gebhart/patrepeval huggingface dataset:
Prediction of Drug-Induced Liver Injury in Micropatterned Co-cultures Containing iPSC-Derived Human Hepatocytes (2015)

Primary human hepatocytes (PHHs) are a limited resource for drug screening, their quality for in vitro use can vary considerably across different lots, and a lack of available donor diversity restricts our understanding of how human genetics affect drug-induced liver injury (DILI). Induced pluripotent stem cell-derived human hepatocyte-like cells (iPSC-HHs) could provide a complementary tool to PHHs for high-throughput drug screening, and ultimately enable personalized medicine. Here, we hypothesized that previously developed iPSC-HH-based micropatterned co-cultures (iMPCCs) with murine embryonic fibroblasts could be amenable to long-term drug toxicity assessment. iMPCCs, created in industry-standard 96-well plates, were treated for 6 days with a set of 47 drugs, and multiple functional endpoints (albumin, urea, ATP) were evaluated in dosed cultures against vehicle-only controls to enable binary toxicity decisions. We found that iMPCCs correctly classified 24 of 37 hepatotoxic drugs (65% sensitivity), while all 10 non-toxic drugs tested were classified as such in iMPCCs (100% specificity). On the other hand, conventional confluent cultures of iPSC-HHs failed to detect several liver toxins that were picked up in iMPCCs. Results for DILI detection in iMPCCs were remarkably similar to published data in PHH-MPCCs (65% versus 70% sensitivity) that were dosed with the same drugs. Furthermore, iMPCCs detected the relative hepatotoxicity of structural drug analogs and recapitulated known mechanisms of acetaminophen toxicity in vitro. In conclusion, iMPCCs could provide a robust tool to screen for DILI potential of large compound libraries in early stages of drug development using an abundant supply of commercially available iPSC-HHs.
Digitoxin kinetics and renal excretion in children (1983)

Digitoxin kinetics were investigated in 11 children, three girls and eight boys, with a mean age of 7.1 yr (5.9 to 9.2). Five children received digitoxin, 17.5 to 20 micrograms/kg IV, and six other children received 20 micrograms/kg as an oral solution. Digitoxin was given as a single dose 24 to 48 hr after cardiac surgery, and patients were monitored in an intensive care unit for 24 hr. Serum and urine digitoxin concentrations were determined by radioimmunoassay. Children had larger apparent volumes of distribution (1 l/kg) than adults (0.57 l/kg). Mean serum elimination t 1/2 was 6.4 days in children (3 to 11.2) and 8.2 days in adults (5.9 to 11.3). Total body clearance was much greater in children (0.085 ml X min-1 X kg-1) than in adults (0.036 ml X min-1 X kg-1). This was because of an increase in metabolic clearance, although there was no difference in renal clearance in children and adults. Absolute oral bioavailability, measured by comparing serum AUCs after intravenous and oral doses, was complete. Peak serum concentrations of 23 to 50 ng/ml developed 90 to 120 min after the oral dose. A single digitalization dose of 20 micrograms/kg was well tolerated and did not induce arrhythmias.
Development of a Test Technique to Determine the Thermal Diffusivity of Large Refractory Ceramic Test Specimens (2011)

A method has been developed to utilize a high‐intensity plasma arc lamp located at Oak Ridge National Laboratory for the measurement of thermal diffusivity of bulk refractory materials at elevated temperatures. The applicability of standardized test methods to determine the thermal diffusivity/conductivity of refractory materials at elevated temperatures is limited to small sample sizes (laser flash) or older test methods (hot wire, guarded hot plate), which have their own inherent problems. A new method, based on the principle of the laser flash method, but capable of evaluating test specimens on the order of 200 mm × 250 mm × 50 mm, has been developed. Tests have been performed to validate the method and preliminary results are presented in this paper.
Kernicterus and central pontine myelinolysis in a 14‐year‐old boy with fulminating viral hepatitis (1980)

Abstract An adolescent boy with severe viral hepatitis and elevated unconjugated bilirubin was diagnosed postmortem to have kernicterus and central pontine myelinolysis. This association has not been reported previously.
Subgraph Enumeration in Dynamic Graphs (2013)

