cssi/SciSciGPT-SciSciNet huggingface dataset:
Mitochondrial Uncoupling Protein 2 Is Present in Human Platelets and Regulates Platelet Activation

Abstract It has long been recognized that platelets contain functional mitochondria and accumulating data suggest that several aspects of mitochondrial function, including reactive oxygen species production, modulate platelet thrombotic function. We have recently shown that platelet mitochondria isolated from patients with Sickle Cell Disease generate significantly greater concentrations of reactive oxygen species than healthy African American subjects and that this mitochondrial oxidant generation contributes to higher levels of basal platelet activation in these patients (Blood. 2014 May 1;123(18):2864-72). Based on these data, we have now investigated the factors that regulate platelet mitochondrial superoxide generation in healthy and Sickle Cell Disease platelets. Here we demonstrate that human platelets express mitochondrial uncoupling protein-2 (UCP2), a protein that is known to decrease the efficiency of oxidative phosphorylation and oxidant generation in other cell types but has previously not been identified in platelets. In this study we show that UCP2 protein is expressed in healthy human platelets and is fully functional as it facilitates proton leak across the inner mitochondrial membrane, leading to decreased mitochondrial membrane potential. Further, we demonstrate that the expression of this protein attenuates platelet mitochondrial superoxide generation, as treatment of platelets with Genipin (2-10µM), a pharmacological inhibitor of UCPs, concentration-dependently increases mitochondrial membrane potential and reactive oxygen species production. Further, an approximately 70% inhibition of UCP activity results in platelet activation demonstrated by increased membrane p-selectin expression (65±7% versus 6±3% in untreated controls) and augmented glycoprotein IIb/IIIa activation (57±9% versus 9±4% in untreated controls). The use of the mitochondrial-targeted antioxidant mitoTEMPO (10µM) decreases genipin-induced superoxide generation and significantly attenuates platelet activation. Notably, preliminary data presented here also suggest that UCP expression is decreased in platelets isolated from Sickle Cell Disease patients (3-fold) compared to healthy African American subjects. Additionally, ongoing studies are investigating platelet function in mice deficient in UCP2. Taken together, these data demonstrate a novel mechanism of regulation of platelet thrombotic function whose physiological relevance is apparent in the context of Sickle Cell Disease. More broadly this study advances the understanding of the role of the mitochondrion in platelet biology and thrombotic disease. Disclosures No relevant conflicts of interest to declare.
Biochemical Methods Used to Study the Gene Expression and Protein Complexes in the Filamentous Fungus Neurospora crassa

Biochemical approaches are powerful tools for investigating mechanisms of biological processes. Here, we describe several biochemical approaches that have been successfully in our laboratory to study the filamentous fungus Neurospora crassa. These approaches include protein extraction and western blot analysis, protein purification using epitope-tagged fusion protein, protein immunoprecipitation (IP) and Chromatin Immunoprecipitation (ChIP) assays. These methods can also be modified for use in other filamentous fungi.
Self-Regulation and Psychopathology: Toward an Integrative Translational Research Paradigm

This article presents a general framework in which different manifestations of psychopathology can be conceptualized as dysfunctions in one or more mechanisms of self-regulation, defined as the ongoing process of managing personal goal pursuit in the face of internal, interpersonal, and environmental forces that would derail it. The framework is based on the assertion that self-regulation is a critical locus for the proximal influence on motivation, cognition, emotion, and behavior of more distal factors such as genetics, temperament, socialization history, and neurophysiology. Psychological theories of self-regulation are ideal platforms from which to integrate the study of self-regulation both within and across traditional disciplines. This article has two related goals: to elucidate how the construct of self-regulation provides a unique conceptual platform for the study of psychopathology and to illustrate that platform by presenting our research on depression as an example.
Managing Quality by Bundling Product and Service Characteristics

Lancaster (1966), demonstrates the usefulness of treating products and services as bundles of characteristics. Product quality is conceptualized as a subset of product characteristics, and can measured by the degree to which their characteristics relate to customer preferences. In this respect, quality management and customer responsiveness overlap. Technologies constrain product characteristics to technically deliverable clusters or bundles. Effective product design and engineering involve efficient bundling of customer oriented characteristics. Thus, quality-based production decisions affect not only supply, but also demand.
The impacts of processing the use of derogatory language in a social work classroom

ABSTRACTClassroom content focused on diversity often includes dialogue and student use of derogatory language, as well as opportunities for self-reflection, modeling, collaboration, and continuous development. This article is a critical reflection by a White teacher, a White student, and a student with Mexican American heritage on a critical incident involving student use of racially derogatory language in a story. The experiences are framed with Mezirow’s accidental disorienting dilemmas and a decolonizing teaching pedagogy, which create an opportunity for transformative learning.The approach resulted in a strong process and storytelling orientation for the class and a deeper appreciation for the power of language.
Incentive based cooperative content caching in Social Wireless Networks

