cssi/SciSciGPT-SciSciNet huggingface dataset:
Gender and the Culture of Computing in Applied IT Education

The "shrinking pipeline" of women who ascend through the ranks in computer science education programs and careers is by now a familiar problem. Women drop out at rates faster than men at all levels of educational and professional advancement, resulting in a gender gap that is especially pronounced at the highest levels of the computing workforce, and that has not narrowed appreciably at any level in over 20 years (Camp, 1997; ITAA, 2005; Vegso, 2005). Efforts to move more women into the pipeline at lower levels have met with limited success (cf. the Carnegie Mellon experience as reported by Margolis & Fisher, 2002); girls and women still express less interest than boys and men in studying computer science and in pursuing information technology (IT) careers (Bentson, 2000; Vegso, 2005). A reason often cited in the literature is the masculine culture of many computer science programs and IT workplaces, which is perceived by many women as alien and unwelcoming (Bentson, 2000; Spertus, 1991; Turkle, 1988). Even when institutions make efforts to treat women and men equally or accord women special consideration in admissions and hiring decisions, attitudes discouraging women from entering computing persist, both within the institutions and in society at large. Sometimes these attitudes are expressed overtly: underground "hacker" culture is notoriously antagonistic to women (Gilboa, 1996), and even mainstream computer aficionados respond with resistance and sexist jokes to proposals to recruit more girls and women to study computer science (Slashdot.org, 2005). Moreover, there is a widespread perception that computer experts are socially-isolated "geeks" or "nerds" obsessed with technology, a mode of being that women, who tend to be more socially oriented, find unappealing (Margolis & Fisher, 2002; Turkle, 1988). Fortunately, the situation for computer science does not tell the whole story. In the latter part of the 20
On Bishops, Popes, Councils, and Statutes

The founding of Saint John hospital by burgher citizens and the role played by several lay members of the community, from the duke, to the castellan, to the aldermen, led to serious anxieties by the bishop of Cambrai. Fearing that he was losing control and concerned about heterodoxy, the bishop introduced a set of statutes to the hospital guaranteeing his position and assuring proper reform at the institution. This chapter considers why the bishop reasserted his power in the greater context of European affairs, namely the major ecumenical councils of Lateran III and Lateran IV, and the more regional French councils of the thirteenth century. As a result, the hospital became linked to important networks that in turn allowed the hospital to prosper before mid-century.
High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer

Most triple negative breast cancers (TNBCs) are aggressively metastatic with a high degree of intra-tumoral heterogeneity (ITH), but how ITH contributes to metastasis is unclear. Here, clonal dynamics during metastasis were studied in vivo using two patient-derived xenograft (PDX) models established from the treatment-naive primary breast tumors of TNBC patients diagnosed with synchronous metastasis. Genomic sequencing and high-complexity barcode-mediated clonal tracking reveal robust alterations in clonal architecture between primary tumors and corresponding metastases. Polyclonal seeding and maintenance of heterogeneous populations of low-abundance subclones is observed in each metastasis. However, lung, liver, and brain metastases are enriched for an identical population of high-abundance subclones, demonstrating that primary tumor clones harbor properties enabling them to seed and thrive in multiple organ sites. Further, clones that dominate multi-organ metastases share a genomic lineage. Thus, intrinsic properties of rare primary tumor subclones enable the seeding and colonization of metastases in secondary organs in these models. It is unclear how intra-tumoral heterogeneity contributes to metastasis. Here the authors study the clonal dynamics of triple negative breast cancer metastasis using patient derived xenografts and demonstrate that primary tumor clones harbor properties that support seeding and colonization of multiple organs.
Correlates of exposure to phenols, parabens, and triclocarban in the Study of Environment, Lifestyle and Fibroids

We performed a cross-sectional analysis to identify correlates of urinary concentrations of seven phenols (bisphenols A, F, and S; 2,4-dichlorophenol; 2,5-dichlorophenol; benzophenone-3; triclosan), triclocarban, and four parabens (butyl, ethyl, methyl, and propyl). We analyzed baseline data from 766 participants in the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study of 1693 Black women aged 23–34 years residing in Detroit, Michigan (2010–2012). We collected data on demographic, behavioral, and anthropometric factors via telephone interviews, clinic visits, and self-administered questionnaires. For each biomarker, we used linear regression models to estimate mean differences in log-transformed, creatinine-corrected concentrations across factors of interest. Each biomarker was detected in >50% of participants. Median creatinine-corrected concentrations were the highest for methyl paraben (116.8 μg/g creatinine), propyl paraben (16.8 μg/g creatinine), and benzophenone-3 (13.4 μg/g creatinine). Variables most strongly associated with biomarker concentrations included season of urine collection, education, and body mass index (BMI). BMI was positively associated with bisphenol A and S and triclocarban concentrations and inversely associated with butyl and methyl paraben concentrations. In this cohort of Black women, exposure to phenols, parabens, and triclocarban was prevalent and several factors were associated with biomarker concentrations.
Business Models: How Firms Make Money

