cssi/SciSciGPT-SciSciNet huggingface dataset:
Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growth in vivo.

// Samuel Jang 1, 2 , Andrew Janssen 2 , Zviadi Aburjania 2 , Matthew B. Robers 3 , April Harrison 2 , Ajitha Dammalapati 2 , Yi-Qiang Cheng 4 , Herbert Chen 2 and Renata Jaskula-Sztul 2 1 Howard Hughes Medical Institute, Birmingham, AL, USA 2 Department of Surgery, School of Medicine, University of Alabama, Birmingham, AL, USA 3 Promega Corporation, Fitchburg, WI, USA 4 UNT System College of Pharmacy, Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA Correspondence to: Renata Jaskula-Sztul, email: rjsztul@uabmc.edu Keywords: thailandepsin A, histone deacetylase inhibitor, neuroendocrine cancer, carcinoid, medullary thyroid cancer Received: June 20, 2017 Accepted: July 23, 2017 Published: August 07, 2017 ABSTRACT Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis -derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer. IC 50 for TDP-A was determined to be 4-6 nM in NE cancer cell lines (BON, MZ-CRC-1, and TT) without cytotoxicity to lung fibroblasts. The binding characteristics of TDP-A to its target HDAC1 was examined using bioluminescence resonance energy transfer (BRET). Western blot and flow cytometry analysis showed that TDP-A induces cell cycle arrest and apoptosis in a dose-dependent manner. TDP-A dose-dependently activated the Notch pathway as measured by increasing functional CBF1-luciferase reporter signal and mRNA and protein expressions of Notch isoforms, which were attenuated by pretreatment with γ-secretase inhibitor DAPT. Furthermore, TDP-A lead to changes in expression level of downstream targets of Notch pathway and reduced expression of NE cancer markers. An in vivo study demonstrated that TDP-A suppressed NE cancer progression. These results show that TDP-A, as a Notch activator, is a promising agent against NE cancers.
Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized 13C MRI

Hyperpolarized 13 C magnetic resonance imaging (MRI) may be used to non-invasively image the transport and chemical conversion of 13 C-labeled compounds in vivo. In this study, we utilize hyperpolarized 13 C MRI to evaluate metabolic markers in the kidneys longitudinally in a mouse model of partial unilateral ureteral obstruction (pUUO). Partial obstruction was surgically induced in the left ureter of nine adult mice, leaving the right ureter as a control. 1 H and hyperpolarized [1-13 C]pyruvate MRI of the kidneys was performed 2 days prior to surgery (baseline) and at 3, 7 and 14 days post-surgery. Images were evaluated for changes in renal pelvis volume, pyruvate, lactate and the lactate to pyruvate ratio. After 14 days, mice were sacrificed and immunohistological staining of both kidneys for collagen fibrosis (picrosirius red) and macrophage infiltration (F4/80) was performed. Statistical analysis was performed using a linear mixed effects model. Significant kidney × time interaction effects were observed for both lactate and pyruvate, indicating that these markers changed differently between time points for the obstructed and unobstructed kidneys. Both kidneys showed an increase in the lactate to pyruvate ratio after obstruction, suggesting a shift towards glycolytic metabolism. These changes were accompanied by marked hydronephrosis, fibrosis and macrophage infiltration in the obstructed kidney, but not in the unobstructed kidney. Our results show that pUUO is associated with increased pyruvate to lactate metabolism in both kidneys, with injury and inflammation specific to the obstructed kidney. The work also demonstrates the feasibility of the use of hyperpolarized 13 C MRI to study metabolism in renal disease.
Kalmár's Argument Against the Plausibility of Church's Thesis

In his famous paper, An Unsolvable Problem of Elementary Number Theory, Alonzo Church (1936) identified the intuitive notion of effective calculability with the mathematically precise notion of recursiveness. This proposal, known as Church's Thesis, has been widely accepted. Only a few papers have been written against it. One of these is Laszlo Kalmar's An Argument Against the Plausibility of Church's Thesis from 1959. The aim of this paper is to present Kalmar's argument and to fill in missing details based on his general philosophical thoughts on mathematics.
Fiscal noting reconsidered: the experience of the states with mandate cost estimation

Ten years after the first comprehensive review of fiscal noting in the states, revisiting the impact of cost analysis on unfunded state mandates yields pessimistic conclusions. More states have adopted fiscal noting over the period, yet few report that the process is successful. The majority of fiscal notes contain no cost estimates at all for a variety of reasons, including lack of time, lack of resources, lack of legislative attention, and perhaps lack of institutional capacity.
Preoperative survival calculator for resectable hepatocellular carcinoma

Background: Estimation of preoperative overall survival (OS) of hepatocellular carcinoma (HCC) may guide surgical decision-making. Methods: OS was analyzed using the National Cancer Data Base from 1998–2012. Patients with HCC who underwent wedge resection, lobectomy or extended lobectomy were selected. Patients who had metastatic disease or previous treatment prior to surgery were excluded. Data was randomly allocated to model building (nb =4,364) and validation cohorts (nv =1,091). Multivariable regression analyses of the nb were used to construct prediction models and optimized using nv. Results: HCC patients (n=5,455) who underwent curative resection had a median OS of 36 months (95% CI, 34–38 months) with 1- and 3-year OS of 73% (95% CI, 72–74%) and 50% (95% CI, 49–51%), respectively. The patient median age was 65, 66% of patients were male, median tumor size was 60 mm; clinical stage 1 =25%, stage 2 =30% and stage 3 =45%. Alpha fetoprotein (AFP) was elevated in 63% of patients. Factors significant in the prediction model included degree of resection, age, race, tumor size, grade, and histologic subtype. Conclusions: A preoperative OS calculator was developed to assist in the treatment evaluation and OS prediction of HCC patients.
A study of the active state in molluscan ventricular muscle.

