gebhart/patrepeval huggingface dataset:
Photocross-linking of the NH2-terminal Region of Taq MutS Protein to the Major Groove of a Heteroduplex DNA (1997)

The MutS DNA mismatch repair protein recognizes heteroduplex DNAs containing mispaired or unpaired bases. To identify regions of MutS protein in close proximity to the heteroduplex DNA, we have utilized the photoactivated cross-linking moiety 5-iododeoxyuridine (5-IdUrd). Nucleoprotein complexes of Thermus aquaticus MutS protein bound to monosubstituted 5-IdUrd-containing heteroduplex DNAs were cross-linked with long-wavelength ultraviolet light. Positioning of the 5-IdUrd moiety at one of three positions within the DNA bulge, two nucleotides upstream or three nucleotides downstream of the unpaired base, resulted in an identical subset of cross-linked peptides as determined by proteolytic fingerprinting. The tryptic peptide cross-linked to an unpaired 5-IdUrd residue was determined by peptide sequencing to correspond to a highly conserved region spanning residues 25-49. Cross-linking to the bulge nucleotide occurred at Phe-39, indicating that this residue contacts, or is in close proximity to, the unpaired base of a heteroduplex DNA. Site-directed mutagenesis resulting in the substitution of Ala for Phe-39 reduced the affinity of the mutant protein for heteroduplex DNA by roughly 3 orders of magnitude, but had no apparent effect on its ability to dimerize, its thermostability, or its ATPase activity. These results implicate the region in the vicinity of Phe-39 as being crucial for heteroduplex DNA binding by Taq MutS protein.
The quasispecies of hepatitis C virus and the host immune response (1997)

Infection with hepatitis C virus (HCV) represents an important public health problem worldwide, because it is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) [110]. Approximately 1% of the world population is infected with HCV, although geographic variation exists and further epidemiological studies are needed to draw a conclusive epidemiological map of HCV infection. The most striking and alarming feature of HCV infection is its high rate of progression to chronicity. Chronic hepatitis C develops in more than 80% of the acutely infected individuals and about 20-35% of them develop cirrhosis during the course of the disease [1, 2, 19, 25]. Currently, HCV-related end-stage liver disease is the leading indication of orthotopic liver transplantation worldwide [141]. Prospective studies of post-transfusion non-A, non-B hepatitis have been fundamental in unravelling the natural history of HCV infection [ 122]. Despite its inevitable progression, the course of chronic hepatitis C is usually indolent and subclinical. The average time to the clinical presentation of chronic hepatitis is about 10 years, to cirrhosis 20 years and to the development of HCC 30 years [64, 133]. In some patients, however, the course of chronic HCV infection may be rapidly progressive, leading to liver-related death within 5 years after infection ([1] and H.J. Alter, unpublished data). The overall rate of liver-related mortality varied markedly in different prospective studies, with a prevalence ranging from 1.6 to 15% [122]. A controlled clinical study conducted by Seeff et al. [111] in elderly subjects who underwent open-heart surgery failed to demonstrate an increase in the mortality rate after a mean follow-up of 18 years for patients who had developed post-transfusion hepatitis C compared to HCV-uninfected control subjects. By contrast, Tong et al. [133] showed a mortal-
Determination of amputation level in ischaemic limbs using tcPO2 measurement (2005)

Our study showed that tcPO2 is a reliable indicator of local ischemia. The integration of this parameter with other personal clinical criteria may be a valuable help to the surgeon in decision making.
Absence of 12/15-Lipoxygenase Expression Decreases Lipid Peroxidation and Atherogenesis in Apolipoprotein E–Deficient Mice (2001)

Enzymatic action of 12/15-LO contributes significantly to atherosclerotic lesion initiation and propagation in this murine model. Strong positive correlations exist between lesion size, isoprostane levels, and MDA-LDL autoantibodies, providing in vivo evidence for an enzymatic (12/15-LO) component to lipid peroxidation and atherogenesis.
A 64,000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen. (1985)

Human cytomegalovirus contains approximately 30 to 35 structural polypeptides. Although antibodies to several of these proteins are made during natural infection, their relationship to T cell recognition of this virus and subsequent control of infection is poorly understood. We have purified one of these proteins (HCMVgp64) that is found in abundance in infected cell lysates in order to delineate the relationship of single viral proteins to the immune response caused by the virus. HCMVgp64 induced T cell reactivity only in individuals with serologic evidence of past infection. In addition, HCMVgp64 elicited similar in vitro immune reactions as the whole virus including T cell proliferation, interleukin 2 production, and receptor expression as well as interferon production. These studies suggest that single proteins of HCMV such as HCMVgp64 are capable of inducing T cell responses and may be important in the development of immune reactivity to HCMV.
In vitro differentiation of epithelial cells from cervical neoplasias resembles in vivo lesions. (1990)

