gebhart/patrepeval huggingface dataset:
Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure (2000)

In human and experimental models of heart failure, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling. The disturbances in calcium metabolism have been shown to contribute significantly to the contractile dysfunction observed in heart failure. We investigated whether increasing SERCA2a expression can improve ventricular function in an animal model of heart failure obtained by creating ascending aortic constriction in rats. After 19-23 wk of banding during the transition from compensated hypertrophy to heart failure (documented by >25% decrease in fractional shortening), rats were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a, n = 13) or beta-galactosidase (Ad.betagal, n = 14) by using a catheter-based technique. The failing hearts infected with Ad. betagal were characterized by a significant decrease in SERCA2a expression and a decrease in SERCA2a activity compared with nonfailing sham-operated rats (n = 11). In addition, these failing hearts had reduced left-ventricular systolic pressure, maximal rate of left-ventricular pressure rise and decline (+dP/dt, -dP/dt), and rate of isovolumic relaxation (tau). Overexpression of SERCA2a restored both SERCA2a expression and ATPase activity to nonfailing levels. Furthermore, rats infected with Ad.SERCA2a had significant improvement in left-ventricular systolic pressure, +dP/dt, -dP/dt, and rate of isovolumic relaxation (tau) normalizing them back to levels comparable to sham-operated rats. In this study, we show that in an animal model of heart failure where SERCA2a protein levels and activity are decreased and severe contractile dysfunction is present, overexpression of SERCA2a in vivo restores both systolic and diastolic function to normal levels.
PIC: Protein Interactions Calculator (2007)

Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bonds, interactions between hydrophobic residues, ionic interactions, hydrogen bonds, aromatic-aromatic interactions, aromatic-sulphur interactions and cation-pi interactions within a protein or between proteins in a complex. Interactions are calculated on the basis of standard, published criteria. The identified interactions between residues can be visualized using a RasMol and Jmol interface. The advantage with PIC server is the easy availability of inter-residue interaction calculations in a single site. It also determines the accessible surface area and residue-depth, which is the distance of a residue from the surface of the protein. User can also recognize specific kind of interactions, such as apolar-apolar residue interactions or ionic interactions, that are formed between buried or exposed residues or near the surface or deep inside.
SEARCH DIRECTING HEURISTICS FOR THE SEQUENTIAL CIRCUIT TEST SEARCH SYSTEM (SCIRTSS) (1975)

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EUVL compatible LER solutions using functional block copolymers (2012)

Directed self assembly (DSA) of block copolymers is an emerging technology for achieving sub-lithographic resolution. We investigate the directed self assembly of two systems, polystyrene-block-poly-DL-lactic acid (PS-b-PDLA) and PSb- poly(methyl methacrylate). For the PS-<i>b</i>-PDLA system we use an open source EUVL resist and a commerciallyavailable underlayer to prepare templates for DSA. We investigate the morphology of the phase separated domains and compare the LER of the resist and the PS-PDLA interface. For the PS-<i>b</i>-PMMA system we again use an open source resist, but the annealing conditions in this case require crosslinking of the resist prior to deposition of the block copolymer. For this system we also investigate the morphology of the phase separated domains and compare the LER of the resist and the PS-PMMA interface.
West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy (2002)

A candidate live attenuated vaccine strain was constructed for West Nile virus (WN), a neurotropic flavivirus that has recently emerged in the U.S. Considerable attenuation for mice was achieved by chimerization with dengue virus type 4 (DEN4). The genes for the structural premembrane and envelope proteins of DEN4 present in an infectious cDNA clone were replaced by the corresponding genes of WN strain NY99. Two of 18 cDNA clones of a WN/DEN4 chimera yielded full-length RNA transcripts that were infectious when transfected into susceptible cells. The two infectious clones shared a motif in the transmembrane signal domain located immediately downstream of the NS2B-NS3 protease cleavage site that separates the DEN4 capsid protein and the WN premembrane protein of the chimera. This motif, Asp and Thr at a position 3 and 6 amino acids downstream of the cleavage site, respectively, was not present in the 16 noninfectious cDNA clones. The WN/DEN4 chimera was highly attenuated in mice compared with its WN parent; the chimera was at least 28,500 times less neurovirulent in suckling mice inoculated intracerebrally and at least 10,000 times less virulent in adult mice inoculated intraperitoneally. Nonetheless, the WN/DEN4 chimera and a deletion mutant derived from it were immunogenic and provided complete protection against lethal WN challenge. These observations provide the basis for pursuing the development of a live attenuated WN vaccine.
New Technology for Deep Light Distribution in Tissue for Phototherapy (2002)

