cssi/SciSciGPT-SciSciNet huggingface dataset:
Challenges in Selecting an Appropriate Heat Stress Index to Protect Workers in Hot and Humid Underground Mines.

Background A detailed evaluation of the underground mine climate requires extensive measurements to be performed coupled to climatic modeling work. This can be labor-intensive and time-consuming, and consequently impractical for daily work comfort assessments. Therefore, a simple indicator like a heat stress index is needed to enable a quick, valid, and acceptable evaluation of underground climatic conditions on a regular basis. This can be explained by the unending quest to develop a “universal index,” which has led to the proliferation of many proposed heat stress indices.
Doubly sparsifying network

We propose the doubly sparsifying network (DSN), by drawing inspirations from the double sparsity model for dictionary learning. DSN emphasizes the joint utilization of both the problem structure and the parameter structure. It simultaneously sparsifies the output features and the learned model parameters, under one unified framework. DSN enjoys intuitive model interpretation, compact model size and low complexity. We compare DSN against a few carefully-designed baselines, and verify its consistently superior performance in a wide range of settings. Encouraged by its robustness to insufficient training data, we explore the applicability of DSN in brain signal processing that has been a challenging interdisciplinary area. DSN is evaluated for two mainstream tasks: electroencephalographic (EEG) signal classification and blood oxygenation level dependent (BOLD) response prediction, and achieves promising results in both cases.
Epithelial Cell Interactions of the Epstein-Barr Virus

The identity and unity of the herpesviruses derive from a commonality of structural features and biology. Remarkably diverse, inhabiting the entire animal kingdom, herpesviruses have a morphology which, while as complex as any of the viruses, is similar both superficially and at the level of the structural organization of their genomes. Linked to structure is a conserved biologic expression, the ability to produce latent as well as active infection. These biologic hallmarks of the herpesviruses are tied to cell type. The virus has a tendency to replicate in one cell type and to cause latent infection in another cell type, carrying the implication that there are both primary and secondary cell targets of herpesvirus infections and that the cell type determines or contributes to the type of virus—cell interaction: dormant or vegetative.
Towards Reversible Basic Linear Algebra Subprograms: A Performance Study

Problems such as fault tolerance and scalable synchronization can be efficiently solved using reversibility of applications. Making applications reversible by relying on computation rather than on memory is ideal for large scale parallel computing, especially for the next generation of supercomputers in which memory is expensive in terms of latency, energy, and price. In this direction, a case study is presented here in reversing a computational core, namely, Basic Linear Algebra Subprograms (BLAS), which is widely used in scientific applications. A new Reversible BLAS (RBLAS) library interface has been designed, and a prototype has been implemented with two modes: (1) a memory-mode in which reversibility is obtained by checkpointing to memory, and (2) a computational-mode in which nothing is saved, and restoration is done entirely via inverse computation. The article is focused on detailed performance benchmarking to evaluate the runtime dynamics and performance effects, comparing reversible computation with checkpointing on both traditional CPU platforms and recent GPU accelerator platforms. For BLAS Level-1 subprograms, data indicates over an order of magnitude speed up of reversible computation compared to checkpointing. For BLAS Level-2 and Level-3, a more complex tradeoff is observed between reversible computation and checkpointing, depending on computational and memory complexities of the subprograms.
Transnasal Transsphenoidal Elevation of Optic Chiasm in Secondary Empty Sella Syndrome Following Prolactinoma Treatment.

Background Prolactinomas are typically treated nonsurgically with a dopamine agonist. Once the tumor shrinks, adjacent eloquent structures, such as the optic apparatus, can become skeletonized and herniate into the dilated parasellar space. Case Description A 48-year-old man with a prolactin-secreting macroadenoma treated with cabergoline presented with progressive bitemporal hemianopsia. Magnetic resonance imaging showed no recurrence of disease and a stretched optic chiasm herniating into an empty sella. Elevation of the optic chiasm via a transnasal transsphenoidal approach with ALLODERM graft and septal cartilage strut was performed. The patient was discharged home the next day with significant improvement in vision; magnetic resonance imaging showed interval elevation of the optic chiasm. Conclusions We review secondary empty sella syndrome and discuss surgical strategies for optic chiasmapexy.
PV[O]H signals intravascular blood loss in the rat

PV[O]H is a new noninvasive optical technique that measures hematocrit and vascular volume with unprecedented sensitivity, precision and bandwidth. We show that PV[O]H can reflect intravascular blood loss in seconds in a rat model.
Anticipatory postural responses prior to protective steps are not different in people with PD who do and do not freeze