The tension-length relationship of mammalian cardiac muscle is characterized by the presence of resting tension on the rising limb of the active tension curve and by the high value of resting tension at the length where active tension is maximal2. This is in contrast to skeletal muscle in which resting tension begins to appear only beyond the length for maximal active tension.
Effects of nutrition and season on the onset of puberty in the beef heifer

Age at puberty is a major determinant of lifetime reproductive efficiency of beef cows. Research conducted during the past 20 yr has documented the major endocrine events leading to first ovulation in heifers. The critical event seems to be a prepubertal increase in pulsatile LH secretion. Environment influences timing of puberty onset in beef heifers. Nutrition and season are two of the better-defined variables that have been studied. Age at puberty is related inversely to plane of nutrition. The effect of nutrition on sexual maturation involves effects on timing of the prepubertal increase in LH secretion and seems to involve the LH pulse generating system located in the hypothalamus. The precise mechanism by which nutrition influences pulsatile LH secretion has not been elucidated, but signals reflecting metabolic status seem to be involved. Seasonal conditions of the early (birth to 6 mo of age) and late (6 to 12 mo of age) postnatal periods also influence timing of puberty onset in the heifer. Autumn-born heifers attain puberty at younger ages than do spring-born heifers, and exposure to spring-summer temperatures and photoperiods during the second 6 mo of life reduces age at puberty regardless of season of birth. Photoperiod may be the major seasonal cue that influences puberty onset in cattle. Limited evidence suggests that melatonin, a pineal hormone, is involved with transducing photic stimuli into neuroendocrine signals that influence LH secretion. If the physiological mechanisms mediating the effects of nutrition and season on timing of puberty onset are determined, then management strategies for reducing age at puberty can be enhanced.
Predictive Maintenance for Supermarket Refrigeration Systems Using Only Case Temperature Data

We present a machine-learning based approach for early detection of issues emerging in refrigeration and cold-storage systems that has the following desirable features: 1) Minimal sensor dependencies: only requires temperature readings and defrost state from the refrigeration cases 2) high precision, and 3) high generalizability of the learnt model. We achieve this by casting the time-series prediction problem as a classification problem, wherein we craft a set of features that capture key time-series characteristics specific to defrost and operating regimes. Our feature extraction employs seasonality-trend decomposition and pattern learning using dynamic time warping and clustering. The extracted features are used to learn a random forest-based binary classifier that can indicate the presence or absence of an issue in any given refrigeration case at any given time. We validate our approach on real data from 2265 refrigeration cases from several large supermarkets. The approach achieves a precision of 89%, lead time of approximately seven days, and a recall of 46% when evaluated on unseen cases.
A simple care bundle to reduce unplanned admission rate for day case pediatric circumcision

BACKGROUND An electronic review of unplanned day case admission rates in our hospital demonstrated an average annual rate for pediatric circumcision of 2%-3% in recent years with high levels of perioperative strong opiate use. This lay above target unplanned admission rates (<2%) set out by the Royal College of Anaesthetists for day case surgery. A targeted quality improvement initiative was undertaken to improve patient flow through the pediatric day case surgery unit for elective circumcision. Among the reasons for unplanned admission, factors modifiable by the anesthetist (pain, postoperative nausea and vomiting, somnolence) are significant contributors. METHODS A prospective audit was undertaken over a 3-month period. Our practice was compared with evidence-based analgesic and antiemetic interventions in accordance the Association of Paediatric Anaesthetists of Great Britain and Ireland. Perioperative strong opiate administration rates occurred in 44% of cases. Four strategic interventions were selected based on quality of evidence, ease of implementation, and low cost: selection of higher concentration local anesthetic use for penile blocks, intravenous dexamethasone, and preoperative paracetamol combined with maximum dose nonsteroidal anti-inflammatory. RESULTS The audit was duplicated a year later demonstrating a significant increase in application of these interventions with a parallel fall in strong opiate use from 44% to 9% and an unprecedented zero unplanned admission rate in our unit for 10 months in a row after implementation. CONCLUSION Regular scrutiny of patient electronic data helps identify high impact areas for audit and intervention. Unplanned admission in pediatric day case surgery is an area amenable to such targeted intervention.
Sperm-like-particle (SLP) behavior in curved microfluidic channels

