cssi/SciSciGPT-SciSciNet huggingface dataset:
The eIF2 Complex and eIF2α

eIF2 is a three-subunit complex that forms the core of the eIF/GTP/Met-tRNAi ternary complex, which is essential for translation initiation. eIF2 cycles between the GTP-bound active and GDP-bound inactive forms. This GTP/GDP cycle is regulated primarily through reversible phosphorylation of the α subunit of eIF2 (eIF2α) by a set of kinases that specifically respond to various stress stimuli. Phosphorylation of eIF2α locks eIF2 in GDP-bound inactive form, thereby reducing protein synthesis and favoring metabolic dormancy required for cell survival under stress. Inversely, nonphosphorylated eIF2α increases protein synthesis and favors cell proliferation. Unsurprisingly, the eIF2 complex, more specifically eIF2α, appears to be an important hub of translation that participates in cell proliferation and survival, malignant transformation, tumor initiation, progression, and metastasis. In this chapter, we will review the molecular and chemical biology of eIF2 with particular emphasis on eIF2α and its regulation by phosphorylation. We will attempt to reconcile seemingly controversial observations related to the involvement of eIF2α and its regulatory kinases in cancer and discuss if and how eIF2 can be targeted for cancer therapy.
Sleep: A Pathway Linking Personality to Mortality Risk.

Abstract Personality and sleep predict longevity; however, no investigation has tested whether sleep mediates this association. Thus, we tested this effect across a 20-year follow-up (N = 3759) in the Midlife Development in the United States cohort (baseline Mage = 47.15) using proportional hazards in a structural equation modeling framework. Lower conscientiousness predicted increased death risk via the direct, indirect, and total effect of quadratic sleep duration. Although there were no other direct personality-mortality effects, higher neuroticism and agreeableness and lower conscientiousness predicted increased death risk via the joint indirect effects of quadratic sleep duration and higher daytime dysfunction. Lower extraversion predicted increased mortality risk via the indirect effect of daytime dysfunction. Our findings have implications for personality-based health interventions.
ACE inhibitor and ARB therapy: Practical recommendations.

Inhibitors of the renin-angiotensin-aldosterone system are cornerstones of therapy of cardiovascular disease.
Hybrid Physical-Deep Learning Model for Astronomical Inverse Problems

We present a Bayesian machine learning architecture that combines a physically motivated parametrization and an analytic error model for the likelihood with a deep generative model providing a powerful data-driven prior for complex signals. This combination yields an interpretable and differentiable generative model, allows the incorporation of prior knowledge, and can be utilized for observations with different data quality without having to retrain the deep network. We demonstrate our approach with an example of astronomical source separation in current imaging data, yielding a physical and interpretable model of astronomical scenes.
Predicting survival in infants born at <27 weeks gestation admitted to an all referral neonatal intensive care unit: a pilot study

There are no available predictive models for survival in extremely preterm (EP) infants admitted to a referral Level IV neonatal intensive care unit (NICU) after the first day of life (DOL). To determine if there are clinical variables present at admission that are associated with survival in an outborn EP population. Data were analyzed from EP infants admitted before DOL 100 from 2008 to 2016 (n = 744). We found that prophylactic indomethacin (OR 1.98 (1.20–3.25) p = 0.007), admit DOL (OR 1.05 (1.02–1.08) p < 0.001), and birth in Franklin County, (OR 2.02 (95% CI, 1.04–3.90) p = 0.04) were all associated with survival. Using ROC analysis, the area under the curve for the provisional survival score was 0.69 (95% CI, 0.64–0.75; p < 0.0001). There are factors on admission to a referral Level IV NICU associated with survival in EP patients.
Negative Pressure Wound Therapy: Basic Science Review

Since the initial publication in 1997 of the basic research behind Negative Pressure Wound Therapy and the additional review in 2006, much additional research has been conducted. This short review highlights some of this additional basic research into the mechanisms and physiological responses to the controlled applicaiton of sub-atmospheric pressure for wound care.
Suppressed threshold voltage roll-off and ambipolar transport in multilayer transition metal dichalcogenide feed-back gate transistors

The layered semiconducting transition metal dichalcogenides (s-TMDs) have attracted considerable interest as the channel material for field-effect transistors (FETs). However, the multilayer s-TMD transistors usually exhibit considerable threshold voltage (Vth) shift and ambipolar behavior at high source-drain bias, which is undesirable for modern digital electronics. Here we report the design and fabrication of double feedback gate (FBG) transistors, i.e., source FBG (S-FBG) and drain FBG (D-FBG), to combat these challenges. The FBG transistors differ from normal transistors by including an extra feedback gate, which is directly connected to the source/drain electrodes by extending and overlapping the source/drain electrodes over the yttrium oxide dielectrics on s-TMDs. We show that the S-FBG transistors based on multilayer MoS2 exhibit nearly negligible Vth roll-off at large source-drain bias, and the D-FBG multilayer WSe2 transistors could be tailored into either n-type or p-type transport, depending on the polarity of the drain bias. The double FBG structure offers an effective strategy to tailor multilayer s-TMD transistors with suppressed Vth roll-off and ambipolar transport for high-performance and low-power logic applications.
COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.
Detecting Off-Task Behavior from Student Dialogue in Game-Based Collaborative Learning

