gebhart/patrepeval huggingface dataset:
Kidney preservation in the next millenium (1999)

For the past decades, severe hypothermia has represented the foundation of organ preservation in clinical transplantation. Beneficial as hypothermia has proven to be in preserving grafts from heart-beating donors, hypothermia does not seem to provide the window necessary for the prospective evaluation of organ function. With the increasing use of non-heart-beating donors, it is logical to propose that if organs are to be evaluated prospectively, it will be necessary to preserve them at warmer temperatures. Since both glomerular and tubular functions are inhibited at temperatures below 18 degrees C, such a goal will necessitate organ preservation at a temperature above 20 degrees C. The principle of preservation at warmer temperatures is not new, but with future developments and approaches, successful realization appears within reach. In this overview, a brief history of previous attempts at warm preservation, in the context of the current status of kidney preservation, is presented. Future developments and approaches, with the potential for prospective testing of the function and enhanced resistance to ischemic damage, will be discussed.
The α2β1 integrin is a metastasis suppressor in mouse models and human cancer (2010)

Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles in tumor progression and metastasis. Although work in preclinical models suggests that β1 integrins may stimulate metastasis of a number of cancers, expression of the β1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the α2β1 integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of α2β1 integrin in normal breast epithelium and loss of α2β1 in poorly differentiated breast cancer. They are also consistent with our systematic analysis of microarray databases of human breast and prostate cancer, which revealed that decreased expression of the gene encoding α2 integrin, but not genes encoding α1, α3, or β1 integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of α2 expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the α2β1 integrin functionally inhibits breast tumor metastasis, and α2 expression may serve as an important biomarker of metastatic potential and patient survival.
Intracellular and extracellular vaccinia virions enter cells by different mechanisms. (1998)

Vaccinia virus (VV) produces two antigenically distinct infectious virions, intracellular mature virus (IMV) and extracellular enveloped virus (EEV). Structurally, EEV consists of an IMV with an additional outer membrane containing proteins that are absent from IMV. EEV is important for virus dissemination both in vitro and in vivo. Studies of EEV entry have been hampered by having two infectious virions and by the rupture of the EEV outer membrane in the majority of EEV virions during their purification. To overcome these problems, we have developed a novel approach to study VV entry that is based on confocal microscopy and does not require EEV purification. This assay relies on immunofluorescent staining and detection of individual, intracellular, uncoated virus cores. By this method, we show that EEV entry, in contrast to IMV, is dependent on a low-pH pathway and that the IMV enwrapped inside the EEV exhibits a low-pH fusogenic activity. Together with neutralization data demonstrating that exposure to low pH disrupts the EEV outer membrane, this study strongly supports a model for EEV entry which consists of binding, endocytosis, low-pH-induced disruption of the EEV outer membrane and fusion of the exposed IMV with the endosomal membrane releasing the core into the cytosol. The roles of the EEV outer membrane in virus dissemination and virus entry are discussed in relation to this model.
PDE isoenzymes as targets for anti-asthma drugs (1995)

Phophodiesterase (PDE) isoenzyme profiles of human cell preparations and tissues have been analysed by a semiquantitative method using selective PDE inhibitors and activators. Neutrophils, eosinophils and monocytes contain PDE IV exclusively. Lymphocytes, alveolar macrophages and endothelial cells contain PDE IV and PDE III, and in addition, PDE I is measured in macrophages and PDE II in endothelial cells. These basal cell-specific PDE isoenzyme profiles appear to be modified by: 1) substrate concentration; 2) kinase-dependent phosphorylation; and 3) regulated rate of synthesis. Therefore, PDE isoenzyme profiles represent dynamic patterns, which apparently adapt to pathological and environmental conditions. In parallel functional studies, the influence of mono-selective (rolipram, PDE IV; motapizone, PDE III), dual-selective (zardaverine) and non-selective (theophylline) PDE inhibitors were compared. Corresponding to isoenzyme analysis, it was demonstrated that both PDE III and PDE IV have to be inhibited for complete suppression of either tumour necrosis factor-alpha (TNF-alpha) release from macrophages, or lymphocyte proliferation (PDE III/IV cells). In eosinophils (PDE IV cells) platelet-activating factor (PAF)-induced chemotaxis or C5a-stimulated degranulation are only weakly inhibited by rolipram alone. After addition of a beta 2-agonist, however, the efficacy of rolipram is enhanced due to concomitant influence of synthesis and breakdown of cyclic adenosine monophosphate (cAMP). Theophylline inhibits PDE isoenzyme activities and functions of inflammatory cells with similar potency, and exhibits higher functional efficacy as compared to rolipram.
Multiwavelength technology for local loop applications (2003)