Microfluidic technology has the potential to separate sperm cells from unwanted debris commonly found in clinical samples while improving the effectiveness of assisted reproductive technologies. In this study, we present an improved model of sperm cell behavior in curved channels based on both 2D COMSOL® simulations and experimental studies. The 2D COMSOL® simulation results show alignment of the sperm like particles, which suggests that sperm should be treated as small, relatively stationary particles rather than larger rotating particles. This understanding helps us generate more precise sperm separations for µTESE samples by enabling the assumption of a small particle rather than a large one. This alignment was also confirmed by observing the alignment angle of all recognizable sperm cells with high-speed imaging near the outlet area of the spiral channel. A series of experiments with sperm cells and microbeads showed clear separation improvement between the new experimental conditions and previous efforts. Sperm were found to behave more similarly to 3 µm beads than to 5 µm beads and that sperm cells may act like particles even smaller than the 3-µm beads. The focused sperm cell stream appeared in the middle area of the channel and the focused RBCs stream appeared at the mid-inner wall area of the channel. Basic biocompatibility testing also suggests that the approach can be used safely in a clinical setting.
Musculoskeletal toxicities in patients receiving concomitant statin and daptomycin therapy.

Purpose This article evaluates the musculoskeletal safety of concomitant therapy with daptomycin and Hydroxymethylglutaryl-coenzyme A (HMG CoA) reductase inhibitors (statins). Summary Often indicated for severe gram-positive infections, daptomycin is commonly administered with statins but there is limited guidance on the appropriate management of concomitant therapy with daptomycin and statins. A narrative review was conducted to review contemporary clinical evidence of the safety of concomitant therapy with daptomycin and statins. A total of 5 studies were identified comparing daptomycin monotherapy versus daptomycin and statin concomitant therapy for the primary outcome of creatine phosphokinase (CPK) elevations in a variety of patient populations with systemic, skin/soft tissue, and bone/joint infections. Of these studies, 4 also compared myalgia or myopathy as a secondary outcome. Case studies, the case-control study and 1 prospective registry comparing statin alone versus daptomycin and statin concomitant therapy were excluded. These studies showed that concomitant therapy with daptomycin and statin was not significantly associated with CPK elevation or higher event rate of myalgia or myopathy, compared to daptomycin monotherapy. Conclusion Published cohort studies do not demonstrate a statistically significant difference in the rate of CPK elevations or musculoskeletal toxicities between patients receiving daptomycin monotherapy and daptomycin plus a statin. Patients receiving statins who start daptomycin therapy should continue statin but with weekly monitoring of CPK levels. Continuation of statins is especially important in high-risk patients receiving statins for secondary prevention for atherosclerotic cardiovascular diseases. If myalgia develops, it is reasonable to evaluate the degree of CPK elevation and reassess the need for statin use during daptomycin treatment.
Controlling spectral selectivity in optoelectronics via photonic band engineering in absorbing media

The most common solution for achieving arbitrary spectral selectivity in optoelectronic devices is adding external filters. Here we propose using semiconductor thin film photonic crystals with relevant photonic bands that fall within the absorbing frequency range of the material for spectral selectivity. Optical simulations show that the in-plane photonic bands couple strongly to normal-incidence external fields, inducing tunable resonance features in the out-of-plane transmission and reflection spectra. Experimentally, we fabricate a proof-of-principle photonic structure with enhanced visible transparency, consisting of a self-assembled polystyrene bead array infiltrated with colloidal quantum dots, showing promise for multijunction and transparent photovoltaics.
Fairness in responsive parallelism

Research on parallel computing has historically revolved around compute-intensive applications drawn from traditional areas such as high-performance computing. With the growing availability and usage of multicore chips, applications of parallel computing now include interactive parallel applications that mix compute-intensive tasks with interaction, e.g., with the user or more generally with the external world. Recent theoretical work on responsive parallelism presents abstract cost models and type systems for ensuring and reasoning about responsiveness and throughput of such interactive parallel programs. In this paper, we extend prior work by considering a crucial metric: fairness. To express rich interactive parallel programs, we allow programmers to assign priorities to threads and instruct the scheduler to obey a notion of fairness. We then propose the fairly prompt scheduling principle for executing such programs; the principle specifies the schedule for multithreaded programs on multiple processors. For such schedules, we prove theoretical bounds on the execution and response times of jobs of various priorities. In particular, we bound the amount, i.e., stretch, by which a low-priority job can be delayed by higher-priority work. We also present an algorithm designed to approximate the fairly prompt scheduling principle on multicore computers, implement the algorithm by extending the Standard ML language, and present an empirical evaluation.
Grouping of objects as a major idea at the primary level

Now serving as a research scientist with the Developing Mathematical Processes curriculum project at the Wisconsin Research and Development Center for Cognitive Learning, James Moser was formerly associate professor of mathematics and education at the University of Colorado. For two years he was president of the Colorado Council of Teachers of Mathematics. He has been a speaker at many NCTM meetings.
Treatment of Acute Cholecystitis: Do Medicaid and Non-Medicaid Enrolled Patients Receive the Same Care?

