gebhart/patrepeval huggingface dataset:
White-Matter Astrocytes, Axonal Energy Metabolism, and Axonal Degeneration in Multiple Sclerosis (2012)

In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which may impair the astrocytic sodium potassium pump and lead to a reduced sodium-dependent glutamate uptake. Astrocytes in MS white matter appear to be deficient in β(2) adrenergic receptors, which are involved in stimulating glycogenolysis and suppressing inducible nitric oxide synthase (NOS2). Glutamate toxicity, reduced astrocytic glycogenolysis leading to reduced lactate and glutamine production, and enhanced nitric oxide (NO) levels may all impair axonal mitochondrial metabolism, leading to axonal degeneration. In addition, glutamate-mediated oligodendrocyte damage and impaired myelination caused by a decreased production of N-acetylaspartate by axonal mitochondria might also contribute to axonal loss. White-matter astrocytes may be considered as a potential target for neuroprotective MS therapies.
Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats. (1999)

These results demonstrate that a recombinant adenoviral vector can achieve the transfer of bFGF gene in vitro and have a protective effect for photoreceptor cells in vivo. Gene therapy with a bFGF-expressing recombinant adenoviral vector may provide a new strategy with which to target retinal degenerative diseases.
Hemostasis and Thrombosis: Basic Principles and Clinical Practice. (1988)

PART I - BASIC PRINCIPLES OF HEMOSTASIS AND THROMBOSIS SECTION A - COAGULATION AND ITS REGULATION SECTION B - FIBRINOLYSIS AND ITS REGULATION 285 SECTION C - PLATELET STRUCTURE AND FUNCTION SECTION D - VASCULAR BIOLOGY, EMBRYOGENESIS, DEVELOPMENT, AND DISORDERS PART II - CLINICAL APPLICATIONS SECTION A - INHERITED HEMORRHAGIC DISORDERS SECTION B - ACQUIRED HEMORRHAGIC DISORDERS SECTION C - THERAPY OF BLEEDING DISORDERS SECTION D - VENOUS THROMBOEMBOLIC DISORDERS SECTION E - CARDIOVASCULARTHROMBOTIC DISEASES SECTION F - COMPLEX THROMBOHEMORRHAGIC DISORDERS SECTION G - THERAPY, NEW DIRECTIONS, AND COMPLICATIONS IN THROMBOTIC DISORDERS
Native Burning in Western North America: Implications for Hardwood Forest Management (2000)

It is now widely acknowledged that frequent low-intensity fires once structured many western forests. What is not generally recognized, however, is that most of those fires were purposefully set by native people, not started by lightning. Data from the Rocky Mountains attest to the widespread use of fire by native people, as does the ecology of aspen, the only common deciduous hardwood in the West. Fire history studies all show that aspen once burned at frequent intervals, yet aspen will readily burn only when the trees are leafless and the understory dry — conditions which occur only early in the spring before leaf-out and understory regrowth, or late in the fall after leaf-drop and the understory has been killed by frost. During both these periods, though, there are few lightning strikes and virtually no lightning- started fires in the Rocky Mountains. Thus if aspen burned frequently in the past, as all evidence indicates it once did, then those fires must have been started by native people, who used fire to modify plant communities for human benefit. Similarly, eastern deciduous forests will readily burn only when leafless, but during that time there are few lightning strikes — one of many indications that aboriginal burning was also common in the eastern U.S.
Developing the next generation of monoclonal antibodies for the treatment of rheumatoid arthritis (2010)

Rheumatoid arthritis is one of the commonest autoimmune diseases affecting 0.8% of the population. Over the last decade the treatment of this chronic disease has been revolutionized by the use of monoclonal antibodies and fusion proteins, targeting molecules like tumour necrosis factor alpha. Nevertheless, approximately one-third of subjects fail to respond to these therapies and therefore significant unmet medical need remains. Following a decade of use, clinical, government and regulatory agency expectations have changed for new antibodies therapies entering this highly competitive area. In this review, we discuss the current advances being made in antibody engineering and how they are being considered and used in the development of the next generation of antibodies to meet future expectations of healthcare providers, physicians and patients. Moreover, we discuss how pattern recognition receptors may provide new antibody tractable targets that may break the cycle of autoimmunity in rheumatoid arthritis.
A functionally active protein import complex from (1992)

