cssi/SciSciGPT-SciSciNet huggingface dataset:
Repurposed agents in the Alzheimer’s disease drug development pipeline

Treatments are needed to address the growing prevalence of Alzheimer’s disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications. These drugs have known safety profiles, pharmacokinetic characterization, formulations, doses, and manufacturing processes. We assessed repurposed AD therapies represented in Phase I, Phase II, and Phase III of the current AD pipeline as registered on ClinicalTrials.gov as of February 27, 2020. We identified 53 clinical trials involving 58 FDA-approved agents. Seventy-eight percent of the agents in trials had putative disease-modifying mechanisms of action. Of the repurposed drugs in the pipeline 20% are hematologic-oncologic agents, 18% are drugs derived from cardiovascular indications, 14% are agents with psychiatric uses, 12% are drug used to treat diabetes, 10% are neurologic agents, and the remaining 26% of drugs fall under other conditions. Intellectual property strategies utilized in these programs included using the same drug but altering doses, routes of administration, or formulations. Most repurposing trials were supported by Academic Medical Centers and were not funded through the biopharmaceutical industry. We compared our results to a European trial registry and found results similar to those derived from ClinicalTrials.gov. Drug repurposing is a common approach to AD drug development and represents 39% of trials in the current AD pipeline. Therapies from many disease areas provide agents potentially useful in AD. Most of the repurposed agents are generic and a variety of intellectual property strategies have been adopted to enhance their economic value.
Non-parametric Bayesian density estimation for biological sequence space with applications to pre-mRNA splicing and the karyotypic diversity of human cancer

Abstract Density estimation in sequence space is a fundamental problem in machine learning that is of great importance in computational biology. Due to the discrete nature and large dimensionality of sequence space, how best to estimate such probability distributions from a sample of observed sequences remains unclear. One common strategy for addressing this problem is to estimate the probability distribution using maximum entropy, i.e. calculating point estimates for some set of correlations based on the observed sequences and predicting the probability distribution that is as uniform as possible while still matching these point estimates. Building on recent advances in Bayesian field-theoretic density estimation, we present a generalization of this maximum entropy approach that provides greater expressivity in regions of sequence space where data is plentiful while still maintaining a conservative maximum entropy character in regions of sequence space where data is sparse or absent. In particular, we define a family of priors for probability distributions over sequence space with a single hyper-parameter that controls the expected magnitude of higher-order correlations. This family of priors then results in a corresponding one-dimensional family of maximum a posteriori estimates that interpolate smoothly between the maximum entropy estimate and the observed sample frequencies. To demonstrate the power of this method, we use it to explore the high-dimensional geometry of the distribution of 5 splice sites found in the human genome and to understand the accumulation of chromosomal abnormalities during cancer progression.
Reflections on History, Gender, (and Beyoncé?): Intersectionality and Interdisciplinarity, Past and Future

In this chapter, Feldstein considers the relationship between intersections of race and gender in US Women’s History scholarship, on the one hand, and the move toward interdisciplinary methodological approaches in which popular culture plays a role, on the other. By offering an overview on key developments in overlapping fields and situating her own work on that trajectory, she suggests that these impulses have not only run parallel but have informed each other.
“Everyone wants to do the model work, not the data work”: Data Cascades in High-Stakes AI

AI models are increasingly applied in high-stakes domains like health and conservation. Data quality carries an elevated significance in high-stakes AI due to its heightened downstream impact, impacting predictions like cancer detection, wildlife poaching, and loan allocations. Paradoxically, data is the most under-valued and de-glamorised aspect of AI. In this paper, we report on data practices in high-stakes AI, from interviews with 53 AI practitioners in India, East and West African countries, and USA. We define, identify, and present empirical evidence on Data Cascades—compounding events causing negative, downstream effects from data issues—triggered by conventional AI/ML practices that undervalue data quality. Data cascades are pervasive (92% prevalence), invisible, delayed, but often avoidable. We discuss HCI opportunities in designing and incentivizing data excellence as a first-class citizen of AI, resulting in safer and more robust systems for all.
Fingerprinting-based Indoor and Outdoor Localization with LoRa and Deep Learning

This paper aims at predicting accurate outdoor and indoor locations using deep neural networks, for the data collected using the Long-Range Wide-Area Network (LoRaWAN) communication protocol. First, we propose an interpolation aided fingerprinting-based localization system architecture. We propose a deep autoencoder method to effectively deal with the large number of missing samples/outliers caused by the large size and wide coverage of LoRa networks. We also leverage three different deep learning models, i.e., the Artificial Neural Network (ANN), Long Short-Term Memory (LSTM), and the Convolutional Neural Network (CNN), for fingerprinting based location regression. The superior localization performance of the proposed system is validated by our experimental study using a publicly available outdoor dataset and an indoor LoRa testbed.
Glutamyl-tRNA as an Intermediate in Glutamate Conversions

