cssi/SciSciGPT-SciSciNet huggingface dataset:
PSSP , a computer program for the crystal structure solution of molecular materials from X-ray powder diffraction data

This work describes the computer program PSSP (powder structure solution program) for the crystal structure solution of molecular solids from X-ray powder diffraction data. This direct-space structure solution program uses the simulated annealing global optimization algorithm to minimize the difference between integrated intensities calculated from trial models and those extracted in a Le Bail fit of the experimental pattern, using a cost function for dealing with peak overlap through defined intensity correlation coefficients, computationally faster to calculate than R{sub wp}. The methodology outlined is applicable to organic solids composed of moderately complex rigid and flexible molecules, using diffraction data up to relatively low resolution. PSSP performance tests using 11 molecular solids with six to 20 degrees of freedom are analyzed.
Molecular and cellular mechanisms of myocardial remodeling.

Myocardial remodeling is inextricably intertwined with the development and progression of heart failure. It is characterized by alterations in ventricular geometry and function. At the cellular level, ventricular remodeling consists of myocyte hypertrophy, neurohumoral activation, matrix remodeling, altered gene expression, immune system activation, and apoptosis. Many factors, including neurohormones, cytokines, growth factors, oxidative stress, and mechanical strain, can trigger the molecular and cellular events observed in remodeling, thus suggesting that they may play a role in myocardial remodeling. A thorough understanding of the cellular and molecular mechanisms involved in myocardial remodeling may lead to novel pharmacologic or genetic therapies for the treatment and prevention of heart failure.
Pathologic characteristics and composition of diet-aggravated atherosclerotic plaques during "regression".

Abstract Atherosclerosis of White Carneau pigeons was exacerbated by feeding an atherogenic diet for 1 yr. A subgroup of the birds was examined to determine the baseline extent and severity of atherosclerosis, the frequency of myocardial infarction, and the biochemical composition of the atherosclerotic lesions. The remaining birds were divided into groups to be examined at 2, 4, 8, 12, and 16 mo after changing the diet to one low in fat and free of cholesterol. The extensiveness of aortic atherosclerosis decreased for 8 mo and then remained unchanged through 16 mo. The free and esterified cholesterol concentration of plaques changed markedly during regression. Both decreased markedly for four months and then remained essentially unchanged for the remainder of the year. As the cholesterol content decreased the collagen content increased. The degree of stenosis from coronary artery atherosclerosis declined during the first 8 mo of regression and then remained essentially unchanged. The regression in coronary artery atherosclerosis was associated with a marked decrease in the frequency of myocardial infarction.
Measuring translational, rotational, and vibrational dynamics in colloids with digital holographic microscopy.

We discuss a new method for simultaneously probing translational, rotational, and vibrational dynamics in dilute colloidal suspensions using digital holographic microscopy (DHM). We record digital holograms of clusters of 1-μm-diameter colloidal spheres interacting through short-range attractions, and we fit the holograms to an exact model of the scattering from multiple spheres. The model, based on the T-matrix formulation, accounts for multiple scattering and near-field coupling. We also explicitly account for the non-asymptotic radial decay of the scattered fields, allowing us to accurately fit holograms recorded with the focal plane located as little as 15 μm from the particle. Applying the fitting technique to a time-series of holograms of Brownian dimers allows simultaneous measurement of six dynamical modes — three translational, two rotational, and one vibrational — on timescales ranging from 10−3 to 1 s. We measure the translational and rotational diffusion constants to a precision of 0.6%, and we use the vibrational data to measure the interaction potential between the spheres to a precision of ∼50 nm in separation distance. Finally, we show that the fitting technique can be used to measure dynamics of clusters containing three or more spheres.
Lipid Agonism, The PIP2 Paradigm of Ligand-Gated Ion Channels

Abstract The past decade, membrane signaling lipids emerged as major regulators of ion channel function. However, the molecular nature of lipid binding to ion channels remained poorly described due to a lack of structural information and assays to quantify and measure lipid binding in a membrane. How does a lipid–ligand bind to a membrane protein in the plasma membrane, and what does it mean for a lipid to activate or regulate an ion channel? How does lipid binding compare to activation by soluble neurotransmitter? And how does the cell control lipid agonism? This review focuses on lipids and their interactions with membrane proteins, in particular, ion channels. I discuss the intersection of membrane lipid biology and ion channel biophysics. A picture emerges of membrane lipids as bona fide agonists of ligand-gated ion channels. These freely diffusing signals reside in the plasma membrane, bind to the transmembrane domain of protein, and cause a conformational change that allosterically gates an ion channel. The system employs a catalog of diverse signaling lipids ultimately controlled by lipid enzymes and raft localization. I draw upon pharmacology, recent protein structure, and electrophysiological data to understand lipid regulation and define inward rectifying potassium channels (K ir ) as a new class of PIP 2 lipid-gated ion channels.
Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators

