gebhart/patrepeval huggingface dataset:
A radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 locus (1992)

We describe a high-resolution radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 (NF2) gene. Eighty-five hamster-human somatic cell hybrids generated by X-irradiation and cell fusion were used to generate the radiation hybrid map. The presence or absence of 18 human chromosome 22-specific markers was determined in each hybrid by using Southern blot hybridization. Sixteen of the 18 markers were distinguishable by X-ray breakage in the radiation hybrids. Analysis of these data using two different mathematical models and two different statistical methods resulted in a single framework map consisting of 8 markers ordered with odds greater than 1000:1. The remaining nonframework markers were all localized to regions consisting of two adjoining intervals on the framework map with odds greater than 1000:1. Based on the RH map, the NF2 region of chromosome 22, defined by the flanking markers D22S1 and D22S28, is estimated to span a physical distance of approximately 6 Mb and is the most likely location for 9 of the 18 markers studied: D22S33, D22S41, D22S42, D22S46, D22S56, LIF, D22S37, D22S44, and D22S15.
Insulin-like growth factors cross the blood-brain barrier. (1994)

Although evidence exists that insulin may cross the blood-brain barrier, little is known about the ability of insulin-like growth factors (IGF-I and -II) to cross this barrier. In the present studies, equimolar concentrations of equal specific activity 125I-labeled IGF-I, IGF-II, or insulin were infused into the carotid artery of anesthetized adult rats. The perfusions were carried out for 3 min in the presence or absence of excess unlabeled ligand or insulin, with three or more animals in each group. Immediately after the perfusion, brains were frozen and sectioned for autoradiography. All ligands were detected in choroid plexus, median eminence, and blood vessels, but [125I]IGF-I and -II were also prominently localized in brain parenchyma. Densitometric analysis of film autoradiographs (28-day exposure for all ligands) revealed that radiolabeled IGFs, especially IGF-I, were significantly more abundant throughout the forebrain than [125I]insulin, especially in the paraventricular nucleus, where [125I]IGF-I was 10-fold and [125I]IGF-II was 5-fold more abundant than [125I]insulin. The difference in [125I]IGF-I vs. [125I]insulin accumulation was confirmed by parallel measurements of radioactivity in anatomically matched brain sections using a gamma-spectrometer. The uptake of radiolabeled IGF-I, IGF-II, and insulin by brain parenchyma and vasculature was completely inhibited by excess (1,000-fold) unlabeled ligand; however, insulin (10,000-fold excess) did not completely abolish [125I]IGF-I and -II accumulation. Microscopic evaluation of nuclear emulsion-coated brain sections revealed that radioactivity associated with [125I]IGF-I and -II perfusions was selectively concentrated in capillaries and medium-sized parenchymal cells in the paraventricular nucleus and, to a lesser extent, the supraoptic nucleus and anterior nucleus of the thalamus, whereas in other brain regions the radioligands were mostly bound to capillaries. These results suggest that radiolabeled IGF-I and -II bind to brain capillaries and cross the blood-brain barrier into brain parenchyma more readily than radiolabeled insulin.
No Effect of 5-Day Treatment with Acetylsalicylic Acid (Aspirin) or the Beta-Blocker Propranolol (Inderal) on Free Cortisol Responses to Acute Psychosocial Stress: A Randomized Double-Blind, Placebo-Controlled Study (2007)

Neither short-term treatment with aspirin nor propranolol altered the acute free cortisol response to psychological stress in healthy adults.
Characterization and Favorable in Vivo Properties of Heterodimeric Soluble IL-15·IL-15Rα Cytokine Compared to IL-15 Monomer* (2013)