Since the discovery of initiator tRNA, a number of reactions have been found that involve modification of amino acids attached to tRNA. These reactions include well-understood processes like the formation of formylmethionyl-tRNA, which serves to initiate peptide chain formation in prokaryotes, or the synthesis of selenocysteine, which functions as the 21st amino acid. Less well understood are the conversions of glutamate. The first conversion serves for the formation of glutamate-1-semialdehyde, the initial precursor of porphyrins (e.g., chlorophylls and hemes). The other known reaction is a transamidation of glutamate attached to tRNAGln, which is a required intermediate in the formation of glutaminyl-tRNA in many organisms and organelles. These conversions of glutamate based on Glu-tRNA as intermediate are the topic of this chapter. Tetrapyrrole-containing compounds, such as hemes and chlorophylls, are essential components of respiratory and photosynthetic reactions. The porphyrin ring of these compounds is derived from eight molecules of 5-aminolevulinic acid (ALA), a precursor whose formation provides a key regulatory control point in heme and chlorophyll biosynthesis.
Comparison of nasal mucosal responsiveness to neuronal stimulation in non-allergic and allergic rhinitis: effects of capsaicin nasal challenge.

Background Neuronal involvement has been implicated in the pathophysiology of non-allergic and allergic rhinitis, contributing to the typical exacerbation of these conditions upon exposure to non-specific environmental irritants. Objectives To determine if non-allergic and allergic rhinitis are characterized by increased responsiveness of the nasal mucosa to sensorineural stimulation. Methods Nasal challenges with capsaicin and its vehicle were performed in three groups of subjects — non-allergic rhinitics, perennial allergic rhinitics, and healthy controls — and resultant symptom scores, glandular secretion reflected by lactoferrin levels, and plasma extravasation reflected by albumin levels in nasal lavage fluid were compared. Results Capsaicin-sensitive nerve stimulation produced increases in symptom scores and lactoferrin levels which were similar among the three groups of subjects. On the other hand, only the group of subjects with allergic rhinitis demonstrated a significant capsaicin-induced increase in albumin levels and a trend in total protein levels. Conclusions We conclude that nonallergic rhinitis is not characterized by increased responsiveness of capsaicin-sensitive nerve fibres; while allergic rhinitis is marked by hyperresponsiveness manifested as increased albumin leakage in nasal fluids. This may reflect the activity of an axonal reflex to sensorineural stimulation.
Comparison of Pressure and LDV Velocity Measurements with Predictions in Transonic Flow

25 Brown, D., Mokry, M., and Ohman, L. H., "Further Calibration of the 15" x 60" Two-Dimensional Test Facility with 6% Open Floor and Ceiling at the Test Section," Project Rept. 5 x 5/0050, Sept. 1971, NRC, Ottawa, Canada. 26 Sells, C. C. L., "Plane Subcritical Flow past a Lifting Airfoil," Proceedings of the Royal Society, Series A. 308, 1968, pp. 371-401. 27 Kacprzynski, J. J., "Fortran IV Program for the CatherallFoster-Sells Method for Calculation of the Plane Inviscid Incompressible Flow past a Lifting Aerofoil," LTR-HA-2, April 1970, NRC, Ottawa, Canada. 28 Kacprzynski, J. J., "Fortran IV Program for the Sells Method for Subcritical Two-Dimensional Inviscid Flow Calculations past a Lifting Aerofoil," LTR-HA-3, April 1970, NRC, Ottawa, Canada. 29 Mokry, M., "Calculation of Flow Past Multi-Component Airfoils in Perforated Wind Tunnel," Proceedings of the 4th Canadian Congress of Applied Mechanics, Montreal, May 1973.
Current-scaling of radiated power for 40-mm diameter single wire arrays on Z

Summary form only given, as follows. In order to estimate the radiated power that can be expected from the next-generation z-pinch driver such as ZR at 28 MA, current-scaling experiments have been conducted on the 18-MA driver Z. We report on the current scaling of single 40-mm diameter tungsten 240-wire arrays with a fixed 110-ns implosion time. The wire diameter is decreased in proportion to the load current. The load current is reduced by reducing the charge voltage on the Marx banks. On one shot firing only 3 of the 4 levels of the Z machine further reduced the load current. The radiated energy scales as the current squared as expected but the radiated power scales as the current to the 3.5 power due to increased pinch instability at lower current. As the current is reduced the rise-time of the x-ray pulse increases and at the lowest current value of 10.4 MA a shoulder appears on the leading edge of the x-ray pulse. We will report on experiments in February 2002 which will attempt to image the pinch along the axis to determine the nature of the reduced stability at lower currents.
Therapy of Esophagitis

Reflux esophagitis is a chronic disorder characterized by the symptoms of heartburn and regurgitation. Heartburn is extremely common in the United States, reportedly experi- enced by approximately 1/3 of the population on a monthly basis and by approximately 1/12 of the population on a daily basis. In addition to heartburn and other symptoms, reflux esophagitis has importance because it results in injury to the esophageal tissues ranging from inflammation to ulceration and healing of these lesions occasionally produces such undesirable complications as stricture formation and the development of the premalignant columnar-lined (Barrett’s) esophagus.
Computing with words beyond quantitative words: Incongruity modeling

