cssi/SciSciGPT-SciSciNet huggingface dataset:
Double-Diffusive Recipes. Part I: Large-Scale Dynamics of Thermohaline Staircases

AbstractThree-dimensional dynamics of thermohaline staircases are investigated using a series of basin-scale staircase-resolving numerical simulations. The computational domain and forcing fields are chosen to reflect the size and structure of the North Atlantic subtropical thermocline. Salt-finger transport is parameterized using the flux-gradient formulation based on a suite of recent direct numerical simulations. Analysis of the spontaneous generation of thermohaline staircases suggests that thermohaline layering is a product of the gamma instability, associated with the variation of the flux ratio with the density ratio . After their formation, numerical staircases undergo a series of merging events, which systematically increase the size of layers. Ultimately, the system evolves into a steady equilibrium state with pronounced layers 20–50 m thick. The size of the region occupied by thermohaline staircases is controlled by the competition between turbulent mixing and double diffusion. Assuming, in acc...
Improving Kernel Density Classifier Using Corrective Bandwidth Learning with Smooth Error Loss Function

In this paper, we propose a corrective bandwidth learning algorithm for Kernel Density Estimation (KDE)-based classifiers. The objective of the corrective bandwidth learning algorithm is to minimize the expected error-rate. It utilizes a gradient descent technique to obtain the appropriate bandwidths. The proposed classifier is called the "Empirical Mixture Model" (EMM) classifier. Experiments were conducted on a set of multivariate multi-class classification problems with various data sizes. The proposed classifier has an error-rate closer to the true model compared to conventional KDE-based classifiers for both small and large data sizes. Additional experiments on standard machine learning datasets showed that the proposed bandwidth learning algorithm performed very well in gen-eral.
A comparison of the Shipley vs. WAIS‐R subtests in predicting WAIS‐R Full Scale IQ

The Shipley and WAIS-R were administered to a diverse psychiatric and neurologic sample of 186 males. Estimates of Full Scale WAIS-R IQ obtained from the Shipley regression equation of Zachary, Crumpton, and Spiegel (1985) yielded a correlation of .73 with WAIS-R IQ, considerably lower than the .85 and .87 reported by the authors. Development of a new regression equation with more variables did not yield a significantly higher correlation. Several individual subtests or pairs of subtests provided equal or better estimates of WAIS-R IQ within the same population and required less administration time. The Shipley is recommended as an adequate IQ estimate when individual testing is not feasible.
Shell Model Calculation of Thermal Expansion of Alkali Halides and Magnesium Oxide

The microscopic Gruneisen parameters and the temperature dependence of the thermal Gruneisen parameter have been calculated in the quasi-harmonic approximation from an anharmonic shell model for MgO, LiF, NaF, NaI, KCl, KBr, KI, RbCl, RbBr, and RbI. The shell model contains six harmonic and five anharmonic parameters which are determined from experimental elastic, dielectric, and optical data. Anharmonic effects are partly eliminated by referring all quantities to constant volume corresponding to 0 °K. The calculated microscopic Gruneisen parameters agree well with the available experimental data for NaI and RbI. For the thermal Gruneisen parameter the agreement with experimental data is in general within the joint experimental error of the thermal data and the empirical input data used to characterize the interatomic forces. The rigid ion model and the shell model with the parameters determined from room-temperature input data give much less satisfactory agreement. The results reproduce also the fact that the magnitude and shape of the Gruneisen function γ(T) are determined mainly by the cation.
Why do we need a new NRC data base

The National Research Council (NRC) feedstuff composition tables have been widely used by nutritionists, feed manufacturers and livestock producers. In spite of changes in crop varieties, soil fertilization practices and processing methods, there has been no systematic up-dating of the tables in recent years. A recent survey comparing the mineral concentrations of common feedstuffs as determined by commercial laboratories with NRC values showed marked discrepancies. For example, the sodium, copper, zinc and manganese concentrations determined by commercial laboratories were much lower than NRC values for several common feedstuffs. In addition, the standard deviations were often nearly equal to the mean values. For the NRC tables to continue as the standard, a systematic up-dating is required where a mean value, standard deviation and the number of samples analyzed is reported for each nutrient.
Private Speech During Problem-Solving Activities in Bilingual Speakers

Based on the tenets of Vygotsky’s sociocultural theory, this research study investigated the private speech produced by 30 adult English/Spanish bilinguals while engaged in a problem-solving activity, with the objective of better understanding the regulatory role that each language plays in the bilingual mind. In order to obtain a spontaneous production of private speech, participants were unknowingly audio-recorded while working in a private room on 15 challenging questions in Spanish, which included problems of logic, mathematics, visual-spatial problems, and kinship questions. The 30 early bilinguals who participated were divided into three groups: The Spanish-dominant group, the English-dominant group, and the balanced group, who consisted of bilinguals who reported to be equally comfortable in both languages. Results showed that bilinguals’ dominant language played an important regulatory role in their verbalized thinking while the other language provided a complementary set of cognitive resources and strategies that were employed when needed.
Polymorphisms in Serine Hydroxymethyltransferase 1 and Methylenetetrahydrofolate Reductase Interact to Increase Cardiovascular Disease Risk in Humans

