cssi/SciSciGPT-SciSciNet huggingface dataset:
Everything You Wanted to Know About PUFs

In typical cryptographic applications, the secret keys are stored in volatile or nonvolatile memory (NVM). In the latter case, they remain in memory and can be retrieved even when the power is turned off. Even volatile memory is vulnerable to attacks if one has physical access to it. Thus the traditional approaches to key storage are not favored, especially in high-security applications.
Study partners should be required in preclinical Alzheimer's disease trials.

In an effort to intervene earlier in Alzheimer’s disease (AD), clinical trials are testing promising candidate therapies in preclinical disease. Preclinical AD trial participants are cognitively normal, functionally independent, and autonomous decision-makers. Yet, like AD dementia trials, preclinical trials require dual enrollment of a participant and a knowledgeable informant, or study partner. The requirement of dyadic enrollment is a barrier to recruitment and may present unique ethical challenges. Despite these limitations, the requirement should continue. Study partners may be essential to ensure participant safety and wellbeing, including overcoming distress related to biomarker disclosure and minimizing risk for catastrophic reactions and suicide. The requirement may maximize participant retention and ensure data integrity, including that study partners are the source of data that will ultimately instruct whether a new treatment has a clinical benefit and meaningful impact on the population health burden associated with AD. Finally, study partners are needed to ensure the scientific and clinical value of trials. Preclinical AD will represent a new model of care, in which persons with no symptoms are informed of probable cognitive decline and eventual dementia. The rationale for early diagnosis in symptomatic AD is equally applicable in preclinical AD—to minimize risk, maximize quality of life, and ensure optimal planning and communication. Family members and other sources of support will likely be essential to the goals of this new model of care for preclinical AD patients and trials must instruct this clinical practice.
Well-to-refinery emissions and net-energy analysis of China’s crude-oil supply

Oil is China’s second-largest energy source, so it is essential to understand the country’s greenhouse gas emissions from crude-oil production. Chinese crude supply is sourced from numerous major global petroleum producers. Here, we use a per-barrel well-to-refinery life-cycle analysis model with data derived from hundreds of public and commercial sources to model the Chinese crude mix and the upstream carbon intensities and energetic productivity of China’s crude supply. We generate a carbon-denominated supply curve representing Chinese crude-oil supply from 146 oilfields in 20 countries. The selected fields are estimated to emit between ~1.5 and 46.9 g CO2eq MJ−1 of oil, with volume-weighted average emissions of 8.4 g CO2eq MJ−1. These estimates are higher than some existing databases, illustrating the importance of bottom-up models to support life-cycle analysis databases. This study provides quantitative insight into China’s energy policy and the economic and environmental implications of China’s oil consumption.
Bone fragility in Turner syndrome: Fracture prevalence and risk factors determined by a national patient survey.

OBJECTIVE Osteoporosis is considered a comorbidity of adult women with Turner syndrome (TS). Limited data are available on fracture prevalence in girls and women with this diagnosis. We aimed to determine the prevalence of fractures in individuals with TS in the United States and identify risk factors for fracture. DESIGN Girls and women with TS were invited to participate in an anonymous, self-report, national survey from November 2016 to March 2017. Non-TS controls were obtained through direct contacts of TS participants. RESULTS During childhood (0-12 years), adolescence (13-25 years) and young adulthood (26-45 years), there was no difference between TS and controls in fracture prevalence. Girls and women with TS were more likely to report upper extremity fractures, whereas controls were more likely to report phalangeal fractures. Older women (>45 years) with TS were more likely to fracture than non-TS controls (P = .01). Balance problems were more common in individuals with TS than controls (26.5% vs 14.8%, P = .0006). In TS, those reporting balance problems were 54% more likely to have a prior fracture than those without balance problems (OR=1.54, 95% CI 1.03, 2.30), even after controlling for age. There was no significant association between balance problems and fractures among controls. CONCLUSIONS In a nationwide survey, there was no difference in fracture prevalence in younger women with TS compared with controls. However, the location of fractures differed. After controlling for age, impaired balance was associated with an increased fracture risk in TS and may be an underrecognized risk factor for fracture in this population.
Applications of Beta Alumina in the Energy Field

During the past decade, several devices based on beta alumina have been proposed for energy storage and conversion: a sodium-sulfur storage battery; a sodium-halogen primary battery; a solid state cell; and a sodium heat engine or thermoelectric converter.
Long Lives: Carnivores

Arachnids clearly dominate this category, and are represented mostly by scorpions and certain large-bodied spiders. The few whip scorpions occurring in deserts should also be included, as should some pseudoscorpions. Scolopendromorph centipedes add moderately to the remaining taxa, as most likely do some of the large carabid beetles, but very little is known about the life histories of either in arid regions.
Post‐orogenic thermal history and exhumation of the northern Appalachian Basin: Low‐temperature thermochronologic constraints

