gebhart/patrepeval huggingface dataset:
p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity (2012)

Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin-stimulated glucose uptake is mediated by the glucose transporter 4 (GLUT4), which is expressed mainly in skeletal muscle and adipose tissue. Insulin-stimulated translocation of GLUT4 from its intracellular compartment to the plasma membrane is regulated by small guanosine triphosphate hydrolases (GTPases) and is essential for the maintenance of normal glucose homeostasis. Here we show that the p75 neurotrophin receptor (p75(NTR)) is a regulator of glucose uptake and insulin resistance. p75(NTR) knockout mice show increased insulin sensitivity on normal chow diet, independent of changes in body weight. Euglycemic-hyperinsulinemic clamp studies demonstrate that deletion of the p75(NTR) gene increases the insulin-stimulated glucose disposal rate and suppression of hepatic glucose production. Genetic depletion or shRNA knockdown of p75(NTR) in adipocytes or myoblasts increases insulin-stimulated glucose uptake and GLUT4 translocation. Conversely, overexpression of p75(NTR) in adipocytes decreases insulin-stimulated glucose transport. In adipocytes, p75(NTR) forms a complex with the Rab5 family GTPases Rab5 and Rab31 that regulate GLUT4 trafficking. Rab5 and Rab31 directly interact with p75(NTR) primarily via helix 4 of the p75(NTR) death domain. Adipocytes from p75(NTR) knockout mice show increased Rab5 and decreased Rab31 activities, and dominant negative Rab5 rescues the increase in glucose uptake seen in p75(NTR) knockout adipocytes. Our results identify p75(NTR) as a unique player in glucose metabolism and suggest that signaling from p75(NTR) to Rab5 family GTPases may represent a unique therapeutic target for insulin resistance and diabetes.
Endogenous Dendritic Cells Are Required for Amplification of T Cell Responses Induced by Dendritic Cell Vaccines In Vivo (2003)

Dendritic cells (DCs) loaded in vitro with Ag are used as cellular vaccines to induce Ag-specific immunity. These cells are thought to be responsible for direct stimulation of Ag-specific T cells, which may subsequently mediate immunity. In this study, in transgenic mouse models with targeted MHC class II expression specifically on DCs, we show that the DC vaccine is responsible only for partial CD4(+) T cell activation, but to obtain optimal expansion of T cells in vivo, participation of endogenous (resident) DCs, but not endogenous B cells, is crucial. Transfer of Ag to endogenous DCs seems not to be mediated by simple peptide diffusion, but rather by DC-DC interaction in lymph nodes as demonstrated by histological analysis. In contrast, injection of apoptotic or necrotic DC vaccines does not induce T cell responses, but rather represents an immunological null event, which argues that viability of DC vaccines can be crucial for initial triggering of T cells. We propose that viable DCs from the DC vaccine must migrate to the draining lymph nodes and initiate a T cell response, which thereafter requires endogenous DCs that present transferred Ag in order induce optimal T cell expansion. These results are of specific importance with regard to the applicability of DC vaccinations in tumor patients, where the function of endogenous DCs is suppressed by either tumors or chemotherapy.
Immunohistochemistry and Quantitative Analysis of Protein Expression (2006)

Abstract Context.—Immunohistochemistry has taken a central role in the field of pathology, and its role is destined to increase as companion diagnostics analogous to the HercepTest are required for new targeted therapeutics. However, the inherent subjectivity of the assessment of an objective value (the in situ protein concentration) suggests that new technologies to measure the protein concentration may be required to achieve the accuracy required for companion diagnostics. Objective.—This article discusses the state of immunohistochemistry and reviews the currently available devices for quantitative in situ assessment of protein expression. Data Sources.—Data for this work were collected from the published literature, the Internet, and from information provided by device vendors. Conclusions.—Although there is a long history of efforts to quantify immunohistochemistry, there has been a lack of broad acceptance because the resultant objective accuracy has not significantly improved outcome measures compared with the traditional, conventional analysis by eye. As the demand grows for companion diagnostics with complex assessment requirements, we are likely to see increased usage of quantitative platforms, especially those with the capacity to do multiplexed analysis. This most likely will be driven by a requirement for outcomes that cannot be achieved by traditional methods.
Field Trials of a Vaccine Against Bovine Mastitis. 1. Evaluation in Heifers (1997)