The enzymes serine hydroxymethyltransferase 1 (gene name SHMT1) and methylenetetrahydrofolate reductase (gene name MTHFR) regulate key reactions in folate-mediated one-carbon metabolism. Common genetic variants with the potential to influence disease risk exist in both genes. A prior report from the Normative Aging Study indicated no association of the SHMT1 rs1979277 SNP with cardiovascular disease (CVD), but a strong gene-gene interaction was detected with MTHFR rs1801133. We investigated the effect of the SHMT1 rs1979277 SNP and the SHMT1 rs1979277-MTHFR rs1801133 interaction in 2 epidemiologic cohort studies. In the Nurses' Health Study (NHS), the MTHFR rs1801133 variant genotypes were associated with an increased CVD risk and there was an interaction between SHMT1 and MTHFR such that the association of the MTHFR rs1801133 CT genotype (vs. CC; the TT genotype could not be evaluated) was stronger in the presence of the SHMT1 rs1979277 TT genotype (OR = 4.34, 95% CI = 1.2, 16.2; P = 0.049). In the Health Professionals Follow-Up Study, the MTHFR rs1801133 genotype was not associated with CVD risk, nor was there an interaction with SHMT1 rs1979277. The association of genetic variation in the SHMT1 gene, alone and in interaction with MTHFR, in relation to CVD risk is relatively understudied at the population level and results in the NHS confirmed a past report of gene-gene interaction, which is consistent with mechanisms suggested by basic science studies.
Similar rates of protein adaptation in Drosophila miranda and D. melanogaster, two species with different current effective population sizes

Adaptive protein evolution is common in several Drosophila species investigated. Some studies point to very weak selection operating on amino-acid mutations, with average selection intensities on the order of Nes ~ 5 in D. melanogaster and D. simulans. Species with lower effective population sizes should undergo less adaptation since they generate fewer mutations and selection is ineffective on a greater proportion of beneficial mutations. Here I study patterns of polymorphism and divergence at 91 X-linked loci in D. miranda, a species with a roughly 5-fold smaller effective population size than D. melanogaster. Surprisingly, I find a similar fraction of amino-acid mutations being driven to fixation by positive selection in D. miranda and D. melanogaster. Genes with higher rates of amino-acid evolution show lower levels of neutral diversity, a pattern predicted by recurrent adaptive protein evolution. I fit a hitchhiking model to patterns of polymorphism in D. miranda and D. melanogaster and estimate an order of magnitude higher selection coefficients for beneficial mutations in D. miranda. This analysis suggests that effective population size may not be a major determinant in rates of protein adaptation. Instead, adaptation may not be mutation-limited, or the distribution of fitness effects for beneficial mutations might differ vastly between different species or populations. Alternative explanation such as biases in estimating the fraction of beneficial mutations or slightly deleterious mutation models are also discussed.
Fluorescence imaging of cardiac propagation: spectral properties and filtering of optical action potentials

Fluorescence imaging using voltage-sensitive dyes is an important tool for studying electrical propagation in the heart. Yet, the low amplitude of the voltage-sensitive component in the fluorescence signal and high acquisition rates dictated by the rapid propagation of the excitation wave front make it difficult to achieve recordings with high signal-to-noise ratios. Although spatially and temporally filtering the acquired signals has become de facto one of the key elements of optical mapping, there is no consensus regarding their use. Here we characterize the spatiotemporal spectra of optically recorded action potentials and determine the distortion produced by conical filters of different sizes. On the basis of these findings, we formulate the criteria for rational selection of filter characteristics. We studied the evolution of the spatial spectra of the propagating wave front after epicardial point stimulation of the isolated, perfused right ventricular free wall of the pig heart stained with di-4-ANEPPS. We found that short-wavelength ( 100 Hz). Both findings are consistent with the reported effect of intrinsic blurring caused by light scattering inside the myocardial wall. The absence of high-frequency spectral components allows the use of aggressive low-pass spatial and temporal filters without affecting the optical action potential morphology. We show examples where the signal-to-noise ratio increased up to 150 with <3% distortion. A generalization of our approach to the rational filter selection in various applications is discussed.
A Digitally Disruptive Supply Chain

It's inevitable—the traditional supply chain will eventually meet the digital frontier. Imagine today's new community of makers sourcing designers to refine their inventions, and 3D printers to generate first-round prototypes. What will this brave new world look like? The future of the supply chain in the digital age…
The Statistical Education of Teachers: Preparing Teachers to Teach Statistics

In an increasingly data-driven world, statistical literacy is becoming an essential competency, not only for researchers conducting formal statistical analyses, but also for informed citizens makin...
Strangi II (or IV?): Fifth Circuit Draws a Line for FLPs under Code Sec. 2036(a)

