gebhart/patrepeval huggingface dataset:
Two Years Follow-up Results of Graspall/Graall-SA2–2008 Study: L-Asparaginase-Loaded Red Blood Cell Combined with Standard EWALL Chemotherapy in Older Patients with Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (Ph-ALL) (2012)

Abstract Abstract 1473 Introduction: L-asparaginase-loaded red blood cells (GRASPA®) has been shown to be a new available option for combining L-asparaginase with standard chemotherapy in different ALL population, including older patients with the disease. Tolerability and preliminary results of efficacy of GRASPA® in GRASPALL/GRAALL-SA2–2008 study have already been presented. We report below the 2-year follow-up efficacy results of this study. Methods: GRASPALL/GRAALL-SA2–2008 study aimed at determining optimal dose of GRASPA® that could be combined with standard EWALL chemotherapy backbone in patients aged &gt;55y with newly diagnosed Ph-ALL. It was an open label Phase II dose escalation study. Primary endpoint combined tolerance and efficacy (asparagine depletion ≥7 days). Three doses of L-Asparaginase-Loaded Red Blood Cells (50, 100 and 150 IU/kg), infused twice during induction cycles, were investigated. EWALL backbone consisted of dexamethasone prephase followed by induction-1 (dexamethasone d1–2/8–11, vincristine d1,8, and idarubicine d1–2/8–9) and induction-2 (cyclophosphamide d15–17 and cytarabine d16–19/23–26). Consolidation consisted of 6 monthly alternating cycles with methotrexate (d1) / E.coli asparaginase (d2) and high-dose cytarabine (d1, 3, 5). Maintenance included mercaptopurine, methotrexate and vincristine/dexamethasone pulses for 2 years. Hematological and molecular Ig/TCR minimal residual disease (MRD) response rates, survival were secondary endpoints. Results: Between March 2009 and October 2010, 30 patients were recruited in 20 centres in France by the GRAALL network. The 50, 100 and 150 dose levels included 3, 13 and 14 patients, respectively. Median age was 67 years (range 59–77). No differences in baseline characteristics were observed across the 3 dose level groups. The tolerability with L-Asparaginase-related side effects is reported below: Overall L-asp expected adverse events tended to be lower in the 100 UI/kg group. Regarding the efficacy and benefit/risk, asparagines depletion, remission rate, EFS and OS are reported below: Three patients received the dose of 50 UI/kg but this dose was insufficient to reach a 7-day asparagine depletion. Survival analysis showed that the dose of 100IU/kg was associated with median OS of 15.6 months an absolute value that compared favorably with historical controls: 8,8 mo (Rousselot et al. Drugs Aging,2011) and 10,5 mo (Hunault et al. Haematologica,2011) Conclusion: GRASPA® at a dose of 100 UI/kg appears to be a safe and active manner to introduce L-asparaginase during initial induction chemotherapy of older patients with Ph- ALL with a sustained asparagine depletion and a good efficacy/safety profile. Disclosures: Godfrin: ERYTECH Pharma: COO Other.
Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR (2016)

Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). We previously disclosed our successful approach to prospectively design potent and blood-brain barrier (BBB) penetrating PI3K inhibitors. The previously disclosed molecules were ultimately deemed not suitable for clinical development due to projected poor metabolic stability in humans. We, therefore, extended our studies to identify a BBB penetrating inhibitor of PI3K that was also projected to be metabolically stable in human. These efforts required identification of a distinct scaffold for PI3K inhibitors relative to our previous efforts and ultimately resulted in the identification of GDC-0084 (16). The discovery and preclinical characterization of this molecule are described within.
DIABETES MANEGEMENT: INSIGHT FROM (1983)