A fundamental problem in many applications involving social and biological networks is to identify and count the number of embeddings of a given small sub graph in a large graph. Often, they involve dynamic graphs, in which the graph changes incrementally (e.g., by edge addition/deletion). We study the Dynamic Sub graph Enumeration (DSE) Problem, where the goal is to maintain a dynamic data structure to solve the sub graph enumeration problem efficiently when the graph changes incrementally. We develop a new data structure that combines two techniques: (i) the color-coding technique of Alon et al., 2008, for enumerating trees, and (ii) a dynamic data structure for maintaining the h-index of the graph (developed by Eppstein and Spiro, 2009). We derive worst case bounds for the update time in terms of the h-index of the graph and the maximum degree. We also study the empirical performance of our algorithm in a large set of real networks, and find significant improvement over the static methods.
Effects of age and gender on sleep-related plasma renin levels (2007)

In young normal males large oscillations of plasma renin activity (PRA) with a 90min periodicity occur, which show a distinct association to the rapid-eye-movement (REM)-nonREM (NREM) sleep cycle. PRA increases during NREM sleep and decreases during REM sleep. Changes during the life span and gender differences were found in sleep- electroencephalogram (EEG) and nocturnal secretion of various hormones. In order to clarify whether aging and gender affect free renin levels, we investigated sleep electroencephalogram (EEG) and PRA in 47 healthy subjects (24 females, 23 males, age 18–69yrs). Simultaneously sleep EEG was recorded (23:00–07:00) during sleep and renin plasma samples were collected every 20 minutes. The characteristical oscillations of renin concentration were preserved during ageing and occur in women and men as well. Similar to previous findings on PRA at daytime in humans, an age related decline of renin mean concentrations was found. Subjects 40 years and younger had higher nocturnal renin levels than those older than 40 years. Furthermore a negative correlation between age and renin mean concentrations was found. As expected slow wave sleep (SWS) showed also a negative correlation with age. Similar to growth hormone and melatonin sleep associated renin secretion appears to decline between adolescence and adulthood. At daytime lower PRA was reported in women than in man. As well we found lower nocturnal renin mean concentrations in women than in man.
Factored spatial and spectral multichannel raw waveform CLDNNs (2016)

Multichannel ASR systems commonly separate speech enhancement, including localization, beamforming and postfiltering, from acoustic modeling. Recently, we explored doing multichannel enhancement jointly with acoustic modeling, where beamforming and frequency decomposition was folded into one layer of the neural network [1, 2]. In this paper, we explore factoring these operations into separate layers in the network. Furthermore, we explore using multi-task learning (MTL) as a proxy for postfiltering, where we train the network to predict "clean" features as well as context-dependent states. We find that with the factored architecture, we can achieve a 10% relative improvement in WER over a single channel and a 5% relative improvement over the unfactored model from [1] on a 2,000-hour Voice Search task. In addition, by incorporating MTL, we can achieve 11% and 7% relative improvements over single channel and unfactored multichannel models, respectively.
The Application of Micro Reactors for Organic Synthesis (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Integrating sphere simulation: application to total flux scale realization (1994)

A method is proposed for realizing the total flux scale of light sources by use of an integrating sphere with an opening to introduce a known amount of flux from a luminous intensity standard or a spectral irradiance standard lamp placed outside the sphere. Computer simulations were made on several models of an integrating sphere, designed to compare the total flux of a test lamp inside the sphere with the flux introduced from an external source. I describe the theory and algorithm of the simulation, present the results of the simulation for varying conditions of sphere geometry such as size and location of the baffles, internal source, and wall reflectance, and predict that one of the models has sufficient accuracy to calibrate lamps for total flux.
Supplementary Figure 1 from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners (2023)

&lt;p&gt;Supplementary Figure 1&lt;/p&gt;
Immunosuppression induite par les UVs (2013)

