gebhart/patrepeval huggingface dataset:
Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. (1997)

Gastrinomas and insulinomas are frequent in multiple endocrine neoplasia type 1 (MEN1). The MEN1 tumor suppressor gene was recently identified. To elucidate the etiological role of the MEN1 gene in sporadic enteropancreatic endocrine tumorigenesis, we analyzed tumors (28 gastrinomas and 12 insulinomas) from 40 patients for MEN1 gene mutations and allelic deletions. One copy of the MEN1 gene was found to be deleted in 25 of 27 (93%) sporadic gastrinomas and in 6 of 12 (50%) sporadic insulinomas. MEN1 gene mutations were identified in 9 of 27 (33%) sporadic gastrinomas and 2 of 12 (17%) insulinomas and were not seen in corresponding germ-line DNA sequence. A specific MEN1 mutation was detected in one gastrinoma and in the corresponding germ-line DNA of a patient who had no family history of MEN1. Somatic MEN1 gene mutations and deletions play a critical role in the tumorigenesis of sporadic gastrinomas and may also contribute to the development of a subgroup of insulinomas.
The one-to-many TCP overlay: a scalable and reliable multicast architecture (2005)

We consider reliable multicast in overlay networks where nodes have finite-size buffers and are subject to failures. We address issues of end-to-end reliability and throughput scalability in this framework. We propose a simple architecture which consists of using distinct point-to-point TCP connections between adjacent pairs of end-systems, together with a back-pressure control mechanism regulating the transfers of adjacent TCP connections, as well as a back-up buffering system handling node failures. This architecture, that we call the one-to-many TCP overlay, is a natural extension of TCP to the one-to-many case, in that it adapts the rate of the group communication to local congestion in a decentralized way via the window back-pressure mechanism. Using theoretical investigations, experimentations in the Internet, and large network simulations, we show that this architecture provides end-to-end reliability and can tolerate multiple simultaneous node failures, provided the backup buffers are sized appropriately. We also show that under random perturbations caused by cross traffic described in the paper, the throughput of this reliable group communication is always larger than a positive constant, that does not depend on the group size. This scalability result contrasts with known results about the non-scalability of IP-supported multicast for reliable group communication.
Method for Measuring Thermal Conductivity of Small Highly Insulating Specimens (2009)

Abstract A hot plate method for the measurement of thermal conductivity is described, which is unique in that it combines all the following capabilities: (1) Measurements of very small specimens, (2) measurements of specimens with thermal conductivity on the same order of that as air, and (3) the ability to use air as a reference material. As with other approaches, care is taken to ensure that the heat flow through the test specimen is essentially one-dimensional. However, unlike other approaches, no attempt is made to use heated guards to minimize the flow of heat from the hot plate to the surroundings. Results indicate that since large correction factors must be applied to account for guard imperfections when specimen dimensions are small, simply measuring and correcting for heat from the heater disk that does not flow into the specimen may be preferable. Extensive computational heat transfer modeling and experimental measurements taken in a prototype apparatus show that this approach is feasible. Suggestions are made for further improvements based on analyses of the generated data.
Synthesis and structure-activity relations of bestatin analogs, inhibitors of aminopeptidase B (1977)

Stereoisomers and analogues of bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, were synthesized and tested for aminopeptidase B and leucine aminopeptidase inhibiting activity. Among the eight stereoisomers, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the L-leucine residue of bestatin was substituted with other amino acids, only the one containing isoleucine showed more activity than bestatin. Norleucine, norvaline, methionine, valine, serine, glutamine, phenylalanine, glutamic acid, proline, and lysine analogues gave, in that order, decreasing activity. Alkyl and phenyl sub stitution for the benzyl group of bestatin decreased the activity markedly. p-Methyl-, p-chloro-, and p-nitrobestatins showed greater activity than bestatin.
Effect of tungsten, molybdenum and silicon additions on the creep resistance of a gamma titanium aluminide alloy (1995)

