gebhart/patrepeval huggingface dataset:
Effect of some sulfonate analogues of ursodeoxycholic acid on biliary lipid secretion in the rat. (1996)

The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (norUDC-SO3Na) and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate (UDC-SO3Na), on biliary lipid secretion was studied in bile fistula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-dependent manner. This suggests that the analogues exert an effect on biliary lipid secretion comparable to that of the naturally occurring bile acid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates but greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC-SO3Na induced cholesterol secretion and phospholipid secretion more significantly than UDC-tau infusion. The increase in phospholipid secretion was particularly pronounced during high-dose administration of norUDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phospholipid output, perhaps as a compensatory mechanism, and the biliary cholesterol/phospholipid ratio was decreased to a greater extent by the sulfonates than by UDC-tau. Consequently, the administration of norUDC-SO3Na or UDC-SO3Na produces a more "stable" bile than UDC-tau, suggesting that these sulfonates possess potential cholelitholytic activity.
Adoptive T-Cell Therapy Using Autologous Tumor-Infiltrating Lymphocytes for Metastatic Melanoma (2012)

Immunotherapy using autologous T cells has emerged to be a powerful treatment option for patients with metastatic melanoma. These include the adoptive transfer of autologous tumor-infiltrating lymphocytes (TILs), T cells transduced with high-affinity T cell receptors against major tumor antigens, and T cells transduced with chimeric antigen receptors composed of hybrid immunoglobulin light chains with endodomains of T-cell signaling molecules. Among these and other options for T-cell therapy, TILs together with high-dose interleukin 2 have had the longest clinical history with multiple clinical trials in centers across the world consistently demonstrating durable clinical response rates near 50% or more. A distinct advantage of TIL therapy making it still the T-cell therapy of choice is the broad nature of the T-cell recognition against both defined and undefined tumors antigens against all possible major histocompatibility complex, rather than the single specificity and limited major histocompatibility complex coverage of the newer T cell receptors and chimeric antigen receptor transduction technologies. In the past decade, significant inroads have been made in defining the phenotypes of T cells in TIL-mediating tumor regression. CD8+ T cells are emerging to be critical, although the exact subset of CD8+ T cells exhibiting the highest clinical activity in terms of memory and effector markers is still controversial. We present a model in which both effector-memory and more differentiated effector T cells ultimately may need to cooperate to mediate long-term tumor control in responding patients. Although TIL therapy has shown great potential to treat metastatic melanoma, a number of issues have emerged that need to be addressed to bring it more into the mainstream of melanoma care. First, we have a reached the point where a pivotal phase II or phase III trial is needed in an attempt to gain regulatory approval of TILs as standard of care. Second, improvements in how we expand TILs for therapy are needed that minimize the time the T cells are in culture and improve the memory and effector characteristics of the T cells for longer persistence and enhanced anti-tumor activity in vivo. Third, there is a critical need to identify surrogate and predictive biomarkers to better select suitable patients for TIL therapy to improve response rate and duration. Overall, the outlook for TIL therapy for melanoma is very bright. We predict that TILs will indeed emerge to become an approved treatment in the upcoming years through pivotal clinical trials. Moreover, new approaches combining TILs with targeted signaling pathway drugs, such as mutant B-RAF inhibitors, and synergistic immunomodulatory interventions enhancing T-cell costimulation and preventing negative regulation should further increase therapeutic efficacy and durable complete response rates.
Broad taxonomic characterization of Verticillium wilt resistance genes reveals an ancient origin of the tomato Ve1 immune receptor (2016)

Plant-pathogenic microbes secrete effector molecules to establish themselves on their hosts, whereas plants use immune receptors to try and intercept such effectors in order to prevent pathogen colonization. The tomato cell surface-localized receptor Ve1 confers race-specific resistance against race 1 strains of the soil-borne vascular wilt fungus Verticillium dahliae which secrete the Ave1 effector. Here, we describe the cloning and characterization of Ve1 homologues from tobacco (Nicotiana glutinosa), potato (Solanum tuberosum), wild eggplant (Solanum torvum) and hop (Humulus lupulus), and demonstrate that particular Ve1 homologues govern resistance against V. dahliae race 1 strains through the recognition of the Ave1 effector. Phylogenetic analysis shows that Ve1 homologues are widely distributed in land plants. Thus, our study suggests an ancient origin of the Ve1 immune receptor in the plant kingdom.
Electric breakdown in ultrathin MgO tunnel barrier junctions for spin-transfer torque switching (2009)