Estate of Strangi v. Commissioner has made its way back and forth between the Tax Court and the United States Court of Appeals for the Fifth Circuit for the last five years, generating four different opinions. When the Tax Court first decided the Strangi case (Strangi I), it held that the IRS was barred from arguing that the value of property transferred to a family limited partnership (FLP) was included in the decedent's gross estate under Code Sec. 2036(a) because the IRS had waited too long before trial to amend its answer attacking the estate's valuation under Code Sec. 2036(a). The Fifth Circuit remanded the case to the Tax Court for a reconsideration of the Code Sec. 2036(a) issue. On remand (Strangi II), the Tax Court held that Code Sec. 2036(a) applied to include the value of the property transferred to the FLP in the decedent's gross estate. The Fifth Circuit affirmed Strangi II in July. Estate planners have been waiting eagerly for the Fifth Circuit's opinion in Strangi II for two reasons. First, the Tax Court held that not only was the property in question included in the decedent's estate under Code Sec. 2036(a)(1), but that Code Sec. 2036(a)(2) also applied. The Tax Court's opinion on the Code Sec. 2036(a)(2) issue could threaten the use of an FLP in an estate plan more than its opinion on the Code Sec. 2036(a)(1) issue. Second, the Fifth Circuit also has issued an opinion in Kimbell v. United States, holding that property transferred to an FLP was not included in a decedent's gross estate under Code Sec. 2036(a). Practitioners had hoped that the Fifth Circuit would follow its Kimbell opinion to hold, in Strangi II, that property transferred by a decedent to an FLP was not included in the decedent's gross estate under Code Sec. 2036(a). These hopes were dashed, however. The Fifth Circuit distinguished the facts in Kimbell from the facts in Strangi II. Strangi II offers some guidance to estate planners in the Fifth Circuit concerning the types of arrangements involving the use of an FLP in an estate plan that may pass muster under Code Sec. 2036(a) and the types of arrangements that will not achieve estate planning goals. This column discusses the Fifth Circuit's opinion in Strangi II and the guidelines that it seems to provide.
Evaluation of Tomato Varieties for Resistance to Greenhouse Whitefly

After preliminary experiments determined the response of the greenhouse whitefly, Trialeurodes vaporariorum (Westwood), to 2 tomato varieties (Delicious and Tiny Tim) (Curry and Pimentel 1971), a more extensive screening test of 90 tomato varieties was initiated. The objective was to find a resistant variety of tomato for further whitefly—tomato investigations.
Dialysis Options for the Elderly Patient with Acute Kidney Injury

Acute kidney injury (AKI) is a common and serious event that most often complicates hospitalization for serious illness [1]. Recent data demonstrates that from 2000 to 2009, the incidence of dialysis-requiring AKI increased from 222 to 533 cases per million person-years, an average increase of 10 % per year [2]. An important factor driving this increase in AKI over the past decade is the older age of the population, which serves as an independent risk factor for the development of AKI. It is now clear that the elderly are at the very highest risk for the development of AKI, and over the past 25 years, the mean age of patients with AKI has increased by at least 5 years and perhaps as much as 15 years [3]. In a large European cohort of patients, the average age of patients with AKI was 76 years [4]. Hsu et al. most recently also demonstrated that not only were elderly patients at higher risk for the most severe form of AKI (that requires dialysis) as compared to younger patients, but that over time the incidence of AKI in the elderly is increasing more rapidly than in younger cohorts [2]. At the more severe extremes of AKI, hospitalized patients with dialysis-requiring AKI are older than their counterparts without dialysis-requiring AKI (63.4 versus 47.6 years) [2].
Frequently Unanswered Questions

Clear requirements and clear documentation make it possible to build high-level models of code that let you clearly describe the design underlying it. To be effective, documentation should start before you write tests or code.
Clinical study of splenectomy in children with chronic primary immune thrombocytopenia

Objective To investigate the clinical efficacy of splenectomy in children with chronic primary immune thrombocytopenia(CITP).Methods 6 children with CITP received splenectomy from June 2005 to December 2013,after getting no response to treatment with IVIG、corticosteroids,immunosuppressive agents,during the period over 1 year,all the patients were more than 6 years old.Results The long-term response rate was 83.3%,1 case was followed up for 8 years,with platelet counts less than 20 ×10~9 /L,although the bleeding symptom improved;another 1 case developed purulent meningitis 6 months later,even after platelet fully recovered.2 years later this patients was diagnosed as Connective Tissue Diseases(undifferentiated).The remaining 4 cases were cured,without any serious complications.Conclusions Splenectomy in children with CITP is safe and effective,for those who were failure to the first-line and second-line treatments.
The Escape Hatch (Expatriation): The Roots and Fruits of Section 6039G

Two weeks ago, the IRS published the latest quarterly notice pursuant to § 6039G. In plain English, the § 6039G list is a list of individuals that expatriated during the quarter preceding publication (here, the second quarter of 2016). For readers that are new to the world of U.S. taxation, the first shock may be that § 6039G even exists. To be clear, since late 1996 the United States has purported to publish the name of every individual losing citizenship. This paper examines why.
Abstract IA25: Mechanisms of protective tumor immunity

