gebhart/patrepeval huggingface dataset:
Effects of Obesity Surgery on Non–Insulin-Dependent Diabetes Mellitus (2002)

Bariatric surgical procedures have proven a much more successful method of weight loss and diabetes control in the obese population than conservative methods. These surgical procedures have proven safe with reported mortality rates of 0% to 1.5%. Bariatric operations may be divided based on the method of weight loss and effect on diabetes. The first category is restrictive and includes vertical banded gastroplasty and adjustable silicone gastric banding. These operations improve diabetes by decreasing food intake and body weight with a slowing of gastric emptying. The second category not only contains restrictive components but also elements of malabsorption. This category includes the Roux-en-Y gastric bypass and biliary-pancreatic diversion, which bypass the foregut. Although all of the surgical procedures for obesity offer improved weight loss and diabetes control compared with conservative methods, the Roux-en-Y gastric bypass and biliary-pancreatic diversion offer superior weight loss and resolution of diabetes. The more dramatic effect seen in the surgical procedures to cause malabsorption is likely secondary to the bypass of the foregut resulting in increased weight loss and elevation of the enteroglucagon level.
Differentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells (2011)

The success of cancer immunotherapy depends on productive tumor cell recognition by killer lymphocytes. γδ T cells are a population of innate-like lymphocytes endowed with strong, MHC-unrestricted cytotoxicity against tumor cells. This notwithstanding, we recently showed that a large proportion of human hematologic tumors is resistant to γδ peripheral blood lymphocytes (PBLs) activated with specific agonists to the highly prevalent Vγ9Vδ2 TCR. Although this probably constitutes an important limitation to current γδ T cell-mediated immunotherapy strategies, we describe here the differentiation of a novel subset of Vδ2(-) Vδ1(+) PBLs expressing natural cytotoxicity receptors (NCRs) that directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells. We show that Vδ1(+) T cells can be selectively induced to express NKp30, NKp44 and NKp46, through a process that requires functional phosphatidylinositol 3-kinase (PI-3K)/AKT signaling on stimulation with γ(c) cytokines and TCR agonists. The stable expression of NCRs is associated with high levels of granzyme B and enhanced cytotoxicity against lymphoid leukemia cells. Specific gain-of-function and loss-of-function experiments demonstrated that NKp30 makes the most important contribution to TCR-independent leukemia cell recognition. Thus, NKp30(+) Vδ1(+) T cells constitute a novel, inducible and specialized killer lymphocyte population with high potential for immunotherapy of human cancer.
Thiol-sensitive mast cell lines derived from mouse bone marrow respond to a mast cell growth-enhancing activity different from both IL-3 and IL-4. (1989)

A series of permanent IL-3-dependent cell lines have been established from normal BALB/c or C3H bone marrow using alpha-thioglycerol-supplemented culture medium and PWM-stimulated spleen cell-conditioned medium as a source of IL-3. The cell lines and derivatives cloned in agar resembled "mucosal type" mast cells with respect to phenotypic and functional properties. In this report we demonstrate that in vitro growth of these mast cell lines was not only dependent on IL-3 and synergistically enhanced by IL-4, but in addition regulated by alpha-thioglycerol which could be replaced by 2-ME or cysteamine. We show that these thiol-sensitive mast cell lines respond to a mast cell growth enhancing activity (MEA) present in spleen cell-conditioned medium and acting in concert with IL-3. Partially purified MEA was not able to stimulate the growth of IL-3-dependent 32Dcl.23 cells, IL-2-dependent CTLL-2 cells or the mouse T cell line F4/4K.6 (L3T4+) adapted to grow in purified IL-4. Moreover, 11B11 hybridoma-derived anti-IL-4 mAb specifically neutralizing mouse Il-4 were unable to abolish the bioactivity of MEA. PWM, CSF-1, GM-CSF, IL-1, IL-2, IL-5, IL-6, IL-7, IFN-gamma, TGF-alpha, TNF-alpha, NGF, or EPO did not substitute for MEA in our standard proliferation assay.
Size-Controlled Synthesis of Gold Nanoparticles from Bulk Gold Substrates by Sonoelectrochemical Methods (2004)