Isolated outer chloroplast envelope membranes were solubilized by digitonin and separated on linear sucrose density gradients. A membrane complex was recovered from the gradients and exhibited characteristics of a protein import apparatus, i.e. the interaction of the complex with the precursor polypeptides depends on the presence of a transit sequence, ATP and protease‐sensitive components. Furthermore, trans‐location intermediates detected in the organellar system are also found after interaction of the precursor polypeptide with the isolated import complex.
Preliminary evidence of clinical activity in a phase I study of CAL-101, a selective inhibitor of the p1108 isoform of phosphatidylinositol 3-kinase (P13K), in patients with select hematologic malignancies (2009)

3543 Background: The class I PI3Ks regulate a variety of cellular functions relevant to oncogenesis, including metabolism, proliferation and survival. The PI3K p110δ isoform is highly expressed in cells of hematopoietic origin and plays a key role in B cell maturation and function. CAL-101 is a potent inhibitor of PI3K p110δ (IC 50 =65 nM) with 40 to 300-fold selectivity compared to other PI3K isoforms. In vitro studies of 0.1 to 10 μM CAL-101 showed inhibition of pAKT expression and/or apoptotic effects against primary chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) cells and against a range of leukemia and lymphoma cell lines. Methods: In an ongoing phase 1 dose escalation study in sequential cohorts of 3 patients with relapsed/refractory CLL or select B-cell non-Hodgkin's lymphoma, CAL-101 is administered orally twice daily for 28 days per cycle. Clinical response is evaluated according to NCI criteria at the end of Cycles 1 and 2 and every 2 cycles thereafter. Results: To date, 6 patients have been treated in the first 2 cohorts at dose levels of 50 mg and 100 mg and the 200 mg cohort is currently enrolling. No treatment-related adverse events greater than grade 1 have been seen, with 2 patients treated for &gt;5 cycles. Mean trough drug levels in the 50 and 100 mg cohorts were 0.3 and 1 μM, respectively, which are in the range required to inhibit PI3K p110δ in vitro. Two of 6 patients attained partial response and 4 have stable disease. Partial responses were observed after 2 cycles of 50 mg in a patient with mantle cell lymphoma with 6 prior therapies, and after 1 cycle of 100 mg in a patient with follicular lymphoma with 6 prior therapies, including autologous stem cell transplant. Disease specific cohort expansion will occur at the maximally tolerated dose, and patients with AML will be added. Updated data will be presented at the meeting. Conclusions: Early results from a phase 1 study of the oral PI3K p110δ inhibitor CAL-101 show that it is well tolerated and has preliminary clinical activity in patients with B-cell malignancies. [Table: see text]
Two classes of CD1 genes (1989)

Herein, we report the DNA sequence of two human CD1 genes, R2 and R3, distinct from those encoding the CD1a, -b and -c antigens. Both genes appear to have an exon/intron structure analogous to the previously analyzed CD1 genes and to be functional on the basis of their sequence. Analysis of the variability patterns, potential intramolecular interactions and predicted secondary structure profile on an alignment of all known CD1 alpha chains suggest some shared structural features with major histocompatibility complex class I molecules in the alpha 1 domains but substantial differences in the alpha 2 domains. Sequence comparison shows that, while R2 is most related to CD1a, -b and -c, albeit to a somewhat lower degree than the latter are to themselves, R3 is more homologous to mouse than to human CD1, suggesting the existence of two functional classes within the CD1 gene family. We propose to retain the non-committal R2 and R3 names until the putative antigens have been identified and their tissue distribution has been established.
Role of Cytokines in Allergic Airway Inflammation (2006)

Asthma is characterized by intense infiltration of eosinophils and CD4+ T cells into the submucosal tissue of airways. Accumulating evidence indicates that T helper type 2 cell-derived cytokines such as interleukin (IL)-4, IL-5 and IL-13 play critical roles in orchestrating and amplifying allergic inflammation in asthma. In addition, it has been suggested that newly identified cytokines including thymic stromal lymphopoietin, IL-25 and IL-33 are involved in the induction of allergic inflammation in asthma. In this review, we discuss the role of individual cytokines in the pathogenesis of asthma.
A NEW HAEMODIALYSIS CATHETER‐LOCKING AGENT REDUCES INFECTIONS IN HAEMODIALYSIS PATIENTS (2008)

The use of a taurolidine/citrate haemodialysis catheter-locking agent in our haemodialysis population has significantly reduced the line sepsis rate, with a positive impact on morbidity, mortality and cost.
A Tactile Sensing and Display System for Surgical Applications (1995)