Magnetic tunnel junctions for spin-transfer torque (STT) switching are prepared to investigate the dielectric breakdown. Intact and broken tunnel junctions are characterized by transport measurements prior to transmission electron microscopy analysis. The comparison to our previous model for thicker MgO tunnel barriers reveals a different breakdown mechanism arising from the high current densities in a STT device: instead of local pinhole formation at a constant rate, massive electromigration and heating leads to displacement of the junction material and voids are appearing. This is determined by element resolved energy dispersive x-ray spectroscopy and three dimensional tomographic reconstruction.
The meniscofemoral ligament (2003)

Summary A cadaveric study of ovine stifles was performed to examine the contribution of the meniscofemoral ligament to the cranio-caudal and internal-external rotatory laxity of this joint in sheep. Twenty ovine stifles were harvested, denuded of muscular attachments, and the femur and tibia fixed in bone pots. These were inserted into a four degree-of-freedom rig incorporated into a materials testing machine. Forces up to a maximum of 100N were applied in the cranial and caudal directions, and the resultant translations and coupled rotations measured. Tibial internal and external rotations in response to a 6Nm torque were also measured. These parameters were assessed at 30, 60, 90 and 110 degrees of flexion in twenty intact stifles. In ten stifles a small posterior arthrotomy was used to divide the caudal cruciate ligament (CCL), followed by division of the meniscofemoral ligament (MFL). The sequence of division was reversed for a further ten stifles. The effects of each intervention on the above parameters were evaluated. Division of the MFL resulted in an increase in caudal translation at all angles of flexion in both the intact and CCL deficient stifle. There was also an increase in internal rotation of the tibia after application of a 6Nm torque. This was significant at 30 and 110 degrees of flexion in the intact stifle and at all angles of flexion in the CCL-deficient stifle. These results indicate a secondary role for the MFL in the cranio-caudal and internal/external rotatory stability of the ovine stifle joint. This is the first study demonstrating a functional role for the MFL in any species, and may have a bearing on stifle injuries.
Electrical and dielectric properties in carbon fiber‐filled LMWPE/UHMWPE composites with different blend ratios (2007)

Abstract Carbon fiber (CF) filled low‐molecular‐weight polyethylene (LMWPE) and ultra‐high molecular weight polyethylene (UHMWPE) composites were prepared by the gelation from solution and the kneading in the melting state. The content of carbon fibers was fixed to be 23.5 vol %. The resistivity, positive temperature coefficient (PTC), and dielectric behaviors of the composites became more pronounced with increasing content of LMWPE with much higher thermal expansion than that of UHMWPE. The PTC effect became most significant, when the blend ratio of LMWPE to UHMWPE was 9/1. Beyond 9/1, the PTC effect was less pronounced. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) revealed that the UHMWPE and LMWPE chains within the composite crystallized independently by gelation from solution and were virtually unaffected by the presence of carbon fibers. Consequently, it was confirmed that carbon fibers selectively were localized in the mixed region of LMWPE and UHMWPE for the composite (3/1 and 6/1) and mainly in the region of LMWPE for the 9/1, 12/1, and 15/1 composites. This indicated that the content of carbon fibers within LMWPE region was the highest for the 9/1 composite and the 9/1 composite provides the most significant PTC effect. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 359–369, 2008
A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and alzheimer disease (1981)

The causes of amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are unknown. Furthermore, treatment for two of these conditions is almost totally lacking. The thesis is presented that each of these disorders is due to lack of a disorder-specific neurotrophic hormone. The hormone would be elaborated or stored in the target of the affected neurons. It would be released by the postsynaptic cell and then exert its effects in a retrograde fashion after being taken up by the presynaptic terminal. In the lower motor neuron syndromes of amyotrophic lateral sclerosis, failure of muscle cells to release the appropriate motor neurotrophic hormone would result in impaired function of anterior horn cells. In Parkinson disease, the neurotrophic failure would be characterized by inability of striatal cells to provide the required dopamine neurotrophic hormone with resulting impairment of substantia nigra cells. In Alzheimer disease, the abnormalities would lie in failure of the hippocampus and cortical cells to supply the relevant cholinergic neurotrophic hormone with resulting impairment of medial septal and nucleus basalis neurons. Central nervous system tissue culture provides a convenient system in which to assay these neurotrophic hormones and should permit a test of the hypothesis.
Nanowires: building blocks for the assembly of integrated nanosystems (2005)