A vaccine was developed against bovine mastitis based on inactivated, highly encapsulated Staphylococcus aureus cells; a crude extract of Staph. aureus exopolysaccharides; and inactivated, unencapsulated Staph, aureus and Streptococcus spp. cells. This vaccine was tested on 30 heifers during a 7-mo period. The 30 heifers were randomly assigned to three groups of 10 heifers each. The prepartum group received two injections of the vaccine at 8 and 4 wk before calving, and the postpartum group received two injections at 1 and 5 wk after calving. The control group received two injections of a placebo at 8 and 4 wk before calving. The vaccine or the placebo was administered subcutaneously in the brachiocephalicus muscle of the neck. The frequencies of intramammary infections caused by Staph. aureus were reduced from 18.8% for heifers in the control group to 6.7 and 6.0% for heifers in the prepartum and postpartum groups, respectively. This protective effect was maintained for at least 6 mo. The relative risk of mastitis caused by Staph. aureus was 0.31 and 0.28 for heifers in the prepartum and postpartum groups, respectively, compared with that for heifers in the control group. The results of the trial indicated the effectiveness of the vaccine in decreasing the incidence of intrammammary infections caused by Staph. aureus. A slight but nonsignificant increase occurred in fat production in the milk of vaccinated cows. The vaccine had no observable effect on somatic cell count or streptococcal infections.
Secretional luciferase of the luminous shrimpOplophorus gracilirostris: cDNA cloning of a novel imidazopyrazinone luciferase (2000)

The deep‐sea shrimp Oplophorus gracilirostris secretes a luciferase that catalyzes the oxidation of coelenterazine to emit blue light. The luciferase ( M r approx. 106 000) was found to be a complex composed of 35 kDa and 19 kDa proteins, and the cDNAs encoding these two proteins were cloned. The expression of the cDNAs in bacterial and mammalian cells indicated that the 19 kDa protein, not the 35 kDa protein, is capable of catalyzing the luminescent oxidation of coelenterazine. The primary sequence of the 35 kDa protein revealed a typical leucine‐rich repeat sequence, whereas the catalytic 19 kDa protein shared no homology with any known luciferases including various imidazopyrazinone luciferases.
Physiological and Molecular Mechanisms of Lymphocyte Homing (1992)

The lymphoid system is functionally compartmentalized in vivo into discrete primary, secondary, and tertiary lymphoid organs. Primary lymphoid tissues--the bone marrow and thymus--are responsible for the production of mature "virgin" lymphocytes. Secondary lymphoid tissues--lymph nodes, the spleen, and gut-associated lymphoid tissues--are specialized for the accumulation and presentation of antigen to both virgin and memory lymphocyte subsets. The remainder of the body's tissues may be considered "tertiary" lymphoid tissues, in that they normally contain only a few lymphoid elements, but in the setting of inflammation can be induced to recruit unique subsets of primarily memory lymphocytes. Each lymphoid tissue is further subdivided into discrete microenvironments, each characterized by a distinct complement of lymphocyte subsets and stromal cells. Lymphocyte homing comprises the physiologic processes by which lymphocytes seek out and localize to particular tissues and to specific microenvironments therein. Homing mechanisms play a major role in the maintenance of these specialized microenvironments and are critical for the dispersal and targeting of naive and memory lymphocyte populations that are required for effective immune surveillance. Here, we provide a brief overview of mechanisms thought to control the homing of lymphocyte populations in vivo, focusing in particular on the adhesive interactions involved in lymphocyte-endothelial cell recognition and in the selective extravasation of lymphocyte populations into secondary and tertiary lymphoid tissues.
Multidimensional tomographic imaging using volume holography (1999)