Nationally, Medicaid enrollees with emergency surgical conditions experience worse outcomes overall when compared with privately insured patients. The goal of this study is to investigate disparities in the treatment of cholecystitis based on insurance type and to identify contributing factors. Adults with cholecystitis at a safety-net hospital in Central Massachusetts from 2017–2018 were included. Sociodemographic and clinical characteristics were compared based on Medicaid enrollment status (Medicare excluded). Univariate and multivariate analyses were used to compare the frequency of surgery, time to surgery (TTS), length of stay (LOS), and readmission rates between groups. The sample (n = 203) included 69 Medicaid enrollees (34%), with a mean age of 44.4 years. Medicaid enrollees were younger (p = 0.0006), had lower levels of formal education (high school diploma attainment, p < 0.0001), were more likely to be unmarried (p < 0.0001), Non-White (p = 0.0012), and require an interpreter (p < 0.0001). Patients in both groups experienced similar rates of laparoscopic cholecystectomy, TTS, and LOS; however, Medicaid enrollees experienced more readmissions within 30 days of discharge (30.4% vs 17.9%, p < 0.001). Despite anticipated population differences, the treatment of acute cholecystitis was similar between Medicaid and Non-Medicaid enrollees, with the exception of readmission. Further research is needed to identify patient, provider, and/or population factors driving this disparity.
Sedimentological and stratigraphic analyses as a guide for reservoir quality prediction and distribution: a case study of X1 and X2 reservoirs in Koca field, Niger delta

The basic architecture of reservoir models is heavily impacted by the stratigraphic interpretation. The estimation of in-place hydrocarbon volumes and recoverable hydrocarbon volumes will rely on the accuracy of predicting and distributing reservoir quality away from well control. In this paper the interpretation of sedimentological and stratigraphic analyses is used to define reservoir geometry, lateral continuity and determine technique needed for 3D static modelling. The objective of this study is to use a sequence stratigraphic framework and depositional model to predict the characteristic fabric of X1 and X2 reservoirs in unknown portions of the field. Log motifs from four wells (Koca-01, Koca-02, Koca-03 and Koca-04) and core report from a nearby well Z07 were used to classify facies types. Biostratigraphy data from Koca-01 were used to identify key stratigraphic markers. A sequence stratigraphic framework of the facies was built and correlated across the field. This interpretation was further used to build a conceptual depositional model that best represented the environment of deposition for these reservoirs. Results show the major facies associations as distributary channels and shoreface sands. X1 and X2 reservoirs are interpreted to be progradational sands within a highstand system tract. Correlation shows good sand connectivity and distribution of gross reservoir thickness in 2D. The depositional model in this paper was used in 3D static models to improve geometric characterization in 3D static modelling.
Comparison of laboratory calibrations of the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) at the beginning and end of the first flight season

Spectral and radiometric calibrations of the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) were performed in the laboratory in June and November, 1987, at the beginning and end of the first flight season. Those calibrations are described along with changes in instrument characteristics that occurred during the flight season as a result of factors such as detachment of the optical fibers to two of the four AVIRIS spectrometers, degradation in the optical alignment of the spectrometers due to thermally-induced and mechanical warpage, and breakage of a thermal blocking filter in one of the spectrometers. These factors caused loss of signal in three spectrometers, loss of spectral resolution in two spectrometers, and added uncertainty in the radiometry of AVIRIS. Results from in-flight assessment of the laboratory calibrations are presented. A discussion is presented of improvements made to the instrument since the end of the first flight season and plans for the future. Improvements include: (1) a new thermal control system for stabilizing spectrometer temperatures, (2) kinematic mounting of the spectrometers to the instrument rack, and (3) new epoxy for attaching the optical fibers inside their mounting tubes.
Walls and Cows: Social Media, Vigilante Vantage, and Political Discourse:

Vigilante groups in the United States and India have used social media to distribute their content and publicize violent spectacles for political purposes. This essay will tackle the spectacle of v...
Magnetic circular dichroism in Archean atmosphere and asymmetric photolysis of biomolecules: enantiomeric excess of prebiotic sugar.

In the terrestrial dipolar magnetic field, magnetic circular dichroism (MCD) of UV sunlight by paramagnetic O2 in an Archean atmosphere (mostly CO2 and N2) results in circular polarization anisotropy (~ 10−10). This is used to calculate enantiomeric excess (EE~10−13) of glyceraldehyde (3-carbon sugar) with a model that includes racemic production and asymmetric photolysis of its enantiomers. The sign and magnitude of enantiomeric excess (EE) vary with the Earth’s latitude. Unlike random noise fluctuation in spontaneous mirror symmetry breaking (SMSB) models, the sign of EE is deterministic and constant over large areas of prebiotic Earth. The magnitude is several orders greater than the mean amplitude of stochastically fluctuating EE. MCD could provide the initial EE for growth of homochirality by asymmetric autocatalysis.
The missing piece in higher education: Latina/o/x parent involvement in the pre-college preparation process from the South Texas border region

This qualitative study examines Latina/o/x parents’ perceptions and involvement in the pre-college process from the South Texas border region. Researchers have expressed student success and the lik...
Nutrient Exposure Alters Microbial Composition, Structure, and Mercury Methylating Activity in Periphyton in a Contaminated Watershed

