gebhart/patrepeval huggingface dataset:
Construction and properties of a turkey herpesvirus recombinant expressing the Marek's disease virus homologue of glycoprotein B of herpes simplex virus (1993)

A herpesvirus of turkeys (HVT) recombinant containing a 3.9 kbp fragment of Marek's disease virus (MDV) DNA encoding MDV glycoprotein B (gB), stably integrated into the thymidine kinase (TK) gene of HVT, has been constructed. The replication of the recombinant in chick embryo fibroblasts (CEF) was comparable to that of wild-type HVT. The recombinant expressed authentic MDV gB and its processed forms (110K, 65K and 48K) in CEF as shown by immunoblotting using an MDV-specific anti-peptide serum. Northern blot analysis showed that MDV gB mRNA was transcribed from MDV promoter sequences flanking the MDV gB open reading frame and also from the HVT TK promoter. However, the level of replication of the recombinant in vivo appeared to be lower than wild-type HVT as shown by the titres of HVT antibodies, determined by ELISA. Pathogenicity tests showed that the recombinant was safe and did not cause microscopic or gross Marek's disease lesions or other abnormalities. The results suggest that HVT has potential as a vector for recombinant vaccines.
κ-Opioid Receptor Agonists Modulate Visceral Nociception at a Novel, Peripheral Site of Action (2000)

kappa-opioid receptor agonists (kappa-ORAs) have been shown to modulate visceral nociception through an interaction with a peripheral, possibly novel, kappa-opioid-like receptor. We used in the present experiments an antisense strategy to further explore the hypothesis that kappa-ORA effects in the colon are produced at a site different from the cloned kappa-opioid receptor (KOR). An antisense oligodeoxynucleotide (ODN) to the cloned rat KOR was administered intrathecally (12.5 microg, twice daily for 4 d) to specifically knock-down the cloned KOR. Efficacy of the KOR antisense ODN treatment was behaviorally evaluated by assessing the antinociceptive effects of peripherally administered kappa- (EMD 61, 753 and U 69,593), mu- (DAMGO) and delta- (deltorphin) ORAs in the formalin test. Intrathecal antisense, but not mismatch ODN blocked the actions of EMD 61,753 and U 69,593 without affecting the actions of DAMGO or deltorphin; a complete recovery of antinociceptive actions of the kappa-ORA EMD 61,753 was observed 10 d after the termination of antisense ODN treatment. In contrast, the ability of EMD 61,753 to dose-dependently attenuate responses of pelvic nerve afferent fibers to noxious colonic distension was unaffected in the same rats in which the antisense ODN effectively knocked-down the KOR as assessed in the formalin test. Additionally, Western blot analysis demonstrated a significant downregulation of KOR protein in the L4-S1 dorsal root ganglia of antisense, but not mismatch ODN-treated rats. The present results support the existence of a non-kappa-opioid receptor site of action localized in the colon.
Phase I Dendritic Cell p53 Peptide Vaccine for Head and Neck Cancer (2014)

Adjuvant p53-specific vaccination of patients with HNSCC was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients' DC required stronger maturation stimuli to reverse immune suppression and improve vaccine efficacy.
Head‐twitch response in rodents induced by the hallucinogen 2,5‐dimethoxy‐4‐iodoamphetamine: a comprehensive history, a re‐evaluation of mechanisms, and its utility as a model (2012)

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT(2) ) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals.
Interleukin-33 Is Biologically Active Independently of Caspase-1 Cleavage (2009)