Cell lines derived from cervical neoplasias, as well as cells from normal cervix and neonatal foreskin were examined in an in vitro culture system (raft system) that allows for stratification and differentiation of epithelial cells at an air-liquid interface. Epithelial cells from human foreskin and ectocervix were observed to differentiate in a manner histologically similar to normal epithelium in vivo as indicated by a single layer of basal cells with a defined mid and upper zone. In contrast, cells expanded from cervical squamous carcinoma explants showed total absence of normal differentiation in the raft system with numerous cells in the upper portion of the stratum exhibiting mitotic figures. Cell cultures derived from low grade cervical intraepithelial neoplasia and condyloma acuminata exhibited partial differentiation in addition to perinuclear clearing, binucleate cells and individual cell keratinization. These studies show that in the raft system, cultured cells derived from tissue biopsies can duplicate many of the histological features observed in cervical neoplasias. In addition, epithelial cells derived from normal fetal ectocervix and electroporated with cloned human papillomavirus (HPV) type 16 DNA exhibited abnormal differentiation patterns similar to those of cervical intraepithelial neoplasia in vivo. This model system will thus be useful for examining the effects of HPV infection on epithelial maturation and for investigating the role of other factors in the progression of cervical malignancies.
Laser Doppler Vibrometry for Structural Dynamic Characterization of Rotating Machinery (2013)

Laser Doppler Vibrometry (LDV) is a well established technique able to accurately measure vibration velocity of any kind of structure in remote, i.e. non-intrusive way, this allowing to overcome the problem of mass loading, typical of contact sensors as accelerometers and strain-gauges, which has strong influence in case of lightweight structures. Moreover, the possibility of driving automatically the laser beam, by means of moving mirrors controlled with galvanometer servo-actuators, permits to perform scanning measurements at different locations with high spatial resolution and reduced testing time and easily measure the operational deflection shapes (ODS) of the scanned surface. The exploitation of the moving mirrors has allowed to drive the laser beam in a continuous way making it to scan continuously over the structure surface and cover it completely. This way of operation, named Continuous Scanning LDV, permits to perform full-field measurements, the LDV output carrying simultaneously the time-and spatial-dependent information related to the structural vibration. A complementary strategy making use of the LDV coupled with moving mirrors is the so called Tracking LDV, where the laser beam is driven to follow a moving object whose trajectory must be known a priori or measured during operation (e.g. via an encoder in the case of rotating structures). In this paper some applications of the Tracking Laser Doppler Vibrometry (TLDV) and Continuous Scanning Laser Doppler Vibrometry (CSLDV) will be described they concerning, specifically modal and vibrational analysis of rotating structures.
Pain Sensations and Reactions (1953)

Journal Article Pain Sensations and Reactions Get access Pain Sensations and Reactions. By James D. Hardy, Ph.D., Associate Professor of Physiology, Cornell University Medical College; Harold G. Wolff, M.D., Professor of Medicine (Neurology), Cornell University Medical College; Helen Goodell, B.S., Research Fellow in Medicine, Cornell University Medical College. Cloth; price $6.50. Pp. 435; illus. 130. Williams & Wilkins Co., Baltimore, Md., 1952. Physical Therapy, Volume 33, Issue 6, 1 May 1953, Page 327, https://doi.org/10.1093/ptj/33.6.327 Published: 01 May 1953
RNA Based Gene Therapy for Dominantly Inherited Diseases (2006)

There are numerous examples in the literature of gene therapy applications for recessive disorders. There are precious few instances, however, of studies conducted to treat dominantly inherited pathologies. The reasons are simple: there are fewer cases of dominantly inherited diseases on one hand, but mostly it is far easier to correct recessive mutations than dominant ones. Typically recessive mutations cause a loss of (or reduced) gene function which can be compensated for by introduction of a replacement allele into the cell. In contrast, dominant negative mutations not only display impaired function, but also exhibit a novel one that is pathologic to the cell. Treating these conditions by gene therapy implies silencing the dominant allele without altering the expression of the wild-type gene. We describe here different strategies aimed at silencing dominant mutations through mRNA destruction and provide examples of their application to known autosomal dominant diseases. An overview of the most common molecular tools (antisense DNA and RNA, ribozymes and RNA interference) suitable to utilize these strategies is also presented and we discuss the relevant aspects involved in the choice of a particular approach in a gene therapy experiment.
Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure (2015)