PPARγ coactivator 1α (PGC-1α) is a potent stimulator of mitochondrial biogenesis and respiration. Since the mitochondrial electron transport chain is the main producer of reactive oxygen species (ROS) in most cells, we examined the effect of PGC-1α on the metabolism of ROS. PGC-1α is coinduced with several key ROS-detoxifying enzymes upon treatment of cells with an oxidative stressor; studies with RNAi or null cells indicate that PGC-1α is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1α null mice are much more sensitive to the neurodegenerative effects of MPTP and kainic acid, oxidative stressors affecting the substantia nigra and hippocampus, respectively. Increasing PGC-1α levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1α is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins.
The Familial Occurrence of the Syndrome of Mid-Late Systolic Click and Late Systolic Murmur

Patients with late systolic murmurs, with and without mid-late systolic extra sounds, have recently been shown to have mitral regurgitation. This syndrome has been found to be familial in each of the four families we have studied. These families were found to have a high prevalence of mid-late systolic extra sounds, late systolic murmurs, pansystolic murmurs, abnormal electrocardiograms, and unexplained premature sudden death. The prognosis for these patients is unknown but is generally considered good. Periodic medical observation of these patients and their families seems warranted, however, in view of the current lack of knowledge concerning the cause of the chest pain, the rate of progression of the mitral regurgitation, the significance of the electrocardiographic abnormalities, the frequency of important arrhythmias, and the mechanism of sudden death. In addition, antibiotic prophylaxis to attempt to prevent bacterial endocarditis seems clearly indicated.
Psychological factors in the failed back

Pain is a complex phenomenon. Lack of understanding of its nature leads to two common mistakes in the failed back, firstly to look for a discrete physical cause and secondly to ascribe pain to psychological causes. This paper explores the nature of pain in the failed back and discusses the implications for treatment.
Stiffness-controlled three-dimensional extracellular matrices for high-resolution imaging of cell behavior

Stiffness-controlled three-dimensional extracellular matrices for high-resolution imaging of cell behavior
MITRE-Bedford ALEMBIC: MUC-4 test results and analysis

This note embodies our analyses of the performance of the ALEMBIC system in the MUC-4 evaluation task. These analyses have provided us with a reasonably good understanding of the principal factors contributing to the system's correct responses and to its errors. This understanding is based in part on interpretations of the performance measures provided by the MUC-4 scoring software; in addition, we performed a number of qualitative and quantitative investigations into linguistic aspects of the messages that underly the system's performance.
Who was Rumpelstiltskin

The author describes the way in which Rumpelstiltskin has perplexed and enthralled readers since the brothers Grimm recovered the tale from the realm of folklore. In standard translation, the story now lives in a fixed literary form and, consequently, in the imagination of every child who has ever heard or read the story--virtually every person in the English-speaking world. Therefore, deeply rooted in childhood experiences, Rumpelstiltskin can be expected to appear in analysis, and he does. The compelling central character is the title figure, Rumpelstiltskin, whose name and actions tell us who he is and what he was intended to 'mean'--especially to his contemplated audience. The original narrators of and listeners to this tale were female visitors to the evening spinning chamber (Spinnstube), where women gathered and told tales to amuse themselves to ward off sleep while they spun. The butt of this story is male impotence and bluster, and the key to the story's meaning arises from matching the etymological roots of the central character's name with his actions as they appear philologically and psychoanalytically.
Impact of proof validation on proof writing in abstract algebra

Many undergraduate students have difficulty writing mathematical proofs even though this skill is important for the development of future teachers and those who may be involved in instruction or training as a graduate student or supervisor. In addition, research indicates that mathematics majors and secondary education mathematics majors possess little ability to determine whether arguments are valid proofs. Asking students to validate proofs using specific activities may not only help undergraduates develop the ability to validate proofs, but also may help increase their own proof writing abilities. The purpose of this study was to investigate the effect of proof validation on the ability to write proofs. Two sections of abstract algebra were the focus of a ‘guided research’ study–one section was taught using a weekly proof validation activity and the other was taught as a control group. Data analysis revealed that the validation group significantly outscored the control group on items involving proof wr...
Delayed failure of a commercial vitreous bonded alumina

The static fatigue resistance of a commercial low-cost alumina is evaluated. Flexural stress rupture results are compared to fracture mechanics crack growth testing. The original goal of this work was to develop satisfactory experimental procedures for the two test methods prior to more extensive testing on high-performance ceramics such as silicon nitride. The static fatigue trends measured by the two methods are comparable at 1000° C. The results are consistent with a model of static fatigue involving microcrack growth, coalescence and fracture due to stress corrosion. Creep deformations are very small, suggesting that creep fracture is not the mechanism of failure. A refined method for double torsion testing is presented.
The role of the pharmaceutical industry in neurologic education.

