cssi/SciSciGPT-SciSciNet huggingface dataset:
Estrogen Reverses HDAC Inhibitor-Mediated Repression of Aicda and Class-Switching in Antibody and Autoantibody Responses by Downregulation of miR-26a.

Estrogen contributes to females' strong antibody response to microbial vaccines and proneness to autoimmunity, particularly antibody-mediated systemic autoimmunity, in females. We have hypothesized that this is due to estrogen-mediated potentiation of class switch DNA recombination (CSR) and somatic hypermutation (SHM). As we have shown, estrogen boosts AID expression, which is critical for both CSR and SHM, through upregulation of HoxC4, which together with NF-κB critically mediates Aicda (AID gene) promoter activation. We contend here that additional regulation of Aicda expression by estrogen occurs through epigenetic mechanisms. As we have shown, histone deacetylase inhibitors (HDIs) short-chain fatty acid (SCFA) butyrate and propionate as well as the pharmacologic HDI valproic acid upregulate miRNAs that silence AID expression, thereby modulating specific antibody responses in C57BL/6 mice and autoantibody responses in lupus-prone MRL/Fas lpr/lpr mice. Here, using constitutive knockout Esr1 -/- mice and B cells as well as conditional knockout Aicda cre/cre Esr1 flox/flox mice and B cells, we showed that the HDI-mediated downregulation of Aicda expression as well as the maturation of antibody and autoantibody responses is reversed by estrogen and enhanced by deletion of ERα or E2 inhibition. Estrogen's reversion of HDI-mediated inhibition of Aicda and CSR in antibody and autoantibody responses occurred through downregulation of B cell miR-26a, which, as we showed, targets Aicda mRNA 3'UTR. miR-26a was significantly upregulated by HDIs. Accordingly, enforced expression of miR-26a reduced Aicda expression and CSR, while miR-26a-sponges (competitive inhibitors of miR-26a) increased Aicda expression and CSR. Thus, our findings show that estrogen reverses the HDI-mediated downregulation of AID expression and CSR through selective modulation of miR-26a. They also provide mechanistic insights into the immunomodulatory activity of this hormone and a proof-of-principle for using combined ER inhibitor-HDI as a potential therapeutic approach.
A mobile app to capture EPA assessment data: Utilizing the consolidated framework for implementation research to identify enablers and barriers to engagement.

Mobile apps that utilize the framework of entrustable professional activities (EPAs) to capture and deliver feedback are being implemented. If EPA apps are to be successfully incorporated into programmatic assessment, a better understanding of how they are experienced by the end-users will be necessary. The authors conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify enablers and barriers to engagement with an EPA app. Structured interviews of faculty and residents were conducted with an interview guide based on the CFIR. Transcripts were independently coded by two study authors using directed content analysis. Differences were resolved via consensus. The study team then organized codes into themes relevant to the domains of the CFIR. Eight faculty and 10 residents chose to participate in the study. Both faculty and residents found the app easy to use and effective in facilitating feedback immediately after the observed patient encounter. Faculty appreciated how the EPA app forced brief, distilled feedback. Both faculty and residents expressed positive attitudes and perceived the app as aligned with the department’s philosophy. Barriers to engagement included faculty not understanding the EPA framework and scale, competing clinical demands, residents preferring more detailed feedback and both faculty and residents noting that the app’s feedback should be complemented by a tool that generates more systematic, nuanced, and comprehensive feedback. Residents rarely if ever returned to the feedback after initial receipt. This study identified key enablers and barriers to engagement with the EPA app. The findings provide guidance for future research and implementation efforts focused on the use of mobile platforms to capture direct observation feedback.
Baring Teeth or Bearing Teeth?: Stereotypical Visual Representations in Informational Picturebooks

Informational picturebooks aim to provide information and facts to child readers. However, few studies investigated how informational picturebooks portray and describe animal subjects. The current ...
A dental filling composite resin restorative with improved antibacterial function and hardness

A novel antimicrobial dental composite resin has been developed and evaluated. Alumina filler particles were covalently coated with an antibacterial resin and blended into a composite resin formula...
Do U.S. Faith-Based Social Service Organizations Resist Collaboration? Examining the Role of Religiosity and Operational Capacity in Interorganizational Partnerships:

Although nonprofit collaboration is commonplace, recent research suggests that faith-based organizations (FBOs) are less likely to collaborate than other nonprofits. This study builds on prior FBO,...
COVID-19: The Use of 3D Printing to Address PPE Shortage during a Pandemic—A Safety Perspective

