gebhart/patrepeval huggingface dataset:
Novel analog of atrial natriuretic peptide selective for receptor-A produces increased diuresis and natriuresis in rats. (1996)

Atrial natriuretic peptide (ANP) binds to natriuretic peptide receptor-A (NPR-A), a membrane guanylyl cyclase, and to natriuretic peptide receptor-C (NPR-C), which plays a role in peptide clearance. Rat ANP (rANP) mutants that bind rat NPR-A selectively over rat NPR-C were isolated from randomized libraries of rANP-display phage by differential panning. One variant was identified with reduced NPR-C binding; rANP (G16R, A17E, Q18A) [rANP(REA18)]. Synthetic rANP(REA18) was equipotent with rANP in stimulating cGMP production from cloned rat NPR-A (ED50 = 1.8 nM) and was reduced in NPR-C binding by approximately 200-fold. When infused into conscious rats at 0.325 microg/min for 30 min rANP elicited an identical decrease in blood pressure compared with 0.25 microg/min of rANP(REA18), however the natriuretic (P < 0.05) and diuretic (P = 0.07) responses to rANP(REA18) were greater. These data are consistent with a role for NPR-C as a local decoy receptor attenuating NPR-A effects in the kidney, where these receptors are coexpressed. Improved NPR-A specificity could provide more effective natriuretic peptides for treatment of acute renal failure or heart failure.
Cellular Senescence: A Translational Perspective (2017)

Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.
A Role for the Neuronal Protein Collapsin Response Mediator Protein 2 in T Lymphocyte Polarization and Migration (2005)

The semaphorin-signaling transducer collapsin response mediator protein 2 (CRMP2) has been identified in the nervous system where it mediates Sema3A-induced growth cone navigation. In the present study, we provide first evidence that CRMP2 is present in the immune system and plays a critical role in T lymphocyte function. CRMP2 redistribution at the uropod in polarized T cells, a structural support of lymphocyte motility, suggests that it may regulate T cell migration. This was evidenced in primary T cells by small-interfering RNA-mediated CRMP2 gene silencing and blocking Ab, as well as CRMP2 overexpression in Jurkat T cells tested in a chemokine- and semaphorin-mediated transmigration assay. Expression analysis in PBMC from healthy donors showed that CRMP2 is enhanced in cell subsets bearing the activation markers CD69+ and HLA-DR+. Heightened expression in T lymphocytes of patients suffering from neuroinflammatory disease with enhanced T cell-transmigrating activity points to a role for CRMP2 in pathogenesis. The elucidation of the signals and mechanisms that control this pathway will lead to a better understanding of T cell trafficking in physiological and pathological situations.
Fluorescently Labeled Peptide Increases Identification of Degenerated Facial Nerve Branches during Surgery and Improves Functional Outcome (2015)

Nerve degeneration after transection injury decreases intraoperative visibility under white light (WL), complicating surgical repair. We show here that the use of fluorescently labeled nerve binding probe (F-NP41) can improve intraoperative visualization of chronically (up to 9 months) denervated nerves. In a mouse model for the repair of chronically denervated facial nerves, the intraoperative use of fluorescent labeling decreased time to nerve identification by 40% compared to surgeries performed under WL alone. Cumulative functional post-operative recovery was also significantly improved in the fluorescence guided group as determined by quantitatively tracking of the recovery of whisker movement at time intervals for 6 weeks post-repair. To our knowledge, this is the first description of an injectable probe that increases visibility of chronically denervated nerves during surgical repair in live animals. Future translation of this probe may improve functional outcome for patients with chronic denervation undergoing surgical repair.
Maintaining Recursive Views of Regions and Connectivity in Networks (2010)