Photodynamic therapy is one of several techniques developed for phototherapy for solid cancers and hematologic malignancies. Photodynamic therapy is a treatment that utilizes a molecular energy exchange between visible light and a photosensitive drug, which results in the production of 1O2, a highly reactive cytocidal oxygen species. The effect is limited to the region where light and drug are combined so that malignant tissue is destroyed and the usual side effects associated with standard cancer therapies are avoided. The light component of photodynamic therapy is customarily generated via dye-pumped or diode lasers. The cost and the complexity of lasers have seriously limited the clinical use of photodynamic therapy for malignancies. A new device technology, based on light-emitting diodes, has been developed (Light Sciences Corporation, Issaquah, WA) that allows light production inside the target tissue. This new technology will expand the current range of indications that are treatable with photodynamic therapy to include moderate- and large-volume refractorytumors. Conventional photodynamic therapy utilizes the delivery of intense light for seconds or minutes. The new approach differs from conventional photodynamic therapy in that it combines a novel interstitial light delivery system with prolonged photoactivation of photosensitive drugs. Prolonging photoactivation time in order to deliver a higher light dose results in an amplification effect, whereby the repeated activation of each photosensitive drug molecule leads to the generation of many thousands of 1O2 molecules. The production of overwhelming numbers of these powerful oxidants in individual cells and the vascular supply of tumors leads to irreversible damage and death of the targeted lesions. Results of preclinical studies have indicated a significant correlation between increased duration of photoactivation and increased volume and depth of photodynamic therapy-induced necrosis. The new developments will enable photodynamic therapy to be used effectively against refractory bulky disease as frontline therapy or in combination with chemotherapy, radiation therapy, or biologics. Perhaps most promising, many patients with advanced refractory disease may now be relieved of symptoms or may return to the treatable population.
β‐lactamase as a probe of membrane protein assembly and protein export (1990)

The enzyme TEM beta-lactamase constitutes a versatile gene-fusion marker for studies on membrane proteins and protein export in bacteria. The mature form of this normally periplasmic enzyme displays readily detectable and distinctly different phenotypes when localized to the bacterial cytoplasm versus the periplasm, and thus provides a useful alternative to alkaline phosphatase for probing the topology of cytoplasmic membrane proteins. Cells producing translocated forms of beta-lactamase can be directly selected as ampicillin-resistant colonies, and consequently a beta-lactamase fusion approach can be used for positive selection for export signals, and for rapid assessment of whether any protein expressed in Escherichia coli inserts into the bacterial cytoplasmic membrane. The level of ampicillin resistance conferred on a cell by an extracytoplasmic beta-lactamase derivative depends on its level of expression, and therefore a beta-lactamase fusion approach can be used to directly select for increased yields of any periplasmic or membrane-bound gene products expressed in E. coli.
Transient gene expression control: effects of transfected DNA stability and trans-activation by viral early proteins. (1985)

The effects of trans-acting factors and transfected DNA stability on promoter activity were examined with chloramphenicol acetyl transferase (CAT) transient expression analysis. With cotransfection into CV-1P and HeLa cells, simian virus 40 T antigen, adenovirus E1a, and herpes-virus IE proteins were compared for their ability to trans-activate a variety of eucaryotic promoters constructed into CAT plasmids. T antigen and the IE protein were promiscuous activators of all the promoters tested [the simian virus 40 late promoter, the adenovirus E3 promoter, the alpha 2(I) collagen promoter, and the promoter of the Rous sarcoma virus long terminal repeat]. Conversely the E1a protein was specific, activating only the adenovirus E3 promoter and suppressing the basal activity of the other promoters. This specificity of activation by E1a contrasted with the high activity generated by all of the promoter-CAT plasmids when transfected into 293 cells, which endogenously produce E1a protein. Examination of transfected 293 cells determined that they stabilized much greater amounts of plasmid DNA than any other cells tested (CV-1P, COS, NIH-3T3, KB). Thus the high activity of nonadenovirus promoter-CAT plasmids in 293 cells results from the cumulative effect of basal promoter activity from a very large number of gene copies, not from E1a activation. This conclusion was supported by similar transfection analysis of KB cell lines which endogenously produce E1a protein. These cells stabilize plasmid DNA at a level comparable to that of CV-1P cells and, in agreement with the CV-1P cotransfection results, did not activate a nonadenovirus promoter-CAT plasmid. These results indicate that the stability of plasmid DNA must be considered when transient gene expression is being compared between cell lines. The use of relative plasmid copy numbers for the standardization of transient expression results is discussed.
Logistic control for fully automated large scale freight transport systems; event based control for the underground logistic system Schiphol (2002)