Alloy development programs involving gamma titanium aluminide alloys have mainly focused on increasing room temperature ductility, but this has been achieved at the expense of creep properties. Since recent engine tests have been successful with materials having a ductility of about 1.5%, this study focuses on the effects of W, Mo and Si additions. The creep rate is reduced by a factor of 30 at 760 C (1,400 F). Microstructure studies described below show that 0.2--2 {micro}m precipitates form during primary creep deformation and these precipitates interfere with dislocation mobility. These precipitates contain higher concentrations of W and Mo than found in the matrix, but they have a crystal structure that correlates with the Ti{sub 5}Si{sub 3} crystal structure. In addition, a substantial fraction of initial creep strain is accommodated by formation of mechanical twins parallel to lamellar planes that refine the lamellar spacing, and these also initiate mechanical twinning in the equiaxed grains.
Acoustic Coordinated Reset Neuromodulation in a Real Life Patient Population with Chronic Tonal Tinnitus (2015)

The field study "RESET Real Life" provides evidence for safety and efficacy of acoustic coordinated reset neuromodulation in a prospective, open-label, real life setting.
Monoclonal antibody‐mediated inhibition of the human HLA alloimmune response to platelet transfusion is antigen specific and independent of Fcγ receptor‐mediated immune suppression (2000)

Presensitization of donor platelets with allo-specific immunoglobulin (Ig)G results in a diminished immune response against subsequent transfusions of platelets. To understand better the mechanism of how alloantibody presensitization results in a decreased alloimmune response, we have used murine monoclonal antibodies directed to polymorphic and non-polymorphic regions of human leucocyte antigen (HLA) as well as platelet-specific molecules. Here, we demonstrated that presensitization with anti-human HLA class I antibodies, as well as beta2-microglobulin-specific antibody, protected against alloantibody production to five subsequent untreated platelet challenges. Use of complement fixing, non-fixing or F(ab')2 fragments of HLA-specific antibody also resulted in complete inhibition of alloantibody production. This protection was not seen when the platelets were presensitized with monoclonal antibodies to CD42a (GPIX), CD32 (low-affinity IgG/Fcgamma receptor) or murine IgG and was thus independent of B-cell FcgammaRII-mediated immune suppression. The inhibition observed was independent of HLA alloantigenic specificity as antibodies directed at the beta2-microglobulin portion of HLA class I were as effective as antibodies against any of the HLA-alpha regions (either polymorphic or non-polymorphic) of class I. This work demonstrates that monoclonal antibody-mediated suppression of the human HLA alloimmune response to platelet transfusion is antigen specific and is independent of FcgammaRII-mediated immune regulation, complement fixing or HLA alloantigenic specificity.
Novel hirudin variants from the leech <i>Hirudinaria manillensis</i> (1993)

Novel hirudin variants isolated from the leech Hirudinaria manillensis, a leech more specialized for mammalian parasitism, are described. Isolation of antithrombin polypeptides was performed by ion-exchange chromatographies followed by an affinity chromatography step on immobilized thrombin. The major active component, antithrombin polypeptide peak 2 (HM2) and a second polypeptide, named HM1, were purified to homogeneity and their complete amino acid sequences were determined. The protein structure of the two hirudin variants include 64 amino acids with 6 cysteine residues at highly conserved positions. Comparison of the amino acid sequences of HM1 and HM2 with other known hirudins shows differences mainly in the central part and in the C-terminal region of the polypeptides. Particularly significant is the lack of a sulfated tyrosine residue in the C-terminal portion of the molecule which is replaced by aspartic acid. Polymerase chain reaction cloning techniques were used to isolate and characterize the cDNAs and determine the genomic structures of these hirudin-like polypeptides. The cDNA clones coding for the two variants indicate the expression of pre-hirudins of 84 amino acids where the first 20 residues constitute the signal peptide required for extracellular secretion. The leader sequence appears to be highly conserved for both isoforms and shares a complete similarity with the partial hirudin variant 2 (HV2) signal peptide sequence previously reported. The HM1 and HM2 gene fragments show the presence of four exons: the first one corresponding to a 20-amino-acid signal peptide while the other three exons share the full primary structure of the antithrombin polypeptides. HM2 was also efficiently produced in recombinant Escherichia coli by expressing a periplasmic construction containing the synthetic gene.
Interaction between IGFBP-5 and TNFR1 (2010)