Each year, the American Academy of Neurology (AAN)’s A.B. Baker Section on Neurologic Education conducts an Education Colloquium at the AAN annual meeting. The goals of the Colloquium are to heighten awareness, stimulate creative approaches, and foster dialogue among members regarding current trends, challenges, and opportunities in neurologic education. The theme of the 2004 Education Colloquium was the role of the pharmaceutical industry in neurologic education. Pharmaceutical companies are increasingly involved in neurologic education, partly because of recent dramatic advances in the pharmacotherapy of neurologic diseases, and partly because of economic trends affecting medicine and academic medical centers. The growing role of the pharmaceutical industry in education has both positive and negative consequences. Neurologists need to be informed about currently available medications and the clinical trials that provide evidence for their effectiveness. A major source of information is the material prepared by the pharmaceutical companies and approved by the Food and Drug Administration for drug labeling. For their part, pharmaceutical companies need to keep abreast of current trends and perceived needs in clinical and academic neurology. Furthermore, researchers in industry and researchers in academic neurology departments both benefit from openly communicating with each other. Thus, there are many ways in which industry involvement in neurologic education is desirable. At the same time, this interaction is fraught with risks, because the priorities of the pharmaceutical industry differ from those of clinical and academic medicine. Pharmaceutical companies will predictably emphasize information that puts their products in the best possible light, introducing biases that can be difficult for trainees and even teachers to recognize (for example, focusing on distinctions that are not clinically meaningful, downplaying adverse results, and minimizing the role of non-pharmacologic management and the use of generic and off-patent drugs). Financial support and personal relationships can improperly influence how neurologists and …
Variational Model for Optimization of Finite-Burn Escape Trajectories Using a Direct Method

A variational model is used to obtain the necessary gradient information for a multiple finite-burn trajectory problem. The augmented state vector includes position, velocity, mass, and control variables such as thrust magnitude, and the variables that describe the time evolution of the thrust direction unit vector. The augmented state vector and its associated state equation are used in the variational model to formulate analytical expressions for the gradients of the problem functions with respect to the problem variables. A general finite-burn trajectory problem is formulated for an inertially fixed thrust vector steering model and a fixed-plane linearly varying thrust vector steering model that constrains the thrust vector to be normal to a rotation axis, which itself is part of the control variable set. Both steering models are used in the optimization of a three-finite-burn lunar-escape-trajectory example, using a direct optimization method with explicit numerical integration. The performance of the optimization procedure is compared for both thrust vector steeringmodels, using variational gradients and standard numerical finite difference gradients. The ability to obtain the most accurate gradient information for the direct optimization of simple finite-burn thrust steering models is a motivation of the current study.
Impaired Glucose Tolerance and Obesity as Effect Modifiers of Ethnic Disparities of the Progression to Diabetes The San Antonio Heart Study

OBJECTIVE The Diabetes Prevention Program (DPP) reported no racial/ethnic differences in the incidence of diabetes in individuals with impaired glucose tolerance (IGT). Therefore, it has been hypothesized that factors associated with racial/ethnic disparities act prior to the development of IGT. Because impaired fasting glucose (IFG) and obesity were also very prevalent in the DPP, we examined IGT, IFG, and obesity as effect modifiers of ethnic disparities in the San Antonio Heart Study. RESEARCH DESIGN AND METHODS Participants were 3,015 Mexican Americans and non-Hispanic whites aged 25–64 years. The median follow-up period was 7.8 years. IGT, IFG, and diabetes were defined by the 2003 American Diabetes Association criteria, and obesity was defined as BMI ≥30 kg/m 2 . RESULTS Mexican Americans had an excess risk of incident IGT (odds ratio 1.48 [95% CI 1.16–1.89]) and incident IFG (1.71 [1.31–2.23]) compared with non-Hispanic whites. Mexican Americans also had a higher incidence of diabetes among individuals who had normal 2-h glucose (2.20 [1.48–3.29]) and IGT (1.72 [1.08–2.74]) at baseline. There was an interaction of obesity on the relationship between ethnicity and progression to IGT or diabetes ( P = 0.034), with Mexican Americans having a greater risk among the nonobese (1.73 [1.36–2.21]) and a comparable risk among the obese (1.08 [0.75–1.56]). CONCLUSIONS Ethnic differences can be detected at both the early and later stages of the diabetes disease process. However, non-Hispanic whites lose much of the ethnic advantage once they have developed obesity.
Electrolytic reductive coupling as a synthetic tool

Abstract The utility of electrolytic reductive coupling as a means for synthesizing a variety of polyfunctional compounds is discussed. Activated olefins function as acceptors towards donors generated by electrolytic induction of (a) other activated olefins, (b) other activated olefinic groups within the same molecule, (c) compounds containing “leaving groups” and (d) azo-compounds and Schiff bases.
466 RIFAMPIN IN ERADICATION OF METHICILLIN/GENTAMICINRESISTANT S. AUREUS FROM AN NICU

An outbreak of infections caused by methicillin- and gentamicin-resistant Staphylococcus aureus (MGRS) occurred in the Children's Memorial Hospital NICU in 1979-80. MGRS was isolated from 44 patients in a 21-month period. Infections included bacteremia (6), ventriculitis (3), osteomyelitis (3), otitis media (2) and surgical wounds (6). Nasal carriage of MGRS of bacteriophage type 29/52 was present in 4/56 (7%) of personnel and in up to 75% of patients. Traditional infection control measures failed to interrupt MGRS transmission; intranasal bacitracin + oral rifampin eradicated nasal carriage in 4/4 adults. Bacitracin alone or treatment of infections with a single antibiotic to which MGRS was sensitive (vancomycin or chloramphenicol) failed to eradicate carriage in 6/6 and 10/11 trials, respectively. Bacitracin + rifampin terminated nasal carriage in 3/6 infants. Treatment with bacitracin + rifampin + IV vancomycin or oral erythromycin terminated carriage in all of 8 patients. This regimen was superior to bacitracin alone (p< 0.001), vancomycin or chloramphenicol alone (p <0.001), and bacitracin + rifampin (p=0.06). All patients treated with the three-drug regimen have remained MGRS-negative for up to 10 months. We conclude that therapy with bacitracin, rifampin, and another antibiotic to which the organism is sensitive is effective in eradicating neonatal MGRS carriage.
Purification and properties of bovine uterine glutamic dehydrogenase: A comparison with the liver enzyme