A business model is the story about how a business works and how all of its activities come together to produce a profit, that is, the business model is the way a firm makes money. Marketing is fundamental to a successful business model because the served market ultimately defines a business. This chapter describes the elements of business models, provides examples of business models, and explores the role of marketing in the identification and implementation of successful business models.
Smart Loads for Power Quality and Battery Lifetime Improvement in Nanogrids

Low-inertia power generation units make nanogrids vulnerable to voltage and power fluctuations leading to unreliable operation and stability deterioration. Smart load is a potential solution for dealing with these stability challenges and improving the power quality in nanogrids. This paper proposes a configuration and control scheme for smart loads to regulate the voltage of critical loads, and consequently compensate the active and reactive power imbalances between generation side and critical load demand in nanogrids. The proposed smart load is capable of mitigating voltage and power oscillations caused by load variations, fluctuations in power generation, abnormal grid conditions, etc. Moreover, implementation of the proposed smart load configuration results in size reduction and lifetime improvement of central battery bank in nanogrids. Several case studies are carried out to validate the viability of the proposed configuration and control scheme for smart loads.
Does Rebound Pain after Peripheral Nerve Block for Orthopedic Surgery Impact Postoperative Analgesia and Opioid Consumption? A Narrative Review

Regional anesthesia has been considered a great tool for maximizing post-operative pain control while minimizing opioid consumption. Post-operative rebound pain, characterized by hyperalgesia after the peripheral nerve block, can however diminish or negate the overall benefit of this modality due to a counter-productive increase in opioid consumption once the block wears off. We reviewed published literature describing pathophysiology and occurrence of rebound pain after peripheral nerve blocks in patients undergoing orthopedic procedures. A search of relevant keywords was performed using PubMed, EMBASE, and Web of Science. Twenty-eight articles (n = 28) were included in our review. Perioperative considerations for peripheral nerve blocks and other alternatives used for postoperative pain management in patients undergoing orthopedic surgeries were discussed. Multimodal strategies including preemptive analgesia before the block wears off, intra-articular or intravenous anti-inflammatory medications, and use of adjuvants in nerve block solutions may reduce the burden of rebound pain. Additionally, patient education regarding the possibility of rebound pain is paramount to ensure appropriate use of prescribed pre-emptive analgesics and establish appropriate expectations of minimized opioid requirements. Understanding the impact of rebound pain and strategies to prevent it is integral to effective utilization of regional anesthesia to reduce negative consequences associated with long-term opioid consumption.
Understanding the pH Dependence of Underpotential Deposited Hydrogen on Platinum

Understanding the pH dependent shift of the oxidation peak of the underpotential deposited hydrogen (Hupd ) in cyclic voltammograms on the Pt surface is of significance in terms of both the fundamentals of electrochemistry and the rational design of catalysts for the hydrogen oxidation/evolution reactions (HOR/HER). In this work, we provide compelling evidence that the pH dependent shift in the Hupd peak on Pt surfaces is driven by the structure of interfacial water rather than the specific adsorption of cations on the electrode surface. Combined cyclic voltammetric and surface enhanced spectroscopic investigations using an organic cation and crown-ether chelated alkali metal cations show that specific adsorption of metal and organic cations on the Pt surface at the conditions relevant to the HOR/HER is unlikely. The vibrational band corresponding to strongly bound water is monitored when the electrode potential is varied in the Hupd range in both acid and base.
Affect Estimation with Wearable Sensors

Affective states are associated with people’s mental health status and have profound impact on daily life, thus unobtrusively understanding and estimating affects have been brought to the public attention. The pervasiveness of wearable sensors makes it possible to build automatic systems for affect tracking. However, constructing such systems is a challenging task due to the complexity of human behaviors. In this work, we focus on the problem of estimating daily self-reported affects from sensor-generated data. We first analyze the intra- and inter-subject differences of self-reported affect labels. Second, we explore different machine learning models as well as label transformation techniques to overcome the individual differences in self-reported responses estimation. We conceptualize three experimental settings including long-term and short-term estimation scenarios. Our experimental results show that the mixed effects model and label transformation can yield better estimation of individual daily affect. This work poses the basis for future sensor-based individualized and real-time affective digital and/or clinical interventions.
Light Activated Anti-Fungal Properties of Imidazolium Functionalized Cationic Conjugated Polymers

Infections caused by pathogenic fungi, especially Candida albicans are a growing global challenge for public health. Current antifungal drugs have been administered commonly to treat Candida infect...
P-HIP: A Lightweight and Privacy-Aware Host Identity Protocol for Internet of Things