We propose the application of volume holography to four-dimensional (4-D) spatiospectral imaging. The proposed systems use materials and techniques developed for holographic data storage and interconnections to capture three-dimensional (3-D) spatial and one-dimensional (1-D) spectral information about a remote light source or scatterer. We analyze case studies of simple architectures using spherical-reference volume holograms as imaging elements in a fluorescence confocal microscope arrangement and demonstrate the equivalence of the holographic degeneracies with a slicing operation on the reconstructing incoherent source. We develop a general theoretical framework for the diffraction of random fields from volume holograms and show that the formulation can be used as an imaging design tool. Applications and future directions are also discussed.
Characterization of novel mutations in the catalytic domain of the PCSK9 gene (2008)

This study has provided novel information about the structural requirements for the normal function of PCSK9. However, more studies are needed to determine the mechanisms by which gain-of-function mutations in PCSK9 cause hypercholesterolemia.
Energetics of walking and running: insights from simulated reduced-gravity experiments (1992)

On Earth, a person uses about one-half as much energy to walk a mile as to run a mile. On another planet with lower gravity, would walking still be more economical than running? When people carry weights while they walk or run, energetic cost increases in proportion to the added load. It would seem to follow that if gravity were reduced, energetic cost would decrease in proportion to body weight in both gaits. However, we find that under simulated reduced gravity, the rate of energy consumption decreases in proportion to body weight during running but not during walking. When gravity is reduced by 75%, the rate of energy consumption is reduced by 72% during running but only by 33% during walking. Because reducing gravity decreases the energetic cost much more for running than for walking, walking is not the cheapest way to travel a mile at low levels of gravity. These results suggest that the link between the mechanics of locomotion and energetic cost is fundamentally different for walking and for running.
Is Sacral Neuromodulation for Fecal Incontinence Worthwhile in Patients With Associated Pelvic Floor Injury? (2010)

Pelvic floor injury is present in the majority of incontinent patients who were eligible for sacral neuromodulation. This type of injury seems to have no detrimental effect on the treatment outcome.
Chicken anemia virus (1998)

Chicken anemia virus is commonly found in commercially produced chickens and has a worldwide distribution. It is difficult to inactivate thermally or with common disinfectants, which limits the utility of normal sanitization practices. The virus is important because of the disease it produces following transovarian transmission and because of its potential for inducing immunosuppression alone or in combination with other infectious agents. Control measures are directed at limiting vertical transmission and preventing coinfections with other lymphocidal agents.
Increased levels of insulin‐like growth factor binding protein‐2 in sera and tumours from patients with colonic neoplasia with and without acromegaly (2001)

Our results describe changes in IGFBP-2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation.
A phase II study of raltitrexed and gemcitabine in patients with advanced pancreatic carcinoma (2005)

Advanced adenocarcinoma of the pancreas has a very poor prognosis. The aim of this study was to assess the efficacy and tolerability of a combination of the chemotherapeutic agents gemcitabine and raltitrexed. Chemonaive patients with advanced adenocarcinoma of the pancreas were treated with a combination of raltitrexed (3.5 mg m(-2) on day 1 of a 21-day treatment cycle) and gemcitabine (800 mg m(-2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle). Between April 2000 and February 2003, 27 patients were enrolled onto the study. The mean duration of treatment was 11 weeks. Four of 27 patients experienced at least one episode of grade 3 or 4 neutropenia. One patient with grade 4 neutropenia died due to sepsis. Four of 27 patients experienced grade 4 diarrhoea. There was one partial remission (4%) and 12 patients experienced disease stabilisation (44%). The 6-month and 1-year survival rates were 37 and 11%, respectively. Symptomatic benefit occurred in seven (26%) patients. We conclude that a combination of raltitrexed and gemcitabine, using the schedule and doses in this study, cannot be recommended for patients with advanced pancreatic cancer.
Plant Genetic Transformation and Gene Expression: A Laboratory Manual (1988)