Diabetes is a major worldwide health problem. The mechanisms by which blood glucose is normally regulated are impaired and an elevated glucose concentration is present in blood. This hyperglycemia can be due to either failure of the ~-cells of the pancreas to secrete the hormone insulin in appropriate amounts and/or failure of the secreted insulin to increase the utilization of blood-borne nutrients by the cells. The most severe form of diabetes is that referred to as Type I diabetes where destruction of the majority of ~-cells occurs; no insu­ lin is available for secretion and therefore the diabetic patient must resort to exogenous insulin treatment, typically multiple subcutaneous injections during the day. A second form of the disease is that refer­ red to as Type II diabetes where usually anonnormalinsulin secretion is present concomitantly with an impaired sensitivity to insulin of gl~ cose utilizing peripheral tissues; even if some Type II diabetics may develop a requirement for exogenous insulin, the disease can be often managed by diet/excercise or by daily treatment with oral agents which force glucose to decrease by acting either on ~-cell sensitivity to glucose or peripheral tissues sensitivity to insulin. Mathematical modeling is increasingly emerging as an effective tool in approaching/guiding the solution to many problems in the area of carbohydrate metabolism /1,2/. Moreover considerable work has also been done on several basic aspects of the modeling process particular­ ly as it relates to endocrine-metabolic sysystems so that an integra­ ted methodology for model formulation, identification and validation has recently become available /3/. In this paper we discuss the use of mathematical models in facing some problems arising in insulin-dependent and -independent diabetes
Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact (2000)

T cell differentiation in the thymus is driven by positive selection through the interaction of alphabeta T cell receptors (TCRs) with self-peptides bound to self-major histocompatibility complex molecules, yet the influence of the peptide sequence on this process remains unknown. To address this issue, we have compared CD4(+) T cell differentiation between two sets of mouse lines in which MHC class II I-A(b) molecules are occupied with either Ealpha chain-derived peptide ((p)Ealpha) or its variant, (p)60K, with one amino acid substitution from leucine to lysine at P5 residue of TCR contacts. Here, we show that despite the comparable expression of I-A(b)-peptide complex in the thymus, this substitution from leucine to lysine affects efficiency of positive selection, resulting in extremely small numbers of CD4(+) T cells to be selected to mature on I-A(b)-(p)60K complex. Furthermore, we show that, although I-A(b)-(p)Ealpha complex selects diverse T cells, T cell repertoire shaped by I-A(b)-(p)60K complex is markedly constrained. Our findings thus suggest that positive selection is both specific and degenerate, depending on the amino acid residues at TCR contacts of the selecting self-peptides.
The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group (2021)

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
Genomic alterations in human mesothelioma including high resolution mapping of common regions of DNA loss in chromosome arm 6q. (2003)

This suggests that at least 3 tumor suppressor genes mapped to chromosome 6q are commonly involved in the pathogenesis of mesothelioma.
Review on energy storage in lead‐free ferroelectric films (2022)

Abstract Rapidly developing electronics industry is striving for higher energy‐storage capability dielectric capacitors for pulsed power electronic devices. Both high dielectric permittivity and high dielectric breakdown strength are essential properties to meet the desired device performance. However, due to materials limitations and their preparation requirements, there are significant challenges which limit the use of current dielectrics in high‐energy storage capacitors. In addition material limitations such as, low dielectric permittivity, low breakdown strength, and high hysteresis loss decrease these materials' energy density and efficiency, restricting potential applications. Thus, a thorough understanding of the implementation, optimization and limitations of ferroelectric, relaxor‐ferroelectric, and anti‐ferroelectric thin films in high‐energy storage dielectric capacitors is an essential and important research topic for the incorporation of these materials in near future applications.
A numerical model of the viscosity of an epoxy prepreg resin system (1999)

Abstract The development of the viscosity of a thermoset material during processing is complicated because of the dependence of the initial material state and the kinetic rate of conversion from a liquid to a solid material. Uncured thermoset materials typically have a low enough viscosity such that the consumption of energy to generate flow is relatively low. However, as the curing process advances, the flow mechanisms become hindered by the development of a network gel during crosslinking. Once the resin has reached the appropriate degree of cure for gelation, the resin system is incapable of large fluid‐like deformations. In this research, the rheological properties of an epoxy resin system used in laminate processing were measured and numerically fit with a modification to the dual Arrhenius model to predict the progression of the viscosity during cure. The numerical results were compared with the experimental measurements, and it was found that the model predicts the experimental observations quite well. It was found that the initial degree of cure of the prepreg is not as significant a factor as the temperature rate dependence on the processing time between the point of flow onset and gelation. However, the minimum viscosity during processing is strongly influenced by the initial degree of cure of the prepreg system.
Cycling pattern and read/bake conditions dependence of random telegraph noise in decananometer NAND flash arrays (2015)