Soft computing and computing with words (CWW) operate with uncertain natural language (NL) statements to make NL statements more exact. Currently these NL statements in CWW are limited by quantitative concepts. This paper expands CWW beyond quantitative words to texts that contain incongruities. Incongruities are common in jokes, ironies and contradictory texts. A dynamic model, an algorithm, and visualization are proposed for recognizing incongruities.
Impaired Release of ATP from Red Blood Cells of Humans with Primary Pulmonary Hypertension

Previously, we reported that in the isolated perfused rabbit lung, red blood cells (RBCs) obtained from either rabbits or healthy humans were a required component of the perfusate to unmask evidence of nitric oxide (NO) participation in regulation of the pulmonary circulation. In addition, we found that mechanical deformation of rabbit and healthy human RBCs released ATP, a known agonist for enhanced NO synthesis. In contrast, RBCs obtained from patients with cystic fibrosis (CF) did not release ATP in response to mechanical deformation. The coexistence of airway disease and alveolar hypoxia in patients with CF precluded the drawing of conclusions relating a defect in RBC ATP release with the pulmonary hypertension associated with CF. Airway disease and alveolar hypoxia are not, however, features of primary pulmonary hypertension (PPH), a human condition of unknown etiology. We postulated that a defect in NO generation might contribute to the increased pulmonary vascular resistance in PPH, and as a first step, we hypothesized that RBCs obtained from patients with PPH would not release ATP. In contrast to RBCs of healthy humans, when RBCs of PPH patients were passed through filters (average pore size 12, 8, or 5 microm), ATP was not released and the RBCs exhibited reduced deformability. Moreover, when incubated with the active cAMP analogue, Sp-cAMP (100 microM), an activator of the CF transmembrane conductance regulator, ATP was not released. These results demonstrate that RBCs obtained from patients with PPH fail to release ATP whether the stimulus is mechanical or pharmacological. Thus, failure of RBCs to release ATP in patients with PPH might be a major pathogenetic factor that accounts for the heretofore unknown etiology of their pulmonary hypertension.
MR-guided vascular interventions

Summary form only given. In modern interventional procedures imaging plays a crucial role. This is especially true for vascular interventional procedures. With accurate determination of lesion position and size in the blood vessels as well as determination of related organ function, vascular interventions can be conducted quickly and accurately. X-ray fluoroscopy is the current standard for many procedures. Although the X-ray fluoroscopy technique is accurate for determining the position of interventional devices, the silhouette appearance of the organs and the invisibility of plaques limit many interventional. procedures. New magnetic resonance imaging (MRI) techniques that combine interventional abilities with versatile imaging capabilities have been developed. Currently, because of these new techniques, selective catheterizations of the coronary arteries can be achieved rapidly. Interventional MRI offers the best alternative to X-ray fluoroscopy for vascular interventions with no risk of ionizing radiation for the patient and new imaging possibilities for the controlled delivery of future treatments.
Space-time coding options for OFDM-based WLANs

Space-time block codes and space-time trellis codes have recently been introduced to improve the performance of wireless systems. In this paper, we reconsider first the design criteria for space-time trellis codes in our context of application that is OFDM-based WLAN. We show by simulations that the rapid Rayleigh fast fading criteria are appropriate and we propose a code optimized accordingly. Then, we compare space-time block coding solutions with trellis-based ones, both including convolutional coding and interleaving. For that purpose, we also designed and simulated a rate 1/2 space-time trellis code, in which the channel and space-time coding are jointly optimized.
Why Me? The Persistence of Negative Appraisals Over the Course of Illness1

This paper examines the relationship of illness appraisals and causal attributions to later psychological adjustment among individuals coping with a chronic illness. Data on threat and challenge appraisals, causal attributions, and depression were collected twice over an 18-month period from patients with recently diagnosed rheumatoid arthritis (RA). Appraisals and attributions were differentially related to psychological adjustment. Challenge appraisals were stable over time but were unrelated to depression. Internal, stable, global attributions about the diagnosis were associated with greater depression at follow-up for subjects who were initially high on the depression measure but were related to lowered depression for individuals with initially low depression. An interaction between initial threat appraisals and depression was also found for depression 18 months later. For individuals with low depression scores initially, threat appraisals were related to greater depression later; when initial depression was high, threat appraisals were unrelated to later depression. In addition, initial threat appraisals mediated the relationship between initial level of depression and rumination (continuing to ask, “Why me?”) 18 months later. These findings are discussed in terms of the failure to achieve some resolution about the place of the illness in one's life and of theories of dysphoric rumination that suggest that negative self-focus contributes to a continuing depressed mood.
Factors affecting the manganese and iron activation of the phospho enol pyruvate carboxykinase isozymes from rabbit