This paper provides new concepts for logistic control of highly automated transport systems. Furthermore, some novel characteristics of logistic control are described. The concepts are illustrated by examples from a large research project on a highly automated transport system, the underground logistic system Schiphol (OLS). The most important aspects of the OLS logistic control are decentralization, distribution, and an event-based information exchange between hierarchical control layers. The logistic control developed for the OLS was tested and evaluated by using a combination of simulation and real (scale) models and prototypes of the equipment that will be used within the OLS. It proves to work very well. In current studies the control concepts of the OLS are introduced for other complex transport systems as well. The first results are very positive.
The N- and C-terminal regions regulate the transport of wheat gamma-gliadin through the endoplasmic reticulum in Xenopus oocytes. (1993)

Following sequestration into the endoplasmic reticulum (ER), wheat storage proteins are naturally either retained and packaged into protein bodies within this organelle or exported to the Golgi apparatus. To identify protein domains that control the sorting of wheat storage proteins within the ER, a wild-type gamma-gliadin storage protein as well as two of its deletion mutants, each bearing either of the two autonomous N- and C-terminal regions, were expressed in Xenopus oocytes. Our results demonstrated that the N-terminal region of the gliadin, which is composed of several tandem repeats of the consensus sequence PQQPFPQ, was entirely retained within the ER and accumulated in dense protein bodies. In contrast, the C-terminal autonomous region was efficiently secreted to the medium. The wild-type gamma-gliadin, containing both regions, was secreted at a lower rate and less efficiently than its C-terminal region. These results suggest that sorting of the wheat gamma-gliadin within the ER may be determined by a balance between two opposing signals: one functions in the retention and packaging of the storage protein within the ER, while the second renders the protein competent for export from this organelle to the Golgi apparatus.
Spontaneous and Nitrosourea-Induced Primary Tumors of the Central Nervous System in Fischer 344 Rats Chronically Exposed to 836 MHz Modulated Microwaves (1999)

We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.
A Position Model in Evaluating the Levels of Information Technology Adoption for SMEs in the Business Network (2003)

Information Technology (IT) is computer application and infrastructure that leverage intra and inter firm process and systems integration [Pant and Ravichandran, 2001]. There are many solutions provided by vendors and different levels of implementations for firms to adopt. Nevertheless, few strategic decision making and categorising models have been developed for managers and industrial practitioners. Based on previous literature, this research is designed to propose a level of IT adoption model by categorising factors. With the empirical data of Taiwanese Small and Medium Enterprises (SMEs), the authors discuss the proposed model in terms of its applicability, limitation, and future research. Moreover, factors such as business network positions and firm sizes are drawn in to enhance current researches on Supply Chain Integration and B2B eCommerce implementation.
Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer (2016)

Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown. Here, we report that multiple immune checkpoints are expressed in TALs and TILs isolated from ovarian tumor-bearing mice. Importantly, blockade of PD-1, LAG-3, or CTLA-4 alone using genetic ablation or blocking antibodies conferred a compensatory upregulation of the other checkpoint pathways, potentiating their capacity for local T-cell suppression that, in turn, could be overcome through combinatorial blockade strategies. Whereas single-agent blockade led to tumor outgrowth in all animals, dual antibody blockade against PD-1/CTLA-4 or triple blockade against PD-1/LAG-3/CTLA-4 resulted in tumor-free survival in 20% of treated mice. In contrast, dual blockade of LAG-3 and CTLA-4 pathways using PD-1 knockout mice led to tumor-free survival in 40% of treated mice, suggesting a hierarchical ordering of checkpoint function. Durable antitumor immunity was most strongly associated with increased numbers of CD8<sup>+</sup> T cells, the frequency of cytokine-producing effector T cells, reduced frequency of Tregs and arginine-expressing monocytic myeloid-derived suppressor cells in the peritoneal TME. These data provide a basis for combinatorial checkpoint blockade in clinical intervention for ovarian cancer.
Myocardial repair with autologous skeletal myoblasts: a review of the clinical studies and problems. (2004)