Abstract 1. 1. SPl-Glutamate dehydrogenase (GDH) has been isolated from cotyledons of pregnant bovine uterus. 2. 2. Although the specific activity of uterine GDH is relatively low, its enzymatic parameters are similar to those of the liver enzyme. 3. 3. The molecular weight of uterine GDH is approximately 240,000; unlike the liver enzyme, it does not display concentration-dependent aggregation. Alanine dehydrogenase activity is confined to a lower molecular weight (mol. wt = 160,000) form, which appears to be in rapid equilibrium with the larger species. 4. 4. The effects of nucleotides, steroid hormones, and diethylstilbestrol upon the enzymatic activity of uterine GDH have been examined.
A novel laser device for all optical wavelength conversion

A widely tunable, narrow-linewidth, simultaneous triple-wavelength oscillation erbium-doped fiber ring laser (EDFRL) has been developed. The EDFRL can produce double-wavelength oscillations with the same linear-polarization output, as well as another widely tunable wavelength oscillation with orthogonal linear-polarization from 1522.2 nm to 1595.9 nm. The long-term stability of the triple-wavelength output was observed with a high signal-to-noise ratio of larger than 40 dB. By using this EDFRL in combination with a 1550-nm semiconductor optical amplifier (SOA), an ultrabroad tunable wavelength converter is demonstrated with uniform efficiency and equalized optical signal-to-noise ratio (OSNR) over a 9.1 THz tuning range through four-wave mixing (FWM) in a SOA. This result is a significant improvement of both the conversion efficiency and the SNR as compared with the conventional FWM-based wavelength converters. We have also investigated the effect of both input power and wavelength of pump P2 on conversion efficiency and OSNR of the wavelength-converted signals
An item response theory investigation of the Family Assessment Form

Abstract Drawing from a sample obtained from a large scale, community-based child maltreatment prevention initiative, factor analysis and item response theory (IRT) were used to examine item discrimination and to identify items on the Family Assessment Form (FAF) that statistically do not add value for predictive modeling. Results suggest a consolidated, six-factor structure in general accordance with the current configuration of the instrument. In addition, 13 of the 59 items are identified as low information, indicating that they do not contribute unique measurement information regarding the underlying dimensions of the FAF. Findings suggest that from a statistical measurement perspective, the FAF can be shortened and retain its internal validity, although from a functional assessment perspective, certain items may need to be retained for comprehensive family assessment and case planning.
Near real time assessment of social media using geo-temporal network analytics

When a crisis occurs, there is often little time to evaluate the situation and determine how best to respond. We use rapid ethnographic methods centered on the construction of geo-temporally contextualized social and knowledge networks. By utilizing a combination of Twitter and news media, the consulate attack in Libya were examined in near real time. In this work we outline a procedure to extract key insights from the event as an event unfolds using a suite of tools developed by a team of researchers from two universities.
Multibody Dynamics: A Formulation Using Kane’s Method and Dual Vectors

This paper proposes a formulation based on Kane’s method to form the dynamic equations of motion of multibody systems using dual vectors. Both holonomic and nonholonomic systems are considered in this formulation. An example of a holonomic and a nonholonomic system is worked out in detail using this formulation. This algorithm is shown to be advantageous for a class of holonomic systems which has cylindrical joints.
Robust algorithms for adaptation set in a general formal framework

This paper presents a general formalism for defining problems of adaptation. Within this formalism a class of algorithms, the sequential reproductive plans, is defined. It is then proved that sequential reproductive plans are robust in the sense that, in environments with a well-defined measure of payoff (utility, performance), any such plan will acquire payoff at a rate which asymptotically approaches the optimum.
Multinuclear Metal Carbonyl Alkoxide and Aryloxide Derivatives as Models for Metal Carbonyls Adsorbed on Metal Oxide Supports

The synthesis and characterization of two tungsten carbonyl dimers containing bridging alkoxide or aryloxide ligands are described. The crystal and molecular structures of [PPN]2[W2(CO)8(OCH2CF3)2], 1, and [Et4N]3[W2(CO)6-(OPh)3]-CH3CN, 2, are reported and compared with the structures of tetranuclear tungsten derivatives previously described. The dimer 1 crystalizes in the triclinic space group P 1 with unit cell parameters a = 13.460(11) A, b = 12.318(5) A, c = 13.842(10) A, α = 82.73(5)°, β = 59.11(5)°, γ= 80.09(5)°, V = 1938(2) A3, and Z = 1. The complex 2 crystalizes in the monoclinic space group P21/n with unit cell parameters a = 11.954(2) A, b = 19.359(4) A, c = 26.462(5) A, β = 102.50(16)°, V = 5979(2) A3, Z = 4. Molecular modeling software was utilized to construct a tetranuclear derivative from 1 similar to the structurally characterized [W(CO)3OH]4−4 tetramer. The two tetramers were found to possess similar molecular parameters. This supports the contention that dimers of type 1 are the precursors of the tetramers. Comparisons of the tungsten alkoxides and aryloxides with the behavior of W(CO)6 on γ-alumina are provided.
Marketing Costs and Instability in the International Grain Trade