Abstract Background Protective stepping after a loss of balance is related to falls. Anticipatory postural responses (APAs) prior to protective stepping can impact step performance, may be larger in people with PD, and have been suggested to be related to freezing of gait (FOG). However, whether people with PD and FOG (PD + FOG) exhibit larger APAs than people with PD and no FOG (PD-FOG) is unknown. Research Question: Determine the impact of freezing status on APAs prior to protective steps, thus providing a better understanding of the link between FOG and APAs. Methods Twenty-eight people with PD (13 PD + FOG) were exposed to 50 support surface translations (25 forward, 25 backward, random order) resulting in protective steps. The size of medio-lateral weight shifts prior to the protective step (i.e. APAs), and the percentage of trials with an APA were calculated via force-plates. FOG status was assessed at the time of testing as well as 3.25(+/-0.43) years later. Participants without FOG at testing, but with FOG at follow-up were identified as “converters”. Results and significance For both forward and backward protective stepping, size and percentage trials with an APA were not statistically different between PD + FOG and PD-FOG, even after excluding converters from the PD-FOG group (p > 0.27 for all). No group by direction interactions were observed. These data suggest that, in mild to moderate PD, an inability to couple APAs with stepping, rather than an inappropriately sized APA, may be most related to freezing of gait.
Hasselmann’s stochastic climate model viewed from a statistical mechanics perspective

Hasselmann’s stochastic climate model asserts that weather fluctuations randomly force the climate system in the same way that fluid molecules force Brownian ink particles. Langevin’s equation is used to model this physical process. This essay compares Hasselmann’s stochastic climate model and its Langevin equation to the role that the Langevin equation plays in the description of a classical N-particle system. The theory of classical N-particle systems is well developed. There exist a well defined hierarchy of models. One distinguishes between the micro-, meso-, and macroscopic levels of description obtained by successive coarse graining. Statistical mechanics and other synthetic analyses relate the different levels to each other. The Langevin equation is a mesoscopic equation. It ignores the details of the molecular interactions but retains information about the distribution of molecules in position and momentum space. The theory of the climate system is less developed. There exists a gallery rather than a hierarchy of models. Hasselmann’s stochastic climate model is a mesoscopic description. It ignores the details of the weather fluctuations. In its original version, it is a cognitive model, aimed at understanding a specific physical process. It has not yet been advanced to a comprehensive and realistic model of the climate system on the mesoscopic level.
Learning to evaluate scientific models

The construction and evaluation of scientific models, together with the iterative modification of these models in response to evidence, constitute paradigmatic scientific practices. If inquiry instruction is to engage students in authentic scientific reasoning, these practices need to become routine in the science curriculum. This paper reports on some of the difficulties middle-school students experience in a learning environment focused on model-and evidence-based reasoning and suggests a promising scaffold to address these difficulties.
The Mechanism of Turbulent Mass Transfer at a Boundary

The fluctuating concentration field is calculated from the mass balance equation using measured values of the fluctuating velocity field. It is found that the concentration boundary-layer acts as a filter in that only velocity fluctuations of much lower frequency than the most energetic velocity fluctuations are effective in transporting mass at large Schmidt numbers. Two parameters characterizing the velocity field emerge as being quite important. These are the limiting behavior of the spectral density function of the normal velocity fluctuations for frequency approaching zero and a scale characterizing the spanwise mixing.
Reflections on Justification and Proof

In this chapter, we explore how investigations into mathematicians’ practice can inform instruction on justification and proof. Each co-author of this practice presents an investigation of how mathematicians use justification and proof in their professional practice and suggests pedagogical implications based upon insights from their investigations.
Abstract WP346: Frequency of Convexal Subarachnoid Hemorrhage in the General Population

Background: Non-traumatic convexal subarachnoid hemorrhages (cSAH) in the elderly can be a manifestation of cerebral amyloid angiopathy (CAA) and predict future intracerebral hemorrhage risk. The f...
Development of a step counting algorithm using the ambulatory tibia load analysis system for tibia fracture patients.

Introduction: Ambulation can be used to monitor the healing of lower extremity fractures. However, the ambulatory behavior of tibia fracture patients remains unknown due to an inability to continuo...
External Validation of Difficult-to-Treat Resistance Prevalence and Mortality Risk in Gram-Negative Bloodstream Infection Using Electronic Health Record Data From 140 US Hospitals

Difficult-to-treat resistance (DTR; ie, co-resistance to all first-line antibiotics) in gram-negative bloodstream infection (GNBSI) is associated with decreased survival in administrative data models. We externally validated DTR prevalence and associated mortality risk in GNBSI using detailed clinical data from electronic health records to adjust for baseline differences in acute illness severity.
Correlation between Dzyaloshinskii-Moriya interaction and orbital angular momentum at an oxide-ferromagnet interface

We report on the Dzyaloshinskii-Moriya (DMI) interaction at the interface between a ferromagnet and an oxide. We demonstrate experimentally that oxides can give rise to DMI. By comparison of systems comprised of $\mathrm{Pt}/\mathrm{C}{\mathrm{o}}_{90}\mathrm{F}{\mathrm{e}}_{10}$/oxide and $\mathrm{Cu}/\mathrm{C}{\mathrm{o}}_{90}\mathrm{F}{\mathrm{e}}_{10}$/oxide, we also show how oxidation of one interface can enhance and add to the total DMI of that generated by the Pt interface. This is due to the fact that the DMI on both interfaces promotes left-handed chirality. Finally, by use of ferromagnetic resonance spectroscopy, we show that the DMI and the spectroscopic splitting factor, which is a measure of the orbital momentum, are correlated. This indicates the importance of hybridization and charge transfer at the oxide interface for the DMI.
A global game of diplomacy

Diplomacy always occurs in the shadow of domestic political competition. We develop a model of top-level diplomatic exchange between an incumbent and a foreign leader, embedded within a global game...
Online Damage Monitoring of SiC f -SiC m Composite Materials Using Acoustic Emission and Deep Learning.