This paper develops an incentive based cooperative content caching framework for Social Wireless Networks (SWNETs) in which content demands are hierarchically heterogeneous. The heterogeneous request model incorporates user preference for different categories/genres, and contents under each category, both following power law distributions at local as well as global levels. Based upon such request generation model, an optimal incentive based Heterogeneous Split Caching algorithm is proposed which can minimize electronic content provisioning cost using cooperative caching policies. Detailed simulation experiments for functional validation and performance evaluation with respect to traditional caching strategies are then performed under various protocol and network parameters. The baseline HSC mechanism is also tested against a special benchmark situation that provides a steady state performance bound, which can occur after an infinite request horizon.
Integrated rheology model: Explosive Composition B-3

Composition B-3 (Comp B-3) is a high explosive formulation composed of 60/40wt% RDX (1,3,5-trinitroperhydro-1,3,5-triazine) /TNT (2,4,6 trinitrotoluene). Above approximately 78°C this formulation p...
From transaction to collaboration: scholarly communications design at UConn Library

The University of Connecticut (UConn) Library, in collaboration with the School of Fine Arts and the UConn Humanities Institute and with support from the Andrew W Mellon Foundation, is developing Greenhouse Studios (GS). GS is a scholarly communications research laboratory dedicated to using collaborative models and design principles in the creation of scholarly works. Scholarship laboratories that function as a combination of a scientific research lab and an art studio are a useful means of advancing the methods and outcomes of scholarly communications. We intend to examine whether flattening hierarchies through the GS model is a significant challenge for librarians who work within transactional models of interaction and are closely tied to faculty-driven service models of research support. Other participants typically thought of as supporting faculty are embedded as equal participants in the design process. We will apply qualitative methods to examine whether the GS design process facilitates development of new models of interaction among faculty, librarians, design technologists and other experts. Preliminary experience finds most participants embrace the collaborative model and are energized by the experience. Our assessment will focus on GS techniques as drivers for role and scholarly output changes, how these experiences might translate into changes in library culture or services, and on practical findings related to space, technology usage and administrative hurdles. This paper is the result of a presentation delivered at CNI (the Coalition for Networked Information) in early 2017 1 and encapsulates our thinking then and now (in early 2018) as we refine our assessment tools.
Metal Complexes in Arthritis

Rheumatoid arthritis is generally described as a chronic inflammatory disease of unknown causation, manifested particularly in the peripheral joints. Approximately 1% of the population of industrialized countries suffer from this disease, although perhaps ten times that number suffer from some sort of rheumatic disorder. The pathogenesis of the disease is linked to a breakdown of the immune system, and disordered immune responses are most likely to be involved in initiation of the disease; the resultant inflammation produces tissue injury and physical debilitation [1].
Differentially Methylated Genes in Saliva are linked to Childhood Stress

Chronic and severe stress exposure in early childhood is associated with the development of psychiatric disorders. Yet, the molecular mechanisms underlying this relationship remain poorly understood. Here, we profile molecular marks (DNA methylation and gene expression) throughout the human genome to determine the associations between childhood stress exposure and gene regulation. To do so, we collected saliva tissue from prepubertal girls (mean age 10.9 ± 1.26 years) who had experienced different levels of childhood adversity, ranging from mild to severe. We found 122 differentially methylated genes (FDR P-value < 0.05) associated with high childhood stress exposures that affect brain development. Of these differentially methylated genes, 12 also differed in gene expression. To further investigate the potential effects of stress exposure on gene regulation, we examined the DNA sequences flanking all the differentially methylated loci. This analysis revealed enrichment of known binding sites for transcription factors, suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these genes. Together, these findings indicate a possible neuromolecular mechanism linking children’s social experiences with risk for anxiety and depressive disorders.
The Gerald R. Ford Administration and the Olympic Movement: Political Games

This article looks at the ways in which the Gerald Ford administration involved itself in the United States Olympic program. Though short in tenure, Ford’s administration dealt with four Olympic-re...
Both Crops Main Crops—Density Constant—Combined Crop Responses

Up to this point responses from both crops have not been combined. Each crop response has been treated independently. Although this might satisfy some experimenters, it is not useful in evaluating cropping systems and in studying results as a farmer would. He would be interested in some combination of yields, Y 1 and Y 2 , say, from both crops. It would appear that a linear combination of a factor times crop 1 yield plus a factor times crop 2 yield would be the type of combination of value to a farmer. In considering such a trait as value of a crop, the value of crop 1 plus the value of crop 2, say, p 1 Y 1 + p 2 Y 2, would be the response of interest. We could equally well consider Y 1 + p 2 Y 2/p 1 as the response variable since the ratio, p 2/p 1, of values might be more stable over time than the actual vaues.
Assessing exhibition swine as potential disseminators of infectious disease through the detection of five respiratory pathogens at agricultural exhibitions

Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.
Functional Assessment of Coronary Artery Disease Using Whole-Heart Dynamic Computed Tomographic Perfusion

Background— Computed tomographic (CT) angiography is an important tool for the evaluation of coronary artery disease but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed. Methods and Results— A total of 20 contrast-enhanced CT volume scans were acquired in 5 swine (40±10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending coronary artery, and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only 2 volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by PFPA=1.01 FFR−0.03 ( R 2=0.85) and PMSM=1.03 FFR−0.03 ( R 2=0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively. Conclusions— A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of coronary artery disease at a relatively low radiation dose.
The LRRC8 volume-regulated anion channel inhibitor, DCPIB, inhibits mitochondrial respiration independently of the channel.