An examination of semiconductor nanowires focused on their fundamental properties and applications in nanoelectronics is presented. First, the transport properties of silicon and germanium/silicon nanowires are described with an emphasis on coherent and ballistic transport. Second, strategies for integrating controlled nanoscale metal-semiconductor junctions, and the properties of single devices and large areas are reviewed. Third, applications of these nanowires device arrays, such as bioelectronic detectors, are described, and strategies for integrated systems are discussed.
Understanding HIV resistance, fitness, replication capacity and compensation: targeting viral fitness as a therapeutic strategy (2004)

The increasingly prevalent emergence of drug-resistant virus strains in patients being treated with highly active antiretroviral regimens and the increasing rates of transmission of drug-resistant virus strains have focused attention on the critical need for additional antiretroviral agents with novel mechanisms of action and enhanced potency. Furthermore, novel means of employing highly active antiretroviral therapy are needed to reduce or eliminate the virological treatment failures that currently occur. Over the past several years, evidence has mounted supporting the fact that the emergence of resistant strains is associated with reductions in viral fitness, yielding decreases in plasma virus load in treated patients harbouring resistant populations of the virus. Additional mutations that serve to modify fitness (compensatory mutations) and mutations that impact the viral replication capacity also emerge under the selective pressure of drug treatment, and have both negative and positive effects on virus growth. Fitness is generally accepted to refer to the ability of HIV to replicate in a defined environment and thus is used to describe the viral replication potential in the absence of the drug. Although viral fitness and replication capacity are related in some ways, it is important to recognise that viral fitness is not the same as viral replication capacity. This review will assess the recent literature on antiviral drug resistance, viral fitness and viral replication capacity, and discuss means by which the adaptability of HIV to respond rapidly to antiviral treatment through mutation may be used against it. This would be done by treating patients with an aim to lock the deleterious mutations into the resistant virus genome, resulting in a positive therapeutic outcome despite the presence of resistance to the selecting agents. The review will specifically discuss the literature on nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, as well as other biological factors involved in viral fitness.
Solder bonding for microelectricalmechanical systems (MEMS) applications (2003)

MEMS fabrication and packaging requires a bonding technology that is universal for all substrates, has high resolution, requires relatively lower temperatures, is reliable and is low cost to implement. The bonding technology presented meets the above standards. The process is substrate independent and involves aligned bonding of two similarly patterned wafers using tin solder as the bonding material. The technique can be used for whole wafer or selected area bonding. The resolution of this technique is only limited by the resolution that can be achieved in the patterning and delineation of the seed metal.
Client-based QoS monitoring and evaluation architecture for network infrastructure and services (2013)

Providing an efficient Quality-of-Service (QoS) measurement model is a challenging problem in today’s mobile computing and telecommunications networks. Currently, most of QoS techniques utilize service measurements that are collected by the network elements (i.e., network-side monitoring) to evaluate the network performance. However, this process does not take into account the service performance from the clients' perspective and might contradict with the Service Level Agreement (SLA). In order to overcome the limitations of service-side QoS monitoring, a number of research studies have been conducted to present alternative architectures and algorithms for client-side QoS service assessment in computer networks. The client-side QoS approach gives the major role to the clients to evaluate the dedicated services through gathering the network measurements and reporting the necessary information. The service providers consider clients’ feedback to revise and resolve service performance issues. This model can be considered as a cooperative approach that provides a compromised service plan for both the service providers and the network clients to achieve a better network service performance.\nIn this research, we study the tradeoffs between network-side and client-side QoS monitoring and present a client-based architecture for the evaluation and prediction of service degradations in mobile networks. The client-side approach should be capable of utilizing multi-level service performance analysis in a scalable mobile network environment. The service performance analysis consists of three levels: service monitoring and evaluation, verifying and enhancing the network measurement accuracy (the collected performance data), and performance prediction in single and multi-hops networks. In addition, this approach should support short and long-term service evaluation scenarios. The short-term scenario gives the ability to service providers to react in a timely manner to the clients' feedback to preserve a certain level of service performance. The long-term scenario helps to clarify the service behavior by predicting the service degradation over the monitoring and evaluation sessions. Furthermore, this scenario allows the service providers to refine the degraded services and maintain the SLA.
Phytochrome assembly. Defining chromophore structural requirements for covalent attachment and photoreversibility. (1992)