Certain medical techniques, such as endoscopic surgery, deprive surgeons of the ability to palpate tissue within the body. We describe a system that can remotely measure small scale shape information and recreate it on the fingertips of the surgeon. A tactile array sensor measures the pressure distribution at its contact area. This is processed to determine the shape of the object it is contacting. This information is then displayed to the surgeon through the shape display. Artery and tumor localization experiments were performed with the system. By placing the shape display on the tip of a two axis manipulator, haptic exploration of a virtual environment was tested. A computer generated model allowed a virtual tumor localization experiment to be performed. Initial results indicate that the system is able to successfully convey shape information.
Neuropsychological Deficits Are Correlated with Frontal Hypometabolism in Positron Emission Tomography Studies of Older Alcoholic Patients (1993)

In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)
Hematopoietic growth factors. (1987)

The process of blood cell formation, by which a small number of self-renewing stem cells give rise to lineage committed pro- genitor cells that subsequently proliferate and differentiate to produce the circulating mature blood cells, is sustained through- out life by a group of glycoprotein hormonal growth factors. These hormones are known collectively as the colony-stimulating factors (CSFs)' (1); the term derives from the in vitro observation that the CSFs stimulate progenitor cells of different hemato- poietic cell lineages to form discrete colonies of recognizable maturing cells. The different factors have been operationally de- fined by prefixes denoting the major type of colony produced, e.g., granulocyte maprophage CSF (GM-CSF). Not only is the presence of CSF5 necessary for the proliferation of progenitor cells but these factors affect the function of mature cells as well (2-8); furthermore, they may be the major regulators ofincreased cell production during states of increased demand. It is not yet clear whether they play a pathogenetic role in some forms of leukemia.
Abstract 3666: Inhibition of the tumor growth and prevention of metastases with MORAb-004, a human monoclonal IgG targeting endosialin/TEM-1 (2011)

Abstract Endosialin/Tumor Endothelial Marker-1 (TEM-1) is a cell surface glycoprotein that is expressed on cells involved in the development of tumor vasculature, primarily pericytes, smooth muscle, and stromal fibroblasts. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including (but not limited to) renal, breast, colon, pancreatic, lung, endometrial, ovarian, melanoma, sarcoma, and neuroectodermal tumors. We are currently evaluating the therapeutic efficacy of MORAb-004, a human monoclonal IgG1 targeting TEM-1, in a Phase I clinical trial. Because MORAb-004 only recognizes human/monkey TEM-1 and has no cross-reactivity with rodent TEM-1, we generated a human TEM-1 knock-in mouse line in order to assess its activity in in vivo tumor models. In a B16-F10 subcutaneous melanoma model we found that MORAb-004 significantly inhibited tumor progression by ∼70%. Moreover, using the Lewis Lung Carcinoma model of metastatic disease our results showed that MORAb-004 had a significant inhibitory effect on the number of lung metastases. Taken together our results demonstrated the ability of MORAb-004 in inhibiting the growth of solid tumors and preventing the emergence of distant metastases. The potential MOA is currently under evaluation and will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3666. doi:10.1158/1538-7445.AM2011-3666
Improved therapeutic efficacy of a monoclonal antibody radioiodinated using N-succinimidyl-3-(tri-n-butylstannyl)benzoate. (1991)

Improvements in efficacy of radioimmunotherapy will require increased tumor uptake relative to normal tissue. We previously demonstrated that labeling the IgG2b glioma-reactive antitenascin monoclonal antibody 81C6 with 131I using N-succinimidyl-3-(tri-n-butylstannyl)benzoate (ATE) increased tumor uptake and tumor-to-normal tissue ratios and decreased deiodination compared with labeling using Iodo-Gen. The present study was conducted to determine whether 131I 81C6 labeled using ATE (81C6 ATE) would demonstrate a therapeutic advantage over 131I 81C6 labeled using Iodo-Gen (81C6 IOD) in treating s.c. D-54 MG human glioma xenografts in athymic mice. The subclass IgG2b MAb 45.6 labeled with 131I using ATE (45.6 ATE) was used as a control. Animals were injected with saline or 500 microCi of 45.6 ATE (23 microCi/microgram), 81C6 ATE (26 microCi/microgram), or 81C6 IOD (24 microCi/microgram). With approximately 150 mm3 initial tumor volumes, growth delay for 81C6 ATE was significantly better by Wilcoxon rank sum analysis than saline (P = 0.0006 to 0.003), 45.6 ATE (P = 0.0006 to 0.002), and 81C6 IOD (P = 0.0008 to 0.007). Biodistribution data from similarly injected animals gave estimated radiation doses to tumor of 7723, 5200, and 1667 rad for 81C6 ATE, 81C6 IOD, and 45.6 ATE, respectively. In addition, 81C6 ATE administered at this dosage to animals with 50% larger initial tumors also improved tumor growth delay in comparison with 81C6 IOD given to animals with standard-size tumors. A similar experiment was conducted at 1000 microCi and, although radiation toxicity was noted in all labeled groups, two animals in the 81C6 ATE group had tumor regression for more than 240 days, and the other groups had no regressors. We conclude that the use of the ATE method may significantly improve the therapeutic efficacy of radioiodinated monoclonal antibodies.
Fetal Cells in Maternal Blood: A Six-Fold Increase in Women who have Undergone Amniocentesis and Carry a Fetus with Down Syndrome: A Multicenter Study (2004)

