gebhart/patrepeval huggingface dataset:
Generation of Immortalized Equine Chondrocytes With Inducible Sox9 Expression Allows Control of Hypertrophic Differentiation (2017)

Immortalization of chondrocytes enables long term in vitro culture; however, the chondrogenic capacity of transformed cells varies, thus highlighting the need to develop a proliferative and tuneable chondrocyte cell line where hypertrophic differentiation can be controlled. In this study the SV40 large T antigen and human telomerase reverse transcriptase were employed to immortalize pooled equine chondrocytes through lentiviral vector mediated transduction either singly or on combination. Transformed chondrocytes proliferated stably over multiple passages, but resulted in significantly lower expression of chondrocyte specific collagen II mRNA (P < 0.0001) and up regulation of the hypertrophic marker collagen X (P < 0.0001) in three dimensional cultures. A Col2a1 promoter driven GFP reporter was constructed for real time monitoring of chondrogenic differentiation and a significant increase in promoter activation was observed in cultures treated with the growth factor TGFβ-3 (P < 0.05). To recapitulate the native articular chondrocyte phenotype we further transduced large T antigen immortalized chondrocytes with lentiviral vectors allowing either constitutive or doxycycline inducible expression of Sox9. In 3D cultures, the Sox9 over-expressing chondrocytes secreted significantly higher levels of extracellular matrix polysaccharide glycosaminoglycan (P < 0.05), while up-regulating collagen II and Aggrecan mRNA (P < 0.05) in both expression systems with a similar patterns observed with imunohistochemical staining. High levels of collagen X mRNA and protein were maintained with constitutive sox9 reflecting hypetrophic differentiation but significantly lower expression could be achieved with inducible Sox9. In conclusion, immortalization of equine chondrocytes results in stable proliferation but a reduction of chondrogenic potential whilst modulation of sox9 expression enabled control of hypertrophic characteristics. J. Cell. Biochem. 118: 1201-1215, 2017. © 2016 Wiley Periodicals, Inc.
Localization of p21-activated Protein Kinase γ-PAK/Pak2 in the Endoplasmic Reticulum Is Required for Induction of Cytostasis (2003)

The intracellular localization and physiological functions of the p21-activated protein kinase gamma-PAK have been examined in human embryonic kidney 293T and COS-7 cells. At 1-4 days post-transfection, cell division is inhibited by the expression of wild type (WT) gamma-PAK and the mutant S490A, whereas cells expressing S490D and the inactive mutants K278R and T402A grow exponentially, indicating a role for gamma-PAK in the induction of cytostasis. WT gamma-PAK and S490A are localized in a region surrounding the nucleus identified as the endoplasmic reticulum (ER), as determined by immunofluorescence, whereas K278R, T402A, and S490D lack localization. As shown by sucrose density gradient centrifugation, WT gamma-PAK, S490A, and endogenous gamma-PAK are distributed among the high density (ER-associated), intermediate density, and low density fractions, whereas the mutants that do not inhibit cell division are present only as soluble enzyme. The amount of endogenous gamma-PAK associated with the particulate fractions is increased 4-fold when cell division is inhibited by ionizing radiation. gamma-PAK in the ER and intermediate density fractions has high specific activity and is active, whereas the soluble form of gamma-PAK has low activity and is activable. The importance of localization of gamma-PAK is supported by data with the C-terminal mutants S490D and Delta 488; these mutants have high levels of protein kinase activity but do not induce cytostasis and are not bound to the ER. A model for the induction of cytostasis by gamma-PAK through targeting of gamma-PAK to the ER is presented in which gamma-PAK activity and Ser-490 are implicated in the regulation of cytostasis.
Preoperative Anxiety and Fear (1996)