Insulin-like growth factor binding protein 5 (IGFBP-5) plays an important role in controlling cell survival, differentiation and apoptosis. Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor 1 (TNFR1). To determine whether IGFBP-5 and TNFR1 interact as members of the same apoptosis pathway, recombinant IGFBP-5 and TNFR1 were isolated. The expression and purification of the full-length TNFR1 and truncated IGFBP-5 proteins were successfully performed in E. coli. The binding of both IGFBP-5 and TNFR1 proteins was detected by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, electron microscopy, and size-exclusion column (SEC) chromatography. IGFBP-5 indeed binds to TNFR1 with an apparent <TEX>$K_D$</TEX> of 9 nM. After measuring the fluorescence emission spectra of purified IGFBP-5 and TNFR1, it was found that the tight interaction of these proteins is accompanied by significant conformational changes of one or both. These results indicate that IGFBP-5 acts potently as a novel ligand for TNFR1.
CABA: Continuous Authentication Based on BioAura (2016)

Most computer systems authenticate users only once at the time of initial login, which can lead to security concerns. Continuous authentication has been explored as an approach for alleviating such concerns. Previous methods for continuous authentication primarily use biometrics, e.g., fingerprint and face recognition, or behaviometrics, e.g., key stroke patterns. We describe CABA, a novel continuous authentication system that is inspired by and leverages the emergence of sensors for pervasive and continuous health monitoring. CABA authenticates users based on their BioAura, an ensemble of biomedical signal streams that can be collected continuously and non-invasively using wearable medical devices. While each such signal may not be highly discriminative by itself, we demonstrate that a collection of such signals, along with robust machine learning, can provide high accuracy levels. We demonstrate the feasibility of CABA through analysis of traces from the MIMIC-II dataset. We propose various applications of CABA, and describe how it can be extended to user identification and adaptive access control authorization. Finally, we discuss possible attacks on the proposed scheme and suggest corresponding countermeasures.
A hybrid method for the vibration analysis of complex structural-acoustic systems (1999)

A new method is presented for the analysis of complex dynamic systems which is based on partitioning the system degrees of freedom into a “global” set and a “local” set. The global equations of motion are formulated and solved in a standard deterministic manner, although due account is taken of the presence of the local degrees of freedom via an approach which is analogous to fuzzy structure theory. The local equations of motion are formulated and solved by using statistical energy analysis (SEA) with due account being taken of power input from the global degrees of freedom. The method can be considered to encompass a number of existing analysis techniques and to form a flexible framework within which a number of detailed modeling strategies can be devised. A simple rod system provides an initial application, and it is shown that the method yields very good results from low to high frequency excitation.
Implementing Cyber Security Requirements and Mechanisms in Microgrids (2015)

A microgrid is a collection of distributed energy resources, storage and loads under common coordination and control that provides a single functional interface to enable its management as a single unit. Microgrids provide several advantages such as power quality control, uninterrupted power supply and integration of renewable resources. However, microgrids are increasingly connected to the Internet for remote control and management, which makes them susceptible to cyber attacks. To address this issue, several pilot deployments have implemented bolt-on security mechanisms, typically focused on securing the protocols used in microgrids. Unfortunately, these solutions are inadequate because they fail to address some important cyber security requirements. This chapter describes the μGridSec methodology, which is intended to provide comprehensive cyber security solutions for microgrid deployments. First, cyber security requirements are derived from relevant industry standards and by studying pilot microgrid deployments. Next, the μGridSec methodology is applied to ensure that appropriate mechanisms are applied to microgrid architectures to meet the cyber security requirements. Finally, a high-level threat model for a representative microgrid architecture is used to identify security threats and demonstrate how μGridSec can address the threats.
Development of a Neisseria meningitidis group B serotype 2b protein vaccine and evaluation in a mouse model (1984)

