gebhart/patrepeval huggingface dataset:
Genetic Heterogeneity of Hepatitis C Virus: Quasispecies and Genotypes (1995)

Worldwide, HCV is a major etiologic agent of chronic hepatitis that may lead to the development of liver cirrhosis and hepatocellular carcinoma. Thus, significant morbidity and mortality is caused by HCV infection and effective control measures against the spread of this virus are needed. Originally, the extent of genetic heterogeneity of HCV was not fully appreciated. However, the breadth of the genetic heterogeneity of HCV is great, and this may have important implications in diagnosis, pathogenesis, treatment, and vaccine development. In an infected individual the HCV genome population circulates as a quasispecies distribution of closely related yet heterogeneous RNA sequences centered around one dominant sequence. The dominant sequence, as well as the consensus sequence, changes sequentially during the course of the infection. A hypervariable region (HVR1) within one of the envelope proteins of HCV (E2) evolves very rapidly. Patients infected with HCV mount a humoral immune response to epitopes of HVR1. However, sequential changes in the consensus sequence of HVR1 during infection result in the generation of variants that are not recognized by preexisting antibodies. This might represent a mechanism by which HCV evades host immune surveillance and establishes and maintains persistent infection. It will be important to determine whether HVR1 of HCV, as was found for the V3 loop of HIV, contains epitopes that elicit neutralizing antibodies against HCV. Furthermore, it will be important to determine whether the quasispecies nature of HCV helps the virus evade the cytotoxic T-cell response of the host. Analysis of complete or partial HCV genomic sequences revealed that HCV exists as multiple, distinct genotypes. A total of nine major genetic groups and at least 30 subgroups have been recognized. To evaluate the current classification of HCV genotypes, we performed phylogenetic analyses of complete and partial nucleotide sequences from isolates that represent all published variants of HCV. Analysis of complete HCV sequences, which represent three major genetic groups, supports the currently used genotype classification scheme. However, analysis of the partial genomic regions (ie, C, E1, and NS5b) of HCV isolates that represent all recognized variants of HCV demonstrates that the genetic relatedness among some of the genotypes was not equivalent in the different gene regions. Furthermore, the distinction among isolates, subtypes, and types of HCV was not always clear. This finding might reflect the shortcomings of analyzing only limited gene regions or may reflect the wide spectrum of genetic variation of HCV.(ABSTRACT TRUNCATED AT 400 WORDS)
Microbial Ecology of a Crewed Rover Traverse in the Arctic: Low Microbial Dispersal and Implications for Planetary Protection on Human Mars Missions (2015)

Between April 2009 and July 2011, the NASA Haughton-Mars Project (HMP) led the Northwest Passage Drive Expedition (NWPDX), a multi-staged long-distance crewed rover traverse along the Northwest Passage in the Arctic. In April 2009, the HMP Okarian rover was driven 496 km over sea ice along the Northwest Passage, from Kugluktuk to Cambridge Bay, Nunavut, Canada. During the traverse, crew members collected samples from within the rover and from undisturbed snow-covered surfaces around the rover at three locations. The rover samples and snow samples were stored at subzero conditions (-20°C to -1°C) until processed for microbial diversity in labs at the NASA Kennedy Space Center, Florida. The objective was to determine the extent of microbial dispersal away from the rover and onto undisturbed snow. Interior surfaces of the rover were found to be associated with a wide range of bacteria (69 unique taxa) and fungi (16 unique taxa). In contrast, snow samples from the upwind, downwind, uptrack, and downtrack sample sites exterior to the rover were negative for both bacteria and fungi except for two colony-forming units (cfus) recovered from one downwind (1 cfu; site A4) and one uptrack (1 cfu; site B6) sample location. The fungus, Aspergillus fumigatus (GenBank JX517279), and closely related bacteria in the genus Brevibacillus were recovered from both snow (B. agri, GenBank JX517278) and interior rover surfaces. However, it is unknown whether the microorganisms were deposited onto snow surfaces at the time of sample collection (i.e., from the clothing or skin of the human operator) or via airborne dispersal from the rover during the 12-18 h layovers at the sites prior to collection. Results support the conclusion that a crewed rover traveling over previously undisturbed terrain may not significantly contaminate the local terrain via airborne dispersal of propagules from the vehicle.
The Impacts of Conflicts on Requirements Uncertainty and Project Performance (2004)

Conflict is a pervasive phenomenon that permeates information systems development and implementation. The literature has indicated that conflicts, due to their association with negative emotion, will negatively influence IS project development, even after controlling for the effects of conflict management and resolution; however, the negative emotional characteristic of conflict alone has a limited explanatory power of IS project success. The purpose of this study is to provide additional insight, by including requirement uncertainty as the mediator variable, of the impacts of conflicts on project performance. Surveys were sent to Taiwan’s top 1600 companies and the results support the hypotheses. The management implications are discussed.
Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells (2000)

