gebhart/patrepeval huggingface dataset:
Phase I, Open-Label, Dose-Escalating Study of a Genetically Engineered Herpes Simplex Virus, NV1020, in Subjects with Metastatic Colorectal Carcinoma to the Liver (2006)

Current regimens of systemic chemotherapy result in only modest lengthening of survival in patients with advanced stage, liver-dominant, metastatic colorectal cancer who have failed first-line chemotherapy. The objective of this study was to investigate the safety and tolerability of NV1020, a replication-competent, attenuated, genetically engineered herpes simplex virus type 1 (HSV-1), in patients with hepatic colorectal metastases refractory to first-line chemotherapy. A phase I, open-label, dose-escalating study of a single 10-min hepatic arterial infusion of NV1020 in four cohorts. Three patients in each cohort received doses of 3 x 10(6), 1 x 10(7), 3 x 10(7), and 1 x 10(8) plaque-forming units. Adverse events were either mild or moderate in severity, and self-limiting. Only three serious adverse events (one transient rise in serum y-glutamyltransferase, one diarrhea, and one leukocytosis) experienced by three patients were considered to be possibly or probably related to NV1020. There were no deaths during the study, and there was no evidence of disseminated herpes infection. Viral presence was detected in only one saliva sample and two serum samples from one asymptomatic patient in the highest dose cohort. In the first week after viral administration only rare and minor increases were noted for tumor necrosis factor-alpha (six samples; three patients; peak, 40 pg/ml), interleukin (IL)-1 (two samples; two patients; peak, 28 pg/ml), and interferon-y (four samples; two subjects; peak, 54 pg/ml). No IL-2 was detected. Mild liver enzyme elevations were self-limiting and not associated with clinical symptoms. We conclude that NV1020, a genetically engineered but replication-competent HSV-1 oncolytic virus, can be safely administered into the hepatic artery without significant effects on normal liver function.
Fishing for the genetic basis of cardiovascular disease (2009)

Cardiovascular disease (CVD) has recently overtaken infectious disease to become the biggest global killer. Genetic factors have emerged as being of major importance in the pathogenesis of CVD. Owing to disease heterogeneity, variable penetrance and high mortality, human genetic studies alone are not sufficient to elucidate the genetic basis of CVD. Animal models are needed to identify novel genes that are involved in cardiovascular pathology and to verify the effect of suspected disease genes on cardiovascular function. An intriguing model organism is the zebrafish danio rerio. Several features of the zebrafish, such as a closed cardiovascular system, transparency at embryonal stages, rapid and external development, and easily tractable genetics make it ideal for cardiovascular research. Moreover, zebrafish are suitable for forward genetics approaches, which allow the unbiased identification of novel and unanticipated cardiovascular genes. Zebrafish mutants with various cardiovascular phenotypes that closely correlate with human disease, such as congenital heart disease, cardiomyopathies and arrhythmias, have been isolated. The pool of zebrafish mutants, for which the causal gene mutation has been identified, is constantly growing. The human orthologues of several of these zebrafish genes have been shown to be involved in the pathogenesis of human CVD. Cardiovascular zebrafish models also provide the opportunity to develop and test novel therapeutic strategies, using innovative technologies such as high throughput in vivo small molecule screens.
Characterization of human telomeric repeat sequences from human herpesvirus 6 and relationship to replication (1995)

Here we examine by polymerase chain reaction amplification followed by cloning and sequence analyses selected regions of the human herpesvirus 6 (HHV-6) genome which contain human telomeric repeats (TTA-GGG). We determine the relative number, arrangement and orientation of the repeats in the unit length genome, in concatemeric replicative intermediates and in heterogeneous (het) regions. We also examine distribution of the repeats in the entire genome (159 kb) and their orientation relative to DNA packaging motifs and the origin of lytic replication. In the prototype orientation the HHV-6 repeat is the related complement, TAACCC. We show that tandem arrays of this repeat are present in the right and left long direct repeats (DRL and DRR, 8 kb each) which bound the long unique sequence (UL, 143 kb). Within each DR there is a left terminal imperfect tandem array and a right terminal perfect tandem array (58 copies). In DR they are each adjacent to DNA packaging motifs, pac1 and pac2, described for herpes simplex virus and human cytomegalovirus, in the arrangement pac1-imperfect repeat-7.2 kb-perfect repeat-pac2. Five independent clones were isolated and sequence determined from junctions of concatemeric replicative intermediates which showed adjacent pac2 and pac1 motifs surrounded by telomeric repeats. Favoured cleavage sites for unit length genomes were indicated which avoided cleavage within the repeats. Analyses of the complete genome showed no tandem repeats within UL but did show a polar distribution of monomeric copies and related sequences around the origin of replication, with an effect on the overall base composition. The implications for virus replication are discussed.
Accurate identification of periodic oscillations buried in white or colored noise using fast orthogonal search (2001)