Le rayonnement UV perturbe le systeme immunitaire cutane et induit une diminution des defenses immunitaires reduisant la capacite de surveillance vis‐a‐vis des tumeurs ou des antigenes viraux ou etrangers (pour revues voir : (Norval, 2002 ; Schwarz, 2010 ; Ullrich et Byrne, 2012 ; Kripke, 2013)). I. Mode d'action des UV Les UV agissent a plusieurs niveaux de la reponse immunitaire : • En alterant le nombre, la morphologie et la fonction des cellules de Langerhans : les cellules de Langerhans vont (...)
Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. (2011)

4037 Background: Response to neoadjuvant chemotherapy is an independent prognostic factor in locally advanced gastric cancer. However, no prospectively tested pretherapeutic parameters predicting response and/or survival in gastric cancer are available in clinical routine so far. Methods: We evaluated the prognostic significance of various clinicopathologic parameters in 410 patients who were treated with neoadjuvant chemotherapy followed by gastrectomy. Clinical and histopathological response evaluation was performed using standardized criteria. A prognostic score was created on the basis of the variables identified in the multivariate analysis. Results: Three pretherapeutic parameters were identified as positive predictive factors for response and prognosis by multivariate analysis: tumor localization in the middle (p=0.001), well differentiated tumors (p=0.001) and intestinal tumor type according to Laurén’s classification (p=0.03). A prognostic index was constructed, dividing the patients into three risk groups: low (n=73), intermediate (n=274) and poor (n=63). The three groups had significantly different clinical (p=0.007) and histopathological response rates (p=0.001) and survival times, with a median survival for the low, intermediate and poor risk groups being not reached, 39.3 and 20.5 months, and the corresponding 5 year survival rates being 65.3%, 41.2%, 21.2% (p<0.001), respectively. Conclusions: A simple scoring system based on three clinicopathologic parameters accurately predicts response and prognosis in neoadjuvant treated gastric cancer. This system provides additional useful information that could be applied to select gastric cancer patients pretherapeutically for different treatment approaches. Prospective testing of the score in an independent patient cohort is warranted.
On the ultimate x-ray detector for angiography (2005)

The purpose of our research is to describe the ultimate X-ray detector for angiography. Angiography is a well established X-ray imaging technique for the examination of blood vessels. Contrast agent is injected followed by X-ray exposures and possible obstructions in the blood vessels can be visualized. Standard angiography primarily inspects for possible occlusions and views the vessels as rigid pipes. However, due to the beating heart the flow in arteries is pulsatile. Healthy arteries are not rigid tubes but adapt to various pressure and flow conditions. Our interest is in the (small) response of the artery on the pulse flow. If the arteries responses elastically on the pulse flow, we can expect that it is still healthy. So the detection of artery diameter variations is of interest for the detection of atherosclerosis in an early stage. In this contribution we specify and test a model X-ray detector for its abilities to record the responses of arteries on pulsatile propagating flow distributions. Under normal physiological conditions vessels respond with a temporal increase in arterial internal cross-sectional area of order 10%. This pulse flow propagates along the arteries in response of the left ventricle ejections. We show results of the detection of simulated vessel distensabilities for the model detector and discuss salient parameters features.
Armanni–Ebstein Lesions: A Need for Clarification (2012)

Armanni-Ebstein lesions were first described by Luciano Armanni, a pathologist at the University of Naples, during autopsy studies undertaken in 1872, as a unique vacuolar nephropathy associated with poorly controlled diabetes that involves selective renal epithelial cell glycogen accumulation. However, within the last two decades, a broader range of vacuolar changes, including lipid deposition, have also been termed Armanni-Ebstein (AE) lesions, creating some confusion on possible etiology. We would suggest that the term AE phenomenon would be best reserved for the original clear cell change associated with glycogen deposition, and that this should be clearly distinguished from subnuclear lipid vacuolization ("basal vacuolization"). Although there is obvious inter-relation between these two types of vacuoles, they appear morphologically and biochemically distinct from each other. More precise classification may assist in clarifying the causal processes and possible diagnostic significance of different types of renal epithelial vacuolization at autopsy.
Phototimer setup for CR imaging (2000)

