gebhart/patrepeval huggingface dataset:
Recovery of infectious virus from full-length cowpox virus (CPXV) DNA cloned as a bacterial artificial chromosome (BAC) (2011)

Transmission from pet rats and cats to humans as well as severe infection in felids and other animal species have recently drawn increasing attention to cowpox virus (CPXV). We report the cloning of the entire genome of cowpox virus strain Brighton Red (BR) as a bacterial artificial chromosome (BAC) in Escherichia coli and the recovery of infectious virus from cloned DNA. Generation of a full-length CPXV DNA clone was achieved by first introducing a mini-F vector, which allows maintenance of large circular DNA in E. coli, into the thymidine kinase locus of CPXV by homologous recombination. Circular replication intermediates were then electroporated into E. coli DH10B cells. Upon successful establishment of the infectious BR clone, we modified the full-length clone such that recombination-mediated excision of bacterial sequences can occur upon transfection in eukaryotic cells. This self-excision of the bacterial replicon is made possible by a sequence duplication within mini-F sequences and allows recovery of recombinant virus progeny without remaining marker or vector sequences. The in vitro growth properties of viruses derived from both BAC clones were determined and found to be virtually indistinguishable from those of parental, wild-type BR. Finally, the complete genomic sequence of the infectious clone was determined and the cloned viral genome was shown to be identical to that of the parental virus. In summary, the generated infectious clone will greatly facilitate studies on individual genes and pathogenesis of CPXV. Moreover, the vector potential of CPXV can now be more systematically explored using this newly generated tool.
MDV3100-08: A phase I open-label, dose-escalation study evaluating the safety, tolerability, and pharmacokinetics of MDV3100 in women with incurable breast cancer. (2012)

TPS668 Background: MDV3100 is a novel, orally administered small molecule that directly binds the androgen receptor (AR) to potently inhibit AR-mediated signaling via three mechanisms: inhibition of androgen binding to AR; inhibition of AR nuclear translocation; and inhibition of nuclear AR association with DNA. MDV3100 is not known to agonize AR signaling, can be taken without prednisone, and demonstrated an overall survival benefit in post-docetaxel prostate cancer at 160 mg/day. AR expression is observed in ~70% of all breast cancer (BCa) regardless of histologic subtypes (estrogen receptor [ER] positive, HER2+, and triple negative [TN] disease). MDV3100 has demonstrated preclinical activity in AR+/TN and AR+/ ER+ BCa and could be a potential therapeutic strategy in patients with AR+ BCa. Methods: This Phase 1 study has 2 stages: a standard 3+3 dose-escalation stage (S1), evaluating safety, tolerability, and pharmacokinetics (PK) of MDV3100, starting at 80 mg MDV3100; and a dose-expansion stage (S2), evaluating the recommended Phase 2 dose in ~15 women with AR+ BCa. All patients must have received ≥2 chemotherapy-containing regimens for their incurable BCa, or ≥3 anti-HER2 containing regimens for their incurable HER2+ BCa to be eligible; ER+ patients must be post-menopausal. In S1, patients will receive their assigned dose of MDV3100 on Day 1, and PK samples will be collected through Day 8. Daily dosing will begin on Day 8 and will continue until predefined discontinuation criterion is met. Dose-limiting toxicities will be recorded through Day 35 and used to determine the Phase 2 dose. Extensive PK sampling is performed on Days 1 and 50 with predose PK samples collected throughout. In S2, patients with AR+ BCa (defined as 10% or more tumor cells with nuclear AR expression) will take daily MDV3100 at the recommended Phase 2 dose; there is no single dose PK period. Tumor tissue submission is mandatory in S2. Safety and tolerability will be documented by frequent assessments of adverse events, vital signs, and laboratory assessments. Tumor assessments occur at 2 months then approximately every 3 months thereafter. Enrollment of 27 subjects is anticipated.
Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs (2007)

Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent "transcriptional noise." Here, we describe an analysis of 3122 long and full-length, noncoding RNAs ("macroRNAs") from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding RNAs is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the macroRNAs' promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1%-5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these macroRNAs' functions.
Quantum Dot−Aptamer Conjugates for Synchronous Cancer Imaging, Therapy, and Sensing of Drug Delivery Based on Bi-Fluorescence Resonance Energy Transfer (2007)

