gebhart/patrepeval huggingface dataset:
Rat dilated cardiomyopathy after autoimmune giant cell myocarditis. (1994)

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36 +/- 0.49 versus 2.69 +/- 0.06 g/kg, respectively; P < .005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)
Impaired Memory Retention and Decreased Long-Term Potentiation in Integrin-Associated Protein-Deficient Mice (1999)

Previously, we have demonstrated that integrin-associated protein (IAP) mRNA level is approximately fourfold higher in rats showing good retention performance (600 sec) than rats showing poor retention performance (< 80 sec) in an inhibitory avoidance learning paradigm. In the present study, we have used the gene-targeted IAP-deficient mice to further investigate the role of IAP involved in memory formation and hippocampal long-term potentiation (LTP) in vivo. Results revealed that there was a significant impairment in memory retention and a significant reduction in the magnitude of LTP in IAP-deficient mice when compared with the wild-type and heterozygote mice, whereas the wild-type and heterozygote animals did not show marked differences on these measures. Furthermore, the impairment in retention performance of IAP-deficient mice was not due to different sensitivities of these animals to the electric shock. When we examined locomotor activity and rotarod treadmill performance, no differences were observed among these three groups of animals either. Western blot analysis confirmed the lack of IAP protein in IAP-deficient mice, whereas IAP expression was similar in both the wild-type and heterozygote controls. These results together demonstrate that IAP plays an important role in the process of memory formation and synaptic plasticity in mice.
Programmed death-1 pathway in cancer and autoimmunity (2014)

Programmed death-1 (PD-1) is a co-receptor that is expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. A major functional role of the PD-1 signaling pathway is the inhibition of self-reactive T cells, which serve to protect against autoimmune diseases. Elimination of the PD-1 pathway can therefore result in the breakdown of immune tolerance that can ultimately lead to the development of pathogenic autoimmunity. Conversely, tumor cells can at times co-opt the PD-1 pathway to escape from immunosurveillance mechanisms. Therefore, blockade of the PD-1 pathway has become an attractive target in cancer therapy. Recent clinical trials have shown that anti-PD-1 agents have profound effects on solid tumor regression. Current approaches include six agents that are either PD-1 and PD-L1 targeted neutralizing antibodies or fusion proteins. More than forty clinical trials are underway to better define the role of PD-1 blockade in variety of tumor types. In this review we will highlight the basic biology of the PD-1 system and discuss its potential roles in both autoimmunity and cancer. We propose that future research on PD-1 may lead to the translation of fundamental regulatory pathways into the development of practical new approaches for the treatment of autoimmune diseases and cancer.
Efficacy of ampicillin versus trimethoprim-sulfamethoxazole in a mouse model of lethal enterococcal peritonitis (1990)

Lethal enterococcal peritonitis in mice was used to compare trimethoprim-sulfamethoxazole (TMP-SMX) therapy with ampicillin therapy. Peritoneal fluid showed a 10(3)-CFU decrease in enterococci with ampicillin compared with TMP-SMX. Mortality of the untreated mice was 100%, compared with 40% for ampicillin and 95% for TMP-SMX, despite adequately measured levels in serum and peritoneal fluid.
The Dorzolamide/Timolol Combination versus Timolol Plus Pilocarpine (1999)

Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.
Anaerobic adaptation in Pseudomonas aeruginosa : definition of the Anr and Dnr regulons (2010)

The anaerobic metabolism of the opportunistic pathogen Pseudomonas aeruginosa is important for growth and biofilm formation during persistent infections. The two Fnr-type transcription factors Anr and Dnr regulate different parts of the underlying network in response to oxygen tension and NO. Little is known about all members of the Anr and Dnr regulons and the mediated immediate response to oxygen depletion. Comprehensive transcriptome and bioinformatics analyses in combination with a limited proteome analyses were used for the investigation of the P. aeruginosa response to an immediate oxygen depletion and for definition of the corresponding Anr and Dnr regulons. We observed at first the activation of fermentative pathways for immediate energy generation followed by induction of alternative respiratory chains. A solid position weight matrix model was deduced from the experimentally identified Anr boxes and used for identification of 170 putative Anr boxes in potential P. aeruginosa promoter regions. The combination with the experimental data unambiguously identified 130 new members for the Anr and Dnr regulons. The basis for the understanding of two regulons of P. aeruginosa central to biofilm formation and infection is now defined.
Estimating the Critical Rotation of a Complex Squirrel-cage Rotor in a Pellet Milling Machine (1986)