Size-controlled gold nanoparticles, ranging from 2 to 15 nm in diameter, were first prepared from gold substrates in 0.1 N HCl aqueous solutions without the addition of any stabilizers by sonoelectrochemical methods. First, an Au substrate was cycled in a deoxygenated aqueous solution containing 0.1 N HCl from −0.28 to +1.22 V vs Ag/AgCl at 500 mV/s with 100 scans. The durations at the cathodic and anodic vertexes are 10 and 5 s, respectively. After this process, Au- and Cl-containing complexes were left in the solution. The Au working electrode was then immediately replaced by a Pt electrode, and cathodic overpotentials of 0.2, 0.4, and 0.6 V from the open circuit potential (OCP) of ca. 0.82 V vs Ag/AgCl were applied under sonification to synthesize Au nanoparticles. The prepared nanoparticles increase in size from 2 to 15 nm with the increase of the cathodic overpotential applied from 0.2 to 0.6 V. Furthermore, the ratio of Au nanoparticles to Au-containing nanocomplexes in solutions can be controlled by adjusting the sonoelectrochemical reduction time.
BJT effect analysis in p- and n-SOI MuGFETs with high-k gate dielectrics and TiN metal gate electrode for a 1T-DRAM application (2011)

This paper presents an analysis of the bipolar effect in triple gate n-and p-SOI devices with high-k/TiN metal gate. High-k dielectrics and thicker TiN achieve a larger trigger voltage. However, a reduced program window is found for MuGFETs with high-k dielectrics. p-FET devices give rise to a smaller sense margin and program window due to the reduced hole mobility. Narrow fin devices exhibit a larger trigger voltage and reduced program window and sense margin for a given Vds.
Clinical application of scaffolds for cartilage tissue engineering (2008)

The purpose of this paper is to review the basic science and clinical literature on scaffolds clinically available for the treatment of articular cartilage injuries. The use of tissue-engineered grafts based on scaffolds seems to be as effective as conventional ACI clinically. However, there is limited evidence that scaffold techniques result in homogeneous distribution of cells. Similarly, few studies exist on the maintenance of the chondrocyte phenotype in scaffolds. Both of which would be potential advantages over the first generation ACI. The mean clinical score in all of the clinical literature on scaffold techniques significantly improved compared with preoperative values. More than 80% of patients had an excellent or good outcome. None of the short- or mid-term clinical and histological results of these tissue-engineering techniques with scaffolds were reported to be better than conventional ACI. However, some studies suggest that these methods may reduce surgical time, morbidity, and risks of periosteal hypertrophy and post-operative adhesions. Based on the available literature, we were not able to rank the scaffolds available for clinical use. Firm recommendations on which cartilage repair procedure is to be preferred is currently not known on the basis of these studies. Randomized clinical trials and longer follow-up periods are needed for more widespread information regarding the clinical effectiveness of scaffold-based, tissue-engineered cartilage repair.
In vivodepletion of CD8+T cells restores hair growth in the DEBR model for alopecia areata (1996)

Alopecia areata (AA) is a putative autoimmune disease in which anagen hair follicles are the target of immune cell attack. While both CD4+ and CD8+ T lymphocytes are prominent in the infiltrate, their respective roles in the pathogenesis of AA remain unknown. Here we directly investigated the activity of CD8+ cells in the inhibition of hair growth using the Dundee experimental bald rat (DEBR) model for AA. Eight lesional DEBRs were fully depleted of their CD8+ cells by intraperitoneal injection of OX-8 monoclonal antibody (MoAb) specific for these cells over a 15-day therapy course. A control group of eight lesional rats was injected with the irrelevant MoAb OX-21. Sequential blood samples were analysed by flow cytometry to observe changes in the CD8+ cell population and macrophotography used to record changes in hair growth activity. All eight CD8+ depleted rats started to regrow hair within 29 days from the start of treatment, the final response ranging from sparse regrowth to a near normal coat. While two rats maintained their new pelage, the remainder lost hair as the CD8+ population in peripheral blood increased. Two of the control rats also showed hair regrowth over the experimental period of 156 days. These results suggest that CD8+ cells play an active part in the pathogenesis of AA. As hair production did not fully recover in all animals, immune mechanisms other than CD8+ cells may be involved in effecting hair loss. However, analysis of CD8+ cell levels in the skin of CD8+ depleted rats may help resolve their full importance in AA.
Pharmacokinetics of the first combination 17β-estradiol/progesterone capsule in clinical development for menopausal hormone therapy (2015)