Abstract Apatite fission‐track (AFT) thermochronology and (U‐Th)/He (AHe) dating, combined with paleothermometers and independent geologic constraints, are used to model the thermal history of Devonian Catskill delta wedge strata. The timing and rates of cooling determines the likely post‐orogenic exhumation history of the northern Appalachian Foreland Basin (NAB) in New York and Pennsylvania. AFT ages generally young from west to east, decreasing from ~185 to 120 Ma. AHe single‐grain ages range from ~188 to 116 Ma. Models show that this part of the Appalachian foreland basin experienced a non‐uniform, multi‐stage cooling history. Cooling rates vary over time, ~1–2 °C/Myr in the Early Jurassic to Early Cretaceous, ~0.15–0.25 °C/Myr from the Early Cretaceous to Late Cenozoic, and ~1–2 °C/Myr beginning in the Miocene. Our results from the Mesozoic are broadly consistent with earlier studies, but with the integration of multiple thermochronometers and multi‐kinetic annealing algorithms in newer inverse thermal modeling programs, we constrain a Late Cenozoic increase in cooling which had been previously enigmatic in eastern U.S. low‐temperature thermochronology datasets. Multi‐stage cooling and exhumation of the NAB is driven by post‐orogenic basin inversion and catchment drainage reorganization, in response to changes in base level due to rifting, plus isostatic and dynamic topographic processes modified by flexure over the long (~200 Myr) post‐orogenic period. This study compliments other regional exhumation data‐sets, while constraining the timing of post‐orogenic cooling and exhumation in the NAB and contributing important insights on the post‐orogenic development and inversion of foreland basins along passive margins.
Post-wildfire recovery of an upland oak−pine forest on the Cumberland Plateau, Kentucky, USA

Many forests within the southern Appalachian region, USA, have experienced decades of fire exclusion, contributing to regeneration challenges for species such as oaks (Quercus spp. L.) and pines (Pinus spp. L.), and threatening the maintenance of oak-dominated forests in the future. While the use of prescribed fire as a forest management tool is increasing within this region, there remains a lack of information on the potential role of wildfire. A wildfire within the Daniel Boone National Forest, Kentucky, USA, provided an opportunity to investigate how wildfire affected forest vegetation response. We examined the effects of fire severity, quantified using composite burn index (CBI), on basal area, stem density, and sapling recruitment for several key species. We also examined the effects of fire severity on understory species richness and illuminated the consequence of non-native species invasions following fire. Our results demonstrated a negative relationship between fire severity and basal area (stems ≥2 cm diameter at breast height; P ≤ 0.001), and a positive relationship with the recruitment of oak and pine saplings (both P ≤ 0.001), oak sapling density (P = 0.012), and non-woody understory species richness (P ≤ 0.001). We also found that increasing fire severity heightened likelihood of invasion by non-native species, specifically princess tree (Paulownia tomentosa [Thunb.] Siebold & Zucc. ex. Steud; P = 0.009) and Chinese silvergrass (Miscanthus sinensis Andersson; P = 0.028). Where it is feasible, public land managers may be able to generate a range of fire severity during future prescribed fires that approximate some characters of wildfire. These fires, when implemented in southern Appalachian upland forests, may help recruit oaks and pines and boost their potential as future canopy dominants. However, the increased occurrence of non-native invasive species invasion following fire conveys the importance of targeted and timely eradication treatments before new populations of non-native species may become established or reproduce, contradicting the ecological benefits of fire.
Analysis of the role of thrombomodulin in all-trans retinoic acid treatment of coagulation disorders in cancer patients

Clinical studies have shown that all-trans retinoic acid (RA), which is often used in treatment of cancer patients, improves hemostatic parameters and bleeding complications such as disseminated intravascular coagulation (DIC). However, the mechanisms underlying this improvement have yet to be elucidated. In vitro studies have reported that RA upregulates thrombomodulin (TM) expression on the endothelial cell surface. The objective of this study was to investigate how and to what extent the TM concentration changes after RA treatment in cancer patients, and how this variation influences the blood coagulation cascade. In this study, we introduced an ordinary differential equation (ODE) model of gene expression for the RA-induced upregulation of TM concentration. Coupling the gene expression model with a two-compartment pharmacokinetic model of RA, we obtained the time-dependent changes in TM and thrombomodulin-mRNA (TMR) concentrations following oral administration of RA. Our results indicated that the TM concentration reached its peak level almost 14 h after taking a single oral dose (110 $$ \frac{mg}{m^2} $$ ) of RA. Continuous treatment with RA resulted in oscillatory expression of TM on the endothelial cell surface. We then coupled the gene expression model with a mechanistic model of the coagulation cascade, and showed that the elevated levels of TM over the course of RA therapy with a single daily oral dose (110 $$ \frac{mg}{m^2} $$ ) of RA, reduced the peak thrombin levels and endogenous thrombin potential (ETP) up to 50 and 49%, respectively. We showed that progressive reductions in plasma levels of RA, observed in continuous RA therapy with a once-daily oral dose (110 $$ \frac{mg}{m^2} $$ ) of RA, did not affect TM-mediated reduction of thrombin generation significantly. This finding prompts the hypothesis that continuous RA treatment has more consistent therapeutic effects on coagulation disorders than on cancer. Our results indicate that the oscillatory upregulation of TM expression on the endothelial cells over the course of RA therapy could potentially contribute to the treatment of coagulation abnormalities in cancer patients. Further studies on the impacts of RA therapy on the procoagulant activity of cancer cells are needed to better elucidate the mechanisms by which RA therapy improves hemostatic abnormalities in cancer.
Parallel edge-based sampling for static and dynamic graphs

