gebhart/patrepeval huggingface dataset:
The coalescent process in models with selection, recombination and geographic subdivision (1991)

A population genetic model with a single locus at which balancing selection acts and many linked loci at which neutral mutations can occur is analysed using the coalescent approach. The model incorporates geographic subdivision with migration, as well as mutation, recombination, and genetic drift of neutral variation. It is found that geographic subdivision can affect genetic variation even with high rates of migration, providing that selection is strong enough to maintain different allele frequencies at the selected locus. Published sequence data from the alcohol dehydrogenase locus of Drosophila melanogaster are found to fit the proposed model slightly better than a similar model without subdivision.
Silicon single-electron quantum-dot transistor switch operating at room temperature (1998)

We fabricated a silicon single-electron quantum-dot transistor, which showed drain current oscillations at room temperature. These oscillations are attributed to electron tunneling through a single silicon quantum dot inside a narrow wire channel. Analysis of its current–voltage characteristic indicates that the energy level separation is about 110 meV and the silicon dot diameter is about 12 nm.
Current challenges in the development of vaccines for pneumonic plague (2008)

Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity.
DNA-Binding and Chromatin Localization Properties of CHD1 (1995)

CHD1 is a novel DNA-binding protein that contains both a chromatin organization modifier (chromo) domain and a helicase/ATPase domain. We show here that CHD1 preferentially binds to relatively long A.T tracts in double-stranded DNA via minor-groove interactions. Several CHD1-binding sites were found in a well-characterized nuclear-matrix attachment region, which is located adjacent to the intronic enhancer of the kappa immunoglobulin gene. The DNA-binding activity of CHD1 was localized to a 229-amino-acid segment in the C-terminal portion of the protein, which contains sequence motifs that have previously been implicated in the minor-groove binding of other proteins. We also demonstrate that CHD1 is a constituent of bulk chromatin and that it can be extracted from nuclei with 0.6 M NaCl or with 2 mM EDTA after mild digestion with micrococcal nuclease. In contrast to another chromo-domain protein, HP1, CHD1 is not preferentially located in condensed centromeric heterochromatin, even though centromeric DNA is highly enriched in (A+T)-rich tracts. Most interestingly, CHD1 is released into the cytoplasm when cells enter mitosis and is reincorporated into chromatin during telophase-cytokinesis. These observations lend credence to the idea that CHD1, like other proteins with chromo or helicase/ATPase domains, plays an important role in the determination of chromatin architecture.
Laminin oligopeptide derivatized agarose gels allow three‐dimensional neurite extension in vitro (1995)

The phenotypic expression of various neural cells is influenced by extracellular matrix (ECM) molecules. This study aims to develop a three-dimensional gel tailored to support neurite extension from neural cells. Laminin-derived (LN) oligopeptides CDP-GYIGSR, a 19-mer IKVAV containing sequence, GRGDSP, a cocktail of the three aforementioned LN peptides (PEPMIX), and a control peptide sequence GGGGG were covalently linked to an agarose hydrogel backbone using the bi-functional coupling agent 1'1, carbonyldiimidazole. Embryonic day 9 chick DRGs and PC12 cells were suspended in three dimensions in underivatized and derivatized agarose gels and neurite extension was analyzed. Agarose gels derivatized with CDPGYIGSR and PEPMIX enhanced neurite outgrowth from DRGs while GRGDSP and IKVAV derivatized gels inhibited neurite extension when compared to underivatized agarose gels. The IKVAV derivatized gels significantly enhanced neurite outgrowth from PC12 cells in comparison to underivatized and other LN peptide derivatized gels. Agarose hydrogels carrying covalently immobilized LN oligopeptides thus evoke specific responses from cells which contain receptors to the peptides used. Agarose hydrogels derivatized with neurite promoting peptide sequences may find applications in various models of in vivo regeneration of nervous tissue.
Micro–Positron Emission Tomography Imaging of Cardiac Gene Expression in Rats Using Bicistronic Adenoviral Vector-Mediated Gene Delivery (2004)

The IRES-based bicistronic adenoviral vector can potentially be used in conjunction with PET for indirect imaging of therapeutic gene expression by replacing 1 of the 2 PET reporter genes with a therapeutic gene of choice.
Photocrosslinkable chitosan as a biological adhesive (2000)