The host identity protocol (HIP) has emerged as the most suitable solution to uniquely identify smart devices in the mobile and distributed Internet-of-Things (IoT) systems, such as smart cities, homes, cars, and healthcare. The HIP provides authentication methods that enable secure communications between HIP peers. However, the authentication methods provided by the HIP cannot be adopted by the IoT devices with limited processing power because of the computation-intensive cryptographic operations involved in hash generation, signature validation, and session-key establishment. Moreover, IoT devices cannot utilize the HIP as is to communicate securely in the low power and lossy networks as there is a considerable communication overhead, such as packet fragmentation and reassembly, for exchanging certificates over a lossy link. Additionally, the use of static host identifiers makes IoT devices vulnerable to cyber espionage and user-targeted attacks. In this article, we propose an authentication scheme, P-HIP, that protects the identity privacy of an IoT device by enabling the device to compute and use unique host identifiers from networks to networks and sessions to sessions. To make the HIP suitable for resource-constrained IoT devices, P-HIP provides methods that unburden IoT devices from computation-intensive operations, such as modular exponentiation, involved in authentication and session-key exchange. Additionally, P-HIP minimizes the communication overheads for exchanging certificates in lossy networks. We implement a prototype of P-HIP on Contiki-enabled IoT that shows P-HIP can reduce computation costs, communication overheads, and the session-key establishment time when used by low-powered devices in a lossy network.
The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test.

Finding new antidepressant agents is of high clinical priority given that many cases of major depressive disorder (MDD) do not respond to conventional monoaminergic antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Recent findings of effective fast-acting antidepressants indicate that there are biological substrates to be taken advantage of for fast relief of depression and that we may find further treatments in this category. In this vein, the cholinergic system may be a relatively overlooked target for antidepressant medications, given its major role in motivation and attention. Furthermore, the classically engaged monoaminergic neurotransmitter systems in depression treatment—serotonin, norepinephrine, and dopamine—interact directly at times with cholinergic signaling. Here we investigate in greater detail how the cholinergic system may impact depression-related behavior, by administering widely ranging doses of the cholinesterase inhibitor drug, donepezil, to C57BL/6J mice in the forced swim test. First, we confirm prior findings that this drug, which is thought to boost synaptic acetylcholine, promotes depression-like behavior at a high dose (2.0 mg/kg, i.p.). But we also find paradoxically that it has an antidepressant-like effect at lower doses (0.02 and 0.2 mg/kg). Further this antidepressant-like effect is not due to generalized hyperactivity, since we did not observe increased locomotor activity in the open field test. These data support a novel antidepressant-like role for donepezil at lower doses as part of an overall u-shaped dose-response curve. This raises the possibility that donepezil could have antidepressant properties in humans suffering from MDD.
Mediated association between spirituality and life satisfaction in chronically ill undergraduate students

Preservation of life satisfaction in the face of a chronic illness is of major importance for psychosocial functioning. We addressed in this study how spirituality relates to global life satisfaction in young people with chronic physical illnesses. Based on social-cognitive theory, the transactional model of stress and coping, and Pargament’s theory of religious coping, a serial mediation model with general self-efficacy beliefs and proactive coping as related linkage variables was proposed. In a cross-sectional design, 304 undergraduate students with different chronic physical diseases completed an online survey. As expected, students higher in spirituality reported higher general self-efficacy beliefs, which subsequently related to better proactive coping and which then subsequently related to higher life satisfaction (Bserial = 0.04, SEserial = 0.02, 95% CI [0.01, 0.09]). There was also a specific indirect effect of spirituality on life satisfaction through self-efficacy beliefs only (Bspecific M1 = 0.12, SEspecific M1 = 0.04, 95% CI [0.05, 0.20]). In addition, a direct association of spirituality and life satisfaction was revealed (Bdirect = 0.15, SEdirect = 0.07, p = .039). Findings indicate an important role of spirituality in well-being. General self-efficacy beliefs and proactive coping were identified as key variables in the relation between spirituality and global life satisfaction.
Association Between Albumin Level and Mortality Among Cardiac Intensive Care Unit Patients.

Purpose:To study the effect of hypoalbuminemia on short- and long-term mortality in Cardiac Intensive Care Unit (CICU) patients.Methods:We reviewed 12,418 unique CICU patients from 2007 to 2018. Hy...
Detecting Adversarial Audio via Activation Quantization Error

The robustness and vulnerability of Deep Neural Networks (DNN) are quickly becoming a critical area of interest since these models are in widespread use across real-world applications (i.e., image and audio analysis, recommendation system, natural language analysis, etc.). A DNN’s vulnerability is exploited by an adversary to generate data to attack the model; however, the majority of adversarial data generators have focused on image domains with far fewer work on audio domains. More recently, audio analysis models were shown to be vulnerable to adversarial audio examples (e.g., speech command classification, automatic speech recognition, etc.). Thus, one urgent open problem is to detect adversarial audio reliably. In this contribution, we incorporate a separate and yet related DNN technique to detect adversarial audio, namely model quantization. Then we propose an algorithm to detect adversarial audio by using a DNN’s quantization error. Specifically, we demonstrate that adversarial audio typically exhibits a larger activation quantization error than benign audio. The quantization error is measured using character error rates. We use the difference in errors to discriminate adversarial audio. Experiments with three the-state-of-the-art audio attack algorithms against the DeepSpeech model show our detection algorithm achieved high accuracy on the Mozilla dataset.
Short Term Complications of the Latarjet Procedure - A Systematic Review