Fixed factors in the international grain-marketing system reduce flexibility and make adjustment to variable trade volumes difficult. A theoretical model is used to show how this causes marketing costs with trade instability to exceed those occurring under stability. Also, it is demonstrated that the marketing system increases the adverse effects of price variation on importers and exporters. Supporting empirical evidence, primarily dealing with ocean shipping, is presented. The results suggest that stable trade volumes may reduce marketing costs significantly. Thus, the marketing system should be considered in questions dealing with instability in the international grain trade.
Stimulation of amino acid incorporation into protein by phage DNA and an RNA polymerase fraction.

Abstract DNA has been implicated in protein synthesis in cell-free systems by the observation that DNase inhibits amino acid incorporation into protein with extracts of Escherichia coli ( Tissieres, Schlessinger, and Gros, 1960 ; Matthaei and Nirenberg, 1961 ) and by the demonstration that DNA stimulates β-galactosidase formation with UV-irradiated extracts of Escherichia coli ( Eisenstadt and Novelli, 1961 ; Novelli, Kameyama, and Eisenstadt, in press. ) This communication describes a phage DNA stimulation of the incorporation of valine-C 14 into protein with fractions of Salmonella typhimurium extracts. The stimulation by the phage DNA is dependent on the addition of purified RNA polymerase with polymerase-poor fractions.
Adaptive, multi-parameter battery state estimator with optimized time-weighting factors

We derive and implement a battery control algorithm that can accommodate an arbitrary number of model parameters, with each model parameter having its own time-weighting factor, and we propose a method to determine optimal values for the time-weighting factors. Time-weighting factors are employed to give greater impact to recent data for the determination of a system’s state. We employ the (controls) methodology of weighted recursive least squares, and the time weighting corresponds to the exponential-forgetting formalism. The output from the adaptive algorithm is the battery state of charge (remaining energy), state of health (relative to the battery’s nominal performance), and predicted power capability. Results are presented for a high-power lithium ion battery.
Molecular, Serological, and Virulence Characteristics of Vibrio parahaemolyticus Isolated from Environmental, Food, and Clinical Sources in North America and Asia

Potential virulence attributes, serotypes, and ribotypes were determined for 178 pathogenic Vibrio parahaemolyticus isolates from clinical, environmental, and food sources on the Pacific, Atlantic, and Gulf Coasts of the United States and from clinical sources in Asia. The food and environmental isolates were generally from oysters, and they were defined as being pathogenic by using DNA probes to detect the presence of the thermostable direct hemolysin (tdh) gene. The clinical isolates from the United States were generally associated with oyster consumption, and most were obtained from outbreaks in Washington, Texas, and New York. Multiplex PCR was used to confirm the species identification and the presence of tdh and to test for the tdh-related hemolysin trh. Most of the environmental, food, and clinical isolates from the United States were positive for tdh, trh, and urease production. Outbreak-associated isolates from Texas, New York, and Asia were predominantly serotype O3:K6 and possessed only tdh. A total of 27 serotypes and 28 ribogroups were identified among the isolates, but the patterns of strain distribution differed between the serotypes and ribogroups. All but one of the O3:K6 isolates from Texas were in a different ribogroup from the O3:K6 isolates from New York or Asia. The O3:K6 serotype was not detected in any of the environmental and food isolates from the United States, and none of the food or environmental isolates belonged to any of the three ribogroups that contained all of the O3:K6 and related clinical isolates. The combination of serotyping and ribotyping showed that the Pacific Coast V. parahaemolyticus population appeared to be distinct from that of either the Atlantic Coast or Gulf Coast. The fact that certain serotypes and ribotypes contained both clinical and environmental isolates while many others contained only environmental isolates implies that certain serotypes or ribotypes are more relevant for human disease.
Combination Therapy When Metformin Is Not an Option for Type 2 Diabetes

Objective: Consensus on combination options for patients with type 2 diabetes mellitus (T2DM) unable to use metformin is lacking. This review summarizes data describing–non-metformin based combination therapy. Data Sources: PubMed searches (January 1990 to August 2014) were conducted with terms for newer drug therapies alone and with the term combination; filters were applied for Clinical Trial, Meta Analysis, and English language. Study Selection and Data Extraction: Results were reviewed for multicenter, randomized controlled trials of non-metformin–based combination therapy conducted in the past 5 years and specific to the US or multinational populations. Data Synthesis: Although multiple injectable and oral agents have been studied in combination with metformin for management of T2DM, data are more limited for combinations without metformin. Combinations of incretins (injectable glucagon-like peptide-1 receptor agonists or oral dipeptidyl peptidase-4 [DPP-4] inhibitors) with a sulfonylurea, thiazolidi...
S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction

The association between inflammation and endoplasmic reticulum (ER) stress has been observed in many diseases. However, if and how chronic inflammation regulates the unfolded protein response (UPR) and alters ER homeostasis in general, or in the context of chronic disease, remains unknown. Here, we show that, in the setting of obesity, inflammatory input through increased inducible nitric oxide synthase (iNOS) activity causes S-nitrosylation of a key UPR regulator, IRE1α, which leads to a progressive decline in hepatic IRE1α-mediated XBP1 splicing activity in both genetic (ob/ob) and dietary (high-fat diet–induced) models of obesity. Finally, in obese mice with liver-specific IRE1α deficiency, reconstitution of IRE1α expression with a nitrosylation-resistant variant restored IRE1α-mediated XBP1 splicing and improved glucose homeostasis in vivo. Taken together, these data describe a mechanism by which inflammatory pathways compromise UPR function through iNOS-mediated S-nitrosylation of IRE1α, which contributes to defective IRE1α activity, impaired ER function, and prolonged ER stress in obesity.
Dermatologic Manifestations and Update of Cat Scratch Disease

Cat scratch disease is a relatively common cause of chronic (three weeks or longer) lymphadenopathy, with 80% of cases occurring in children and adolescents. This self-limited infection caused by a small, gram-negative, pleomorphic bacillus has been identified in ocular granuloma, skin inoculation lesions, and lymph node specimens. Dermatologic manifestations observed prospectively in 908 patients included primary cat scratch inoculation papules, pustules or rarely, vesicles. Occasionally, enanthematous mucous membrane (oral, ocular) primary inoculation lesions were observed. About 5% of patients have generalized macular, maculopapular, morbilliform, and rarely petechial, usually nonpruritic exanthem. Rarely, erythema nodosum or multiforme and ecchymoses with petechial rashes are seen. Thrombocytopenic purpura is extremely uncommon. Unusual manifestations such as the oculoglandular syndrome of Parinaud, encephalopathy, or severe systemic disease occur in about 10% of patients. Management consists of symptomatic treatment and occasional aspiration of a suppurative node. The disease usually resolves spontaneously in two to four months.
Long term outcomes of posterior leaflet folding valvuloplasty for mitral valve regurgitation

Background: Posterior mitral valve leaflet prolapse due to degenerative mitral valve disease has been treated with tissue sparing repair techniques since 2002. The simplified foldoplasty technique effectively lowers the height of the redundant posterior leaflet and creates an optimal coaptation line for the anterior leaflet that results in excellent long term durability, freedom from reoperation, and return of functional status. Methods: Patient demographics and in-hospital outcome data were extracted from electronic medical records of 229 patients, aged 60.6±13.7 years who underwent the procedure for mitral valve repair (MVR) involving the posterior leaflet from myxomatous disease between 2002 and 2014. Parametric analyses were performed on outcomes data, while long-term survival was assessed by Kaplan-Meier analyses. Results: Concomitant coronary bypass surgery was performed on 32/229 (14%) patients, the mean perfusion time was 119±40 min, and the mean cross clamp time was 86±31 min. Post-operative mortality was 2/229 (0.9%), reoperation for bleeding occurred in 4 (1.7%) and postoperative stroke in 4 (1.7%) patients. Long term follow up rate was 100% and the mean study follow-up duration was 6.8±2.3 years. Overall late mortality rate was 24/229 (14.9%), and mitral valve re-intervention was performed on 7 patients (4.3%). NYHA class III/IV and clinically significant MR at follow up were significantly lower compared to preoperative values (both P<0.001). Conclusions: Our results encourage further use of this simple and effective technique in patients with isolated posterior leaflet prolapse.
A. E. Housman and Faulkner's Nobel Prize Speech: a Note

The address which William Faulkner delivered in Stockholm on 10 December 1950, upon being awarded the Nobel Prize, is a challenge to his fellow writers to recall that ‘the problems of the human heart in conflict with itself’ are the true subject of art. The artist who forgets this, Faulkner warned, ‘writes not of love but of lust’ if he does not dedicate himself to ‘the old verities and truths of the heart, the old universal truths’, then his art is ‘ephemeral and doomed’; and the artist himself ‘labors under a curse’.
Shared Gene Expression Alterations in Prostate Cancer and Histologically Benign Prostate from Patients with Prostate Cancer

Prostate cancer (PCa) field effect alterations provide important clues regarding the initiation of these tumors and suggest targets for prevention or biomarkers for early detection. However, biomarkers of PCa field effects that have passed independent validation are lacking, largely because these alterations are subtle and difficult to distinguish from unrelated small changes in gene expression. We hypothesized that shared expression alterations in PCa and benign prostates containing PCa (BPCs) would have a higher potential for independent validation than alterations identified in BPCs alone. Expression analyses were performed on 37 PCas and 36 unmatched BPCs and were contrasted with 28 benign prostates (BPs) from patients free of PCa. Most of the protein-coding genes and nonexonic RNAs selected according to the hypothesis were validated by quantitative RT-PCR in an independent set of 51 BPCs and BPs. A statistical model based on two markers distinguished BPCs from BPs in the RT-PCR set and in an external microarray (area under the curve = 0.84 and 0.90, respectively). In addition, genes with predominant expression in stroma were identified by expression profiling of pure stroma and epithelial cells. Pathway analysis identified dysregulated platelet-derived growth factor receptor signaling in BPC stroma. These results validate our approach for finding PCa field effect alterations and demonstrate a PCa transcriptome fingerprint in nonneoplastic cells in prostates containing cancer.
Surgical therapy for epidermoid carcinoma of the anal canal: An NSQIP assessment of short-term outcomes