A photocrosslinkable chitosan to which both azide and lactose moieties were introduced (Az-CH-LA) was prepared as a biological adhesive for soft tissues and its effectiveness was compared with that of fibrin glue. Introduction of the lactose moieties resulted in a much more water-soluble chitosan at neutral pH. Application of ultraviolet light (UV) irradiation to photocrosslinkable Az-CH-LA produced an insoluble hydrogel within 60 s. This hydrogel firmly adhered two pieces of sliced ham with each other, depending upon the Az-CH-LA concentration. The binding strength of the chitosan hydrogel prepared from 30-50 mg/mL of Az-CH-LA was similar to that of fibrin glue. Compared to the fibrin glue, the chitosan hydrogel more effectively sealed air leakage from pinholes on isolated small intestine and aorta and from incisions on isolated trachea. Neither Az-CH-LA nor its hydrogel showed any cytotoxicity in cell culture tests of human skin fibroblasts, coronary endothelial cells, and smooth muscle cells. Furthermore, all mice studied survived for at least 1 month after implantation of 200 microL of photocrosslinked chitosan gel and intraperitoneal administration of up to 1 mL of 30 mg/mL of Az-CH-LA solution. These results suggest that the photocrosslinkable chitosan developed here has the potential of serving as a new tissue adhesive in medical use.
RETRACTED ARTICLE: MicroRNA-302b suppresses cell proliferation by targeting EGFR in human hepatocellular carcinoma SMMC-7721 cells (2013)

miR-302b suppresses HCC growth may due to targeting the EGFR/AKT2/CCND1 pathway.
Pulmonary vein isolation with a multielectrode basket catheter. (2007)

Pulmonary vein (PV) isolation (PVI) techniques have evolved as a curative treatment of atrial fibrillation (AF) since PVI guided by circumferential mapping with a circular catheter was initially proposed. A multielectrode basket catheter (MBC) is also useful for PVI because of some advantages; (1) an MBC provides some information about the PV anatomy on the fluoroscopic image, (2) an MBC can utilize the non-fluoroscopic navigation system, (3) an MBC enables the direct three-dimensional mapping around the PV ostium and antrum, (4) the distal electrodes of the MBC can be used to monitor some activation changes within the PV in real time and thereby indicate the effects of ablation at the ostium and antrum as radiofrequency lesions are created. PVI with an MBC is an effective and safe procedure to cure AF by integrating the PV anatomy and electrophysiology in combination with a non-fluoroscopic three-dimensional navigation system for the ablation catheter.
Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Death Receptor 5 Networks That Are Highly Organized (2012)

Recent evidence suggests that TNF-related apoptosis-inducing ligand (TRAIL), a death-inducing cytokine with anti-tumor potential, initiates apoptosis by re-organizing TRAIL receptors into large clusters, although the structure of these clusters and the mechanism by which they assemble are unknown. Here, we demonstrate that TRAIL receptor 2 (DR5) forms receptor dimers in a ligand-dependent manner at endogenous receptor levels, and these receptor dimers exist within high molecular weight networks. Using mutational analysis, FRET, fluorescence microscopy, synthetic biochemistry, and molecular modeling, we find that receptor dimerization relies upon covalent and noncovalent interactions between membrane-proximal residues. Additionally, by using FRET, we show that the oligomeric structure of two functional isoforms of DR5 is indistinguishable. The resulting model of DR5 activation should revise the accepted architecture of the functioning units of DR5 and the structurally homologous TNF receptor superfamily members.
An introduction to multicarrier modulation (2000)

OFDM is a powerful modulation technique that increases bandwidth efficiency and simplifies the removal of distortion, due to a multipath channel. Advances in fast Fourier transform technology enable OFDM to be efficiently implemented in hardware, even for a large number of subbands. OFDM is currently being used for a number of different applications. This increased popularity will lead to exciting developments in OFDM transmitter and receiver technology.
Signal Regulatory Protein (SIRPα), a Cellular Ligand for CD47, Regulates Neutrophil Transmigration (2002)