Purpose The purpose of this study is to evaluate the short-term complication rate following the open and arthroscopic Latarjet procedures and to meta-analyze the studies comparing the 2 approaches. Methods PubMed was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to find clinical and biomechanical studies comparing complication rates in open and arthroscopic Latarjet procedures. A literature search of MEDLINE, Embase, and the Cochrane Library was performed based on the PRISMA guidelines. Clinical studies reporting on the complications following the open or arthroscopic Latarjet were included. Meta-analysis was performed for comparative studies using Review Manager, version 5.3. A P value of Results Overall, 89 studies (Level of Evidence [LOE] I: 2, LOE II: 2, LOE III: 24, LOE IV: 61) met inclusion criteria, with 7175 shoulders. Following the open Latarjet procedure, the overall complication rate was 6.1%, with a 1.9% occurrence of graft-related complications, 1.1% hardware, 1.1% wound, 0.9% nerve, and 1.2% other complications. Following the arthroscopic Latarjet procedure, the overall complication rate was 6.8%, with a 3.2% occurrence of graft-related complications, 1.9% hardware, 0.5% wound, 0.7% nerve, and 0.5% other complications. Complications were reported in 7 studies comparing 379 patients treated with the open Latarjet and 531 treated with the arthroscopic Latarjet, with no statistically significant difference between the two (P = .81). Conclusion Our study established that the overall complication rate following the Latarjet procedure was 6%-7%, with the most common complication being graft-related. Furthermore, based on the current evidence, there is no significant difference in the complication rate between the open and arthroscopic Latarjet procedures.
Ultra-Sensitive and Selective Detection of DNA and Protein Biomarkers Using Frequency-Locked Microtoroid Optical Resonators

We use frequency-locked microtoroid optical resonators to detect protein and DNA biomarkers at attomolar to femtomolar concentrations, depending on the target. We measure binding affinities and validate our results against existing technologies.
Epitopedia: identifying molecular mimicry of known immune epitopes

Abstract Motivation Upon infection, pathogen epitopes stimulate the host’s immune system to produce antibodies targeting the pathogen. Molecular mimicry (structural similarity) between an infecting pathogen and host proteins or pathogenic proteins the host has previously encountered can impact the immune response of the host. The ability to identify potential molecular mimicry for a pathogen can illuminate immune effects with importance to pathogen treatment and vaccine design. Summary Epitopedia allows for identification of regions with three-dimensional molecular mimicry between a protein in a pathogen with known epitopes in the host. Results SARS-CoV-2 Spike returns molecular mimicry with 14 different epitopes including integrin beta-1 from Homo sapiens, lethal factor precursor from Bacillus anthracis, and pollen allergen Phl p 2 from Timothy grass. Availability Epitopedia is primarily written in Python and relies on established software and databases. Epitopedia is available at https://github.com/cbalbin-FIU/Epitopedia under the opensource MIT license and is also packaged as a docker container at https://hub.docker.com/r/cbalbin/epitopedia. Contact cbalbin@fiu.edu, jliberle@fiu.edu
Professional Preparation: Faculty Practices for NCLEX-RN® Success.

Davis proposed that there are three overlapping phases of a caring relationship to NCLEX-RN® preparation, grounded in Peplau’s theory. Faculty members’ perspectives on successful strategies related...
Evaluating changes in credit rating quality of U.S. farmer cooperatives

Abstract The default of a cooperative has significant implications on cooperative members and the agricultural supply chain. Therefore, monitoring and even predicting future changes in creditworthiness is of value to cooperative managers and their lenders. However, we know little about farmer cooperatives' credit profiles and behavior because their financial statements are seldom shared. Using a Moody’s credit rating model and a unique data set, this article estimates Markov chains to evaluate changes in farmer cooperatives’ credit quality. The unconditional (one-size-fits-all) probability matrix, as is typically estimated, is shown to not be appropriate in describing credit rating transitions. Results also show cooperatives do not exhibit rating change momentum since a downgrade is not likely to be followed by another downgrade in the next period. Credit ratings of farmer cooperatives with less than $20 million in net sales follow a first-order Markov chain with stationary probabilities and the cooperatives with net sales of more than $250 million follow a zero-order Markov chain. This article adds to the limited research available on the credit rating behavior of farmer cooperatives. Cooperative managers, directors, and lenders can utilize these findings to make more informed decisions to impact future credit ratings.
Kemp-Vincent Rally Test of Tennis Skill