The COVID-19 pandemic created a global health crisis that impacted the supply of personal protective equipment and created a shortage of much-needed face shields and masks for essential workers. During this time, a community of manufacturers, academic institutes, and hobbyists came together and tried to address the supply shortage by providing 3D-printed face shields and masks. Although the Secretary of U.S. Department of Human and Health Services and the Food and Drug Administration relaxed some of the liability and product regulations regarding 3D-printed medical supplies during the pandemic, the safety of 3D-printed face shields and masks is still a concern. In this Review, we have highlighted some of the safety concerns related to printing materials, design consideration, waste generation and disposal, intellectual property and manufacturing regulations, and the sanitization of 3D-printed personal protective equipment.
Imaging transient solidification behavior

Solidification processing offers the first opportunity to control microstructure, properties, and performance in metallic alloy components. Until recently, microstructural evaluations were limited to post-solidification characterization by destructive methods. We review the development of time-resolved, in situ imaging techniques capable of capturing solid–liquid interfacial evolution in metallic alloys with high spatial and temporal resolution under diverse solidification conditions relevant for applications ranging from conventional directional solidification, crystal growth, and casting, to welding and additive manufacturing. These experiments enable direct visualization of transient behaviors that would otherwise remain unknown, uniquely providing insights into the physics that impact microstructure and defect development, and strategies for microstructural control and defect mitigation. Understanding microstructural evolution and the characteristics that form under various solidification conditions is essential for the development of multiscale, experimentally informed predictive modeling. This is highlighted by solidification simulations that utilize in situ measurements of solidification dynamics from state-of-the-art experimental techniques.
Predicting Risk of Sport-Related Concussion in Collegiate Athletes and Military Cadets: A Machine Learning Approach Using Baseline Data from the CARE Consortium Study.

To develop a predictive model for sport-related concussion in collegiate athletes and military service academy cadets using baseline data collecting during the pre-participation examination. Baseline assessments were performed in 15,682 participants from 21 US academic institutions and military service academies participating in the CARE Consortium Study during the 2015–2016 academic year. Participants were monitored for sport-related concussion during the subsequent season. 176 baseline covariates mapped to 957 binary features were used as input into a support vector machine model with the goal of learning to stratify participants according to their risk for sport-related concussion. Performance was evaluated in terms of area under the receiver operating characteristic curve (AUROC) on a held-out test set. Model inputs significantly associated with either increased or decreased risk were identified. 595 participants (3.79%) sustained a concussion during the study period. The predictive model achieved an AUROC of 0.73 (95% confidence interval 0.70–0.76), with variable performance across sports. Features with significant positive and negative associations with subsequent sport-related concussion were identified. This predictive model using only baseline data identified athletes and cadets who would go on to sustain sport-related concussion with comparable accuracy to many existing concussion assessment tools for identifying concussion. Furthermore, this study provides insight into potential concussion risk and protective factors.
Distinguishing Transdiagnostic versus Disorder-Specific Pathways between Ruminative Brooding and Internalizing Psychopathology in Adolescents: A Latent Variable Modeling Approach.

Rumination is correlated with diverse types of internalizing problems, but the extent to which it relates to a higher-order internalizing spectrum versus disorder-specific pathology is unclear. Using a quantitative model of the internalizing dimension, we compared the strength of transdiagnostic versus diagnosis-specific pathways from brooding—the most depressogenic component of rumination—to major depressive disorder (MDD) in adolescents. Community-recruited mid-adolescents (N = 241, Mage = 15.90 years, 53% female) completed semi-structured interviews of anxiety and depressive conditions and a self-report brooding measure. Confirmatory factor analysis revealed good fit for a one-factor model of internalizing conditions. Results revealed a large, significant factor correlation between brooding and the internalizing factor (r = 0.55), with some evidence for a more modest specific link between brooding and the unique component of the MDD diagnosis (r = 0.17; approximately one-third as large as the transdiagnostic pathway). These cross-sectional associations were generally consistent across two assessment waves separated by 19 months. We concluded that brooding is better conceptualized as a common characteristic of all internalizing problems in adolescence, rather than a specific feature of MDD. Preregistered hypotheses, data analysis code, and correlation matrices for this study are posted at https://osf.io/dax7u/ .
Epitranscriptomic Modifications Modulate Normal and Pathological Functions in CNS

RNA is more than just a combination of four genetically encoded nucleobases as it carries extra information in the form of epitranscriptomic modifications. Diverse chemical groups attach covalently to RNA to enhance the plasticity of cellular transcriptome. The reversible and dynamic nature of epitranscriptomic modifications allows RNAs to achieve rapid and context-specific gene regulation. Dedicated cellular machinery comprising of writers, erasers, and readers drives the epitranscriptomic signaling. Epitranscriptomic modifications control crucial steps of mRNA metabolism such as splicing, export, localization, stability, degradation, and translation. The majority of the epitranscriptomic modifications are highly abundant in the brain and contribute to activity-dependent gene expression. Thus, they regulate the vital physiological processes of the brain, such as synaptic plasticity, neurogenesis, and stress response. Furthermore, epitranscriptomic alterations influence the progression of several neurologic disorders. This review discussed the molecular mechanisms of epitranscriptomic regulation in neurodevelopmental and neuropathological conditions with the goal to identify novel therapeutic targets.
Reimagining Account and Allocation Management for Advanced Research Computing