Collaborative game-based learning environments integrate game-based learning and collaborative learning. These environments present students with a shared objective and provide them with a means to communicate, which allows them to share information, ask questions, construct explanations, and work together toward their shared goal. A key challenge in collaborative learning is that students may engage in unproductive discourse, which may affect learning activities and outcomes. Collaborative game-based learning environments that can detect this off-task behavior in real-time have the potential to enhance collaboration between students by redirecting the conversation back to more productive topics. This paper investigates the use of dialogue analysis to classify student conversational utterances as either off-task or on-task. Using classroom data collected from 13 groups of four students, we trained off-task dialogue models for text messages from a group chat feature integrated into Crystal Island: EcoJourneys, a collaborative game-based learning environment for middle school ecosystem science. We evaluate the effectiveness of the off-task dialogue models, which use different word embeddings (i.e., word2vec, ELMo, and BERT), as well as predictive off-task dialogue models that capture varying amounts of contextual information from the chat log. Results indicate that predictive off-task dialogue models that incorporate a window of recent context and represent the sequential nature of the chat messages achieve higher predictive performance compared to models that do not leverage this information. These findings suggest that off-task dialogue models for collaborative game-based learning environments can reliably recognize and predict students’ off-task behavior, which introduces the opportunity to adaptively scaffold collaborative dialogue.
Pushing the Envelope in Battery Estimation Algorithms

Accurate estimation of lithium-ion battery health will (a) improve the performance and lifespan of battery packs in electric vehicles, spurring higher adoption rates, (b) determine the actual extent of battery degradation during usage, enabling a health-conscious control, and (c) assess the available battery life upon retiring of the vehicle to re-purpose the batteries for "second-use" applications. In this paper, the real-time validation of an advanced battery health estimation algorithm is demonstrated via electrochemistry, control theory, and battery-in-the-loop (BIL) experiments. The algorithm is an adaptive interconnected sliding mode observer, based on a battery electrochemical model, which simultaneously estimates the critical variables such as the state of charge (SOC) and state of health (SOH). The BIL experimental results demonstrate that the SOC/SOH estimates from the observer converge to an error of 2% with respect to their true values, in the face of incorrect initialization and sensor signal corruption.
Early (1-Year) Class II Donor Specific Antibodies without Complement-Binding Appears Benign after Heart Transplantation

Purpose The development of donor specific antibody (DSA) has been reported to have poor outcome after heart transplantation (HTx). DSA particularly class II, may result in graft dysfunction, increased mortality, development of cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE). These class II DSA appear to form later after heart transplant. It is not firmly established whether early class II DSA (within the first year after transplant) has adverse clinical effects. Methods Between 2010-15, we assessed 35 HTx patients (pts) who developed de novo class II DSA in the 1 year after HTx. Each pt had subsequent follow up of 5 years for mortality, development of CAV, as defined by stenosis ≥30% by angiography), and development of NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, defibrillator/pacemaker implant, stroke). In subgroup analysis, class II DSA was divided into those DSA that were complement-binding (C1q+) compared to those without complement-binding. All DSA pts were compared to pts without DSA (n=413). Results At 5 years after HTx, there appeared to be no difference between groups in 5-year survival, 5-year freedom from CAV and NF-MACE. Those DSA that were C1q+ had significantly lower 5-year survival and freedom from NF-MACE compared to DSA pts without C1q+ and to the control group. (see table) Conclusion Early de novo class II DSA that are not complement-binding do not appear to result in increased mortality or development of CAV or NF-MACE. However, early class II DSA that are complement-binding, appear to impact outcome.
FOIA's Common Law