Abstract The Kemp-Vincent Rally Test of tennis skill was constructed to overcome the criticisms of available tennis skills tests. The major criticisms have been that current tests do not measure skills under game conditions, require the use of special equipment or line markings, and the time involved in their administration is prohibitive. In the Kemp-Vincent Rally Test the students rally as in a game situation, a relatively short time period is involved, and no special equipment or court markings are needed. The validity of the Kemp-Vincent Rally Test was found to be .84 for beginners and .93 for intermediate players when correlated with round robin tournament rankings. When validated against the Iowa revision of the Dyer test, the validity coefficient was .80. Test-retest reliability coefficients were .86 for beginners and .90 for intermediate players.
A Conditional Mixture Model for Correlation Coefficients

Recall again the guiding concern is to characterize histograms of the form of Figure 1.1. A fundamental problem is to assess the variability of the population correlation coefficients underlying such histograms. That appears achievable. In addition, estimates can be given of the number of different ρ that a given data set can support. Once having determined the number of different ρ, maximum likelihood point estimates of each ρ can be obtained.
Isolation and Properties of a Ribosome-bound Factor Required for ppGpp and pppGpp Synthesis in Escherichia coli

Abstract A scheme for isolating the stringent factor, a factor which stimulates the pyrophosphorylation of GTP and GDP, from high salt extracts of ribosomes derived from stringent strains of Escherichia coli is reported. The stringent factor was purified 400-fold from the high salt-ribosome eluates. The final preparation was judged to be 85% homogeneous by sedimentation and electrophoretic criteria. The results of sodium dodecyl sulfate-gel ionophoresis and sedimentation analysis indicated that the factor is a protein consisting of a single polypeptide chain with a molecular weight of 77,000. In addition to the stringent factor, the conversion of GTP to the guanosine polyphosphates, ppGpp and pppGpp, was shown to require ATP, Mg2+, and ribosomes. The in vitro reaction was further characterized with respect to kinetic parameters, substrate specificity, and its sensitivity to known inhibitors of the in vivo synthesis of ppGpp. From measurements of stringent factor activity in fractions obtained by differential centrifugation of crude cell extracts it was concluded that essentially all of the factor in the extracts was bound to ribosomes. Extracts prepared from several different relaxed mutants were shown to be devoid of stringent factor activity. Evidence is presented that it is the stringent factor rather than the ribosomes which is impaired in these mutants. The implication of these results in relation to the function of the rel gene and the control mechanism underlying the stringent response is discussed.
Pericardial effusions in bacterial meningitis are not common.

We read with interest the paper entitled "The Frequency of Pericardial Effusions in Bacterial Meningitis" by Laird and colleagues (Pediatrics 63:764-770, 1979). In our view, the authors9 conclusions that "pericardial infection is common in patients with meningitis, but that it is usually of no clinical significance and resolves with antibiotic therapy" are unjustified from the evidence presented. It is well recognized that echocardiography is a sensitive method for detecting the presence of a pericardial effusion, but unfortunately, there are no echocardiographic features which define the etiology of the effusion.
The tragic vision of politics: Hans J. Morgenthau

The probing of the theorist of the moral pretension of the national interest puts him an awkward position by making him suspect of being indifferent to all truth and morality. This is why there are so many ideologies and so few theories. Hans J. Morgenthau Hans Morgenthau is the intellectual father of postwar realism and arguably the most important international relations theorist of his generation. His textbook went through six editions, one of them posthumous, and was almost universally read by undergraduate and graduate students of international relations over a span of three decades. Because of Morgenthau, realism became the dominant paradigm in the field and maintained this position throughout the Cold War. In the 1980s, neorealism gained wide currency, and graduate students increasingly read Kenneth Waltz in lieu of Morgenthau as their introduction to the study of international relations. In the aftermath of the Cold War, scholars interested in power and its consequences are looking to more traditional forms of realism for insights. Morgenthau and his ideas are once again timely and need to be put into historical and intellectual context for a new generation of readers. Like Thucydides and Clausewitz, Morgenthau has been misinterpreted. Critics misread his insistence on the enduring and central importance of power in all political relationships as an endorsement of European-style Realpolitik and its axiom that might makes right.
Multiple-camera/motion stereoscopy for range estimation in helicopter flight

Pilot aiding to improve safety and reduce pilot workload to detect obstacles and plan obstacle-free flight paths during low-altitude helicopter flight is desirable. Computer vision techniques provide an attractive method of obstacle detection and range estimation for objects within a large field of view ahead of the helicopter. Previous research has met considerable success by using an image sequence from a single moving camera in solving this problem. The major limitations of single camera approaches are that no range information can be obtained near the instantaneous direction of motion or in the absence of motion. These limitations can be overcome through the use of multiple cameras. This paper presents a hybrid motion/stereo algorithm which allows range refinement through recursive range estimation while avoiding loss of range information in the direction of travel. A feature-based approach is used to track objects between image frames. An extended Kalman filter combines knowledge of the camera motion and measurements of a feature's image location to recursively estimate the feature's range and to predict its location in future images. Performance of the algorithm will be illustrated using an image sequence, motion information, and independent range measurements from a low-altitude helicopter flight experiment.
Model Generation of Neural Network Ensembles Using Two-Level Cross-Validation