Though they are the backbone of a center’s infrastructure and store some of its most vital information, often times, the databases responsible for tracking project allocations, job accounting, storage commitments, and other core center information aren’t designed with the proper attention and thought to scale and adapt with the center as it grows and changes. Off-the-shelf solutions for these data stores are limited, and come with their own assumptions. As the field of research computing and thus the demands on the center continue to evolve, so to must the accounting solutions be able to accommodate the changing mission and goals. Many centers develop their own solutions in house, which requires additional effort to build and maintain. In this work, we present a data model which attempts to provide a more generalized solution to this problem, as well as a feature-rich set of tools provided by leveraging the powerful and widely-used Django web framework and ORM, which we call OpenAcct. We explore other solutions to this data management problem including both vendor-provided and in-house developed options. We then discuss the details of the data model, before demonstrating the capabilities of the application layer. Finally, future plans for the project are discussed.
PROBABILISTIC EVALUATION OF LOADS

The loads that affect geotechnical designs are reviewed, characterizing the uncertainties in each load component. Probabilistic models for evaluating each component are examined. Whenever data are available, the level of variabilities and uncertainties associated with the effect of each component on the foundation is assessed. Satisfactory performance of a geotechnical system relies, in part, on a good understanding of the characteristics of the loads and environments to which the system is subjected. Uncertainties do exist in these factors. For dynamic loads due to earthquake excitation and wave action, both their magnitude and frequencies of occurrences over the expected duration of the system could not be known. The long-term stability of soil slope would also be dependent on stochastic fluctuation of the pore pressure due to seasonal variation and other temporal changes in the environment. (ASCE)
Transcription induces the formation of a stable RNA.DNA hybrid in the immunoglobulin alpha switch region.

We previously showed that the in vitro transcription of a negatively supercoiled plasmid containing the murine IgA switch region caused the formation of fewer supercoiled conformers of the plasmid due to the presence of a stable RNA.DNA hybrid. Here, we demonstrate that the RNA.DNA hybrid is approximately 140 nucleotides, and it forms regardless of the initial topological state of the transcription template. Transcription of the switch region in a relaxed closed circular plasmid generates positively supercoiled plasmid conformers that revert to their original relaxed state when treated with RNase H. Conformers that have incorporated a stable RNA transcript are also observed when nicked circular and linear plasmids containing the IgA switch sequences are transcribed with 32P-labeled nucleotide triphosphates. Once formed, the RNA.DNA hybrid is stable to both thermal and superhelical stress, tolerating temperatures in excess of 95 degrees C and restraining approximately 12 positive supercoils in the plasmid.
The Role of the Computer in Team Problem-Solving: Critiquing or Partial Automation?

A testbed was developed for studying the effects of different computer system designs on human-computer team problem-solving, using the real-world task of antibody identification. The computer inte...
An adaptive tracking controller for a brushless DC motor with reduced overparameterization effects

Using the integrator backstepping approach, the authors develop a full state feedback, adaptive position tracking controller for a brushless DC (BLDC) motor turning a robotic load. The proposed controller ensures global asymptotic tracking for the rotor position and velocity despite the parametric uncertainties throughout the entire electromechanical system. The overparameterization problem commonly associated with backstepping-type controllers is greatly reduced. Experimental results are used to validate the performance of the controller. >
The Chemistry and Biological Activities of the Natural Products AAl-Toxin and the Fumonisins

The fumonisins and AAL-toxin are structurally-related natural products produced by fungi (22, 23, 24). Fumonisin B1 [FB1] has been recognized since 1988 as a mammalian toxin (36, 37, 44, 52). More recently, FB1 has been shown to be a phytotoxin as well (1,2,3). AAL-toxin has been known to produce symptoms of stem canker disease on susceptible (asc/asc) tomatoes (9, 48, 56, 58). Our research has focused on evaluating the potential of the class of natural products defined by AAL-toxin and the fumonisims for the development of improved weed control agents. This work has involved the development of improved methods for the isolation, purification and characterization of these toxins. Useful methods have been developed for assessing phytotoxicity of these toxins with various weed species, and for estimating mammalian toxicity. A series of analogs has been obtained, either derivatizing the parent toxins or by de novo synthesis, and evaluated for phytotoxicity and mammalian cytotoxicity. Characterization of the toxins has included studies on their mode of action in plant tissue, their ability to act as sphingosine analogs and their stereochemistry.
Peyer's Patch Lymphocytes: Demonstration of the Integrity of Afferent and Efferent T-Cell Functions in the Guinea Pig and Rat