Timed assays in which GTP and GDP were separated and quantitated by HPLC were developed and used to study the metal activation of the mitochondrial and cytosolic isozymes of phosphoenolpyruvate carboxykinase purified from rabbit liver. These assays allowed both directions of catalysis to be studied under similar conditions and in the absence of coupling enzymes. The mitochondrial enzyme is rapidly inactivated by preincubation with Fe2+, as had been shown previously for the cytosolic isozyme. The greatest activation by Fe2+ was obtained by adding micromolar Fe2+ immediately after enzyme to form the complete assay mixture that also contained millimolar Mg2+. In the direction of synthesis of OAA from Pep, the K0.5 values for Mn2+ and Fe2+ were in the 3-7 microM range when a nonchelating buffer, Hepes, was used. The buffer used strongly affected activation by Fe2+ at pH 7.4; activation was eliminated in the case of phosphate and K0.5 increased several-fold over that obtained with Hepes when imidazole was used. In non-chelating buffer, the pH optimum was near 7.4 for both isozymes and for both directions of catalysis. However, the near optimal pH range extended below 7.4 for the direction of oxaloacetate synthesis while the range was above 7.4 for Pep synthesis. In the direction of oxaloacetate synthesis: (1) Both isozymes required the presence of micromolar Mn2+ or Fe2+ in addition to millimolar Mg2+ in order to shown significant activity. (2) Fe2+ was as effective an activator as Mn2+ at pH 7 and below. In the direction of Pep synthesis: (1) Micromolar Mn2+ was a much better activator than Fe2+ at the higher pH values needed for optimal activity in this direction. (2) With increasing pH, decreasing activation was obtained with Fe2+ while the activity supported by Mg2+ alone increased. The results demonstrate the potential for regulation of either isozyme of Pep carboxykinase by the availability of iron or manganese.
Large-scale power-combining and linearization in watt-class mmWave CMOS power amplifiers

Switching-class PAs employing device-stacking have been recently explored to meet the challenge of efficient power amplification at mmWave frequencies at moderate power levels of around 20dBm. In this paper, we propose the use of a single-step, large-scale (8-way), 75%-efficient lumped quarterwave power combiner that is co-designed with stacked Class-Elike PA unit cells to enable a Q-band 45nm SOI CMOS PA with a peak Psat of 27.2dBm (>0.5W), peak PAE of 10.7% and 1dB flatness in Psat over nearly the entire Q-band (3346GHz). This measured output power level is approximately 5 × higher than prior reported mmWave silicon PAs. In order to support complex modulations with high average-efficiency, we also propose a novel linearizing architecture that combines largescale power combining, supply-switching for efficiency under backoff and dynamic load modulation for linearization. A second fully-integrated 42.5GHz 45nm SOI CMOS PA is implemented based on this architecture and achieves 60% of the peak efficiency at 6dB back-off.
Metabolic Syndrome and Employer Sponsored Medical Benefits: An Actuarial Analysis

Abstract Objective Metabolic syndrome, a cluster of cardiometabolic risk factors, is associated with a twofold increased risk of developing artherosclerotic cardiovascular disease and a fivefold increased risk of developing diabetes, compared to individuals without metabolic syndrome. For a typical employer-sponsored health benefits program and population, we estimate the medical cost generated by employees and covered dependents with and without metabolic syndrome, with an emphasis on costs associated with cardiovascular events. Methods National Health and Nutrition Examination Survey (NHANES) 1999 to 2000 and NHANES 2001 to 2002 data sets were used to identify the prevalence of metabolic syndrome (based on National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] criteria) in the 20- to 69-year-old age group and calculate the Framingham risk score for coronary artery disease (CAD) and stroke events. We created a 3-year event model and performed Monte Carlo simulation to produce event occurrence for each individual. Results were tabulated for people with and without metabolic syndrome and adjusted for a typical working-age demographic mix. MedStat Marketscan™ was used to develop costs of CAD and stroke events and the incremental contributing cost of metabolic syndrome. We applied these costs to working-age cohorts with and without metabolic syndrome to calculate the cost difference between cohorts. Results Working-age individuals with metabolic syndrome had significantly higher medical costs compared to those without metabolic syndrome: $626 per member per month (PMPM) for those with metabolic syndrome compared to $367 PMPM for those without metabolic syndrome. Of the $259 excess medical cost for individuals with metabolic syndrome, $46 is because of additional cardiovascular events and $213 is because of the expense of higher prevalence of comorbidities, particularly cardiovascular disease and diabetes. Conclusions These findings show that most cardiovascular cost and risk borne by employers is concentrated in the one-third of the working-age population with metabolic syndrome. Employers need resources and approaches for treating and managing metabolic syndrome that combine health, wellness, and medical management programs to enhance screening, identification, and treatment of the risk-factor components of metabolic syndrome.
From Message Posting to Learning Dialogues: Factors affecting learner participation in asynchronous discussion