There has been a resurgence of interest in the volume-regulated anion channel (VRAC) since the recent cloning of the LRRC8A-E gene family that encodes VRAC. The channel is a heteromer comprised of LRRC8A and at least one other family member; disruption of LRRC8A expression abolishes VRAC activity. The best-in-class VRAC inhibitor, DCPIB, suffers from off-target activity toward several different channels and transporters. Considering that some anion channel inhibitors also suppress mitochondrial respiration, we systematically explored whether DCPIB inhibits respiration in wild type (WT) and LRRC8A-knockout HAP-1 and HEK-293 cells. Knockout of LRRC8A had no apparent effects on cell morphology, proliferation rate, mitochondrial content, or expression of several mitochondrial genes in HAP-1 cells. Addition of 10 µM DCPIB, a concentration typically used to inhibit VRAC, suppressed basal and ATP-linked respiration in part through uncoupling the inner mitochondrial membrane (IMM) proton gradient and membrane potential. Additionally, DCPIB inhibits the activity of complex I, II, and III of the electron transport chain (ETC). Surprisingly, the effects of DCPIB on mitochondrial function are also observed in HAP-1 and HEK-293 cells which lack LRRC8A expression. Finally, we demonstrate that DCPIB activates ATP-inhibitable potassium channels comprised of heterologously expressed Kir6.2 and SUR1 subunits. These data indicate that DCPIB suppresses mitochondrial respiration and ATP production by dissipating the mitochondrial membrane potential and inhibiting complexes I-III of the ETC. They further justify the need for the development of sharper pharmacological tools for evaluating the integrative physiology and therapeutic potential of VRAC in human diseases.
Stochastic simulation of streamflow and spatial extremes: a continuous, wavelet-based approach

Abstract. Stochastically generated streamflow time series are used for various water management and hazard estimation applications. They provide realizations of plausible but as yet unobserved streamflow time series with the same temporal and distributional characteristics as the observed data. However, the representation of non-stationarities and spatial dependence among sites remains a challenge in stochastic modeling. We investigate whether the use of frequency-domain instead of time-domain models allows for the joint simulation of realistic, continuous streamflow time series at daily resolution and spatial extremes at multiple sites. To do so, we propose the stochastic simulation approach called Phase Randomization Simulation using wavelets (PRSim.wave) which combines an empirical spatio-temporal model based on the wavelet transform and phase randomization with the flexible four-parameter kappa distribution. The approach consists of five steps: (1) derivation of random phases, (2) fitting of the kappa distribution, (3) wavelet transform, (4) inverse wavelet transform, and (5) transformation to kappa distribution. We apply and evaluate PRSim.wave on a large set of 671 catchments in the contiguous United States. We show that this approach allows for the generation of realistic time series at multiple sites exhibiting short- and long-range dependence, non-stationarities, and unobserved extreme events. Our evaluation results strongly suggest that the flexible, continuous simulation approach is potentially valuable for a diverse range of water management applications where the reproduction of spatial dependencies is of interest. Examples include the development of regional water management plans, the estimation of regional flood or drought risk, or the estimation of regional hydropower potential. Highlights. Stochastic simulation of continuous streamflow time series using an empirical, wavelet-based, spatio-temporal model in combination with the parametric kappa distribution. Generation of stochastic time series at multiple sites showing temporal short- and long-range dependence, non-stationarities, and spatial dependence in extreme events. Implementation of PRSim.wave in R package PRSim: Stochastic Simulation of Streamflow Time Series using Phase Randomization.
Cognitive Functions Predict Trajectories of Sleepiness Over 10 Years: A Population-Based Study

Background Excessive daytime sleepiness is associated with chronic disorders of aging and mortality. Because longitudinal data are limited on the development of sleep disturbances and cognitive changes in older adults, we investigated the demographic, clinical, and cognitive predictors of self-reported daytime sleepiness over a period of 10 years. Methods We jointly modeled latent trajectories over time of sleepiness, cognitive domains, and informative attrition and then fit models to identify cognitive trajectories and baseline characteristics that predicted the trajectories of sleepiness. Results Three latent trajectory groups were identified: emerging sleepiness, persistent sleepiness, and consistently low daytime sleepiness accounting for attrition in all groups. Compared with low sleepiness, emerging sleepiness was significantly associated with declining attention and subjective memory complaints; persistent sleepiness was associated with lower baseline scores in all cognitive domains, declining language trajectory, and more subjective memory complaints. Conclusions These findings suggest that persistent sleepiness and emerging daytime sleepiness are associated with cognitive decline and multiple morbidities, albeit more subtly in emerging daytime sleepiness. Furthermore, these data suggest that change in the cognitive domain of attention and subjective memory complaints may be early indicators of future sleep disturbance.
Structure of eukaryotic DNA polymerase δ bound to the PCNA clamp while encircling DNA.