The data management community has recently begun to consider declarative network routing and distributed acquisition: e.g., sensor networks that execute queries about contiguous regions, declarative networks that maintain shortest paths, and distributed and peer-to-peer stream systems that detect transitive relationships among data at the distributed sources. In each case, the fundamental operation is to maintain a view over dynamic network state. This view is typically distributed, recursive, and may contain aggregation, e.g., describing shortest paths or least costly paths. Surprisingly, solutions to computing such views are often domain-specific, expensive, and incomplete. We recast the problem as incremental recursive view maintenance given distributed streams of updates to tuples: new stream data becomes insert operations and tuple expirations become deletions. We develop techniques to maintain compact information about tuple derivability or data provenance. We complement this with techniques to reduce communication: aggregate selections to prune irrelevant aggregation tuples, provenance-aware operators that determine when tuples are no longer derivable and remove them from the view, and shipping operators that reduce the information being propagated while still maintaining correct answers. We validate our work in a distributed setting with sensor and network router queries, showing significant gains in communication overhead without sacrificing performance.
LAN emulation on an ATM network (1995)

The authors evaluate architecture alternatives relating to the provision of a LAN emulation service over a connection-oriented ATM network, and present the LAN emulation architecture as actually adopted by the ATM Forum LANE SWG. The role of servers is discussed as is the provision of broadcast/multicast services.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Phase II Randomized Study of Subcutaneous Ixekizumab, an Anti–Interleukin‐17 Monoclonal Antibody, in Rheumatoid Arthritis Patients Who Were Naive to Biologic Agents or Had an Inadequate Response to Tumor Necrosis Factor Inhibitors (2014)

Ixekizumab improved RA signs and symptoms in RA patients who were either naive to biologics treatment or had an inadequate response to TNF inhibitors. The safety profile was similar to that of other biologic agents, with no unexpected safety concerns.
Herpes simplex virus vectors and gene transfer to brain. (1994)

Experiments are in progress to engineer herpes simplex virus type 1 as a gene transfer vector for the nervous system. This virus is well suited for this purpose due to its ability to persist for long periods in a latent state in neurons wherein lytic genes are inactive and a unique viral promoter is capable of inducing transcription from the latent viral genome. The virus can be highly cytotoxic for neurons, however, and thus genes which initiate the lytic cycle must be deleted from the genome in order to force the virus into latency. Candidate genes include the immediately early functions ICP0, ICP27, ICP4 and the virus host shut-off function. The design of a suitable promoter regulator capable of expressing foreign genes during latency must also be developed. Many promoters including strong viral promoters and neuronal-specific cellular promoters have proved to be inadequate due to the transient nature of their activity from the viral vector genome and the viral latency promoter region appears to be weakly active in brain. Current efforts concern the development of auto-regulatable promoters which can remain active even if the viral genome is bound by chromatin.
Mechanisms of the Shape Evolution of CdSe Nanocrystals (2001)

The temporal shape evolution of CdSe quantum confined nanorods (quantum rods) in nonaqueous solvents with organometallic precursors was studied quantitatively and systematically. The experimental results revealed three distinguishable stages in the shape evolution. At high monomer concentrations, nanocrystals grow exclusively along the c-axis of the wurtzite structure, making this axis the long axis of the rods. At intermediate concentrations, nanocrystals grow simultaneously in three dimensions. At low monomer concentrations, the aspect ratio decreases in a process controlled by intraparticle diffusion on the surface of the nanocrystals. This intraparticle ripening stage is different from normal Ostwald ripening, which occurs at lower monomer concentrations and is by monomer migration from small to larger ones. Addition of hexylphosphonic acid or tetradecylphosphonic acid, strong cadmium ligands, is important mainly because it enables the high monomer concentrations needed for the growth of quantum rods. A simple model is proposed to explain the growth of faceted CdSe nanocrystals on the basis of diffusion control.
New Paradigm for Lymphocyte Granule-mediated Cytotoxicity (1996)