This research investigates cross-validation techniques for performing neural network ensemble generation and performance evaluation. The chosen framework is the Neural Network Ensemble Simulator (NNES). Ensembles of classifiers are generated using level-one cross-validation. Extensive modeling is performed and evaluated using level-two cross-validation. NNES 4.0 automatically generates unique data sets for each student and each ensemble within a model. The results of this study confirm that level-one cross-validation improves ensemble model generation. Results also demonstrate the value of level-two cross-validation as a mechanism for measuring the true performance of a given model.
The ovarian mesothelioma

Abstract Neoplasms arising from the surface or lining cells of the ovary are classically referred to under such general terms as cystadenocarcinoma, papillary carcinoma, and undifferentiated cancer. Evidence is presented in this discussion to support the thesis that such lesions are mesotheliomas, and that such a thesis can be defended embryologically, histologically, and clinically.
Activity of HMR3004 against Mycobacterium avium complex in vitro, in human macrophages and in beige mice

Objective To evaluate in vitro, in a cultured macrophage system and in beige mice, the potential therapeutic activity of HMR3004, a new ketolide, against organisms of the Mycobacterium avium complex (MAC). Methods The activity of HMR 3004 against MAC was evaluated in vitro (BACTEC) method) in the human macrophage system and in the beige mouse model. Results HMR3004 was inhibitory for 50% of 24 MAC strains at 8 mg/L and for 90% of the MAC strains at 16 mg/L by the radiometric macrobroth dilution method. The activity in vitro was improved if the MIC determination was carried out at pH 7.2 instead of pH 6.8. When tested in the macrophage system against three strains of MAC, HMR3004 showed inhibitory activity when used at 0.25 mg/L compared with untreated controls. Administration of HMR3004 to beige mice infected with MAC 101 strain caused significant reduction in the number of bacteria in the blood, liver and spleen. The reductions were dose-related, with 200 mg/kg per day for 4 weeks being more effective than 100 mg/kg per day or 50 mg/kg per day (although a dose-dependent relationship was not observed in mortality). Conclusion The ketolide HMR3004 has been shown to be active against MAC, and further assessment of both the therapeutic and prophylactic activity are warranted.
Maintenance of euglycemia is impaired in gluconeogenesis-inhibited iron-deficient rats at rest and during exercise

To evaluate the hypothesis that mild iron deficiency increases dependence upon gluconeogenesis, control and mildly iron-deficient (Hb = 80 +/- 2 g/L) rats were injected with mercaptopicolinic acid (MPA), a known inhibitor of gluconeogenesis, or with injection vehicle (sham) and studied at rest or after 30 min of treadmill running (13.4 m/min, 0% grade). Liver glycogen concentration was lower in resting iron-deficient rats than in resting control rats, but iron deficiency did not influence arterial substrates or hormones in sham-treated rats. Glucose and insulin concentrations were less in resting control and iron-deficient MPA-treated rats than in sham-treated animals. However, arterial lactate was greater in resting iron-deficient MPA-treated rats than control MPA-treated animals, and glucagon and epinephrine were greater in resting iron-deficient MPA-treated rats than in iron-deficient sham-treated animals, indicating that gluconeogenesis is more important to maintenance of euglycemia in resting iron-deficient animals than in controls. Moderate exercise stimulated glucose metabolism in iron-deficient rats, as evidenced by the lower arterial glucose and higher arterial lactate when compared with resting iron-deficient rats. However, MPA treatment did not clearly establish differences between iron-deficient and control rats after exercise. Therefore, changes in substrate and hormone concentrations in resting iron-deficient MPA-treated rats indicate that dependence on gluconeogenesis for maintenance of euglycemia is greater at rest with dietary iron deficiency. Furthermore, consistent with previously published results for severely iron-deficient rats, results from the present investigation indicate that dependence on glucose metabolism is greater during moderate exercise in mildly iron-deficient rats.
Comparison of an Interstitial Cystitis/Bladder Pain Syndrome Clinical Cohort with Symptomatic Community Women from the RAND Interstitial Cystitis Epidemiology Study