We report a novel quantum dot (QD)-aptamer(Apt)-doxorubicin (Dox) conjugate [QD-Apt(Dox)] as a targeted cancer imaging, therapy, and sensing system. By functionalizing the surface of fluorescent QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), we developed a targeted QD imaging system (QD-Apt) that is capable of differential uptake and imaging of prostate cancer cells that express the PSMA protein. The intercalation of Dox, a widely used antineoplastic anthracycline drug with fluorescent properties, in the double-stranded stem of the A10 aptamer results in a targeted QD-Apt(Dox) conjugate with reversible self-quenching properties based on a Bi-FRET mechanism. A donor-acceptor model fluorescence resonance energy transfer (FRET) between QD and Dox and a donor-quencher model FRET between Dox and aptamer result when Dox intercalated within the A10 aptamer. This simple multifunctional nanoparticle system can deliver Dox to the targeted prostate cancer cells and sense the delivery of Dox by activating the fluorescence of QD, which concurrently images the cancer cells. We demonstrate the specificity and sensitivity of this nanoparticle conjugate as a cancer imaging, therapy and sensing system in vitro.
Real-time processing of image sources using binary space partitioning (2006)

The current state of the art of virtual reality allows a user to interact with computer-generated visual worlds and provides a high level of realism. The immersion can be increased significantly by simulating in addition the corresponding room acoustics. A correct acoustical impression is reached by the reproduction of binaural signals and at present already satisfies high demand, but for interactive systems it is mostly limited to sources located in the free field, that is, the filters used for computation are applicable for anechoic environments only. Current real-time-capable room acoustical simulations for virtual environments are mostly based on the principles of geometrical acoustics. However, these approaches do not provide an exact reproduction of a room's sound properties under real-time conditions because of high computation demands, and they are therefore limited to the simulation of just plausible sound fields. Hence faster algorithms are required to further enhance the room acoustical simulation. A modification of the commonly known image source method is presented, which reduces the computation demands of this highly time-expensive approach remarkably. Binary space partitioning trees are used for a fast determination of audible image sources, and an efficient data structure with respect to the real-time auralization process is introduced. Thus a faster determination of the binaural room impulse response is obtained, which is essential for a real-time-capable auralization process. In addition, geometrical relations are used more efficiently to prevent the generation of redundant image sources and to increase the performance of this algorithm. Furthermore, experiments have been carried out to show the current hardware limitations for this modified image source method.
High Failure Rate of the ViroSeq HIV-1 Genotyping System for Drug Resistance Testing in Cameroon, a Country with Broad HIV-1 Genetic Diversity (2011)

ABSTRACT The ViroSeq HIV-1 genotyping system is used in many African countries for drug resistance testing. In this study, we used a panel of diverse HIV-1 group M isolates circulating in Cameroon to show that the performance of this assay can be altered by the sequence variation of non-B HIV-1 strains that predominate in African settings.
Enabling Quantitative Analysis in Ambient Ionization Mass Spectrometry: Internal Standard Coated Capillary Samplers (2013)

We describe a sampling method using glass capillaries for quantitative analysis of trace analytes in small volumes of complex mixtures (~1 μL) using ambient ionization mass spectrometry. The internal surface of a sampling glass capillary was coated with internal standard then used to draw liquid sample and so transfer both the analyte and internal standard in a single fixed volume onto a substrate for analysis. The internal standard was automatically mixed into the sample during this process and the volumes of the internal standard solution and sample are both fixed by the capillary volume. Precision in quantitation is insensitive to variations in length of the capillary, making the preparation of the sampling capillary simple and providing a robust sampling protocol. Significant improvements in quantitation accuracy were obtained for analysis of 1 μL samples using various ambient ionization methods.
Serum Urate Levels and Gout Flares (2006)

The failure of allopurinol users to achieve target SUA levels of <6.0 mg/dL may be attributed to lack of awareness of optimal SUA, allopurinol dosing, compliance, and efficacy. Patients who did not achieve target SUA were at increased flare risk.
Identification, molecular cloning and sequence analysis of a gene cluster encoding the Class II fructose 1,6‐bisphosphate aldolase, 3‐phosphoglycerate kinase and a putative second glyceraldehyde 3‐phosphate dehydrogenase of Escherichia coli (1989)

To investigate a possible chromosomal clustering of glycolytic enzyme genes, the complete nucleotide sequence of the 8029 bp insert of Escherichia coli DNA in the ColE1 plasmid pLC33-5 of the Clarke and Carbon collection (Clark and Carbon, 1976) was determined. Genes (pgk, fda) encoding the phosphoglycerate kinase and Class II fructose 1,6-bisphosphate aldolase, respectively, of E. coli were identified. The phosphoglycerate kinase was found to be highly homologous in primary structure to the same enzyme from eukaryotic organisms. A further large open reading frame, designated gapB, was also identified, which on the basis of sequence homology, appears to encode another glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase. This putative gene differs significantly from that (designated gapA) already identified as coding for this enzyme in E. coli and which maps elsewhere on the chromosome. The products, if any, of several other open reading frames remain to be identified.
A human monoclonal antibody specific to placental alkaline phosphatase, a marker of ovarian cancer (2013)