Efficacious cancer immunotherapies will likely require combinations of strategies that enhance tumor antigen presentation and antagonize negative immune regulatory circuits. We demonstrated that vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF followed by antibody blockade of CTLA-4 accomplishes clinically significant tumor destruction with minimal toxicity in a majority of stage IV metastatic melanoma and some advanced ovarian carcinoma patients. The extent of tumor necrosis in post-treatment biopsies was linearly related to the natural logarithm of the ratio of infiltrating CD8+ effector T cells to FoxP3+ Tregs, suggesting that further Treg inhibition might increase the frequency of clinical responses. Through an analysis of cytokine deficient mice, we delineated a critical role for GM-CSF in Treg homeostasis. GM-CSF is required for the expression of the phosphatidylserine binding protein MFG-E8 in antigen presenting cells, whereas the uptake of apoptotic cells by phagocyte-derived MFG-E8 maintains peripheral Treg activity. The pharmacologic inhibition of MFG-E8 function through genetic or engineering-based approaches blocks Treg induction, which intensifies vaccine-induced responses, leading to the regression of established tumors in mice. The clinical translation of these therapeutic strategies to Phase I testing in humans is underway. The detailed analysis of patients achieving sustained clinical benefits from irradiated, autologous GM-CSF secreting tumor cell vaccines and CTLA-4 antibody blockade also affords a rich opportunity to identify antigens associated with immune-mediated tumor destruction and to delineate mechanisms of therapeutic immunity. In this regard, we have identified antibodies against a panel of secreted and cell surface proteins that play important roles in tumor development and immune evasion. Isolation of the rare, antigen-specific memory B cells directed towards these important targets provides new opportunities for developing human monoclonal antibodies for cancer immunotherapy. Citation Format: Glenn Dranoff. Mechanisms of protective tumor immunity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA25.
Image acquisition in general radiography: The utilisation of DDR.

Abstract Objective This article explores image acquisition with DDR. General radiographic technology continues to advance therefore it remains paramount to continually reflect on DDR hardware and software amongst radiographers in an imaging modality that constitutes approximately 90% of all radiological examinations. Method This article reports findings from a wider ethnographic study of two general radiography environments in the United Kingdom (UK). Participant observation and semi-structured interviews were the methods used to uncover original data. Results Two key themes are discussed. Firstly, ‘the extent of DDR knowledge' amongst radiographers is examined. The findings uncover that not all radiographers have an adequate knowledge base with DDR technology. Secondly, ‘pitfalls and near misses with DDR' is discussed. This theme highlights the potential danger of radiographers ‘over-repeating' X-ray examinations, coincided with the occurrence of radiological incidents whereby a patient is exposed to ionising radiation with no added benefit. Conclusion This paper concludes by challenging the current ‘skill base' to operate DDR equipment. In addition, new pitfalls and near misses are highlighted, which may help forestall radiation incidents in the future. Dose and image optimisation remain central tenets to the role of the radiographer. Advances in knowledge Few studies have challenged image acquisition with DDR. This study adds to existing knowledge by uncovering original phenomena that may initiate discussions within the radiography community and continually enhance healthcare delivery.
Snap-through under unilateral displacement control with constant velocity

Abstract When the side of a beverage can or the domed lid of a jar is pushed inward, all or part of the structure may suddenly snap into an inverted configuration. The velocity of the pushing motion affects this instability. Most previous analyses of snap-through have considered force control (increasing the pushing force, e.g., a weight). Snap-through under dynamic, unilateral displacement control is investigated here, with the indentor moving at constant velocity (as in a universal testing machine) until snap-through occurs. Shallow elastic arches with immovable pinned ends are analyzed. Attention is focused on the critical height of the indentor at which snap-through is initiated. The effects of the indentor velocity, indentor location along the span, initial arch height, and damping magnitude are investigated. In addition, experiments are conducted on shallow buckled beams, which behave similarly to arches. Usually, the higher the indentor velocity, the further the indentor must move before snap-through occurs.
CURRENT APPLICATIONS OF TEMPORALLY CODED APERTURES IN NUCLEAR MEDICINE

Publisher Summary This chapter describes current application of temporally coded apertures in nuclear medicine. Since 1972, application of coded apertures in nuclear medicine has been investigated as an alternative to lead collimators and pinholes for forming images of the in vivo distribution of gamma-emitting radioactive tracers. The temporal function employed is one of the many available pseudorandom binary sequences. Each pinhole on the aperture plate describes the same binary transmission sequence but out of phase with all of the others. This approach requires that the coded image be recorded as a function of time, and decoding is then accomplished by performing a temporal cross-correlation between the transmission function and the coded image. Apart from the increased efficiency and three-dimensional response, coded apertures feature other properties of interest in nuclear medicine. The field of view for objects close to the aperture approaches the size of the aperture plate rather than zero as is the case for a single pinhole.
Sleep and Rehabilitation: A Guide for Health Professionals, by Julie M. Hereford: Thorofare, NJ: SLACK Inc., 2014, 440 pages, softcover, $58.98