The combination 17β-estradiol/progesterone product demonstrates bioavailability similar to those of the respective reference products of estradiol and progesterone. If regulatory approval is obtained, this new hormone therapy would be the first treatment of menopause symptoms to combine progesterone with 17β-estradiol in an oral formulation.
Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer (2014)

Significance Mass spectrometry imaging (MSI) technology represents a highly promising approach in cancer research. Here, we outline current roadblocks in translational MSI and introduce a comprehensive workflow designed to address current methodological limitations. An integrated bioinformatics platform is presented that allows intuitive histology-directed interrogation of MSI datasets. We show that this strategy permits the analysis of multivariate molecular signatures with direct correlation to morphological regions of interest, which can offer new insights into how different tumor microenvironmental populations interact with one another and generate novel region-of-interest specific biomarkers and therapeutic targets.
Early-Life Adversity and Choice of the Social Work Profession (2006)

Abstract Social work students have reported comparatively high incidences of adverse early-life experiences, yet little is known about the extent of these experiences among professional social workers or how they may affect the choice of social work. This study addresses many of the shortcomings of previous studies, with respondents drawn from a national random sample of social workers and a comparison group made up of college-educated professional persons outside of social work. The findings reveal that the social work sample was not characterized by greater early-life adversity than that found among professional persons generally. Possible interpretations include an association between early-life adversity and shorter stays in the profession, and cohort differences in occupational choice influences.
Practical Aspects and Applications of Radial Flow Chromatography (2000)

Traditionally, axial flow columns have been utilized for protein purification: samples are applied to the top of the column and separated down the vertical length. A piston presses against the top of the resin bed to ensure an evenly packed bed and to remove dead spaces that develop during resin compression. This forms part of the head plate of the column, which generally has to be removed before packing the column.
The IP 3 Receptor as a Hub for Bcl-2 Family Proteins in Cell Death Control and Beyond (2014)

Bcl-2 family proteins generally have a proapoptotic or antiapoptotic role. In addition to their known roles at the mitochondria, Bcl-2 family proteins also influence signaling at the endoplasmic reticulum by binding to the inositol 1,4,5-trisphosphate receptor (IP3R), the most ubiquitous intracellular Ca(2+) channel. Surprisingly, multiple Bcl-2 family proteins target different sites on the IP3R to elicit various effects on IP3R function, which suggests that the IP3R is an important hub for Bcl-2 family proteins in various physiological settings.
Tolvrije digitale toegang tot de Sonttolregisters (2012)

Interview met George Welling en Willem Veluwenkamp.
Wanneer je tussen 1497 en 1857 met je laadruim vol goederen door de Sont voer en je betaalde geen tol aan de Deense koning, dan werd je vanaf slot Kronborg bestookt met kanonskogels. Als je dan toch nog levend aan wal kwam, mocht je ook nog eens de kosten van de
kanonskogel betalen. De meeste schippers droegen wel keurig hun tol af en streken hun grootzeil als eerbetoon aan de Deense koning. Dat heeft een schat aan gegevens voor onderzoek opgeleverd: de Sonttolregisters.
Trans-activation by thyroid hormone receptors: functional parallels with steroid hormone receptors. (1989)

The effects of thyroid hormones are mediated through nuclear receptor proteins that modulate the transcription of specific genes in target cells. We previously isolated cDNAs encoding two different mammalian thyroid hormone receptors, one from human placenta (hTR beta) and the other from rat brain (rTR alpha), and showed that their in vitro translation products bind thyroid hormones with the characteritistic affinities of the native thyroid hormone receptor. We now demonstrate that both of the cloned receptors activate transcription from a thyroid hormone-responsive promoter in a hormone-dependent manner, with rTR alpha eliciting a greater response than hTR beta. The putative functional domains of the thyroid hormone receptors were examined by creating chimeric thyroid hormone/glucocorticoid receptors, producing receptors with hybrid functional properties. These experiments support the proposal that the thyroid hormone receptors are composed of interchangeable functional domains, and indicate that the mechanism of hormone-inducible gene regulation has been conserved in steroid and thyroid hormone receptors.
Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding (2011)

Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.
Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries. (1992)

The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.
Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer (2011)