Generating true learning dialogue as opposed to a collection of loosely affiliated posted messages on a class discussion board can be challenging. This paper presents the results of a cross‐case analysis of nine naturalistic case studies of online classes, looking at how activity design and facilitation factors affected various dimensions of student participation. Findings show that use of guidelines, deadlines and feedback and type of instructor presence affect the resulting discourse in an online class. Additionally, the paper explores how particular types of learning activities are better suited to generating discussion than others and how the integration of discussion activities with the rest of the course activities and requirements impacts learner motivation and participation.
Lithium and lithium ion batteries for applications in microelectronic devices: A review

Batteries employing lithium chemistry have been intensively investigated because of their high energy attributes which may be deployed for vehicle electrification and large-scale energy storage applications. Another important direction of battery research for micro-electronics, however, is relatively less discussed in the field but growing fast in recent years. This paper reviews chemistry and electrochemistry in different microbatteries along with their cell designs to meet the goals of their various applications. The state-of-the-art knowledge and recent progress of microbatteries for emerging micro-electronic devices may shed light on the future development of microbatteries towards high energy density and flexible design.
Using Qualitative Methods in Evaluation Research An Illustrative Bibliography

This article describes the ways in which qualitative methods have been viewed relative to evaluation research. The topics included in the bibliography cover a broad area including the changing climate in evaluation research, the philosophical and conceptual background behind this approach to research, actual evaluation efforts which employed qualitative methods, the use of various data gathering techniques, and how one "makes sense" of these data. It is hoped that the bibliography will serve as a resource to those who choose to use such procedures in their evaluation research as well as testimony to the feasibility and utility qualitative methods offers evaluation researchers and policy makers.
Developing guidelines for assessing visual analytics environments

In this article, we develop guidelines for evaluating visual analytics environments based on a synthesis of reviews for the entries to the 2009 Visual AnaLytics Science and Technology [VAST] Symposium Challenge and from a user study with professional intelligence analysts. By analyzing the 2009 VAST Challenge reviews, we gained a better understanding of what is important to our reviewers, both visual.ization researchers and professional analysts. We also report on a small user study with professional analysts to determine the important factors that they use in evaluating visual analysis systems. We also looked at guidelines developed by researchers in various domains and synthesized the results from these three efforts into an initial set for use by others in the community. One challenge for future visual analytics systems is to help in the generation of reports. In our user study, we also worked with analysts to understand the criteria they used to evaluate the quality of analytic reports. We propose that this knowledge will be useful as researchers look at systems to automate some of the report generation.1 From these two efforts, we produced some initial guidelines for evaluating visual analytics environments and for the evaluation of analytic reports. It is important to understand that these guidelines are initial drafts and are limited in scope as the visual analytics systems we evaluated were used in specific tasks. We propose these guidelines as a starting point for the Visual Analytics Community.
Aperture matching for an infinite circular polarized array of rectangular waveguides

This paper studies the polarization of the main beam radiated from an infinite array of rectangular waveguides, and in particular, illustrates the matching procedure for the design of a circularly polarized array. It is demonstrated that the use of resonant irises at the waveguide openings together with a conventional matching junction inside the waveguides can improve both the power and the axial ratio of the main beam in a circularly polarized array. In general, a good matching design is the one which gives a proper compromise between the power and the polarization, and is not necessarily the one minimizing the reflection.
Tensile behavior of a nanocrystalline Ni–Fe alloy

Abstract The tensile properties, deformation and fracture behavior of an electrodeposited nanocrystalline Ni–15% Fe alloy with an average grain size of 9 nm were investigated. The combination of high strength (2.4 GPa), good tensile elongation (6%) and reasonable fracture toughness (16 MPa m1/2) obtained for this material suggests that nanocrystalline face-centered cubic metals are inherently ductile and have attractive mechanical properties. The large tensile elongation is proposed to be associated with the persistence of strain hardening at large strains. The results of this study reveal that plastic instability precedes fracture and the degree of reduction in area is much higher under plane stress condition. It is shown that at the nanoscale, consistent with theoretical predictions, the crack follows an intergranular path, but crack propagation is accompanied by considerable plasticity. According to a detailed fractographic analysis, a fracture scenario is established aimed at understanding the tensile fracture process in nanocrystalline face-centered cubic metals.
Acetylcholine Concentrations and Turnover in Rat Brain Structures during Anesthesia with Halothane, Enflurane, and Ketamine

Acetylcholine and choline concentrations in brain structures of rats during anesthesia with halothane (0.7-1.0 per cent inspired), enflurane (2.7-3.0 per cent, inspired) and ketamine (40 mg/kg, iv) were measured by gas chromatography. The turnover rate (biosynthesis) of acetylcholine in vivo was estimated by infusing phosphoryl(Me-14C)choline intravenously, determining specific activities of choline and acetylcholine, and applying principles of steady-state kinetics to compute the fractional rate constant of acetylcholine. Acetylcholine concentrations in brain structures did not change during anesthesia. Halothane decreased the acetylcholine turnover rates in all parts of the brain. Enflurane decreased the acetylcholine turnover rate in the cerebral cortex only, but not in the caudate nucleus, the hippocampus, and the hypothalamic and thalamic regions. During anesthesia with ketamine, acetylcholine turnover rates were reduced in the caudate nucleus and the hippocampus, but not in the cerebral cortex and the hypothalamic and thalamic regions. The results suggest that acetylcholine turnover rate and utilization are related to anesthetic induced electrophysiologic changes in cortical and subcortical structures.
Conteúdo estomacal dos tubarões azul (Prinace glauca) e anequim (Isurus oxyrinchus) em águas oceânicas no sul do Brasil