Sleep and Rehabilitation: A Guide for Health Professionals by Julie M. Hereford, PT, DPT, is an amazingly informative resource on the topic of sleep and its effects on the rehabilitation process. T...
Replications of implicit theory of mind tasks with varying representational demands

Abstract We attempted to reproduce three tests of theory of mind in infants using implicit tasks that have been previously reported in the literature. These efforts were intended as initial steps in larger projects aimed at building on past research to better understand infants’ theory of mind capacities and their relationship to preschoolers’ explicit theory of mind. One task fully replicated evidence of 2-year-old children’s sensitivity to others’ ignorance. The results of another task testing for similar capacities in 18-month-old infants also elicited behavior similar to the original findings, although in that case we only conducted one of two conditions critical for demonstrating that performance depended upon theory of mind capacities. In contrast, our violation of expectation tasks failed to reproduce evidence that, by 18 months of age, infants form specific expectations about the actions an agent will engage in on the basis of false beliefs. Instead, looking times were consistent with infants having no clear prediction about the agent's actions under conditions of false belief. We discuss factors that might account for our failure to reproduce the previously reported violation of expectation results on which we were attempting to build. However, we also discuss the consistency of our data with other findings and hypotheses regarding early-developing theory of mind, and consider the possibility that they reflect the veridical abilities of 18-month-old infants, who may track others’ knowledge and ignorance but may not consistently represent the contents of others’ beliefs.
Effect of Intercalated Metals on the Electrocatalytic Activity of 1T-MoS2 for the Hydrogen Evolution Reaction

We show that intercalation of cations (Na+, Ca2+, Ni2+, and Co2+) into the interlayer region of 1T-MoS2 is an effective strategy to lower the overpotential for the hydrogen evolution reaction (HER). In acidic media the onset potential for 1T-MoS2 with intercalated ions is lowered by ∼60 mV relative to that for pristine 1T-MoS2 (onset of ∼180 mV). Density functional theory (DFT) calculations show a lowering in the Gibbs free energy for H-adsorption (ΔGH) on these intercalated structures relative to intercalant-free 1T-MoS2. The DFT calculations suggest that Na+ intercalation results in a ΔGH close to zero. Consistent with calculation, experiments show that the intercalation of Na+ ions into the interlayer region of 1T-MoS2 results in the lowest overpotential for the HER.
Spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucleus and unfolding of the mutant protein. Studies of the pathology of SBMA subjects have revealed nuclear aggregates of the mutant androgen receptor, loss of lower motor neurons in the brainstem and spinal cord, and both neurogenic and myopathic changes in skeletal muscle. Mechanisms underlying disease pathogenesis include toxicity in both lower motor neurons and skeletal muscle, where effects on transcription, intracellular transport, and mitochondrial function have been documented. Therapies to treat SBMA patients remain largely supportive, although experimental approaches targeting androgen action or promoting degradation of the mutant androgen receptor protein or the encoding RNA are under active study.
PS7:135 Amg 592 is an investigational il-2 mutein that induces highly selective expansion of regulatory t cells

Background AMG 592 is an investigational IL-2 mutein designed for greater regulatory T-cell (Treg) selectivity and longer half-life than recombinant IL-2 (aldesleukin). We investigated the tolerability of AMG 592 and its effects on expansion of Tregs, conventional effector T-cells (Tcon), and natural killer (NK) cells. Methods AMG 592 activity, in comparison with aldesleukin, was assessed by in vitro phosphorylated STAT5 (pSTAT5), Treg/Tcon/NK cell expansion, and cytokine production in primary human peripheral blood mononuclear cells (hPBMC). Effects on body temperature (Temp), C-reactive protein (CRP), and peripheral Treg/Tcon/NK cell numbers were evaluated in cynomolgus monkeys (CM). In an FIH study, healthy volunteers received single ascending SC AMG 592 doses (n=6/dose; 8 cohorts) or placebo (n=2/dose) for 28 days. Adverse events (AEs), pharmacokinetics (PK), pharmacodynamics, and cytokines were evaluated. Results In hPBMC cultures, AMG 592 caused more selective Treg response (pSTAT5, proliferation) and lower proinflammatory cytokine levels than aldesleukin. Dose-dependent expansion of FoxP3 +Tregs was associated with increased Temp and CRP in aldesleukin-treated but not in AMG 592-treated CM. In the FIH study, AMG 592 was well tolerated, with no serious AEs. The most common AE across cohorts was grade 1 painless erythema at/near the injection site which resolved without treatment. Preliminary PK results indicate dose-related increases in AMG 592 serum exposure. AMG 592 caused robust, dose-dependent Treg expansion relative to Tcon in all treated individuals. Expanded Tregs had increased CD25 and FoxP3, and were enriched for recent thymic emigrants. At the highest dose, increase in Treg: Tcon ratio peaked at day 8 (~4 fold vs baseline) and remained elevated up to day 29. AMG 592-mediated Treg expansion was highly selective, with no directional change in NK cell numbers and minimal increase in Tcon; there were no increases in serum proinflammatory cytokines IL-6, TNFα, or IFN-γ above the limits of detection. Conclusion AMG 592 caused dose-dependent, selective Treg expansion in healthy volunteers. Lack of proinflammatory cytokines and reduced inflammation markers suggest a wider therapeutic margin, and sustained Treg elevation implies less frequent dosing, compared with aldesleukin. Further investigation of AMG 592-induced Treg-mediated restoration of immune homeostasis in inflammatory and autoimmune diseases is warranted.
Acute dietary nitrate supplementation does not attenuate oxidative stress or the hemodynamic response during submaximal exercise in hypobaric hypoxia