These studies reinforce the concept that Peyer's patch lymphocytes have the same immunologic potential as those in other peripheral lymphoid compartments.
Multi-kernel probability distribution regressions

This paper presents a multi-layer reproducing kernel Hilbert space (RKHS) approach for probability distribution to real and probability distribution to function regressions. The approach maps the distributions into RKHS by distribution embeddings and, then, constructs a multi-layer RKHS within which the multi-kernel distribution regression can be implemented using an existing kernel regression algorithm, such as kernel recursive least squares (KRLS). The numerical simulations on synthetic data obtained via Gaussian mixtures show that the proposed approach outperforms existing probability distribution (DR) regression algorithms by achieving smaller mean squared errors (MSEs) and requiring less training samples.
Social enterprise businesses: A strategy for creating good jobs for people with disabilities

Over the last ten years, there has been tremendous growth in social enterprise businesses, defined as nonprofit or forprofit business ventures that strive to achieve a quantifiable double bottom line of financial and social returns. In many cases, these are revenue-generating businesses run by nonprofit organizations that understand and already provide services to the individuals they would employ through the business. Social enterprise businesses are self-sustaining and adopt commercial strategies to increase their effectiveness. This approach has been particularly promising in creating new opportunities for individuals with disabilities in emerging industries and increasing employment of people with disabilities. The purpose of this article is to describe and profile two different models of social enterprise businesses funded by Kessler Foundation that employ people with disabilities in integrated settings earning market-driven pay rates.
Real-/spl mu/ bounds based on fixed shapes in the Nyquist plane: parabolas, hyperbolas, cissoids, nephroids, and octomorphs

In this paper we introduce new bounds for the real structured singular value. The approach is based on absolute stability criteria with plant-dependent multipliers that exclude the Nyquist plot from fixed plane curve shapes containing the critical point -1+j0. Unlike half-plane and circle-based bounds the critical feature of the fixed curve bounds is their ability to differentiate between the real and imaginary components of the uncertainty. Since the plant-dependent multipliers have the same functional form at all frequencies, the resulting graphical interpretation of the absolute stability criteria are frequency independent in contrast to the frequency-dependent off-axis circles that arise in standard real-/spl mu/ bounds.
Disk Entry: A Complication of Transforaminal Epidural Injection—A Case Report

Correctly identifying the etiology of low back pain can be challenging. The importance of making an expedient, accurate diagnosis of lumbar radicular pain cannot be overemphasized, as proper treatment is based on the outcome. The application of fluoroscopically guided, contrast enhancement during spinal injections is commonly performed, but is not without complications. Intradiskal placement of contrast dye during lumbar transforaminal epidural injection is important to identify, as serious potential complications, such as diskitis, may occur. Additionally, postprocedure assessment may not be accurate if contrast placement is not correctly identified. This case report reviews the literature on complications of transforaminal steroid injection and presents the first documentation of intradiskal placement of contrast dye in the United States. A 72-year-old man presenting with a right L4 radiculopathy underwent a fluoroscopically guided, contrast-enhanced lumbar transforaminal epidural steroid injection and experienced intradiskal placement of contrast as a complication of this procedure. Although the patient was treated prophylactically and achieved good results, the need for fluoroscopy and contrast enhancement during performance of spinal injections is reemphasized.
Regulation of Cerebral Artery Smooth Muscle Membrane Potential by Ca2+‐Activated Cation Channels

Arterial tone is dependent on the depolarizing and hyperpolarizing currents regulating membrane potential and governing the influx of Ca2+ needed for smooth muscle contraction. Several ion channels have been proposed to contribute to membrane depolarization, but the underlying molecular mechanisms are not fully understood. In this review, we will discuss the historical and physiological significance of the Ca2+-activated cation channel, TRPM4, in regulating membrane potential of cerebral artery smooth muscle cells. As a member of the recently described transient receptor potential super family of ion channels, TRPM4 possesses the biophysical properties and upstream cellular signaling and regulatory pathways that establish it as a major physiological player in smooth muscle membrane depolarization.
Comments on ‘Error in Economics: Toward a More Evidence-Based Methodology’ by Julian Reiss

We find prejudices in favor of theory, as far back as there is institutionalized science. Plato and Aristotle frequented the Academy at Athens. That building is located on one side of the Agora, or market place. It is almost as far as possible from the Herculaneum, the temple to the goddess of fire, the patron of the metallurgists. It is ‘on the other side of the tracks’. True to this class distinction, we all know a little about Greek geometry and the teachings of the philosophers. Who knows anything about Greek metallurgy? Yet perhaps the gods speak to us in their own way. Of all the buildings that once graced the Athenian Agora, only one stands as it always was, untouched by time or reconstruction. That is the temple of the metallurgists. The academy fell down long ago. It has been rebuilt–partly by money earned in the steel mills of Pittsburgh. (Hacking 1983)
Long-term variations in the surface air 7Be concentration and climatic changes.

