gebhart/patrepeval huggingface dataset:
CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. (2011)

TPS199 Background: The prognosis for patients (pts) with AML is variable and dependent on the presence of mutations in the FLT3 tyrosine kinase. Internal tandem duplications (ITD) in the juxtamembrane region and mutations in the tyrosine kinase domain (TKD) cause constitutive activation of FLT3 and lead to blast proliferation. Preclinical data suggested that chemotherapy combined with FLT3 inhibitors, including midostaurin, could synergistically kill leukemic cells. In a phase Ib study of midostaurin 50 mg BID with chemotherapy, 92% of FLT3mut pts and 74% of FLT3WT pts achieved a CR. OS of FLT3mut pts was similar to FLT3WT pts (Stone, ASH 2009), supporting the rationale for the ongoing study (NCT00651261). Methods: This is a CALGB-led intergroup, international, randomized, double-blind, PBO controlled trial of adult (age 18-59), untreated FLT3mut AML pts treated with induction chemotherapy and 4 post-remission cycles of high dose ara-C with PBO or midostaurin 50 mg BID on d8-21 of each cycle, followed by 1 yr of midostaurin or PBO. This is the first large study to use molecular screening of FLT3 mutation and ITD allelic ratio at baseline to stratify pts. The primary endpoint is OS (not censored for stem cell transplantation [SCT]). Secondary objectives include EFS and CR. Prognostic impact of FLT3 autophosphorylation and comparison of mutation status at baseline and at relapse are being investigated. A review of blinded rates of SCT and FLT3 TKD mutations demonstrated that both are higher than assumptions used in initial trial design. Since SCT and FLT3 TKD both lead to better prognosis, OS estimates are impacted. Thus, sample size was increased by 200 pts (N=714) to maintain 90% power for the original treatment effect. An OS analysis with censoring at the time of SCT has been added as a secondary endpoint. Over 2470 pts have been preregistered. Reporting of FLT3 mutation status has been rapid at all global diagnostic laboratories (approximately 26 hrs in the North American reference lab at OSU). 564 pts have been enrolled to date; expected accrual completion is 2011.
Surgical oncology : current concepts and practice (1990)

Carcinoma of the oesophagus, A. Watson the management of gastric cancer, D. Cunningham carcinoma of the pancreas and biliary system, D.C. Carter colorectal cancer, C.S. McArdle endocrine tumours, J.R. Farndon breast cancer, C.S. McArdle kidney, Alistair W.S. Ritchie bladder cancer, G.D. Chisholm prostate, David Kirk testis cancer, S.B. Kaye tumours of the head and neck, Ian A. McGregor management of cutanuous malignant melanoma, Rona M. MacKie bone and soft tissues, K. Pooley lymphoma, M. Soukop principles of cancer therapy, M.A. Cornbleet recent advances in cancer research, David J. Kerr.
A BUMPY AND DANGEROUS RIDE ALONG THE LOCAL HIGHWAY (1990)

This article reports on the very large variation in the ways that local authorites and their agents manage and carry out maintenance work on local roads, and on steps being taken to remedy this situation. The condition of roads in the UK is worse than in 1977, when the National Road Condition Survey began. The announced 2 billion capital programme for local roads over the next 3 years is not considered particularly generous. However, the recent local authority associations' seminar on the revised code of practice for highway maintenance blamed some local authorities as well as the British Government for neglect of local roads. The associations want the new maintenance code implemented within three years, and are pressing their members to meet the efficiency savings identified by the Audit Commission. In February 1990, a more detailed questionnaire was sent to local authorities, asking about implementation progress or plans on each of the code's recommendations and details of financial policies. Hitherto, only a few local authorities have implemented the code fully. While praising the code, the Department of Transport is increasing spending on maintenance of bridges and other structures, while reducing cyclical maintenance.
Drinking, Driving, and the Price of Automobile Insurance (1994)