Recent studies have demonstrated that CD47 plays an important role in regulating human neutrophil (PMN) chemotaxis. Two ligands for CD47, thrombospondin and SIRPalpha, have been described. However, it is not known if SIRP-CD47 interactions play a role in regulating PMN migration. In this study, we show that SIRPalpha1 directly binds to the immunoglobulin variable domain loop of purified human CD47 and that such SIRP-CD47 interactions regulate PMN transmigration. Specifically, PMN migration across both human epithelial monolayers and collagen-coated filters was partially inhibited by anti-SIRP monoclonal antibodies. Similar kinetics of inhibition were observed for PMN transmigration in the presence of soluble, recombinant CD47 consisting of the SIRP-binding loop. In contrast, anti-CD47 monoclonal antibodies inhibited PMN transmigration by markedly different kinetics. Results of signal transduction experiments suggested differential regulation of PMN migration by SIRP versus CD47 by phosphatidylinositol 3-kinase and tyrosine kinases, respectively. Immunoprecipitation followed by Western blotting after SDS-PAGE under nonreducing conditions suggested that several SIRP protein species may be present in PMN. Stimulation of PMN with fMLP resulted in increased surface expression of these SIRP proteins, consistent with the existence of intracellular pools. Taken together, these results demonstrate that PMN migration is regulated by CD47 through SIRPalpha-dependent and SIRPalpha-independent mechanisms.
DeepTLR: A single deep convolutional network for detection and classification of traffic lights (2016)

Reliable real-time detection of traffic lights is a major concern for the task of autonomous driving. As deep convolutional networks have proven to be a powerful tool in visual object detection, we propose DeepTLR, a camera-based system for real-time detection and classification of traffic lights. Detection and state classification are realized using a single deep convolutional network. DeepTLR does not use any prior knowledge about traffic light locations. Also the detection is executed frame by frame without using temporal information. It is able to detect traffic lights on the whole camera image without any presegmentation. This is achieved by classifying each fine-grained pixel region of the input image and performing a bounding box regression on regions of each class. We show that our algorithm is able to run on frame-rates required for real-time applications while reaching notable results.
Characteristics of carotid atherosclerotic plaques of chronic lipid apheresis patients as assessed by In Vivo High-Resolution CMR - a comparative analysis (2012)

Results of this study suggest that, despite a severer risk profile for cardiovascular complications in LA-patients, chronic LA is associated with significantly lower lipid content in carotid plaques compared to plaques of patients without LA with similar degrees of stenosis, which is characteristic of clinically stable plaques.
Sodium Lauryl Sulfate, a Microbicide Effective Against Enveloped and Nonenveloped Viruses (2002)

The number of individuals infected with human immunodeficiency virus (HIV) and other pathogens causing sexually transmitted diseases (STDs) is growing dramatically worldwide. Globally, heterosexual transmission may account for as much as 85-90% of new cases of HIV infection. Latex condoms represent an effective barrier against sexually transmitted pathogens, but unfortunately, their use is not generalized. Therefore, there is an urgent need to develop safe and potent topical microbicides under the control of women to efficiently reduce the spread of sexually transmitted infections. Sodium lauryl sulfate (SLS), an anionic surfactant with protein denaturing potency, is a potent inhibitor of the infectivity of several enveloped (Herpes simplex viruses, HIV-1, Semliki Forest virus) and nonenveloped (papillomaviruses, reovirus, rotavirus and poliovirus) viruses. The mechanism of action of SLS involves the solubilization of the viral envelope and/or the denaturation of envelope and/or capsid proteins. Studies have shown that SLS is not toxic for cultured cell lines of different origins at concentrations that inactivate HIV-1, herpes and human papillomavirus in vitro. In addition, intravaginal pretreatment of mice with a gel formulation containing SLS, completely protected animals against Herpes simplex virus type-2 infection. The gel formulation containing SLS was also well-tolerated following repeated intravaginal administrations to rabbits. Taken together, these data suggest that SLS represents a potential candidate for the use as a topical microbicide to prevent the sexual transmission of HIV-1, herpes, human papillomavirus and possibly other sexually transmitted pathogens. The impact of such a preventive tool on public health can be enormous.
Time-Resolved Fluorescence Allows Selective Monitoring of Trp30 Environmental Changes in the Seven-Trp-Containing Human Pancreatic Lipase (2003)