SiCf-SiCm composites are being actively developed as fuel cladding for improving accident tolerance of light water reactor fuel. Online monitoring of the degradation process in SiCf-SiCm composites is of great importance to ensure the safety of the nuclear reactor system. The degradation monitoring task can be mapped as a classification problem: given the Acoustic Emission(AE) events at a given timeslot, the model is expected to predict which one of the following three stages the material is in: elastic, matrix-driven and fiber-driven cracking. In this paper, degradation tests on SiCf-SiCm composite tubes were conducted using a bladder-based internal pressure technique with AE monitoring. We then trained a deep learning based end-to-end convolutional neural network (CNN) model for online monitoring of the damage progression process of SiCf-SiCm composite tubes using the AE data as the raw input. As a comparison, we also applied Random Forest (RF) with expert-crafted audio event features to the damage stage prediction problem. Experimental results show that both RF and CNN models yield good results but on average our end-to-end CNN models outperform the RF models due to its high-level feature extraction capability. The CNN model with single events can reach an average prediction accuracy of 84.4% compared to 74% of the RF models. Combining multiple audio samples typically improves the accuracy of the models with RF accuracy reaching 82.8% and CNN accuracy reaching 86.6%.
Renovation in hospitals: Training construction crews to work in health care facilities.

Background Health care facilities require frequent renovations to maintain or enhance their service, and to meet the dynamic demands of their patients. Construction activities in active health care facilities are a significant contributor to various challenges that range from infection to death. It is therefore essential to minimize the adverse impacts of construction activities on health care units as well as their adjacent sites. Methods A questionnaire was developed to study current training modules to prepare construction crews to work in health care environments. The survey was disseminated among professionals of the top 15 health care contractors. A total of 129 individuals participated, and their responses were analyzed using descriptive and categorical statistics. Results This study investigates current training practices regarding (1) the level of training, (2) the frequency of training, and (3) the impact that the sensitivity of the project has on the training. To effectively prepare construction crews, special training must be provided to them. Conclusions There are uncertainties about the sufficiency and impact of the existing training. Existing trainings are tailored for upper management positions, and the amount/frequency of training for construction crews are substantially low. Findings of this study contribute to characterizing the activities and conditions pertaining to training of construction crews.
The GENDULF Algorithm: Mining Transcriptomics to Uncover Modifier Genes for Monogenic Diseases

Modifier genes are believed to account for the clinical variability observed in many Mendelian disorders, but their identification remains challenging due to the limited availability of genomics data from large patient cohorts. Here, we present GENDULF (GENetic moDULators identiFication), one of the first methods to predict disease modifiers from healthy and diseased tissue gene expression data. When applied to cystic fibrosis, GENDULF successfully identifies multiple, previously established disease modifiers, including EHF, SLC6A14, and CLCA1. It is then utilized in spinal muscular atrophy (SMA) and predicts U2AF1 as a modifier whose under-expression correlates with higher SMN2 pre-mRNA exon 7 retention. Indeed, knockdown of U2AF1 in SMA patient-derived cells leads to increased full-length SMN2 transcript and SMN protein expression. Taking advantage of the increasing availability of transcriptomic data, GENDULF is a novel tool to predict genetic disease modifiers, providing insights into disease pathogenesis and uncovering novel therapeutic targets.
Structure based virtual screening identifies novel competitive inhibitors for the sialoglycan binding protein Hsa

Infective endocarditis (IE) is a cardiovascular disease often caused by bacteria of the viridans group of streptococci, which includes Streptococcus gordonii and Streptococcus sanguinis. Previous research has found that a serine-rich repeat (SRR) proteins on the S. gordonii bacterial surface play a critical role in pathogenesis by facilitating bacterial attachment to sialyated glycans displayed on human platelets. Despite its important role in disease progression, there are currently no anti-adhesive drugs available on the market. Here, we performed structure-based virtual screening using an ensemble docking approach followed by consensus scoring to identify novel inhibitors against the sialoglycan binding domain of the SRR adhesin protein Hsa from the S. gordonii strain DL1. In silico cross screening against the glycan binding domains of closely related SRR proteins from five other S. gordonii or S. sanguinis strains was also performed to further reduce false positives. Using our in silico screening strategy we successfully predicted nine compounds which were able to displace the native ligand (sialyl-T antigen) in an in vitro assay and bind competitively to adhesin protein Hsa (~20% hit rate).
Research on Voltage Distribution Characteristics of Double-Break Vacuum Circuit Breakers