Abstract We have used EML Surface Air Sampling Program (SASP) data to analyze the long-term trend in 7Be surface concentration and address possible correlation between this long-term trend and climatic changes, namely changes in precipitation patterns and temperature. In this paper we present 7Be concentration data from 23 sites, spanning over 25 years, all over the world, and extract long-term trend parameter using two independent techniques. The 7Be concentrations in most stations show a pronounced decreasing trend, potentially corresponding to statistically significant changes in transporting 7Be from upper atmosphere source to these sites. Weak negative correlation between 7Be concentration and amount of precipitation was also observed. However, more data from more representative sites around the world are needed the statistical robustness of this trend.
Reducing cardiovascular disease risk with diet.

Objective: Past research efforts to determine the influence of the diet on cardiovascular (CV) health have focused on the individual roles of specific dietary components with debatable success. Awareness of the impact and complexity of nutrient interactions has expanded in recent years to include assessment of dietary patterns as they contribute to lower CV disease risk. Research Methods and Procedures: In a series of multicenter studies, we compared a comprehensive, prepared meal plan, formulated to meet recommended intake levels of macro- and micronutrients, with a self-selected diet based on the exchange system. The three studies comprised adult participants with hypertension, hyperlipidemia, and type 2 diabetes (n = 560, 251, and 330, respectively). The first two studies (10 weeks) varied by the amount of contact with study personnel, and the third study assessed long-term effects over 52 weeks. Outcome measures included: blood pressure, lipid and lipoprotein levels, glycemic control, homocysteine, compliance, quality of life, and weight. Results: The first study demonstrated significant improvements in all measures, with greater improvements with the prepared meal plan compared with the self-selected diet. The second study, designed to parallel the contact frequency that would occur in a real world clinical setting, also produced significant improvements in multiple CV risk factors. In the long-term study, in addition to sustained improvements in risk factors, significant weight loss was achieved and maintained over the 52 weeks. Discussion: These trials demonstrate that regular consumption of a nutritionally complete diet offers multiple, concurrent clinical benefits for reducing CV disease risk and body weight.
Rotational viscosity of nematic liquid crystals A critical examination of existing models

Abstract A simple electro-optical method was developed to characterize the temperature dependent viscoelastic coefficient of six nematic liquid crystals with different conjugation lengths. Results were then used to test seven most frequently used models for rotational viscosity (y1). Computer results show that some models fit certain specific liquid crystals but, in general, two models fit all the experimental data. These two models are y 1 = α2 S 2 exp[E/k(T - T 0)] and y 1 = (α1 S + α2 S 2) exp (E/kT), with α1, α2 E, and T 0 as adjustable parameters.
Low HDL cholesterol, aggression and altered central serotonergic activity.

Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8±7.1) were assessed with the DSM-III-R, the Buss–Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown–Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and ‘high’ self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, ‘high’ feelings and increased ‘activation-euphoria’ following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense ‘high’ and ‘activation-euphoria’ responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.
Fe2+-Tetracycline-Mediated Cleavage of the Tn10 Tetracycline Efflux Protein TetA Reveals a Substrate Binding Site near Glutamine 225 in Transmembrane Helix 7