Purpose: The RAND Interstitial Cystitis Epidemiology survey estimated that 2.7% to 6.5% of United States women have urinary symptoms consistent with a diagnosis of interstitial cystitis/bladder pain syndrome. We describe the demographic and clinical characteristics of the symptomatic community based RAND Interstitial Cystitis Epidemiology cohort, and compare them with those of a clinically based interstitial cystitis/bladder pain syndrome cohort.Materials and Methods: Subjects included 3,397 community women who met the criteria for the RAND Interstitial Cystitis Epidemiology high sensitivity case definition, and 277 women with an interstitial cystitis/bladder pain syndrome diagnosis recruited from specialist practices across the United States (clinical cohort). Questions focused on demographic information, symptom severity, quality of life indicators, concomitant diagnoses and treatment.Results: Average symptom duration for both groups was approximately 14 years. Women in the clinical cohort reported wors...
Structure and Catalytic Properties of an Engineered Heterodimer of Enolase Composed of One Active and One Inactive Subunit

Enolase is a dimeric enzyme that catalyzes the interconversion of 2-phospho-D-glycerate and phosphoenolpyruvate. This reversible dehydration is effected by general acid-base catalysis that involves, principally, Lys345 and Glu211 (numbering system of enolase 1 from yeast). The crystal structure of the inactive E211Q enolase shows that the protein is properly folded. However, K345 variants have, thus far, failed to crystallize. This problem was solved by crystallization of an engineered heterodimer of enolase. The heterodimer was composed of an inactive subunit that has a K345A mutation and an active subunit that has N80D and N126D surface mutations to facilitate ion-exchange chromatographic separation of the three dimeric species. The structure of this heterodimeric variant, in complex with substrate/product, was obtained at 1.85 A resolution. The structure was compared to a new structure of wild-type enolase obtained from crystals belonging to the same space group. Asymmetric dimers having one subunit exhibiting two of the three active site loops in an open conformation and the other in a conformation having all three loops closed appear in both structures. The K345A subunit of the heterodimer is in the loop-closed conformation; its Calpha carbon atoms closely match those of the corresponding subunit of wild-type enolase (root-mean-squared deviation of 0.23 A). The kcat and kcat/Km values of the heterodimer are approximately half those of the N80D/N126D homodimer, which suggests that the subunits in solution are kinetically independent. A comparison of enolase structures obtained from crystals belonging to different space groups suggests that asymmetric dimers can be a consequence of the asymmetric positioning of the subunits within the crystal lattice.
Rapid electrodialytic clean-up of biological samples for high-performance liquid chromatography.

Abstract A sample clean-up system employing electrodialysis with size-selective and charge-selective membranes is described. When applied to the treatment of 0.5-ml milk samples containing sulfamethazine, the system produced an undiluted, clear solution in 3 rain and eliminated the components in untreated milk that caused column fouling and double peaks. In contrast to conventional liquid- and solid-phase extraction procedures, electrodialytic clean-up is readily automated and uses no organic solvents.
Apikal‐hypertrophe Kardiomyopathie – klinische und diagnostische Charakteristik anhand eines Fallberichtes

Zusammenfassung: Retrosternales Druckgefuhl und Schmerz mit Ausstrahlung in den Hals und zwischen die Schulterblatter ist neben Dyspnoe eines der haufigsten Symptome bei der nichtobstruktiven hypertrophen Kardiomyopathie. Eine Abgrenzung zu den im klinischen Alltag haufiger vorkommenden Krankheitsbildern wie koronare und hypertensive Herzkrankheit kann mittels nichtinvasiver diagnostischer Masnahmen gelegentlich schwierig sein und bedarf manchmal der Zuhilfenahme invasiver Untersuchungsmethoden. Wir berichten im Rahmen der folgenden Kasuistik von einer 77jahrigen Patientin mit einer mehrjahrigen Anamnese von Thoraxschmerz, wobei die sichere Diagnose einer apikal-hypertrophen Kardiomyopathie erst im Rahmen der Herzkatheteruntersuchung zu stellen war.
Buckling of spherical cap gridshells: A numerical and analytical study revisiting the concept of the equivalent continuum

Abstract The use of gridshell structures in architecture and structural engineering has risen in the past decade, yet fundamental research on the mechanics of such structures is lacking. The majority of gridshells built use either quadrilateral or triangular grids. In this paper, we assess the effect of the grid shape (triangular or quadrilateral), the grid spacing, and the span-to-height ratio on the failure load of spherical cap gridshells. The failure load is calculated using finite element methods and analytical methods derived from the equivalent continuum. Both a linear eigenvalue and a nonlinear analysis using geometric imperfections are performed and compared. While a triangular grid is expected to be greater in structural capacity, it is found that for shallower shells there is less of a structural advantage to using a triangular grid. Further, the triangular grid is highly sensitive to imperfections whereas a quadrilateral grid is not. The equivalent continuum defined by area equivalence provides a conservative estimate for the buckling load and multiple definitions of the equivalent continuum can be used to establish a practical design tool in the early phases of design. By understanding the fundamental mechanical behavior of gridshells, design guidelines aimed to maximize their capacity and efficiency and intended to facilitate the discussion between architect and engineer are proposed.
Synthesis and structures of two new mixed antimony-iron carbonyl clusters: [R4N][SbFe4(CO)16] (R = Me, Et) and [Et4N]2[Sb2Fe6(CO)20]