The purpose of this study was to investigate changes in oxidative stress, arterial oxygen saturation (SaO2), blood pressure (BP), and heart rate (HR) during exercise in hypobaric hypoxia following ...
A near-linear algorithm for projective clustering integer points

We consider the problem of projective clustering in Euclidean spaces of non-fixed dimension. Here, we are given a set P of n points in Rm and integers j ≥ 1, k ≥ 0, and the goal is to find j k-subspaces so that the sum of the distances of each point in P to the nearest subspace is minimized. Observe that this is a shape fitting problem where we wish to find the best fit in the L1 sense. Here we will treat the number j of subspaces we want to fit and the dimension k of each of them as constants. We consider instances of projective clustering where the point coordinates are integers of magnitude polynomial in m and n. Our main result is a randomized algorithm that for any e > 0 runs in time O(mn polylog(mn)) and outputs a solution that with high probability is within (1 + e) of the optimal solution.To obtain this result, we show that the fixed dimensional version of the above projective clustering problem has a small coreset. We do that by observing that in a fairly general sense, shape fitting problems that have small coresets in the L∞ setting also have small coresets in the L1 setting, and then exploiting an existing construction for the L∞ setting. This observation seems to be quite useful for other shape fitting problems as well, as we demonstrate by constructing the first "regular" coreset for the circle fitting problem in the plane.
Acute Adrenal Insufficiency

Acute adrenal insufficiency is a rare disorder with a high morbidity and mortality if allowed to progress unrecognized. This disorder is most commonly caused by autoimmune (idiopathic) adrenalitis, with a high prevalence in women. Presentation is highly variable from chronic nonspecific symptoms to an acute decompensation in hemodynamic status. Treatment is safe and effective. Early recognition and intervention remain significant steps in altering the course of adrenal insufficiency.
Targeting Th17 cells in CNS immune pathology

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoreactive T lymphocytes. A new class of CD4+ T cells, the Th17 lineage, has recently been described and has been implicated in initiating immune responses against CNS autoantigens. Findings in experimental autoimmune encephalomyelitis (EAE, the animal model for MS) suggest that targeting Th17 cells may have a beneficial outcome for patients suffering from MS. Several existing and emerging therapeutic strategies are discussed based on the manner in which they target Th17-mediated autoimmunity: lymphocyte depletion, prevention of Th17 development, and prevention of Th17 function. T cell-ablating agents are not Th17 specific and are associated with toxicity and opportunistic infections. The prevention of Th17 differentiation can be achieved experimentally by neutralizing cytokines required for Th17 development and by the administration of cytokines or other chemicals that interfere with differentiation; however, these strategies may also lead to disease. Prevention of functional Th17 responses can be accomplished by inhibiting leukocyte trafficking or by neutralizing IL-17. While several promising therapeutic candidates have been identified using EAE and clinical experimentation, both the risks of immunomodulation as well as the efficacy of such candidates in human patients need to be completely characterized and carefully considered.
Singular perturbation analysis of integral equations

On etudie quelques equations integrales lineaires de Volterra ou de Fredholm a perturbations singulieres. On etablit les estimations d'erreur
18-OR : INCIDENCE OF HLA ANTIBODIES AFTER ISLET CELL TRANSPLANTATION: INITIAL RESULTS OF THE CLINICAL ISLET TRANSPLANTATION (CIT) CONSORTIUM TRIAL

Aim Alloreactivity to pancreatic islet cell transplantation (IT) has been reported previously particularly for those IT recipients with a history of sensitization events prior to transplant. The aim of this CIT Consortium study was to determine the incidence of HLA alloimmunization and characterize donor-specific antibody (DSA) profiles after IT. Methods We conducted a prospective, single-arm, Phase III study of IT alone (CIT-07) in T1D in subjects 18 to 65 years of age in 12 transplant centers. Standardized procedures were used for islet manufacturing, patient selection, immunosuppression (Sirolimus, Tacrolimus, Etanercept, Rabbit ATG), transplantation and care. Anti-HLA antibody screening was performed using multiple solid phase assay platforms including the LABScreen® Single Antigen assay at Day 75, Months 6, 9, 12, 18 and 24 after IT. Analyses of antibody specificity included HLA class I (A, B, C) and class II (DR, DQA, DQB, DP). Subjects with HLA antibodies (MFI > 3,000) or pre-transplant DSA (MFI > 700-1,000) were deemed ineligible. CPRA was calculated using an MFI cut off value of 3,000. DSA was defined as bead reactivity with an absolute MFI > 1,000 and an increase in MFI > 50% when compared to pre-IT reactivity. Results Patients received an initial transplant between October of 2008 and September of 2012 Study follow-up will be complete in May of 2014. 48 subjects were transplanted and followed for at least 24 months. 25 of the 48 subjects received a second transplant and 1 subject received a third transplant. An interim analysis through April of 2013 showed that 3/48 (6%) developed DSA while on IS. The PRA remained negative in all patients without DSA. The follow up period ranged from 364 to 1571 days with a median of 736 days. Conclusions The CIT-07 protocol shows a low incidence of PRA or DSA using standardized procedures for islet manufacturing, patient selection and care, and HLA antibody testing. Future studies should evaluate long-term outcomes after DSA development.
Musings on the future direction of One Health, William Hunting and tuberculosis, while listening to blackbirds sing.