The Freedom of Information Act (FOIA) replaced the near-total control that agencies held over their records with a judicially enforceable “right” of public access to agency information. Underscoring the importance of this statutory right, FOIA rejected the judiciary’s traditional respect for agency expertise. It instead places the burden of proof on the government and mandates de novo review in litigation. And yet, agencies still effectively control the terms of information disclosure. The government wins nine out of every ten FOIA cases in court. This ratio is a startling departure from other areas of administrative law, where agencies generally enjoy much lower win rates. This Article provides a framework for understanding this tension. Tracing FOIA’s doctrines to their roots, it finds that FOIA jurisprudence reflects the well-established “administrative common law” approach that courts apply elsewhere in administrative law. Specifically, courts have used functional or policy-based reasoning to transport preexisting evidentiary and administrative law doctrines to FOIA litigation, often in ways that challenge statutory text. Because these pre-FOIA doctrines overwhelmingly empowered the executive, the ensuing doctrines that courts grafted onto FOIA (“FOIA’s common law”) predictably and consistently favor agencies. Recognizing FOIA doctrine as a subset of administrative common law holds broader implications. It provides a meaningful baseline for critique by situating FOIA within a larger debate over the judiciary’s proper role in the administrative state. It also offers new perspectives on how Congress can counteract the inertial forces driving FOIA’s common law. Finally, it informs the debate over administrative common law by showing the method’s resilience in an area where Congress has been uniquely active.
Transitioning to online instruction: Strong ties and anxiety

We surveyed a national sample of United States physics faculty about the COVID-19 transition to online learning. Most faculty had 1–2 weeks to prepare and no experience with teaching online. They relied on department peers to discuss approaches and used lecture adaptations such as video conferencing rather than new curricular elements. Their responses were empathetic to the students’ situation, and 90% believed they were average or above at implementing online instruction. Faculty’s preference for local resources and existing methods suggests that in a crisis, strong network ties will dominate as information sources, with consequences for professional development and instructional change.
Structural Neuroimaging Findings Related to Adult Non-CNS Cancer and Treatment: Review, Integration, and Implications for Treatment of Cognitive Dysfunction

Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.
The enigma of insulin resistance and hypertension: Insulin resistance, blood pressure, and the circulation

The epidemiologic link between obesity and hypertension is more clearly emerging to be one between insulin resistance and hypertension. Relative insulin resistance occurs not only in obese hypertensive patients but also in non-obese lean essential hypertensive patients. Although insulin has complex actions on the circulation, plausible mechanisms by which insulin might raise blood pressure include renal sodium retention and stimulation of the sympathetic nervous system. However, the evidence that insulin can actually raise blood pressure in the long-term is lacking. Since hypertension does not develop in all obese or insulin-resistant subjects, the relationship must be modulated by other genetic or environmental factors. Obesity, diminished physical conditioning, aging, and diabetes are ubiquitous contributors to relative insulin resistance and all are associated with a tendency for blood pressure to rise. Conditions and agents associated with acquired insulin resistance and secondary forms of hypertension include pregnancy, oral contraceptives, acromegaly, and glucocorticoids. Although type 2 non-insulin-dependent diabetes is a state of increased insulin resistance, hypertension is partly sustained by secondary renal mechanisms. Future research should identify the genetic and environmental determinants of insulin resistance in hypertension and utilize these in therapy.
Regulation and mechanism of phosphoribosylpyrophosphate synthetase. 3. Kinetic studies of the reaction mechanism.

Abstract An analysis of the kinetic mechanism of phosphoribosylpyrophosphate (PRPP) synthetase has been carried out with highly purified preparations of the enzyme from Salmonella typhimurium. The enzyme requires both MgATP2- as a substrate and free Mg2+ ion as an essential activator. This conclusion is supported by kinetic analysis and by studies of partial inhibition of PRPP synthetase by low concentrations of Ca2+ ions in the presence of excess MgCl2. The kinetics of Mg2+ and MgATP2- interaction with PRPP synthetase in the presence of saturating concentrations of ribose 5-phosphate is consistent with random, rapid equilibrium binding of Mg2+ and MgATP2- prior to rate-limiting breakdown of the central complex to yield products. The analysis of the kinetics was greatly facilitated by a computer program which calculated free Mg2+ concentration and the concentration of three Mg2+ complexes in a system in which Mg2+ is in equilibrium with three ligands. The results of initial velocity studies of the PRPP synthesis (forward) and ATP synthesis (reverse) reactions and product inhibition studies are consistent with an Ordered Bi Bi mechanism in which MgATP2- binds to the enzyme first and PRPP dissociates last. A previous study of partial exchange reactions catalyzed by PRPP synthetase (Switzer, R. L., J. Biol. Chem., 245, 483 (1970)) suggested an enzyme-pyrophosphate intermediate in the reaction. However, the characteristics of the over-all exchange reactions catalyzed by the enzyme indicated that such a derivative, if it participates in the over-all reaction, is not kinetically significant as a free intermediate. The present studies confirm this conclusion.
Analysis of Monosaccharides

This unit presents methods for assaying sialic acids, reducing sugars, and hexosamines. The BCA assay detects free reducing terminii in sugars released from glycoconjugates by appropriate treatments. Assays employing Ehrlich reagent (DMAB) detect hexosamines and N-acetylhexosamines, including a method for hydrolyzing the glycosidic linkages of the hexosamines and a method for re-N-acetylation. The TBA and DMB assays can be used to quantitate and fractionate free forms of many types of sialic acids. Techniques for liberating the sialic acids from the parent glycoconjugates are also provided.
Studies on metalloflavoproteins. V. The action of silicomolybdate in the reduction of cytochrome c by aldehyde oxidase.