The DNA polymerase (Pol) δ of Saccharomyces cerevisiae (S.c.) is composed of the catalytic subunit Pol3 along with two regulatory subunits, Pol31 and Pol32. Pol δ binds to proliferating cell nuclear antigen (PCNA) and functions in genome replication, repair, and recombination. Unique among DNA polymerases, the Pol3 catalytic subunit contains a 4Fe-4S cluster that may sense the cellular redox state. Here we report the 3.2-A cryo-EM structure of S.c. Pol δ in complex with primed DNA, an incoming ddTTP, and the PCNA clamp. Unexpectedly, Pol δ binds only one subunit of the PCNA trimer. This singular yet extensive interaction holds DNA such that the 2-nm-wide DNA threads through the center of the 3-nm interior channel of the clamp without directly contacting the protein. Thus, a water-mediated clamp and DNA interface enables the PCNA clamp to "waterskate" along the duplex with minimum drag. Pol31 and Pol32 are positioned off to the side of the catalytic Pol3-PCNA-DNA axis. We show here that Pol31-Pol32 binds single-stranded DNA that we propose underlies polymerase recycling during lagging strand synthesis, in analogy to Escherichia coli replicase. Interestingly, the 4Fe-4S cluster in the C-terminal CysB domain of Pol3 forms the central interface to Pol31-Pol32, and this strategic location may explain the regulation of the oxidation state on Pol δ activity, possibly useful during cellular oxidative stress. Importantly, human cancer and other disease mutations map to nearly every domain of Pol3, suggesting that all aspects of Pol δ replication are important to human health and disease.
A practical six-step synthesis of (S)-camptothecin.

An asymmetric synthesis of (S)-camptothecin (1) has been accomplished in six steps starting from two commercially available heterocycles.
RhoA mediates stress fiber strain site recognition by the LIM protein testin

The actin cytoskeleton is a key regulator of mechanical processes in cells. The family of LIM domain proteins have recently emerged as important mechanoresponsive cytoskeletal elements capable of sensing strain in the actin cytoskeleton. The mechanisms regulating this mechanosensitive behavior, however, remain poorly understood. Here we show that the LIM domain protein testin is peculiar in that despite the full-length protein primarily appearing diffuse in the cytoplasm, the C-terminal LIM domains alone recognize strained actin while the N-terminal domains alone recognize unstrained actin. Phosphorylation and cancer related mutations in the dimerization regions of testin, however, reveal its mechanosensitivity and cause it to relocate to focal adhesions and sites of strain in the actin cytoskeleton. Finally, we demonstrate activated RhoA causes WT testin to adorn stress fibers and become mechanosensitive. Together, our data show that testin9s mechanoresponse is regulated in cells and provide new insights into LIM domain protein recognition of the actin cytoskeleton mechanical state.
Constructive Neutral Evolution 20 Years Later

Evolution has led to a great diversity that ranges from elegant simplicity to ornate complexity. Many complex features are often assumed to be more functional or adaptive than their simpler alternatives. However, in 1999, Arlin Stolzfus published a paper in the Journal of Molecular Evolution that outlined a framework in which complexity can arise through a series of non-adaptive steps. He called this framework Constructive Neutral Evolution (CNE). Despite its two-decade-old roots, many evolutionary biologists still appear to be unaware of this explanatory framework for the origins of complexity. In this perspective piece, we explain the theory of CNE and how it changes the order of events in narratives that describe the evolution of complexity. We also provide an extensive list of cellular features that may have become more complex through CNE. We end by discussing strategies to determine whether complexity arose through neutral or adaptive processes.
Clinical Y-view versus 3-dimensional assessments of intramuscular fat in patients with full-thickness rotator cuff tears.