We use a previously introduced fast orthogonal search algorithm to detect sinusoidal frequency components buried in either white or colored noise. We show that the method outperforms the correlogram, modified covariance autoregressive (MODCOVAR) and multiple-signal classification (MUSIC) methods. Fast orthogonal search method achieves accurate detection of sinusoids even with signal-to-noise ratios as low as -10 dB, and is superior at detecting sinusoids buried in 1/f noise. Since the utilized method accurately detects sinusoids even under colored noise, it can be used to extract a 1/f noise process observed in physiological signals such as heart rate and renal blood pressure and flow data.
Polyacrylic acid‐induced resistance to tobacco mosaic virus in tobacco cv. Xanthi (1975)

SUMMARY Polyacrylic acid (PA) of molecular weight 1700A, 1700B and 3500 caused resistance to infection with tobacco mosaic virus in tobacco cv. Xanthi‐nc, when sprayed on the leaves or watered into the soil. The numbers of lesions produced in the treated plants were between 27 and 97% fewer than in the untreated plants depending on the concentration of PA, its molecular weight and the method of application. Some resistance was caused against potato virus X and potato virus Y but only at concentrations that were harmful to the plants. It appears that PA activates a mechanism responsible for localizing viruses in hypersensitive plants.
Poly (ADP-Ribose) Polymerase Inhibition Prevents Spontaneous and Recurrent Autoimmune Diabetes in NOD Mice by Inducing Apoptosis of Islet-Infiltrating Leukocytes (2003)

Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that consumes NAD in response to DNA strand breaks. The PARP inhibitor nicotinamide prevents NAD consumption and protects islet beta-cells from chemically induced necrosis but not cytokine-induced apoptosis. Therefore, it is unclear how nicotinamide protects NOD mice from autoimmune diabetes in which apoptosis is the mode of beta-cell death. To investigate the mechanism of diabetes prevention by PARP inhibition, we studied the effects of a novel, potent PARP inhibitor, PJ34, a phenanthridinone derivative, on diabetes development in NOD mice and on diabetes recurrence in diabetic NOD mice transplanted with syngeneic islets. PJ34 administration from age 5 or 15 weeks significantly decreased insulitis, beta-cell destruction and diabetes incidence, and protection from diabetes continued for 12 weeks after PJ34 therapy was stopped. Similarly, syngeneic islet graft survival was prolonged and outlasted therapy in PJ34-treated mice. Immunohistochemical studies revealed significantly fewer leukocytes in islet grafts of PJ34-treated mice, together with increased apoptosis of these cells and decreased expression of the T helper 1-type cytokine interferon (IFN)-gamma. These results suggest that PARP inhibition protects against autoimmune beta-cell destruction in NOD mice by inducing apoptosis of islet-infiltrating leukocytes and decreasing IFN-gamma expression in the islets.
Customer Evaluation of Telephone Circuits with Delay (1966)

In 1964 tests were begun in which customers making transatlantic calls, to which varying amounts of delay had been added, were interviewed after call completion to determine the circuit quality. These tests were continued in 1965 using the Early Bird satellite which some customers used extensively before being interviewed. During this period a number of different echo suppressors were also tested. Results show that the quality of telephone circuits with echo suppressors decreases with increasing delay, that previous satellite calls have no effect on the customer's opinion of his present call, and that no echo suppressor was superior for all delays although some appear to be better for the longer delays.
Application of photovoltaic solar cells in planar antenna structures (2003)

