gebhart/patrepeval huggingface dataset:
Cell Lines: A Tool for In Vitro Drug Metabolism Studies (2008)

Primary cultured hepatocytes are a valuable in vitro model for drug metabolism studies. However, their widespread use is greatly hindered by the scarcity of suitable human liver samples. Moreover, the well-known in vitro phenotypic instability of hepatocytes, the irregular availability of fresh human liver for cell harvesting purposes, and the high batch-to-batch functional variability of hepatocyte preparations obtained from different human liver donors, seriously complicate their use in routine testing. To overcome these limitations, different cell line models have been proposed for drug metabolism screening. Human liver-derived cell lines would be ideal models for this purpose given their availability, unlimited life-span, stable phenotype, and the fact that they are easy to handle. However, the human hepatoma cells currently used (i.e. HepG2, Mz-Hep-1) show negligible levels of drug-metabolizing and do not constitute a real alternative to primary hepatocytes. Different strategies have been proposed to generate metabolically competent immortalized hepatocytes (transformation of human hepatocytes with plasmids encoding immortalizing genes, hepatocyte-like cells derived from stem cells, cell lines generated from transgenic animals, hepatocyte/hepatoma hydrid cells). Moreover, recombinant models heterologously expressing P450 enzymes in different host cells have been developed and successfully used in drug metabolism testing. In addition, new strategies have recently been explored to upregulate the expression of drug-metabolizing enzymes in cell lines of a human origin (i.e. transfection with expression vectors encoding key hepatic transcription factors). Among metabolic-based drug-drug interactions, P450 inhibition seems to be the most important. A major application of recombinant models expressing a single P450 is the screening of potential enzyme inhibitors. Therefore, pharmaceutical companies increasingly make use of cell lines to speed up the selection of new drugs with favourable pharmacokinetic and metabolic properties.
Pharmacokinetics and pharmacodynamics of <i>nab</i> ‐paclitaxel in patients with solid tumors: Disposition kinetics and pharmacology distinct from solvent‐based paclitaxel (2014)

The aim of this study was to characterize population pharmacokinetics and the exposure-neutropenia relationship with nanoparticle albumin-bound (nab)-paclitaxel in patients with solid tumors. Plasma and blood concentrations of paclitaxel and neutrophil data were collected from 150 patients with various solid tumors over the nab-paclitaxel dose range of 80-375 mg/m(2). Data were analyzed using nonlinear mixed-effect modeling or logistic regression. Pharmacokinetics of nab-paclitaxel were described by a 3-compartment model with saturable distribution and elimination. The rapid disappearance of circulating paclitaxel was driven by its fast distribution to peripheral compartments; maximum rate for saturable distribution (325000 μg/h) was 40-fold greater than that for saturable elimination (8070 μg/h). Albumin was a significant covariate of paclitaxel elimination (P < .001), while total bilirubin, creatinine clearance, body size, age, sex, and tumor type had no significant or clinically relevant effect. The probability of experiencing a ≥ 50% reduction in neutrophils was best correlated to the duration above the drug concentration of 720 ng/mL. At a given exposure level, neutropenia development was positively correlated with increasing age but not significantly influenced by hepatic function, tumor type, sex, or dosing schedule. Covariate analyses supports exposure-matched dose adjustments in patients with moderate to severe hepatic impairment.
The genera Spongiococcum and Neospongiococcum. II. Species of Neospongiococcum with labile walls,<sup>2</sup> (1971)

Several species of the genus Neospongiococcum are described. The cell walls of these species, unlike other species of the genus, apparently are not composed of cellulose. Methods to determine cell wall composition, adapted from techniques previously used to study composition of cell walls of vascular plants, are described.
Clinical utility of a two-site immunoradiometric assay for creatine kinase-MB in the detection of perioperative myocardial infarction. (1983)