Abstract Rationale and Objectives. Recent evidence suggests an inhomogeneous distribution of intramuscular rotator cuff fat infiltration (FI) in a small sample of individuals with rotator cuff tears, yet clinically just a few slices at the scapular Y-view are used to evaluate FI in patients with rotator cuff tears. The purpose of this study was to determine if assessment of FI using the scapular Y-view is representative of the entire muscle in patients with full-thickness rotator cuff tears, and whether this varies by tear size. Materials and methods Patients (N = 25) diagnosed with full-thickness rotator cuff tear and confirmed with magnetic resonance imaging (MRI) were included. Fat-water sequences were used to objectively quantify mean FI (%) in the entire 3D muscle and the mean from 3 slices at the Y-view. Mixed-model 2 × 2 ANOVAs were used to assess for differences between methods, and if results vary by tear-size. Results There were no statistically significant differences between mean amount of FI of the entire 3D muscle and mean Y-view in the supraspinatus or infraspinatus muscles (p > 0.05). Additionally, this did not differ across tear size groups (p > 0.05). Conclusion Results of this study suggest FI assessed in the Y-view is not different (mean difference
“Ain’t I Got a Right to the Tree of Life?”: Examining Special Education through the Application of Afro-Humanity

In this manuscript we chart the intersection of dis/ability and Afro-humanity. We propose that Afro-humanity is a contextual paradigm within African-centred ideology that can be applied to explore the ways in which disability may be perceived differently when applying a specific, cultural philosophical lens. We also explore the process of decolonization, whereby African American parents, with a child identified with an intellectual disability, reorient themselves to a way of thinking that is more emancipatory. The parents act in a way that challenge concepts about human cognitive variance and notions of dis/ability in school settings. Drawing on such a model as Afro-humanity, we argue for a more equitable approach to community and educational engagement for Black students labelled with dis/abilities.
New results and open problems related to non-standard stringology

There are a number of string matching problems for which the best known algorithms rely on algebraic convolutions (an approach pioneered by Fischer and Paterson [FP74]). These include for instance the classical string matching with wild cards and the k-mismatches problem. In [MP94], the authors studied generalizations of these problems which they called the non-standard stringology. There they derived upper and lower bounds for non-standard string matching problems.
DOES BREAST-FEEDING INCREASE THE CHILD'S RISK OF BREAST CANCER?

Wide publicity has been given to the recommendation by an experimental scientist that mothers with a family history of breast cancer should not nurse their daughters for fear of increasing the child9s risk of developing breast cancer.1 Because 5% of U.S. women develop this neoplasm,2 a substantial proportion of families have a member with breast cancer, and would be affected by the recommendation. The experimental basis for the advice against breast-feeding should be weighed against the epidemiological evidence concerning transmission of mammary cancer from mother to daughter. In particular, the risk of transmitting breast cancer to the child should be evaluated against the benefits derived from breast-feeding.
Thomas More on the Sadness of Christ: From Mystagogy to Martyrdom

Thomas More presents us with a wonderful example of martyrological exegesis where his exegetical work was intended to inspire his readers to live the virtues, to follow Christ, and to provide consolation amidst tribulation. Such exegesis aimed to aid the reader to live the martyrdom required in ordinary life and beyond that, if necessary, with mental anguish, physical torture, and even death on behalf of Christ. Before examining More's work, I first situate this discussion within the broader conversation concerning modern biblical interpretation- in particular the notion of senses of Scripture - therein explaining how I shall be using terms like mystagogy and martyrdom in this article. I shall then examine More's spiritual exegesis of Jesus' passion narratives, paying particular attention to the agony in the garden. I shall conclude with a look at the saint's life, which provides a background for his interpretation of Scripture.
Role of Glutathione in the Morphogenesis of the Bacterial Spore Coat

There is a marked increase in the half-cystine content of bacterial spores, especially the coat layers at the time of formation of the outer coat. When a cysteine auxotroph of Bacillus cereus T is grown on limiting cysteine, the spores contain the normal content of half-cystine, suggesting an alternate source. Glutathione appears to be such a supply of cysteine since it is hydrolyzed during sporulation and there are increased activities of the hydrolyzing enzymes at the same time. In addition, a cysteine auxotroph with a second alteration, a temperature-sensitive glutathione disulfide reductase, produces lysozyme-sensitive spores at 40 C. These spores appear to be defective in the formation of outer spore coat. During sporulation at 40 C, the double mutant accumulates oxidized glutathione which is a poor substrate for the hydrolytic enzymes. As a result, sporulating cells are deficient in half-cystines which are essential for outer spore coat morphogenesis. This alteration can be overcome by a shift to 30 C or by addition of cystinyl-pencillamine or cysteinyl-glycine to cultures sporulating at 40 C.
Identifying Magnitudes and Locations of Multiple Loads and the Resultant of a Distributed Load on a Slender Beam Using Strain Gage Based Methods

Unique strain gage based methods are developed to identify magnitudes and locations of multiple loads and the resultant of a distributed load on a slender beam. Four uniaxial strain gages mounted to the bottom surface of the beam create a force transducer capable of identifying the magnitude and location of a load inside the weight area, where the load can be a concentrated or distributed load. For the case of multiple loads separated by two or more strain gage locations, uniaxial strain gages forming multiple force transducers can still identify the magnitudes and locations of all the loads. However, this creates an ill-posed problem for loads separated by only one strain gage location. A new method has been developed using two shear gages mounted on the neutral axis of the beam, one on each side of a load, to identify the magnitude of the load in this case. A combination of two uniaxial strain gages and two shear gages, with one uniaxial strain gage and one shear gage at the same location on each side of a load, can be used to identify the location of the load. The strain gage based methods are experimentally validated on a prismatic beam with rest boundary conditions.
Diagnostic screening for mucopolysaccharidoses types I–VII by fluorophore‐labelled carbohydrate PAGE