The TetA(B) protein (Fig. ​(Fig.1)1) encoded by the tetA(B) gene on Tn10 represents class B of a set of seven related TetA tetracycline efflux pumps from gram-negative bacteria (9, 20). All TetA proteins produce resistance to the antibiotic tetracycline, an inhibitor of protein synthesis, by exporting it out of the cell as a divalent cation chelate (48) in exchange for a proton (16, 45). Transcription of tetA is blocked by the repressor TetR and is inducible by low levels of tetracycline, which reversibly binds to and inactivates the repressor (12). TetA is located in the cytoplasmic membrane and has been extensively characterized in relation to its topology, structure, and the importance of various residues to its function (26, 39, 41, 46). FIG. 1. Model of TetA protein from Tn10. The protein has 401 residues. Transmembrane alpha helices are represented by gray rectangles numbered TM1, TM2, etc., which each span the membrane. The helices are connected by putative extramembrane loops; the boundaries ... Along with a few other well-studied transporters, such as lactose permease LacY (36), melibiose carrier MelB (2), sugar phosphate carrier UhpT (7), and glucose transporter GLUT1 (42), TetA is representative of transport proteins in the major facilitator superfamily, each typically having 12 transmembrane alpha helices configured as two related halves of six transmembrane helices each (30, 35). A model for LacY based on the average predicted tertiary structure of many such proteins has been proposed (see reference 5). A model for TetA has also been put forward (41). A trimeric structure for TetA has been seen in two-dimensional crystals at low (17 A) resolution (49). Possible substrate binding regions of TetA have been defined by mutations that alter substrate specificity or affinity (6, 38, 43, 46). Mutations at other regions that may be involved in substrate binding have also been described (17, 18, 41). However, the location of the TetA substrate binding site is not known. Chelated ferrous ion (Fe2+) in the presence of oxygen and reducing agent can lead to cleavage of an amide bond of a protein backbone, resulting in fragments with (in some cases) unblocked amino termini that can be sequenced (15, 31, 33). The cleavage sites indicate regions in close proximity to the Fe2+. This technique was used with Fe2+ chelated to tetracycline to map the inducer binding site in the tet repressor TetR (3). The results agreed with the location of the divalent cation in the Mg2+-tetracycline (MgTc) ligand obtained earlier by X-ray crystallography (3, 14), confirming the validity of the method. We now describe similar experiments on the TetA(B) efflux pump protein.
Sacroiliac Joint Dysfunction: Evaluation and Treatment

AbstractSacroiliac joint (SIJ) dysfunction is once again garnering attention as a treatable diagnosis for the millions of individuals suffering from acute and chronic low back pain. Theoretically, excessive or restricted motion at the SIJ can alter the mechanics of the spine and pelvis causing pain. Often the clinician's history and physical examination are nonspecific in the evaluation of low back pain and a high index of suspicion is required to consider SIJ dysfunction as the cause for the patient's symptoms. Multiple physical examination maneuvers exist to detect SIJ dysfunction, but none are individually sensitive or specific enough to diagnose SIJ dysfunction alone. The clinician should learn 3 to 5 tests that can easily be performed and replicated for the evaluation of SIJ dysfunction and use them consistently in patients presenting with low back pain. Sacroiliac joint anesthetic blocks using computed tomography (CT) or fluoroscopic-guided injection are considered the gold standards for diagnosing ...
Effects of amine-borane structure on the stoichiometry, rate and mechanism of reaction with hypochlorous acid: hydride oxidation versus B-chlorination

Abstract Various ring substituted benzylamine-boranes as well as α-methyl- and N -methylbenzylamine-borane undergo hydride oxidation and N-chlorination on reaction with NaOCl whereas N , N -dimethylbenzylamine-borane is subject to B-chlorination producing a mixture of amine chloroboranes. Results are consistent with previously established patterns of reactivity with alkyl- and non-aromatic heterocyclic secondary amine-boranes being subject to oxidation and their tertiary counterparts to B-chlorination. Current studies reveal the borane adducts of tertiary amines in the quinoline series to react via oxidative pathways. Ring or α-methyl substitution has a negligible effect on the rate of benzylamine-borane oxidation whereas N-methyl substitution causes a three-fold decrease. The benzylamine-borane reaction displays a modest substrate isotope effect ( k BH3 / k BD3 ≅1.3), a pronounced inverse solvent isotope effect ( k D2O / k H 2 O 3) and a pH dependence of rate that indicates saturation kinetics below pH 7.5. It is suggested that both oxidation and B-chlorination involve bimolecular rate-limiting attack of HOCl on amine-borane with different intimate mechanisms arising from correspondingly different activated complexes. A low reactivity of quinoline-monochloroborane with hypochlorite precludes the involvement of a chloroborane as a common intermediate in both processes. The activation free-energy for chlorination of trimethylamine-borane is higher than δ G ≠ values obtained for oxidation of isoquinoline-borane and for a series of benzylamine-boranes. Activation enthalpies are relatively low for both processes. Unlike the chlorination reaction where the entropy term is negligible, δ S ≠ for oxidation accounts for about 20–30% of the activation barrier. It is proposed that details of amine structure determine the mode of attack of amine-borane by HOCl with steric factors playing a dominant role.
Oxide shell reduction and magnetic property changes in core-shell Fe nanoclusters under ion irradiation

Ion irradiation effects are studied on the Fe-based core-shell nanocluster (NC) films with core as Fe and shell as Fe3O4/Fe3N. These NC films were deposited on Si substrates to thickness of ∼0.5 μm using a NC deposition system. The films were irradiated at room temperature with 5.5 MeV Si2+ ions to ion fluences of 1015 and 1016 ions/cm2. It is found that the irradiation induces grain growth, Fe valence reduction in the shell, and crystallization or growth of Fe3N. The film retained its Fe-core and its ferromagnetic properties after irradiation. The nature and mechanism of oxide shell reduction and composition dependence after irradiation were studied by synthesizing additional NC films of Fe3O4 and FeO + Fe3N and irradiating them under the same conditions. The presence of nanocrystalline Fe is found to be a major factor for the oxide shell reduction. The surface morphologies of these films show dramatic changes in the microstructures due to cluster growth and agglomeration as a result of ion irradiation.
Method of initial functions for axially symmetric elastic bodies