Blue shark and shortfin mako shark are the main pelagic elasmobranchs species often captured on tuna longlining in Southern Brazil, during the second and third quarters of the year. A total of 68 stomachs of blue shark and 32 stomachs of shortfin mako shark were collected between August 1990 and June 1991. Results in the IRI (Index of Relative Importance) diagrams show that there is a better representativity in the percentages of IRI, when analysis do not take into consideration isolated cephalopod beaks. A taxonomic list of 31 identified taxa is presented, being 25 at genus level and 17 at species level. Shortfin mako shark was observed having an icthyophagous habit, with predominance of Teleostei, Brama brama, and Lepidocybium flavobrunneum. The main items observed for blue shark, with a teuthophagous habit, were the cephalopods Chiroteuthis verany, Moroteuthis robsoni and Ancistrocheirus lesueuri, although Lepidocibium flavobrunneum was the second prey item in IRI.
A child with spider bite and glomerulonephritis: a diagnostic challenge

A previously healthy 7-year-old white boy presented to St. Louis Children's Hospital with a 1-day history of headache, malaise, temperature of 38.7 degrees C, and a progressively erythematous, tender calf with central dusky purpura. On the morning of admission, his mother noticed a 2-mm crust on the patient's right calf with a 3-cm x 3-cm area of surrounding erythema. No history of recent trauma or bite was obtained. He had suffered two episodes of nonbloody, nonbilious emesis during the last day. In addition, over the previous 12 h, he presented brown urine without dysuria. His mother and brother had suffered from gastroenteritis over the previous week without bloody diarrhea. On initial physical examination, there was a 6-cm x 11-cm macular tender purpuric plaque with a central punctum on the right inner calf, which was warm and tender to the touch, with erythematous streaking towards the popliteal fossa (Fig. 1). The inguinal area was also erythematous with tender lymphadenopathy and induration, but without fluctuance. Laboratory studies included an elevated white blood cell count of 20, 800/microL with 6% bands, 86% segs, and 7% lymphocytes, hemoglobin of 12.5 g/dL, hematocrit of 35.1%, and platelets of 282,000/microL. The prothrombin time/activated partial tissue thromboplastin was 10. 4/28.0 s (normal PT, 9.3-12.3 s; normal PTT, 21.3-33.7 s) and fibrinogen was 558 mg/dL (normal, 192-379 mg/dL). Urinalysis showed 1+ protein, 8-10 white blood cells, too numerous to count red blood cells, and no hemoglobinuria. His electrolytes, blood urea nitrogen (BUN), and creatine were normal. The urine culture was negative. Blood culture after 24 h showed one out of two bottles of coagulase negative Staphylococcus epidermidis. The patient's physical examination was highly suggestive of a brown recluse spider bite with surrounding purpura. Over the next 2 days, the surrounding rim of erythema expanded. The skin within the plaque cleared and peeled at the periphery. The coagulase negative staphylococci in the blood culture were considered to be a contaminant. Cefotaxime and oxacillin were given intravenously. His leg was elevated and cooled with ice packs. The patient's fever resolved within 24 h. The lesion became less erythematous and nontender with decreased warmth and lymphadenopathy. The child was discharged on Duricef for 10 days. Because the patient experienced hematuria rather than hemoglobinuria, nephritis was suggested. In this case, poststreptococcal glomerulonephritis was the most likely cause. His anti-streptolysin-O titer was elevated at 400 U (normal, <200 U) and C3 was 21.4 mg/dL (normal, 83-177 mg/dL). His urine lightened to yellow-brown in color. His blood pressure was normal. Renal ultrasound showed severe left hydronephrosis with cortical atrophy, probably secondary to chronic/congenital ureteropelvic junction obstruction. His right kidney was normal.
“Rolling Refreshers”: A novel approach to maintain CPR psychomotor skill competence

Abstract Objectives High quality CPR skill retention is poor. We hypothesized that "just-in-time" and "just-in-place" training programs would be effective and well-accepted to maintain CPR skills among PICU staff. Methods "Rolling Refreshers", a portable manikin/defibrillator system with chest compression sensor providing automated corrective feedback to optimize CPR skills, were conducted daily in the PICU with multidisciplinary healthcare providers. Providers practiced CPR until skill success was attained, prospectively defined as 38mm during continuous CPR. Providers completing ≥2 refreshers/month (Frequent Refreshers [FR]) were compared to providers completing Results Over 15 weeks, 420 PICU staff were "refreshed": 340 nurses, 34 physicians, 46 respiratory therapists. A consecutive sample of 20 PICU staff was assessed before subsequent refresher sessions (FREQ n =10, INFREQ n =10). Time to achieve CPR skill success was significantly less in FREQ (median 21s, IQR: 15.75–30s) than in INFREQ (median 67s, IQR: 41.5–84s; p n =9) rated "Rolling Refresher" training as effective (mean=4.2; Likert scale 1–5; standard deviation 0.67). Conclusions A novel "Rolling Refresher" CPR skill training approach using "just-in-time" and "just-in-place" simulation is effective and well received by PICU staff. More frequent refreshers resulted in significantly shorter times to achieve proficient CPR skills.
Human natural killer cells

Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells “see,” lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.
Solid state structure of the (2,4-dimethylpentadienyl)iron dicarbonyl dimer

Abstract A solid state structural investigation of the Fe(2,4-dimethylpentadienyl)(CO)2 dimer has revealed a structure quite similar to that of the known cis isomer of [Fe(C5H5(CO)2]2. A lengthening of the FeFe bond by ca. 0.08 A can be correlated with substantial intramolecular steric crowding.
Comparison of statistical methods for estimation of nutrient load to surface reservoirs for sparse data set: application with a modified model for phosphorus availability

Abstract Nutrient budget models for lakes and reservoirs critically respond to the input pollutant loading, yet little consensus exists on how to estimate the load, particularly for the common but challenging case of sparse nutrient concentration measurements and abundant input flow data. A statistical load calculation using cluster (in this case, annual) mean concentration and stratified (monthly) flow was compared to estimates by sample mean and ratio estimator methods for phosphorus loading to Whitney Reservoir in North Central Texas. The results varied considerably for the various estimator methods during the six-year study period with the cluster and stratified mean approach estimating extreme high loading periods not captured by the other methods. The variable loading patterns were then tested in phosphorus budget model simulations for Whitney Reservoir that considered vertical stratification of the water column, water–sediment phosphorus interaction, and seasonal variations in water quality. For independently determined settling, interlayer dispersion, recycling rates, and sediment burial rates estimated for the respective loading calculation, the cluster and stratified mean loading pattern provided a better statistical fit of phosphorus concentration measurements in the epilimnion than when ratio estimator load calculations were used. The two loading functions described hypolimnion concentration data equally well. The lesson of this exercise is that various methods of load estimation should be examined in order to develop as reliable a management model as possible when only a sparse data set is available for calibration.
Progress toward the synthesis of piperazimycin A : exploration of the synthesis of γ-hydroxy and γ-chloropiperazic acids

Abstract Employing Hamada’s chemistry with MAOS optimization of several steps, an expedient route to key (3 S ,5 S )- and (3 R ,5 R )-γ-hydroxy and (3 R ,5 S )-γ-chloropiperazic acids, was developed en route to a total synthesis of piperazimycin A.
Variation between end-of-life health care costs in Los Angeles and San Diego: why are they so different?

Abstract Context: Small area differences in health care use between Boston, Massachusetts, and New Haven, Connecticut, are well known. However, we do not know whether factors believed to account for these variations explain differences between other geographic areas. Objective: To explore differences in health care use between the California counties of Los Angeles (LA) and San Diego. Method: Medicare data were obtained form the Dartmouth interactive website. In addition, hospital-level data were obtained for the California Office of Statewide Health Planning and Development (OSPHD). Health outcomes and self-reported disease prevalence were estimated from the California Health Interview Survey (CHIS). Results: Physician supply was comparable between LA and San Diego. Fees per unit service were also equivalent. Hospital beds beds per 10,000 population were 35% higher in LA. Intensity of service use, particularly during the last 2 years of life, was significantly higher in LA, and costs were dramatically hi...
Generating knock-in parasites: Integration of an ornithine decarboxylase transgene into its chromosomal locus in Leishmania donovani

Leishmania null mutants created by targeted gene replacement are typically complemented with chimeric episomes harboring the replaced gene in order to validate that the observed phenotype is due to the specific gene deletion. However, the current inventory of available episomes for complementation of genetic lesions in Leishmania is unstable in the absence of drug selection, and levels of gene expression cannot be controlled, especially in vivo. To circumvent this impediment, a strategy to re-introduce the targeted gene into the original chromosomal locus to generate “knock-in” parasites within selectable null backgrounds has been developed. A genomic fragment encompassing the ornithine decarboxylase locus and lacking heterologous DNA sequences was transfected into ornithine decarboxylase-deficient Leishmania donovani. The construct randomly integrated into either chromosomal allele by homologous recombination restoring polyamine prototrophy and revealing that LdODC was functionally expressed in the knock-in clones. This strategy offers a mechanism for complementing a genetic lesion amenable to positive selection in a manner that facilitates stable gene expression from its original locus in the absence of continuous drug pressure.
On a class of threshold AR(k) processes