The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis. The flt3 ligand (flt3L) is a growth factor for hematopoietic progenitors and induces hematopoietic progenitor and stem cell mobilization in vivo. In addition, when mice are treated with flt3L immature B cells, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo. To further elucidate the role of flt3L in hematopoiesis, mice lacking flt3L (flt3L−/−) were generated by targeted gene disruption. Leukocyte cellularity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), and spleen. Thymic cellularity, blood hematocrit, and platelet numbers were not affected. Significantly reduced numbers of myeloid and B-lymphoid progenitors were noted in the BM of flt3L−/− mice. In addition a marked deficiency of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c++ CD8−) and lymphoid-related (CD11c++ CD8+) DC numbers were affected. We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes.
Integrated web and telephone service creation (2002)

We describe a system for creating, maintaining, and analyzing interactive services that require access from multiple devices. The system augments the infrastructure of the World Wide Web with Mawl, an application-oriented language for specifying form-based services in a device-independent manner, and TelePortal, a software/hardware platform that enables telephone access to Web content via standard interactive voice response (IVR) platforms. Service creators link service logic and presentation with templates written in an extension of the HyperText Markup Language (HTML). HTML is extended with marks for dynamic content (Meta-HTML) and with marks specific to a user interface or access device. Documents to be interpreted by TelePortal are written in the Phone Markup Language (PML). Together, Mawl and TelePortal provide a new way to create integrated services, as well as IVR services. The ability to develop such services in a single environment appears to be unique.
5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins. (1994)

A short, proline-rich region spanning residues 566-577 in human 5-lipoxygenase is a binding site for the Src homology 3 (SH3) domain of growth factor receptor-bound protein 2 (Grb2), an "adaptor" protein for tyrosine kinase-mediated cell signaling. Purified 5-lipoxygenase bound to glutathione S-transferase fusion products of Grb2 and a truncated version of Grb2 containing its SH3 domain. A peptide corresponding to the proline-rich, SH3-binding motif inhibited formation of the 5-lipoxygenase.Grb2 complex in vitro. The peptide also inhibited the redistribution of 5-lipoxygenase from the cytosol to the membrane in intact or permeabilized neutrophils activated by calcium ionophore A23187. 5-Lipoxygenase did not bind to the SH3 domains of other signaling proteins, such as GTPase-activating protein and phospholipase C gamma; however, it bound to certain cytoskeletal proteins including alpha-actinin and actin. 5-Lipoxygenase contains a consensus guanine nucleotide-binding site at residues 296-299, and guanine nucleotides inhibit 5-lipoxygenase activity in vitro. Our results suggest that 5-lipoxygenase may have a previously unrecognized role in tyrosine kinase signaling, distinct from its catalysis of lipid mediator formation. Our results also clarify the molecular basis for compartmentalization and translocation of 5-lipoxygenase in myeloid cells, implying that it binds to proteins other than its activating protein.
An extended Kalman filter for quaternion-based orientation estimation using MARG sensors (2002)

Presents an extended Kalman filter for real-time estimation of rigid body orientation using the newly developed MARG (magnetic, angular rate, and gravity) sensors. Each MARG sensor contains a three-axis magnetometer, a three-axis angular rate sensor, and a three-axis accelerometer. The filter represents rotations using quaternions rather than Euler angles, which eliminates the long-standing problem of singularities associated with attitude estimation. A process model for rigid body angular motions and angular rate measurements is defined. The process model converts angular rates into quaternion rates, which are integrated to obtain quaternions. The Gauss-Newton iteration algorithm is utilized to find the best quaternion that relates the measured accelerations and earth magnetic field in the body coordinate frame to calculated values in the earth coordinate frame. The best quaternion is used as part of the measurements for the Kalman filter. As a result of this approach, the measurement equations of the Kalman filter become linear, and the computational requirements are significantly reduced, making it possible to estimate orientation in real time. Extensive testing of the filter with synthetic data and actual sensor data proved it to be satisfactory. Test cases included the presence of large initial errors as well as high noise levels. In all cases the filter was able to converge and accurately track rotational motions.
ATM-mediated Transcriptional Elevation of Prion in Response to Copper-induced Oxidative Stress (2008)