S.220-223
Progress measures, immediate determinacy, and a subset construction for tree automata (1992)

<p>Using the concept of progress measure, we give a new proof of Rabin's fundamental result that the languages defined by tree automata are closed under complementation.</p><p>To do this we show that for certain infinite games based on tree automata, an <em>immediate determinacy</em> property holds for the player who is trying to win according to a Rabin acceptance condition. Immediate determinacy is stronger than the <em> forgetful determinacy</em> of Gurevich and Harrington, which depends on more information about the past, but applies to another class of games.</p><p>Next, we show a graph theoretic duality theorem for winning conditions. Finally, we present an extended version of Safra's determinization construction. Together, these ingredients and the determinacy of Borel games yield a straightforward recipe for complementing tree automata.</p><p>Our construction is almost optimal, i.e. the state space blow-up is essentially exponential --- thus roughly the same as for automata on finite or infinite words.</p><p>To our knowledge, no prior constructions have been better than double exponential.</p>
Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients (2006)

Objective. To obtain a global view of the immunological alterations occurring in early systemic sclerosis (SSc) by transcriptional profiling of peripheral blood cells (PBCs). Methods. Oligonucleotide microarrays were used to compare PBC gene expression profiles in 18 SSc cases (<2 yr duration) and 18 controls matched for race, gender and ethnicity. SSc cases had no prior or current exposure to cytotoxic drugs. PAXgene tubes were used to stabilize RNA during phlebotomy. Changes in gene expression were independently validated by real-time polymerase chain reaction. Results. SSc PBCs demonstrated differential expression of 18 interferon-inducible genes. Six of these genes were identical to the interferon signature genes in lupus peripheral blood mononuclear cells. Notably, SSc PBCs also had increased expression of allograft inflammatory factor (AIF1) and several selectins and integrins involved in cellular adhesion to the endothelium. Global analysis of 284 known biological pathways revealed that 13 were differentially regulated in SSc PBCs, including two pathways (IL2RB and GATA3) that lead to T H 2 polarization. Conclusions. Transcriptional profiling reliably discriminates between PBCs from SSc and normal donors despite the fact that they represent a heterogeneous cell population. Multiple biological pathways were differentially regulated in SSc PBCs, but a common thread across these pathways was alterations in protein tyrosine kinase 2b and mitogen-activated protein kinase signalling. Although the SSc PBC gene expression profile demonstrated some parallels with the lupus interferon gene signature, there was also increased expression of transcripts encoding proteins that target PBCs to the endothelium, which might be relevant to the vasculopathy of SSc.
Chloride-hydrogen antiporters ClC-3 and ClC-5 drive osteoblast mineralization and regulate fine-structure bone patterning in vitro (2015)

Osteoblasts form an epithelium-like layer with tight junctions separating bone matrix from extracellular fluid. During mineral deposition, calcium and phosphate precipitation in hydroxyapatite liberates 0.8 mole of H(+) per mole Ca(+2). Thus, acid export is needed for mineral formation. We examined ion transport supporting osteoblast vectorial mineral deposition. Previously we established that Na/H exchangers 1 and 6 are highly expressed at secretory osteoblast basolateral surfaces and neutralize massive acid loads. The Na/H exchanger regulatory factor-1 (NHERF1), a pdz-organizing protein, occurs at mineralizing osteoblast basolateral surfaces. We hypothesized that high-capacity proton transport from matrix into osteoblast cytosol must exist to support acid transcytosis for mineral deposition. Gene screening in mineralizing osteoblasts showed dramatic expression of chloride-proton antiporters ClC-3 and ClC-5. Antibody localization showed that ClC-3 and ClC-5 occur at the apical secretory surface facing the bone matrix and in membranes of buried osteocytes. Surprisingly, the Clcn3(-/-) mouse has only mildly disordered mineralization. However, Clcn3(-/-) osteoblasts have large compensatory increases in ClC-5 expression. Clcn3(-/-) osteoblasts mineralize in vitro in a striking and novel trabecular pattern; wild-type osteoblasts form bone nodules. In mesenchymal stem cells from Clcn3(-/-) mice, lentiviral ClC-5 shRNA created Clcn3(-/-), ClC-5 knockdown cells, validated by western blot and PCR. Osteoblasts from these cells produced no mineral under conditions where wild-type or Clcn3(-/-) cells mineralize well. We conclude that regulated acid export, mediated by chloride-proton exchange, is essential to drive normal bone mineralization, and that CLC transporters also regulate fine patterning of bone.
Using fiber Bragg grating in geothermal monitoring (2010)