Some of the possible options for the exploitation of wavelength division multiplexing (WDM) techniques in the local loop are illustrated. It is noted that few-wavelength systems will probably be the first systems to be exploited, and early practical realizations are discussed. It is further suggested that the fuller exploitation of the optical spectrum available will be via much more extensive high-density WDM. Techniques are described showing that these opportunities could rapidly follow from few-wavelength systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhanced Bone Morphogenetic Protein-2-Induced Ectopic and Orthotopic Bone Formation by Intermittent Parathyroid Hormone (1–34) Administration (2010)

Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1-34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n = 9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1-34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1-34) resulted in significantly (p < 0.05) enhanced BMD and bone volume in the BMP-2 composites at both implantation sites. Despite its effect on BMD in the humerus and vertebra, PTH (1-34) treatment had no significant effect on BMD and bone volume in the empty femoral defects and the ectopically or orthotopically implanted empty composites. Histological analysis showed that the newly formed bone had a normal woven and trabecular appearance. Overall, this study suggests that intermittent administration of a low PTH dose alone has limited potential to enhance local bone regeneration in a critical-sized defect in rats. However, when combined with local BMP-2-releasing scaffolds, PTH administration significantly enhanced osteogenesis in both ectopic and orthotopic sites.
Long‐term follow‐up of cancer and leukemia group B studies in acute myeloid leukemia (1997)

BACKGROUND During the past 3 decades, the Cancer and Leukemia Group B (CALGB) has conducted numerous large clinical trials in adult patients with acute myeloid leukemia. METHODS Updated data were obtained for 9 trials initiated by the CALGB between 1974 and 1992. The updated data were compared with the original published results. RESULTS It was apparent from all the studies that hazard rates for death and relapse are greatest in the first year, decrease substantially between Years 1 and 2, then decrease further between Years 2 and 3. Rates of death and relapse are quite low after 3-4 years. Large numbers of patients are long-term disease free survivors. Overall, these patients have excellent function and a normal quality of life. CONCLUSIONS Patients with AML who are in complete remission for 3-4 years can be assured that late relapse and death are relatively uncommon events. It is inadvisable to publish results of large studies until this minimal level of follow-up has been reached. Cancer 1997; 80:2210-4. © 1997 American Cancer Society.
KATP Channel Openers Inhibit Lymphatic Contractions and Lymph Flow as a Possible Mechanism of Peripheral Edema (2020)

Pharmacological openers of ATP-sensitive potassium (K<sub>ATP</sub>) channels are effective antihypertensive agents, but off-target effects, including severe peripheral edema, limit their clinical usefulness. It is presumed that the arterial dilation induced by K<sub>ATP</sub> channel openers (KCOs) increases capillary pressure to promote filtration edema. However, K<sub>ATP</sub> channels also are expressed by lymphatic muscle cells (LMCs), raising the possibility that KCOs also attenuate lymph flow to increase interstitial fluid. The present study explored the effect of KCOs on lymphatic contractile function and lymph flow. In isolated rat mesenteric lymph vessels (LVs), the prototypic K<sub>ATP</sub> channel opener cromakalim (0.01-3 µmol/l) progressively inhibited rhythmic contractions and calculated intraluminal flow. Minoxidil sulfate and diazoxide (0.01-100 µmol/l) had similar effects at clinically relevant plasma concentrations. High-speed in vivo imaging of the rat mesenteric lymphatic circulation revealed that superfusion of LVs with cromakalim and minoxidil sulfate (0.01-10 µmol/l) maximally decreased lymph flow in vivo by 38.4% and 27.4%, respectively. Real-time polymerase chain reaction and flow cytometry identified the abundant K<sub>ATP</sub> channel subunits in LMCs as the pore-forming Kir6.1/6.2 and regulatory sulfonylurea receptor 2 subunits. Patch-clamp studies detected cromakalim-elicited unitary K<sup>+</sup> currents in cell-attached patches of LMCs with a single-channel conductance of 46.4 pS, which is a property consistent with Kir6.1/6.2 tetrameric channels. Addition of minoxidil sulfate and diazoxide elicited unitary currents of similar amplitude. Collectively, our findings indicate that KCOs attenuate lymph flow at clinically relevant plasma concentrations as a potential contributing mechanism to peripheral edema. SIGNIFICANCE STATEMENT: ATP-sensitive potassium (K<sub>ATP</sub>) channel openers (KCOs) are potent antihypertensive medications, but off-target effects, including severe peripheral edema, limit their clinical use. Here, we demonstrate that KCOs impair the rhythmic contractions of lymph vessels and attenuate lymph flow, which may promote edema formation. Our finding that the K<sub>ATP</sub> channels in lymphatic muscle cells may be unique from their counterparts in arterial muscle implies that designing arterial-selective KCOs may avoid activation of lymphatic K<sub>ATP</sub> channels and peripheral edema.
Effects of dexmedetomidine on delirium duration of non-intubated ICU patients (4D trial): study protocol for a randomized trial (2018)