The immune system can both promote and suppress cancer. Chronic inflammation and proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are considered to be tumour promoting. In contrast, the exact nature of protective antitumour immunity remains obscure. Here, we quantify locally secreted cytokines during primary immune responses against myeloma and B-cell lymphoma in mice. Strikingly, successful cancer immunosurveillance mediated by tumour-specific CD4(+) T cells is consistently associated with elevated local levels of both proinflammatory (IL-1α, IL-1β and IL-6) and T helper 1 (Th1)-associated cytokines (interferon-γ (IFN-γ), IL-2 and IL-12). Cancer eradication is achieved by a collaboration between tumour-specific Th1 cells and tumour-infiltrating, antigen-presenting macrophages. Th1 cells induce secretion of IL-1β and IL-6 by macrophages. Th1-derived IFN-γ is shown to render macrophages directly cytotoxic to cancer cells, and to induce macrophages to secrete the angiostatic chemokines CXCL9/MIG and CXCL10/IP-10. Thus, inflammation, when driven by tumour-specific Th1 cells, may prevent rather than promote cancer.
Protease‐Catalyzed Formation of CN Bonds (2004)

This chapter contains sections titled: Optimization of Proteases for Synthesis: Selection of Current Techniques Substrate Engineering Classical Concept of Leaving-group Manipulation Substrate Mimetics-mediated Syntheses Enzyme Engineering Chemical Enzyme Modifications Genetic Enzyme Modifications Conclusions References
Relationships between morphology and physiology of pyramid‐pyramid single axon connections in rat neocortex in vitro. (1994)

1. Double intracellular recordings were made from 1163 pairs of pyramidal neurones in layer V-VI of the rat somatomotor cortex in vitro using sharp electrodes filled with biocytin. Monosynaptically connected pairs of cells were identified when an action potential in one could elicit a constant latency excitatory postsynaptic potential (EPSP) in the other and the cells were filled with biocytin. Labelled cells were subsequently identified histologically with avidin-horseradish peroxidase. 2. Thirty-four pairs of cells were found to be monosynaptically connected. Fifteen of these pairs were sufficiently stable for electrophysiological recordings and three of these were recovered sufficiently to permit full morphological reconstruction. 3. The EPSP recorded between the first pair of pyramids varied in amplitude between 0 and 3 mV (mean 1.33 +/- 1.06 mV) and fluctuated considerably (coefficient of variation, 0.796). This was largely due to a high incidence of apparent failures of transmission. On reconstruction two boutons from the presynaptic pyramid axon were in close apposition to the proximal portions of basal dendrites of the postsynaptic cell. 4. In the second pair of pyramids the EPSP had a mean amplitude of 1.06 mV, and displayed a 10-90% rise time of 2.8 ms and a width at half-amplitude of 23 ms. This EPSP did not alter significantly with changes in membrane potential at the soma. The presynaptic axon closely apposed the distal apical dendrite of the postsynaptic cell in eight places. 5. In the third pair of pyramids, the EPSPs, recorded at a relatively depolarized membrane potential, were long lasting and could elicit slow dendritic spikes with long and variable latencies. These slow spikes suggested that the postsynaptic recording site was dendritic and on reconstruction a possible location was identified on the apical dendrite. A total of five presynaptic boutons closely apposed three separate, proximal branches of the postsynaptic apical dendrite. 6. These results provide the first illustration of a morphological basis for variations in functional properties of pyramid-pyramid connections in the neocortex.
The structural acoustics and active control of interior noise in a ribbed cylindrical shell (1996)

Numerical studies are carried out regarding the structural acoustics of a ribbed aluminum cylindrical shell structure intended to represent the essential structural features of a small aircraft fuselage. Calculations are made to determine both the wall normal displacements and the interior acoustic pressures for the case in which the shell wall is forced dynamically at a point. The structural responses are further decomposed into their frequency-wave-number components. Through a series of comparisons between those responses for an infinite shell, the ribbed vacuum-filled shell, and the ribbed air-filled shell, the relevant structural acoustic mechanisms are interpreted. The frequencies at which interior acoustic ‘‘resonances’’ are observed are connected to specific mechanisms, including cavity responses driven by structural modes, cavity modes forcing the structure, and mixed structure/air-cavity modes. Numerically based active control experiments are carried out using end actuation, and the relative performance of this control ‘‘system’’ is compared when operating on the various mode types.
An animal model of chronic inflammatory pain: Pharmacological and temporal differentiation from acute models (2005)

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.