Human pluripotent stem cells (PSCs) show epiblast-type pluripotency that is maintained with ACTIVIN/FGF2 signaling. Here, we report the acquisition of a unique stem cell phenotype by both human ES cells (hESCs) and induced pluripotent stem cells (iPSCs) in response to transient (24-36 h) exposure to bone morphogenetic protein 4 (BMP4) plus inhibitors of ACTIVIN signaling (A83-01) and FGF2 (PD173074), followed by trypsin dissociation and recovery of colonies capable of growing on a gelatin substratum in standard medium for human PSCs at low but not high FGF2 concentrations. The self-renewing cell lines stain weakly for CDX2 and strongly for NANOG, can be propagated clonally on either Matrigel or gelatin, and are morphologically distinct from human PSC progenitors on either substratum but still meet standard in vitro criteria for pluripotency. They form well-differentiated teratomas in immune-compromised mice that secrete human chorionic gonadotropin (hCG) into the host mouse and include small areas of trophoblast-like cells. The cells have a distinct transcriptome profile from the human PSCs from which they were derived (including higher expression of NANOG, LEFTY1, and LEFTY2). In nonconditioned medium lacking FGF2, the colonies spontaneously differentiated along multiple lineages, including trophoblast. They responded to PD173074 in the absence of both FGF2 and BMP4 by conversion to trophoblast, and especially syncytiotrophoblast, whereas an A83-01/PD173074 combination favored increased expression of HLA-G, a marker of extravillous trophoblast. Together, these data suggest that the cell lines exhibit totipotent potential and that BMP4 can prime human PSCs to a self-renewing alternative state permissive for trophoblast development. The results may have implications for regulation of lineage decisions in the early embryo.
GD3‐replica peptides selected from a phage peptide library induce a GD3 ganglioside antibody response (2006)

GD3-replica peptides were obtained from a phage peptide library and an anti-GD3 monoclonal antibody (Mab) (4F6), and anti-GD3 Mabs were generated by immunizing a peptide GD3P4. A Mab, 3D2 was found to recognize GD3 by immunohistochemical approaches. Amino acid analysis of heavy and light chain variable regions of 4F6 and 3D2 showed that the respective chains had the same length, and only a few different amino acid substitutions were found. The present data indicate that the immunogenic GD3P4 is processed in a certain size and exposed on the antigen-presenting cells with a molecular shape quite similar to that of the GD3 epitope in 4F6.
Ethidium Bromide as a Cooperative Effector of a DNA Structure (1972)

A salt-induced cooperative conformational transition of a synthetic DNA, poly(dG-dC), is reversed by addition of ethidium bromide. Binding of the dye at high salt concentrations is highly cooperative. Circular dichroism spectra of the complex and the kinetic data support a model for this cooperative binding that is formally equivalent to the "allosteric" one proposed for oligomeric proteins by Monod et al. Thus, double-helical DNA of at least one defined sequence can undergo a cooperative conformational change in solution, with simple salts and drug molecules as antagonistic effectors. Such transitions may be involved in regulatory phenomena operating directly at the level of nucleic acid structure.
Error Analysis for Estimation of Trace Vapor Concentration Pathlength in Stack Plumes (2003)

Near-infrared hyperspectral imaging is finding utility in remote sensing applications such as detection and quantification of chemical vapor effluents in stack plumes. Optimizing the sensing system or quantification algorithms is difficult because reference images are rarely well characterized. The present work uses a radiance model for a down-looking scene and a detailed noise model for dispersive and Fourier transform spectrometers to generate well-characterized synthetic data. These data were used with a classical least-squares-based estimator in an error analysis to obtain estimates of different sources of concentration-pathlength quantification error in the remote sensing problem. Contributions to the overall quantification error were the sum of individual error terms related to estimating the background, atmospheric corrections, plume temperature, and instrument signal-to-noise ratio. It was found that the quantification error depended strongly on errors in the background estimate and second-most on instrument signal-to-noise ratio. Decreases in net analyte signal (e.g., due to low analyte absorbance or increasing the number of analytes in the plume) led to increases in the quantification error as expected. These observations have implications on instrument design and strategies for quantification. The outlined approach could be used to estimate detection limits or perform variable selection for given sensing problems.
Reconfigurable Factory-wide Resource-based System Integration for Control (2006)