Background Although modern therapy for anal canal cancer typically consists of combined chemoradiation therapy (CRT), surgery remains an option for patients with small lesions, for palliative purposes, and for failure of nonoperative management. This study assesses the short-term outcomes of surgical management for epidermoid carcinoma of the anal canal using a large nationwide database. Methods We performed a retrospective review of 30-d outcomes using American College of Surgeons National Surgical Quality Improvement Program database (2005–2009) for all patients with the primary diagnosis of anal canal cancer undergoing oncologic or palliative surgery. We defined preoperative CRT using standard National Surgical Quality Improvement Program time frames of 30 and 90 d, respectively, before surgery. Results We identified 295 patients (mean age, 58.6 y; 54% female; 77% white). A total of 34 patients received prior CRT and had age, body mass index, American Society of Anesthesiologists class, and preoperative laboratory values similar to those without CRT; the only significant differences was a lower hematocrit and platelet count in the CRT group. For the entire cohort, 30% (N = 89) underwent local excision (LE), 24% (N = 71) diversion, and 46% (N = 135) abdominoperineal resection (APR). Complications occurred in 23.7% of the entire cohort, and overall complication rates significantly differed based on the type of procedure [3.4% for LE and 18.3% for diversion, versus 40% for APR (P < 0.001)]. Only operative approach significantly affected morbidity, as patients receiving APR had a 1.67-fold (range, 1.14–2.45; P = 0.008) increased risk of complications. The 30-d mortality for the entire cohort was 2.7%, and was highest in the diversion group (7%) compared with the APR (1.5%) and local excision groups (1.1%; P = 0.036). However, by multivariate analysis, the only factors associated with death were preoperative sepsis (hazard ratio [HR] = 27.5; P = 0.005), lack of functional independence (HR = 26.3; P = 0.001), hypertension (HR = 14.4; P = 0.028), and prior alcohol use (HR = 21.4; P = 0.026). Chemoradiation therapy use did not have a significant effect on complication (36.0% versus 40.9%; P = 0.651) or mortality rates (0% versus 1.8%; P = 0.497). Conclusions Surgical intervention for anal canal cancer remains a necessary option for select patients. Morbidity rates vary significantly based on the type of treatment; operative approach is the primary factor associated with postoperative short-term complications. When surgery is required, recent CRT is not associated with a higher complication rate. With proper perioperative care and surgical technique, mortality rates remain low, and the increased death rate with diversion, even in the short term, likely represents advanced disease.
Activation of the Rat Kidney Mineralocorticoid Receptor

Activation of the rat kidney mineralocorticoid receptor was investigated using diethylaminoethyl (DEAE)-cellulose, DNA-cellulose, and gel permeation chromatography. Specific labeling of the mineralocorticoid receptor was achieved by labeling with [3H]aldosterone in the presence of the pure glucocorticoid RU28362. The specificity of labeling was confirmed by the lack of immunoreactivity of [3H]aldosterone-labeled material with the monoclonal antiglucocorticoid receptor antibody BURG-1. The unactivated aldosterone-mineralocorticoid receptor complex did not bind to DNA-cellulose, was eluted from DEAE-cellulose at relatively high salt (195 mM KCl) concentration, and had an apparent Stokes radius when chromatographed on Sephacryl S300 of 6.3 nm. After activation, the aldosterone-mineralocorticoid receptor complex had increased affinity for DNA-cellulose and decreased affinity for DEAE-cellulose and appeared as a smaller complex when chromatographed on Sephacryl S300. These changes were blocked by sodium molybdate. Our results indicate that activation of the rat kidney mineralocorticoid receptor is analogous to activation of the glucocorticoid receptor and suggest that activation of the mineralocorticoid receptor involves dissociation of a multimeric receptor form.
MIMO radar for direction finding with exploitation of time-frequency representations

In this paper we consider the exploitation of spatial time-frequency distribution (STFD) in multiple-input multiple-output (MIMO) radar systems. STFD has been found useful in solving various array processing problems, such as direction finding and blind separation, where nonstationary signals are involved. Such treatment has been primarily limited to traditional array processing whereas its use in MIMO radar scenario has received less attention. The emphasis of this paper lies in the reexamination of the STFD framework in an MIMO radar platform for the processing of maneuvering targets with nonstationary signatures. Within this framework, we consider the use of joint transmit and receive apertures for the enhancement and improved estimation of time-frequency signature and the application of STFD in joint direction-of-departure (DOD) and direction-of-arrival (DOA) estimations. As a result, it becomes clear that STFD is effective in MIMO radar processing when the targets are of signatures that are highly localized in the time-frequency domain.
SATELLITE ABSORPTION LINES AND THE TEMPERATURE DEPENDENCE OF X-RAY ABSORPTION FEATURES IN HIGH-TEMPERATURE PLASMAS