Lymphocyte granule-mediated apoptosis is postulated to entail the formation of membrane pores by perforin. Then soluble granzyme reaches the cytosol either through these pores or by reparative pinocytosis. We demonstrate here that Jurkat cells bind and internalize granzyme B via high affinity binding sites without toxic consequence. Apoptosis occurs, however, if sublytic perforin is added to targets washed free of soluble granzyme B. We suggest that granule-mediated apoptosis mimics viral strategies for cellular entry. Accordingly, co-internalization of granzyme B with adenovirus, a virus that escapes endosomes to reach the cytosol, also induced apoptosis. Poly(ADP-ribose) polymerase cleavage and processing of CPP32, ICE-LAP3, and Mch2 were detected at 30 min, while cytosolic acidification and DNA fragmentation occurred at 60 min. Annexin V binding and membrane permeabilization arose at 4 h. The concurrent activation of the Ced-3 proteases differed from the rate at which each cysteine protease is cleaved in vitro by granzyme B. Thus, granzyme B may not directly process these proteases in whole cells but rather may function by activating a more proximal enzyme. These results indicate that adenovirus-mediated delivery of granzyme B is suitable for elucidating biochemical events that accompany granule-mediated apoptosis.
A comparison of once-daily tramadol with normal release tramadol in the treatment of pain in osteoarthritis. (2002)

Tramadol OD was at least as effective and well tolerated as normal release tramadol in the management of OA pain. However, OD tramadol offers the advantage of a reduced dosing regimen, which is especially valuable in the elderly population.
Interleukin 1: a regulatory role in glucocorticoid-regulated hepatic metabolism. (1986)

The purpose of this study was to investigate the effect of interleukin 1 (IL 1) on glucocorticoid-regulated hepatic metabolism. Steroid binding in liver cytosol, plasma glucose, plasma corticosterone, and phosphoenolpyruvate carboxykinase (PEPCK) activity were assayed in C3H/HeJ mice after IL 1 administration. Mice received 5 pyrogenic U (PU) of rabbit IL 1 i.p. and were sacrificed 4 hr later. In adrenal-intact mice, steroid binding and plasma glucose were significantly decreased (63 and 64% of control) and plasma corticosterone was significantly elevated threefold. In adrenalectomized mice, IL 1 (5 PU) treatment produced similar results in steroid binding (66% of control) and plasma glucose (71% of control). PEPCK was measured in intact mice fasted overnight and treated with 5 PU of IL 1. PEPCK was induced in fasted control animals (23.1 +/- 1.4 U/mg) vs fed control animals (15.9 +/- 0.7 U/mg). IL 1 treatment inhibited the induction of PEPCK in fasted animals (13.4 +/- 2.0 U/mg) and caused a significant decrease in steroid binding (78% of fasted control) and plasma glucose (82% of fasted control). No difference in plasma corticosterone was seen in IL 1-treated mice and fasted control mice. These data indicate that IL 1 decreases intracellular steroid receptors, resulting in decreased induction of PEPCK and subsequent reduced gluconeogenesis and plasma glucose. We propose that IL 1 plays a regulatory role in glucocorticoid-regulated hepatic metabolism.
Linewidth requirements for optical synchronous detection systems with nonnegligible loop delay time (1992)

The spectral spreads of quadrature-phase-shift-keying (QPSK) modulation and minimum shift keying (MSK) modulation are narrower than those of other kinds of modulation with the same bit rate. Therefore, they are attractive for systems limited by electrical bandwidth and available optical frequency. The synchronous demodulation offers better sensitivity than differential demodulation. However, the propagation delay time of the phase locked loop affects the performance of synchronous detection systems. Therefore, linewidth requirements while considering the loop delay time must be considered in designing these systems. The linewidth requirements for BPSK, QPSK, and MSK homodyne/heterodyne detection systems are obtained by applying the Pade approximation in evaluating the receivers' performance. A change in the power penalty with respect to the change in these values is also obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regenerative treatment strategies in spinal surgery (2007)