Next generation of manufacturing systems will need to be reconfigurable-capable of producing exactly the volume and type of products desired, exactly when demanded by the market- in order to accommodate the rapid changes in product design necessitated by ever-changing customer demands. The corresponding factory control systems will consist of a conglomeration of hardware and software resources that must work together to achieve factory-wide targets of throughput and quality. This paper addresses the requirement of consolidation of software and hardware control with the design of a factory-wide resource-based reconfigurable control system. This system extends reconfigurable software event-based control by considering a manufacturing system as a set of decentralized resources of both hardware and software instead of a set of dissimilar components. Central to the solution is a mechanism for embedding control rules in a database to determine appropriate actions corresponding to events
Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways (2011)

More than 2% of adults harbor a pancreatic cyst, a subset of which progresses to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and solid pseudopapillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10 ± 4.6, 27 ± 12, 16 ± 7.6, and 2.9 ± 2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of the von Hippel-Lindau gene (VHL), a key component of the VHL ubiquitin ligase complex that has previously been associated with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.
The Gene for Heparin-Binding Epidermal Growth Factor-Like Growth Factor is Stress-Inducible: Its Role in Cerebral Ischemia (1999)

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor-alpha (TGF-alpha) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the likelihood that HB-EGF is a neuroprotective factor in cerebral ischemia.
3D Optical flow analysis of a pulsed contrast agent in the bloodstream. Application to virtual angiography and Magnetic Particle Imaging (2015)

Nowadays, cardiovascular diseases remain a subject of major concern for healthcare and an important economic burden in developed countries. With the progress of medicine, medical imaging systems have allowed to detect cardiovascular pathologies at an early stage, and to monitor their evolution through advanced data analysis tools. The measurement of blood flow, in particular, is a precious information for a physician. Today, numerous blood flow estimation techniques have been developed and applied in clinical routines and medical research. One of them resorts to the injection of a contrast product in the arterial blood. The propagation of tracer throughout the bloodstream and its spatiotemporal modulation delivers the information of blood flow patterns in 2D image sequences. However, 3D+T contrast systems have not reached a clinical stage yet. The goal of this thesis is to provide the future 3D+T contrast systems with a general framework of blood flow estimation. A variational formulation of optical flow is presented, including different prior knowledge concerning the contrast concentration, and blood flow properties inspired from fluid mechanics. Subsequently, the fruitfulness of the optical flow estimation algorithm is evaluated on CFD based virtual angiography, with a sensitivity analysis on flow rate and algorithm parameters. Finally, a simplified version of the optical flow approach is tested on 3D+T early MPI evaluation. First, an in vitro flow experiment is proposed with a modulated contrast injection and secondly a blood flow analysis on in vivo data is demonstrated. All in all, this thesis investigates the original subject of blood flow estimation and the analysis of 3D blood flow patterns. The technical contribution consists in the creation of a new optical flow algorithm dedicated to time-resolved contrast information in the cardiovascular system. The underlying clinical contribution is a full pipeline for blood flow estimation, starting from the acquisition procedure with contrast modulation, to the optical flow computation, and the in silico validation.
Cellular processing of a multibranched lysine core with tumor antigen peptides and presentation of peptide epitopes recognized by cytotoxic T lymphocytes on antigen-presenting cells. (2002)

We showed that pRL1a multiple antigen peptide (MAP)-sensitized dendritic cell (DC) and P815 cell lysis by pRL1a-specific B-24 CTL was blocked by incubating target cells at 4 degrees C during sensitization. The finding suggested that pRL1a MAP was mostly internalized in DC and P815 cells and produced pRL1a peptide epitopes for presentation with H-2L(d). Furthermore, we showed that sensitization with pRL1a MAP was inhibited by the addition of chloroquine, cycloheximide, and brefeldin A to the culture, but not by the addition of inhibitors for lysosomal proteases or proteasome. Inhibition of sensitization by the addition of chloroquine to the culture suggested the requirement of acidification of the endosomal compartment for pRL1a MAP processing. Inhibition of sensitization by the addition of cycloheximide and brefeldin A to the culture indicated the requirement of newly generated MHC class I antigen molecules and the involvement of transport of the peptide MHC class I complex from the endoplasmic reticulum to the Golgi. The findings suggested that pRL1a MAP in the endosomal compartment leaked to the cytosol, and degraded, and the pRL1a peptide produced was presented by the MHC class I pathway.