This study describes premium penalties imposed by insurers for drunk driving and other chargeable accidents, assesses why variations in premiums for drivers with clean records and adverse records differ across states and insurers, and determines the effect of imposing penalties on persons convicted of drunk driving. There are significant differences among insurers in treatment of violators, both in underwriting and in premium setting-which are in part attributable to state policies, such as imposition of take-all-comer rules. Imposing premium surcharges for a charge of drunk driving has a significant deterrent effect on the probability of drinking and driving.
Simple and rapid measurement of human T lymphocytes and their subclasses in peripheral blood. (1980)

A simple and rapid method for the determination of human T lymphocyte subclasses in buffy coat preparations or whole blood is described. This technique uses flow cytometry to distinguish lymphocytes from other leukocytes on the basis of their light-scattering properties. Lymnphocyte subclasses were enumerated by cellular immunofluorescence; the immunofluorescent signals were produced by monoclonal antibodies to surface differentiation antigens on T cells. Conventional techniques of enumerating T lymphocyte subclasses entail time-consuming (up to 2 days) density gradient and E rosette enrichement, and require at least 20 ml of blood. The method described here uses as little as 50 microliters of whole blood for each antibody tested and produces results within in 2 hr.
Nontranslational three-dimensional profilometry by chromatic confocal microscopy with dynamically configurable micromirror scanning (2000)

A confocal microscope profilometer, which incorporates chromatic depth scanning with a diffractive optical element and a digital micromirror device for configurable transverse scanning, provides three-dimensional (3D) quantitative measurements without mechanical translation of either the sample or the microscope. We used a microscope with various objective lenses (e.g., 40x, 60x, and 100x) to achieve different system characteristics. With a 100x objective, the microscope acquires stable measurements over a 320 microm x 240 microm surface area with a depth resolution of 0.39 microm at a 3-Hz scan rate. The total longitudinal field of view is 26.4 microm for a wavelength tuning range of 48.3 nm. The FWHM value of the longitudinal point-spread function is measured to be 0.99 microm. We present 3D measurements of a four-phase-level diffractive element and an integrated-circuit chip. The resolution and the accuracy are shown to be equivalent to those found with use of conventional mechanical scanning.
Towards a therapeutic inhibition of dystrophin exon 23 splicing in mdx mouse muscle induced by antisense oligoribonucleotides (splicomers): target sequence optimisation using oligonucleotide arrays (2004)

These results suggest that correctly designed splicomers may have direct therapeutic value in vivo, not only for DMD, but also for a range of other genetic disorders.
Skeletal Myoblast-Seeded Vascularized Tissue Scaffolds in the Treatment of a Large Volumetric Muscle Defect in the Rat Biceps Femoris Muscle (2017)

High velocity impact injuries can often result in loss of large skeletal muscle mass, creating defects devoid of matrix, cells, and vasculature. Functional regeneration within these regions of large volumetric muscle loss (VML) continues to be a significant clinical challenge. Large cell-seeded, space-filling tissue-engineered constructs that may augment regeneration require adequate vascularization to maintain cell viability. However, the long-term effect of improved vascularization and the effect of addition of myoblasts to vascularized constructs have not been determined in large VMLs. Here, our objective was to create a new VML model, consisting of a full-thickness, single muscle defect, in the rat biceps femoris muscle, and evaluate the ability of myoblast-seeded vascularized collagen hydrogel constructs to augment VML regeneration. Adipose-derived microvessels were cultured with or without myoblasts to form vascular networks within collagen constructs. In the animal model, the VML injury was created in the left hind limb, and treated with the harvested autograft itself, constructs with microvessel fragments (MVF) only, constructs with microvessels and myoblasts (MVF+Myoblasts), or left empty. We evaluated the formation of vascular networks in vitro by light microscopy, and the capacity of vascularized constructs to augment early revascularization and muscle regeneration in the VML using perfusion angiography and creatine kinase activity, respectively. Myoblasts (Pax7+) were able to differentiate into myotubes (sarcomeric myosin MF20+) in vitro. The MVF+Myoblast group showed longer and more branched microvascular networks than the MVF group in vitro, but showed similar overall defect site vascular volumes at 2 weeks postimplantation by microcomputed tomography angiography. However, a larger number of small-diameter vessels were observed in the vascularized construct-treated groups. Yet, both vascularized implant groups showed primarily fibrotic tissue with adipose infiltration, poor maintenance of tissue volume within the VML, and little muscle regeneration. These data suggest that while vascularization may play an important supportive role, other factors besides adequate vascularity may determine the fate of regenerating volumetric muscle defects.
GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans (2019)