Earthquake precursor monitoring is the foundation of earthquake prediction and geothermal monitoring is one of the basic methods of earthquake precursor monitoring. High temperature well contains more information and therefore its monitoring is more important. However, electric sensors are hard to meet the monitoring requirements of high sensitivity and long lifetime. For a better observation of the earthquake precursor, a high sensitive fiber Bragg grating (FBG) temperature sensor is designed to monitoring a well at 87.5±1◦C. The performance of the FBG sensor demonstrates that it’s quite possible that applying FBG to high-sensitivity temperature-monitoring fields, such as geothermal monitoring. As far as we known, it is the first time that trying a high sensitive FBG temperature sensor in a practical application, let alone in the field of geothermal monitoring.
The American Psychiatric Press Textbook of Psychopharmacology (1995)

This text is divided into four sections. The first provides a review of biological and psychopharmacological areas including neurotransmitters, receptors, molecular neurobiology, biochemical anatomy, electrophysiology, animal models and pharmokinetics. The second section presents the classes of psychiatric drugs, including anxiolytics and antidepressants, antipsychotics, treatments for bipolar disorder and other agents. The third section reviews biological studies by their disease categories, such as mood disorders, schizophrenia, anxiety disorders, alzheimers disease, psychoactitive dependence disorders and eating disorders. The final section covers recent psychopharmacological treatments for each type of disorder as well as special settings. It also includes an appendix on promising new agents in Europe and Canada.
Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans (2005)

The outer layer of the Candida albicans cell wall is enriched in highly glycosylated mannoproteins that are the immediate point of contact with the host and strongly influence the host-fungal interaction. N-Glycans are the major form of mannoprotein modification and consist of a core structure, common to all eukaryotes, that is further elaborated in the Golgi to form the highly branched outer chain that is characteristic of fungi. In yeasts, outer chain branching is initiated by the action of the alpha1,6-mannosyltransferase Och1p; therefore, we disrupted the C. albicans OCH1 homolog to determine the importance of outer chain N-glycans on the host-fungal interaction. Loss of CaOCH1 resulted in a temperature-sensitive growth defect and cellular aggregation. Outer chain elongation of N-glycans was absent in the null mutant, demonstrated by the lack of the alpha1,6-linked polymannose backbone and the underglycosylation of N-acetylglucosaminidase. A null mutant lacking OCH1 was hypersensitive to a range of cell wall perturbing agents and had a constitutively activated cell wall integrity pathway. These mutants had near normal growth rates in vitro but were attenuated in virulence in a murine model of systemic infection. However, tissue burdens for the Caoch1delta null mutant were similar to control strains with normal N-glycosylation, suggesting the host-fungal interaction was altered such that high burdens were tolerated. This demonstrates the importance of N-glycan outer chain epitopes to the host-fungal interaction and virulence.
Optimizing reference values for the measurement of alpha 1-antitrypsin in serum: comparison of three methods. (1983)

We studied three methods (rate nephelometry, radial immunodiffusion, and trypsin-inhibitory capacity) for their ability to detect those individuals with a deficiency of alpha1-antitrypsin. The phenotype represented in 170 serum samples was determined by isoelectric focusing as the reference method. All three methods correctly identified Pi Z, Pi S, and Pi SZ phenotypes but varied in their ability to detect Pi MZ and Pi MS phenotypes. The rate-nephelometric method was the least sensitive in detecting Pi MZ and Pi MS variants because of the inappropriately low reference interval suggested by the manufacturer. We found that the three screening methods are comparable when the limiting values are properly selected. We suggest that the reference value for the rate-nephelometric method be increased from 0.85 g/L to 1.40 g/L to improve the sensitivity of the test.
A zinc finger protein RHL41 mediates the light acclimatization response in <i>Arabidopsis</i> (2000)