Voltage sharing technology of vacuum circuit breaker is the key to popularizing the application of the series-connected breaks. Based on the equivalent circuit of double-break circuit breaker's static voltage distribution, this paper introduced effect of shunt capacitor on double break, and the possibility of parallel voltage sharing resistive-capacitance circuit is analyzed from the attenuation amplitude and oscillation frequency of reburning current oscillation; Parameter requirements of the high voltage break's self-capacitance are analyzed to achieve self-voltage sharing in a typical 40.5kV double-break circuit breaker, and the accuracy is verified by finite element simulation software. The research provides new ideas and methods for the development of multiple break vacuum circuit breakers.
Force-based assessment distinguishes between the age-related and post-stroke changes in the neural control of reaching

Abstract Background and Purpose The way we move changes throughout our lifetime and often we move less as we age. Distinguishing the motor deficits caused by a stroke from changes in motion due to normal aging is important for the accurate assessment of post-stroke recovery and to determine the effectiveness of treatment. The whole repertoire of complex human motion is enabled by forces applied by our muscles and controlled by the nervous system. However, the current medical standard for assessing motor deficits is based on quantifying movement, without a comprehensive analysis of the active forces that cause this movement. The objective here is to estimate active muscle forces from the quantitative recording of motion. Methods The motion of twenty-two people was captured when reaching to virtual targets in a center-out task. Eight of the participants had chronic hemiparesis after a stroke, and another six participants were of similar age to the stroke participants. All participants served as their own controls. We used inverse dynamic analysis to derive muscle moments, which were the result of the neural control signals to muscles and caused the recorded multijointed movements. These muscle moments were separated into forces that were related only to movement production from those only related to posture maintenance against gravity. We then compared these muscle forces between limbs to assess how stroke in one hemisphere disrupts the control signals in individuals with hemiparesis compared to the young and age-matched individuals. Results We show that both aging and stroke causes the control signals from dominant and non-dominant hemispheres to be less symmetrical in a pattern that indicates worsening neural control of intersegmental dynamics. We also show that the force-based assessment provides consistently higher quality measures of individual motor deficits due to stroke compared to traditional motion-based assessment. Using the force-based assessment, but not motion-based assessment, it was possible to distinguish the motor deficits due to stroke from age-related movement variability. Conclusions The results of our study show that it is feasible to distinguish between age-related and stroke-related deficits in the neural control of reaching using inverse dynamic analysis of motion. This is useful for objective home-based monitoring using wearable and mobile devices of patients recovering from a stroke and elderly people at risk of disability. Our results further indicate that the disruption of the neural control of intersegmental dynamics contributes not only to motor deficits after stroke but also to the inefficiency of movement in the elderly.
Momentary interpersonal processes of suicidal surges in borderline personality disorder.

Background Suicide rates are high in borderline personality disorder (BPD) where interpersonal problems trigger intense affective dysregulation and impulses to act on suicidal thoughts. To date, however, no study has examined how interpersonal stressors contribute to momentary within-person links among affect and impulsivity with suicidal ideation (SI), and how those links vary over time in people's daily lives. Methods A total of 153 individuals diagnosed with BPD and 52 healthy controls completed a 21-day ecological momentary assessment protocol. Of these 153 individuals with BPD, 105 had a history of suicide attempts. Multilevel structural equation modeling was used to examine dynamic links among interpersonal perceptions, affect, state impulsivity, and suicidal intent. Results Aggregated across interactions, lower perceived warmth in others was associated with SI. This direct relationship, however, did not extend to momentary within-person associations. Instead, interpersonal conflicts were linked to SI indirectly via greater negative affect and lower positive affect. While a robust within-person link between interpersonal perceptions and impulsivity emerged, impulsivity did not account for the relationship between interpersonal perceptions and SI. Conclusion This intensive longitudinal study illustrates momentary interpersonal signatures of an emerging suicidal crisis. Among people with BPD at high risk for suicide, interpersonal triggers initiate a cascade of affective dysregulation, which in turn gives rise to SI.
An Interdisciplinary, Project-Based Inquiry into the Chemistry and Geology of Alkaline Surface Lake Waters in the General Chemistry Laboratory

A new project-based laboratory (PJBL) was developed for general chemistry students to tackle the steps involved in chemical water quality analysis using an accessible, real-world hydrologic system (the lakes of the Lower Grand Coulee, Washington). This PJBL was developed in a joint general chemistry and environmental geology course by a chemist–geologist teaching team, and it emphasized an interdisciplinary approach for a more complete understanding of the geochemistry of the lake system. Students worked through the project following industry protocols for sample collection in the field, chemical laboratory determination of dissolved solids, alkalinity, and dissolved metals, and interpretation of the results within the unique geological context of the lakes. Foundational concepts in solution chemistry, such as solubility product, pH, and alkalinity, were essential in the discussion of the lake water trends and broader geologic processes. In particular, students could relate chemical weathering of basaltic bedrock to the measured lake water constituents and could observe how the groundwater- and evaporation-controlled fluxes of water in the closed basin produced a downstream increase in alkalinity and dissolved load. Collectively, the steps involved in the project meet the essential criteria (as defined by other authors) for a complete chemistry PJBL. This PJBL can be readily adapted to a wide range of groundwater or surface water systems and can be framed in a more or less interdisciplinary context. Many students, without prompting and on confidential evaluations, rated this as the most valuable learning experience in the year-long academic coursework.
Quantum Interferences in Ultraclean Carbon Nanotubes.