We conduct a thorough investigation of random telegraph noise (RTN) dependence on program/erase and read/bake conditions in state-of-the-art 1X and 2X Flash NAND technologies. We demonstrate that RTN depends only on the cycle number and not on the program level or cycling pattern. Moreover, if the cumulative distribution of RTN is considered, a negligible temperature dependence appears, in apparent contrast with thermal activation of single-trap time constants. RTN appears also to be independent of the read and bake temperature, although a slight asymmetry in the distribution tails is induced by charge detrapping. A Monte Carlo model is also presented to account for the experimental observations.
ChemInform Abstract: Oxidation of Alkynes Using PdCl2/CuCl2 in PEG as a Recyclable Catalytic System: One‐Pot Synthesis of Quinoxalines. (2010)

Abstract Internal alkynes are readily oxidized to the corresponding diketones under conditions A).
Selected Biological Processes (2005)

This chapter contains sections titled: Biological Oscillations Glycolytic Oscillations: The Higgins-Sel'kov Oscillator Other Modes of Behavior Coupling of Oscillators Sustained Oscillations in Signaling Cascades Cell Cycle Steps in the Cycle Minimal Cascade Model of a Mitotic Oscillator Models of Budding Yeast Cell Cycle Aging Evolution of the Aging Process Accumulation of Defective Mitochondria Synthesis Rates Radical Levels Dilution of Membrane Damage The Equations Choice of Parameters and Simulation Results
Prenatal alcohol exposure alters phosphorylation and glycosylation of proteins in rat offspring liver (2009)

To gain more insights into the translational and PTM that occur in rat offspring exposed to alcohol in utero, 2-D PAGE with total, phospho- and glycoprotein staining and MALDI-MS/MS and database searching were conducted. The results, based on fold-change expression, revealed a down-regulation of total protein expression by prenatal alcohol exposure in 7-day-old and 3-month-old rats. There was an up-regulation of protein phosphorylation but a down-regulation of glycosylation by prenatal alcohol exposure in both age groups. Of 31 protein spots examined per group, differentially expressed proteins were identified as ferritin light chain, aldo-keto reductase, tumor rejection antigen gp96, fructose-1,6-bisphosphatase, glycerol-3-phosphate dehydrogenase, malate dehydrogenase, and gamma-actin. Increased phosphorylation was observed in proteins such as calmodulin, gluthatione S-transferase, glucose regulated protein 58, alpha-enolase, eukaryotic translation elongation factor 1 beta-2, riboprotein large P2, agmatinase, ornithine carbamoyltransferase, quinolinate phosphoribosyltransferase, formimidoyltransferase cyclodeaminase, and actin. In addition, glycosylation of adenosine kinase, adenosylhomocysteine hydrolase, and 3-hydroxyanthranilate dioxygenase was reduced. Pathways affected by these protein alterations include cell signaling, cellular stress, protein synthesis, cytoskeleton, as well as glucose, aminoacid, adenosine and energy metabolism. The activity of the gluconeogenic enzyme fructose-1,6-bisphosphatase was elevated by prenatal alcohol. The observations may have important physiological implications.
Design and Self-Assembly of Open, Regular, 3D Mesostructures (1999)

Self-assembly provides the basis for a procedure used to organize millimeter-scale objects into regular, three-dimensional arrays ("crystals") with open structures. The individual components are designed and fabricated of polyurethane by molding; selected faces are coated with a thin film of liquid, metallic alloy. Under mild agitation in warm, aqueous potassium bromide solution, capillary forces between the films of alloy cause self-assembly. The structures of the resulting, self-assembled arrays are determined by structural features of the component parts: the three-dimensional shape of the components, the pattern of alloy on their surfaces, and the shape of the alloy-coated surfaces. Self-assembly of appropriately designed chiral pieces generates helices.
EUROSCAN, a Randomized Trial of Vitamin A and N-Acetylcysteine in Patients With Head and Neck Cancer or Lung Cancer (2000)