Graph sampling is an important tool to obtain small and manageable subgraphs from large real-world graphs. Prior research has shown that Induced Edge Sampling (IES) outperforms other sampling methods in terms of the quality of subgraph obtained. Even though fast sampling is crucial for several workflows, there has been little work on parallel sampling algorithms in the past. In this paper, we present parIES - a framework for parallel Induced Edge Sampling on shared-memory parallel machines. parIES, equipped with optimized load balancing and synchronization avoiding strategies, can sample both static and streaming dynamic graphs, while achieving high scalability and parallel efficiency. We develop a lightweight concurrent hash table coupled with a space-efficient dynamic graph data structure to overcome the challenges and memory constraints of sampling streaming dynamic graphs. We evaluate parIES on a 16-core (32 threads) Intel server using 7 large synthetic and real-world networks. From a static graph, parIES can sample a subgraph with > 1.4B edges in
The Impact of Objectives on Firm Decisions: Bank and Credit Union Lending in the Great Recession

Credit unions lent significantly more than profit-maximizing banks during the Great Recession. Loan growth rates were higher for the $1.3 trillion industry by as much as 10 percentage points at the peak of the crisis. Using a newly constructed database containing balance sheet information and loan-level activity, I compare institutions that faced identical borrowers in the same local credit markets and control for crises exposures to show that the effect is supply-driven. Further, the lending difference was sustained by 15-20 percent lower profit margins. Loan pricing, informational advantages, taxes, or the regulatory environment do not explain the results. Rather, member-oriented non-profit objectives precluded the slow economic recovery of credit unions after the financial crisis.
Novel Noninvasive Diagnostics

Molecular diagnostics have revolutionized human oncology to allow early detection, targeted therapy, monitoring throughout treatment, and evidence of recurrence. By identifying genetic signatures associated with cancers, liquid biopsy techniques have been developed to diagnose and monitor cancer in noninvasive or minimally invasive ways. These techniques offer new opportunities for improving cancer screening, diagnosis, and monitoring the impact of therapy on the patients over time. Liquid biopsy also drives drug development programs. Similar diagnostics hold promise for comparable results in the veterinary field. Several noninvasive/minimally invasive techniques have been described in veterinary medicine that could be referred to as liquid biopsy.
Spliceosomal Mutations Induce R Loop-Associated ATR Signaling

Recurrent missense mutations in genes encoding RNA splicing factors (e.g. U2AF1, SRSF2 and SF3B1) are among the most frequently identified genetic alterations in myeloid malignancies (i.e. myelodysplastic syndromes [MDS], chronic myelomonocytic leukemia, and acute myeloid leukemia). Although genetically-engineered mouse models of the most common mutant alleles (U2AF1-S34F, SRSF2-P95H, SF3B1-K700E) recapitulate the sequence-specific changes in RNA splicing observed inprimary clinical samples carrying these mutations, the precise roles of splicing factor mutations in MDS pathobiology and leukemogenesis are not fully understood. We recently reported that RNA splicing perturbation, either by pharmacologic compounds or by expressing spliceosomal mutations, led to R loop accumulation (Nguyen HD et al, Mol Cell, 2017). R loops are transcription intermediates containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA). Aberrant R loop accumulation can lead to genomic instability. We showed that Replication Protein A (RPA), a ssDNA-binding protein, localized at R loop and promoted R loop resolution via cooperation with RNaseH1, an enzyme that specifically hydrolyzes RNA:DNA hybrids. Moreover, RPA was phosphorylated at R loops. Given that RPA also interacts directly with the ATR-ATRIP kinase complex, we postulated that the R loop-induced phosphorylation of RPA could be mediated by ATR-ATRIP. Here, we demonstrate that RNA splicing perturbations induce R loop-associated RPA phosphorylation mediated by ATR. HeLa or K562 cells that stably expressed transgenic U2AF1-wild-type (WT) or mutant S34F protein at similar levels to endogenous U2AF1 were selected for this study. To detect phosphorylated-RPA (p-RPA), we performed immunofluorescence staining and western blot analysis, and observed higher levels of p-RPA in U2AF1-S34F expressing cells than in U2AF1-WT expressing cells. Conditional induction of RNaseH1 to remove R loops in S34F mutant cells reduced the elevated p-RPA to a level similar to WT cells (Fig. 1A). In addition, p-RPA was suppressed by an ATR inhibitor (ATRi, VE-821, Fig. 1B), but not an ATM inhibitor (ATMi, Ku-55933), suggesting that p-RPA is triggered by R loops in an ATR-dependent manner. The effect of VE-821 on S34F mutants was validated inan MTS-based cell viability assay. In WT cells, the IC50 of VE-821 was 10.4 +/- 0.8 µM whereas in S34F mutants IC50 dropped significantly to 2.9 +/- 0.2 µM (p Disclosures No relevant conflicts of interest to declare.
A Single-Path Reconfigurable Frequency Multiplier for 28/39 GHz Dual-Band Transceivers