Electronic analogs of optical interferences are powerful tools to investigate quantum phenomena in condensed matter. In carbon nanotubes (CNTs), it is well established that an electronic Fabry-Perot interferometer can be realized. Other types of quantum interferences should also arise in CNTs, but have proven challenging to realize. In particular, CNTs have been identified as a system to realize the electronic analog of a Sagnac interferometer---the most sensitive optical interferometer. To realize this Sagnac effect, interference between nonidentical transmission channels in a single CNT must be observed. Here, we use suspended, ultraclean CNTs of known chiral index to study both Fabry-Perot and Sagnac electron interferences. We verify theoretical predictions for the behavior of Sagnac oscillations and the persistence of the Sagnac oscillations at high temperatures. As suggested by existing theoretical studies, our results show that these quantum interferences may be used for electronic structure characterization of carbon nanotubes and the study of many-body effects in these model one-dimensional systems.
Prediction of Success in Crowdfunding Platforms

Membership platforms serve as a source of constant earning to the independent creators who create media content such as images, videos, podcasts that are patronized by creators' followers. This mechanism leads to build the platform where the patrons contribute to raise funds to promote the creator. Patreon is one of the largest membership-based platforms that crowdfunds the media content-based projects. Predicting the success of crowdfunding projects is equally important for projects' creators and investors. In this research we resort to supervised machine learning techniques to provide decision-making supports for prediction of success or failure of such project. By comparing Naive Bayes, Logistic regression and Random Forest classifiers we demonstrate that Random Forest classifier with an accuracy of 71.5% outperforms the other two classifiers in success prediction. The findings will help the creators to better decide on their projects and improve their fan/follower base using different social media platforms.
RGB-D Mapping: Using Depth Cameras for Dense 3D Modeling of Indoor Environments

RGB-D cameras are novel sensing systems that capture RGB images along with per-pixel depth information. In this paper we investigate how such cameras can be used in the context of robotics, specifically for building dense 3D maps of indoor environments. Such maps have applications in robot navigation, manipulation, semantic mapping, and telepresence. We present RGB-D Mapping, a full 3D mapping system that utilizes a novel joint optimization algorithm combining visual features and shape-based alignment. Visual and depth information are also combined for view-based loop closure detection, followed by pose optimization to achieve globally consistent maps.We evaluate RGB-D Mapping on two large indoor environments, and show that it effectively combines the visual and shape information available from RGB-D cameras.
Better Slicing of Programs with Jumps and Switches

Program slicing is an important operation that can be used as the basis for programming tools that help programmers understand, debug, maintain, and test their code. This paper extends previous work on program slicing by providing a new definition of "correct" slices, by introducing a representation for C-style switch statements, and by defining a new way to compute control dependences and to slice a program-dependence graph so as to compute more precise slices of programs that include jumps and switches. Experimental results show that the new approach to slicing can sometimes lead to a significant improvement in slice precision.
Identification of an N-acetylglucosaminyltransferase in Dictyostelium discoideum that transfers an "intersecting" N-acetylglucosamine residue to high mannose oligosaccharides.

Abstract Glycoproteins synthesized by the cellular slime mold Dictyostelium discoideum have been shown to contain asparagine-linked high-mannose oligosaccharides which have an N-acetylglucosamine group in a novel intersecting position (attached beta 1-4 to the mannose linked alpha 1-6 to the core mannose). We have used crude membrane preparations from vegetative D. discoideum (strain M4) to characterize the enzyme activity responsible for catalyzing the transfer of GlcNAc to the intersecting position of high-mannose oligosaccharides. UDP-GlcNAc:oligosaccharide beta-N-acetylglucosaminyltransferase activity in these preparations attaches GlcNAc to the mannose residue-linked alpha 1-6 to the beta-linked core mannose of the following Man9GlcNAc oligosaccharide as shown by the arrow. (formula; see text) It will also attach GlcNAc to the same intersecting position and/or to the bisecting position (beta-linked core mannose) of the following Man5GlcNAc oligosaccharide. (formula; see text) An analysis of the pH profiles, effects of heat denaturation, and substrate inhibitions on the addition of GlcNAc to either the intersecting or bisecting position of this Man5GlcNAc oligosaccharide indicates that a single enzyme activity is responsible for transferring GlcNAc to both positions. Various oligosaccharides were assayed to determine the substrate specificity of the transferase activity. These data indicate that both the mannose-attached alpha 1-3 and the mannose-attached alpha 1-6 to the mannose receiving the GlcNAc play a critical role in substrate suitability; absence of the alpha 1-6 mannose results in at least a 90% decrease in activity, while absence of the alpha 1-3 mannose results in a completely inactive substrate. This suggests that the minimal substrate is the disaccharide Man alpha 1-3Man.
Induction of Hippocampal Long-Term Depression Requires Release of Ca2+ from Separate Presynaptic and Postsynaptic Intracellular Stores