Increasing evidence suggests that the cellular prion protein (PrP(C)) plays a protective role in response to oxidative stress, but the molecular mechanism is unclear. Here, we demonstrate that murine neuro-2a and human HeLa cells rapidly respond to an increase of intracellular copper concentration by up-regulating ataxia-telangiectasia mutated (ATM)-mediated transcription of PrP(C). Copper stimulation activates ATM by phosphorylation at Ser-1981, which leads to phosphorylation of p53 at Ser-15 and the initiation of the mitogen-activated protein kinase kinase/extracellular-related kinases/extracellular-related kinases (MEK/ERK)/Sp1 pathway. As results, Sp1 and p53 bind to the PrP promoter, leading to increase PrP(C) expression. Elevated PrP(C) correlates with reduction of intracellular copper concentration and suppression of Cu(II)-induced accumulation of reactive oxygen species and cell death. Depletion of PrP(C), ATM, p53, and/or Sp1 further demonstrates that ATM is a key regulatory protein to promote activation of p53 and Sp1 leading to PrP(C) elevation, which is required to reduce Cu(II) toxic effects and may play an important role in modulation of intracellular copper concentration.
Tuberculosis in Wild and Domestic Mammals (2014)

Different animal species vary in their susceptibilities to infection by the different types of virulent tubercle bacilli: Mycobacterium tuberculosis, M. africanum, M. bovis, and M. avium. Liquefication promotes extracellular multiplication of tubercle bacilli to tremendous numbers, and cavity formation allows these bacilli to spread through the air passages to other parts of the lung and to other people. When pasteurization was adopted, there was usually a concomitant decrease in tuberculosis in children. Tubercle bacilli that are inhaled usually lodge in alveolar spaces, where they are ingested by alveolar macrophages. When the organism multiplies within the phagocyte, the host cell may die, resulting in the development of a microscopic tubercle. Wild mammals found to have tuberculous lesions at necropsy after natural death are usually without prior suspicion of tuberculosis. Tuberculous lesions from camelines, cervines, and wild bovines closely resemble those of domestic bovines. In nonhuman primates, M. bovis, M. africanum, and M. tuberculosis can produce extensive disease involving the parenchyma of the lung as well as extrapulmonary tissues. Recently, there has been increased interest in the isolation of M. avium complex serovars 1, 4, and 8 from patients with AIDS and from nonimmunocompromised patients. Some of the same serovars have been isolated from domestic and wild animals. Although M. avium has been isolated from environmental specimens (i.e., soil and water), no definitive information on a common source(s) of these bacteria for animals and humans is available.
Relaxin Modulates Cardiac Fibroblast Proliferation, Differentiation, and Collagen Production and Reverses Cardiac Fibrosis in Vivo (2004)

Cardiac fibrosis is a key component of heart disease and involves the proliferation and differentiation of matrix-producing fibroblasts. The effects of an antifibrotic peptide hormone, relaxin, in inhibiting this process were investigated. We used rat atrial and ventricular fibroblasts, which respond to profibrotic stimuli and express the relaxin receptor (LGR7), in addition to two in vivo models of cardiac fibrosis. Cardiac fibroblasts, when plated at low density or stimulated with TGF-beta or angiotensin II (Ang II), accelerated fibroblast differentiation into myofibroblasts, as demonstrated by significantly increased alpha-smooth muscle actin expression, collagen synthesis, and collagen deposition (by up to 95% with TGF-beta and 40% with Ang II; all P < 0.05). Fibroblast proliferation was significantly increased by 10(-8) m and 10(-7) m Ang II (63-75%; P < 0.01) or 0.1-1 microg/ml IGF-I (27-40%; P < 0.05). Relaxin alone had no marked effect on these parameters, but it significantly inhibited Ang II- and IGF-I-mediated fibroblast proliferation (by 15-50%) and Ang II- and TGF-beta-mediated fibroblast differentiation, as detected by decreased expression of alpha-smooth muscle actin (by 65-88%) and collagen (by 60-80%). Relaxin also increased matrix metalloproteinase-2 expression in the presence of TGF-beta (P < 0.01) and Ang II (P < 0.05). Furthermore, relaxin decreased collagen overexpression when administered to two models of established fibrotic cardiomyopathy, one due to relaxin deficiency (by 40%; P < 0.05) and the other to cardiac-restricted overexpression of beta2-adrenergic receptors (by 58%; P < 0.01). These coherent findings indicate that relaxin regulates fibroblast proliferation, differentiation, and collagen deposition and may have therapeutic potential in diseased states characterized by cardiac fibrosis.
Steric inhibition of human immunodeficiency virus type-1 Tat-dependent trans-activation in vitro and in cells by oligonucleotides containing 2'-O-methyl G-clamp ribonucleoside analogues (2003)