In 144 patients, creatine kinase MB was measured serially at 0, 8, 16, 24, 48, and 72 hr using a two-site immunoradiometric assay (IRMA). Cardiac enzymes were also measured, including SGOT, LDH, total CPK, and CK-MB by electrophoresis. The presence of perioperative myocardial infarction (poMI) was established in 24 patients by the appearance of new electrocardiographic Q waves and/or new wall motion abnormalities detected by radionuclide ventriculography. In patients without poMI, CK-MB (IRMA) was elevated (6.4 +/- 4.9 equivalent units per liter) at 0-8 hr but decreased to 3.4 +/- 1.3 EU/l by 16 hr. In patients with poMI, peak values occurred at 16-24 hr (21.0 +/- 19.8 EU/l). Using a threshold value of 8.5 EU/l, patients with poMI could be distinguished from those without with 97% accuracy (sensitivity = 88%, specificity = 99%). The CK-MB (IRMA) was more reliable than the other enzyme assays, for which we used both empirically elevated threshold values based upon previous experience, and also threshold values retrospectively optimized for the study population. We conclude that the CK-MB (IRMA) can serve as a valuable postoperative screening test for poMI.
Frameless Stereotactic Neurosurgery: Two Steps towards the Holy Grail of Surgical Navigation (1999)

The holy grail of surgical navigation is to provide precise continuous feedback during surgery about the target and its surrounding structures. The first step was the ability of hardware and software technology to allow patient-to-image registration using a multi-potentiometer position-sensing articulated arm system. We used such a system (OAS; Radionics, Burlington, Mass., USA) in 169 consecutive patients with common intracranial lesions. We achieved a mean application accuracy of 2.5 mm, which was sufficiently reliable for most neurosurgical procedures. However, to get the feedback information, the surgeon has to look away from the operative field to the workstation monitor. As psychological studies of manual workers including surgeons indicated that performance is better when the worker is looking in a downward gaze at his hands, the natural progression was to project feedback information between the eyes and the hands. Therefore, the second step was to link tracking technology to the surgical microscope with head-up display. We used such a system (SMN-Zeiss, Germany) in 65 consecutive patients with a mean application accuracy of 1.4 mm. This was again sufficiently reliable for neuronavigation. The head-up display provided continuous feedback to the surgeon about the target, risk zones and areas of interest without the need to interrupt the procedure to get such information. Furthermore, the use of the focal length of SMN with autofocus to perform the registration improved the application accuracy of this technology. The ability of the software to process all MRI sequences (T(1), T(2), MPR and CISS) allowed us to use a variety of image sequences to delineate the lesion more exquisitely.
RCTP: Region Correlated Temporal Prefetcher (2017)

Hardware prefetcher is an essential component of modern processors that helps in boosting system performance by fetching the data before processor demands for the same. Hardware prefetching techniques have been proposed to exploit various kinds of access patterns. However, there are applications that are highly irregular in nature that evolved in the past decade, and have massive memory footprint. Temporal prefetching techniques are effective in predicting the future addresses of these irregular applications. Prior works on temporal prefetching use large data structures to store temporal patterns and future memory accesses are predicted using these patterns. However, these techniques predict future accesses only when there is a pattern that is already trained for a given cache line address. To address this issue, we propose Region Correlated Temporal Prefetcher (RCTP). Our technique correlates temporal patterns of memory regions and predicts future accesses for the region whose patterns are yet to be populated. Thus, RCTP helps in predicting cache line addresses whose first access is yet to happen unlike the traditional temporal prefetchers. We evaluate RCTP on SPEC CPU 2006, CRONO, and PBBS benchmark suites. RCTP outperforms the state-of-the-art temporal prefetcher named ISB by 26%, and a recent delta prefetcher called VLDP by 6%. This improvement comes with a hardware overhead of 1KB over ISB; however, RCTP does not require off-chip storage, unlike other temporal prefetchers.
Funktionelle Trimethylphosphanderivate, XVIII [1]. Methyl(phosphinomethyl)silane und -stannane / Functional Trimethylphosphane Derivatives, XVIII [1]. Methyl(phosphinomethyl)silanes and -stannanes (1983)