Had the term ‘One Health’ been in use 130 years ago, it is highly likely that this journal’s first editor, William Hunting, would have used it in the first edition of The Veterinary Record . The issue, published in July 1888, includes a report of a meeting of the Scottish Metropolitan Veterinary Medical Society at which there had been a lengthy discussion about the prevalence and implications of bovine tuberculosis (TB) in the 300 or so dairies in Edinburgh and its suburbs. It had only been a few years earlier, in 1882, that Robert Koch had reported his discovery that tuberculosis was caused by a bacillus;1 yet the discussion clearly indicated the concern of the society’s members over the transmission of bovine TB to children drinking the milk from the dairies. Given that both the medical and veterinary professions previously believed that heredity and environment were the major factors causing tuberculosis, Koch’s discovery represented a paradigm shift in understanding the causation of the disease and those present at the Scottish meeting believed that the government had the power under the Contagious Diseases (Animals) Acts to intervene and control bovine TB to prevent its transmission to people. However, it would take another 70 years or so before the risk of bovine TB spreading from infected cattle to people was finally solved. In 2005, in response to a spate of emerging diseases at the turn of the 21st century, and in the tradition of William Hunting, Martin Alder and Graham Easton, editors of Vet Record and The BMJ , had the foresight to recognise the importance of drawing attention to the concept of One Medicine (in its transition to One Health), a tradition that has been continued in this celebratory edition by Adele Waters and Fiona Godlee current editors of Vet …
Pixel-Parallel Architecture for Neuromorphic Smart Image Sensor with Visual Attention

Power reduction and speedup of computer vision designs remain of high interest as image resolutions continue to increase. Neuromorphic-circuits, emulating the behavior of the nervous system, aspire to achieve this goal. In this paper, we present a pixel-parallel 3D-architecture of a neuromorphic image sensor that uses different sampling frequencies in different regions of an image. We design the model as a bottom-up 3D-architecture composing of several hierarchical computational planes where each plane performs different image processing algorithms in parallel. The on-chip attention module dynamically detects regions with relevant information and produces a feedback path to sample those regions with a higher clock frequency, whereas regions with low spatial and temporal information receive less attention. The results show that by sampling non-relevant regions with a lower frequency, the sensor can reduce redundancy and enable high-performance computing at low power.
TRPC6 inactivation does not affect loss of renal function in nephrotoxic serum glomerulonephritis in rats, but reduces severity of glomerular lesions

Canonical transient receptor potential-6 (TRPC6) channels have been implicated in a variety of chronic kidney diseases including familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) and renal fibrosis following ureteral obstruction. Here we have examined the role of TRPC6 in progression of inflammation and fibrosis in the nephrotoxic serum (NTS) model of crescentic glomerulonephritis. This was assessed in rats with non-functional TRPC6 channels due to genomic disruption of an essential domain in TRPC6 channels (Trpc6del/del rats) and wild-type littermates (Trpc6wt/wt rats). Administration of NTS evoked albuminuria and proteinuria observed 4 and 28 days later that was equally severe in Trpc6wt/wt and Trpc6del/del rats. By 28 days, there were dense deposits of complement and IgG within glomeruli in both genotypes, accompanied by severe inflammation and fibrosis readily observed by standard histological methods, and also by increases in renal cortical expression of multiple markers (α-smooth muscle actin, vimentin, NLRP3, and CD68). Tubulointerstitial fibrosis appeared equally severe in Trpc6wt/wt and Trpc6del/del rats. TRPC6 inactivation did not protect against the substantial declines in renal function (increases in blood urea nitrogen, serum creatinine and kidney:body weight ratio) in NTS-treated animals, and increases in a urine maker of proximal tubule pathology (β2-macroglobulin) were actually more severe in Trpc6del/del animals. By contrast, glomerular pathology, blindly scored from histology, and from renal cortical expression of podocin suggested a partial but significant protective effect of TRPC6 inactivation within the glomerular compartment, at least during the autologous phase of the NTS model.
Variations on the Oral Case Presentation

There are several variations on the standard oral case presentation that can be used according to the clinical setting, the status of the patient, and the priorities and preferences of the care team. This chapter discusses specific approaches to night float and transfer presentations, SOAP-style presentations for work rounds, emergency room and outpatient clinic presentations, bedside presentations, and calls to consultants. Skills required for the various types of presentations include reassessment of initial clinical reasoning and decision-making, analysis of interval data, triage and identification of life-threatening problems, and production of a concise synopsis of a case. SNAPPS, a method for medical students to show their thinking and clinical reasoning in the outpatient clinic, is also discussed.
An optimal Bayesian predictive probability design for phase II clinical trials with simple and complicated endpoints.