Two methods are given in this paper for calculating, at the design stage, the critical or whirling speed of a squirrel cage rotor, which is part of a pellet mill used to reduce grain or pellets to powder. Knowledge of the critical speed is vital in this application, since, if the rotor becomes unstable, transverse flexural motion may occur resulting in catastrophic failure of the mill due to the elimination of the small clearance between the rotor and its casing. An experimental technique is described which has been used to non-destructively test the rotor in order to check the calculated values. The technique involves the observation of the Fourier transform of the rotor response to an impulsive force. The critical speed is estimated from the frequency of the fundamental transverse flexural mode of vibration of the rotor. The average of the two calculated values agrees with the experimental value within 1%.
Translocation of SAPK/JNK to Mitochondria and Interaction with Bcl-xL in Response to DNA Damage (2000)

Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala-115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.
Two distinct pathways for cAMP-mediated down-regulation of the β2-adrenergic receptor (1989)

We have studied cyclic AMP-mediated regulation of the beta 2-adrenergic receptor (beta 2AR). The effects of cAMP were assessed in Chinese hamster fibroblast (CHW) cells expressing either the wild type human beta 2AR receptor (CH-beta 2) or mutated forms of the receptor lacking the consensus sequences for phosphorylation by the cAMP-dependent protein kinase. Treatment of the CH-beta 2 cells with the cAMP analogue dibutyryl cAMP (Bt2cAMP) induces a time-dependent "down-regulation" of the number of beta 2AR. This down-regulation of the receptors is accompanied by a decline in the steady state level of beta 2AR mRNA. Moreover, the treatment with Bt2cAMP induces an increase in the phosphorylation level of the membrane-associated beta 2AR. Both the reduction in beta 2AR mRNA and the enhanced phosphorylation of the receptor are rapid and precede the loss of receptor. The down-regulation of beta 2AR induced by Bt2cAMP is concentration-dependent and mimicked by the other biologically active cyclic nucleotide analogue, 8-Br-cAMP, by forskolin, and by the phosphodiesterase inhibitor, isobutylmethylxanthine. In the CHW cell lines expressing receptors lacking the putative protein kinase A phosphorylation sites, the Bt2cAMP-induced phosphorylation of beta 2AR is completely abolished. In these cells the down-regulation of beta 2AR receptor number produced by cAMP is significantly slowed, whereas the reduction in beta 2AR mRNA level is equivalent to that observed in CH-beta 2 cells. These data indicate that there are at least two pathways by which cAMP may decrease the number of beta 2ARs in cells: one involves phosphorylation of the receptor by the cAMP-dependent protein kinase and the other leads to a reduction in steady state beta 2AR mRNA levels.
Genome-wide SNP assay reveals structural genomic variation, extended homozygosity and cell-line induced alterations in normal individuals (2006)

The recent hapmap effort has placed focus on the application of genome-wide SNP analysis to assess the contribution of genetic variability, particularly SNPs, to traits such as disease. Here, we describe the utility of genome-wide SNP analysis in the direct detection of extended homozygosity and structural genomic variation. We use this approach to assess the frequency of genomic alterations resulting from the lymphoblast immortalization and culture processes commonly used in cell repositories. We have assayed 408 804 SNPs in 276 DNA samples extracted from Epstein-Barr virus immortalized cell lines, which were derived from lymphocytes of elderly neurologically normal subjects. These data reveal extended homozygosity (contiguous tracts >5 Mb) in 9.5% (26/272) and 340 structural genomic alterations in 182 (66.9%) DNA samples assessed, 66% of which did not overlap with previously described structural variations. Examination of DNA extracted directly from the blood of 30 of these subjects confirmed all examined instances of extended homozygosity (6/6), 75% of structural genomic alteration <5 Mb in size (12/16) and 13% (1/8) of structural genomic alteration >5 Mb in size. These data suggest that structural genomic variation is a common phenomenon in the general population. While a proportion of this variability may be caused or its relative abundance altered by the immortalization and clonal process this will have only a minor effect on genotype and allele frequencies in a large cohort. It is likely that this powerful methodology will augment existing techniques in the identification of chromosomal abnormalities.
Functional Identification of SLC5A8, a Tumor Suppressor Down-regulated in Colon Cancer, as a Na+-coupled Transporter for Short-chain Fatty Acids (2004)