Abstract Mono-and polydentate phosphanes Me (4-x) E(CH 2 PMe 2 ) x (E = Si, Sn) are prepared by the reaction of LiCH 2 PMe 2 with Me (4-x) ECl x . They are easily deprotonated at the methylen carbon atom. The preparation of BrCH 2 CMe 2 CH 2 PMe 2 and Me 2 C(CH 2 PMe 2 ) 2 is also described. The complex formation ability is shown by the isolation of the tetrahedral nickel(0) complex [Me 2 Si(CH 2 PMe 2 ) 2 ] 2 Ni, where the diphosphane acts as a bidentate chelating ligand with heteroelement bridges. The new compounds are characterized by means of NMR spectroscopy.
Glucoamylase Research: An Overview (1995)

Abstract This paper reviews the main features of glucoamylase research describing essentially more recent developments on microorganisms, production and properties of glucoamylases. It is an important industrial enzyme and is widely used in starch saccharification, brewing and distilling industry. Glucoamylase can be derived from a wide variety of sources including plants, animals and microorganisms. Most of the production techniques essentially, however, are based on microbial sources. It is an extracellular enzyme and has got second place (next to proteases) in world's distribution and sales among industrial enzymes. Most of the production of glucoamylase is carried out using liquid fermentation process. Technique of solid state fermentation, however, have also been employed for its production and recently this technique is gaining renewed interest from researchers for its production. The paper also describes aspects related with the purification and characterization of glucoamylase enzyme.
Senselessness and sensibility: suicide and university culture (2008)

In the wake of yet another young suicide in the Welsh town of Bridgend, and in the context of rising emotional problems among young people in Britain, Meghan Benton reflects on the suicide of her ex‐boyfriend at the age of 18, and asks what can be done to better protect at‐risk young people, particularly pressurised students.
Oxidized phospholipids induce anergy in human peripheral blood T cells (2008)

Lipids are key regulators of immune responses. In this study we investigated the direct impact of oxidized phospholipids (ox-PL) on T cell activation and function. We could demonstrate that ox-PL strongly inhibit proliferation of purified human T cells induced with anti-CD3/CD28 or anti-CD3/CD63 mAb, whereas proliferation of naive T cells from human cord blood was not affected by ox-PL. Unoxidized phospholipids showed no such effect. Inhibition of T cell proliferation by ox-PL was not due to cell death. Moreover, T cell proliferation triggered by PMA/ionomycin activation was not diminished by ox-PL. T cells activated in the presence of ox-PL produced and released low amounts of IFN-gamma and IL-2, whereas IL-4 was only slightly diminished. Ox-PL prevented the expression of de novo synthesized activation markers (CD25, MHC class II) but not expression of CD63 or CD69. We further observed that T cells stimulated in the presence of ox-PL are poorly cytotoxic T cells. Most importantly, T cells activated in the presence of ox-PL failed to proliferate in response to restimulation. This hypo-proliferative state was accompanied with an up-regulation of early growth response gene 3 and Casitas B-lineage lymphoma protein B. Taken together, our results demonstrate that ox-PL are potent and specific regulators of T cell activation and function.
SIMULATION ANALYSIS ON THE FRESH AIR HANDLING UNIT WITH LIQUID DESICCANT TOTAL HEAT RECOVERY (2007)