A 2-year supplementation of retinyl palmitate and/or N-acetylcysteine resulted in no benefit-in terms of survival, event-free survival, or second primary tumors-for patients with head and neck cancer or with lung cancer, most of whom were previous or current smokers.
Dynamic identification of phosphopeptides using immobilized metal ion affinity chromatography enrichment, subsequent partial β ‐elimination/chemical tagging and matrix‐assisted laser desorption/ionization mass spectrometric analysis (2004)

The enrichment of phosphopeptides using immobilized metal ion affinity chromatography (IMAC) and subsequent mass spectrometric analysis is a powerful protocol for detecting phosphopeptides and analyzing their phosphorylation state. However, nonspecific binding peptides, such as acidic, nonphosphorylated peptides, often coelute and make analyses of mass spectra difficult. This study used a partial chemical tagging reaction of a phosphopeptide mixture, enriched by IMAC and contaminated with nonspecific binding peptides, following a modified beta-elimination/Michael addition method, and dynamic mass analysis of the resulting peptide pool. Mercaptoethanol was used as a chemical tag and nitrilotriacetic acid (NTA) immobilized on Sepharose beads was used for IMAC enrichment. The time-dependent dynamic mass analysis of the partially tagged reaction mixture detected intact phosphopeptides and their mercaptoethanol-tagged derivatives simultaneously by their mass difference (-20 Da for each phosphorylation site). The number of new peaks appearing with the mass shift gave the number of multiply phosphorylated sites in a phosphopeptide. Therefore, this partial chemical tagging/dynamic mass analysis method can be a powerful tool for rapid and efficient phosphopeptide identification and analysis of the phosphorylation state concurrently using only MS analysis data.
Synthesis of a New Heterobifunctional Linker, N-[4-(Aminooxy)butyl]maleimide, for Facile Access to a Thiol-Reactive 18F-Labeling Agent (2003)

A new heterobifunctional linker containing an aldehyde-reactive aminooxy group and a thiol-reactive maleimide group, namely N-[4-(aminooxy)butyl]maleimide, was synthesized as a stable HCl salt by O-alkylation of either N-hydroxyphthalimide or N-(4-monomethoxytrityl)hydroxylamine, followed by N-alkylation of maleimide, in an overall yield of 18% (seven steps) or 29% (five steps), respectively. This heterobifunctional linker allowed a simple and efficient synthesis of a maleimide-containing thiol-reactive (18)F-labeling agent. Thus, N-[4-[(4-[(18)F]fluorobenzylidene)aminooxy]butyl]maleimide (specific activity: approximately 3000 Ci/mmol at end of synthesis) was synthesized in two steps involving the preparation of 4-[(18)F]fluorobenzaldehyde, followed by its aminooxy-aldehyde coupling reaction to the heterobifunctional linker, with an overall radiochemical yield of approximately 35% (decay corrected) within approximately 60 min from end of bombardment. Initial (18)F-labeling experiments were carried out using a thiol-containing tripeptide glutathione (GSH) and a 5'-thiol-functionalized oligodeoxynucleotide (5'-S-ODN) in phosphate-buffered saline (PBS, pH 7.5). After standing at room temperature for 10 min, the (18)F-labeled GSH and 5'-S-ODN were obtained in (18)F-labeling yields of approximately 70% and approximately 5% (decay-corrected), respectively. The heterobifunctional linker is easy to synthesize and provides a facile access to the maleimide-containing thiol-reactive (18)F-labeling agent, which could be advantageously employed in the development of (18)F-labeled biomomolecules for use with positron emission tomography.
Development of the Large Scanning Mirror Using Fe-Based Metallic Glass Ribbon (2011)