Abstract A silicomolybdate complex has been prepared which will accelerate the reduction of cytochrome c by acetaldehyde in the presence of aldehyde oxidase or xanthine oxidase, but which is without effect upon interaction of these enzymes with other electron acceptors, viz. ferricyanide, 2,6-dichlorophenolindophenol, benzyl viologen, and molecular oxygen. The optimum ratio of molybdenum to silica was found to be ten. Phosphomolybdate will substitute for the silica complex but is not as active in the reduction of cytochrome c. Reduction of either silico- or phosphomolybdate requires the presence of the enzyme, but interaction of the reduced complex and ferricytochrome c is extremely rapid and non-enzymic.
Sukuk in its Infancy: Misstep and Sequel

This article discusses the 2008 "clarification" of the Sukuk Standard of the Accounting and Auditing Organization for Islamic Financial Institutions (AAOIFI). The clarification was issued by the Shariah Committee of AAOIFI in response to a review of all outstanding sukuk at the time. The clarification focused, in particular, on sukuk al-musharaka. Musharaka are profit-and-loss sharing partnerships. The use of the musharaka sukuk increased dramatically in the 2006-2008 period. The AAOIFI Shariah Committee determined that a significant portion of those sukuk were not compliant with the Shariah, and issued the clarification. The clarification focuses, primarily, on three structural infirmities: (a) the absence of enterprise ownership; (b) interest-free loans made to sukuk holders where no profits were available to be distributed to those sukuk holders; and (c) guaranteed returns of principal to the sukuk holders. The AAOIFI Shariah Committee, quite accurately, characterized the offending sukuk al-musharaka as "bonds", noting that sukuk are not bonds - they are securitizations of different types.
Dynamics of dibutyryl cyclic AMP- and prostaglandin E2-mediated suppression of lipopolysaccharide-induced tumor necrosis factor alpha gene expression.

Abstract The regulation of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF) production by prostaglandin E2 (PGE2), forskolin, and dibutyryl cyclic AMP (cAMP) was examined at the cellular and molecular levels. The above three agents could suppress LPS (100 ng/ml)-stimulated TNF production by immunologically activated murine macrophages (M phi s) in a dose-dependent manner. The concomitant addition of PGE2, dibutyryl cAMP, or forskolin to LPS-challenged M phi s resulted in 50% inhibition of TNF production at 10(-7), 3 X 10(-6), and 3 X 10(-5) M, respectively. Interestingly, delaying the addition of PGE2 or dibutyryl cAMP by 1.5 h post-LPS stimulation was also effective in suppressing the production of TNF bioactivity, but only dibutyryl cAMP was effective when its addition was delayed by 3 h. Northern (RNA) blot analysis of mRNA isolated from LPS-challenged M phi s treated with PGE2 or dibutyryl cAMP corroborated the bioactivity data. The delayed addition of PGE2 or dibutyryl cAMP by 1.5 h post-LPS stimulation resulted in a suppression of TNF mRNA accumulation by 50 to 70%. These data support the concept that LPS is a potent stimulus for M phi-derived TNF production and that this mediator is a very proximal signal in LPS-mediated disease states. Thus, therapeutic approaches that target the suppression of TNF in LPS-dependent disease states may be limited by the rapid expression of this mediator.
A Feedback-Insensitive Isopropylmalate Synthase Affects Acylsugar Composition in Cultivated and Wild Tomato

Acylsugars are insecticidal specialized metabolites produced in the glandular trichomes of plants in the Solanaceae family. In the tomato clade of the Solanum genus, acylsugars consist of aliphatic acids of different chain lengths esterified to sucrose, or less frequently to glucose. Through liquid chromatography-mass spectrometry screening of introgression lines, we previously identified a region of chromosome 8 in the Solanum pennellii LA0716 genome (IL8-1/8-1-1) that causes the cultivated tomato Solanum lycopersicum to shift from producing acylsucroses with abundant 3-methylbutanoic acid acyl chains derived from leucine metabolism to 2-methylpropanoic acid acyl chains derived from valine metabolism. We describe multiple lines of evidence implicating a trichome-expressed gene from this region as playing a role in this shift. S. lycopersicum M82 SlIPMS3 (Solyc08g014230) encodes a functional end product inhibition-insensitive version of the committing enzyme of leucine biosynthesis, isopropylmalate synthase, missing the carboxyl-terminal 160 amino acids. In contrast, the S. pennellii LA0716 IPMS3 allele found in IL8-1/8-1-1 encodes a nonfunctional truncated IPMS protein. M82 transformed with an SlIPMS3 RNA interference construct exhibited an acylsugar profile similar to that of IL8-1-1, whereas the expression of SlIPMS3 in IL8-1-1 partially restored the M82 acylsugar phenotype. These IPMS3 alleles are polymorphic in 14 S. pennellii accessions spread throughout the geographical range of occurrence for this species and are associated with acylsugars containing varying amounts of 2-methylpropanoic acid and 3-methylbutanoic acid acyl chains.
Nanoindentation Probing of Environmental Effects on Polymer Coating Properties