Proteoglycans, constituents of the extracellular matrix of various tissues, are proteins that contain covalently linked glycosaminoglycans (GAG). They are processed by proteases and endoglycosidases into highly sulphated, high-molecular-weight polysaccharides. In the lysosomes these GAG are degraded further, in a sequential manner, to lower-molecular-weight fragments and monomers by specific sulphatases and exoglycosidases acting on the non-reducing end of the GAG molecules. In the mucopolysaccharidoses (MPS), lysosomal degradation proceeds normally until a linkage is reached at the non-reducing terminus for which a specific enzyme is lacking. Sequential degradation stops at this point, resulting in the accumulation of chondroitin (CS a and c), dermatan (DS), heparan (HS) and keratan (KS) ; however, degradation by endoglycosidases continues. These enzymes produce the lower-molecular-weight fragments found in the urine and tissues of MPS patients. One can speculate that each of the enzyme deficiencies should present a different array of residual GAG fragments. The definitive diagnosis of the MPS rests upon the determination of specific enzyme activities ; however, these studies are restricted to a few specialized laboratories and are not amenable to general screening. For such purposes, methods should be rapid, reliably identify most of the MPS defects, and exclude normal patients from the numerous cases suspected on the basis of their clinical presentation. All the existing non-enzymatic screening methods for MPS are based on the detection of CS a and c, DS, HS and KS by thin-layer chromatography (TLC) and combined cellulose acetate gel electrophoresis (Dembure and Roesel 1991). It is the purpose of this communication to report a new screening protocol based on the detection of GAG fragments using fluorophore-assisted carbohydrate electrophoresis (GLYKO-FACE kit).
ORGANOMETALLIC DERIVATIVES OF OROTIC ACID. CO-LABILIZING ABILITY OF THE AMIDO GROUP IN CHROMIUM AND TUNGSTEN CARBONYL COMPLEXES

of M(CO)5THF with the tetraethylammonium salt of the corresponding acid or uracil. These complexes have been characterized in solution by IR and 13C NMR spectroscopy and in the solid state by X-ray crystallography. The geometry of the metal dianions in 1 and 2 is that of a distorted octahedron consisting of four carbonyl ligands and a nearly planar five-membered orotate chelate ring, bound through the N1 and one of its carboxylate oxygen atoms. The uracil ring, including the exocyclic oxygens, itself deviates from planarity by only 0.009 A. However, the structure of complex 3, which closely resembles that of complexes 1 and 2, has a puckered uracil ring. The structure of complex 4 consists of the uracilate ligand bound through the deprotonated N1 to a tungsten pentacarbonyl fragment. Although the orotate complexes are resistant to thermal decarboxylation, they readily undergo decarbonylation reactions. In this regard, quantitative investigations of the lability of the carbonyl ligands on complexes 1-4 have been carried out. All complexes exhibited a low energy barrier for CO dissociation as demonstrated by 13 CO exchange studies. For example, the first-order rate constants for intermolecular CO exchange in complexes 2 and 3 were measured to be 6.05 10 -4 and 3.17 10 -3 s -1 at 0 °C, respectively. This facile CO dissociation is attributed to competition of the metal center with the uracil ring for the ﷿ donation of electron density from the deprotonated N1 atom of the orotate ligand. As expected, this interaction is enhanced when the pseudoaromaticity of the uracil ring is disrupted in complex 3. The activation parameters for the intermolecular exchange of CO in complex 2 were determined to be ¢H q ) 63.2 ( 3.8 kJ/mol and ¢S q )- 82.8 ( 13.0 J/mol‚K, values consistent with a bond-making/bond-breaking (M‚‚‚CO/M CN) mechanistic pathway. The rate of intermolecular CO exchange was similarly examined in complex 4. The uracilate ligand displayed a ﷿ donating capability comparable to that seen for chloride in the W(CO)5Cl - anion but much less ﷿ donor character than the phenoxide ligand in W(CO)5OPh - . The activation parameters of the CO exchange process in complex 4 were found to be ¢H ‡ ) 106.9 ( 4.3 kJ/mol and ¢S q ) 16.3 ( 13.7 J/mol‚K.
Synthesis of bi-substrate state mimics of dihydropteroate synthase as potential inhibitors and molecular probes.