In order to achieve the large scanning angle without mechanical failure during actuation, the micro-mirror structure was fabricated using Fe-based metallic glass (MG) ribbon. High values of mechanical strength and elastic strain limit are desired for the torsion bar for providing high performance of the mirror, including large tilting angle and good stability. MG materials guarantee superior value of elastic strain limit and fracture toughness resulting from its amorphous structure without line defects like dislocations and grain boundaries. We chose Fe-base MG material for mirror actuation according to its good soft magnetic properties and simple structure without any further step of integration of magnetic material. Millimeter-size mirror device was successfully fabricated by laser machining techniques from Fe-based MG ribbon. Extremely large optical tilting angle of exceeding 100° was obtained on activation of the mirror by magnetic force when electrical current of 100 mA was applied. Large tilting angle of the mirror is due to the torsion bar which was fabricated with Fe-based MG material that has large elastic strain limit and high fracture toughness.
Hand Link Modeling and Motion Generation from Motion Capture Data Based on 3D Joint Kinematics (2005)

&lt;div class="htmlview paragraph"&gt;Characterization of the human hand motion necessary to manipulate hand-held equipment requires accurate capture and reconstruction of the arbitrary subject's hand motions with respect to the object. The present study used an individual link structure modeled from optical motion capture data to perform this task and compared the results against those obtained by medical imaging. Posture data was captured while grasping several cylinders, and the captured data were utilized to generate new postures to grasp cylinders of arbitrary diameter.&lt;/div&gt;
HIP INSTABILITY: CAUSES AND MANAGEMENT OPTIONS (2018)

Recurrent dislocation following total hip arthroplasty (THA) is a complex, multifactorial problem that has been shown to be the most common indication for revision THA. At our center, we have tried...
Examination of complex oligosaccharides by matrix‐assisted laser desorption/ionization mass spectrometry on time‐of‐flight and magnetic sector instruments (1994)

Abstract Matrix‐assisted laser desorption/ionization (MALDI) spectra of underivatized oligosaccharides of the type attached to asparagine in glycoproteins ( N ‐linked oligosaccharides) were examined with linear time‐of‐flight (TOF) and magnetic sector instruments using 2,5‐dihydroxybenzoic acid (2,5‐DHB), α‐cyano‐4‐hydroxycinnamic acid, sinapinic acid, 1,4‐dihydroxynaphthalene‐2‐carboxylic acid or 2‐(4‐hydroxyphenylazo)benzoic acid (HABA) as the matrices. All compounds formed abundant [M + Na] + ions with the strongest signals being obtained from 2,5‐DHB after recrystallization of the initially dried sample spot from ethanol. Only traces of fragmentation were detected from neutral oligosaccharides on the TOF system but more abundant fragment ions (about 5% relative abundance) were present in the spectra from the magnetic sector instrument. Fragmentation was dominated by Y‐type glycosidic cleavages (Domon and Costello nomenclature) between all sugar residues yielding sequence and branching information. Sialic acid‐containing oligosaccharides generally produced the sodium adduct of the sodium salt and gave much weaker signals than the neutral sugars in the positive‐ion mode. There was also considerable loss of the sialic acid moleties as the result of fragmentation on the magnetic sector instrument. The least fragmentation of both neutral and acidic sugars was caused by 2.5 DHB, which proved to be the most appropriate matrix for examination of oligosaccharide mixtures. Much better resolution of the oligosaccharides was obtained than by traditional methods such as the use of Bio‐Gel P‐4 gel filtration column chromatography. It is worth noting also that the measurements were considerably faster (a few minutes as opposed to about 16 h). In addition, no radiolabelling was necessary as required for detection on the P‐4 columns. Mixtures of oligosaccharides from several glycoproteins (ribonuclease B, human immunoglobulin G (IgG) transferrin, bovine fetuin and chicken ovalbumin) were examined and the patterns of the identified oligosaccharides were found to agree closely with the known compositions of the sugar mixtures. The mass spectrometric resolution on the magnetic sector instrument was very much better (up to 3000, FWHM) than could be obtained with the linear TOF systems (200–400). The technique was used as a detection system for the products of exoglycosidase digestion in experiments to determine the detailed structure of the oligosaccharide chains from human IgG.