gebhart/patrepeval huggingface dataset:
Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma. (1992)

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.
The search for new vaccines against tuberculosis (2001)

The failure of the BCG vaccine for tuberculosis in large, controlled clinical trials, coupled with the gradual consensus that it is mostly ineffective in preventing adult pulmonary disease in endemic areas, has led to a concerted effort to develop a new generation of vaccines. This work is ongoing in a variety of areas, including DNA vaccines, subunit vaccines, recombinant vaccines, and auxotrophic vaccines. Several such candidates are giving promising results in mouse and guinea pig, aerosol-challenge infection models and should move to clinical trials in the near future.
Hepatitis C virus genotypes in Singapore and Indonesia (1995)

5' untranslated and partial core (C) region sequence of hepatitis C virus (HCV) in 21 Singaporean and 15 Indonesian isolates were amplified by reverse-transcription polymerase chain reaction and sequenced with the use of conserved primer sequences deduced from HCV genomes identified in other geographical regions. The HCV genotypes are predominantly that of Simmonds type 1 and less of type 2 and 3 with the latter genotype currently not detected in Indonesia. The 5' untranslated sequences are related to HCV-1. DK-7 (Denmark), US-11 (United States of America), HCV-J4, SA-10 (South Africa), T-3 (Taiwan), HCV-J6, HCV-J8, Eb-1 and Eb-8. When compared with the prototype HCV-1, insertions are found within the 5' untranslated region of Singaporean isolates and not in the Indonesians. There are Singaporean and Indonesian isolates that have sequences within the 5' untranslated region that differ slightly from each other. Microheterogeneity is observed in the core region of two Singaporeans and one Indonesian isolate. Finally, not all HCV isolates can be amplified with the conserved core sequence primers when compared with the ease with which these isolates can be amplified with 5' untranslated region conserved primers.
Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription. (1989)

Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.
High-flow-velocity and shear-rate imaging by use of color Doppler optical coherence tomography (1999)

Color Doppler optical coherence tomography (CDOCT) is capable of precise velocity mapping in turbid media. Previous CDOCT systems based on the short-time Fourier transform have been limited to maximum flow velocities of the order of tens of millimeters per second. We describe a technique, based on interference signal demodulation at multiple frequencies, to extend the physiological relevance of CDOCT by increasing the dynamic range of measurable velocities to hundreds of millimeters per second. The physiologically important parameter of shear rate is also derived from CDOCT measurements. The measured flow-velocity profiles and shear-rate distributions correlate very well with theoretical predictions. The multiple demodulation technique, therefore, may be useful to monitor blood flow in vivo and to identify regions with high and low shear rates.
Hydrodynamic Properties of a New Percutaneous Intra-aortic Axial Flow Pump (2000)

Cardiac intervention, myocardial infarction, or postoperative heart failure will sometimes create a need for circulatory support. For this purpose, a new, minimally invasive intra-aortic cardiac support system with a foldable propeller has been developed. In animals, the pump has been shown to have a positive hemodynamic influence, and the present study evaluates the hydraulic properties of the pump in a bench test. The axial flow pump is a catheter system with a distal motor driven foldable propeller (0-15,000 revolutions per minute). To protect the aortic wall, filaments forming a cage surround the propeller. In the present study, tests were done with two different pumps, one with and one without the cage. Two different models were used, one for testing pressure generation and one for obtaining flow-pressure characteristics. Propellers and tubes with different diameters were studied, and pressure and flow characteristics were measured. The mathematical relationships between pressure and rotational speed, pressure, and diameter of propeller and tube were determined. There was a positive relationship between the revolutions per minute and the generated pressure, a positive relationship between the diameter of the propeller and pressure, and a negative relationship between the diameter of the tube and the generated pressure. Within the physiologic range of cardiac output, there was a small drop in pressure with increasing flow in the tubes with a small diameter. With an increasing diameter of the tube, a smaller pressure drop was seen with increasing flow. The present cardiac support system has hydraulic properties, which may be of clinical relevance for patients with left ventricular heart failure.
S 15535, a benzodioxopiperazine acting as presynaptic agonist and postsynaptic 5‐HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine (1999)