Absorption spectroscopy can be used to diagnose compressed layers in spherical targets imploded by means of high-intensity laser irradiation (B. Yaakobi {ital et} {ital al}., Opt. Commun. 34, 213 (1980)). In appropriately designed experiments, absorption lines are formed by 1{ital s}-2{ital p} absorption transitions in the heliumlike through fluorinelike species of certain ions in the shell that surrounds the strong continuum source in the compressed core of the target. These transitions form a distinct, broad linelike absorption band for each ion species. The areal density of each species can be inferred from the attenuation in the spectrum within its respective absorption band and from the known cross sections for each 1{ital s}-2{ital p} transition. Earlier analyses have assumed that all such transitions begin from states in the ground configuration of each species (A. Hauer {ital et} {ital al}., Phys. Rev. A 34, 411 (1986)), but, in fact, most of the absorption can be due to satellite absorption transitions originating from states in excited configurations which are, in total, less opaque than transitions originating from the ground configuration. As a result, the opacity becomes temperature dependent through the temperature dependence of the populations of excited configurations. This is illustrated for themore » specific case of chlorine, and approximate results, based on the screened hydrogenic approximation, are obtained for other elements. Estimates of areal density that include only the ground configuration can be too low by as much as 33%.« less
Inorganic and organometallic polymers

This article provides an inexhaustive overview of research selected from the 2012 scientific literature involving polymers with inorganic elements as a key part of their structure.
Ethics of paid organ donation and the use of executed prisoners as donors: A dialectic with Professors Cameron and Hoffenberg

The essay by Professors Cameron and Hoffenberg on practice guideline development activities, and in March “Ethics and the International Society of Nephrology: 1996, they issued a “Joint Statement of Principles RelatPaid organ donation and the use of executed prisoners ing to Practice Guideline Development” [2]. as donors” in this issue of Kidney International [1] raises More recently, the American Society of Nephrology procedural as well as substantive issues for consideration and Renal Physicians Association have appointed a task by the International Society of Nephrology (ISN). I first force to develop evidence-based clinical practice guidereview the procedural issues of whether the ISN should lines on the selection of patients (that is, the indications) (1) propose or endorse guidelines on ethical issues in for dialysis of acute and of chronic renal failure and also nephrology and (2) establish ethical requirements for to address the forgoing or discontinuation of dialysis. members who receive financial support. Thereafter, I These guidelines are expected to be available in the discuss the substantive issues of (1) paid organ donation fall of 1999 and will meet the needs of United States and (2) the transplantation of organs of executed prisnephrologists. They are unlikely, however, to be univeroners. sally applicable. Thus, if global or even European guidelines are desired, the ISN may wish to commission or facilitate such an undertaking. PROCEDURAL ISSUE I
Expression Pattern of Small Nucleolar RNA Host Genes and Long Non-Coding RNA in X-rays-Treated Lymphoblastoid Cells

A wide variety of biological effects are induced in cells that are exposed to ionizing radiation. The expression changes of coding mRNA and non-coding micro-RNA have been implicated in irradiated cells. The involvement of other classes of non-coding RNAs (ncRNA), such as small nucleolar RNAs (snoRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs) in cells recovering from radiation-induced damage has not been examined. Thus, we investigated whether these ncRNA were undergoing changes in cells exposed to ionizing radiation. The modulation of ncRNAs expression was determined in human TK6 (p53 positive) and WTK1 (p53 negative) cells. The snoRNA host genes SNHG1, SNHG6, and SNHG11 were induced in TK6 cells. In WTK1 cells, SNHG1 was induced but SNHG6, and SNHG11 were repressed. SNHG7 was repressed in TK6 cells and was upregulated in WTK1 cells. The lncRNA MALAT1 and SOX2OT were induced in both TK6 and WTK1 cells and SRA1 was induced in TK6 cells only. Interestingly, the MIAT and PIWIL1 were not expressed in TK6 cells before or after the ionizing radiation treatment. The MIAT and PIWIL1 were upregulated in WTK1 cells. This data provides evidence that altered ncRNA expression is a part of the complex stress response operating in radiation-treated cells and this response depends on functional p53.
The mercury game: evaluating a negotiation simulation that teaches students about science-policy interactions

Environmental negotiations and policy decisions take place at the science-policy interface. While this is well known within academic literature, it is often difficult to convey how science and policy interact to students in environmental studies and sciences courses. We argue that negotiation simulations, as an experiential learning tool, are one effective way to teach students about how science and policy interact in decision-making. We developed a negotiation simulation, called the mercury game, based on the global mercury treaty negotiations. To evaluate the game, we conducted surveys before and after the game was played in university classrooms across North America. For science students, the simulation communicates how politics and economics affect environmental negotiations. For environmental studies and public policy students, the mercury simulation demonstrates how scientific uncertainty can affect decision-making. Using the mercury game as an educational tool allows students to learn about complex interactions between science and society and develop communication skills.