We sought to compare self-assessments of preoperative anxiety levels and selection of worst fears by surgical patients with the assessments made by the anesthesia and surgery residents providing intraoperative care for those patients. One hundred inpatients at a Veterans Affairs hospital (Group 1) and 45 patients at a University hospital (Group 2) were asked to complete a brief questionnaire; the residents were asked to complete the same questionnaire. Group 1 results showed that median patient visual analog scale (VAS) scores were lower for anxiety about anesthesia compared to surgery (16 vs 22, P <or=to 0.05). Anesthesia resident VAS scores were higher than patient or surgery resident scores. Neither type of resident was able to predict their individual patient's VAS score (Kendall's tau). The fear chosen with the greatest incidence by Group 1 patients and residents was "whether surgery would work." A significant number of residents (34%, anesthesia or surgery, P <or=to 0.05) matched their patients' fear choice. Residents commonly chose fears related to their specialty (e.g., anesthesia residents chose anesthesia-related fears more often than surgery residents, 50% vs 28%, P <or=to 0.001). In Group 2, residents demonstrated an improved ability to predict patient scores. For instance, both surgery and anesthesia residents were able to predict individual University patient VAS scores (P <or=to 0.01). The fear chosen with the greatest frequency by Group 2 patients was "pain after the operation." Sixty percent of anesthesia residents matched their patients' fear choice (P <or=to 0.001). This study indicates a variable ability of anesthesia and surgery residents to predict patient anxiety and fear which may be due, in part, to difficulty in understanding a Veterans Affairs hospital patient population. (Anesth Analg 1996;83:1285-91)
Clinicopathologic features of non-small cell lung cancer (NSCLC) harboring an NTRK gene fusion. (2017)

11580 Background: Gene fusions involving NTRK1/2/3 can generate oncoproteins containing the kinase domains of TRKA/B/C, respectively. Inhibition of TRK signaling has led to dramatic responses across tumor types with NTRK fusions. An estimated 0.1 – 1% of NSCLCs harbor NTRK fusions. To date, clinical and radiographic responses to TRK inhibitors have been reported for 2 NTRK fusion-positive NSCLCs (Farago et al., 2015; Hong et al., 2016). Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion NSCLCs are not well characterized. Methods: Physicians across multiple institutions contributed deidentified cases to an NTRK fusion NSCLC database. A central pathologist (M.M.) reviewed tumor histology in cases with available tissue. Results: 10 NSCLC cases with NTRK gene fusions were identified. Of these, TRK kinase domain-containing potentially activating fusions were verified by next-generation sequencing (NGS) in 7, forming the study cohort. Fusions involved NTRK1 (6) and NTRK3 (1) with 6 different partners. Four (57%) patients were male. Median age at diagnosis was 47.6 years (range 27.9 – 86.0). The average smoking pack year history was 8.9 (range 0 to 30). Five (71%) presented with metastatic disease. No concurrent alterations in KRAS, EGFR, ALK, ROS1, or other known drivers were identified in the study cohort cases. On pathologic review of 4 cases, all were adenocarcinoma, including 2 invasive mucinous adenocarcinomas and 1 adenocarcinoma with neuroendocrine features. Of the 3 remaining non-study cohort cases, 1 was a non-kinase domain-containing NTRK1 fusion with a concurrent KRAS G12C mutation, 1 was an NTRK2 intragenic deletion disrupting the exon 18 3’ splice site, and 1 was an NTRK1 alteration detected by FISH but not verified by NGS and with a concurrent HER2 L755P mutation. Conclusions: NTRK fusions occur in both men and women across wide ranges in age and smoking history. We therefore suggest that all NSCLC adenocarcinomas without other oncogenic driver alterations be screened for NTRK fusions. Notably, not all NTRK alterations are activating, requiring validation of the specific position of the fusion.
Improving Credit Risk Scorecards with Memory-Based Reasoning to Reject Inference with SAS ® Enterprise Miner ™ (2010)