1 The effect of S 15535 (4-benzodioxan-5-yl)1-(indan-2-yl)piperazine), an agonist at presynaptic and antagonist at postsynaptic 5-HT1A receptors, on the impairment of spatial learning caused by intrahippocampal scopolamine in a two-platform spatial discrimination task was studied. 2 Scopolamine (4.0 microg microl-1), injected bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. 3 Administered subcutaneously 30 min before each training session, S 15535 1.0 (but not 0.3) mg kg-1 did not modify choice accuracy but prevented its impairment by intrahippocampal scopolamine. 4 WAY 100635, a 5-HT1A receptor antagonist, injected into the dorsal raphe at 1.0 microg 0.5 microl-1 5 min before scopolamine, had no effect on choice accuracy and latency or errors of omission and did not modify the effect of scopolamine but completely antagonized the effect of S 15535 (1.0 mg kg-1) on scopolamine-induced impairment of choice accuracy. 5 The results confirm a previous report (Carli et al., 1998) that stimulation of presynaptic 5-HT1A receptors in the dorsal raphe counteracts the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. 6 Drugs that stimulate action on presynaptic 5-HT1A receptors, such as S 15535 and other partial 5-HT1A receptors agonists, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.
Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. (1996)

The mouse Rad51 gene is a mammalian homologue of the Escherichia coli recA and yeast RAD51 genes, both of which are involved in homologous recombination and DNA repair. To elucidate the physiological role of RAD51 protein, the gene was targeted in embryonic stem (ES) cells. Mice heterozygous for the Rad51 null mutation were intercrossed and their offspring were genotyped. There were no homozygous (Rad51-/-) pups among 148 neonates examined but a few Rad51-/- embryos were identified when examined during the early stages of embryonic development. Doubly knocked-out ES cells were not detected under conditions of selective growth. These results are interpreted to mean that RAD51 protein plays an essential role in the proliferation of cell. The homozygous Rad51 null mutation can be categorized in cell-autonomous defects. Pre-implantational lethal mutations that disrupt basic molecular functions will thus interfere with cell viability.
Infectious Causes of Uveitis in the Developing World (2000)

Infectious causes of uveitis are common in the developing world and include some causes that are rarely encountered in industrialized nations, such as tuberculosis, leptospirosis, leprosy, onchocerciasis, and cystercicosis. Ocular toxoplasmosis occurs in all countries but is more common in Central and South America, the South Pacific, and western Europe. AIDS-related opportunistic infections occur wherever HIV infection is prevalent, including North and South America, western and eastern Europe, the former Soviet Union, sub-Saharan Africa, and South and Southeast Asia. Physicians who care for patients in the developing world should consider these infectious possibilities whenever their patients develop uveitis.
Thermal analysis of hydrosilylation of 1-dodecene on porous silicon surface (2003)

Hydrosilylation of 1-dodecene on porous silicon surface has been studied by calorimetric methods. Using unpurified and purified 1-dodecene, it was possible to distinguish the reactions arising from oxidation from those due to hydrosilylation reactions. A surprising change from an exothermic reaction to an endothermic one was observed above 130 °C. A possible origin for this has been proposed, based on breaking of the double bond in the 1-dodecene molecule leaving CHx-termination on the PSi surface. The density functional calculations and measured FTIR spectra are presented as supporting evidence for the explanation given.
Alzheimer Disease as a Vascular Disorder (2002)

Since the value of scientific evidence generally revolves around probability and chance, it is concluded that the data presented here pose a powerful argument in support of the proposal that AD should be classified as a vascular disorder. According to elementary statistics, the probability or chance that all these findings are due to an indirect pathological effect or to coincidental circumstances related to the disease process of AD seems highly unlikely. The collective data presented in this review strongly support the concept that sporadic AD is a vascular disorder. It is recommended that current clinical management of patients, treatment targets, research designs, and disease prevention efforts need to be critically reassessed and placed in perspective in light of these important findings.
Insulin-like Growth Factor-I Receptor Internalization Regulates Signaling via the Shc/Mitogen-activated Protein Kinase Pathway, but Not the Insulin Receptor Substrate-1 Pathway (1998)