ClinicalTrials.gov , ID: NCT 03317067 . Registered on 23 October 2017.
Original Article: Real time reverse transcription (RRT)‐polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs (2010)

Two RRT PCRs for the purposes of (i) generic detection of SIV and H1N1v infection in European pigs, and for (ii) specific detection of H1N1v (pandemic influenza) infection were validated.
Experiments in social data mining (2003)

Social data mining systems enable people to share opinions and benefit from each other's experience. They do this by mining and redistributing information from computational records of social activity such as Usenet messages, system usage history, citations, or hyperlinks. Some general questions for evaluating such systems are: (1) is the extracted information valuable? and (2) do interfaces based on the information improve user task performance? We report here on TopicShop , a system that mines information from the structure and content of Web pages and provides an exploratory information workspace interface. We carried out experiments that yielded positive answers to both evaluation questions. First, a number of automatically computable features about Web sites do a good job of predicting expert quality judgments about sites. Second, compared to popular Web search interfaces, the TopicShop interface to this information lets users select significantly more high-quality sites, in less time and with less effort, and to organize the sites they select into personally meaningful collections more quickly and easily. We conclude by discussing how our results may be applied and considering how they touch on general issues concerning quality, expertise, and consensus.
Mycobacterium smegmatis laminin‐binding glycoprotein shares epitopes with Mycobacterium tuberculosis heparin‐binding haemagglutinin (2001)

Mycobacterium tuberculosis, the causative agent of tuberculosis, produces a heparin-binding haemagglutinin adhesin (HBHA), which is involved in its epithelial adherence. To ascertain whether HBHA is also present in fast-growing mycobacteria, Mycobacterium smegmatis was studied using anti-HBHA monoclonal antibodies (mAbs). A cross-reactive protein was detected by immunoblotting of M. smegmatis whole-cell lysates. However, the M. tuberculosis HBHA-encoding gene failed to hybridize with M. smegmatis chromosomal DNA in Southern blot analyses. The M. smegmatis protein recognized by the anti-HBHA mAbs was purified by heparin-Sepharose chromatography, and its amino-terminal sequence was found to be identical to that of the previously described histone-like protein, indicating that M. smegmatis does not produce HBHA. Biochemical analysis of the M. smegmatis histone-like protein shows that it is glycosylated like HBHA. Immunoelectron microscopy demonstrated that the M. smegmatis protein is present on the mycobacterial surface, a cellular localization inconsistent with a histone-like function, but compatible with an adhesin activity. In vitro protein interaction assays showed that this glycoprotein binds to laminin, a major component of basement membranes. Therefore, the protein was called M. smegmatis laminin-binding protein (MS-LBP). MS-LBP does not appear to be involved in adherence in the absence of laminin but is responsible for the laminin-mediated mycobacterial adherence to human pneumocytes and macrophages. Homologous laminin-binding adhesins are also produced by virulent mycobacteria such as M. tuberculosis and Mycobacterium leprae, suggesting that this adherence mechanism may contribute to the pathogenesis of mycobacterial diseases.
Purification of MEA, a mast cell growth-enhancing activity, to apparent homogeneity and its partial amino acid sequencing. (1990)

A novel growth factor for bone marrow derived murine mucosal type mast cells has been isolated from the conditioned medium of the Mlsa-reactive mouse Th cell line MLS-4.2. In proliferation assays this growth factor synergizes, like IL-4, with IL-3 on established mast cell lines and was therefore termed MEA: mast cell growth enhancing activity. MEA was characterized as a glycoprotein with a Mr range between 37,000 and 43,000. Apparent homogeneity was obtained by using a four-step purification scheme including cation exchange chromatography, Procion red affinity chromatography, IEF, and gel filtration. Inasmuch as MEA was N-terminally blocked during automated Edman-degradation, peptide fragments after digestion with trypsin were used for partial amino acid sequence determination. All evaluable MEA peptide fragments showed complete sequence homology to a recently purified and cloned novel T cell growth factor (P40/TCGF III), the mouse homologue of human IL-9.
A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice (2007)