Fetal nucleated red blood cells (FNRBCs) circulate in the maternal blood throughout pregnancy. Even if the frequency of fetal cells in the maternal circulation remains to be ascertained, complications of pregnancy such as fetal cells aneuploidies, preeclampsia, abnormal Doppler of the uterine artery without symptoms of preeclampsia, fetal growth restriction and polyhydramnios are associated with an increased feto-maternal trafficking. Based on these observations, previous studies have suggested that determination of the fetal nucleated red blood cell count (FNRBCC) might be a useful non-invasive screening test, either alone or in combination with existing maternal tests, for the non-invasive assessment of aneuploidies, in particular Down syndrome (DS). In this paper we have evaluated the distribution of FNRBCC in a set of 18 normal pregnancies and 18 pregnancies with a trisomy 21-affected fetus, matching for gestational age, maternal age, and, when possible, fetal gender, in order to quantify the difference in the number of fetal cells between the two populations. Maternal blood was collected from each pregnant woman two to three weeks after amniocentesis after knowing the cytogenetic results. Correlation of FNRBCC with the gestational week and clinical status (affected vs. non affected) by multiple regression analysis provided significant results (p < 0.001). Adjusted values of FNRBCC were 48 +/- 10.2 in controls and 301 +/- 17.01 in DS cases, corresponding to a 6.27 fold increase. These retrospective results prompt a prospective evaluation of the use of FNRBCC for screening purposes.
Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogs (1993)

A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalmido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB. One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by > 95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent.
Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: A stereological study using the cavalieri and optical disector methods (1996)

The total number of neurons within six subdivisions of the rat basal ganglia was estimated using unbiased stereological counting methods and systematic random sampling techniques. Six young adult rats were perfuse-fixed, their right cerebral hemispheres were embedded in glycolmethacrylate, and a complete set of serial 40-mu m sections was cut through each hemisphere. After a random start, a systematic subset (e.g., every tenth) of these sections was used to estimate the total volume of each subdivision using Cavalieri's method. The same set of sampled sections was used to estimate the number of neurons in a known subvolume (i.e., the Nv) by the optical disector method. The product of the total volume and the Nv by these methods yields an unbiased estimate of the total number of neurons. It was found that the right basal ganglia consisted, on average, of 2.79 million neostriatal or caudate-putamen neurons (with a coefficient of variation of 0.07), 46,000 external globus pallidus neurons (0.11), 3,200 entopeduncular/internal globus pallidus neurons (0.10), 13,600 subthalamic neurons (0.10), 7,200 substantial nigra pars compacta neurons (0.15), and 26,300 substantia nigra pars reticulata neurons (0.07).
Blind speech separation combining DOA estimation and assignment problem approaches (2011)

In this paper, we propose an effective method for blind speech separation of convolutive mixtures in the frequency domain. The main difficulty in a frequency approach is the permutation problem. In the proposed method, we use two previous approaches to solve permutation ambiguity in the two-channel model: direction of arrival (DOA) estimation approach and assignment problem (AP) approach. We discuss the advantages and disadvantages of the two approaches, and integrate them to use the both advantages. Computer simulation experiments with speech data are presented to illustrate the proposed method.
Syntagms and paradigms in zoomusicology (1997)

Distributional analysis allows us to show a very strong convergence between the surface syntactic structures of animal signals and the same aspects of human syntax. This convergence corroborates other indices, suggesting that the resemblance between animal signals and human music is more than superficial. The passage from syntagms to paradigms is inevitable in zoomusicology. Whether it implies a conscious sonorous organization in the animal, is a question that can be asked only after analyses have been completed; it cannot be decided in advance. The question is in any case closely linked to that of music itself. There is description and discussion of paradigmatic aspects, and thus of implied mental categories and sonorous organizations, with the help of examples taken in particular from the skylark alauda arvensis. These show convergence with the known procedures of musical variation, leading to an evaluation of the degree of specificity. The limits and usefulness of semiotics in the domain of zoomusicology are sketched; can one speak, in the absence of a semantics or symbolics, of a conceptual tool that remains faithful to primitive structuralism?