Insulin-like growth factor-I (IGF-I) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins, including insulin receptor substrate-1 (IRS-1) and the Shc proteins. Following hormone binding, IGF-I receptors cluster into clathrin-coated pits and are internalized via an endocytotic mechanism. This study investigates the relationship between IGF-I receptor internalization and signaling via IRS-1 and Shc. A mutation in the C terminus of the IGF-I receptor decreased both the rate of receptor internalization and IGF-I-stimulated Shc phosphorylation by more than 50%, but did not affect IRS-1 phosphorylation. Low temperature (15 degrees C) decreased IGF-I receptor internalization and completely inhibited Shc phosphorylation. Although receptor and IRS-1 phosphorylation were decreased in accordance with delayed binding kinetics at 15 degrees C, the ratio of IRS-1 to receptor phosphorylation was increased more than 2-fold. Dansylcadaverine decreased receptor internalization and Shc phosphorylation, but did not change receptor or IRS-1 phosphorylation. Consistent with these findings, dansylcadaverine inhibited IGF-I-stimulated Shc-Grb2 association, mitogen-activated protein kinase phosphorylation, and p90 ribosomal S6 kinase activation, but did not affect the association of phosphatidylinositide 3-kinase with IRS-1 or activation of p70 S6 kinase. These data support the concept that Shc/mitogen-activated protein kinase pathway activation requires IGF-I receptor internalization, whereas the IRS-1 pathway is activated by both cell surface and endosomal receptors.
Specific Interaction in Vitro and in Vivo of Glyceraldehyde-3-phosphate Dehydrogenase and LA Protein with Cis-acting RNAs of Human Parainfluenza Virus Type 3 (1996)

Human parainfluenza virus type 3 (HPIV3) genome RNA is transcribed and replicated by the virus-encoded RNA-dependent RNA polymerase, and specific cellular proteins play a regulatory role in these processes. To search for cellular proteins potentially interacting with HPIV3 cis-acting regulatory RNAs, a gel mobility shift assay was used. Two cellular proteins specifically interacted with the viral cis-acting RNAs containing the genomic 3′-noncoding region and the plus-sense leader sequence region. Surprisingly, by biochemical and immunological analyses, one of the cellular proteins was identified as the key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The other protein was characterized as the autoantigen, LA protein. Both GAPDH and LA protein also interacted with the same cis-acting RNA sequences in vivo and were found to be associated with the HPIV3 ribonucleoprotein complex in the infected cells. By double immunofluorescent labeling, GAPDH was found to be co-localized with viral ribonucleoprotein in the perinuclear region. These observations strongly suggest that cellular GAPDH and LA Protein participate in the regulation of HPIV3 gene expression. Human parainfluenza virus type 3 (HPIV3) genome RNA is transcribed and replicated by the virus-encoded RNA-dependent RNA polymerase, and specific cellular proteins play a regulatory role in these processes. To search for cellular proteins potentially interacting with HPIV3 cis-acting regulatory RNAs, a gel mobility shift assay was used. Two cellular proteins specifically interacted with the viral cis-acting RNAs containing the genomic 3′-noncoding region and the plus-sense leader sequence region. Surprisingly, by biochemical and immunological analyses, one of the cellular proteins was identified as the key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The other protein was characterized as the autoantigen, LA protein. Both GAPDH and LA protein also interacted with the same cis-acting RNA sequences in vivo and were found to be associated with the HPIV3 ribonucleoprotein complex in the infected cells. By double immunofluorescent labeling, GAPDH was found to be co-localized with viral ribonucleoprotein in the perinuclear region. These observations strongly suggest that cellular GAPDH and LA Protein participate in the regulation of HPIV3 gene expression.
The ERBB4/HER4 Intracellular Domain 4ICD Is a BH3-Only Protein Promoting Apoptosis of Breast Cancer Cells (2006)

ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e., EGFR, ERBB2/HER2/NEU, and ERBB3), which are associated with aggressive forms of human cancers, ERBB4 expression seems to be selectively lost in tumors with aggressive phenotypes. Consistent with this observation, we show that ERBB4 induces apoptosis when reintroduced into breast cancer cell lines or when endogenous ERBB4 is activated by a ligand. We further show that ligand activation and subsequent proteolytic processing of endogenous ERBB4 results in mitochondrial accumulation of the ERBB4 intracellular domain (4ICD) and cytochrome c efflux, the essential and committed step of mitochondrial regulated apoptosis. Our results indicate that 4ICD is functionally similar to BH3-only proteins, proapoptotic members of the BCL-2 family required for initiation of mitochondrial dysfunction through activation of the proapoptotic multi-BH domain proteins BAX/BAK. Similar to other BH3-only proteins, 4ICD cell-killing activity requires an intact BH3 domain and 4ICD interaction with the antiapoptotic protein BCL-2, suppressed 4ICD-induced apoptosis. Unique among BH3-only proteins, however, is the essential requirement of BAK but not BAX to transmit the 4ICD apoptotic signal. Clinically, cytosolic but not membrane ERBB4/4ICD expression in primary human breast tumors was associated with tumor apoptosis, providing a mechanistic explanation for the loss of ERBB4 expression during tumor progression. Thus, we propose that ligand-induced mitochondrial accumulation of 4ICD represents a unique mechanism of action for transmembrane receptors, directly coupling a cell surface signal to the tumor cell mitochondrial apoptotic pathway.
Synthesis, cloning and expression of the single-chain Fv gene of the HPr-specific monoclonal antibody, Jel42. Determination of binding constants with wild-type and mutant HPrs (1999)