Autism spectrum disorders (ASDs) are characterized by impairments in social behaviors that are sometimes coupled to specialized cognitive abilities. A small percentage of ASD patients carry mutations in genes encoding neuroligins, which are postsynaptic cell-adhesion molecules. We introduced one of these mutations into mice: the Arg451-->Cys451 (R451C) substitution in neuroligin-3. R451C mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly, these behavioral changes were accompanied by an increase in inhibitory synaptic transmission with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C substitution represents a gain-of-function mutation. These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C knockin mice may be a useful model for studying autism-related behaviors.
Surface crosslinking of polyethylene and adhesive joint strength (1974)

Exposure of polyethylene film to UV radiation at wavelengths of ≤2537 Å is sufficient to induce surface crosslinking and to facilitate the formation of strong adhesive joints to these surfaces with conventional adhesives. Reduction of the vapor pressure in the reaction vessel to about 1 torr apparently maximizes the efficiency of the crosslinking process. Examination of the treated films which have been exposed for times necessary to form strong adhesive joints has revealed an absence of surface oxidation. It appears that crosslinking to improve the mechanical strength of the surface region of the polyethylene is sufficient to allow the formation of strong adhesive joints.
Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Can Regulate Dendritic Cell–induced Activation and Cytotoxicity of CD8+ T Cells Independently of CD4+T Cell Help (1999)

The mechanisms that regulate the strength and duration of CD8(+) cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8(+) T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8(+) T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti-CTLA-4 mAb greatly enhanced the accumulation, activation, and cytotoxic activity of CD8(+) T cells induced by immunization with Ag on dendritic cells (DC). This enhanced response did not require the expression of MHC class II molecules on DC or the presence of CD4(+) T cells. These results demonstrate that CTLA-4 blockade is able to directly enhance the proliferation and activation of specific CD8(+) T cells, indicating its potential for tumor immunotherapy even in situations in which CD4(+) T cell help is limited or absent.
Mechanisms of altered vagal control in heart failure: influence of muscarinic receptors and acetylcholinesterase activity (2003)

Parasympathetic control of the heart is attenuated in heart failure (HF). We investigated possible mechanisms and sites of altered vagal control in dogs with HF induced by rapid pacing. Muscarinic blockade reduced the R-R interval by 308 ms in controls but only by 32 ms in HF, indicating low levels of resting vagal tone. Vagomimetic doses of atropine sulfate prolonged the R-R interval by 109 ms in controls and increased standard deviation of the R-R interval by 66 ms but only by 46 and 16 ms, respectively, in HF. Bradycardia elicited by electrical stimulation of the vagus nerve was also attenuated in the HF group. Conversely, muscarinic receptor activation by bethanechol, and indirectly by neostigmine, elicited exaggerated R-R interval responses in HF. To investigate possible mechanisms, we measured muscarinic receptor density (Bmax) and acetylcholinesterase activity in different areas of the heart. In sinoatrial nodes, Bmax was increased (230 +/- 75% of control) and acetylcholinesterase decreased (80 +/- 6% of control) in HF. We conclude that muscarinic receptors are upregulated and acetylcholinesterase is reduced in the sinus node in HF. Therefore, reduced vagal control in HF is most likely due to changes of presynaptic function (ganglionic), because postsynaptic mechanisms augment vagal control in HF.
Accurate Measurement of RF Power Deposition During 3T MRI. (2010)

Accurate knowledge of the specific absorption rate (SAR) during an MRI scan is vitally important for patient safety (1). Precise measurement of the total power deposited in the body enables correct SAR prediction and monitoring. The existence of many cases of scanner-associated RF burns reported to the FDA (2), and the irreproducibility of scanner-reported SAR for implanted devices (3), suggests that accurate scanner-independent measures of RF power deposition/exposure during MRI are needed (4).

Monitoring power delivered to the body by the scanner is complicated because of losses in the RF transmission chain elements including cables, switches, quadrature-hybrid (Q-Hybrid) plus coil losses. Another challenge is that MRI RF signals have a high dynamic range of peak vs average power, as well as a low duty cycle, that hamper commercial power meter operation and consequent power measurements.

In this study we characterize losses in an RF power chain for a 1H body coil in a 3T clinical scanner. RF power in the transmission chain was measured for four volunteers of different body mass indices (BMI) and weights.