SLC5A8, a tumor suppressor gene down-regulated in human colon cancer, codes for a transporter in the Na(+)/glucose cotransporter gene family, but the definitive functional identity of the transporter protein is not known. Since this gene is expressed abundantly in the colon where short-chain fatty acids are generated by bacterial fermentation, we tested the hypothesis that it codes for a Na(+)-coupled transporter for these fatty acids. The coding region of SLC5A8 mRNA was amplified from human intestine and expressed heterologously in Xenopus laevis oocytes. Transport function was monitored by uptake of radiolabeled substrates and by substrate-induced currents under voltage-clamp conditions. Uptake of short-chain fatty acids (lactate, pyruvate, acetate, propionate, and butyrate) in oocytes expressing SLC5A8 was severalfold higher than in uninjected oocytes. Exposure of SLC5A8-expressing oocytes to these fatty acids induced inward currents under voltage-clamp conditions in a Na(+)-dependent manner. These currents were saturable and the substrate concentrations needed for half-maximal induction of the current were in the range of 0.08-2.5 mm. The substrate-induced currents decreased as the carbon chain length of the substrates increased. The Na(+)-activation kinetics indicated involvement of more than one Na(+) ion in the activation process. Direct measurements of substrate (propionate) and charge transfer showed that three positive charges are transferred into oocytes per substrate molecule. These studies establish the functional identity of SLC5A8 as a Na(+)-coupled transporter for short-chain fatty acids.
Adaptive Time-Slice Block-Matching Optical Flow Algorithm for Dynamic Vision Sensors (2018)

Dynamic Vision Sensors (DVS) output asynchronous log intensity change events. They have potential applications in high-speed robotics, autonomous cars and drones. The precise event timing, sparse output, and wide dynamic range of the events are well suited for optical ﬂow, but conventional optical ﬂow (OF) algorithms are not well matched to the event stream data. This paper proposes an event-driven OF algorithm called adaptive block-matching optical ﬂow (ABMOF). ABMOF uses time slices of accumulated DVS events. The time slices are adaptively rotated based on the input events and OF results. Compared with other methods such as gradient-based OF, ABMOF can efﬁciently be implemented in compact logic circuits. We developed both ABMOF and Lucas-Kanade (LK) algorithms using our adapted slices. Results shows that ABMOF accuracy is comparable with LK accuracy on natural scene data including sparse and dense texture, high dynamic range, and fast motion exceeding 30,000 pixels per second.
Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer's disease. (2006)

Presymptomatic FAD individuals show widespread MRglc reductions consistent with the typical AD PET pattern in the relative absence of structural brain atrophy. These data further suggest that PET MRglc measures may serve as biomarkers for the preclinical diagnosis of AD.
Interlocking Nailing of Complex Fractures of the Femur and Tibia (1986)

The interlocking nail widens the range of indications for medullary osteosynthesis of femoral and tibial shaft fractures. Stability is achieved by transverse threaded bolts in prefabricated holes in the nail, which anchor the implant directly to cortical bone, thereby controlling length, alignment, and rotation of the limb. Two hundred eighty-three femoral and 401 tibial fractures were treated with an interlocking nail and followed for an average of 20 months. Overall, 97% of the femurs and 94.3% of the tibias were judged to have an excellent or good result, based on both clinical and radiographic parameters. Delayed union or nonunion requiring bone grafts occurred in 2% of the femurs and 0.7% of the tibias following interlocking nailing. Deep infection developed in 2.4% of the femurs and 2.2% of the tibias. All of these patients eventually healed their fractures without evidence of chronic osteomyelitis. The main advantage of interlocking nails is that surgery can be performed using closed nailing techniques, allowing early protected weight-bearing and joint motion. The rates of nonunion and infection are very low, and there is little risk of refracture after implant removal.
Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast (2012)

LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.
Delivering interactive multimedia documents over networks (1992)