Studies have suggested that an increase in intracellular [Ca2+] is necessary for the induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, and that release of Ca2+ from intracellular storage pools can be necessary to induce LTP. We investigated whether release of Ca2+ from intracellular stores also is required for the induction of LTD at Schaffer collateral-CA1 synapses in hippocampal slices. Both thapsigargin (1 microM) and cyclopiazonic acid (1 microM), compounds that deplete all intracellular Ca2+ pools by blocking LTP-dependent Ca2+ uptake into intracellular compartments, blocked the induction, but not maintenance, of LTD by low-frequency stimulation (LFS) (1 Hz/15 min) without affecting baseline synaptic transmission. Washout of the reversible inhibitor cyclopiazonic acid restored the ability to induce LTD. In contrast, thapsigargin did not block depotentiation of LTP by 1 Hz LFS, suggesting that LTP causes a reduction in the threshold [Ca2+] necessary for LTD. Selective depletion of the ryanodine receptor-gated Ca2+ pool by bath application of ryanodine (10 microM) also blocked the induction of LTD, indicating a requirement for Ca(2+)-induced Ca2+ release. Impalement of CA1 pyramidal neurons with microelectrodes containing thapsigargin (500 nM to 200 microM) prevented the induction of LTD at synapses on that neuron without blocking LTD in the rest of the slice. In contrast, similar filling of CA1 pyramidal neurons with ryanodine (2 microM to 5 mM) did not block the induction of LTD. From these data, we conclude that the induction of LTD requires release of Ca2+ both from a presynaptic ryanodine-sensitive pool and from postsynaptic (presumably IP3-gated) stores.
Anionic synthesis of chain‐end functionalized polymers using 1,1‐diphenylethylene derivatives. Preparation of 4‐hydroxyphenyl‐terminated polystyrenes

A new, general functionalization reaction for polymeric organolithium compounds was developed based on their quantitative reaction with 1,1-diphenylethylene derivatives. The utility of this method was demonstrated by preparation of 4-hydroxyphenyl-terminated polystyrene (2b) by reaction of polystyryllithium in benzene at room temperature with 1-[4-(tert-butyldimethylsiloxy)phenyl]-1-phenylethylene (1a) followed by hydrolysis with dilute hydrochloric acid. The course of the functionalization reaction was monitored by ultraviolet-visible spectroscopy at 406 nm. Polystyrene 2b was characterized by size exclusion chromatography, thinlayer chromatography, membrane osmometry, end-group titration and both 1H and 13C NMR spectroscopy. All experimental evidence is consistent with quantitative functionalization via the 1,1-diphenylethylene derivative.
Designing Product Families for a Changing Market Space

The Product Platform Constructal Theory Method (PPCTM) provides designers with an approach for synthesizing multiple modes of managing customization in the development of product platforms. An assumption underlying PPCTM is that the extent of the market space is known and is fixed. In this paper, we introduce PPCTM-RCM (Robust to Changes in Market) that facilitates designing product platforms when the extent of the market space is expected to change. The PPCTM-RCM is illustrated via example problem, namely, the design of a product platform for a line of customizable pressure vessels. Our focus in this paper is on highlighting features of the method rather than results per se.Copyright © 2005 by ASME
Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans.

Objectives. The present study was designed to test the hypothesis that long-term dietary supplementation with the nitric oxide precursor l-arginine would enhance vascular or platelet-derived nitric oxide activity, or both, and thereby inhibit platelet reactivity in hypercholesterolemic humans. Background. We have shown that reduced vascular activity of nitric oxide in hypercholesterolemic rabbits can be restored by l-arginine supplementation. The improvement in nitric oxide activity is associated with an inhibition of platelet aggregation ex vivo. This effect is most likely due to increased elaboration of endothelium- or platelet-derived nitric oxide, or both, because the inhibition of platelet reactivity was associated with elevation of intraplatelet cyclic guanosine monophosphate and was reversed by the nitric oxide synthase antagonist N-methyl-arginine. Methods. In a double-blinded, randomized, placebo-controlled trial, hypercholesterolemic patients were assigned to l-arginine hydrochloride, 8.4 g/day orally, or placebo for 2 weeks. Platelet-rich plasma was obtained for aggregometry induced by collagen (1 to 10 μg/ml) at four points: baseline, after 2 weeks of treatment, after a 2-week washout and after a long-term washout of 16 weeks on average. Aggregation was quantified by light transmittance and expressed as a percent transmittance observed with platelet-poor plasma. Results. Compared with normocholesterolemic control subjects, platelets from hypercholesterolemic subjects stimulated with 5 μg/ml of collagen showed increased aggregability (68.6% in hypercholesterolemic patients vs. 54.5% in normocholesterolemic control subjects, p ≤ 0.02). After 2 weeks of treatment with l-arginine (but not placebo), platelet reactivity was modestly reduced; this effect persisted for 2 weeks after discontinuation of arginine (52.6% in arginine-treated patients vs. 65.1% in normocholesterolemic control subjects, p = 0.07). After 18 weeks (i.e., 16 weeks after discontinuing arginine treatment), the platelets of hypercholesterolemic patients once again became hyperaggregable, and the extent of platelet aggregation was significantly increased compared with the 4-week point (73.6% after vs. 52.6% during arginine treatment, p < 0.01). No significant change in platelet reactivity was seen in placebo-treated hypercholesterolemic patients throughout the study. l-Arginine treatment was well tolerated without side effects. Conclusions. This double-blinded, placebo-controlled study demonstrates that dietary supplementation with l-arginine can modestly attenuate the increased platelet reactivity seen in hypercholesterolemic patients. The data are consistent with our previous studies in hypercholesterolemic animals, demonstrating that l-arginine restores endogenous nitric oxide activity and inhibits platelet aggregation. Enhancement of endogenous nitric oxide activity is a potential novel therapeutic strategy worthy of further study. (J Am Coll Cardiol 1997;29:479–85)
Keap1, the Sensor for Electrophiles and Oxidants that Regulates the Phase 2 Response, Is a Zinc Metalloprotein†