Most existing phase II clinical trial designs focus on conventional chemotherapy with binary tumor response as the endpoint. The advent of novel therapies, such as molecularly targeted agents and immunotherapy, has made the endpoint of phase II trials more complicated, often involving ordinal, nested, and coprimary endpoints. We propose a simple and flexible Bayesian optimal phase II predictive probability (OPP) design that handles binary and complex endpoints in a unified way. The Dirichlet-multinomial model is employed to accommodate different types of endpoints. At each interim, given the observed interim data, we calculate the Bayesian predictive probability of success, should the trial continue to the maximum planned sample size, and use it to make the go/no-go decision. The OPP design controls the type I error rate, maximizes power or minimizes the expected sample size, and is easy to implement, because the go/no-go decision boundaries can be enumerated and included in the protocol before the onset of the trial. Simulation studies show that the OPP design has satisfactory operating characteristics.
Core Hippo pathway components act as a brake on Yap and Taz in the development and maintenance of the biliary network

ABSTRACT The development of the biliary system is a complex yet poorly understood process, with relevance to multiple diseases, including biliary atresia, choledochal cysts and gallbladder agenesis. We present here a crucial role for Hippo-Yap/Taz signaling in this context. Analysis of sav1 mutant zebrafish revealed dysplastic morphology and expansion of both intrahepatic and extrahepatic biliary cells, and ultimately larval lethality. Biliary dysgenesis, but not larval lethality, is driven primarily by Yap signaling. Re-expression of Sav1 protein in sav1−/− hepatocytes is able to overcome these initial deficits and allows sav1−/− fish to survive, suggesting cell non-autonomous signaling from hepatocytes. Examination of sav1−/− rescued adults reveals loss of gallbladder and formation of dysplastic cell masses expressing biliary markers, suggesting roles for Hippo signaling in extrahepatic biliary carcinomas. Deletion of stk3 revealed that the phenotypes observed in sav1 mutant fish function primarily through canonical Hippo signaling and supports a role for phosphatase PP2A, but also suggests Sav1 has functions in addition to facilitating Stk3 activity. Overall, this study defines a role for Hippo-Yap signaling in the maintenance of both intra- and extrahepatic biliary ducts.
The Gendered Patterns of Climate Information Service Use in Africa

Climate information services (CIS) are increasingly viewed as a means to achieve greater resilience to climate hazards. However, the architecture of CIS is not always sensitive to the needs of all of its users. To understand better how to engage users through CIS requires an approach that highlights decision‐making processes relevant to both the material and non‐material elements of one’s livelihood. This research, as part of the wider USAID-funded Climate Information Services Research Initiative (CISRI) uses the Livelihoods as Intimate Government (Carr 2014) framework to understand the more non‐material processes relevant to livelihood decision‐making. Through this approach, we were able to identify gendered patterns of climate information services in Sub‐Saharan Africa and uncover how one’s gender identity impacts one’s modes of agricultural production, access to land, information, and capital, thus highlighting how certain users may be limited or excluded from CIS. The results of this work include recommendations on how to best refine systems of monitoring and evaluation of CIS programs in Africa.
Recent progress in the concurrent atomistic-continuum method and its application in phonon transport

This work presents the recent progress in the development of the concurrent atomistic-continuum (CAC) method for coarse-grained space- and time-resolved atomistic simulations of phonon transport. Application examples, including heat pulses propagating across grain boundaries and phase interfaces, as well as the interactions between phonons and moving dislocations, are provided to demonstrate the capabilities of CAC. The simulation results provide visual evidence and reveal the underlying physics of a variety of phenomena, including phonon focusing, wave interference, dislocation drag, interfacial Kapitza resistance caused by quasi-ballistic phonon transport, etc. A new method to quantify fluxes in transient transport processes is also introduced.
Peacebuilding and Displacement in Northern Uganda: A Cross-Sectional Study of Intentions to Move and Attitudes Towards Former Combatants

Using data from a cross-sectional survey of internally displaced populations in northern Uganda, this article analyses individual-level determinants of attitudes toward peacebuilding processes, including returning home and the reintegration of former combatants. We find that perceptions of social services and livelihood opportunities at the current place of living and at return or resettlement sites influence individuals’ decisions to move as do attitudes toward former combatants. Furthermore, we show that internally displaced persons are a specific group with needs and attitudes that differ from those of others. Such empirical information must be taken into account for the successful development and implementation of peace and reconstruction programmes.