The conversion of mercury (Hg) to monomethylmercury (MMHg) is a critical area of concern in global Hg cycling. Periphyton biofilms may harbor significant amounts of MMHg but little is known about the Hg-methylating potential of the periphyton microbiome. Therefore, we used high-throughput amplicon sequencing of the 16S rRNA gene, ITS2 region, and Hg methylation gene pair (hgcAB) to characterize the archaea/bacteria, fungi, and Hg-methylating microorganisms in periphyton communities grown in a contaminated watershed in East Tennessee (United States). Furthermore, we examined how nutrient amendments (nitrate and/or phosphate) altered periphyton community structure and function. We found that bacterial/archaeal richness in experimental conditions decreased in summer and increased in autumn relative to control treatments, while fungal diversity generally increased in summer and decreased in autumn relative to control treatments. Interestingly, the Hg-methylating communities were dominated by Proteobacteria followed by Candidatus Atribacteria across both seasons. Surprisingly, Hg methylation potential correlated with numerous bacterial families that do not contain hgcAB, suggesting that the overall microbiome structure of periphyton communities influences rates of Hg transformation within these microbial mats. To further explore these complex community interactions, we performed a microbial network analysis and found that the nitrate-amended treatment resulted in the highest number of hub taxa that also corresponded with enhanced Hg methylation potential. This work provides insight into community interactions within the periphyton microbiome that may contribute to Hg cycling and will inform future research that will focus on establishing mixed microbial consortia to uncover mechanisms driving shifts in Hg cycling within periphyton habitats.
Feature Selection on a Flare Forecasting Testbed: A Comparative Study of 24 Methods

The Space-Weather ANalytics for Solar Flares (SWAN-SF) is a multivariate time series benchmark dataset recently created to serve the heliophysics community as a testbed for solar flare forecasting models. SWAN-SF contains 54 unique features, with 24 quantitative features computed from the photospheric magnetic field maps of active regions, describing their precedent flare activity. In this study, for the first time, we systematically attacked the problem of quantifying the relevance of these features to the ambitious task of flare forecasting. We implemented an end-to-end pipeline for preprocessing, feature selection, and evaluation phases. We incorporated 24 Feature Subset Selection (FSS) algorithms, including multivariate and univariate, supervised and unsupervised, wrappers and filters. We methodologically compared the results of different FSS algorithms, both on the multivariate time series and vectorized formats, and tested their correlation and reliability, to the extent possible, by using the selected features for flare forecasting on unseen data, in univariate and multivariate fashions. We concluded our investigation with a report of the best FSS methods in terms of their top-k features, and the analysis of the findings. We wish the reproducibility of our study and the availability of the data allow the future attempts be comparable with our findings and themselves.
Dissecting ITC data of metal ions binding to ligands and proteins.

Abstract Background ITC is a powerful technique that can reliably assess the thermodynamic underpinnings of a wide range of binding events. When metal ions are involved, complications arise in evaluating the data due to unavoidable solution chemistry that includes metal speciation and a variety of linked equilibria. Scope of review This paper identifies these concerns, provides recommendations to avoid common mistakes, and guides the reader through the mathematical treatment of ITC data to arrive at a set of thermodynamic state functions that describe identical chemical events and, ideally, are independent of solution conditions. Further, common metal chromophores used in biological metal sensing studies are proposed as a robust system to determine unknown solution competition. Major conclusions Metal ions present several complications in ITC experiments. This review presents strategies to avoid these pitfalls and proposes and experimentally validates mathematical approaches to deconvolute complex equilibria that exist in these systems. General significance This review discusses the wide range of complications that exists in metal-based ITC experiments. It provides a starting point for scientists new to this field and articulates concerns that will help experienced researchers troubleshoot experiments. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.
LUCIA: An Open Source 3D Expressive Avatar for Multimodal h.m.i.

LUCIA is an MPEG-4 facial animation system developed at ISTC-CNR. It works on standard Facial Animation Parameters and speaks with the Italian version of FESTIVAL TTS. To achieve an emotive/expressive talking head LUCIA was built from real human data physically extracted by ELITE optic-tracking movement analyzer. LUCIA can copy a real human being by reproducing the movements of passive markers positioned on his face and recorded by the ELITE device or can be driven by an emotional XML tagged input text, thus realizing true audio/visual emotive/expressive synthesis. Synchronization between visual and audio data is very important in order to create the correct WAV and FAP files needed for the animation. LUCIA’s voice is based on the ISTC Italian version of FESTIVAL-MBROLA packages, modified by means of an appropriate APML/VSML tagged language. LUCIA is available in two different versions: an open source framework and the “work in progress” WebGL.
Direct effects of ethane dimethanesulphonate on epididymal function in adult rats. An in vitro demonstration.