Induction of the phase 2 response, a major cellular reaction to oxidative/electrophile stress depends on a protein triad: actin-tethered Keap1 that binds to Nrf2. Inducers react with Keap1 releasing Nrf2 for nuclear translocation and activation of the antioxidant response element (ARE), which regulates phase 2 genes. The primary sensors for inducers are certain uniquely reactive cysteine thiols of Keap1. Recombinant murine Keap1 contains 0.9 zinc atoms per monomer as determined by inductively coupled plasma-optical emission spectrometry: its zinc content depends on the metal composition of the overexpression medium. Simultaneous direct measurement of bound zinc using a pyridazoresorcinol chelator and protein thiol groups using 4,4'-dipyridyl disulfide has established that (i) zinc is bound to reactive cysteine thiols of Keap1 and is displaced stoichiometrically by inducers, (ii) with these cysteines mutated to alanine, the affinity for zinc is reduced by nearly 2 orders of magnitude, and (iii) the association constant of Keap1 for zinc is 1.02 (+/-0.19) x 10(11) M(-)(1), consistent with a Zn(2+) metalloprotein. Co(2+) substitution for Zn(2+) yields an optical spectrum consistent with tetrahedral metal coordination. Coincident binding of inducers and release of zinc alters the conformation of Keap1, as shown by a profound decline of its tryptophan fluorescence and depression of fluorescence of a hydrophobicity probe. Thus, regulation of the phase 2 response involves chemical modification of critical cysteine residues of Keap1, whose reactivity is modulated by zinc binding. Keap1 is a zinc-thiol protein endowed with a delicate switch controlled by both metal-binding and thiol reactivity.
History-in-person: the cultural production of populism among Kentucky's small-scale family farmers

How does an ideology such as populism persist and shift across generations? How do people come to embody such an ideology? This article focuses on a grassroots community association to illustrate how enduring ideologies are culturally produced and transformed. Drawing on oral history interviews and field research with an organization of Kentucky small-scale family farmers, and drawing on Holland and Lave's (2001) concept of history-in-person, I argue that enduring ideologies and attendant identities persist and shift through contentious confluences of individual biographies, citizen's groups, and societal institutions. I contend that the history-in-person approach informed by experience-near data offers an insider's view useful to explaining how durable and contentious ideologies and identities persist and change over time.
Impact of the front metal layout on the fill factor of GaSb-based photovoltaics grown on n-type substrate

An optimization it done on the fill factor of an M BE-grown p-on-n (iaSb photovoltaic by reducing the series resistance brought on by the layout of the front metal electrodes while simultaneously minimizing their coverage area. The optimization indicates a variation in the substrate carrier lifetime.
The rate enhancement produced by the ribosome: an improved model.

As a model for mechanistic comparison with peptidyl transfer within the ribosome, the reaction of aqueous glycinamide with N-formylphenylalanine trifluoroethyl ester (fPhe-TFE) represents an improvement over earlier model reactions involving Tris. The acidity of trifluoroethanol (pKa 12.4) resembles that of tRNA (12.98) more closely than do the acidities of model reactants described earlier, and the reactivity of the simple nucleophile glycinamide is free of potential complications that arise from alternative reaction pathways available to Tris. At 25 °C, the uncatalyzed reaction of glycinamide with fPhe-TFE proceeds with a second-order rate constant of 3 × 10-5 M-1 s-1; ΔH⧧ = +7.8 kcal/mol; TΔS⧧ = −15.7 kcal/mol. The ribosomal reaction of puromycin with fMet-tRNA proceeds 3 × 107-fold more rapidly, with a second-order rate constant (kcat/Km) of 1 × 103 M-1 s-1; ΔH⧧ = +16.0 kcal/mol; TΔS⧧ = +2.0 kcal/mol. That rate enhancement, an order of magnitude larger than estimated earlier, is fully explained by the...
TAT transduction: the molecular mechanism and therapeutic prospects