A family of applications that consists of interactive multimedia documents, such as electronic magazines and interactive TV shows, is examined and the links between application architecture, user behavior, and network performance are investigated. The kinds of application-specific information that influence the end-to-end quality of service are discussed. The architecture and dynamics of the interactive document in terms of presentation objects (P-Objects), which are the segments of information accessed by the application and which are described according to their size, media composition, and access links, are described. The same structural characteristics that may make an interactive multimedia document appealing to the end user are the characteristics that are helpful during dynamic network performance optimization. This observation is based on the hypothesis that the P-Objects' access graph, together with viewing time statistics, is the information most useful to the network delivery control mechanism for optimizing network performance. Preliminary guidelines for both network and application designers to address each other's concerns are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Developmental regulation of the human embryonic beta-like globin gene is mediated by synergistic interactions among multiple tissue- and stage-specific elements. (1993)

The stage-specific regulation of mammalian embryonic globin genes has been an experimentally elusive problem, in part because of the developmentally early timing of their expression. We have carried out a systematic analysis of truncation and internal deletion mutations within the 5'-flanking region of the human embryonic beta-like globin gene (epsilon) in erythroid and nonerythroid cell lines. Within a 670-bp region upstream from the constitutive promoter are multiple positive and negative control elements. Of these, a positive regulatory element (epsilon-PRE II) which is active only in embryonic erythroid cells is of particular interest. Remarkably, although it is inactive on its own, in the presence of other sequences located further upstream, it confers tissue- and developmental stage-specific expression on a constitutive epsilon-globin or heterologous promoter. The activity of epsilon-PRE II is also modulated by another positive regulatory domain located further downstream to direct erythroid cell-specific, but little or no embryonic stage-specific, transcription. A nuclear factor highly enriched in embryonic erythroid cells binds specifically within a 19-bp region of epsilon-PRE II. Nuclei from adult erythroid cells also contain a factor that binds to this region but forms a complex of faster electrophoretic mobility. We speculate that interactions between epsilon-PRE II and other upstream control elements play an important role in the developmental regulation of the human embryonic beta-like globin gene.
Comparativein Vitroandin VivoStudies on the Biological Characteristics of Recombinant Human Follicle-Stimulating Hormone (1991)

The in vitro and in vivo activities of recombinant human FSH (recFSH) produced by a Chinese hamster ovary cell line were studied and compared with those of natural FSH preparations. The specific FSH activities of recFSH established by immunoassay and in vivo bioassay were greater than 10,000 IU/mg protein and considerably higher than the activities of tested urinary FSH references, while the in vivo bio/immuno ratios of these preparations were not significantly different. Compared to a highly purified pituitary standard (IS 83/575), recFSH had a comparable high specific in vivo bioactivity, but the specific immunoreactivity of IS 83/575 was about 2 times lower. In receptor displacement and in vitro bioassay studies recFSH provided dose-response curves parallel to those of pituitary and urinary FSH references. When equal amounts of immunoreactivity FSH were tested, recFSH and urinary and pituitary FSH displayed comparable activities in both assays. The in vitro bioactivity of recFSH could be neutralized effectively by each of three monoclonal antibodies raised against recFSH (alpha-specific), urinary FSH (beta-specific), and pituitary FSH (alpha beta-specific), respectively. Moreover, 50% inhibition of comparable responses induced by recFSH, urinary "pure" FSH, or pituitary FSH was established by the same amount of monoclonal antibody. These results support the structural and functional similarity of recFSH and natural FSH. To test whether recFSH is capable of inducing LH-specific biological responses, the in vitro induction of testosterone production in mouse Leydig cells was assessed. At least 16 IU recFSH/ml incubate were needed to increase testosterone production, indicating that the intrinsic LH bioactivity of recFSH is negligible (less than 0.025 mIU LH/IU FSH). The in vivo efficacy of recFSH was examined by treating immature female hypophysectomized rats during 4 days with recFSH only or with recFSH supplemented with hCG. RecFSH only treatment increased ovarian weight and aromatase activity in a dose-dependent manner. When recFSH dosages providing submaximal responses were supplemented with 1 IU hCG, both ovarian weight and aromatase activity were largely augmented. Neither recFSH nor urinary pure FSH, administered in a high dose was able to increase plasma estradiol levels, while ovarian weight and aromatase activity were increased to the same extent. However, when recFSH was supplemented with only 0.1 IU hCG, a 3-fold increase in median plasma estradiol levels was obtained. These findings support the two-cell two-gonadotropin theory, holding that both FSH and LH are required for estrogen biosynthesis, but also reveal that only very small amounts of LH activity are sufficient to increase estrogen secretion up to measurable plasma levels.(ABSTRACT TRUNCATED AT 400 WORDS)