It was recently demonstrated that the Leydig cell toxicant ethane dimethanesulphonate (EDS) produces multiple effects on the epididymis after a single in vivo exposure. To determine whether any of the perturbations were mediated by a direct action of the compound, we used a novel system for the coculture of epididymal epithelial cells and sperm from the caput epididymidis. This system maintains the morphologic integrity and cell polarity of the epididymal epithelial cells before and during coculture, and the sperm recovered after coculture have intact plasma and acrosomal membranes. In addition, several functions required for epididymal sperm maturation are expressed, including the secretion of protein by the epididymal epithelium, the association of secreted protein with the plasma membrane of cocultured sperm, and the acquisition of progressive motility by cocultured sperm. In vitro exposure of epididymal epithelial cells and sperm to EDS results in a significant decline in protein secretion by the epithelial cells during coculture, and in particular, a dose-dependent decline in a 36- to 38-kd protein (PI 4.0 to 4.5) and a 34- to 36-kd protein (PI 4.5 to 5.0). Moreover, these and other proteins are not recovered from the sperm membrane of cocultured sperm after EDS treatment. Finally, EDSmore » results in a dose-dependent decline in the percentage of both motile and progressively motile sperm recovered after coculture compared with that of sperm from untreated cocultures.« less
Managing urban/industrial wood fuel supply and demand in africa

This paper develops a strategy for the continuing and improved supply of woodfuels to urban and industrial consumers in Sub-Sahara Africa. It argues that continued use of these fuels is not only a necessity, but is also in the best economic interest of most of the countries in this region. It shows that intensified and more orderly utilization of woodfuels can help to enhance, rather than impinge upon environmental parameters. Some examples are provided that illustrate how such strategies can be put into practice.
Cytokine activation of the hypothalamo–pituitary–adrenal axis

Abstract The discovery that peripheral administration of interleukin-1 (IL-1) to rats potently activated the hypothalamo–pituitary–adrenocortical (HPA) axis, initiated a new understanding of the interactions between the immune system and the brain. It was proposed, and widely accepted that the increase in circulating concentrations of glucocorticoids provided a negative feedback to limit immune activity, and to prevent autoimmunity. Administration of certain other cytokines (interleukin-6, IL-6, tumor necrosis factor α, and certain interferons) also activates the HPA axis, but none is as potent or as effective as IL-1. This chapter reviews the evidence that cytokines activate the HPA axis, and the mechanisms by which they do so. Many of the cytokines appear to act via the brain, resulting in the activation of the corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus. However, direct actions of cytokines on the anterior pituitary and on the adrenal cortex may also occur. Interestingly, some cytokines (most notably IL-1 and IL-6) appear to activate the HPA axis at multiple levels, and by multiple mechanisms. This suggests that the ability of IL-1 and IL-6 (and possibly other cytokines) to elevate circulating glucocorticoids may be critical to the survival of the organism.
MACEDON: methodology for automatically creating, evaluating, and designing overlay networks

Currently, researchers designing and implementing large-scale overlay services employ disparate techniques at each stage in the production cycle: design, implementation, experimentation, and evaluation. As a result, complex and tedious tasks are often duplicated leading to ineffective resource use and difficulty in fairly comparing competing algorithms. In this paper, we present MACEDON, an infrastructure that provides facilities to: i) specify distributed algorithms in a concise domain-specific language; ii) generate code that executes in popular evaluation infrastructures and in live networks; iii) leverage an overlay-generic API to simplify the interoperability of algorithm implementations and applications; and iv) enable consistent experimental evaluation. We have used MACEDON to implement and evaluate a number of algorithms, including AMMO, Bullet, Chord, NICE, Overcast, Pastry, Scribe, and SplitStream, typically with only a few hundred lines of MACEDON code. Using our infrastructure, we are able to accurately reproduce or exceed published results and behavior demonstrated by current publicly available implementations.
A polynomial time algorithm for computing the area under a GDT curve

Background Progress in the field of protein three-dimensional structure prediction depends on the development of new and improved algorithms for measuring the quality of protein models. Perhaps the best descriptor of the quality of a protein model is the GDT function that maps each distance cutoff θ to the number of atoms in the protein model that can be fit under the distance θ from the corresponding atoms in the experimentally determined structure. It has long been known that the area under the graph of this function (GDT_A) can serve as a reliable, single numerical measure of the model quality. Unfortunately, while the well-known GDT_TS metric provides a crude approximation of GDT_A, no algorithm currently exists that is capable of computing accurate estimates of GDT_A.
A Study of the Factors Involved in the Production of Gastric Ulcers by the Restraint Technique