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.
Response to Drs. Mishkin (2001)

TO THE EDITOR: We appreciate Drs. Daniel and Seymour Mishkin's interest in our study (1) and their comments corroborating that a subgroup of subjects with functional bowel complaints may have SIBO as defined by breath test.
Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function (2001)

Platelet activation is normally induced by primary agonists such as adenosine diphosphate (ADP), thrombin, and collagen, whereas other agonists, such as epinephrine, can play important accessory roles. It is now reported that the macrophage-derived chemokine (MDC), thymus activation-regulated chemokine (TARC), and stromal cell-derived factor one (SDF-1) are highly effective activators of platelet function under a variety of conditions, stimulating platelet shape change, aggregation, and adhesion to collagen or fibrinogen. Chemokine-mediated platelet activation was rapid and maximal (less than 5 seconds) under arterial flow conditions and depended strongly on the presence of low levels of primary agonists such as ADP or thrombin. Concentrations of ADP (0.05-0.25 microM) or thrombin (0.005-0.02 U/mL) that induced minimal aggregation caused major aggregation acting in combination with the chemokines. The ability of apyrase to block chemokine-dependent aggregation or adhesion was consistent with an important role for ADP. Chemokine-stimulated aggregation was also insensitive to indomethacin, suggesting that the activation of cyclo-oxygenase is not involved. TARC, MDC, and SDF-1 increased intracellular calcium concentrations [Ca(2+)](i) when combined with low levels of ADP. The MDC and TARC receptor CCR4 was expressed on platelets, and an anti-CCR4 antibody blocked aggregation induced by TARC or MDC. Treatment of platelets with SDF-1 and MDC rapidly exposed P-selectin (CD62P) on the cell surface but did not induce the secretion of serotonin. These findings suggest that the chemokines MDC, TARC, and SDF-1, which may be produced during inflammatory responses, coupled with low levels of ADP or thrombin, can serve as strong stimuli for activating platelet function.
Forskningsbaserad matematikundervisning : möjligt i teorin, men går det i praktiken? (2011)

Elevens tro pa sin egen formaga visade sig vara en av nyckelfaktorerna nar skolkontoret i Umea kommun, Specialpedagogiska skolmyndigheten samt det matematikdidaktiska forskarnatverket vid Umea univ ...
Interferon-induced 2-5A synthetase activity in human peripheral blood mononuclear cells after immunization with influenza virus and rubella virus vaccines (1984)

The interferon-induced enzyme 2-5A synthetase can be a sensitive indicator of activation of the human interferon system during viral infection or interferon therapy. To determine the response of the human interferon system to viral antigens, the level of 2-5A synthetase activity was monitored in peripheral blood mononuclear cells of healthy adults before and after immunization with influenza or rubella virus vaccine. The influenza virus-vaccinated individuals demonstrated increases in enzyme activity on days 1 and 11 in vivo, whereas those vaccinated with rubella virus vaccine showed an increase only on day 11. The difference in the day 1 in vivo 2-5A synthetase response in the two vaccinated groups could be demonstrated by in vitro incubations of peripheral blood mononuclear cells isolated approximately 90 days postvaccination with the two vaccines. The day 11 increase of enzyme activity in the rubella virus group showed a positive correlation with an increase in serum antibody titer, suggesting activation of the interferon system during antibody production in vivo after human exposure to virus antigens. The demonstration of increased 2-5A synthetase activity at specific times postimmunization in this investigation indicates that the interferon system is involved in the human in vivo response to virus vaccination.
Improved Assessment of T-Cell Receptor (TCR) VB Repertoire in Clinical Specimens: Combination of TCR-CDR3 Spectratyping with Flow Cytometry-Based TCR VB Frequency Analysis (2002)

Antigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a T-cell population, (ii) the quantity of T-cell responses (i.e., the number of responding T cells within the CD4/CD8 population), and (iii) the "quality" of T cells (defined by the T-cell receptor [TCR] structure). Several methods to measure T-cell responses are now available including evaluation of T-cell precursors using limiting dilution, the enzyme-linked immunospot assay, ex vivo TCR variable (v)-segment analysis determined by flow cytometry, and TCR-CDR3 length analysis (spectratyping), as well as identification of peptide-specific T cells using major histocompatibility complex (MHC) class I tetramers containing appropriate peptides. Until now, only a limited set of MHC-peptide complexes have been available as tetramer complexes. We demonstrate that CD8(+) or CD4(+) T cells in patients with cancer can be molecularly defined using a combination of spectratyping (TCR structure and "molecular composition") plus the implementation of an antibody panel directed against 21 individual VB TCR chains ("quantity" of T-cell families). This approach is instrumental in defining and comparing the magnitudes of CD4(+) or CD8(+) T-cell responses over time in individual patients, in comparing the TCR VA and VB repertoire in different anatomic compartments, and in comparing the TCR VA-VB diversity with that in normal healthy controls. This method provides the means of objectively defining and comparing the TCR repertoire in patients undergoing vaccination protocols and underlines the necessity to calibrate the TCR-CDR3 analysis with a qualitative assessment of individual TCR VB families.
Sequence Requirements of the 5-Enolpyruvylshikimate-3-Phosphate Synthase 5'-Upstream Region for Tissue-Specific Expression in Flowers and Seedlings (1990)

Philip N. Benfey, Hiroshi Takatsuji, Ling Ren, Dilip M. Shah, Nam-Hai Chua, Sequence Requirements of the 5-Enolpyruvylshikimate-3-Phosphate Synthase 5′-Upstream Region for Tissue-Specific Expression in Flowers and Seedlings, The Plant Cell, Vol. 2, No. 9 (Sep., 1990), pp. 849-856
Murine concanavalin A-induced hepatitis is prevented by interleukin 12 (IL-12) antibody and exacerbated by exogenous IL-12 through an interferon-γ-dependent mechanism (2000)

Concanavalin A (ConA)-induced hepatitis is a cell-mediated immunoinflammatory condition similar to human autoimmune hepatitis. We investigated the role of interleukin 12 (IL-12) in hepatitis induced in NMRI and C57/BL6 mice by a single injection of ConA. Recombinant murine IL-12 administered 24 hours and 1 hour prior to ConA exacerbated both transaminase activities in plasma and histologic signs of hepatitis. These markers of liver injury were significantly reduced by prophylactic, but not therapeutic treatment with anti-IL-12 monoclonal antibody (mAb). The disease-modulatory effects of IL-12 and anti-IL-12 mAb were associated with profound and reverse modifications of a ConA-induced increase in the circulating levels of IL-4, IL-6, interferon gamma (IFN-γ) and tumor necrosis factor (TNF). Relative to control animals receiving ConA alone, the plasma levels of these cytokines were all augmented in IL-12/ConA-treated mice and diminished in anti-IL-12 mAb/ConA-treated mice. Anti-IFN-γ mAb also impeded the appearance of IL-12/ConA-induced hepatitis. Thus, IL-12-induced production of IFN-γ might play a role in mediating the hepatitis-inducing effect of ConA. However, IL-12p40-deficient C57/BL6 mice were as susceptible as wild-type controls to the hepatitis-inducing effect of ConA.
Determination of 2‐methoxyestradiol in human plasma, using liquid chromatography/tandem mass spectrometry (2005)