Intervertebral disc degeneration is considered a major source of low back pain. Recent advances in regenerative medicine have led to promising new approaches for the biological treatment of disc degeneration. Treatment modalities include the administration of growth factors, the application of autologous or allogenic cells, gene therapy, in situ therapy and the introduction of biomaterials or a combination thereof. Promising experimental results in vitro and in animal studies support the potential feasibility of these treatment modalities in clinical studies. We will review the current literature on regenerative treatment strategies and discuss potential drawbacks as well as opportunities in translating current knowledge into clinical practice. Major obstacles to regenerative treatment strategies might be insufficient nutritional supply, pain mediating factors and functionally impaired donor cells. Therefore, for clinical application, patient selection will be essential. Molecular, cellular and radiological diagnostic tools to evaluate the eligibility of patients for particular treatment strategies need to be developed. In spinal surgery, two approaches are conceivable. Patients operated on lumbar disc herniations often develop back pain due to disc degeneration months to years after surgery. Here, additional regenerative interventions would have a preventive intention, whereas interventions for painful degenerative disc disease as an alternative to spinal fusion or disc arthroplasty would be a curative approach.
Superior Penetration and Retention Behavior of 50 nm Gold Nanoparticles in Tumors (2012)

Nanoparticles offer potential as drug delivery systems for chemotherapeutics based on certain advantages of molecular drugs. In this study, we report that particle size exerts great influence on the penetration and retention behavior of nanoparticles entering tumors. On comparing gold-coated Au@tiopronin nanoparticles that were prepared with identical coating and surface properties, we found that 50 nanoparticles were more effective in all in vitro, ex vivo, and in vivo assays conducted using MCF-7 breast cells as a model system. Beyond superior penetration in cultured cell monolayers, 50 nm Au@tiopronin nanoparticles also penetrated more deeply into tumor spheroids ex vivo and accumulated more effectively in tumor xenografts in vivo after a single intravenous dose. In contrast, larger gold-coated nanoparticles were primarily localized in the periphery of the tumor spheroid and around blood vessels, hindering deep penetration into tumors. We found multicellular spheroids to offer a simple ex vivo tumor model to simulate tumor tissue for screening the nanoparticle penetration behavior. Taken together, our findings define an optimal smaller size for nanoparticles that maximizes their effective accumulation in tumor tissue.
Altered brain fyn kinase in a murine acquired immunodeficiency syndrome (1996)

Mice infected with the replication-defective virus (BM5def) in the LP-BM5 murine leukemia virus (MuLV) mixture develop an immune deficiency syndrome and encephalopathy characterized by impaired spatial learning and memory as demonstrated in the Morris water maze. However, the molecular mechanism (or mechanisms) underlying this cognitive deficit remains unknown. Here we report that brain fyn kinase, which has been proposed to be involved in spatial learning and memory, was unresponsive to glutamatergic stimulation in mice with MAIDS. Thus, whereas application of glutamate to hippocampal slices from control mice increased fyn protein tyrosine kinase (PTK) activity more than 2.5-fold, these changes were significantly impaired in LP-BM5 MuLV-infected mice. Moreover, mice with MAIDS exhibited an abnormal histological distribution of fyn PTK in the hippocampus. These findings suggest that virus-associated disruption of fyn kinase-mediated signaling contributes to the cognitive deficits observed in mice with MAIDS and other retrovirus-induced encephalopathies.
Narrow-Band Imaging in Digestive Endoscopy (2007)

The application of opto-electronics in video-endoscopes improves the accuracy in diagnosis, through image processing and digital technology. Narrow Band Imaging (NBI), consists of using interference filters for the illumination of the target in narrowed blue and green bands of the spectrum. NBI is combined with magnifying endoscopy using an objective macro or an optical zoom. The NBI technique developed by Olympus Medical Systems is now available in the most recent models of video-endoscopes that use the non-sequential system of illumination (Lucera Spectrum) or the sequential R/G/B system of illumination (Exera II). The major contribution of the technique is in the characterization (analysis after detection) of the flat and superficial neoplastic areas of the digestive mucosa, with a specific application to the identification of intestinal metaplasia and early neoplastic changes in the Barrett's esophagus. The technique also proves helpful for the assessment of the vascular pattern in chronic inflammatory disorders of the digestive mucosa.
Implications of dietary oils and polyunsaturated fatty acids in the management of cutaneous disorders (1989)