Placental alkaline phosphatase (PLAP) is a promising ovarian cancer biomarker. Here, we describe the isolation, affinity-maturation and characterization of two fully human monoclonal antibodies (termed B10 and D9) able to bind to human PLAP with a dissociation constant (Kd) of 10 and 30 nM, respectively. The ability of B10 and D9 antibodies to recognize the native antigen was confirmed by Biacore analysis, FACS and immunofluorescence studies using ovarian cancer cell lines and freshly-frozen human tissues. A quantitative biodistribution study in nude mice revealed that the B10 antibody preferentially localizes to A431 tumors, following intravenous administration. Anti-PLAP antibodies may serve as a modular building blocks for the development of targeted therapeutic products, armed with cytotoxic drugs, radionuclides or cytokines as payloads.
Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma (2007)

The STAT3 transcription factor is critical for cytokine signaling and the acute phase response, but its role in allergic asthma is largely undefined. To investigate the role of STAT3 in mediating allergic inflammation, we used chemical and genetic approaches to inactivate STAT3 in the airway epithelium of mice. In a murine model of chronic asthma, we demonstrate that the administration of house dust mite (HDM) leads to robust STAT3 activation in the airway epithelium, smooth muscle, and immune cells in the lungs of C57BL/6 mice. To investigate the role of STAT3 in HDM-induced airway inflammation, a conditional knockout of STAT3 in the airway epithelium was generated, e-STAT3-/-. We determined that e-STAT3-/- mice had a significant decrease in HDM-induced airway eosinophilia, lung Th2 accumulation, and chemokines compared with wild-type animals. Importantly, the e-STAT3-/- mice had a significant decrease in airway hyperresponsiveness to methacholine. The administration of two STAT kinase inhibitors diminished STAT3 activation and markedly abrogated the HDM-induced lung inflammation. These findings suggest that STAT3 acts as a novel epithelial regulator of the allergic response by altering Th2 cell recruitment and effector function, and thus, targeting this molecule may provide the basis for a novel asthma therapy.
Precision displacement measurement by active laser heterodyne interferometry (1991)

We demonstrate an active laser heterodyne interferometer which can automatically compensate environmental disturbances and is capable of precision displacement measurement. Two Zeeman He-Ne lasers were employed. Laser II was used as the light source to stabilize the interferometer by using a piezomirror in a feedback loop. The hetereodyne signal of the two lasers was used to directly calibrate mirror displacement, with the wavelength of laser I tuned to compensate change in the interference signal due to displacement only. Separation of the contributions to the interference signal from displacement and external disturbances was accomplished by using polarization optics. This interferometer was used to measure the hysteresis of a piezoelectric transducer (PZT) over a dynamic range of 0.5 microm with a resolution of +/-0.8 nm.
Profiling Skype video calls: Rate control and video quality (2012)

Video telephony has recently gained its momentum and is widely adopted by end-consumers. But there have been very few studies on the network impacts of video calls and the user Quality-of-Experience (QoE) under different network conditions. In this paper, we study the rate control and video quality of Skype video calls. We first measure the behaviors of Skype video calls on a controlled network testbed. By varying packet loss rate, propagation delay and bandwidth, we observe how Skype adjusts its rates, FEC redundancy and video quality. We find that Skype is robust against mild packet losses and propagation delays, and can efficiently utilize the available network bandwidth. We also find that Skype employs an overly aggressive FEC protection strategy. Based on the measurement results, we develop rate control model, FEC model, and video quality model for Skype. Extrapolating from the models, we conduct numerical analysis to study the network impacts of Skype. We demonstrate that user back-offs upon quality degradation serve as an effective user-level rate control scheme. We also show that Skype video calls are indeed TCP-friendly and respond to congestion quickly when the network is overloaded.
Wireless Sensors Powered by Microbial Fuel Cells (2005)

Monitoring parameters characterizing water quality, such as temperature, pH, and concentrations of heavy metals in natural waters, is often followed by transmitting the data to remote receivers using telemetry systems. Such systems are commonly powered by batteries, which can be inconvenient at times because batteries have a limited lifetime and must be recharged or replaced periodically to ensure that sufficient energy is available to power the electronics. To avoid these inconveniences, a microbial fuel cell was designed to power electrochemical sensors and small telemetry systems to transmit the data acquired by the sensors to remote receivers. The microbial fuel cell was combined with low-power, high-efficiency electronic circuitry providing a stable power source for wireless data transmission. To generate enough power for the telemetry system, energy produced by the microbial fuel cell was stored in a capacitor and used in short bursts when needed. Since commercial electronic circuits require a minimum 3.3 V input and our cell was able to deliver a maximum of 2.1 V, a DC-DC converter was used to boost the potential. The DC-DC converter powered a transmitter, which gathered the data from the sensor and transmitted it wirelessly to a remote receiver. To demonstrate the utility of the system, temporal variations in temperature were measured, and the data were wirelessly transmitted to a remote receiver.
VE-cadherin antibody accelerates neutrophil recruitment in vivo (1997)