This paper presents a single-output frequency multiplier, operating either as doubler or tripler for LO generation in 5G dual-band transceivers. The multiplier consists of differential pair, followed by a wideband 1-bit phase shifter that enables summation/cancellation of odd or even current harmonics. A frequency-reconfigurable driver amplifier, based on variable transmission lines, is integrated to boost the output power and signal purity. The multiplier can generate frequencies in the range of 21-23 GHz and 31.5-34.5 GHz with output power>2 dBm with a fixed 5 dBm input, while maintaining harmonic rejection of over 25 dBc. The IC is implemented in 120 nm SiGe BiCMOS process, occupies area of 0.63 mm2 and consumes 60 mW.
DEPRESSION IN CAREGIVERS OF VETERANS: THE INTERACTION OF PERCEIVED SOCIAL SUPPORT AND AGE

Caregiving is a risk factor for increased psychological stress and depression (Pinquart & Sorensen, 2003). Perceived social support (PSS) is strongly associated with emotional well-being and, for informal family caregivers, may be an important predictor of caregiver psychological outcomes. Although much is known about the effects of global PSS, there is a gap in research regarding numerous identified functional dimensions of support, particularly among family caregivers. Thus, this secondary data analysis examined how dimensions of PSS predict depression, and the moderating effects of age on this relationship, utilizing data from 240 family caregivers of elderly veterans receiving outpatient care at the Atlanta VA. The analysis utilizes a multidimensional measure of PSS (Sherbourne & Stewart, 1991) with four sub scales: emotional/informational, tangible, affectionate, and positive social interaction. Preliminary OLS regression analyses, regressing depression on relevant demographic variables and PSS domains, revealed a significant overall model (p < .001). All domains besides tangible support significantly predicted depression. Because age was the only demographic variable associated with depression, we tested hypotheses of an interaction of PSS and age with PROCESS macro (Hayes, 2017). Moderation analyses revealed a significant interaction of support and age on caregiver depression (p = .0145). Of unique social support dimensions, only emotional/informational social support interacted with age (p = .0075), demonstrating decreased depression at high levels of emotional/informational support, but a weaker effect for those of increased age. The original study was supported by the U.S. Department of Veterans Affairs Rehabilitation R&D Service.
Literary Strains: The Challenges of Making Meaning and Promoting Peace Through Written Works

In “Literary Strains,” Rice draws upon examples of writing after the 1994 genocide in Rwanda, as well as the preceding essays, to explore literature’s role in bearing witness. For Rice, writing has the potential to “recreate the past, revive individual memory, contribute to collective and historical memory,” while also participating in moves towards justice. Recognizing the “shortcomings of memory” especially after traumatic events, she claims that literature can bring about self-awareness, revealing prejudices, presuppositions, and stereotypes. Different kinds of literature have the potential to nuance and complexify understandings of reality, encouraging readers and writers to look at the world differently and move beyond binary ways of perception. In this way, literature can contribute to laying further foundations for understanding between traumatized individuals and divided communities.
How do clinical research coordinators learn Good Clinical Practice? A mixed-methods study of factors that predict uptake of knowledge:

Background:Good Clinical Practice is an international standard for the design and conduct of clinical trials to ensure ethical and scientific integrity. Recent National Institutes of Health policy ...
Compaction and Performance of Warm-Mix Asphalt with High-Reclaimed Asphalt Pavement

AbstractIncorporation of high contents of reclaimed asphalt pavement (RAP) in asphalt mixes produced at warm-mix asphalt (WMA) temperatures raises questions about the interaction between the RAP an...
The strong heritability of gender dysphoria

Abstract A major and important change in the assessment of gender dysphoria (i.e., being unhappy with one’s biological sex) occurred when the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) changed this diagnosis from gender identity disorder in DSM-IV-TR to the current diagnostic term, Gender Dysphoria. This chapter reviews studies of gender dysphoria and concludes that gender dysphoria is most likely a highly heritable trait, although heretofore unidentified environmental conditions may contribute to its expression. It is also concluded that the gender dysphoria is neither a rare nor a very rare condition.
Higher-order demand-driven symbolic evaluation

Symbolic backwards execution (SBE) is a useful variation on standard forward symbolic evaluation; it allows a symbolic evaluation to start anywhere in the program and proceed by executing in reverse to the program start. SBE brings goal-directed reasoning to symbolic evaluation and has proven effective in e.g. automated test generation for imperative languages. In this paper we define DDSE, a novel SBE which operates on a functional as opposed to imperative language; furthermore, it is defined as a natural extension of a backwards-executing interpreter. We establish the soundness of DDSE and define a test generation algorithm for this toy language. We report on an initial reference implementation to confirm the correctness of the principles.
Tupperware and Flowerville: Consumerism, identity politics, and intertextuality in David’s Story and Ulysses

Consumerism, as represented in Zoe Wicomb’s David’s Story (2000) and James Joyce’s Ulysses (1922), provides a useful theoretical model for rethinking the relationships between earlier texts and the...
Management of Waldenström macroglobulinemia in 2020.