We consider the model $$Z_t = \sum\limits_{i = 1}^k {\phi (i,j)Z_{t - i} } + a_t (j)when\left[ {Z_{t - 1} ,Z_{t - 2,...,} Z_{t - k} } \right]^\prime \in R(j),$$ where {R(j);1⩽j⩽ l}is a partition of ℝk, and for each 1⩽j⩽l,{at(j);t⩾ 0} are i.i.d. zero-mean random variables, having a strictly positive density. Sufficient conditions are obtained for this process to be transient. In addition, for a particular class of such models, necessary and sufficient conditions for ergodicity are obtained. Least-squares estimators of the parameters are obtained and are, under mild regularity conditions, shown to be strongly consistent and asymptotically normal.
Gametophytes of Four Tropical Fern Genera Reproducing Independently of Their Sporophytes in the Southern Appalachians

Vegetative reproduction and dispersal by way of gemmae are known to occur in four types of fern gametophytes. Although they belong to basically tropical rain-forest genera, all four types have now been discovered growing natu rally in the vicinity of Highlands, North Carolina, as clones on shady, damp rocks. Their sporophytes were rare or absent. The gametophytes are now identified as Grammitis nimbata (Jenm.) Proctor, Grammitidaceae; Hymenophyllum tunbridg ense (L.) J.Sm., Hymenophyllaceae; Vittaria lineata (L.) J.Sm., Vittariaceae; and Trichomanes, probably representing several species, Hynmenophyllaceae. Identifi cation of the Grammitis was facilitated by the presence of some juvenile or dwarfed sporophytes; this constitutes the first report of this species, genus, and family for temperate North America. Growth and spread of fern gametophytes independently of, and distant from, the corresponding sporophytes is a novel phenomenon which should be investigated in other parts of the world.
p53 is involved in tumor necrosis factor-α-induced apoptosis in the human prostatic carcinoma cell line LNCaP

The human prostatic carcinoma cell line LNCaP is sensitive to TNF-alpha treatment and expresses wild-type p53. To analyse the possible role of p53 in TNF-alpha-mediated apoptosis, we generated a derivative of LNCaP, LN-56, expressing a dominant-negative element of p53, GSE56. P53 inactivation in LN-56 was associated with an increased resistance to apoptosis induced by TNF-alpha. Surface expression of TNF-alpha receptors was unchanged in LN-56 compared to LNCaP. TNF-alpha treatment resulted in accumulation of p53 in LNCaP and upregulation of p21/WAF1. Activation of caspase-7 and PARP proteolysis were delayed in LN-56 under TNF-alpha treatment. TNF-alpha-induced apoptosis in LNCaP cells was accompanied by caspase-dependent proteolysis of p21/WAF1 and Rb, which was significantly attenuated in LN-56. Cytochrome c release was induced by TNF-alpha treatment in both cell lines, but caspase-9 was not activated. LNCaP and LN-56 were injected s.c. in nude mice and tumors were identified in all LN-56, but not LNCaP, bearing mice indicating that p53 plays an important role in growth control of prostatic neoplasms. Interestingly, accumulation of p53 in TNF-alpha-treated LNCaP cells was decreased in the presence of the caspase inhibitor Z-VAD-FMK, suggesting a new role of activated caspases in acceleration of p53 response. In summary, these results indicate that p53 is involved in TNF-alpha-mediated apoptosis in LNCaP.
A Maximum Entropy Analysis of Protein Orientations Using Fluorescence Polarization Data from Multiple Probes

Abstract Techniques have recently become available to label protein subunits with fluorescent probes at predetermined orientation relative to the protein coordinates. The known local orientation enables quantitative interpretation of fluorescence polarization experiments in terms of orientation and motions of the protein within a larger macromolecular assembly. Combining data obtained from probes placed at several distinct orientations relative to the protein structure reveals functionally relevant information about the axial and azimuthal orientation of the labeled protein segment relative to its surroundings. Here we present an analytical method to determine the protein orientational distribution from such data. The method produces the broadest distribution compatible with the data by maximizing its informational entropy. The key advantages of this approach are that no a priori assumptions are required about the shape of the distribution and that a unique, exact fit to the data is obtained. The relative orientations of the probes used for the experiments have great influence on information content of the maximum entropy distribution. Therefore, the choice of probe orientations is crucial. In particular, the probes must access independent aspects of the protein orientation, and two-fold rotational symmetries must be avoided. For a set of probes, a "figure of merit" is proposed, based on the independence among the probe orientations. With simulated fluorescence polarization data, we tested the capacity of maximum entropy analysis to recover specific protein orientational distributions and found that it is capable of recovering orientational distributions with one and two peaks. The similarity between the maximum entropy distribution and the test distribution improves gradually as the number of independent probe orientations increases. As a practical example, ME distributions were determined with experimental data from muscle fibers labeled with bifunctional rhodamine at known orientations with respect to the myosin regulatory light chain (RLC). These distributions show a complex relationship between the axial orientation of the RLC relative to the fiber axis and the azimuthal orientation of the RLC about its own axis. Maximum entropy analysis reveals limitations in available experimental data and supports the design of further probe angles to resolve details of the orientational distribution.