Abstract Method of initial functions for an axially symmetric state of stress in elasto-dynamic problems has been formulated which gives a complete choice in prescribing the boundary conditions in terms of either stresses or displacements, or a combination of stresses and displacements. The general dynamic response of the elastic body has been derived in the form of a set of transcendental partial differential equations from which the initial functions can be evaluated in terms of prescribed boundary conditions. The method is applied, as an illustration, to the flexural theory of circular plate subjected to antisymmetric lateral loads. Numerical examples of free vibrations of circular plates are given. The results are compared with solutions from classical theory.
Adjunctive gabapentin in treatment-resistant depression: a retrospective chart review.

Abstract Background: Previous studies in predominantly bipolar patients have suggested that gabapentin may be useful in treating mood disorders. This report describes its efficacy and tolerability as an adjunctive agent in treatment-resistant depression. Methods: A chart review was conducted on 27 outpatients presenting with a depressive disorder in whom gabapentin was added to ongoing treatment with a conventional antidepressant to which patients had not responded after at least 6 weeks. The majority of patients had either prominent anxiety or a history of soft bipolar features, but patients with bipolar I disorder were excluded. Clinical state and adverse effects were assessed retrospectively at each visit. Results: Mean gabapentin trial duration was 15.2±7.8 weeks, with a mean final dose of 904±445 mg/day (range, 300–1800 mg/day). Clinician-rated measures of clinical state improved significantly from baseline to endpoint. Overall, 37.0% (n=10) of patients were responders at endpoint; another 18.5% (n=5) manifested a transient response not sustained to endpoint. Gabapentin was well tolerated; the most common adverse effects were fatigue, sedation, dizziness, and gastrointestinal symptoms. Limitations: Treatment was uncontrolled and efficacy assessments were retrospective. Conclusion: These findings suggest that gabapentin may be of adjunctive benefit in the management of treatment-resistant depression.
Numerical simulations of multiphoton ionization and above-threshold electron spectra.

We study above-threshold ionization (ATI) of a one-dimensional model atom in a time-varying external laser field. The time-dependent Schr\"odinger equation is integrated in space and time using the Crank-Nicholson method, and the photoelectron energy spectrum is then computed by projecting the wave function onto the energy eigenstates of the time-independent zero-field Hamiltonian. We demonstrate an intensity-dependent ponderomotive shift of the ionization threshold, find a free-electron scaling of the number of ATI peaks with intensity and frequency of the field, and contrast the numerical simulations with two simple Keldysh-type models. For certain field parameters we encounter turn-on transients in the form of ``energy-nonconserving'' substructure within each ATI peak. Effects on the results of the physical parameters such as length and shape of the laser pulse on one hand, and of the iteration parameters on the other, are discussed in detail.
Intra-arterial thrombolysis for central retinal artery occlusion in United States: Nationwide In-patient Survey 2001-2003.

BACKGROUND Intra-arterial thrombolysis (IAT) has been used as a treatment modality for central retinal artery occlusion (CRAO). However, national estimates of such practice and associated outcomes are not available. We performed this study to determine the frequency and outcomes of thrombolysis among adult patients hospitalized in United States (US) for CRAO. METHODS We determined the rates, hospital outcomes, and hospital charges incurred for patients with CRAO treated with thrombolysis using Nationwide Inpatient Survey (NIS) and compared them with patients treated without thrombolysis. NIS is the largest all-payer inpatient care database in the US approximating a 20-percent stratified sample of US community hospitals. RESULTS There were 1379 admissions for primary diagnosis of CRAO in 2001-2003. IAT was used in 27(1.9%) of the patients with CRAO. There was no in-hospital mortality or intracranial hemorrhage reported among any patient with CRAO treated with thrombolysis. All patients treated with IAT were discharged home. IAT was exclusively used in urbanteaching hospitals. CONCLUSIONS There is potential of benefit from IAT in CRAO, which is only offered in certain centers. Clinical trials are needed to demonstrate this beneficial effect.
Health outcomes in women with physical and sexual intimate partner violence exposure.