The management of Waldenstrom macroglobulinemia (WM) has evolved tremendously with recent genomic discoveries that correlate with clinical presentation and could help to tailor treatment approaches. The current diagnosis of WM requires clinicopathological criteria, including bone marrow involvement by lymphoplasmacytic lymphoma cells, a serum immunoglobulin M (IgM) monoclonal paraprotein, and presence of the MYD88 L265P mutation. Once the diagnosis is established, the relationship between the patient's symptoms and WM should be carefully investigated, because therapy should be reserved for symptomatic patients. Bone marrow involvement and serum levels of IgM, albumin, and β2-microglobulin can be used to estimate the time until treatment initiation. The treatment of WM patients should be highly personalized, and the patient's clinical presentation, comorbidities, genomic profile, and preferences, as well as toxicity of the treatment regimens, should be taken into account. Alkylating agents (bendamustine, cyclophosphamide), proteasome inhibitors (bortezomib, carfilzomib, ixazomib), anti-CD20 monoclonal antibodies (rituximab, ofatumumab), and Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, zanubrutinib) are safe and highly effective treatment options in patients with WM. Because novel covalent and noncovalent BTK inhibitors (tirabrutinib, vecabrutinib, LOXO-305, ARQ-531), BCL2 antagonists (venetoclax), and CXCR4-targeting agents (ulocuplumab, mavorixafor) are undergoing clinical development in WM, the future of WM therapy certainly appears bright and hopeful.
Adding cognitive therapy to antidepressant medications decreases suicidal ideation.

Abstract Background Psychotherapy for depression and antidepressant medications have both been associated with decreases in suicidal ideation. Studies have not examined whether adding psychotherapy to antidepressant medications further reduces suicidal ideation relative to medications alone in adults. Methods Participants (N = 452) were randomized to 7 months of treatment with antidepressant medications or combined treatment with both medications and cognitive therapy for depression. We examined change in the suicide items from the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) across treatment using Bayesian generalized linear mixed models for non-continuous outcomes. Results Suicidal ideation decreased across treatment. When measured with the BDI, participants receiving both cognitive therapy and antidepressant medications showed 17% greater reductions in suicidal ideation relative to those receiving medications alone; this effect remained significant when controlling for depression severity. While the same pattern was observed when suicidal ideation was measured with the HDRS, the effect was smaller (7%) and not statistically significant. When BDI and HDRS scores were combined, participants receiving both therapy and medications showed 9% greater reductions in suicidal ideation relative to those receiving medications alone; this effect was marginally significant when controlling for depression severity. Limitations This is a secondary analysis of a randomized clinical trial designed to treat depression, in which suicidal ideation was assessed using single-item measures. Conclusions Adding cognitive therapy to antidepressant medications may reduce suicidal ideation to a greater extent than medications alone. Pending replication, combination treatment may be preferred for individuals with suicidal ideation. Trial registration: clinicaltrials.gov Identifier: NCT00057577
A Cost-Effectiveness Analysis of Nivolumab plus Ipilimumab Versus Pembrolizumab plus Axitinib and Versus Avelumab plus Axitinib in First-Line Treatment of Advanced Renal Cell Carcinoma

Abstract Background There now exist several viable first-line treatment options for metastatic renal cell carcinoma, making the choice of initial therapy difficult. Metrics other than patient factors may be necessary in selecting the most appropriate therapy. We aimed to assess the cost-effectiveness of the three combination therapies currently approved in treatment-naive advanced or metastatic renal cell carcinoma: nivolumab plus ipilimumab (NI), pembrolizumab plus axitinib (PA), and avelumab plus axitinib (AA) from US payer perspective. Patients and Methods Our analysis was performed based on previously obtained data derived from progression free survival and overall survival curves from CheckMate 214, KEYNOTE 426, and JAVELIN Renal 101. Results The total cost of each treatment was found to be $437,556.12 for NI, $450,597.15 for PA, and $542,882.34 for AA, with QALY of 4.04, 3.77, and 2.95 for each combination, respectively. ICER of NI versus PA was ($47,504.73/QALY); of NI versus AA was ($96,533.11/QALY); of PA versus AA was ($113,015.87/QALY). Net health benefit scaled against a WTP threshold of $150,000 per QALY was positive for NI versus PA at 0.36 and versus AA at 1.79, and this index was also positive for PA versus AA at 1.43, indicating that the additional value of these therapies versus their alternatives is more than the extra cost. Conclusion NI was found to be the most cost-effective treatment option over the other considered therapies. PA was found to be cost-effective compared to AA. When patient factors such as social issues and pre-existing conditions do not dictate their first-line therapy, clinicians may use this additional data to make financially conscious choices. Microabstract : There exist several viable first-line treatment options for metastatic renal cell carcinoma, making choice of initial therapy difficult. Metrics other than patient factors, such as cost, may assist in selecting the most appropriate therapy. Using data from CheckMate 214, KEYNOTE 426, and JAVELIN Renal 101, and including costs of medication administration, monitoring, and adverse events, a cost-effectiveness analysis revealed that nivolumab plus ipilimumab is more cost-effective than both pembrolizumab plus axitinib and avelumab plus axitinib.
From Private-Law Roots to International Norm: An Investigation into Moral Damage and Pecuniary Reparations in Transnational and International Law

