gebhart/patrepeval huggingface dataset:
Pathogenesis of Borna disease in rats: evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation (1987)

Borna disease virus is an uncharacterized agent that causes sporadic but fatal neurological disease in horses and sheep in Europe. Studies of the infection in rats have shown that the agent has a strict tropism for neural tissues, in which it persists indefinitely. Inoculated rats developed encephalitis after an incubation period of 17 to 90 days. This report shows that the incubation period is the time required for transport of the agent in dendritic-axonal processes from the site of inoculation to the hippocampus. The immune responses to the agent had no effect on replication or transport of the virus. The neural conduit to the brain was proven by intranasal inoculation of virus that resulted in rapid transport of the agent via olfactory nerves to the hippocampus and in development of disease in 20 days. Virus inoculation into the feet resulted in spread along nerve fibers from neuron to neuron. There was sequential replication in neurons of the dorsal root ganglia adjacent to the lumbar spinal cord, the gracilis nucleus in the medulla, and pyramidal cells in the cerebral cortex, followed by infection of the hippocampal neurons and onset of disease. This progression required 50 to 60 days. The exclusiveness of the neural conduit was proven by failure to cause infection after injection of the virus intravenously or into the feet of neurectomized rats.
Efficiencies of coated and perforated semiconductor neutron detectors (2005)

Previous experimental results indicated that boron-filled perforations within a semiconductor diode detector increase the thermal neutron detection efficiency. In the present work, two basic perforation designs, circular holes and parallel trenches, are analyzed using a Monte Carlo approach for use as high-efficiency thermal neutron detectors. The modeling results indicate that thermal-neutron intrinsic detection efficiencies exceeding 25% can be realized for single coated devices, and efficiencies exceeding 50% can be realized for doubled or "sandwiched" devices.
A capacitively based MEMS affinity glucose sensor (2009)

This paper presents a capacitively based MEMS affinity sensor for continuous glucose monitoring applications. This sensor consists of a vibrating Parylene diaphragm, which is remotely driven by a magnetic field and situated inside a microchamber. A solution of poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA), a biocompatible glucose-sensitive polymer, fills the microchamber, which is separated from its surroundings by a semi-permeable membrane. As glucose concentration is varied, viscosity changes induced by glucose/polymer binding cause a detectable change in the Parylene diaphragm vibration which can be measured capacitively. The response time of the sensor to glucose concentration changes is approximately 3 minutes which can be further improved with optimized device designs. The device has been tested at physiologically relevant glucose concentrations ranging from 27 to 324 mg/dL, showing excellent reversibility and stability.
Binaural Cue Coding Applied to Stereo and Multi-Channel Audio Compression (2002)

LCAV
Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo (2007)

Melanoma tumor antigen p97 or melanotransferrin (MTf) is an iron (Fe)-binding protein with high homology to serum transferrin. MTf is expressed at very low levels in normal tissues and in high amounts in melanoma cells although its function remains elusive. To understand the function of MTf, we utilized whole-genome microarray analysis to examine the gene expression profile of five models after modulating MTf expression. These models included two new stably transfected MTf hyper-expression models (SK-N-MC neuroepithelioma and LMTK- fibroblasts) and one cell type (SK-Mel-28 melanoma) where MTf was down-regulated by post-transcriptional gene silencing. These findings were compared with alterations in gene expression identified using the MTf-/- mice. In addition, the changes identified from the microarray data were also assessed in a new model of MTf down-regulation in SK-Mel-2 melanoma cells. In the cell line models, MTf hyper-expression led to increased proliferation, whereas MTf down-regulation resulted in decreased proliferation. Across all five models of MTf down- and up-regulation, we identified three genes modulated by MTf. These included ATP-binding cassette subfamily B member 5, whose change in expression mirrored MTf down- or up-regulation. In addition, thiamine triphosphatase and transcription factor 4 were inversely expressed relative to MTf levels across all five models. The products of these three genes are involved in membrane transport, thiamine phosphorylation and proliferation/survival, respectively. This study identifies novel molecular targets directly or indirectly regulated by MTf and the potential pathways involved in its function, including modulation of proliferation.
Nucleic Acid Aptamers: Clinical Applications and Promising New Horizons (2011)

Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic. Since the discovery of aptamers in the early 1990s, great efforts have been made to make them clinically relevant for diseases like cancer, HIV, and macular degeneration. In the last two decades, many aptamers have been clinically developed as inhibitors for targets such as vascular endothelial growth factor (VEGF) and thrombin. The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials. With advances in targeted-therapy, imaging, and nanotechnology, aptamers are readily considered as potential targeting ligands because of their chemical synthesis and ease of modification for conjugation. Preclinical studies using aptamer-siRNA chimeras and aptamer targeted nanoparticle therapeutics have been very successful in mouse models of cancer and HIV. In summary aptamers are in several stages of development, from pre-clinical studies to clinical trials and even as FDA approved therapeutics. In this review, we will discuss the current state of aptamers in clinical trials as well as some promising aptamers in pre-clinical development.
Genome editing: the road of CRISPR/Cas9 from bench to clinic (2016)

Molecular scissors engineered for site-specific modification of the genome hold great promise for effective functional analyses of genes, genomes and epigenomes and could improve our understanding of the molecular underpinnings of disease states and facilitate novel therapeutic applications. Several platforms for molecular scissors that enable targeted genome engineering have been developed, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and, most recently, clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated-9 (Cas9). The CRISPR/Cas9 system's simplicity, facile engineering and amenability to multiplexing make it the system of choice for many applications. CRISPR/Cas9 has been used to generate disease models to study genetic diseases. Improvements are urgently needed for various aspects of the CRISPR/Cas9 system, including the system's precision, delivery and control over the outcome of the repair process. Here, we discuss the current status of genome engineering and its implications for the future of biological research and gene therapy.
Modulation of activity by Arg407: structure of a fungal α-1,2-mannosidase in complex with a substrate analogue (2008)

Class I alpha-mannosidases (glycoside hydrolase family GH47) play key roles in the maturation of N-glycans and the ER-associated degradation of unfolded glycoproteins. The 1.95 A resolution structure of a fungal alpha-1,2-mannosidase in complex with the substrate analogue methyl-alpha-D-lyxopyranosyl-(1',2)-alpha-D-mannopyranoside (LM) shows the intact disaccharide spanning the -1/+1 subsites, with the D-lyxoside ring in the -1 subsite in the 1C4 chair conformation, and provides insight into the mechanism of catalysis. The absence of the C5' hydroxymethyl group on the D-lyxoside moiety results in the side chain of Arg407 adopting two alternative conformations: the minor one interacting with Asp375 and the major one interacting with both the D-lyxoside and the catalytic base Glu409, thus disrupting its function. Chemical modification of Asp375 has previously been shown to inactivate the enzyme. Taken together, the data suggest that Arg407, which belongs to the conserved sequence motif RPExxE, may act to modulate the activity of the enzyme. The proposed mechanism for modulating the activity is potentially a general mechanism for this superfamily.
Imatinib mesylate (STI-571) reduces Bcr-Abl-mediated vascular endothelial growth factor secretion in chronic myelogenous leukemia. (2002)