Although serotype 2 remains the predominant cause of group B Neisseria meningitidis disease in many parts of the world, most cases of this disease are now due to serotype 2b rather than 2a. For this reason, we adapted the serotype 2a vaccine method of C. E. Frasch and M. S. Peppler (Infect. Immun. 37:271-280, 1982) to the production of a serotype 2b protein vaccine. A spontaneously occurring nonencapsulated mutant of the group B serotype 2b strain 3006 was obtained by selection on group B antiserum agar. Serotype 2b outer membrane protein vaccines were prepared with less than 1% lipoplysaccharide contamination. The immunogenicity of these vaccines was evaluated in mice in the presence and absence of meningococcal group B and group C capsular polysaccharides. The group B and group C polysaccharides equally potentiated the antibody response to the serotype 2b protein. Addition of aluminum hydroxide or aluminum phosphate markedly improved the antibody response to the serotype 2b protein, but aluminum hydroxide-adjuvanted vaccines consistently elicited higher antibody levels. Aluminum hydroxide-adsorbed serotype 2a and 2b protein vaccines were evaluated for induction of cross-protective bactericidal antibodies. The 2a vaccines were 2a specific, whereas the 2b vaccines elicited antibodies strongly bactericidal for both 2a and 2b meningococcal strains and protected against bacteremia in a mouse model. It may therefore be possible to provide protection against both 2a and 2b disease by using an aluminum hydroxide-adsorbed protein vaccine containing a single serotype 2 protein component.
Real-time calculation of a limiting form of the Renyi entropy applied to detection of subtle changes in scattering architecture (2009)

Previously a new method for ultrasound signal characterization using entropy H(f) was reported, and it was demonstrated that in certain settings, further improvements in signal characterization could be obtained by generalizing to Renyi entropy-based signal characterization I(f)(r) with values of r near 2 (specifically r=1.99) [M. S. Hughes et al., J. Acoust. Soc. Am. 125, 3141-3145 (2009)]. It was speculated that further improvements in sensitivity might be realized at the limit r-->2. At that time, such investigation was not feasible due to excessive computational time required to calculate I(f)(r) near this limit. In this paper, an asymptotic expression for the limiting behavior of I(f)(r) as r-->2 is derived and used to present results analogous to those obtained with I(f)(1.99). Moreover, the limiting form I(f,infinity) is computable directly from the experimentally measured waveform f(t) by an algorithm that is suitable for real-time calculation and implementation.
Molecular Properties That Define the Activities of Antibiotics in <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> (2018)

The permeability barrier of Gram-negative cell envelopes is the major obstacle in the discovery and development of new antibiotics. In Gram-negative bacteria, these difficulties are exacerbated by the synergistic interaction between two biochemically distinct phenomena, the low permeability of the outer membrane (OM) and active multidrug efflux. In this study, we used Pseudomonas aeruginosa and Escherichia coli strains with controllable permeability barriers, achieved through hyperporination of the OMs and varied efflux capacities, to evaluate the contributions of each of the barriers to protection from antibacterials. We analyzed antibacterial activities of β-lactams and fluoroquinolones, antibiotics that are optimized for targets in the periplasm and the cytoplasm, respectively, and performed a machine learning-based analysis to identify physicochemical descriptors that best classify their relative potencies. Our results show that the molecular properties selected by active efflux and the OM barriers are different for the two species. Antibiotic activity in P. aeruginosa was better classified by electrostatic and surface area properties, whereas topology, physical properties, and atom or bond counts best capture the behavior in E. coli. In several cases, descriptor values that correspond to active antibiotics also correspond to significant barrier effects, highlighting the synergy between the two barriers where optimizing for one barrier promotes strengthening of the other barrier. Thus, both barriers should be considered when optimizing antibiotics for favorable OM permeability, efflux evasion, or both.
An experimental study on the short-channel effects in undergated polysilicon thin-film transistors with and without lightly doped drain structures (1993)

