme Court opinions. It also attempts to identify some causes of this expansion, arguing that the nature of religious sovereignty itself makes delimitation of such autonomy claims difficult or impossible. It ends by calling for alternate approach, in which the rhetoric of sovereignty and “freedom of the church” is abandoned altogether and which specifies carefully those issues that the courts may and may not decide when religious institutions are involved.
Weakly non-Boussinesq convection in a gaseous spherical shell.

We examine the dynamics associated with weakly compressible convection in a spherical shell by running 3D direct numerical simulations using the Boussinesq formalism [Spiegel and Veronis, Astrophys. J. 131, 442 (1960)]. Motivated by problems in astrophysics, we assume the existence of a finite adiabatic temperature gradient $\mathbf{\ensuremath{\nabla}}{T}_{\mathrm{ad}}$ and use mixed boundary conditions for the temperature with fixed flux at the inner boundary and fixed temperature at the outer boundary. This setup is intrinsically more asymmetric than the more standard case of Rayleigh-B\'enard convection in liquids between parallel plates with fixed temperature boundary conditions. Conditions where there is substantial asymmetry can cause a dramatic change in the nature of convection and we demonstrate that this is the case here. The flows can become pressure- rather than buoyancy-dominated, leading to anomalous heat transport by upflows. Counterintuitively, the background temperature gradient $\mathbf{\ensuremath{\nabla}}\overline{T}$ can develop a subadiabatic layer (where $\mathbit{g}\ifmmode\cdot\else\textperiodcentered\fi{}\mathbf{\ensuremath{\nabla}}\overline{T}l\mathbit{g}\ifmmode\cdot\else\textperiodcentered\fi{}\mathbf{\ensuremath{\nabla}}{T}_{\mathrm{ad}}$, where $\mathbit{g}$ is gravity) although convection remains vigorous at every point across the shell. This indicates a high degree of nonlocality.
Rearranging the Nernst equation to make a dosage-controllable membrane delivery system

Abstract Electrochemically induced or augmented membrane-based drug delivery is a well-known art. However, it is often difficult to obtain a quantifiable relationship between quantity of drug delivered and voltage or current used. Described here is an alternative way of doing electrochemically induced membrane drug delivery where the membrane is smart and turns itself off when the desired amount of drug has been delivered. Furthermore, the amount of drug delivered at shut off is exactly quantifiable by a rearranged (exponential) form of the well-known Nernst concentration-cell equation. We demonstrate this concept with a simple prototype system based on a commercial anion exchange membrane. For this system, the drug molecule must be an anion, and nitrate was used as the surrogate drug anion here.
Rebuilding the bridge between transcription and translation.

In Bacteria, ribosomes may bind to the nascent RNA emerging from the transcribing RNA polymerase and initiate translation. Transcription-translation coupling plays diverse roles in cellular physiology, including attenuation control, mRNA surveillance, and maintenance of genome integrity. While the existence of coupling is broadly accepted, its mechanism and ubiquity are debated. Structural evidence supports mutually exclusive modes of RNA polymerase-ribosome contacts. In a model based on nuclear magnetic resonance data, NusG binds to a ribosomal protein S10 and acts as an adapter between RNA polymerase and the 30S subunit. Recent single-particle cryo electron microscopy analyses of RNA polymerase bound to 30S and 70S ribosomes revealed extensive, and very distinct, contacts which are incompatible with bridging by NusG. In this issue of Molecular Microbiology, Saxena et al. provide the first evidence for NusG-mediated coupling in vivo. Their results demonstrate that Escherichia coli NusG interacts with the 70S ribosomes through a previously established interface and that these interactions are required for survival when translation elongation is hindered to weaken coupling. Future studies will address a likely possibility that distinct bridging mechanisms underpin context-dependent coupling in the cell.
State space modeling and feedback control of five-phase permanent magnet assisted synchronous reluctance motor under open phase faults

This paper presents an analysis of the state space modeling (SSM) and feedback control method of a five-phase permanent magnet assisted synchronous reluctance motor (PMa-SynRM) under open phase faults. Primarily, the reliability of an electrical machine is of prime concern for the safety-critical applications. Therefore, the innovative and reliable control methods are required to derive better fault tolerant operation of a five-phase PMa-SynRM successfully. Classical control methods have been widely accepted to control the electric machines. However, modern control technique is better suited for controlling any multi-input and multi-output (MIMO) system, for example, direct and quadratic axis control of the electric machine. However, the performance of the modern control method has been limitedly studied under different open phase fault conditions in PMa-SynRM. This paper develops a modern control technique which utilizes a state space equivalent model (SSEM) of the PMa-SynRM under different open phase faults. The SSEM is used to develop the state feedback control method. For further analyzing stability criterion a Lyapunov function is used along with detail explanation of the proposed theory. The stability analysis are carried out through extensive MATLAB simulation.
Polydnaviruses as Endocrine Regulators

Publisher Summary This chapter summarizes the evidence that parasitoid viruses function as endocrine regulators in the host–parasitoid–polydnavirus relationship and ultimately act as endocrine disruptors leading to death of the host. Parasitoids are insect parasites that ultimately kill their host prior to its reproductive stage. Killing the host is the essence of being a parasitoid. Hence this explains their exploitation in biological control to reduce host pest populations. Many species of parasitized host lepidopteran larvae are developmentally arrested in their terminal instar when their parasitoids emerge and the normal endocrine signals accompanying pupation are suppressed. Additionally, the host stops feeding prior to parasitoid emergence from the host and this anorexia is irreversible. Many of the host–parasitoid systems described deals with larval–larval or egg–larval parasitoids. Because the host continues to feed and molt following parasitization, these braconid parasitoids are classified as koinobionts.
α - and β -mannosidoses

Clinical, pathological and biochemical findings in the mannosidoses are described. Family studies showed granulocyte-rich white cell fractions to be the tissue of choice for carrier detection in β-mannosidosis. Metabolic labelling studies using [3H] mannose demonstrated accumulation of Manβ1-4GlcNAc in cultured skin fibroblasts from a patient with this condition. Alternative methods of egress from lysosomes were suggested for this compound by its secretion into culture medium and apparent reduction of storage with time in cultures. β-mannosidase deficient goats are not thought to be a true animal model of the human condition, as although they showed a similar enzyme deficiency, the clinical presentation is much more severe and the major storage material (Manβ1-4GlcNAcβ1-4GlcNAc) is different.
A giant ankyrin-B mechanism for neuro-diversity/divergence through stochastic ectopic axon projections

ANK2 is a high-confidence autism spectrum disorder (ASD) gene where affected individuals exhibit diverse symptoms with a wide range of IQ. We report a cellular mechanism resulting in stochastic brain connectivity that provides a rationale for both gain and loss of function due to ANK2 mutation. Deficiency of giant ankyrin-B (ankB), the neurospecific ANK2 mutation target, results in ectopic CNS axon tracts associated with increased axonal branching. We elucidate a mechanism limiting axon branching, whereby giant ankB is recruited by L1CAM to periodic axonal plasma membrane domains where it coordinates cortical microtubules and prevents microtubule stabilization of nascent axon branches. Heterozygous giant ankB mutant mice exhibit innate social deficits combined with normal/enhanced cognitive function. Thus, giant ankB-deficiency results in gain of aberrant structural connectivity with penetrant behavioral consequences that may contribute to both high and low- function ASD and other forms of neurodiversity/divergence.