Many business elements are used to develop credit scorecards. Reject inference, related to the issue of sample bias, is one of the key processes required to build relevant application scorecards and is vital in creating successful scorecards. Reject inference is used to assign a target class (that is, a good or bad designation) to applications that were rejected by the financial institution and to applicants who refused the financial institution’s offer. This paper uses real-world data to present an example of using memorybased reasoning as a reject inference technique. SAS® Enterprise Miner™ software is used to perform the analysis. The paper discusses the technical concepts in reject inference and the methodology behind using memory-based reasoning as a reject inference technique. Several misclassification measures are reported to determine how well memory-based reasoning performs as a reject inference technique. In addition, a macro to determine how to pick the number of neighbors for the memory-based reasoning technique is given and discussed. This macro is implemented in a SAS® Enterprise Miner™ code node. OVERVIEW OF SCORECARDS Credit scorecard development is a method of modeling potential risk of credit applicants. It involves using different statistical techniques and past historical data to create a scorecard that financial institutions use to assess credit applicants in terms of risk. A scorecard model is built from a number of characteristic inputs. Each characteristic can have a number of attributes. In the example scorecard shown in Figure 1, age is a characteristic and “25<=AGE<33” is an attribute. Each attribute is associated with a number of scorecard points. These scorecard points are statistically assigned to differentiate risk, based on the predictive power of the variables, correlation between the variables, and business considerations.
ChemInform Abstract: Synthesis of Benzotriazine and Aryltriazene Derivatives Starting from 2‐Azidobenzonitrile Derivatives. (2011)

Abstract The reactions of 2‐azidobenzonitrile derivatives (I) with alkyl magnesium halides give benzotriazines in moderate yields accompanied by aminobenzonitriles (IV).
Conditional estimation after a two‐stage diagnostic biomarker study that allows early termination for futility (2012)

Many biomarkers identified in marker discovery are shown to have inadequate performance in validation studies. This motivates the use of group sequential designs that allow early termination for futility. However, an option for early termination will lead to biased estimates for studies that reach full enrollment. We propose conditional estimators and confidence intervals that correct for this bias assuming that an unadjusted estimator exists that has an independent increments covariance structure. The proposed estimators and confidence intervals are applied to conditional estimation of the receiver operating characteristic curve and the positive predictive value curve after a two-stage study that allows early termination for futility, and their performance is evaluated by simulation.
In vitro Interactions of 51r in Human Red Blood Cells and Hemolysates1,2 (1981)

The intracellular distribution of radioactivity was studied in normal and sickle erythrocytes labeled with sodium 51Cr chromate. Both types of cells had a higher fraction of 51Cr bound to hemoglobin when labeled in the presence of ACD at a pH of 7.09 than when labeled in the presence of CPD at a pH of 5.96. Citrate at a pH of 5.96 or less entered the red blood cells and decreased the 51Cr binding hemoglobin. Binding of 51Cr to hemoglobin within the red cells was also reduced when the ATP and DPG levels in the red blood cells were elevated. Studies with hemoglobin solution showed that 51Cr binding to hemoglobin was influenced by 2,3-DPG, ATP and citrate.
Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma (1999)

Although immunostaining cannot distinguish between active and inactive forms of MMPs, the presence of MMP-3 and MMP-9 within endobronchial biopsy specimens, the co-localisation to inflammatory cells of relevance to asthma (mast cells and eosinophils), and the identification of matrix binding, indicative of MMP-matrix interactions, points to the potential for disease related changes in MMP release that influence airway remodelling in asthma.
REFRACTIVE SURGICAL PROBLEM (2005)

Journal of Cataract & Refractive Surgery: November 2005 - Volume 31 - Issue 11 - p 2048-2049 doi: 10.1016/j.jcrs.2005.11.035
CCC - integrated multiscale study of salt cavern abandonment in the Netherlands (2022)

The KEM-17 project of the Dutch State Supervision of Mines presented a critical review of concepts of cavern abandonment and related science. It recommended that analyses of cavern abandonment are done as an integrated project, addressing (i) micro-scale physical processes, (ii) cavern scale models based on field scale experiments and numerical models, (iii) the salt dome scale, to model the far field of the salt caverns. The Cavern Closure Consortium (CCC) project is based on this, focusing on the Haaksbergen and Heiligerlee cavern fields in the Netherlands. We build on (i) innovative deformation experiments, integrated with state of the art microstructural analysis to define constitutive equations for deformation and permeation, focusing on the poorly understood domain below 8 MPa differential stress, (ii) numerical finite element models of the cavern field combined with cavern-scale field experiments to define the closure parameters and temperature evolution of the cavern, and (iii) state of the art numerical models at the scale of the whole salt pillow or salt dome to define the "ist-Zustand". All these contributions are closely integrated and will lead to much improved prediction of the evolution of the caverns after closure and abandonment.
Locating closed streamlines in 3D vector fields (2002)