Recourse to pecuniary awards as a remedy for moral damage (also called non-pecuniary damage) has become an international norm in modern times. The impetus or inspiration for this development at the top came from below, that is it came from the private law traditions of civil law and common law, though of course it may be debated as to which tradition was the decisive influence. What seems important is that the notions which emerged at the transnational and international levels have surpassed the products of those traditions. The assimilated ideas received and redeveloped at the supranational level have, in turn, passed back down to national courts and national laws. This has an impact in both common law and civil law. There has been a constant circulation and rotation of ideas passing back and forth through various conduits which link the vertical levels. By investigating the evolution and growth of the concept of moral damage and the generalised remedy to compensate it, this article will attempt to throw light upon the process by which ideas derived from private law spread, evolve and re-emerge as norms of international law.
Structural stability of tight-pitched damascene interconnects

The impact of cohesive forces in ruthenium (Ru) is studied for tighter interconnect technologies; such forces can result in bending of lines at these pitches. The sensitivity of these forces to process variations such as aspect ratio of lines, trench profiles, and critical dimensions are studied. It is observed that lower aspect ratio and higher dielectric modulus alleviate the effects of these cohesive forces. An ab-initio molecular dynamics model is used to compare behavior of Ru with that of copper. Higher surface energy of Ru potentially contributes to this bending phenomenon.
Finite Element Analysis and Structural Optimization of Vehicle Wheels

This paper describes the application of the MSC/NASTRAN finite element program to the structural analysis of automotive vehicle wheels and the optimization of wheel designs subject to both NVH and fatigue related constraints. Common wheel design considerations are discussed including wheel tests for both fatigue and stiffness. Techniques for the finite element modelling of wheels subjected to such loadings are described including MSC/NASTRAN cyclic symmetry capabilities, solid element modelling and plate element modelling of wheels. The use of OPUS (Optimization Process Utility System) interfaced with MSC/NASTRAN for automated design optimization is described. Its application to the structural optimization of a cast aluminum wheel using gage related design variables and both NVH and fatigue related constraints is described. It is concluded that such analytical techniques represent a practical approach to the design, structural analysis, and optimization of automotive vehicle wheels.
ACE inhibitors in renal disease

Recent experimental studies suggest that the resistance state of the preglomerular and postglomerular capillary arterioles may determine if a particular class of antihypertensive agents will protect the kidney from hemodynamically mediated glomerular injury. This review discusses (1) the effects of angiotensin II on the renal microcirculation, (2) the pathophysiology of essential hypertensive renal disease, (3) the renal pharmacology of angiotensin-converting enzyme (ACE) inhibitors, and (4) the hypothesis that renal protection is dependent on control of systemic and glomerular hypertension.
Simulation-assisted learning by competition: effects of noise differences between training model and target environment

The problem of learning decision rules for sequential tasks is addressed, focusing on the problem of learning tactical plans from a simple flight simulator where a plane must avoid a missile. The learning method relies on the notion of competition and employs genetic algorithms to search the space of decision policies. Experiments are presented that address issues arising from differences between the simulation model on which learning occurs and the target environment on which the decision rules are ultimately tested. Specifically, either the model or the target environment may contain noise. These experiments examine the effect of learning tactical plans without noise and then testing the plans in a noisy environment, and the effect of learning plans in a noisy simulator and then testing the plans in a noise-free environment. Empirical results show that, while best result are obtained when the training model closely matches the target environment, using a training environment that is more noisy than the target environment is better than using using a training environment that has less noise than the target environment.
An in-situ field ion microscope study of irradiated tungsten

Abstract The mobility of single self-interstitial atoms was studied in a series of in situ field ion microscope (FIM) experiments. High purity (≲ 1.5 × 10−6 at. fr. impurity level) W specimens were irradiated with 20 kev W+ ions under ultra-high vacuum (∼ 10−10 torr) conditions at temperatures between 8°K. The specimens were examined directly at the irradiation temperature employing the pulse field evaporation technique. The initial state of damage at 15°K consisted of depleted zones within 100 A of the irradiated surface, and a distribution of immobile self-interstitial atoms which were distributed throughout the bulk of the specimen, and which originated at the depleted zones. Direct observation of the FIM specimens during subsequent annealing experiments between 15°K and 120°K showed that these self-interstitial atoms underwent long-range migration (i.e. distances of ∼ 200 A) in Stage I, and were mobile at temperatures as low as ∼ 28°K. Warming these same specimens to 298°K (∼ middle of Stage II) follo...
The Effects of Supergiants on the Infrared Light Distribution in Galaxies