The new interleukin (IL)-1 family cytokine IL-33 is synthesized as a 30-kDa precursor. Like pro-IL-1beta, human pro-IL-33 was reported to be cleaved by caspase-1 to generate an 18-kDa fragment, which is sufficient to activate signaling by the IL-33 receptor T1/ST2. However, the proposed caspase-1 cleavage site is poorly conserved between species. In addition, it is not clear whether caspase-1 cleavage of pro-IL-33 occurs in vivo and whether, as for IL-1beta, this cleavage is a prerequisite for IL-33 secretion and bioactivity. In this study, we further investigated caspase-1 cleavage of mouse and human pro-IL-33 and assessed the potential bioactivity of the IL-33 precursor. We observed the generation of a 20-kDa IL-33 fragment in cell lysates, which was enhanced by incubation with caspase-1. However, in vitro assays of mouse and human pro-IL-33 indicated that IL-33 is not a direct substrate for this enzyme. Consistently, caspase-1 activation in THP-1 cells induced cleavage of pro-IL-1beta but not of pro-IL-33, and activated THP-1 cells released full-length pro-IL-33 into culture supernatants. Finally, addition of full-length pro-IL-33 induced T1/ST2-dependent IL-6 secretion in mast cells. However, we observed in situ processing of pro-IL-33 in mast cell cultures, and it remains to be determined whether full-length pro-IL-33 itself indeed represents the bioactive species. In conclusion, our data indicate that pro-IL-33 is not a direct substrate for caspase-1. In addition, our results clearly show that caspase-1 cleavage is not required for pro-IL-33 secretion and bioactivity, highlighting major differences between IL-1beta and IL-33.
Mechanism of flexural resonance frequency shift of a piezoelectric microcantilever sensor during humidity detection (2008)

We have examined the flexural resonance frequency shift of a piezoelectric microcantilever sensor (PEMS) during humidity detection and have shown that the flexural resonance frequency shift of the PEMS during detection was a result of Young's modulus change of its piezoelectric layer. Because of the piezoelectric layer's Young's modulus change, the PEMS flexural resonance frequency shift was more than 300 times larger than could be accounted for by mass loading.
Molecular Regulation of Hepatic Fibrosis, an Integrated Cellular Response to Tissue Injury (2000)

Encapsulation of injury with fibrosis is a highly evolved response of adult tissues. In liver, the components of the process have been greatly clarified, leading to a coherent view of how wound healing occurs in response to injury. Hepatic fibrogenesis provides an important biological and clinical context for emerging concepts in molecular biochemistry that is relevant to many other tissues.
Changes in Risk Factors for Hypoxic‐ischaemic Seizures in Term Infants (1997)

Term infants with seizures and evidence of perinatal asphyxia were prospectively identified in 1 city and 2 time periods: 1978-1981 and 1991. Infants with multiple congenital abnormalities, hypocalcaemia or infection were excluded. Although there was little change in the overall incidence of neonatal seizures between 1978-1981 (1.9 per 1,000) and 1991 (1.78 per 1,000, N.S.) there was a marked reduction in small for dates infants with seizures: 8 of 19 infants in 1978-1981 compared to none of 16 in 1991 (p < 0.005). In contrast, infants > or = 41 weeks continued to show a markedly increased risk for asphyxia (relative risk 4.48, 95% CI: 1.7-12.3). The mechanism of this improved outcome for small for gestational age infants is unknown, but speculatively may be due to improved obstetric monitoring techniques allowing early identification of compromised infants.
An Access Scheme for High Speed Packet Data Service on IS-95 Based CDMA (2005)

In this work, we study a simple admission control scheme for high speed packet data service over the reverse link of an IS-95 based CDMA air interface. A preliminary version of this scheme was originally proposed in [3] and admits data users on a burst level. In this work, we study the performance and design tradeoffs through simulations. The basic tradeoff is the coverage of high speed packet data service and its impact on outage experienced by the voice users. The results indicate that through limiting the region where high speed data service is available, the performance impact on voice users can be made small. It is possible to extend the region of coverage of high speed data by using more complex schemes proposed in [3]. These schemes are subject of future work.
Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. (1993)