The analysis and visualization of flows is a central problem in visualization. Topology based methods have gained increasing interest in recent years. This article describes a method for the detection of closed streamlines in 3D flows. It is based on a special treatment of cases where a streamline reenters a cell to prevent infinite cycling during streamline calculation. The algorithm checks for possible exits of a loop of crossed faces and detects structurally stable closed streamlines. These global features are not detected by conventional topology and feature detection algorithms.
[Influence of solid dispersion technique combination on dissolution of tanshinone IIA]. (2009)

As compared to single use of PVPK30 or F68, the combination of PVPK30 and F68 improve the dissolution rate and solubility of TS IIA significantly in the prepared solid dispersions (P<0.01). The application of complex carriers in solid dispersion technology should be paid more attention to improvement of poorly soluble drugs dissolution in the future.
Leptospira interrogans Prevents Macrophage Cell Death and Pyroptotic IL-1β Release through Its Atypical Lipopolysaccharide (2023)

Leptospira interrogans are bacteria that can infect all vertebrates and are responsible for leptospirosis, a neglected zoonosis. Some hosts, such as humans, are susceptible to the disease, whereas mice are resistant and get chronically colonized. Although leptospires escape recognition by some immune receptors, they activate the NOD-like receptor pyrin 3-inflammasome and trigger IL-1β secretion. Classically, IL-1β secretion is associated with lytic inflammatory cell death called pyroptosis, resulting from cytosolic LPS binding to inflammatory caspases, such as caspase 11. Interestingly, we showed that L. interrogans and Leptospira biflexa do not trigger cell death in either murine, human, hamster, or bovine macrophages, escaping both pyroptosis and apoptosis. We showed, in murine cells, that the mild IL-1β secretion induced by leptospires occurred through nonlytic caspase 8-dependent gasdermin D pore formation and not through activation of caspase 11/noncanonical inflammasome. Strikingly, we demonstrated a potent antagonistic effect of pathogenic L. interrogans and their atypical LPS on spontaneous and Escherichia coli LPS-induced cell death. Indeed, LPS of L. interrogans efficiently prevents caspase 11 dimerization and subsequent massive gasdermin D cleavage. Finally, we showed that pyroptosis escape by leptospires prevents massive IL-1β release, and we consistently found no major role of IL-1R in controlling experimental leptospirosis in vivo. Overall, to our knowledge, our findings described a novel mechanism by which leptospires dampen inflammation, thus potentially contributing to their stealthiness.
Current European data collection on emergency department presentations with acute recreational drug toxicity: Gaps and national variations (2014)

The systematic collection of data on ED presentation of toxicity related to NPS and classical drugs in Europe is scarce; the existing collection is limited to single centres, single countries, groups of patients or not focused on novel drugs; the collection of data is highly variable between the different countries. Euro-DEN, a European Commission funded project, aims at closing some of these gaps.
Advancements in 3D Drillstring Mechanics: From the Bit to the Topdrive (2006)

Abstract The well trajectories becoming more and more complex (Extended Reach Drilling, Horizontal or Multilateral Drilling, Ultra-Deep Drilling, 3D wells….), the associated drillstring composition being unconventional and the material being used to its operating limit, the necessity to have a tool that predicts realistically forces, bending moment and contact loads along the wellbore is essential. To simulate the mechanical behavior of the drillstring, the industry generally uses a stiff-string model for the bottom bole assembly (BHA) to predict drilling trajectories, and a soft-string model for the entire drillstring to calculate torque and drag. The conventional soft-string model gives a good approximation of forces and contact loads in the drillstring for very smooth well trajectories, but is inappropriate when the trajectory becomes tortuous (micro or macro-tortuosity) or complex, as the drillstring no longer contacts the low side of the borehole. An advanced numerical method has been applied to address the 3D mechanical problem of a complete drillstring moving and freely rotating inside a wellbore: computation of the unknown contacts between the drillstring and the wellbore. As this new model does not use the time consuming finite element analysis, it can be used in real-time drilling operation at the rig to monitor torque and drag. For the first time, it is even possible to perform simultaneously a torque and drag, buckling and directional analysis while drilling. The power of a 3D visualization of the drillstring deformed inside the wellbore enables to localize easily contact loads on any drillstring component, from the drilling bit (including side force at the bit and tilt) to the top drive or rotary table (hook load and rotary torque at surface), facilitating drilling problems analysis. This paper will describe the fundamentals of the model developed and shows the differences between the conventional soft-string model and the advanced stiff-string model in terms of tension, torque and contact points between the drillstring and the wellbore, for many actual wells. With the help of the 3D visualization software, this paper will show the cases where the drill pipe contacts the high side of the borehole, or goes up to the right or the left side of the borehole depending on the right or left turn rate of the well trajectory. This new model should improve significantly the torque-drag and buckling calculations and the understanding of the drillstring contributions to overall drilling performance.
Ultrathin Die Pick-Up for 3D Chip Stacking (2019)