Assembly of holophytochrome in the plant cell requires covalent attachment of the linear tetrapyrrole chromophore precursor, phytochromobilin, to a unique cysteine in the nascent apoprotein. In this investigation we compare chromophore analogs with the natural chromophore precursor for their ability to attach covalently to recombinant oat apophytochrome and to form photoactive holoproteins. Ethylidene-containing analogs readily form covalent adducts with apophytochrome, whereas chromophores lacking this double bond are poor substrates for attachment. Kinetic measurements establish that although the chromophore binding site on apophytochrome is best tailored to phytochromobilin, apophytochrome will accommodate the two analogs with modified D-rings, phycocyanobilin and phycoerythrobilin. The phycocyanobilin-apophytochrome adduct is photoactive and undergoes a light-induced protein conformational change similar to the native holoprotein. By contrast, the phycoerythrobilin adduct is locked into a photochemically inactive protein conformation that is similar to the red light-absorbing Pr form of phytochrome. These results support the hypothesis that the photoconversion from Pr to Pfr, the far red light- absorbing form of phytochrome, involves the photoisomerization of the C15 double bond. Knowledge gained from these studies provides impetus for rational design of chromophore analogs whose insertion into apophytochrome should elicit profound changes in light-mediated plant growth and development.
Regulation in vivo of the growth of Leydig cell tumors by antisense ribonucleic acid for parathyroid hormone-related peptide. (1995)

PTH-related peptide (PTHrP) has been shown to be the major mediator of hypercalcemia of malignancy, but may also exert effects on cell growth and differentiation. The Leydig cell tumor H-500, when implanted in Fischer rats, produces abundant PTHrP and eventually causes the death of the host animal. In the present study we have used antisense RNA technology to block the effects of PTHrP in H-500 Leydig tumor cells in vivo. The full-length rat PTHrP complementary DNA encoding amino acid -36-->141 was subcloned as an EcoRI-BglII insert in the antisense orientation into the mammalian expression vector pRc/CMV to produce the plasmid pRc-PAS. This plasmid was then stably transfected into the H-500 Leydig tumor cells with a Lipofectin reagent. After selection with the neomycin derivative G-418, a stable cell line, H-500-PTHrP-AS, was obtained which showed 80% inhibition of endogenous PTHrP messenger RNA compared to wild-type or vector-only transfected H-500 cells. Conditioned culture medium from these experimental cells showed a marked decrease in PTHrP immunoreactivity and in the ability of the medium to stimulate adenylate cyclase in UMR-106 rat osteosarcoma cells. Furthermore, inhibition of PTHrP production resulted in a significant increase in the doubling time of the H-500 cells. Transfection of the experimental plasmid into Rat-2 fibroblasts, which do not produce PTHrP, had no effect on cell growth. Control and experimental cells were then implanted sc into male Fischer rats. Animals were killed at timed intervals, and their tumor volumes were determined. Experimental animals receiving cells transfected with antisense PTHrP plasmid showed near-normal levels of plasma calcium and decreased expression of tumoral PTHrP messenger RNA. These animals also showed a 30-70% lower tumor volume during the course of the experiment compared to control animals. These studies have demonstrated that PTHrP can play a role as a promoter of tumor growth in vitro and in vivo.
Allogeneic stimulation of cytotoxic T cells by supported planar membranes. (1984)

Phospholipid vesicles containing the transmembrane protein H-2Kk spontaneously fuse to form planar membranes when incubated on treated glass surfaces. Pattern photobleaching of fluorescent lipid probes indicates that these planar membranes are continuous and that the lipids are as mobile as they are in conventional fluid bilayers or monolayers. H-2Kk molecules in these planar membranes are immobile. These membranes stimulate cytotoxic T lymphocytes when cultured with immune spleen cells. The response to H-2Kk in planar membranes is greatly enhanced by the addition of supernatant from concanavalin A-stimulated spleen cells, indicating that relatively little antigen processing or presentation by accessory cells occurs. Cytotoxic T cells induced by purified alloantigen are found to be as susceptible to antibody blockade as are effectors from conventional mixed lymphocyte culture, where the antibody is directed against a T-cell surface antigen reputed to strengthen target cell adhesion through an interaction independent of major histocompatibility antigens.
Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents. (1998)

The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.
AAV-Mediated Knock-Down of HRC Exacerbates Transverse Aorta Constriction-Induced Heart Failure (2012)

Increased Ca(2+) leak and cytosolic Ca(2+) concentration due to a partial KD of HRC could enhance activity of CaMKII and phosphorylation of p38 MAPK, causing the mitochondrial death pathway observed in TAC-FH. Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through perturbed SR-mediated Ca(2+) cycling.