Human pancreatic lipase (HPL, triacylglycerol acylhydrolase, EC 3.1.1.3) is a carboxyl esterase which hydrolyzes insoluble emulsified triglycerides and is essential for the efficient digestion of dietary fats. Though the three-dimensional structure of this enzyme has been determined, monitoring the conformational changes that may accompany the binding of various substrates and inhibitors is still of interest. Because of its sensitivity and ease of use, fluorescence spectroscopy of the intrinsic Trp residues is ideally suited for this purpose. However, the presence of seven Trp residues spread all over the HPL structure renders the interpretation of the fluorescence changes difficult with respect to the identification and location of the conformational or environmental changes taking place at the various Trp residues. In this context, the aim of this work was to investigate the contribution of the individual Trp residues to the fluorescence properties of HPL. To this end, we analyzed the steady-state and time-resolved fluorescence parameters of five single-point mutants in which one Trp residue was substituted with a weakly fluorescent Phe residue. In addition to the Trp residues at positions 30, 86, and 252, strategically located with respect to the active site, we also mutated Trp residues at positions 17 and 402, as representative residues of the HPL N- and C-terminal domains, respectively. Taken together, our data suggested that the solvent-exposed Trp30 residue contributed to at least 44% of the overall fluorescence of wild-type HPL. Moreover, we found that the long-lived fluorescence lifetime (6.77 ns) of wild-type HPL could be specifically attributed to Trp30, a feature that enables selective monitoring of its environmental changes. Additionally, Trp residues at positions 17 and 402 strongly contributed to the 1.61 ns lifetime of HPL, while Trp residues at positions 86 and 252 contributed to the 0.29 ns lifetime.
Cytoskeletal reorganization by soluble Wnt‐3a protein signalling (1998)

Our findings suggest that Wnt-3a protein, in the soluble form, can act to re-organize cytoskeletal structures.
T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression (2018)

Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI treatment. These patients can still respond to an infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in melanoma patients who failed multiple CPI therapy.
The human MDR3 P‐glycoprotein promotes translocation of phosphatidylcholine through the plasma membrane of fibroblasts from transgenic mice (1994)

The mouse mdr2 P-glycoprotein (P-gp) and its human MDR3 homologue are present in high concentrations in the canalicular membrane of hepatocytes. Mice lacking this protein are unable to secrete phosphatidylcholine (PC) into bile, suggesting that this P-gp is a PC translocator. We have tested this in fibroblasts from transgenic mice expressing the MDR3 gene under a vimentin promoter. Transgenic and control fibroblasts were incubated with [14C]choline to label PC. When the labeled cells were incubated with a PC transfer protein and acceptor liposomes, transfer of radioactive PC was enhanced in transgenic cells relative to the wild type controls. We conclude that the MDR3 P-glycoprotein is able to promote the transfer of PC from the inner to the outer leaflet of the plasma membrane, supporting the idea that this protein functions as a PC flippase.
A hemisphere array for non-invasive ultrasound brain therapy and surgery (2000)

Ultrasound phased arrays may offer a method for non-invasive deep brain surgery through the skull. In this study a hemispherical phased array system is developed to test the feasibility of trans-skull surgery. The hemispherical shape is incorporated to maximize the penetration area on the skull surface, thus minimizing unwanted heating. Simulations of a 15 cm radius hemisphere divided into 11, 64, 228 and 512 elements are presented. It is determined that 64 elements are sufficient for correcting scattering and reflection caused by trans-skull propagation. An optimal operating frequency near 0.7 MHz is chosen for the array from numerical and experimental thermal gain measurements comparing the power between the transducer focus and the skull surface. A 0.665 MHz air-backed PZT array is constructed and evaluated. The array is used to focus ultrasound through an ex vivo human skull and the resulting fields are measured before and after phase correction of the transducer elements. Finally, to demonstrate the feasibility of trans-skull therapy, thermally induced lesions are produced through a human skull in fresh tissue placed at the ultrasound focus inside the skull.
P0546EARLY, BUT NOT LATE, CONTRALATERAL NEPHRECTOMY OVERCOMES PROGRESSION TO CKD AFTER UNILATERAL ISCHEMIC INJURY (2020)