Abstract [R 4 N][SbFe 4 (CO) 16 ] ([R 4 N][I], R = Me, Et) was prepared by the oxidation of [R 4 N] 3 [SbFe 4 (CO 16 )] with two equivalents of [Cu(MeCN) 4 ][BF 4 ]. Single crystal X-ray diffraction of [Me 4 N][I] shows that it crystallizes in the triclinic centrosymmetric space group P 1 with a 11.840(3) A, b 12.550(3) A, c 10.500(2) A, α 94.41(2)°, β 101.14(2)°, γ 89.20(2)°, V 1526.3(6) A 3 and Z = 2. Full matrix least squares refinement on a basis of 5072 unique reflections led to R = 0.036, R w = 0.049. The anion has a highly distorted tetrahedral core in which the four-coordinate antimony atom is surrounded by two isolated Fe(CO) 4 units and an Fe 2 (CO) 8 group. Photolysis of [Et 4 N][I] with UV light gave as the only cluster product [Et 4 N] 2 [Sb 2 Fe 6 (CO) 20 ] ([Et 4 N] 2 [II]) which can also be prepared by the reaction of [Et 4 N] 2 [Fe 4 (CO) 13 ] with SbCl 3 . It crystallizes with 0.941(9) molecule of solvent CH 2 Cl 2 in orthorhombic accentric space group P 2 1 2 1 2 1 with a 15.962(6) A, b 25.878(6) A, c 10.035(2) A, V 5384(2) A 3 and Z = 4. The anion has a distorted trans -Sb 2 Fe 4 octahedral core in which each Sb atom is bonded to an external Fe(CO) 4 unit. Full matrix least squares refinement on a basis of 4007 unique reflections converged with R = 0.040 and R w = 0.049.
Evaluation of 6β-Hydroxycortisol, 6β-Hydroxycortisone, and a Combination of the Two as Endogenous Probes for Inhibition of CYP3A4 In Vivo

An endogenous probe for CYP3A activity would be useful for early identification of in vivo cytochrome P450 (CYP) 3A4 inhibitors. The aim of this study was to determine whether formation clearance (CL(f)) of the sum of 6β-hydroxycortisol and 6β-hydroxycortisone is a useful probe of CYP3A4 inhibition in vivo. In human liver microsomes (HLMs), the formation of 6β-hydroxycortisol and 6β-hydroxycortisone was catalyzed by CYP3A4, and itraconazole inhibited these reactions with half maximal inhibitory concentration (IC(50))(,u) values of 3.1 nmol/l and 3.4 nmol/l, respectively. The in vivo IC(50,u) value of itraconazole for the combined CL(f) of 6β-hydroxycortisone and 6β-hydroxycortisol was 1.6 nmol/l. The greater inhibitory potency in vivo is probably due to circulating inhibitory itraconazole metabolites. The maximum in vivo inhibition was 59%, suggesting that f(m,CYP3A4) for cortisol and cortisone 6β-hydroxylation is ~60%. Given the significant decrease in CL(f) of 6β-hydroxycortisone and 6β-hydroxycortisol after 200-mg and 400-mg single doses of itraconazole, this endogenous probe can be used to detect moderate and potent CYP3A4 inhibition in vivo.
Structure of Leishmania major methionyl-tRNA synthetase in complex with intermediate products methionyladenylate and pyrophosphate

Abstract Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions of people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 A resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg 2+ ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of Escherichia coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS–tRNA Met complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme.
Chemical and functional studies on the importance of purple membrane lipids in bacteriorhodopsin photocycle behavior

In native purple membrane (PM), there are approximately 1 squalene, 2 glycolipid sulfate (GLS), and 6 phospholipid (PL) molecules per bacteriorhodopsin (BR) monomer. Brief (approximately 2 min) exposure to 0.1% Triton X-100 removes about 25%, 20%, and 6% of squalenes, GLS, and PL, respectively (this paper) while causing profound changes in the BR photocycle, including the loss of 'photocooperativity'. The BR photocycle in Triton-treated PM can be restored to near normal behavior by reconstitution with native PM lipids. Isolated squalenes are not effective whereas PL alone partially restores normal photocycle characteristics.
Periods of Connected Networks and Powers of Nonnegative Matrices

Let P be an irreducible N × N matrix having nonnegative entries, and consider the directed network containing arc i, j if and only if Pij is positive. Theorem 1 expresses the period of this network in terms of any of its arborescences. Theorem 2 shows that if the network's period is one and if node i is contained in a cycle of length n, then the ith row and column of Pt are positive for t ≥ N-1n. Theorem 3 shows how to compute the network's period with work proportional to the number of its arcs.