Interleukin-15 (IL-15), a 114-amino acid cytokine related to IL-2, regulates immune homeostasis and the fate of many lymphocyte subsets. We reported that, in the blood of mice and humans, IL-15 is present as a heterodimer associated with soluble IL-15 receptor α (sIL-15Rα). Here, we show efficient production of this noncovalently linked but stable heterodimer in clonal human HEK293 cells and release of the processed IL-15·sIL-15Rα heterodimer in the medium. Purification of the IL-15 and sIL-15Rα polypeptides allowed identification of the proteolytic cleavage site of IL-15Rα and characterization of multiple glycosylation sites. Administration of the IL-15·sIL-15Rα heterodimer reconstituted from purified subunits resulted in sustained plasma IL-15 levels and in robust expansion of NK and T cells in mice, demonstrating pharmacokinetics and in vivo bioactivity superior to single chain IL-15. These identified properties of heterodimeric IL-15 provide a strong rationale for the evaluation of this molecule for clinical applications.
Frequency oftau mutations in three series of non-Alzheimer's degenerative dementia (1999)

Splice-site and missense mutations have been identified in tau associated with frontotemporal dementia with parkinsonism linked to chromosome 17. In this study we assessed the genetic contribution of tau mutations to three patient series with non-Alzheimer's (non-AD) degenerative dementia. The groups included (1) a community-based dementia series from Minnesota, MN; (2) a referral series with clinicopathological tauopathy; and (3) a pathologically confirmed familial frontotemporal dementia series from Manchester, UK. Comparing the three clinical series: in the stringently diagnosed Manchester frontotemporal dementia series, tau mutations were present in 13.6% of cases (three splice-site mutations); in the clinicopathological referral series that used more general inclusion criteria, 3 cases with P301L mutations were observed, which represents a lower mutation frequency of 3.6% (9.4% in familial cases); in contrast, tau mutations were not detected in the Minnesota community-based dementia series, suggesting the occurrence of these mutations in dementia generally is rare (<0.2%). These data identify the prevalence of mutations in three different clinical settings and indicate that this figure is sensitive to the diagnostic criteria used in each patient series.
A mm-wave tapered slot antenna with improved radiation pattern (2002)

We have proposed a new configuration of Tapered Slot Antenna (TSA) with an improved radiation pattern. The new design has a tapered section expressed by the Fermi-Dirac distribution function. At 60 GHz, the H-plane side lobe level of the antenna is 5-dB lower than that of conventional TSA's such as Linearly Tapered Slot Antennas. We also present a new technique for reducing the width of a TSA without degradation of radiation pattern.
Are crossbars really dead? (1995)

Crossbar switches are rarely considered for large, scalable multiprocessor interconnect systems because they require O(n 2 ) switching elements, are difficult to control efficiently and are hard to implement once their size becomes too large to fit on one integrated circuit. However these problems are technology dependent and a recent innovation in fiber optic devices has led to a new implementation of crossbar switches that does not share these problems while retaining the full advantages of a crossbar switch: low latency, high throughput, complete connectivity and multi-cast capability. Moreover, this new technology has several characteristics that allow a distributed control system which scales linearly in the number of attached nodes.The innovation that led to this research is an optical and-gate that can be used to demultiplex multiple high speed data streams that are carried on one common optical medium. Optical time domain multiplexing can combine the data from many nodes and broadcast the result back to all nodes. This paper discusses OTDM technology only to the extent necessary to understand its characteristics and capabilities. The main contribution lies in the description and analysis of interconnect architectures that utilize OTDM to achieve a level performance that is beyond electronic means. It is expected that cost-reduced OTDM systems will become competitive with the next generation of interconnect systems.
Erratum: Intermediate Nonlinear Evolution of the Parker Instability: Formation of Convection-Induced Discontinuities and Absence of Finite-Time Singularities [Phys. Rev. Lett.96, 065001 (2006)] (2006)

Received 23 February 2006DOI:https://doi.org/10.1103/PhysRevLett.96.129901©2006 American Physical Society
Molecular Basis for the Selectivity and Specificity of Ligand Recognition by the Family 16 Carbohydrate-binding Modules from Thermoanaerobacterium polysaccharolyticum ManA (2007)