A large and diverse spectrum of oncogenes has been implicated as a contributor to angiogenesis in solid tumors based, in part, on its ability to induce proangiogenic growth factors such as vascular endothelial growth factor (VEGF), and the fact that various anti-oncogenic signaling inhibitor drugs have been shown to reverse such proangiogenic effects both in vitro and in vivo. Because leukemias are now also considered to be angiogenesis-dependent malignancies, we asked whether a similar paradigm might exist for the BCR-ABL oncogene and the Bcr-Abl targeting drug, STI-571 (imatinib mesylate), in the context of chronic myelogenous leukemia (CML) cells. We found that levels of VEGF expression in BCR-ABL-positive K562 cells were reduced in vitro by treatment with STI-571 in a dose-dependent fashion. Transfection of BCR-ABL into murine myeloid 32D and human megakaryocyte MO7e hematopoietic cells resulted in enhanced VEGF expression, which could be further elevated by the exposure to cytokines such as interleukin 3 and granulocyte macrophage colony-stimulating factor. We also found that conditioned media taken from 32D-p210-transfected cells could stimulate human umbilical vein endothelial cells by increasing phosphorylation of VEGF-R2/KDR and the downstream serine/threonine kinase PKB/Akt, an important regulator of endothelial cell survival. Moreover, amplification of BCR-ABL in STI-571-resistant cells was associated with elevated VEGF expression levels which could be reversed by treatment with higher concentrations of STI-571. Taken together, our results implicate BCR-ABL as a possible regulator of CML angiogenesis and raise the possibility that STI-571 could mediate some of its anti-CML properties in vivo through an angiogenesis-dependent mechanism.
Nicotine tartrate liquid enemas for mildly to moderately active left‐sided ulcerative colitis unresponsive to first‐line therapy: a pilot study (1997)

Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.
Prostanoids and Related Compounds. V. Synthesis of 6-Aza-5-oxo-2,3,4-trinor-1,5-inter-m-phenylene Prostacyclin Derivatives. (1991)

6-Aza-5-oxo-2, 3, 4-trinor-1, 5-inter-m-phenylene protacyclin derivatives were synthesized by use of 1, 3-dipolar cycloaddition as a key step.
A disease-associated cellular immune response in type 1 diabetics to an immunodominant epitope of insulin (2001)

The 9-23 amino acid region of the insulin B chain (B9-23) is a dominant epitope recognized by pathogenic T lymphocytes in nonobese diabetic mice, the animal model for type 1 diabetes. We describe herein similar (B9-23)-specific T-cell responses in peripheral lymphocytes obtained from patients with recent-onset type 1 diabetes and from prediabetic subjects at high risk for disease. Short-term T-cell lines generated from patient peripheral lymphocytes showed significant proliferative responses to (B9-23), whereas lymphocytes isolated from HLA and/or age-matched nondiabetic normal controls were unresponsive. Antibody-mediated blockade demonstrated that the response was HLA class II restricted. Use of the highly sensitive cytokine-detection ELISPOT assay revealed that these (B9-23)-specific cells were present in freshly isolated lymphocytes from only the type 1 diabetics and prediabetics and produced the proinflammatory cytokine IFN-gamma. This study is, to our knowledge, the first demonstration of a cellular response to the (B9-23) insulin epitope in human type 1 diabetes and suggests that the mouse and human diseases have strikingly similar autoantigenic targets, a feature that should facilitate development of antigen-based therapeutics.
Serum sialyl Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer. (1992)

We conclude that a positive STN-antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.
Establishment, molecular rescue, and expression of 123AV16-1, a tumor-reactive human monoclonal antibody. (1994)

The human monoclonal antibody (mAb) 123AV16-1 was generated by Epstein-Barr virus transformation of peripheral blood lymphocytes from a colorectal patient undergoing active specific immunotherapy with an autologous tumor cell-Bacille Calmette-Guérin vaccine. Direct immunohistochemical staining of tumor and normal pairs of tissues indicated that this human IgA1, lambda 2 mAb preferentially reacted with colon tumor epithelium. To generate a recombinant derivative of this Epstein-Barr virus-transformed cell line, we isolated the expressed complete heavy and light chain genes by a novel strategy and cloned them into modified pSV2-neo and pSV2-gpt expression vectors. The recombinant 123AV16-1 human mAb was expressed in both a murine myeloma and a human-murine heteromyeloma and was secreted as both monomers and dimers. The recombinant 123AV16-1 mAb expressed by both cell lines reacted with human colon tumor xenografts in a manner similar to the mAb derived from the Epstein-Barr virus-transformed cell line, indicating that the antibody specificity was not appreciably altered during the molecular rescue, cloning, or expression.
The Relationship Between the Perceived Value of Professional Development, Job Satisfaction, and Intent to Leave (2020)