The increasing emergence of resistant bacteria drives us to design and develop new antimicrobial agents. Pursuant to that goal, a new targeting approach of the dihydropteroate synthase enzyme, which serves as the site of action for the sulfonamide class of antimicrobial agents, is being explored. Using structural information, a new class of transition state mimics has been designed and synthesized that have the capacity to bind to the pterin, phosphate and para-amino binding sites. The design, synthesis and evaluation of these compounds as inhibitors of Bacillus anthracis dihydropteroate synthase is described herein. Outcomes from this work have identified the first trivalent inhibitors of dihydropteroate synthase whose activity displayed slow binding inhibition. The most active compounds in this series contained an oxidized pterin ring. The binding of these inhibitors was modeled into the dihydropteroate synthase active site and demonstrated a good correlation with the observed bioassay data, as well as provided important insight for the future design of higher affinity transition state mimics.
POTENTIATION BY ENALAPRILAT OF FENOLDOPAM-EVOKED NATRIURESIS IS DUE TO BLOCKADE OF INTRARENAL PRODUCTION OF ANGIOTENSIN-II IN RATS

We have previously shown that the natriuretic response to DA-1 receptor agonist fenoldopam is markedly potentiated by angiotensin converting enzyme inhibitor captopril. Since inhibition of angiotensin converting enzyme can lead to decreased production of angiotensin-II and increased levels of kinins (e.g., bradykinin), it is likely that both of these mechanisms might be involved in this phenomenon. However, it is not known whether and to what degree the accumulation of kinins contributes to the overall potentiation of natriuretic response to fenoldopam seen during angiotensin converting enzyme inhibition. In the present study, we have examined the effect of angiotensin converting enzyme inhibitor enalaprilat and angiotensin-II receptor antagonist losartan as well as bradykinin-2 receptor antagonist HOE 140 on fenoldopam-induced natriuresis. Intravenous infusion of fenoldopam (1 μg/kg/min) for 30 min produced significant increases in urine output and urinary sodium excretion without causing any changes in glomerular filtration rate, renal blood flow and mean arterial blood pressure, a phenomenon suggestive of a direct tubular site of action. In animals treated with either the angiotensin converting enzyme inhibitor enalaprilat or angiotensin-II receptor antagonist losartan, the diuretic and natriuretic effects of fenoldopam were potentiated to a similar degree. Whereas no significant changes in glomerular filtration rate occurred when fenoldopam alone was given to control rats, in animals treated with either enalaprilat or losartan, fenoldopam produced a modest but significant increase in glomerular filtration rate. In a separate group of animals, the effects of bradykinin-2 receptor antagonist HOE 140 on potentiation of fenoldopam-induced natriuresis by enalaprilat was examined. It was found that the magnitude of changes in urine output, sodium excretion and glomerular filtration rate in animals receiving pretreatment with both enalaprilat and HOE 140 were similar to those with enalaprilat pretreatment alone. These findings suggest that the potentiation of natriuretic response to fenoldopam by enalaprilat is solely due to blockade of angiotensin-II production and kinins do not appear to contribute to this phenomenon.
Some features of base pair mismatch repair and its role in the formation of genetic recombinants

For the formation of recombinants involving closely linked markers, two distinct processes play a role. The recombinational interaction between homologous DNA molecules results in the presence of heteroduplex DNA joining the parental components of the recombinant. The presence of markers distinguishing the parents in the region of heteroduplex DNA can result in base pair mismatches. The post recombination repair of such mismatches can contribute to the separation of closely linked markers. The processes responsible for such repair also play roles in mutation avoidance. The specificities, functions and contribution to the formation of recombinants for closely linked markers of the processes inEscherichia coli are described.
Evidence for two ferryl species in chloroperoxidase compound II.

Using a combination of density functional calculations and Mossbauer spectroscopy, we have examined chloroperoxidase compound II (CPO-II). The Mossbauer spectrum of CPO-II suggests the presence of two distinct ferryl species in an ∼70:30 ratio. Density functional calculations and cryogenic reduction and annealing experiments allow us to assign the major species as an Fe(IV)OH intermediate. The Mossbauer parameters of the minor component are indicative of an authentic iron(IV)oxo species, but we have found the 70:30 ratio to be pH invariant. The unchanging ratio of component concentrations is in agreement with CPO-II's visible absorption spectrum, which shows no change over the enzyme's range of pH stability.
Correlating the excited state relaxation dynamics as measured by photoluminescence and transient absorption with the photocatalytic activity of Au@TiO2 core–shell nanostructures

The spectroscopic and photocatalytic properties of a series of Au@TiO2 core–shell nanostructures are characterized. The crystallinity of the TiO2 shells was varied by changing the etching and calcination conditions. Measurements of the photoluminescence, transient absorption, and H2 production rate permit us to look for correlations between the spectroscopic and catalytic behaviors. We found that there is a strong effect of crystallinity on the H2 production rate and also the stretched exponential lifetime of the photoluminescence created by short-wavelength (266 and 300 nm) photoexcitation. As the TiO2 crystallinity is increased, the photoluminescence lifetime increases from 22 to 140 ps in a 1 ns detection window, while the H2 production rate increases by a factor of ∼4. There is no discernible effect of crystallinity on the photoluminescence dynamics excited at 350 or 430 nm, or on the electronic dynamics measured by femtosecond transient absorption after excitation at 300 nm. We hypothesize that high-energy photons create reactive and emissive charge-separated states in parallel, and that both species are subject to similar electron–hole recombination processes that depend on sample crystallinity. Based on our observations, it can be concluded that the photoluminescence dynamics may be used to evaluate the potential performance of this class of photocatalysts.
Rape Myths: History, Individual and Institutional-Level Presence, and Implications for Change