Enzymes that hydrolyze complex polysaccharides into simple sugars are modular in architecture and consist of single or multiple catalytic domains fused to targeting modules called carbohydrate-binding modules (CBMs). CBMs bind to their ligands with high affinity and increase the efficiency of the catalytic components by targeting the enzymes to its substrate. Here we utilized a multidisciplinary approach to characterize each of the two family 16 carbohydrate-binding domain components of the highly active mannanase from the thermophile Thermoanaerobacterium polysaccharolyticum. These represent the first crystal structures of family 16 CBMs. Calorimetric analysis showed that although these CBMs demonstrate high specificity toward beta-1,4-linked sugars, they can engage both cello- and mannopolysaccharides. To elucidate the molecular basis for this specificity and selectivity, we have determined high resolution crystal structures of each of the two CBMs, as well as of binary complexes of CBM16-1 bound to either mannopentaose or cellopentaose. These results provide detailed molecular insights into ligand recognition and yield a framework for rational engineering experiments designed to expand the natural repertoire of these targeting modules.
Development of an automated digestion and droplet deposition microfluidic chip for MALDI-TOF MS (2008)

An automated proteolytic digestion bioreactor and droplet deposition system was constructed with a plastic microfluidic device for off-line interfacing to matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The microfluidic chips were fabricated in poly(methyl methacrylate) (PMMA), using a micromilling machine and incorporated a bioreactor, which was 100 microm wide, 100 microm deep, and possessed a 4 cm effective channel length (400 nL volume). The chip was operated by pressure-driven flow and mounted on a robotic fraction collector system. The PMMA bioreactor contained surface immobilized trypsin, which was covalently attached to the UV-modified PMMA surface using coupling reagents N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and hydroxysulfosuccinimide (sulfo-NHS). The digested peptides were mixed with a MALDI matrix on-chip and deposited as discrete spots on MALDI targets. The bioreactor provided efficient digestion of a test protein, cytochrome c, at a flow rate of 1 microL/min, producing a reaction time of approximately 24 s to give adequate sequence coverage for protein identification. Other proteins were also evaluated using this solid-phase bioreactor. The efficiency of digestion was evaluated by monitoring the sequence coverage, which was 64%, 35%, 58%, and 47% for cytochrome c, bovine serum albumin (BSA), myoglobin, and phosphorylase b, respectively.
An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5' noncoding region. (1995)

Translation of the human hepatitis C virus (HCV) RNA genome occurs by a mechanism known as "internal ribosome entry." This unusual strategy of translation is employed by naturally uncapped picornaviral genomic RNAs and several cellular mRNAs. A common feature of these RNAs is a relatively long 5' noncoding region (NCR) that folds into a complex secondary structure harboring an internal ribosome entry site (IRES). Evidence derived from the use of dicistronic expression systems, combined with an extensive mutational analysis, demonstrated the presence of an IRES within the HCV 5'NCR. The results of our continued mutational analysis to map the critical structural elements of the HCV IRES has led to the identification of a pseudoknot structure upstream of the initiator AUG. The evidence presented in this study is based upon the mutational analysis of the putative pseudoknot structure. This is further substantiated by biochemical and enzymatic probing of the wild-type and mutant 5'NCR. Further, the thermodynamic calculations, based upon a modified RNAKNOT program, are consistent with the presence of a pseudoknot structure located upstream of the initiator AUG. Maintenance of this structural element is critical for internal initiation of translation. The pseudoknot structure in the 5'NCR represents a highly conserved feature of all HCV subtypes and members of the pestivirus family, including hog cholera virus and bovine viral diarrhea virus.
Managing DSRC and WAVE Standards Operations in a V2V Scenario (2010)