Humidity and temperature control accessories for Hysitron Triboscope have been developed to study the environmental influence on in situ properties of drying coatings. Mechanical properties of drying poly (vinyl alcohol) (PVOH) and poly (vinyl pyrrolidone) (PVP) coatings on silicon wafer were measured under different humidities. The modulus results were compared with outputs of elastic, plastic and viscoelastic theories of indentation testing.
Multinationals FDI and uncertainty: A reply

Abstract The preceding paper is a comment on a paper by Firoozi published in this journal, and seeks to identify a flaw in the Firoozi paper. This reply shows that the comment is a special case of the general results presented previously.
Analytical determination of nicotine in tobacco by supercritical fluid chromatography–ion mobility detection

Abstract A preliminary investigation using supercritical fluid chromatography–ion mobility detector (SFC–IMD) to analyze the nicotine contained in tobacco was carried out. Nicotine in commercially available cigarettes and tobacco leaves was extracted into chloroform and determined by an IMD after SFC separation. The detection limit was at the picogram level for nonselective monitoring and the subnanogram level for nicotine selective detection. This system provided a simple analytical method for the analysis of nicotine and other alkaloids in tobacco. Compared to currently utilized methods, the SFC–IMD provided advantages of high sensitivity, nicotine specific detection and lower instrumentation cost. The potential of combining online supercritical fluid extraction with SFC–IMD for analysis of alkaloids in tobacco was demonstrated.
Transcriptional Regulation of Cortical Neuron Migration by POU Domain Factors

The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamination by genetic analysis of the roles of the class III POU domain transcription factors, Brn-1 and Brn-2, expressed during the development of the forebrain and coexpressed in most layer II-V cortical neurons. Brn-1 and Brn-2 appear to critically control the initiation of radial migration, redundantly regulating the cell-autonomous expression of the p35 and p39 regulatory subunits of Cdk5 in migrating cortical neurons, with Brn-1(-/-)/Brn-2(-/-) mice exhibiting cortical inversion.
Deformation and bonding processes in aluminum ultrasonic wire wedge bonding

The ultrasonic wire bonding (UWB) process has been examined using transmission electron microscopy (TEM) and standard wire pull testing techniques. Al-0.5 wt.% Mg wires 75 μm in diameter were bonded to pure and alloyed Al substrates. The bonding parameters, surface roughness, and surface contamination levels were variables in the experiments. Cross-section TEM specimens were made from these samples. TEM analysis was conducted on the wire, wire/substrate interface and substrate. Pull tests showed that for the Al substrates the surface roughness or the presence of contamination did not effect the bond strength, whereas for contaminated stainless steel substrates, a three μm surface finish resulted in the highest bond pull strength. The TEM observations revealed features such as low-angle grain boundaries, dislocation loops and the absence of a high dislocation density, indicating that the wire and substrate were dynamically annealed during bonding. Based on the width of a zone near a grain boundary in the wire which was depleted of dislocation loops, it was estimated that local heating equivalent to a temperature of 250° C for 90 msec was achieved in the wire during bonding. No evidence was found for melting along the bond interface, indicating that UWB is a solid-state process. Based on the TEM observationsof the bond interface and the pull tests, it is concluded that the ultrasonic vibrations clean the surfaces to be joined to the extent that a good bond can be obtained by intimate metal-metal contact in the clean areas.
Alterations in forebrain catecholamine metabolism produced by cerebellar lesions in the rat

Projections from the midline cerebellar nuclei to norepinephrine (NE) and dopamine (DA) cell groups in the brain stem have been demonstrated histologically. To determine if these connections are significant biochemically, unilateral electrolytic lesions were placed in either vermis or paravermis and levels of DA, NE and gamma-aminobutyric acid (GABA) were measured in each half of the forebrain at 1 1/2, 3 or 6 weeks.
Research- based Practice with Women Who Have Had Miscarriages

Design: The research program included three phases: interpretive theory generation, descriptive survey and instrument development, and experimental testing of a theory-based intervention. Methods: Research methods included interpretive phenomenologE factor analysis, and ANCOVA. Findings: A theory of caring and a model of what it is like to miscarry were generated, refined, and tested. A case study shows one woman’s response to miscarrying and illustrates clinical application of the caring theory. Conclusions: The Miscarriage Model is a useful framework for anticipating the variety of responses women have to miscarrying. The caring theory is an effective and sensitive guide to clinical practice with women who miscarry.
Rousseau’s philosophy of transformative, ‘denaturing’ education