A study was performed to investigate the feasibility of using the standard deviation (sigma) of the pixel values in a computed radiography (CR) image and a measure of the median incident exposure on the imaging plate (IP) as parameters for setting up phototimers in a CR system. Slabs of Lucite 4-, 6-, and 8-in.-thick were imaged with a CR system at 70, 90, and 125 kVp at various mA s values both with grid and without grid. Incident IP exposures were measured with an ionization chamber. Images were analyzed on a workstation. The sigma's in the "flat field" images were found to be approximately related to the mean incident exposure E by the relationship: sigma is proportional to E(-1/2), indicating the quantum-noise-limited operation of the system. Derived relationships between the reading sensitivity of the (IP) reader (S number) and sigma can be used to obtain images with a specific noise level. At our institution, where a 400 speed screen-film system is used for general radiography and 200 speed for chest radiography, radiologists generally find CR image quality acceptable when sigma < or = 11 (S< or =400) for general radiography (50-90 kVp), and sigma < or =8 (S< or =200) for chest radiography (125 kVp). However, factors other than the amount of x-ray quanta that form the useful image, such as the image processing mode and the amount of collimation, may affect both the sensitivity value and the image quality.
Glucocorticoid receptor: A potent cellular & gene therapy target for cancer and cancer stem cells (2017)

Glucocorticoid receptor (GR) is expressed in the cytoplasm of almost all cells, if not all of cancer and non-cancer cells. Moreover, unlike many other factors implicated with cancer, it is neither overexpressed nor is it expressed on cell-membrane surface to qualify logically as a viable target for treating cancer. GR is importantly linked with alternate pathway of energy metabolism in cancer cells and our research indicated that cancer cells possibly tend to avoid activation of GR which would have otherwise instigate that energy demanding alternate pathway called gluconeogenesis. We discovered a way to induce cancer cell-selective GR-transactivation which leads to among many things, gluconeogenesis, reversal of epithelial-to-mesenchymal transition (EMT), drug- sensitization in drug-resistant cancer cells etc. Thus, we proved, although it warrants further studies, that GR in cancer cells behave differently and hence it can be a viable target for the treatment of cancer.
Variation in Early-Onset Sepsis Risk Assessment in Asymptomatic Term and Near-Term Infants in Portugal (2021)

Introduction: Identification of well-appearing infants at risk for early-onset sepsis presents an ongoing challenge. Several guidelines advise categorical risk assessment strategies, resulting in excessive laboratory tests, admissions, and antibiotic use. Currently, approaches using multivariate risk assessment or serial clinical observation are gaining ground. The primary objective of this study was to describe early-onset-sepsis risk management across a national sample of postnatal wards. Methods: A Web-based survey was sent to 51 neonatal units in Portugal, between April and June 2021, to assess local management protocol for term and near-term newborns at risk for early-onset sepsis. Results: Thirty-four responses were obtained (out of a total of 65 161 deliveries in 2020). Sociedade Portuguesa de Neonatologia guidelines were followed in 17 out of 34 units. Most units (31/34) used categorical risk assessment and three used serial clinical observation. The considered risk factors differed and the most frequently identified included chorioamnionitis (33/34) and prolonged rupture of membranes (31/34). The most frequent timing for sepsis evaluation was between 6 and 12 hours of life and included blood count and C-reactive protein in all units. Most units (29/33) opted for empiric antibiotics, according to clinical assessment and C-reactive protein values. Antibiotic therapy is started in all cases of chorioamnionitis in 12 out of 34 units. Asymptomatic infants with negative cultures are treated for five or more days in 16 out of 34 units, and in 22 units this is done in the neonatal unit. The majority (25/34) considers possible to adopt a serial clinical evaluation approach. Main concerns were local staff resources (16/24). Discussion: There is wide variability regarding early-onset-sepsis risk assessment in Portugal. Therefore, it is crucial to standardize clinical pathways to avoid unnecessary interventions.
Serum Chemerin Levels Vary with Time of Day and Are Modified by Obesity and Tumor Necrosis Factor-α (2010)