The Dedicated Short-Range Communications (DSRC) standards suite is based on multiple cooperating standards mainly developed by the IEEE. In particular, we focus this paper on the core design aspects of DSRC which is called Wireless Access in Vehicular Environment (WAVE). WAVE is highlighted in IEEE 1609.1/.2/.3/.4. The DSRC and WAVE standards have been the center of major attention in both research and industrial communities. In 2008, WAVE standard was the third best seller standards in the history of the IEEE. This attention reflects the potential of WAVE to facilitate much of the vehicular safety applications. In this paper we present a fairly detailed tutorial of the WAVE standards. We extend the paper by describing some of the lessons learned from particular design approaches. We direct the reader to the landmark research papers in relevant topics. We alert the reader about major open research issues that might lead to future contribution to the WAVE design.
Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model (2016)

Blocking Cx43 hemichannels after light damage can significantly improve functional outcomes of neurons in both the rod and cone photo-transduction pathways in the light-damaged animal model, likely by reducing choroid inflammation and suppressing the glial-mediated inflammatory response. These data may have relevance for the treatment of conditions such as diabetic retinopathy and age-related macular degeneration.
Increased Number of Islet-Associated Macrophages in Type 2 Diabetes (2007)

Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune cells were observed in human type 2 diabetic patients, high-fat-fed C57BL/6J mice, the GK rat, and the db/db mouse. When cultured islets were exposed to a type 2 diabetic milieu or when islets were isolated from high-fat-fed mice, increased islet-derived inflammatory factors were produced and released, including interleukin (IL)-6, IL-8, chemokine KC, granulocyte colony-stimulating factor, and macrophage inflammatory protein 1alpha. The specificity of this response was investigated by direct comparison to nonislet pancreatic tissue and beta-cell lines and was not mimicked by the induction of islet cell death. Further, this inflammatory response was found to be biologically functional, as conditioned medium from human islets exposed to a type 2 diabetic milieu could induce increased migration of monocytes and neutrophils. This migration was blocked by IL-8 neutralization, and IL-8 was localized to the human pancreatic alpha-cell. Therefore, islet-derived inflammatory factors are regulated by a type 2 diabetic milieu and may contribute to the macrophage infiltration of pancreatic islets that we observe in type 2 diabetes.
Factor IX Fukuoka. Substitution of ASN92 by His in the second epidermal growth factor-like domain results in defective interaction with factors VIIa/X. (1993)

Hemophilia B Fukuoka, a moderately severe bleeding disorder, is a naturally occurring mutant of factor IX. Plasma from our patient had 3% clotting activity even though 64% of factor IX antigen was present. The purified mutant protein was cleaved normally by factor Xla, factor VIIa-tissue factor complex, or RVV-X (factor X-activating enzyme from Russell's viper venom), yielding a two-chain factor IXa. Amino acid composition and sequence analyses of one of the lysyl endopeptidase peptides derived from factor IX Fukuoka revealed that Asn92 in the second epidermal growth factor (EGF)-like domain had been replaced by His. The active site of the factor IXa Fukuoka was normally competent for the incorporation of p-aminobenzamidine and for the hydrolysis of a synthetic substrate, N alpha-benzyloxycarbonyl-L-arginine p-nitrobenzyl ester. Factor Xa formation by factor IXa Fukuoka was only 8% of the normal factor IXa, even in the presence of polylysine, and only 0.2% of the normal in the system containing phospholipids, Ca2+, and factor VIIIa, thereby indicating a functional defect in interaction of the mutant with factors VIIIa/X. Furthermore, catalytic efficiency (kcat/Km) of factor IXa Fukuoka toward factor X in the presence of Ca2+, phospholipids, and factor VIIIa was only 2.3% of the normal factor IXa. These results suggest that an Asn-to-His substitution at position 92 in the second EGF-like domain of factor IX Fukuoka would have an untoward effect on the specific conformational state of factor IX for binding with factors VIIIa/X.
Salivary Testosterone in Men: Further Evidence of a Direct Correlation with Free Serum Testosterone* (1981)