Organizations striving to remain competitive compete in the war for talent in order to recruit and retain employees. Studies assessing intent to leave and turnover suggest numerous strategies to mitigate the revolving door of employees quitting jobs (Allen, 2008; Allen, Bryant, & Vardaman 2010; Lee, Hom, Eberly, & Li, 2018). This study assesses the relationship between the perceived value of professional development, job satisfaction, and intent to leave. Results of the study reveal as one finds professional development, valuable job satisfaction increases. In assessing the relationship between professional development and intent to leave, the results of the study suggest that as professionals find professional development more valuable, intent to leave decreases. Finally, in assessing the relationship between job satisfaction and intent to leave, the results of this study align with previous research. As job satisfaction increases, intent to leave decreases. Researchers such as Allen (2008), Allen et al. (2010), Shuck (2014), and The Conference Board (2018) assert the investment in professional development for employees may improve job satisfaction. Findings from this research confirm the association between professional development and job satisfaction. Therefore, organizations should strive to provide professional development opportunities for employees. Additionally, organizations should consistently seek feedback from employees to determine the professional development needs of employees to improve job satisfaction and mitigate intent to leave (Lee, 2018).
A New Global Effort to Control Malaria (2002)

The time has come to resurrect a worldwide effort to control malaria, following decades of neglect during which the disease has resurged in many parts of sub-Saharan Africa and other endemic regions.
Memristor-Based Material Implication (IMPLY) Logic: Design Principles and Methodologies (2013)

Memristors are novel devices, useful as memory at all hierarchies. These devices can also behave as logic circuits. In this paper, the IMPLY logic gate, a memristor-based logic circuit, is described. In this memristive logic family, each memristor is used as an input, output, computational logic element, and latch in different stages of the computing process. The logical state is determined by the resistance of the memristor. This logic family can be integrated within a memristor-based crossbar, commonly used for memory. In this paper, a methodology for designing this logic family is proposed. The design methodology is based on a general design flow, suitable for all deterministic memristive logic families, and includes some additional design constraints to support the IMPLY logic family. An IMPLY 8-bit full adder based on this design methodology is presented as a case study.
Flexible polyimide-based intracortical electrode arrays with bioactive capability (2001)

The promise of advanced neuroprosthetic systems to significantly improve the quality of life for a segment of the deaf, blind, or paralyzed population hinges on the development of an efficacious, and safe, multichannel neural interface for the central nervous system. The candidate implantable device that is to provide such an interface must exceed a host of exacting design parameters. We present a thin-film, polyimide-based, multichannel intracortical Bio-MEMS interface manufactured with standard planar photo-lithographic CMOS-compatible techniques on 4-in silicon wafers. The use of polyimide provides a mechanically flexible substrate which can be manipulated into unique three-dimensional designs. Polyimide also provides an ideal surface for the selective attachment of various important bioactive species onto the device in order to encourage favorable long-term reactions at the tissue-electrode interface. Structures have an integrated polyimide cable providing efficient contact points for a high-density connector. This report details in vivo and in vitro device characterization of the biological, electrical and mechanical properties of these arrays. Results suggest that these arrays could be a candidate device for long-term neural implants.
Human Monoclonal Antibodies (1985)

The monoclonal antibody technology has had a major impact on the serological and biochemical analysis of human tumor antigens. Monoclonal antibodies have rapidly led to the identification and characterization of a large number of antigenic determinants on cancer cells. To date, most of these monoclonal antibodies have been of mouse or rat origin. Antigens recognized by these reagents have therefore been defined generally by their immunogenicity in the mouse or rat, and they do not necessarily correspond to antigens that are immunogenic in humans.
Approach to Control the Corrosion of Magnesium by Alloying (2003)