Summary 1.Six species of experimental animals were tested for the production of gastric ulcers by restraining the animals in wire screen for 24 hours. Mice, rats, guinea pigs, and hamsters had an incidence of gastric ulceration of 92, 86, 46, and 4 per cent, respectively. Gastric ulcers were not induced in rabbits or monkeys by the restraint technique. 2.As the time period of the restraint of the rat was increased from 6 to 24 hours, the incidence of gastric ulcer increased. Recovery of the stomach to normal after 24 hours of restraint required 72 hours. 3.The incidence of gastric ulcers in rats that were deprived of food was found to be higher than that of fed rats, when both groups were restrained for the same time period. Food deprivation also prolonged the time required for the gastric mucosa to return to normal. 4.Younger rats (50 to 185 gm.) had a higher incidence of gastric ulcers than older rats (over 250 gm.) when both groups were subjected to short periods of restraint. Weight did not seem to be an important variable when the rats were restrained for a period of 24 hours. 5.Repeated periods of restraint, 18 hours a day, increased the incidence and severity of gastric ulcers. Rumen ulcers were produced by this procedure. 6.In rats, 8 days after operation, hypophysectomy and bilateral subdiaphragmatic vagotomy did not reduce significantly the incidence of animals with ulcers. Bilateral adrenalectomy significantly increased the incidence and severity of the ulcers produced by restraint. 7.The restraint technique provides a simple, rapid, nonsurgical means of producing ulcers in the glandular portion of the stomach.
Protein‐based Artificial Enzymes

Originally published in: Artificial Enzymes. Edited by Ronald Breslow. Copyright © 2005 Wiley-VCH Verlag GmbH & Co. KGaA Weinheim. Print ISBN: 3-527-31165-1 The sections in this article are Introduction Artificial Nucleases Based on DNA and RNA Binding Proteins Introduction Artificial Nucleases from Native Protein Scaffolds OP Nuclease Design by Mutagenesis and Chemical Modification Additional Applications for OP Conjugates A Fe-EDTA Artificial Nuclease Concluding Remarks Catalysts Based on Hollow Lipid-binding Proteins Lipid-binding Proteins Initial Work Exploiting the Advantage of a Protein-based Scaffold Catalytic Turnover with Rate Acceleration Modulation of Cofactor Reactivity with Metal Ions Chemogenetic Approach Adding Functional Groups within the Cavity Scaffold Redesign Hydrolytic Reactions A Flavin-containing Conjugate Some Limitations Myoglobin as a Starting Point for Oxidase Design Artificial Metalloproteins and Myoglobin Non-covalent Attachment of a Redox Center Dual Anchoring Strategy Antibodies as Scaffolds for Catalyst Design Antibodies as Specificity Elements Incorporation of an Imidazole Functional Group into an Antibody for Catalysis Comparison of Imidazole-containing Antibodies Produced by Chemical Modification and Site-directed Mutagenesis Conclusions Keywords: artificial enzymes; protein-based artificial enzymes; artificial nucleases; DNA and RNA binding proteins; catalysts; hollow lipid-binding proteins; myoglobin; starting point for oxidase design; antibodies scaffolds for catalyst design
32 – Venous Thromboembolism: Gender Effects and Gender-Specific Risk Factors for Women

This chapter discusses the symptoms, epidemiology, and risk factors of venous thromboembolism (VTE). It focuses on gender-specific risk factors for VTE among women, as well as on special considerations in the diagnostic and therapeutic approaches to VTE in the pregnant patients. The incidence of VTE increases markedly with increasing age. The incidence of VTE does not appear to vary significantly by gender, as evidenced by a lack of consistency in the magnitude and even direction of effect of gender in a variety of epidemiologic studies of varying designs. The main influence of gender upon VTE is the relationship between female gender and several well-recognized clinical risk factors for VTE-Oral contraceptives (OCs) use, hormone replacement therapy (HRT), estrogen receptor modulator therapy, and pregnancy. The fact that women of childbearing age do not appear to have a substantially greater incidence of VTE compared with age-matched men may reflect an offsetting of these female-specific risk factors by other risk factors that are more common in men, such as trauma. Hormonal therapies are associated with a 2- to 3-fold increase in VTE incidence. The pregnancy state is associated with a 3- to 5-fold increase in VTE risk, and thromboembolism is a major cause of peripartum death.
The development of sleeping and waking states in high-risk preterm infants☆

Abstract This study examined the development of sleeping and waking states in high-risk preterm infants. Thirty-seven preterm infants were observed from 7 p.m. to 11 p.m. weekly from the time their conditions were no longer critical until term age or hospital discharge. An average of 3.6 observations was conducted on each infant between 29 and 39 weeks conceptional age (CA). During the observations, the occurrence of eight sleep-wake states was recorded every 10 s. The intensity of rapid eye movements in active sleep and the regularity of respiration in quiet sleep were also rated. Similar state patterns were found at all ages, with active sleep the most frequent state, quiet sleep the second most frequent, and drowsiness and sleep-wake transition third and fourth. Waking states made up only small percentages of the observations at every age. Despite these similarities, four states exhibited significant changes over age: the amount of active sleep decreased, and fuss, cry, and quiet sleep increased. The organization of the sleep states also increased, as evidenced by an increase in the percent of active sleep with rapid eye movements and an increase in the regularity of respiration in quiet sleep. The severity of illness experienced by the infants had only minor effects on these patterns. These findings demonstrate that even high-risk infants show behavioral states by 29 weeks CA and that considerable state development occurs over the preterm period. Additional research is needed to determine the effects of time of day, caregiving environments, and specific insults on state development.
Southern California Structure, Sea-Floor Spreading, and History of the Pacific Basin