Contents: Vectors for the transformation of plant cells using Agrobacterium Transformation of dicotyledenous plant cells using the Ti plasmid of Agrobacterium tumefaciens and the Ri plasmid of A. rhizogenes Transformation of plant cells by DNA-mediated gene transfer The isolation of plant nucleic acids DNA restriction and analysis by Southern hybridization Analysis of gene organization and expression in plants.
PML in a Patient Treated with Fumaric Acid (2013)

Two cases of progressive multifocal leukoencephalopathy (PML) are reported in patients with psoriasis who were treated with fumarates, one with Fumaderm and the other with a compound containing dimethyl fumarate. The manufacturer of Fumaderm comments on the reports.
The regulation of IL-10 production by immune cells (2010)

Interleukin-10 (IL-10), a cytokine with anti-inflammatory properties, has a central role in infection by limiting the immune response to pathogens and thereby preventing damage to the host. Recently, an increasing interest in how IL10 expression is regulated in different immune cells has revealed some of the molecular mechanisms involved at the levels of signal transduction, epigenetics, transcription factor binding and gene activation. Understanding the specific molecular events that regulate the production of IL-10 will help to answer the remaining questions that are important for the design of new strategies of immune intervention.
Chemical coding of the human gastrointestinal nervous system: Cholinergic, VIPergic, and catecholaminergic phenotypes (2003)

The aim of this investigation was to identify the proportional neurochemical codes of enteric neurons and to determine the specific terminal fields of chemically defined nerve fibers in all parts of the human gastrointestinal (GI) tract. For this purpose, antibodies against the vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), vasoactive intestinal peptide (VIP), and protein gene product 9.5 (PGP 9.5) were used. For in situ hybridization (35)S-labeled VMAT1, VMAT2, and VAChT riboprobes were used. In all regions of the human GI tract, 50-70% of the neurons were cholinergic, as judged by staining for VAChT. The human gut unlike the rodent gut exhibits a cholinergic innervation, which is characterized by an extensive overlap with VIPergic innervation. Neurons containing VMAT2 constituted 14-20% of all intrinsic neurons in the upper GI tract, and there was an equal number of TH-positive neurons. In contrast, DBH was absent from intrinsic neurons. Cholinergic and monoaminergic phenotypes proved to be completely distinct phenotypes. In conclusion, the chemical coding of human enteric neurons reveals some similarities with that of other mammalian species, but also significant differences. VIP is a cholinergic cotransmitter in the intrinsic innervation of the human gut. The substantial overlap between VMAT2 and TH in enteric neurons indicates that the intrinsic catecholaminergic innervation is a stable component of the human GI tract throughout life. The absence of DBH from intrinsic catecholaminergic neurons indicates that these neurons have a dopaminergic phenotype.
Controlled formulation of monodisperse double emulsions in a multiple-phase microfluidic system (2005)

This paper gives an overview of our recent work on the use of microfluidic devices to formulate double emulsions. Key issues in the controlled encapsulation of highly monodisperse drops include: (a) regular periodicity in the formation of micro droplets due to the interplay between viscous shearing and interfacial tension in low Reynolds number streams; (b) serially connected hydrophobic and hydrophilic microchannels to form aqueous and organic drops consecutively. Water-in-oil-in-water emulsions and oil-in-water-in-oil emulsions can both be produced by reversing the order of hydrophobic and hydrophilic junctions. Alternating formation of aqueous droplets at a cross junction has enabled the production of organic droplets that encase two aqueous droplets of differing compositions.
Chemical probing of virginiamycin M-promoted conformational change of the peptidyl-transferase domain (1994)

Previous findings suggest the location of the central loop of domain V of 23S rRNA within the peptidyltransferase domain of ribosomes. This enzymatic activity is inhibited by some antibiotics, including type A (virginiamycin M or VM) and type B (virginiamycin S or VS) synergimycins, antibiotics endowed with a synergistic action in vivo. In the present work, the ability of VM and VS to modify the accessibility of 23S rRNA bases within ribosomes to chemical reagents has been explored. VM afforded a protection of rRNA bases A2037, A2042, G2049 and C2050. Moreover, when ribosomes were incubated with the two virginiamycin components, the base A2062, which was protected by VS alone, became accessible to dimethyl sulphate (DMS). Modified reactivity to chemical reagents of different rRNA bases located either in the central loop of domain V or in its proximity furnishes experimental evidence for conformational ribosome alterations induced by VM binding.
Biosynthesis of cinnamamide and detection of phenylalanine ammonia-lyase in Streptomyces verticillatus (1970)