Dynamical models require good estimates of the stellar surface mass density in galaxies. Surface brightness measurements in principle can trace the locations of the stars, but optical wavelength images are often confused by dust extinction and dominated by the light from a relatively few, bright young stars. Near–infrared images are much less affected by dust extinction (A k ≈ 0.1A v ) and, for a normal stellar population, relatively unaffected by the presence of young stars. For example, in a population of stars similar to that found in the disk of the Milky Way ∼92% of the total light at K is due to giant stars, ∼ 7% due to main sequence stars, and only ∼ 1% due to supergiants. Since main sequence stars, which dominate the mass, and giants are well–mixed in older populations (see Aaronson 1977 and Frogel 1988), K images should trace the mass effectively.
Comparison of the LTQ-Orbitrap Velos and the Q-Exactive for proteomic analysis of 1–1000 ng RAW 264.7 cell lysate digests

Rational There is interest in extending bottom-up proteomics to the smallest possible sample size. We investigated the performance of two modern instruments for the analysis of samples ranging from 1 ng to 1 µg of RAW 264.7 cell lysate digests.
Characterization of the pH-dependent Interaction between the Gap Junction Protein Connexin43 Carboxyl Terminus and Cytoplasmic Loop Domains

A prevailing view regarding the regulation of connexin43 (Cx43) gap junction channels is that, upon intracellular acidification, the carboxyl-terminal domain (Cx43CT) moves toward the channel opening to interact with specific residues acting as a receptor site. Previous studies have demonstrated a direct, pH-dependent interaction between the Cx43CT and a Cx43 cytoplasmic loop (Cx43CL) peptide. This interaction was dependent on alpha-helical formation for the peptide in response to acidification; more recent studies have shown that acidification also induces Cx43CT dimerization. Whether Cx43CT dimerization is an important structural component in Cx43 regulation remains to be determined. Here we used an assortment of complimentary biophysical techniques to characterize the binding of Cx43CT or its mutants to itself and/or to a more native-like Cx43CL construct (Cx43CL(100-155), residues 100-155). Our studies expand the observation that specific Cx43CT domains are important for dimerization. We further show that properties of the Cx43CL(100-155) are different from those of the Cx43CL peptide; solvent acidification leads to Cx43CL(100-155) oligomerization and a change in the stoichiometry and binding affinity for the Cx43CT. Homo-Cx43CT and Cx43CL(100-155) oligomerization as well as the Cx43CT/Cx43CL(100-155) interaction can occur under in vivo conditions; moreover, we show that Cx43CL(100-155) strongly affects resonance peaks corresponding to Cx43CT residues Arg-376-Asp-379 and Asn-343-Lys-346. Overall, our data indicate that many of the sites involved in Cx43CT dimerization are also involved in the Cx43CT/Cx43CL interaction; we further propose that chemically induced Cx43CT and Cx43CL oligomerization is important for the interaction between these cytoplasmic domains, which leads to chemically induced gating of Cx43 channels.
Mothers’ beliefs about infant size: Associations with attitudes and infant feeding practices

Abstract Few studies have examined maternal attitudes toward infant body size, but extant work suggests there might be less negativity toward overweight sizes and less positivity toward thin sizes for infants than older children. Fifty mothers of 12 to 25 month-old infants completed questionnaires examining attitudes toward infants', children's and their own body sizes, as well as their feeding practices. Most mothers reported ideal body sizes similar to their infants' current body sizes, but mothers reported thinner ideals for girls than boys. Mothers showed the least thin idealization and overweight devaluation when rating infant bodies compared to rating older children and adults. Mothers’ perceptions of which infant body types were overweight were related to restrictive feeding practices. Mothers who perceived their infants as thin engaged in pressuring feeding practices. Results suggest some weight bias in mothers of infants and highlight the need for longitudinal studies examining mechanisms behind these varying attitudes.
Credibility, respectability, suggestibility, and spirit travel: Lurena Brackett and animal magnetism.

In the 1830s, when 20-year-old medical student Charles Poyen (1815-1844) began the demonstration tour that led to the popularization of animal magnetism in New England, he met with considerable resistance from both the medical profession and the general public. Skeptics argued that the phenomena apparently demonstrated during mesmeric sessions were so extraordinary that they had to be the result of intentional deception. The deception argument was bolstered by referencing the then popular prejudices against the working-class women who served as mesmeric subjects. Conveniently, these prejudices included belief in a special talent for deception that was not found in women from more respectable backgrounds. Mesmerists defended themselves against accusations of dishonesty by publicizing the achievements of Lurena Brackett (1816-1857), a young woman who escaped the prejudices associated with the working-class mesmeric subjects but still demonstrated apparently extraordinary mesmeric phenomena. The well-publicized story of Lurena regaining her sight during mesmeric seances is acknowledged as important in establishing the popularity of mesmerism in the United States. Lurena's supporters argued that her respectable background made deception impossible. This article uses Shorter's work on the history of hysteria and Trembinski's analysis of the history of trauma to argue that some of the seemingly extraordinary phenomena observed during a mesmeric seance can be better understood with reference to conversion disorder and the concept of hypnotic suggestion rather than intentional deception. While Lurena's respectability made her audience ready to accept her credibility, a conversion disorder would have produced the physical symptoms that responded so convincingly to mesmerism. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
The Behavior of Jet Streams over Eastern North America during January and February 1948

A graph of the latitude of jet streams at 80° W longitude for a 49-day period in the winter of 1947–8 shows that the jet stream undergoes changes which appear as discontinuities on such a graph. Several cases are discussed which illustrate the manner in which these discontinuities appear. The new jets so formed then appear to experience a southward displacement before their disappearance. Accompanying the southward displacement at this longitude is a disappearance of the solenoidal field accompanying the jet in the lower troposphere, and an increase of the potential temperature in the center of the jet. DOI: 10.1111/j.2153-3490.1950.tb00320.x
Understanding the effect of carbonate ion on cisplatin binding to DNA.