Research into the mechanism of protein transduction has undergone a renaissance in the past five years as many groups have sought to understand the behavior of transducing peptides to harness their enormous therapeutic and diagnostic potential. The field has benefited greatly from rigorous cell biological and biophysical studies of the mechanism used by cell penetrating peptides to enter cells and deliver their cargo. The recent identification of fluid phase endocytosis as the mode of cellular entry for TAT and other protein transduction domains has enhanced our understanding of how transduction facilitates intracellular delivery. Many outstanding questions and contradictions still remain to be resolved in the field. Nevertheless, the current body of work regarding the mechanism of uptake gives a much clearer picture of how these macromolecules enter cells and how we might enhance the bioavailability to take advantage of them clinically.
Dynamic, object-oriented parallel processing

Mentat, a dynamic, object-oriented parallel-processing system that provides tools for constructing portable, medium-grain parallel software by combining an object-oriented approach with an underlying layered virtual-machine model is described. Mentat's three primary design objectives-high performance through parallel execution, easy parallelism, and software portability across a wide range of platforms-are reviewed. The performance of four applications of Mentat on two platforms-a 32-node Intel iPSC/2 hypercube and a network of 16 Sun IPC Sparcstations-are examined. The applications are DNA and protein sequence comparison, image convolution, Gaussian elimination and partial pivoting, and sparse matrix-vector multiplication. The performance of Mentat in these applications is compared to that of object-oriented parallel-processing systems, compiler-based distributed-memory systems, portable parallel-processing systems, and hand-coded implementations of the same applications. >
The Effect of Heat Transfer Coefficient, Local Wet Bulb Temperature and Droplet Size Distribution Function on the Thermal Performance of Sprays

Energy balance considerations indicate that the droplet heat transfer coefficient, local wet bulb temperature, and droplet size distribution function are the basic parameters affecting spray system thermal performance. Within the range of available experimental data, results indicate that the Ranz-Marshall correlation gives an agreement to within +- 5.0 percent of measured droplet temperatures at the pond surface for a medium wind range of between 2.5 and 5 m/s. The local wet bulb temperature is taken as the arithmetic mean of the initial and final wet bulb temperatures. For wind speeds greater than 3.5 m/s, the local wet bulb can be taken as the ambient. The modified log normal distribution of Mugele and Evans provides the best description of the droplet size distribution. Further, through the introduction of a correction term, the Spray Energy Release (SER) can be deduced from single droplet information.
Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Opioids

Abstract Of late, the realization that unrelieved pain continues to be a prevalent problem despite the availability of effective analgesic agents has encouraged a movement toward establishing a balance between the prevention of drug misuse, abuse, and diversion, and the provision of adequate pain control. In this and other publications, opioids have been acknowledged as essential medications that are necessary for the relief of chronic, pain-inducing conditions. Yet, it is still important to integrate risk management into programs of care and for clinicians to develop skills to minimize risks of misuse, abuse, and diversion of medications. Despite opioids’ historical longevity and established place in the armamentarium of analgesics for control of both acute and chronic pain, recent advancements in the field warrant reconsideration of the available data on opioids. For example, developments in pharmacogenomics research have demonstrated that the intrinsic analgesic mechanisms, pharmacokinetics, and metabolism of opioids are dictated by an individual’s genetics. This has important clinical ramifications. Because each patient has a unique genetic background, analgesic regimens need to be individualized for each patient to maximize analgesic opioid effects and minimize side effects. Moreover, opioid rotation should be considered when analgesia to a particular pharmacotherapy is inadequate or induces significant adverse effects.
Multiple Mechanisms Are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

The number of distinct signaling pathways that can transactivate the epidermal growth factor receptor (EGFR) in a single cell type is unclear. Using a single strain of human mammary epithelial cells, we found that a wide variety of agonists, such as lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-α, require EGFR activity to induce ERK phosphorylation. In contrast, hepatocyte growth factor can stimulate ERK phosphorylation independent of the EGFR. EGFR transactivation also correlated with an increase in cell proliferation and could be inhibited with metalloprotease inhibitors. However, there were significant differences with respect to transactivation kinetics and sensitivity to different inhibitors. In particular, IGF-1 displayed relatively slow transactivation kinetics and was resistant to inhibition by the selective ADAM-17 inhibitor WAY-022 compared with LPA-induced transactivation. Studies using anti-ligand antibodies showed that IGF-1 transactivation required amphiregulin production, whereas LPA was dependent on multiple ligands. Direct measurement of ligand shedding confirmed that LPA treatment stimulated shedding of multiple EGFR ligands, but paradoxically, IGF-1 had little effect on the shedding rate of any ligand, including amphiregulin. Instead, IGF-1 appeared to work by enhancing EGFR activation of Ras in response to constitutively produced amphiregulin. This enhancement of EGFR signaling was independent of both receptor phosphorylation and PI-3-kinase activity, suggestive of a novel mechanism. Our studies demonstrate that within a single cell type, the EGFR autocrine system can couple multiple signaling pathways to ERK activation and that this modulation of EGFR autocrine signaling can be accomplished at multiple regulatory steps.