A liquid desiccant fresh air processor is presented whose driven force is low-grade heat (65~70℃ hot water). Inside the processor, the desired cooling source for air’s dehumidification is indoor exhaust air’s evaporative cooling energy. Multi-stage structure is used to get higher total heat recovery efficiency of indoor exhaust air. The mathematical model of the fresh air processor is set up and realized by SIMULINK procedure. As the practical liquid desiccant fresh air processor is developed, its performance is tested with average COP (cooling load divided by heat source) 1.3. Besides, the inside detailed parameters of practical facility for each heat transfer unit are acquired through testing. By comparing the tested and simulated data, the mathematical model is corrected by changing the main heat transfer units’ characteristic coefficients, such as the volumetric mass transfer coefficient of air-water evaporative cooling module and the KA of sensible heat exchangers. Finally, using the corrected simulation model, the control strategy of the fresh air-handling unit is discussed, which indicates the imported strong solution’s flowrate and the number of working stages are two effective regulated parameters and can be controlled singly or together at different outdoor conditions and for different indoor demands.
Model for a thermoelectric enzyme glucose sensor (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModel for a thermoelectric enzyme glucose sensorMichael J. Muehlbauer, Eric J. Guilbeau, and Bruce C. ToweCite this: Anal. Chem. 1989, 61, 1, 77–83Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://doi.org/10.1021/ac00176a016RIGHTS & PERMISSIONSArticle Views205Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes. (1997)

Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.
Trapping of silylenes by 9,10-dimethylanthracene: 2,3,5,6-dibenzo-7-silabicyclo[2.2.1]hepta-2,5-dienes (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrapping of silylenes by 9,10-dimethylanthracene: 2,3,5,6-dibenzo-7-silabicyclo[2.2.1]hepta-2,5-dienesAkira Sekiguchi and Robert WestCite this: Organometallics 1986, 5, 9, 1911–1913Publication Date (Print):September 1, 1986Publication History Published online1 May 2002Published inissue 1 September 1986https://pubs.acs.org/doi/10.1021/om00140a029https://doi.org/10.1021/om00140a029research-articleACS PublicationsRequest reuse permissionsArticle Views134Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
SARS-CoV2 infection impairs the metabolism and redox function of cellular glutathione (2021)

Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were investigated for the first time in SARS-CoV2-infected Vero E6 cells, a reliable and well-characterized in vitro model of this infection. SARS-CoV2 markedly decreased the levels of cellular thiols, essentially lowering the reduced form of glutathione (GSH). Such an important defect occurred early in the CPE process (in the first 24 hpi). Thiol analysis in N-acetyl-Cys (NAC)-treated cells and membrane transporter expression data demonstrated that both a lowered uptake of the GSH biosynthesis precursor Cys and an increased efflux of cellular thiols, could play a role in this context. Increased levels of oxidized glutathione (GSSG) and protein glutathionylation were also observed along with upregulation of the ER stress marker PERK. The antiviral drugs Remdesivir (Rem) and Nelfinavir (Nel) influenced these changes at different levels, essentially confirming the importance or blocking viral replication to prevent GSH depletion in the host cell. Accordingly, Nel, the most potent antiviral in our in vitro study, produced a timely activation of Nrf2 transcription factor and a GSH enhancing response that synergized with NAC to restore GSH levels in the infected cells. Despite poor in vitro antiviral potency and GSH enhancing function, Rem treatment was found to prevent the SARS-CoV2-induced glutathionylation of cellular proteins. In conclusion, SARS-CoV2 infection impairs the metabolism of cellular glutathione. NAC and the antiviral Nel can prevent such defect in vitro.
Discontinuation rates of topical glaucoma medications in a managed care population. (2002)

In this managed care setting, rates of discontinuation in patients initially treated with latanoprost were lower than those of patients receiving comparator drugs.
Correction of Ligament and Bone Defects in Total Arthroplasty of the Severely Valgus Knee (1993)

One hundred thirty-five knees with valgus deformity were treated with a minimally constrained, cementless total knee replacement using intramedullary alignment for the femur and tibia. Mean valgus angle before surgery was 16 degrees; mean valgus angle after surgery was 7 degrees. Neither alignment nor varus-valgus stability deteriorated during the six-year follow-up period, but the knees with greater than 25 degrees deformity had a tendency to increase posterior laxity. Severely deformed knees required bone grafting of the medial femoral and tibial surfaces. A technique was developed to resect the distal femur measured from the medial femoral condyle and to maintain joint line position. Patellar subluxation and dislocation occurred in fewer than 1% of the cases. Despite the absence of rotational constraint at the articular surface, there was no tendency for patellar stability to deteriorate over time.