Arabidopsis thaliana plants showed an increased tolerance to high-intensity light when pre-exposed to medium-intensity light. This response, known as light acclimatization, depended on the quantity of light, the period of irradiation, and the quality of light. Among characterized acclimatization-induced cDNA clones, we identified a zinc finger protein rhl41 (responsive to high light) gene, that was rapidly up-regulated in proportion to the time of irradiation and the light intensity. Transgenic Arabidopsis plants over-expressing the rhl41 gene showed an increased tolerance to high-intensity light, and also morphological changes of thicker and dark green leaves. Interestingly, the palisade parenchyma was highly developed in the leaves of the transgenic plants, which is one of the long-term acclimatization responses in Arabidopsis plants. The anthocyanin content (a light protectant) as well as the chlorophyll content also increased. Antisense transgenic plants exhibited decreased tolerance to high irradiation. We propose that the RHL41 zinc finger protein has a key role in the acclimatization response to changes in light intensity.
<i>α‐N</i>‐Protected dipeptide acids: a simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide (2013)

The importance of dipeptides both in medicinal and pharmacological fields is well documented and many efforts have been made to find simple and efficient methods for their synthesis. For this reason, we have investigated the synthesis of α-N-protected dipeptide acids by reacting the easily accessible mixed anhydride of α-N-protected amino acids with free amino acids under different reaction conditions. The combination of TBA-OH and DMSO has been found to be the best to overcome the low solubility of amino acids in organic solvents. Under these experimental conditions, the homogeneous phase condensation reaction occurs rapidly and without detectable epimerization. The present method is also applicable to side-chain unprotected Tyr, Trp, Glu, and Asp but not Lys. This latter residue is able to engage two molecules of mixed anhydride giving the corresponding isotripeptide. Moreover, the applicability of this protocol for the synthesis of tri- and tetrapeptides has been tested. This approach reduces the need for protecting groups, is cost effective, scalable, and yields dipeptide acids that can be used as building blocks in the synthesis of larger peptides.
Wireless intraocular pressure sensor using stretchable variable inductor (2017)

This paper reports the design, fabrication, and characterization of a wireless, flexible, passive pressure sensor that enables real-time intraocular pressure (IOP) monitoring. It employs a novel approach that measures the strain on the sclera of eye-ball using integrated planar stretchable variable inductor. Major reduction in fabrication complexity is achieved in contrast to the state-of-the-art solutions which are based on variable capacitors. Our device potentially improves the stability of long-term measurement by eliminating baseline drift due to leaks within sealed capacitive chambers. Implantation in the sclera reduces energy absorption by tissue, thereby improving inductive coupling efficiency between the implanted sensor and the external coil. This will significantly facilitate the commercialization of minimally invasive, in-vivo IOP sensing devices for Glaucoma patients. Devices are packaged using Parylene-C, which ensures the mechanical flexibility and biocompatibility of the sensor.
Serum immunoerythropoietin levels in patients with cancer receiving cisplatin-based chemotherapy (1991)

Serum immunoerythropoietin (SIE) levels were studied of 25 randomly chosen cancer patients undergoing cisplatin-based chemotherapy and ten head and neck cancer patients who were studied prospectively before and during cisplatin-based therapy. The SIE levels were determined by standard radioimmunoassay, and the results were interpreted relative to erythropoietin levels and hematocrits of 17 aplastic or nutritionally anemic patients who were believed to have a normal erythropoietin response. Of the 25 randomly chosen patients, SIE levels were inappropriately low in four patients. In this population, there was a greater likelihood of erythropoietin deficiency in the patients with a hematocrit less than 30% compared with those with higher values (P less than 0.001), although there was no correlation between SIE level and the amount of cisplatin these patients received or their degree of renal impairment. Of the ten head and neck cancer patients, five were found to have inappropriately low SIE levels before therapy, and two additional patients had a decrease of SIE levels during therapy, in one patient to an abnormally low level. The anemia associated with malignancy was concluded to be in part associated with a relative erythropoietin deficiency, and in certain individuals, cisplatin therapy may contribute to that deficiency.