Abstract Background and Aims It is increasingly clear that acute kidney injury (AKI) can result in the development of chronic kidney disease (CKD) in humans. Murine renal unilateral ischemia-reperfusion injury (UIRI) models this AKI-to-CKD progression in the injured kidney in the presence of its healthy counterpart (Le Clef et al, Plos One 2016). In mice, we and others demonstrated that contralateral nephrectomy (Nx), when performed shortly after UIRI (i.e. 3 days), is able to significantly attenuate the progression to CKD. Although non-translatable, Nx can be considered an experimental therapeutic intervention that incites inherent physiological recovery mechanisms in the kidney. Here, we investigate in rats to what extent contralateral Nx is able to attenuate or revert CKD progression when performed well beyond the acute injury phase, i.e. with increased Nx delay time after UIRI. Method AKI was induced in male Wister rats by left UIRI for 60 min at 35°C core body temperature after which contralateral Nx was performed 3, 10 or 20 days later, or no Nx was performed. Control animals underwent sham-UIRI and sham-Nx 3 days later. Renal function was assessed by serum creatinine and transcutaneous GFR measurement 24h and 72h after Nx and weekly thereafter. Rats were euthanized 11 weeks after Nx. Kidneys were weighed and histology was evaluated by PAS stain for overall morphology and Sirius Red stain for interstitial fibrosis. Results When no Nx was performed, renal function of the injured kidney decreased 44% compared to control animals at week 11. Nx at day 3 induced full functional recovery from week 5 after Nx on, whereas Nx at day 10 and 20 both lead to a persistent 20% loss of renal function at week 9 after Nx (p&amp;lt;0.05). Nx at day 3 was able to attenuate renal atrophy and fibrotic tubulointerstitial expansion. Nx at day 10 and 20 were less efficient and led to 1.6 (p&amp;gt;0.05) and 2.6 (p&amp;lt;0.05) fold increase of tubulointerstitial area compared to controls. Nx at day 3 and 10 induced a significant increase in renal mass-to-body weight ratio compared to control from 2.9±0.1 mg/g (control) to 4.6±0.4 mg/g (day 3) and 4.8±0.3 mg/g (day 10) respectively. When Nx was performed at day 20 or no Nx was performed, renal mass-to-body weight ratio did not differ significantly from control animals, however, parallel with renal function, histopathology was considerably worse. Conclusion Early contralateral Nx after UIRI rescues renal function and morphology, whereas delayed Nx does not allow full recovery of the injured kidney. There was no additional functional loss when Nx was performed on day 20 versus day 10, though, histopathology aggravated. These results imply that a damaged kidney loses its intrinsic (compensatory) recovery potential over time and that an early intervention is crucial for averting CKD outcome after AKI.
FALCON: Boosting Knowledge for Answer Engines (2000)

This paper presents the features of Falcon, an answer engine that integrates dierent forms of syntactic, semantic and pragmatic knowledge for the goal of achieving better performance. The answer engine handles question reformulations, finds the expected answer type from a large hierarchy that incorporates the WordNet semantic net and extracts answers after performing unifications on the semantic forms of the question and its candidate answers. To rule out erroneous answers, it provides a justification option, implemented as an abductive proof. In TREC-9, Falcon generated a score of 58% for short answers and 76% for long answers.
Neurotrophic molecules (1989)

Neurotrophic molecules have a profound influence on developmental events such as naturally occurring cell death, differentiation, and process outgrowth. Despite their striking effects on developing neurons, a role for these molecules in the pathogenesis or therapy of neurological disease has not yet been defined. However, a variety of recent advances promise to provide the techniques necessary to assess the potential relevance of neurotrophic molecules to clinical neurology. In this article we review recent investigations into the biological effects, regulation of production, and mechanisms of action of the best characterized trophic molecule, nerve growth factor. In addition we review studies characterizing brain-derived neurotrophic factor and other putative neurotrophic molecules. Finally, we discuss how pharmacological effects of these molecules may be relevant to the therapy of disease states as well as neural regeneration.