An excellent correlation was found between salivary testosterone (T) and serum T concentrations, as measured by RIA. Using polyacrylamide gel electrophoresis, we have demonstrated that sex steroid-binding globulin could not be identified in the saliva of men with serum sex steroid-binding globulin. After exogenous T administration, saliva and serum T rose abruptly and in parallel. Salivary T concentrations in male patients with thyrotoxicosis were similar to those in normal males, whereas the serum T and sex steroid-binding globulin values were significantly higher in the hyperthyroid patients. This study demonstrates that salivary T levels may be used as an index of free serum T.
Hereditary "pure" spastic paraplegia: a study of nine families. (1993)

The genetic and clinical features of 46 patients in nine families with "pure" hereditary spastic paraplegia are described. Inheritance was autosomal dominant in seven families and autosomal recessive in two. In dominant kinships, five families corresponded to type I with onset below 35 years, and two to type II with onset over 35 years. In early onset dominant families, in spite of apparent complete penetrance before 20, variable expression and incomplete penetrance occurred. Irrespective of genetic type, serial evaluation revealed that the main symptom consisted of slowly progressive spastic gait, extremely variable in severity, associated in some patients with decreased vibratory sense and micturition disorders generally as late features. In dominant families, the disease tended to be more severe in late onset cases. No patient had symptoms in the upper limbs and plantar responses were flexor in six symptomatic patients. Central motor conduction time studied by transcranial magnetic stimulation was always normal in the upper limbs and increased in the lower limbs in five of the eight patients on whom it was performed. Monomorphic and stereotyped clinical pattern in this series does not support the concept of multisystem involvement of the central nervous system as a hallmark of the disease.
Fast Random Walk with Restart and Its Applications (2006)

How closely related are two nodes in a graph? How to compute this score quickly, on huge, disk-resident, real graphs? Random walk with restart (RWR) provides a good relevance score between two nodes in a weighted graph, and it has been successfully used in numerous settings, like automatic captioning of images, generalizations to the "connection subgraphs", personalized PageRank, and many more. However, the straightforward implementations of RWR do not scale for large graphs, requiring either quadratic space and cubic pre-computation time, or slow response time on queries. We propose fast solutions to this problem. The heart of our approach is to exploit two important properties shared by many real graphs: (a) linear correlations and (b) block- wise, community-like structure. We exploit the linearity by using low-rank matrix approximation, and the community structure by graph partitioning, followed by the Sherman- Morrison lemma for matrix inversion. Experimental results on the Corel image and the DBLP dabasets demonstrate that our proposed methods achieve significant savings over the straightforward implementations: they can save several orders of magnitude in pre-computation and storage cost, and they achieve up to 150x speed up with 90%+ quality preservation.
Neural Stem Cell Transplantation Benefits a Monogenic Neurometabolic Disorder During the Symptomatic Phase of Disease (2009)

Although we and others have demonstrated that neural stem cells (NSCs) may impact such neurogenetic conditions as lysosomal storage diseases when transplanted at birth, it has remained unclear whether such interventions can impact well-established mid-stage disease, a situation often encountered clinically. Here we report that when NSCs were injected intracranially into the brain of adult symptomatic Sandhoff (Hexb(-/-)) mice, cells migrated far from the injection site and integrated into the host cytoarchitecture, restoring beta-hexosaminidase enzyme activity and promoting neuropathologic and behavioral improvement. Mouse lifespan increased, neurological function improved, and disease progression was slowed. These clinical benefits correlated with neuropathological correction at the cellular and molecular levels, reflecting the multiple potential beneficial actions of stem cells, including enzyme cross-correction, cell replacement, tropic support, and direct anti-inflammatory action. Pathotropism (i.e., migration and homing of NSCs to pathological sites) could be imaged in real time by magnetic resonance imaging. Differentially expressed chemokines might play a role in directing the migration of transplanted stem cells to sites of pathology. Significantly, the therapeutic impact of NSCs implanted in even a single location was surprisingly widespread due to both cell migration and enzyme diffusion. Because many of the beneficial actions of NSCs observed in newborn brains were recapitulated in adult brains to the benefit of Sandhoff recipients, NSC-based interventions may also be useful in symptomatic subjects with established disease.