Radioactivity from L-phenylalanine-carboxyl- 14 C was incorporated specifically into the carboxyl group of cinnamamide by cultures of Streptomyces verticillatus. L-Phenylalanine ammonia-lyase (EC. 4.3.1.5) could be extracted from the mycelium. Cultures grown in defined medium produced little cinnamamide unless supplemented with L-phenylalanine; phenylalanine ammonia-lyase activity in the mycelium was directly related to the yield of cinnamamide.
Enhancement of in vivo cell-mediated immune responses by three distinct cytokines. (1990)

The ability of recombinant/purified cytokines to augment delayed-type hypersensitivity (DTH) responses was investigated. Suboptimal doses of haptenized SC were treated in vitro with purified or recombinant derived cytokines and tested for their ability to enhance DTH in vivo. With the use of this protocol, it was shown that both human and mouse rIL-6, as well as mouse rTNF-alpha, potentiated DTH in a dose-dependent manner. In accordance with these data, IL-6/TNF-alpha-containing supernatant from long term nonlymphoid cell lines also possessed the ability to augment DTH. By using the same protocol, we have also identified T cell hybridomas that produce DTH-augmenting activity constitutively. The hybridoma-derived factor, termed the T cell enhancing factor (TCEF), was functionally distinguishable from the defined cytokines IL-1 through IL-6, IFN-gamma, and TNF by bioassay. Furthermore, RNA derived from the hybridoma failed to hybridize with cDNA probes specific for IL-1 to IL-6, IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF. Further characterization of the serum-free conditioned media derived from the hybridoma indicated that the TCEF was a soluble acid labile glycoprotein (Mr greater than 30,000). Finally, we investigated the cellular requirements for DTH augmentation by IL-6, TNF-alpha, and TCEF; all are dependent upon the presence of T cells in the immunizing inoculum. We propose that these cytokines play a critical role in the development of DTH responses in vivo.
A new two-photon ghost imaging experiment with distortion study (2007)

Differing from the early principle demonstrations, this practical ghost imaging experiment reports the first set of two-photon images captured by a photon counting CCD camera by means of jointly counting ‘reflected’ photons from the object. Interestingly, the CCD camera was not ‘looking’ at the object at all. Instead, the CCD camera was facing the chaotic light source. The output of the CCD camera was used for coincidence registration of the two-photon joint-detection events with another photon counting detector which simply collects all randomly reflected photons from the surface of the object. It is also interesting to find that the observed two-photon images are ‘distortion-free’, i.e. any disturbances made along the light path has no effect on the quality of the image. These experimental observations are not only useful for practical field-applications, but also important from a fundamental point of view. It rejects the ‘projection shadow’ idea in a non-deniable way and further explores the two-photon interference nature of thermal light ghost imaging.
Closed Intramedullary Derotational Osteotomy and Hip Arthroscopy for Cam Femoroacetabular Impingement From Femoral Retroversion (2014)

Femoral retroversion is an uncommon cause of cam femoroacetabular impingement that may require surgical treatment beyond arthroscopic or open femoroplasty. We present the case of a young adult with bilateral severe femoral retroversion in whom such treatment failed. We discuss the rationale, surgical technique, and outcome of this patient, who underwent bilateral closed intramedullary derotational proximal femoral osteotomies and interlocked nailing with adjunctive pre- and post-osteotomy hip arthroscopies. Clinical improvement with normal foot progression angles, radiographic union, and resolution of bilateral cam femoroacetabular impingement from femoral retroversion was achieved. This surgery permits rapid institution of weight-bearing ambulation and an early rehabilitative program. Femoral retroversion may be an underappreciated and insufficiently treated cause of cam femoroacetabular impingement that may be readily detected and successfully remedied with this less invasive procedure.