For Magnesium alloys there are more fields as transport, communications or batteries. One is the use as bioresorbable implant in bone surgery. This saline area has high demands concerning corrosion resistance and is therefore used as main target for alloy development with the leading aspect of corrosion but regarding mechanical properties. A step-by-step building of alloy systems leads to an enhancement of the corrosion resistance by factors. These alloys are composed using common and newly defined principles of corrosion resisting alloying and processing parameters as extruding and heat treatment which aim for the enhancement of corrosion resistance. The final step is the validation of corrosive and mechanical characteristics of Fluorine-alloyed LAE-alloys in comparison to standard alloys as well in laboratory testing as in-vivo-implant in genuine pig [1].
Bringing host-cell takeover by pathogenic bacteria to center stage (2011)

Intracellular pathogenic bacteria contrive processes in their host cell to create a niche for their own reproduction. One way that has emerged by which bacteria do that is delivery of secreted virulence factors, SVFs, to the cytoplasm of the host cells using the bacterial type IV secretion system, T4SS. These SVFs modulate the activity of their target host proteins, which in turn control key cellular processes. A major mechanism for the evolution of SVFs that modulate targets that do not exist in the bacterial kingdom is horizontal gene transfer. Recently, a number of bacterial SVFs were shown to act on two types of targets in host cells. First, a group of several SVFs modulate the activity and localization of one protein: Rab1 GTPase, a key regulator of intracellular trafficking. Second, ankyrin repeats-containing SVFs, referred to by microbiologists as Anks, interact with various binding proteins, which in turn regulate a myriad of cellular processes, including apoptosis. Modulation of trafficking and apoptosis are two examples of how invading bacteria takeover their host phagocyte, which instead of destroying the bacteria becomes a factory for its reproduction.
Animal Model of Adenine-Induced Chronic Renal Failure in Rats (1986)

Long-term feeding of adenine to rats produced metabolic abnormalities resembling chronic renal failure in humans. Among the disturbances produced were azotemia, accumulation of uremic toxins, metabolic imbalances of amino acids and electrolytes, and hormonal imbalances. The pathological findings in the kidneys of these experimental rats revealed lesions of proximal tubules, of some distal tubules and of glomeruli. Contracted kidneys were found in the rats with severe perturbations. Our results suggest that long-term adenine feeding provides a model which would be useful to study chronic renal failure.
Seven-year follow-up of combined cataract extraction and viscocanalostomy (2006)

Phacoviscocanalostomy was safe and effective for the management of eyes with coexisting cataract and medically uncontrolled glaucoma. It provided a stable and sustained reduction in IOP with a minimum requirement for topical medication.
Monoclonal antibodies to type IV collagenase recognize a protein with limited sequence homology to interstitial collagenase and stromelysin (1988)

Type IV collagenase is a metalloproteinase associated with metastatic tumor cells. It specifically cleaves the triple helical basement membrane (type IV) collagen molecule at a single site. Monoclonal antibodies which block the activity of the human type IV collagenase were developed and used to purify this antigen. The purified type IV collagenase was partially sequenced following cyanogen bromide and trypsin cleavage. The amino acid sequence of the human type IV collagenase fragments revealed a region homologous to the human interstitial collagenase and stromelysin. However, several sequences in type IV collagenase were identified which are distinct from the latter. Polyclonal antibodies were raised against a synthetic peptide derived from such a sequence. Following affinity purification, the antibodies recognized the denatured human type IV collagenase in Western immunoblotting. These data indicate that type IV collagenase is a distinct member of a general family of metalloproteinases.
Reactions of organolithium compounds with sulfonate esters. A novel sulfone synthesis (1976)

The reaction of a variety of organolithium compounds with sulfonate esters leads to nucleophilic substitution on sulfur, resulting in the formation of sulfones in moderate to high yields. Several new sulfones were prepared by this method.