Naturally processed peptides were acid extracted from immunoaffinity-purified HLA-DR2, DR3, DR4, DR7, and DR8. Using the complementary techniques of mass spectrometry and Edman microsequencing, > 200 unique peptide masses were identified from each allele, ranging from 1,200 to 4,000 daltons (10-34 residues in length), and a total of 201 peptide sequences were obtained. These peptides were derived from 66 different source proteins and represented sets nested at both the amino- and carboxy-terminal ends with an average length of 15-18 amino acids. Strikingly, most of the peptides (> 85%) were derived from endogenous proteins that intersect the endocytic/class II pathway, even though class II molecules are thought to function mainly in the presentation of exogenous foreign peptide antigens. The predominant endogenous peptides were derived from major histocompatibility complex-related molecules. A few peptides derived from exogenous bovine serum proteins were also bound to every allele. Four prominent promiscuous self-peptide sets (capable of binding to multiple HLA-DR alleles) as well as 84 allele-specific peptide sets were identified. Binding experiments confirmed that the promiscuous peptides have high affinity for the binding groove of all HLA-DR alleles examined. A potential physiologic role for these endogenous self-peptides as immunomodulators of the cellular immune response is discussed.
Ge-Sb-Se glass fiber-optics for in-vivo mid-infrared optical biopsy (2016)

In the UK, it is now recognised that 1 in 2 people born after 1960 will develop some form of cancer during their lifetime. Diagnosing patients whilst in the early stages drastically improves their chances of survival but up until now the gold standard for cancer detection is via a lengthy excision biopsy procedure, which relies on the skill of a histopathologist. Evidently, the need for a faster solution is paramount. The mid-infrared (MIR) spectral region covers the wavelengths 3-25 &mu;m and characteristic vibrational spectra unique to each molecular type. Subtle changes in the specific spectral response within this region are indicative of changes within the cells relative to normal cells, signifying the presence or absence of a disease. Our goal is to carry out disease diagnosis in vivo. Reaching these wavelengths has previously presented difficulties as conventional MIR blackbody light sources are weak and optical fibers for transmitting MIR light to/from tissue in vivo can be limited by strong material absorption such as silica glass &gt;2.4 &mu;m and tellurite, and heavy metal fluoride, &gt;4.75 &mu;m. However, chalcogenide glasses have been shown to transmit MIR light out to 25 &mu;m. This paper reports on a glass composition in the Ge-Sb-Se system and its suitability as an optical fiber for the transmission of MIR to and from tissue samples, enabling in vivo mapping for an immediate diagnostic response- a technique termed ‘optical biopsy’.
Nonlinear EEG analysis in epilepsy (2005)

This overview presents potential applications of nonlinear time series analysis using EEGs derived from epilepsy patients. Apart from diagnostically oriented topics including localization of epileptic foci in different anatomical locations during the seizure-free interval I discuss possibilities for seizure anticipation which is one of the most challenging aspects of epileptology.
Inhibition of Histone Lysine Methylation Enhances Cancer–Testis Antigen Expression in Lung Cancer Cells: Implications for Adoptive Immunotherapy of Cancer (2011)

Cancer-testis antigens (CTA), such as NY-ESO-1, MAGE-A1, and MAGE-A3, are immunogenic proteins encoded by genes, which are normally expressed only in male germ cells but are activated by ill-defined epigenetic mechanisms in human tumors, including lung cancers. Previously, we reported induction of these CTAs in cancer cells, but not normal cells, by DNA-demethylating agents and histone deacetylase inhibitors using clinically achievable exposure conditions. In the present study, we evaluated chromatin alterations associated with repression/activation of cancer-testis genes in lung cancer cells to further develop gene-induction regimens for cancer immunotherapy. Repression of NY-ESO-1, MAGE-A1, and MAGE-A3 coincided with DNA hypermethylation, recruitment, and binding of polycomb-group proteins, and histone heterochromatin modifications within the promoters of these genes. Derepression coincided with DNA demethylation, dissociation of polycomb proteins, and presence of euchromatin marks within the respective promoters. Short hairpin RNAs were used to inhibit several histone methyltransferases (KMT) and histone demethylases (KDM) that mediate histone methylation and repress gene expression. Knockdown of KMT6, KDM1, or KDM5B markedly enhanced deoxyazacytidine (DAC)-mediated activation of these cancer-testis genes in lung cancer cells. DZNep, a pharmacologic inhibitor of KMT6 expression, recapitulated the effects of KMT6 knockdown. Following DAC-DZNep exposure, lung cancer cells were specifically recognized and lysed by allogeneic lymphocytes expressing recombinant T-cell receptors recognizing NY-ESO-1 and MAGE-A3. Combining DNA-demethylating agents with compounds, such as DZNep, that modulate histone lysine methylation may provide a novel epigenetic strategy to augment cancer-testis gene expression as an adjunct to adoptive cancer immunotherapy.
Photoswitched Cell Adhesion on Surfaces with RGD Peptides (2005)