Rape myths, which are present at both the individual and institutional/societal levels, are one way in which sexual violence has been sustained and justified throughout history. In light of an increasing accumulation of rape myth research across a variety of disciplines, this paper proposes to use a feminist lens to provide an overview of the historical origins of rape myths, to document the current manifestations of these myths in American society, and to summarize the current body of research literature. We focus on the history of several specific rape myths (i.e., “husbands cannot rape their wives,” “women enjoy rape,” “women ask to be raped,” and “women lie about being raped”) and how these particular myths permeate current legal, religious, and media institutions (despite their falsehood). The paper concludes with suggestions for further research and describes how existing evidence could be used to aid in eradicating rape myths at both the individual and institutional levels.
Dichotic word-perception of aphasic and normal subjects.

The present investigation examined the role of the right cerebral hemisphere in linguistic perception following a left cerebral insult which had resulted in aphasia. Auditory dichotic procedures we...
Prediction of Stability in Pharmaceutical Preparations XII: Solvolysis of various alkyl sydnones

The kinetics of solvolysis of various alkyl sydnones—furfuryl, methyl, propyl, phenethyl, isopropyl, s -butyl, t -butyl, and 1,1,3,3 tetramethylbutyl, have been studied spectrophotometrically as a function of pH and temperature; rate-pH profiles have been determined. The order of reactivity on alkaline catalyzed solvolysis generally decreased in the order cited. Except for the furfuryl sydnone, the order of reactivity reversed on acid catalyzed solvolysis. The heats of activation for a specific type solvolysis were generally similar, and the greatest differences were in the entropies of activation. Only in the specific cases of 1,1,3,3-tetramethylbutyl, t -butyl, and furfuryl sydnones was a solvent or pH-independent solvolysis observed. In the alkaline pH range, the spectra shifts to that of the N -nitroso alkylamino acetic acid, whereas in acid solution absorbance is lost with time.
The anodization products of tantalum in the fused LiClKCl eutectic

Abstract Voltammetry, cyclic voltammetry and chronopotentiometry of Ta in the LiClKCl eutectic melt showed that anodization of Ta metal produces Ta(V), Ta(IV) and a lower state (probably Ta(II)). Ta(V) slowly volatilized from the melt at 450°C. The Ta(V) ⇌ Ta(IV) redox reaction is reversible with an approximate E ° = −0·67V. Both Ta(IV) and Ta(II) are reduced to solid products, probably to the metal, in the vicinity of −1·7 and −2·2 volts (all potentials vs standard Pt(II) Pt/(0)). Spectra show that Ta(V) in the melt is present as [TaCl 6 ] − .
Differential Expression of a Sodium-Phosphate Cotransporter Among Vibrio vulnificus Strains

Vibrio vulnificus is an estuarine bacterium with pathogenic potential. Its three known biotypes differ in host distribution. We have found the nptA gene for a sodium-phosphate cotransporter, which is rare in bacteria, in each biotype. nptA transcript abundance differed significantly among biotypes, leading to the hypothesis that transcript levels differ under environmental conditions associated with estuarine and host environments. nptA transcript abundance was assessed in V. vulnificus biotypes 1 (C and E genotypes), 2 and 3 strains under varied salinity, phosphate concentration, and pH. Differences in transcript abundance separated strains into two groups. Type C and biotype 3 strains formed Group 1, while type E and biotype 2 strains formed Group 2. Group 2 strains had significantly greater nptA RNA transcript abundance than Group 1. Transcript abundance in the two groups also responded differently to pH and salinity, suggesting differential regulation of nptA in response to environmental conditions. Comparison of the deduced amino acid sequences of NptA among strains resulted in strain grouping similar to that based on transcript abundance. Variation in transcript abundance between groups may affect the ability of V. vulnificus strains to colonize hosts and/or to compete as free-living bacteria in various habitats.
Fast H 2 -based integral equation solvers with an optimal H 2 -representation for large-scale electromagnetic analysis

We propose an algorithm to construct an optimal H2-based representation of integral operators, which has both optimized H2-partition and minimized rank, for accelerating integral equation based solutions of large-scale electromagnetic problems. The computational cost of this algorithm is small, since the cost associated with each admissible block depends on the block rank only. The proposed algorithm is also kernel independent. With the proposed H2-representation, both H2-based fast direct and iterative solvers are developed. They significantly outperform state-of-the-art H2-based solvers in computational efficiency without sacrificing accuracy.