Rousseau’s political philosophy presents the great legislator as a civic educator who must over time transform naturally self-loving egoists into citizens animated by a general will without destroying freedom. This is an educational process which is ‘denaturing’ but which aims to produce autonomous adults who can ultimately say to their teacher (with Rousseau’s Emile) that they have chosen to ‘remain what you have made me’. The problem of finding a stable equilibrium between denaturing education, political stability and adult autonomy is the central and distinctive difficulty of Rousseau’s social thought, as the paper illustrates and explains by means of a series of structured comparisons with, especially, the philosophies of Plato, Kant, Hegel and Diderot.
Awareness and knowledge of the intrauterine device in adolescents.

Abstract Background The purpose of this study was to explore intrauterine device (IUD) awareness and knowledge in a diverse, multiethnic population. Methods We conducted a self-administered, anonymous survey addressing awareness of the IUD as a contraceptive method and knowledge about aspects of IUD use in a group of women aged 14 to 19 years. Demographic and medical information was obtained to compare awareness and knowledge between demographic groups. Chi-square, Fisher exact test, and t tests were used for analysis. Multiple logistic regression was utilized to confirm relationships. Results Of the 106 respondents, 76.4% (81/106) were sexually active and 56.6% (60/106) reported a history of ever being pregnant. There were 21.1% (33/106) of respondents who had heard of the IUD as a contraceptive method. Of the subjects who had heard of the IUD, 39.4 % (13/33) were able to identify key features of the IUD. Although a history of pregnancy was predictive of having heard of the IUD, age, insurance status, education, and all other demographic factors were not associated with IUD awareness. Conclusion Over 70% of the adolescents had not heard of the IUD and less than half of adolescents who had heard of the IUD were able to identify key features about this contraceptive method. The lack of knowledge of this effective and safe contraceptive option is concerning given that most participants were at high risk for unintended pregnancy.
Hyaluronan promotes the chondrocyte response to BMP-7

Summary Objective Chondrocytes exhibit specific responses to bone morphogenetic proteins (BMPs) and transforming growth factor-βs (TGF-βs). The bioactivity of these growth factors is regulated by numerous mediators. In our previous study, Smad1 was found to interact with the cytoplasmic domain of the hyaluronan receptor CD44. The purpose of this study was to determine the ability of hyaluronan in the pericellular matrix to modulate the chondrocyte responses to BMP-7 or TGF-β1. Experimental design Nuclear translocation of Smad1, Smad2 and Smad4 was studied in bovine articular chondrocytes in response to BMP-7 and TGF-β1. The effects of matrix disruption by hyaluronidase treatment and the initiation of matrix repair by the addition of hyaluronan on the nuclear translocation of Smad proteins, Smad1 phosphorylation and luciferase expression by a CD44 reporter construct in response to BMP-7 were also studied. Results The disruption of the hyaluronan-dependent pericellular matrix of chondrocytes resulted in diminished nuclear translocation of endogenous Smad1 and Smad4 in response to BMP-7; however, the nuclear translocation of Smad2 and Smad4 in these matrix-depleted chondrocytes in response to TGF-β1 was not diminished. Incubation of the matrix-depleted chondrocytes with exogenous hyaluronan restored Smad1 and Smad4 nuclear translocation and increased pCD44(499)-Luc luciferase expression in response to BMP-7. Both exogenous hyaluronan and matrix re-growth enhanced by hyaluronan synthase-2 (HAS2) transfection restored Smad1 phosphorylation. Conclusions Disruption of hyaluronan–CD44 interactions has little effect on the TGF-β responses; however, re-establishing CD44–hyaluronan ligation promotes a robust cellular response to BMP-7 by articular chondrocytes. Thus, changes in cell–hyaluronan interactions may serve as a mechanism to modulate cellular responsiveness to BMP-7.
A method for MSE differential proteomic analysis of archival formalin-fixed celloidin-embedded human inner ear tissue