The role of carbonate in the binding of cis-diamminedichloroplatinum(II) to DNA was investigated in order to understand the potential involvement of carbonato-cisplatin species in the mechanism of action of platinum anticancer agents. Cisplatin was allowed to react with both double- and single-stranded DNA in carbonate, phosphate, and HEPES buffers, and the products were analyzed by agarose gel electrophoresis and enzymatic digestion/mass spectrometry, respectively. The data from these experiments demonstrate (1) that carbonate, like other biological nucleophiles, forms relatively inert complexes with platinum that inactivate cisplatin and (2) that the major cisplatin−DNA adduct formed is a bifunctional cross-link. These results are in accord with previous studies of cisplatin−DNA binding and reveal that the presence of carbonate has no consequence on the nature of the resulting adducts.
Characterizing permanent magnet blocks with Helmholtz coils

Abstract Most of the insertion devices to be installed at the Advanced Photon Source will utilize permanent magnets in their magnetic structures. The quality of the spectral output is sensitive to the errors in the field of the device which are related to variations in the magnetic properties of the individual blocks. The Advanced Photon Source will have a measurement facility to map the field in the completed insertion devices and equipment to test and modify the magnetic strength of the individual magnet blocks. One component of the facility, the Helmholtz coil permanent magnet block measurement system, has been assembled and tested. This system measures the total magnetic moment vector of a block with a precision better than 0.01% and a directional resolution of about 0.05°. The design and performance of the system will be presented.
Sailfish (Istiophorus Platypterus) Spawning and Larval Environment in a Florida Current Frontal Eddy

Abstract Fronts and eddies are widely hypothesized to be critical spawning habitat for large pelagic fishes, due to increased larval and/or adult feeding opportunities at these features. We examined sailfish (Istiophorus platypterus) spawning around a cyclonic, submesoscale (∼13 × 7 km) Florida Current frontal eddy. The temporal progression of eddy dynamics over a 65 h period was determined using ocean color satellite imagery, continuous surface measurements along the cruise track, and non-linear least-squares fitting of the positions of three drifters deployed within the eddy. A peak in larval sailfish densities (n = 2435, stations = 49), composed primarily of yolk-sac and first-feeding larvae, occurred at the eddy frontal zone. A majority of these larvae were estimated to have been spawned during the formation of the eddy. A comparison between the distribution of similar-age sailfish and scombrid larvae indicated that the peak in larval sailfish density likely resulted from spawning directly at the front, rather than transport by convergent flow. The first-feeding prey items of larval sailfish (Farranula and Corycaeus copepods) were most abundant at the frontal zone and to a lesser extent inside the eddy. Egg distributions were used to indirectly assess the distribution of adult sailfish prey items. Euthynnus alleteratus and Auxis spp. eggs were in highest abundance outside the eddy, while the eggs of small carangids were in highest abundance at the eddy frontal zone. Overall, this study indicates that sailfish spawn at small-scale oceanographic features that provide a favorable feeding environment for their larvae and potentially also for the adults.
Police Officers’ and Paramedics’ Experiences with Overdose and Their Knowledge and Opinions of Washington State’s Drug Overdose–Naloxone–Good Samaritan Law

Opioid overdoses are an important public health concern. Concerns about police involvement at overdose events may decrease calls to 911 for emergency medical care thereby increasing the chances than an overdose becomes fatal. To address this concern, Washington State passed a law that provides immunity from drug possession charges and facilitates the availability of take-home-naloxone (the opioid overdose antidote) to bystanders in 2010. To examine the knowledge and opinions regarding opioid overdoses and this new law, police (n = 251) and paramedics (n = 28) in Seattle, WA were surveyed. The majority of police (64 %) and paramedics (89 %) had been at an opioid overdose in the prior year. Few officers (16 %) or paramedics (7 %) were aware of the new law. While arrests at overdose scenes were rare, drugs or paraphernalia were confiscated at 25 % of the most recent overdoses police responded to. Three quarters of officers felt it was important they were at the scene of an overdose to protect medical personnel, and a minority, 34 %, indicated it was important they were present for the purpose of enforcing laws. Police opinions about the immunity and naloxone provisions of the law were split, and we present a summary of the reasons for their opinions. The results of this survey were utilized in public health efforts by the police department which developed a roll call training video shown to all patrol officers. Knowledge of the law was low, and opinions of it were mixed; however, police were concerned about the issue of opioid overdose and willing to implement agency-wide training.