Coastal southern California is east of the Darwin Rise and west of the East Pacific Rise. Accordingly, southern California structural history has implications regarding Pacific Ocean Basin history, particularly the age and nature of the Darwin and East Pacific Rises and the Murray fracture zone, using the sea-floor-spreading model. The Darwin Rise is related to the Franciscan and has a minimum age range of Jurassic to early Late Cretaceous. The Murray fracture zone can be dated through paleogeographic reconstruction of the Late Cretaceous-Early Tertiary coastal sequence; it formed later than Maestrichtian, but no later than middle Eocene time. During the Miocene, the East Pacific Rise moved eastward under the Coast Ranges at a rate of 5.6 cm/yr, producing volcanism and rift topography as it passed, and reaching the site of the Gulf of California in latest Miocene time.
Noise spectra of sodium and hydrogen ion transport at a cation membrane—solution interface

Abstract The noise spectra accompanying transport of Na+ and H+ at a cation membrane—solution interface were studied as a function of concentration and current density. Low-current spectra, below the critical current density (CCD), were characteristic of diffusion. Spectra measured above the CCD showed steep slopes and there is now evidence indicating differences between H+ and Na+. There is also evidence indicating a change in transport mode at currents above approximately twice the CCD. The intensity of the spectra above the CCD is discussed here for the first time. An approximately fourth-power dependence on excess current (above the CCD) is found at sufficiently high current, which appears to require a far from equilibrium mechanism. The best available interpretation is hydrodynamic turbulence at high current; however, an alternate possibility, electrochemical instability, as suggested by Rubinstein (7), is also discussed.
Annexin-A7 protects normal prostate cells and induces distinct patterns of RB-associated cytotoxicity in androgen-sensitive and -resistant prostate cancer cells.

The tumor suppressor role of annexin-A7 (ANXA7) was previously demonstrated by cancer susceptibility in Anxa7(+/−)-mice and by ANXA7 loss in human cancers, especially in hormone-resistant prostate tumors. To gain mechanistic insights into ANXA7 tumor suppression, we undertook an in vitro study in which we compared wild-type (WT)-ANXA7 and dominant-negative (DN)-ANXA7 effects to a conventional tumor suppressor p53 in prostate cancer cells with different androgen sensitivity. Unlike p53 (which caused cell growth arrest and apoptosis to a noticeable extent in benign PrEC), WT-ANXA7 demonstrated profound cytotoxicityin androgen-sensitive LNCaP as well as in the androgen-resistant DU145 and PC3 prostate cancer cells, but not in PrEC. In androgen-sensitive LNCaP, WT-ANXA7 decreased low-molecular-weight (LMW) AR protein forms and maintained higher retinoblastoma 1 (RB1)/phospho-RB1 ratio. In contrast, DN-ANXA7 (which lacks phosphatidylserine liposome aggregation properties) increased LMW-AR forms and hyperphosphorylated RB1 that was consistent with the lack of DN-ANXA7 cytotoxicity. According to the microarray-based Ingenuity Pathways Analysis, a major WT-ANXA7 effect in androgen-sensitive LNCaP constituted of upregulation of the RB1-binding transcription factor E2F1 along with its downstream proapoptotic targets such as ASK1 and ASPP2. These results suggested a reversal of the RBdependent repression of the proapoptotic E2F-mediated transcription. However, DN-ANXA7 increased RB1/2 (but not E2F1) expression and induced the proliferation-promoting ERK5, thereby maintaining the RB-dependent repression of E2F-mediated apoptosis in LNcaP. On the other hand, in androgen-resistant cells, WT-ANXA7 tumor suppressor effects involved PTEN and NFkB pathways. Thus, ANXA7 revived the RB-associated cell survival control and overcame androgen resistance and dysfunctional status of major tumor suppressors commonly mutated in prostate cancer. Published 2009 UICC.
Hume on sympathy

Analyse de la sympathie chez Hume dans le contexte de sa theorie des passions, et en termes des notions de relation, d'impression, et d'idees. La sympathie est la conversion d'une idee en impressions. La sympathie rend possible l'approbation morale.
Standard Errors of Measurement for the Various MMPI Subscales

If an individual takes more than one MMPI the subscale scores are likely to vary. The individual giving the test may wish to identify significant changes between subscale scores. Standard errors of measurement may be beneficial in this regard. The purpose of this study was to compute the standard errors of measurement for each of the MMPI subscales. A table is also provided for individuals who wish to use these data.
Isolation of a guanylate cyclase inhibitor from the balsam pear (Momordica charantia abreviata).

Summary The balsam pear ( Momordica charantia abreviata ) is a plant which grows wild throughout subtropical regions including the Gulf Coast and Florida. The ripe fruit is highly toxic and produces mild hypoglycemia. Preparations of the ripe fruit and the leaves but not the unripe fruit or seeds inhibited guanylate cyclase activity whereas adenylate cyclase activity was unaffected. The guanylate cyclase inhibitor (GCI) has been purified about 30-fold has an estimated molecular weight of 5000 to 50,000 and is acid stable and heat labile. GCI blocked the activation of guanylate cyclase by nitroso chemical carcinogens, and therefore, may be useful in studying mechanisms of chemical carcinogenesis.