• A major proinflammatory metabolite of arachidonic acid, leukotriene B<sub>4</sub>, is known to accumulate in the lesions of psoriasis. Most of this metabolite is biosynthesized by the polymorphonuclear cells that infiltrate into the psoriatic lesions. Epidermal 15-lipoxygenase, on the other hand, metabolizes arachidonic acid into 15-hydroxyeicosatetraenoic acid (15-20:4n-6), presumably serving as a negative feedback to inhibit the local generation of leukotriene B<sub>4</sub>-Eicosapentaenoic acid, a major polyunsaturated fatty acid in fish oil, and γ-linolenic acid, a poly-unsaturated fatty acid in certain vegetable oils, are both metabolized by epidermal 15-lipoxygenase into 15-hydroxyeicosapentaenoic acid (15-OH-20:5n-3) and 15-hydroxyeicosatriaenoic acid (15-OH-20:3n-3), respectively. Both of these monohydroxy acids are potent in vitro inhibitors of leukotriene B<sup>4</sup>generation. It seems reasonable, therefore, that adequate dietary supplementation with eicosapentaenoic acid or γ-linolenic acid may offer a novel and nontoxic approach to suppressing cutaneous inflammatory disorders. (<i>Arch Dermatol</i>1989;125:241-245)
Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25-q27. (1995)

Affected-sib-pair analyses were performed using 104 Caucasian families to map genes that predispose to insulin-dependent diabetes mellitus (IDDM). We have obtained linkage evidence for D6S446 (maximum lod score [MLS] = 2.8) and for D6S264 (MLS = 2.0) on 6q25-q27. Together with a previously reported data set, linkage can be firmly established (MLS = 3.4 for D6S264), and the disease locus has been designated IDDM8. With analysis of independent families, we confirmed linkage evidence for the previously identified IDDM3 (15q) and DDM7 (2q). We also typed additional markers in the regions containing IDDM3, IDDM4, IDDM5, and IDDM8. Preliminary linkage evidence for a novel region on chromosome 4q (D4S1566) has been found in 47 Florida families (P < .03). We also found evidence of linkage for two regions previously identified as potential linkages in the Florida subset: D3S1303 on 3q (P < .04) and D7S486 on 7q (P < .03). We could not confirm linkage with eight other regions (D1S191, D1S412, D4S1604, D8S264, D8S556, D10S193, D13S158, and D18S64) previously identified as potential linkages.
Crossing Chronic Total Occlusions of the Iliac and Femoral-Popliteal Vessels and the Use of True Lumen Reentry Devices (2006)

Treatment of chronic total occlusions of the iliac and femoral-popliteal vessels with endovascular techniques has become the standard approach for shorter lesions and is increasingly applied to long, complex arterial occlusive lesions. As the complexity of the arterial occlusions increases, the demands for technical skills and devices needed to successfully cross and treat the occlusion also increases. We describe here our technique for treatment of iliac and femoral-popliteal occlusions. Important aspects of that that have allowed for a high technical success include (1) the use of hydrophilic wires and catheters to traverse occlusions in the subintimal plane, (2) femoral access with axially supported catheters or sheaths to apply the force needed for successful recanalization, and (3) the use of true lumen reentry devices when, after crossing the occlusion, the wire or catheter cannot be manipulated into the true lumen beyond the occlusion.
The development and use of microcarrier and glass sphere culture techniques for the production of herpes simplex viruses. (1981)

Two high productivity monolayer culture methods, the microcarrier and glass sphere culture, were compared for their capacity to support the growth of MRC-5 and Vero cells, and Herpes simplex type 2 virus. Cell growth was similar in both systems giving yields of 14 X 10(5)/cm2 in microcarrier and 18 X 10(5)/cm2 in glass sphere cultures with yields of Vero cells being marginally better than MRC-5 cells. Virus yields were only slightly lower in these cultures than in small scale stationary cultures and confirmed the fact that MRC-5 cells produce twice as much HSV-2 as Vero cells, thus neutralising the growth advantage of these cells. Techniques for harvesting the virus in small volumes need to be improved in order to get a high titre suspension from the high capacity cultures.