We report the synthesis of a novel 2'-O-methyl (OMe) riboside phosphoramidite derivative of the G-clamp tricyclic base and incorporation into a series of small steric blocking OMe oligonucleotides targeting the apical stem-loop region of human immunodeficiency virus type 1 (HIV-1) trans- activation-responsive (TAR) RNA. Binding to TAR RNA is substantially enhanced for certain single site substitutions in the centre of the oligonucleotide, and doubly substituted anti-TAR OMe 9mers or 12mers exhibit remarkably low binding constants of <0.1 nM. G-clamp-containing oligomers achieved 50% inhibition of Tat-dependent in vitro transcription at approximately 25 nM, 4-fold lower than for a TAR 12mer OMe oligonucleotide and better than found for any other oligonucleotide tested to date. Addition of one or two OMe G-clamps did not impart cellular trans-activation inhibition activity to cellularly inactive OMe oligonucleotides. Addition of an OMe G-clamp to a 12mer OMe-locked nucleic acid chimera maintained, but did not enhance, inhibition of Tat-dependent in vitro transcription and cellular trans-activation in HeLa cells. The results demonstrate clearly that an OMe G-clamp has remarkable RNA-binding enhancement ability, but that oligonucleotide effectiveness in steric block inhibition of Tat-dependent trans-activation both in vitro and in cells is governed by factors more complex than RNA-binding strength alone.
Architectural Control in “Living” Free Radical Polymerizations: Preparation of Star and Graft Polymers (1995)

The use of multifunctional initiators such as 1 in a novel “living” free radical polymerization process allows the preparation of low polydispersity star and graft copolymers with accurate control over the molecular weight of each arm.
Multilayer-Assembled Microchip for Enzyme Immobilization as Reactor Toward Low-Level Protein Identification (2005)

A microchip reactor has been developed on the basis of a layer-by-layer approach for fast and sensitive digestion of proteins. The resulting peptide analysis has been carried out by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Natural polysaccharides, positively charged chitosan (CS), and negatively charged hyaluronic acid (HA) were multilayer-assembled onto the surface of a poly(ethylene terephthalate) (PET) microfluidic chip to form a microstructured and biocompatible network for enzyme immobilization. The construction of CS/HA assembled multilayers on the PET substrate was characterized by AFM imaging, ATR-IR, and contact angle measurements. The controlled adsorption of trypsin in the multilayer membrane was monitored using a quartz crystal microbalance and an enzymatic activity assay. The maximum proteolytic velocity of the adsorbed trypsin was approximately 600 mM/min mug, thousands of times faster than that in solution. BSA, myoglobin, and cytochrome c were used as model substrates for the tryptic digestion. The standard proteins were identified at a low femtomole per analysis at a concentration of 0.5 ng/muL with the digestion time <5s. This simple technique may offer a potential solution for low-level protein analysis.
Effect of rotation and translation on the expected benefit of an ideal method to correct the eye’s higher-order aberrations (2001)

An ideal correcting method, such as a customized contact lens, laser refractive surgery, or adaptive optics, that corrects higher-order aberrations as well as defocus and astigmatism could improve vision. The benefit achieved with this ideal method will be limited by decentration. To estimate the significance of this potential limitation we studied the effect on image quality expected when an ideal correcting method translates or rotates with respect to the eye's pupil. Actual wave aberrations were obtained from ten human eyes for a 7.3-mm pupil with a Shack-Hartmann sensor. We computed the residual aberrations that appear as a result of translation or rotation of an otherwise ideal correction. The model is valid for adaptive optics, contact lenses, and phase plates, but it constitutes only a first approximation to the laser refractive surgery case where tissue removal occurs. Calculations suggest that the typical decentrations will reduce only slightly the optical benefits expected from an ideal correcting method. For typical decentrations the ideal correcting method offers a benefit in modulation 2-4 times higher (1.5-2 times in white light) than with a standard correction of defocus and astigmatism. We obtained analytical expressions that show the impact of translation and rotation on individual Zernike terms. These calculations also reveal which aberrations are most beneficial to correct. We provided practical rules to implement a selective correction depending on the amount of decentration. An experimental study was performed with an aberrated artificial eye corrected with an adaptive optics system, validating the theoretical predictions. The results in a keratoconic subject, also corrected with adaptive optics, showed that important benefits are obtained despite decentrations in highly aberrated eyes.
The hybrid model: a new pharmacokinetic model for computer-controlled infusion pumps (1994)

Classical pharmacokinetic models used in computer-controlled infusion pumps (CCIPs) assume instantaneous mixing of drug in blood; however, the average recirculation time of blood in man is approximately one minute. To investigate the effects of recirculation dynamics on the transient performance of CCIPs, we propose a hybrid physiologically-based pharmacokinetic model for the narcotic alfentanil. A three-compartment model was derived from the response of the hybrid model to a short infusion and used to compute a CCIP infusion targeting 450 micrograms/l. For this infusion, the hybrid model predicts that the arterial plasma concentration will overshoot the target concentration by 39 percent with an average prediction error of 3 percent. The overshoot and average prediction error increase to 100 and 25 percent respectively when using a three-compartment pharmacokinetic model derived from a bolus. The overshoot can be reduced by decreasing the maximum possible infusion rate, or by increasing the zero-order hold infusion interval.