Neutrophils enter sites of inflammation by crossing the endothelial lining of the blood vessel wall. VE-cadherin is an endothelial specific, homophilic adhesion molecule located at the lateral cell surface. We have generated a monoclonal antibody against mouse VE-cadherin which inhibits electrical resistance of endothelial cell monolayers in vitro as well as aggregation of VE-cadherin transfected cells. In vivo, this antibody was found to increase vascular permeability and to accelerate the entry of neutrophils into chemically inflamed mouse peritoneum. Thus, VE-cadherin is essential for the integrity of the endothelial barrier in vivo. Our data suggest that opening of VE-cadherin mediated endothelial cell contacts may be a relevant step during neutrophil extravasation.
Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning (2015)

The outcomes of adult acute lymphoblastic leukemia (ALL) patients with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) are unsatisfactory. Therefore, allogeneic (allo) HSCT has been applied to those patients in first complete remission (CR1), and has shown a long-term survival rate of approximately 50 %. In terms of myeloablative conditioning (MAC) regimen, higher dose of cyclophosphamide (CY) and total body irradiation (TBI) (the standard CY + TBI) has been generally applied to allo HSCT. Other MAC regimens such as busulfan-based or etoposide-based regimens have also been used. Among those, medium-dose etoposide (ETP) in addition to the standard CY + TBI conditioning regimen appears to be promising for allo HSCT in adult ALL when transplanted in ALL patients aged under 50 years in CR1 and also in CR2, showing an excellent outcome without increasing relapse or transplant-related mortality (TRM) rates. By contrast, reduced-intensity conditioning (RIC) regimens have also been applied to adult ALL patients and favorable outcomes have been obtained; however, relapse and TRM rates remain high. Therefore, an allo HSCT conditioning regimen which deserves further study for adult ALL patients aged under 50 years in CR1 and CR2 appears to be medium-dose ETP + CY + TBI and RIC is suitable for patients aged over 50 years or for younger patients with comorbid conditions. On the contrary, new therapeutic strategies for adult ALL patients are increasingly utilized with better outcomes; namely, various tyrosine kinase inhibitors for Philadelphia chromosome (Ph)-positive ALL, human leukocyte antigen-haploidentical HSCT, and pediatric-inspired regimens for Ph-negative ALL. Therefore, the optimal treatment modality should be selected considering patient's age, Ph-positivity, donor availability, risk classification, efficacy, and safety.
Neuritin: A gene induced by neural activity and neurotrophins that promotes neuritogenesis (1997)

Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression. A cDNA encoding a glycosylphoshatidylinositol-anchored protein was identified by screening for hippocampal genes that are induced by neural activity. This molecule, named neuritin, is expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. These data implicate neuritin as a downstream effector of activity-induced neurite outgrowth.
Molecular cloning and expression of Pgp-1. The mouse homolog of the human H-CAM (Hermes) lymphocyte homing receptor. (1989)

Mouse phagocytic glycoprotein-1 (Pgp-1; Ly-24) is a 95-kDa glycoprotein of unknown function that has served as an important T cell/leukocyte differentiation marker. Recent work has suggested that it may be related to a human 85- to 95-kDa glycoprotein (termed variously the Hermes Ag/lymphocyte homing receptor, ECMRIII, P80, and CD44) that is involved in lymphocyte binding to high endothelial venules in the process of lymphocyte homing, and has been implicated in other cell adhesion events. The widespread expression of this molecular class in diverse organ systems suggests a broad role in cellular adhesion, and has led to the unifying designation homing-cellular adhesion molecule (H-CAM). By using human H-CAM cDNA probes, we have isolated a full-length cDNA for the mouse homolog. Comparison of the human and mouse sequences reveals that an N-terminal domain homologous to cartilage proteoglycan core and link proteins, as well as the C-terminal transmembrane and cytoplasmic sequences, are highly conserved (89% and 86% identity, respectively). In contrast, a proximal extracellular domain thought to serve as a target for O-glycosylation and chondroitin sulfate attachment has undergone substantial divergence (only 42% identity). Transient expression of the cDNA in CHO cells followed by immunologic staining confirms that this mouse H-CAM cDNA encodes Pgp-1.1, one of two known Pgp-1 alloantigens.
Virtual meetings with desktop conferencing (1998)

Teleconferencing has come a long way since its early days as little more than three-way calling services over the telephone. Today's virtual meetings boil down to collaborative computing on desktops or laptop computers. Using the communications protocol of the Internet, today's desktop conferencing can incorporate audio, video, shared documents and engineering drawings, whiteboard for diagrams, and/or text chat for meetings held in the relative comfort of an office.