Coating of surfaces by RGD peptides is well-known. Herein we describe the possibility to switch cell adhesion properties by changing the distance and orientation of the RGD peptides to the surface. A set of RGD peptides of the type cyclo(-RGDfK-) was synthesized containing the photoswitchable 4-[(4-aminophenyl)azo]benzocarbonyl central unit as spacer between the acrylamide anchor and the RGD peptide. PMMA (poly methyl methacrylate) surfaces were coated with these peptides. Control of adhesion stimulation by irradiation with 366 or 450 nm light could be achieved.
Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization (2000)

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and has a very poor prognosis. Fifty primary HCC cases have been analyzed in the present study to explore the association between genomic alteration in primary HCC and clinical features. Several recurrent chromosomal abnormalities were identified in this study. The most frequently detected chromosomal gains involved chromosome arms 1q (33/50 cases, 66%), 8q (24/50 cases, 48%), and 20q (10/50 cases, 20%). High-copy-number amplifications involving 1q (4 cases), 8q (3 cases), and 20q (3 cases) were detected, and a minimum overlapping amplified region at 1q12–q22 was identified. The most frequently detected loss of chromosomal material involved 16q (35/50 cases, 70%), 17p (26/50 cases, 52%), 19p (21/50 cases, 42%), 4q (20/50 cases, 40%), 1p (18/50 cases, 36%), 8p (16/50 cases, 32%), and 22q (14/50 cases, 28%). The associations between genomic alterations detected in the present study and clinical features including clinical stage, tumor size, HBV infection, chronic liver disease, and liver cirrhosis were explored. Our CGH results suggest that the gain of 20q and deletion of 8p are late genetic alterations in HCC, because the incidence of these alterations was obviously increased in the advanced clinical stages. Another finding showed that loss of 8p and gain of 8q and 20q are associated with tumor size. The recurrent gain and loss of chromosomal regions identified in this study provide candidate regions that may contain oncogenes or tumor suppressor genes respectively involved in HCC development and progression. © 2000 Wiley-Liss, Inc.
Quantification of Biomolecules by External Electrospray Ionization Fourier Transform Mass Spectrometry (1997)

Fourier transform mass spectrometry (FTMS) is well-known for its capabilities in structural characterization of molecules. Recent developments in radio frequency excitation, linearized trapping, and accumulation of ions generated from external sources have improved the potential of FTMS for quantitative analysis. Here, a commercial external electrospray ionization FTMS, employing a linearized ion trap (the Infinity Cell) and an ion accumulation procedure in which ions are deflected off-axis and injected into the trap, is evaluated as an analytical method for quantifying amino acids, peptides, and proteins. Linear response over approximately 2-3 orders of magnitude is observed for singly-charged ions with low coefficients of variation (generally < 10%), and the calibration curves generated can be used to quantify structurally similar analytes with < 4% relative error, as shown here for quantification of leucine enkephalin from curves generated by methionine enkephalin. Similar precision is obtained for multiply-charged lysozyme, but over only 1.5 orders of magnitude. Some m/z discrimination is observed as a function of trap accumulation potential for a two-component cytochrome c/lysozyme mixture. The results are promising because they suggest that quantification using liquid chromatography coupled to electrospray FTMS is possible.
CFTR in Calu-3 human airway cells: channel properties and role in cAMP-activated Cl- conductance (1994)