Proteomic analysis of cadaveric formalin-fixed, celloidin-embedded (FFCE) temporal bone tissue has the potential to provide new insights into inner ear disorders. We have developed a liquid chromatography-mass spectrometry (LC-MS) method for tissue sections embedded with celloidin. Q-TOF (Quadrupole-time of flight mass spectrometry) MS(E) (mass spectrometry where E represents collision energy) and Identity(E)™ were used in conjunction with nano-UPLC (capillary ultrahigh pressure liquid chromatography) for robust identification and quantification of a large number of proteins. Formalin-fixed paraffin-embedded (FFPE) mouse liver sections were used to evaluate formalin de-cross-linking by five different methods. Unfixed fresh mouse liver tissue was used as a control. Five different methods for preparation of FFPE tissue for MS analysis were compared, as well as four methods for celloidin removal with FFCE mouse liver tissue. The methods judged best were applied to FFCE 20 μm sections of mouse inner ear samples, and FFCE 20 μm human inner ear and human otic capsule bone sections. Three of the five-tissue extraction methods worked equally in detecting peptides and proteins from FFPE mouse liver tissue. The modified Liquid Tissue kit protocol was chosen for further studies. Four different celloidin removal methods were compared and the acetone removal method was chosen for further analysis. These two methods were applied to the analysis of FFCE inner ear and otic capsule sections. Proteins from all major cellular components were detected in the FFCE archival human temporal bone sections. This newly developed technique enables the use of FFCE tissues for proteomic studies.
Cultured human ankle and knee cartilage differ in susceptibility to damage mediated by fibronectin fragments

According to numerous cadaveric, radiographic, and clinical studies, ankle and knee joints differ in susceptibility to osteoarthritis. To test for biochemical differences in susceptibility to damage, a chondrocytic chondrolysis system has been utilized. In this system, fibronectin fragments are added to cultured cartilage explants, resulting in enhanced release of catabolic cytokines, induction of matrix metalloproteinases, temporary suppression of proteoglycan synthesis, and consequently, severe loss of cartilage proteoglycan. We found that the addition of an amino-terminal thrombin-generated 29-kDa fibronectin fragment to cultured knee cartilage from 14 donors (average age: 53 years) usually caused a 30-50% decrease in proteoglycan content by day 7. However, of the ankle cartilage specimens examined from 21 donors (average age: 50 years), only three showed damage by day 7, one by day 14, and six by day 21, and 11 were not damaged until day 28. For eight of the donors (average age: 44 years), both knee and ankle cartilages were obtained: this allowed comparison between tissues from the same donor. The analysis showed that the ankle cartilage was much more refractory to damage than was the knee cartilage from the same donor. These data clearly show differences between ankle and knee cartilage in susceptibility to the fibronectin fragments and suggest the feasibility of use of these fragments for discerning differences in homeostasis of the ankle and knee cartilage.
THE RELATIONSHIP OF GAMMA-1A GLOBULIN AND REAGIN IN CORD SERA.

Abstract 1. Gamma-1A globulin and P-K activity were absent in 25 of 26 cord sera of babies born to atopic mothers. In the one exception, both appeared in the cord serum and were absent on rebleeding the infant at eight days. The 26 mothers were skin-test positive to mixed grass and had spring hay fever, 13 had positive P-K tests including the mother of the infant with cord serum reagin, and all had gamma-1A in their blood. Gamma-1A globulin was present in all of 58 sera from normal mothers and was present in 1/58 of the respective cord sera giving an over-all incidence for the presence of gamma-1A in the cord of 2/84. All normal maternal and cord sera were devoid of P-K activity. 2. Gamma-1M globulin was detected in all of 49 maternal-cord serum pairs (part of the atopic group included). The cord gamma-1M concentration appeared to be in 1/10 to 1/20 that of the maternal level. 3. Gamma-2 globulin was detected in 15/15 pairs and appeared to be present in approximately equal concentrations in maternal and cord sera.
Elevated NADH-dehydrogenase activity characterizes the rostral gustatory zone of the solitary nucleus in rat.

Abstract The regional distribution of NADH-dehydrogenase (NADH-DH, EC 1.6.99.3) activity was examined in the nucleus of the solitary tract (NST) in the rat, with specific emphasis given to the rostral gustatory zone. Activity of NADH-DH in the rostral gustatory zone was compared to intermediate and caudal divisions of the NST which receive projections from the glossopharyngeal and vagus nerves. Animals received injections of horseradish peroxidase (HRP) in the anterior tongue, or applications of HRP crystals to the cut chorda tympani nerve to visualize chorda tympani terminal fields in the rostral NST. Tissue was subsequently reacted for NADH-dehydrogenase and transported HRP using sequential histochemical procedures. Results show that relative activity of NADH-DH is highest in areas of the NST that receive projections from the chorda tympani nerve. Lateral divisions of the NST, which receive projections from the lingual-trigeminal nerve, show moderate enzymatic activity, but such activity is quantitatively lower than that observed in the chorda tympani terminal field. Intermediate and caudal portions of the NST show the lowest NADH-DH activity of all NST regions examined. These results confirm that histochemistry for NADH-dehydrogenase can serve as an endogenous marker for chorda tympani terminal fields in the rostral NST.
RELATION OF CERVICAL SYMPATHETIC NERVES TO ACTIVITY OF THE THYROID