Chemerin is an adipokine with important regulatory roles in adipogenesis. In humans, serum total chemerin (i.e. prochemerin plus chemerin) levels are positively associated with body mass index and metabolic syndrome. However, the mechanisms that increase serum chemerin concentration are unknown. We hypothesized that chronic low-grade inflammation that occurs in obesity promotes chemerin production by adipocytes. Consistent with this, TNFalpha treatment of 3T3-L1 adipocytes increased bioactive chemerin levels in the cell media as detected using a CMKLR1 cell-based bioassay. This effect was blocked by the protein synthesis inhibitor cycloheximide and protein secretion inhibitor brefeldin A, indicating that TNFalpha may enhance prochemerin synthesis and secretion from adipocytes. In vivo, TNFalpha produced a time-dependent increase in serum total chemerin and bioactive chemerin. Bioactive chemerin was produced by primary mouse adipocytes and hepatocytes. Only primary adipocyte-derived chemerin was responsive to TNFalpha regulation implicating adipocytes as a potential source of elevated serum chemerin after TNFalpha exposure in vivo. In lean mice, serum total chemerin levels oscillated with peak levels occurring during daytime and trough levels at night. Comparatively, leptin- and leptin receptor-deficient obese mice, which have elevated adipose tissue expression of TNFalpha, displayed elevated serum total chemerin levels with an enhanced oscillatory pattern. In summary, our novel results identified TNFalpha as a positive regulator of adipocyte-derived chemerin. We corroborate the finding of elevated chemerin in obese humans by identifying elevated serum levels of total chemerin in two obese mouse models with a corresponding alteration in the rhythmic pattern of serum chemerin levels.
Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus (2013)

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging highly pathogenic virus causing almost 50 % lethality in infected individuals. The development of a small-animal model is critical for the understanding of this virus and to aid in development of countermeasures against MERS-CoV. We found that BALB/c, 129/SvEv and 129/SvEv STAT1 knockout mice are not permissive to MERS-CoV infection. The lack of infection may be due to the low level of mRNA and protein for the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), in the lungs of mice. The low level of DPP4 in the lungs likely contributes to the lack of viral replication in these mouse models and suggests that a transgenic mouse model expressing DPP4 to higher levels is necessary to create a mouse model for MERS-CoV.
Lysosomal membrane permeabilization causes secretion of IL-1β in human vascular smooth muscle cells (2018)

These data support a novel role of LMP as a single stimulus for the secretion of IL-1β from hVSMCs, implying the possibility that hVSMCs are an important initiator of the sterile inflammatory response caused by lysosomal disintegration.
텐서보팅을 이용한 K-means 군집화의 초기 파라메터 결정 (2009)

The major problem in K-means clustering is to determine the number of clusters and their starting centroids. The quality of the resulting clusters is largely dependent on the estimation of K. In this paper, we investigate a novel method based on tensor voting to estimate these initial parameters. (d+1)-D tensor voting is applied on d-dimensional data to generate a saliency map. Major peaks in the saliency map are detected to decide the number of clusters. Experimental results attained from 1-D, 2-D data points and in color image segmentation show that our method can estimate the number of clusters successfully. The proposed method can also solve some other issues in K-means clustering such as empty clusters and outliers. Empty clusters can be obtained if no points are allocated to a cluster during the assignment step. And when outliers are present, the resulting cluster centroids may not be as representative as they otherwise would be.
Simultaneous extraction of bulk lifetime and surface recombination velocities from free carrier absorption transients (1994)

Bulk lifetime and surface recombination velocities at both the front and the rear surfaces are important parameters that affect the performance of solar cells. In an earlier work [G. S. Kousik, Z. G. Ling and P. K. Ajmera, J. Appl. Phys. 72, 141 (1992)], a detailed theoretical analysis for a contactless nondestructive technique to obtain these parameters is presented. Here, the experimentally measured data using this new approach was presented. Moreover, the earlier analytical work has now been extended to also provide an estimate of the sensitivity of the extracted parameters to errors in experimental measurements. Results on measurements on single crystal silicon wafers are provided as an example.