Objective: To examine health outcomes in women with exposure to physical intimate partner violence (IPV), sexual IPV or sexual and physical IPV and the added health burden of sexual IPV. Methods: Randomly sampled insured women (2876) completed a telephone interview to assess lifetime exposure to physical IPV only, sexual IPV only, or physical and sexual IPV (Behavioral Risk Factor Surveillance System) and mental, social, and physical health (Short Form-36, Center for Epidemiologic Studies-Depression, Presence of Symptoms surveys). The first analysis compared the health of women with physical IPV, sexual IPV, or both physical and sexual IPV with the health of women with no IPV exposure. The second compared the health of women with sexual IPV only or physical and sexual IPV with the health of women with physical IPV only. Results: Compared to never abused women, pronounced adverse health effects were observed for women with sexual IPV exposure (with or without physical IPV). SF-36 scores ranged from 4.28 to...
Nephnologists’ and Internal Medicine Physicians’ Expectations of Renal Dietitians and General Dlinical Dietitians

Abstract Objective To document and compare nephrologists' and internal medicine physicians' expectations of renal dietitians and general clinical dietitians. Design Subjects completed a mailed survey. Respondents provided demographic information and used a 5-point Likert scale to note whether each of 14 job functions was appropriate for general clinical dietitians, renal dietitians, or both. Subjects Five hundred forty-one physicians registered with the Ohio State Medical Board (OSMB) were surveyed. Within this group were 283 nephrologists (the population of nephrologists registered with the OSMB) and 258 internal medicine physicians (selected randomly by the OSMB). A total of 133 physicians (25%) returned the survey; 119 surveys were usable: 70 from nephrologists and 49 from internists. Statistical analyses performed A composite variable was created by coding and summing physicians' responses regarding dietitian job functions. This variable was averaged for both physician categories. A t test was conducted to compare composite variable results between the two physician groups. Results At least 50% of nephrologists and internists agreed that both types of dietitians should conduct nutrition assessments, determine patients' energy needs, evaluate medication-nutrient interactions, recommend diet and tube-feeding orders, instruct patients about physician-ordered diets, and teach nutrition concepts to hospital interns. Few physicians agreed that either type of dietitian should order diets, tube feedings, or diet instructions. Applications/conclusions Clinical dietitians can educate physicians about dietitians' roles informally in their institutions and formally by supporting programs like The American Dietetic Association Physician Nutrition Education Program. In addition, dietetics educators can hone their students' communication and problem-solving skills to promote positive physician-dietitian interaction. J Am Diet Assoc. 1997;97:1389-1393.
Nonlinear pharmacokinetics of visnagin in rats after intravenous bolus administration

Ammi visnaga L. (syn. Khella, Apiaceae) preparations have traditionally been used in the Middle East for the treatment of kidney stone disease. Visnagin, a furanocoumarin derivative, is one of the main compounds of Ammi visnaga with potential effects on kidney stone prevention. To date, no information is available about the pharmacokinetic (PK) properties of visnagin. It was the aim of the study to characterize the PK properties of visnagin after intravenous (i.v.) bolus administration in rats and to develop an adequate model for the description of the observed data, including model parameter estimates. Therefore, three doses of visnagin (1.25, 2.5, and 5mg/kg) solubilized in 25% Captisol® were administered by i.v. bolus injection to male Sprague-Dawley rats. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Both non-compartmental and compartmental PK analyses were performed. A stepwise model building approach was applied including nonlinear mixed effect modeling for final model selection and to obtain final model estimates in NONMEM VI. The average areas under the curve (AUC(0-last)) after doses of 1.25, 2.5, and 5mg/kg were 1.03, 3.61, and 12.6 mg *h/l, respectively. The shape of the plasma concentration-time profiles and the observed disproportionate increase in AUC(0-last) with increasing dose suggested nonlinearity in the elimination of visnagin. A two-compartment Michaelis-Menten model provided the best fit with following typical values of the parameter estimates: 2.09 mg/(l*h) (V(max)), 0.08 mg/l (K(M)), 0.175 l (V(C)), 1.0 h⁻¹ (k₁₂), and 1.22 h⁻¹ (k₂₁). Associated inter-subject variability estimates (% CV) for V(max), K(M) and V(C) were 21.8, 70.9, and 9.2, respectively. Intra-subject variability (constant CV error model) was estimated to be 7.0%. The results suggest the involvement of a saturable process in the elimination of visnagin, possibly an enzyme or transporter system.
Dirac theory of nucleon-nucleus collective excitation

We obtain the relativistic distorted wave impulse approximation amplitude for nucleon-nucleus collective transitions using an eikonal formalism. The effect of the Darwin term is to suppress the upper-to-upper contribution and enhance the lower-to-lower compared with a nonrelativistic treatment. In collective transitions these combine in a way that results in a transition density proportional to the derivative of the total Dirac distortion including quadratic and spin-orbit pieces. This leads to the same phenomenologically successful relations between elastic and inelastic amplitudes as in the Schroedinger description for collective transitions and promises a better treatment of noncollective transitions. We comment on the vanishing of P-A in this treatment.