The monoclonal antibody Jel42 is specific for the Escherichia coli histidine-containing protein, HPr, which is an 85 amino acid phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system. The binding domain (Fv) has been produced as a single chain Fv (scFv). The scFv gene was synthesized in vitro and coded for pelB leader peptide-heavy chain-linker-light chain-(His)(5) tail. The linker is three repeats from the C-terminal repetitive sequence of eukaryotic RNA polymerase II. This linker acts as a tag; it is the antigen for the monoclonal antibody Jel352. The codon usage was maximized for E.coli expression, and many unique restriction endonuclease sites were incorporated. The scFv gene incorporated into pT7-7 was highly expressed, yielding 10-30% of the cell protein as the scFv, which was found in inclusion bodies with the leader peptide cleaved. Jel42 scFv was purified by denaturation/renaturation yielding preparations with K(d) values from 20 to 175 nM. However, based upon an assessment of the amount of active refolded scFv, the binding dissociation constant was estimated to be 2.7 +/- 2.0 nM compared with 2.8 +/- 1.6 and 3.7 +/- 0.3 nM previously determined for the Jel42 antibody and Fab fragment respectively. The effect of mutation of the antigen HPr on the binding constant of the scFv was very similar to the properties determined for the antibody and the Fab fragment. It was concluded that the small percentage ( approximately 6%) of refolded scFv is a true mimic of the Jel42 binding domain and that the incorrectly folded scFv cannot be detected in the binding assay.
Development, principles, and applications of automated ice fabric analyzers (2003)

We review the recent development of automated techniques to determine the fabric and texture of polycrystalline ice. The motivation for the study of ice fabric is first outlined. After a brief introduction to the relevant optical concepts, the classic manual technique for fabric measurement is described, along with early attempts at partial automation. Then, the general principles behind fully automated techniques are discussed. We describe in some detail the similarities and differences of the three modern instruments recently developed for ice fabric studies. Next, we discuss briefly X-ray, radar, and acoustic techniques for ice fabric characterization. We also discuss the principles behind automated optical techniques to measure fabric in quartz rock samples. Finally, examples of new applications that have been facilitated by the development of the ice fabric instruments are presented.
Perception of ultrasonic haptic feedback on the hand (2014)

Ultrasonic haptic feedback is a promising means of providing tactile sensations in mid-air without encumbering the user with an actuator. However, controlled and rigorous HCI research is needed to understand the basic characteristics of perception of this new feedback medium, and so how best to utilise ultrasonic haptics in an interface. This paper describes two experiments conducted into two fundamental aspects of ultrasonic haptic perception: 1) localisation of a static point and 2) the perception of motion. Understanding these would provide insight into 1) the spatial resolution of an ultrasonic interface and 2) what forms of feedback give the most convincing illusion of movement. Results show an average localisation error of 8.5mm, with higher error along the longitudinal axis. Convincing sensations of motion were produced when travelling longer distances, using longer stimulus durations and stimulating multiple points along the trajectory. Guidelines for feedback design are given.
Fast phase transitions induced by picosecond electrical pulses on phase change memory cells (2008)

The reversible and fast phase transitions induced by picosecond electrical pulses are observed in the nanostructured GeSbTe materials, which provide opportunities in the application of high speed nonvolatile random access memory devices. The mechanisms for fast phase transition are discussed based on the investigation of the correlation between phase transition speed and material size. With the shrinkage of material dimensions, the size effects play increasingly important roles in enabling the ultrafast phase transition under electrical activation. The understanding of how the size effects contribute to the phase transition speed is of great importance for ultrafast phenomena and applications.