Calu-3, a cell line derived from a lung adenocarcinoma, forms tight junctions, expresses cystic fibrosis transmembrane conductance regulator (CFTR), and secretes Cl- in response to adenosine 3',5'-cyclic monophosphate (cAMP)-elevating agents. Anion conductance of Calu-3 cells was assessed with isotopic flux and patch-clamp methods at 22 degrees C. Iodide efflux was increased by cAMP-elevating agents and brief trypsin treatment. A 7.1 +/- 0.4-pS voltage-independent Cl- channel with linear current-voltage relation was the most common channel observed in cell-attached recordings and was identified as CFTR on the basis of shared features with recombinant CFTR. In unstimulated cells, the mean minimum number of active CFTR channels per patch was 1 +/- 1 (n = 12), increasing to 6 +/- 8 (n = 40) after stimulation with cAMP-elevating agents or after brief trypsin treatment. Channel closure after excision was biexponential with tau 1 approximately 4 s and tau 2 approximately 79 s; typically channels were open continuously until closing permanently. In 11 of 12 excised patches, channels were reactivated by exposure to cAMP-dependent protein kinase (PKA) plus ATP. Efficacy of reactivation was inversely related to the duration from excision to addition of PKA. Channels were blocked by 20-40 microM 5-nitro-2-(3-phenylpropylamino)benzoate on cytosolic but not external side. Active CFTR channels were recorded in 83% of total patches. Other types of Cl- channels were observed in 5 of 52 (10%) cell-attached patches and in 17 of 34 (50%) excised patches, including an outwardly rectifying channel in 2 patches. CFTR channels are the predominant pathway for cAMP-stimulated Cl- conductance in Calu-3 cells; the long open times in the absence of ATP are not explained by present models of CFTR activation.
Brain Amyloid — A Physicochemical Perspective (1996)

The ability to form stable cross-beta fibrils is an intrinsic physicochemical characteristic of the human beta-amyloid peptide (A beta), which forms the brain amyloid of Alzheimer's disease (AD). The high amyloidogenicity and low solubility of this hydrophobic approximately 40-mer have been barriers to its study in the past, but the availability of synthetic peptide and new physical methods has enabled many novel approaches in recent years. Model systems for A beta aggregation (relevant to initial nidus formation) and A beta deposition (relevant to plaque growth and maturation) in vitro have allowed structure/activity relationships and kinetics to be explored quantitatively, and established that these processes are biochemically distinct. Different forms of the peptide, with different physiochemical characteristics, are found in vascular and parenchymal amyloid. Various spectroscopic methods have been used to explore the three-dimensional conformation of A beta both in solution and in solid phase, and demonstrated that the peptide adopts a different configuration in each state. A significant conformational transition is essential to the transformation of A beta from solution to fibril. These observations suggest new therapeutic targets for the treatment of AD.
Simulation Study of Turbine Meter for the Measurement of Solid Flow (2003)

A numerical study of the dynamic behaviour of a turbine meter measuring solid flowrate is carried out by use of the discrete element method. The simulation was conducted with a cylindrical standpipe of 30d in diameter and 100d high, filled with 30000 mono-sized spheres of diameter d, and a turbine fixed at the centre of the standpipe at height of 20d. The dependence of the rotation speed of turbine on flowrate was first measured and shown to be qualitatively comparable to the experimental measurement in the literature. The forces and torques acting on a turbine originated from its interaction with neighbouring particles were then analysed in terms of spatial and statistical distributions. The results are found to be useful to understand the underlying working principles.
[Rh-D genotyping for exon 2, 5 and 7 of German and Japanese blood donors with sequence specific polymerase chain reaction]. (1997)

RHD genotyping from fetal cells was applied for the detection of the RHD gene in the fetus of immunized Rh-D-negative women. Additionally, RHD genotyping was applied for the characterization of Rh-D variants. Although 44 nucleotide substitutions are known to code for 35 amino acid differences between the RHCE and the RHD gene, only a few polymorphisms have been investigated yet. We investigated 7 RHD-specific nucleotides on exons 2, 5, and 7 with sequence-specific primers and 1 nucleotide with ligation-based typing. All RHD genotyping results were correlated with serological results and established genotyping methods in 116 German and 98 Japanese blood donors, because different genetic sequences coding for Rh-D polypeptides have been described in different ethnic groups. Sequence-specific amplification of D-specific sequences was concordant with the serological result in all blood donors tested. However, ligation-based typing on exon 5 gave false-negative results in 7 donors. In summary, 5 new sequence-specific PCRs have been evaluated for further characterization of Rh-D variants. Furthermore, the methods described allow nested PCR and thus may help in determination of the fetal RhD status from maternal peripheral blood during pregnancy.