Short-channel effects are studied for undergated polysilicon thin-film transistors (TFTs). Although a simple lightly doped drain (LDD) structure can minimize the effects, a much longer LDD region is required than in a bulk transistor. In addition to significant effects similar to bulk transistors, the leakage current is more affected by variations of the channel length and drain bias than it is in a bulk transistor due to the granular structures of the polysilicon films and the enhanced junction field in the fully depleted structure. As results, variations of the ON current, OFF current, and their ratio are dramatic without the LDD structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Intraocular lens to correct corneal coma (2007)

We present a new methodology to obtain, to the best of our knowledge, the first intraocular lens (IOL) designed to balance the coma induced by the cornea due to the global ocular tilt. This lens is designed to mimic the situation naturally occurring in the normal healthy eye. The new proposed IOL provides an improved optical quality for all lens powers.
Fabrication of Silk Microneedles for Controlled‐Release Drug Delivery (2011)

Abstract Microneedles are emerging as a minimally invasive drug delivery alternative to hypodermic needles. Current material systems utilized in microneedles impose constraints hindering the further development of this technology. In particular, it is difficult to preserve sensitive biochemical compounds (such as pharmaceuticals) during processing in a single microneedle system and subsequently achieve their controlled release. A possible solution involves fabricating microneedles systems from the biomaterial silk fibroin. Silk fibroin combines excellent mechanical properties, biocompatibility, biodegradability, benign processing conditions, and the ability to preserve and maintain the activity of biological compounds entrained in its material matrix. The degradation rate of silk fibroin and the diffusion rate of the entrained molecules can be controlled simply by adjusting post‐processing conditions. This combination of properties makes silk an ideal choice to improve on existing issues associated with other microneedle‐based drug delivery system. In this study, a fabrication method to produce silk biopolymer microstructures with the high aspect ratios and mechanical properties required to manufacture microneedle systems is reported. Room temperature and aqueous‐based micromolding allows for the bulk loading of these microneedles with labile drugs. The drug release rate is decreased 5.6‐fold by adjusting the post‐processing conditions of the microneedles, mainly by controlling the silk protein secondary structure. The release kinetics are quantified in an in vitro collagen hydrogel model, which allows tracking of the model drug. Antibiotic loaded silk microneedles are manufactured and used to demonstrate a 10‐fold reduction of bacterial density after their application. The processing strategies developed in this study can be expanded to other silk‐based structural formats for drug delivery and biologicals storage applications.
Experimental Investigation of Friction Stir Seal Welding of Tube–Tubesheet Joints (2014)

To ensure heat exchanger tube–tubesheet joints tightness, industrial standards may recommend performing a combination of roller expansion and seal welding, using conventional fusion welding processes. Solid state friction stir welding (FSW) has several advantages over the conventional fusion welding but has not yet proven its usefulness in seal and strength welding of heat exchanger tube–tubesheet joints where the available space is very limited and weld pass is of a relatively complex contour. In this work, a newly designed tool and procedure have been developed to friction stir seal weld tube–tubesheet joints. The effects of process conditions such as welding speed and tool offset on dependent process parameters including welding loads and joint quality have been investigated on a 6xxx-series aluminum three-tube test cell. The results of the investigation revealed that the quality of the seal weld of tube–tubesheet joints is affected by the above parameters. Lower weld speeds increase the size of the heat-affected zone while higher speeds lead to larger weld defects. Better weld quality is obtained when the center of the pin tool is offset from the tube–tubesheet interface by an amount lower than 40% of the pin diameter.