A liquid chromatography/tandem mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of 2-methoxyestradiol (2ME2) in human plasma. Sample pretreatment involved liquid-liquid extraction with ethyl acetate of 0.3-mL aliquots of plasma spiked with the internal standard, deuterated 2ME2 (2ME2-d5). Separation was achieved on a Zorbax Eclipse C18 column (2.1 x 50 mm, i.d., 5 microm) at room temperature using a gradient elution with methanol and water at a flow rate of 0.25 mL/min. Detection was performed using atmospheric pressure chemical ionization MS/MS by monitoring the ion transitions from m/z 303.1 --> 136.8 (2ME2) and m/z 308.1 --> 138.8 (2ME2-d5). Calibration curves were linear in the concentration range of 1-100 ng/mL. The accuracy and precision values, obtained from three different sets of quality control samples analyzed in quintuplicate on four separate occasions, ranged from 105-108% and from 3.62-5.68%, respectively. This assay was subsequently used for the determination of 2ME2 concentration in plasma of a patient with cancer after a single oral administration of 2ME2 at a dose of 2200 mg.
Recognizing and Treating Nonmotor Disorders Associated with Parkinson's Disease (1998)

Abstract Recognizing the nonmotor symptoms associated with Parkinson's disease (PD) is necessary to determine effective treatment regimens and achieve patients' maximum mobility, as well as enhance their quality of life. The Unified Parkinson's Disease Rating Scale (UPDRS) is a useful tool for the clinician in evaluating the entire patient. In this article, the nonmotor disorders related to PD are reviewed, with specific attention to the first and last sections of the UPDRS, which cover mentation and complications of therapy, respectively. Various treatment regimens for these nonmotor symptoms are presented. Other autonomic nervous system symptoms associated with PD, which are not assessed in the UPDRS, are also discussed.
Increased tumorigenicity of rat colon carcinoma cells after ?1,2-fucosyltransferaseFTA anti-sense cDNA transfection (1999)

Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H increases tumor cell motility and tumorigenesis. Alpha1,2-fucosylation is a key step in the synthesis of these antigens. Two alpha1,2-fucosyltransferases, expressed in colorectal carcinomas, have been characterized (FUT1 and FUT2 in humans, FTA and FTB in rats). To define the relative contribution of each of these enzymes in tumor cell behavior, we have used an anti-sense transfection approach in rat colon carcinoma PROb cells, which synthesize mRNA encoding for both enzymes. We have previously reported that anti-sense transfection of a cDNA fragment of the FTB enzyme decreased H antigenic cell-surface levels and concomitantly decreased tumorigenicity. H antigens, detected by antibodies specific for H type 1, 3 or 4, were detected only on a splice variant of CD44 containing the product of exon v6. We now report the anti-sense transfection of an FTA cDNA fragment into PROb cells, which resulted in decreased enzymatic activity on a type 2 precursor and decreased cell-surface H type 2 antigen exclusively. Compared to controls, FTA anti-sense-transfected cells were significantly more tumorigenic in syngeneic animals but not in immunodeficient SCID mice. The UEA-I lectin, specific for H type 2, revealed that these structures were present on the CD44v6 variant and on an uncharacterized 80-kDa glycoprotein. Our results indicate that FTA and FTB fucosylate distinct glycan chains in the same cell, leading to opposite effects, under control of the immune system.
Antioxidant supplementation in sepsis and systemic inflammatory response syndrome (2007)

Three antioxidant nutrients have demonstrated clinical benefits and reached level A evidence: a) selenium improves clinical outcome (infections, organ failure); b) glutamine reduces infectious complication in large-sized trials; and c) the association of eicosapentaenoic acid and micronutrients has significant anti-inflammatory effects. Other antioxidants are still on the clinical benchmark level, awaiting well-designed clinical trials.
A grafting approach to obtain site-specific metal-binding properties of EF-hand proteins (2003)

The EF-hand calcium-binding loop III from calmodulin was inserted with glycine linkers into the scaffold protein CD2.D1 at three locations to study site-specific calcium binding properties of EF-hand motifs. After insertion, the host protein retains its native structure and forms a 1:1 metal-protein complex for calcium and its analog, lanthanum. Tyrosine-sensitized Tb3+ energy transfer exhibits metal binding and La3+ and Ca2+ compete for the metal binding site. The grafted EF-loop III in different environments has similar La3+ binding affinities, suggesting that it is largely solvated and functions independently from the host protein.