Stem cell therapy for myocardial repair after myocardial infarction is a new and promising treatment modality. Currently, bone marrow derived stem cells are used in clinical studies to evaluate its beneficial effect on repair of infarcted/hibernating myocardium in the subacute phase after myocardial infarction. Whereas skeletal myoblasts are nowadays under investigation in the setting of scar repair in chronic congestive heart failure patients. The mechanism of bone marrow derived stem cells is probably mainly related to induction and stimulation of angiogenesis, whereas skeletal myoblasts are more likely to contribute to recovery of left ventricular function by the direct engraftment of contractile cells and hypothetically indirect by stimulation of native and circulation stem cells to home into the scarred tissue. This review will focus on the use of skeletal myoblasts in all clinical studies presented sofar and will discuss several issues like: different transplantation methods, potential mechanism of effect, potential risks like arrhythmia and future concepts. As the target population of skeletal myoblast transplantation is chronic post myocardial infarction heart failure patients, ventricular arrhythmias are very likely to occur. This review will specially address the presence of ventricular arrhythmias observed in some clinical studies and the pre-clinical data on the electrophysiology of skeletal myotubes and its relationship to the surrounding myocardium.
Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus (2013)

Influenza virus has the ability to evade host immune surveillance through rapid viral genetic drift and reassortment; therefore, it remains a continuous public health threat. The development of vaccines producing broadly reactive antibodies, as well as therapeutic strategies using human neutralizing monoclonal antibodies (HuMAbs) with global reactivity, has been gathering great interest recently. Here, three hybridoma clones producing HuMAbs against influenza B virus, designated 5A7, 3A2 and 10C4, were prepared using peripheral lymphocytes from vaccinated volunteers, and were investigated for broad cross-reactive neutralizing activity. Of these HuMAbs, 3A2 and 10C4, which recognize the readily mutable 190-helix region near the receptor binding site in the hemagglutinin (HA) protein, react only with the Yamagata lineage of influenza B virus. By contrast, HuMAb 5A7 broadly neutralizes influenza B strains that were isolated from 1985 to 2006, belonging to both Yamagata and Victoria lineages. Epitope mapping revealed that 5A7 recognizes 316G, 318C and 321W near the C terminal of HA1, a highly conserved region in influenza B virus. Indeed, no mutations in the amino acid residues of the epitope region were induced, even after the virus was passaged ten times in the presence of HuMAb 5A7. Moreover, 5A7 showed significant therapeutic efficacy in mice, even when it was administered 72 hours post-infection. These results indicate that 5A7 is a promising candidate for developing therapeutics, and provide insight for the development of a universal vaccine against influenza B virus.
Palmar Skin Blood Flow and Temperature Responses Throughout Endoscopic Sympathectomy (2004)

Thoracic surgical sympathectomy is often performed to treat primary palmar and axillary hyperhidrosis. An increase in palmar skin temperature is frequently used to identify the success of the procedure. Because changes in palmar skin temperature occur secondary to changes in skin blood flow, the objective of this study was to test the hypothesis that monitoring palmar skin blood flow would provide greater temporal resolution relative to monitoring palmar skin temperature. In 11 patients with palmar and/or axillary hyperhidrosis, we measured palmar skin temperature and blood flow (via laser Doppler flowmetry) throughout the sympathectomy procedure. Five minutes after the initial cautery, skin blood flow increased from 48 +/- 7 perfusion units to 121 +/- 17 perfusion units (P <0.001), whereas no significant change in temperature was observed (31.0 degrees C +/- 0.5 degrees C to 31.3 degrees C +/- 0.5 degrees C; P >0.05). The time required to reach peak skin blood flow (22 +/- 3 min) was significantly less than the time required to reach peak skin temperature (34 +/- 0.3 min; P <0.001). Finally at 5, 10, and 15 min after the initial cautery, skin blood flow increased to a larger percentage of the total increase in skin blood flow relative skin temperature (all P <0.006). These data suggest that monitoring skin blood flow provides greater temporal resolution when compared with monitoring skin temperature during thoracic sympathectomy. However, the initial cautery of the parietal pleura over the ganglion may result in increases in skin blood flow before physical disruption of the ganglion. This occurrence may limit the utility of skin blood-flow measurements in identifying the success of the procedure.