Ultrathin die pick-up is studied for 3D IC applications. Failure modes are identified as follows: 1) no pick-up due to insufficient peeling; 2) die crack created by ejector; 3) neighboring die crack due to ejector push-up. Optimal dicing tape is selected along with pick-up process tuning. By using optimal dicing tape, pick-up process window is identified for 20 and 30 μm thickness Si die with 8x8 and 12x12 mm die size. The failure modes of “die crack created by ejector” and “neighboring die crack” occur when push height is large and/or pickp-up time is short. The failure mode of “no pickup” occurs at insufficient push height. Finally, pick-up conditions with 100% yield are identified with ≤ 1 sec pick-up time.
NO-char reactions: Kinetics and transport aspects (1991)

The reaction chemistry of NO with carbons is quite complex. This study details many different aspects of this chemistry. The choice was made to study the reaction chemistry using carbons derived from phenolic resins. These chars are microporous and have porosity characteristics similar to those of coal chars, but have the advantage that they are relatively free of potentially catalytic impurities. The results have been noted to be quite similar to results obtained on a variety of very different carbons, as reported in the literature. The reaction behavior was studied over a range of NO pressures up to 10.1kPa, and at temperatures between 323K and 1073K. The reaction behavior is an extremely sensitive function of temperature. 87 refs., 51 figs., 26 tabs. (VC)
Molecular Biology and Therapeutics in Musculoskeletal Oncology* (2009)

Guise, Theresa A. MD1; O'Keefe, Regis MD, PhD2; Randall, R. Lor MD3; Terek, Richard M. MD4 Author Information
Chalcogenide waveguides on a sapphire substrate for 3-5 µm wavelengths applications (2014)

Arsenic tri-Sulfide Chalcogenide strip waveguides on a sapphire substrate were fabricated and characterized. The substrate material enables efficient transmission of 3–5µm wavelengths through the waveguide, and numerical simulations reveal benefits over silica and silicon substrates.
Characterization of a Ca/sup 2 +/, calmodulin-dependent protein kinase which is able to phosphorylate native and protease cleaved purified hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (1986)

The authors have extensively purified a low molecular weight Ca/sup 2 +/, calmodulin-dependent protein kinase from rat brain cytosol. This kinase (M/sub r/ 120,000) is able to phosphorylate both native and soluble purified HMG-CoA reductase. The concomitant inactivation and phosphorylation of purified HMG-CoA reductase was completely dependent on Ca/sup 2 +/ and calmodulin. Incubation of phosphorylated /sup 32/P-HMG-CoA reductase was associated with the loss of /sup 32/P-radioactivity and reactivation of inactive enzyme. Maximal phosphorylation of purified HMG-CoA reductase involved the introduction of approximately 0.5 mol phosphate/53,000 enzyme fragment. The apparent Km for purified HMG-CoA reductase was .045 mg/ml. Microsomal native HMG-CoA reductase (M/sub r/ 100,000) was also phosphorylated and inactivated following incubation with calmodulin stimulated kinase, calmodulin, Ca/sup 2 +/ and Mg-ATP; dephosphorylation (reactivation) was catalyzed by the phosphoprotein phosphatase. The isolation and characterization of the M/sub r/ 120,000 calmodulin-binding enzyme complex provides additional insights into the mechanisms of the Ca/sup 2 +/ dependent regulation of HMG-CoA reductase phosphorylation. Based on these data and the authors previous in vitro and in vivo studies, they now propose that HMG-CoA reductase activity is modulated by three separate kinase systems.