ALTHOUGH much evidence for and against the secretory innervation of the thyroid gland has been published, the most striking evidence in support L. of the concept has been provided by the experiments of Haney (i). In his experiments the cervical sympathetic nerve was stimulated in a group of rabbits after their basal metabolic rate had been determined. Two days after the stimulation of the nerve the rate of energy metabolism began to increase; it reached a maximum of 29% above the control level at from 11 to 15 days and declined to the control level at from 41 to 60 days. Friedgood and Bevin (2) repeated the experiments of Haney. In 12 rabbits no change occurred in the rate of metabolism; in 8 the rate was elevated from 12 to 19% during only one or two determinations; and in 2 the rate was definitely elevated for a short period, as observed by Haney.
Ni Cósmico, Ni Democrático: El "Contracanto A Walt Whitman" De Pedro Mir

In "Countersong to Walt Whitman" (1952), the Dominican author Pedro Mir recasts in epic form the social history of the United States as an experiment destined to fail because of its capitalist roots. Mir reads Whitman's Leaves of Grass through "Democratic Vistas" and thus grounds the voice in a concrete social and historical context. Mir's extensive poem is not only a countersong to the poetic "I" of Leaves of Grass but a reply to American nationalist discourse as read in "Democratic Vistas." This article explores the ways in which Mir implements the arsenal of techniques proper to the epic genre to undo Whitman's voice and strings a narrative that places Whitman's persona in a past that never was—all of which, contrary to what Mir proposes, fail to deliver the transcendent Whitman from a political ideology. Ironically, Mir reproduces the authoritarian voice of the very monolithic ideology he aims to deconstruct.
The Informational Role of Option Trading Volume in Equity Index Options Markets

This paper examines the dynamic relations between future price volatility of the S&P 500 index and trading volume of S&P 500 options to explore the informational role of option volume in predicting the price volatility. The future volatility of the index is approximated alternatively by implied volatility and by EGARCH volatility. Using a simultaneous equation model to capture the volume-volatility relations, the paper finds that strong contemporaneous feedbacks exist between the future price volatility and the trading volume of call and put options. Previous option volumes have a strong predictive ability with respect to the future price volatility. Similarly, lagged changes in volatility have a significant predictive power for option volume. Although the volume-volatility relations for individual volatility and volume terms are somewhat different under the two volatility measures, the results on the predictive ability of volume (volatility) for volatility (volume) are broadly similar between the implied and EGARCH volatilities. These findings support the hypothesis that both the information- and hedge-related trading explain most of the trading volume of equity index options.
Inositol phosphosphingolipid phospholipase C1 regulates plasma membrane ATPase (Pma1) stability in Cryptococcus neoformans

Cryptococcus neoformans is a facultative intracellular pathogen, which can replicate in the acidic environment inside phagolysosomes. Deletion of the enzyme inositol-phosphosphingolipid-phospholipase-C (Isc1) makes C. neoformans hypersensitive to acidic pH likely by inhibiting the function of the proton pump, plasma membrane ATPase (Pma1). In this work, we examined the role of Isc1 on Pma1 transport and oligomerization. Our studies showed that Isc1 deletion did not affect Pma1 synthesis or transport, but significantly inhibited Pma1 oligomerization. Interestingly, Pma1 oligomerization could be restored by supplementing the medium with phytoceramide. These results offer insight into the mechanism of intracellular survival of C. neoformans.
Dairy food consumption and body weight and fatness studied longitudinally over the adolescent period.

Dairy food consumption and body weight and fatness studied longitudinally over the adolescent period
Self-consciousness, self-determination, and imagination in Kant

I argue for a basically Sartrean approach to the idea that one's self-concept, and any form of knowledge of oneself as an individual subject, presupposes concepts and knowledge about other things. The necessity stems from a pre-conceptual structure which assures that original self-consciousness is identical with one's consciousness of objects themselves. It is not a distinct accomplishment merely dependent on the latter. The analysis extends the matter/form distinction to concepts. It also requires a distinction between two notions of consciousness: one relates to the employment of already formed concepts, the other to the structures of imaginative apprehension that help to constitute (empirical) concepts from the start. We need to see that (1) so far as objects are only conceptualized appearances, the material through which we apprehend them must be reflected in that apprehension itself; (2) the corresponding material consists of a manifold of pre-conceptually active anticipations and retentions concerning the course of one's own experience. The resultant structure imposes an orientation on the world of appearances that does not derive from a concept of oneself as an individual in it, but that nevertheless provides the only possible basis for such a concept. One's self-concept, at least as empirical subject, is simply that ofwhatever subject is indicated, in an appropriate way, by that orientation.
Solitons in chiral-spin liquids.

We consider the low-lying states of a class of tight-binding models related to the parity- and time-reversal-breaking chiral-spin liquid, which describes a magnetically frustrated Mott insulator. In precise analogy with the soliton excitations of polyacetylene, the presence of a midgap state bound to topological disruptions of the chiral order leads to neutral, spin-1/2 spinors and charge-e, spinless holons.