gebhart/patrepeval huggingface dataset:
Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling (2012)

Cerebral cavernous malformation (CCM) involves the homozygous inactivating mutations of one of three genes, ccm1, -2, or -3 resulting in hyperpermeable blood vessels in the brain. The CCM1, -2, and -3 proteins form a complex to organize the signaling networks controlling endothelial cell physiology including actin dynamics, tube formation, and adherens junctions. The common biochemical defect with the loss of CCM1, -2, or -3 is increased RhoA activity leading to the activation of Rho-associated coiled coil-forming kinase (ROCK). Inhibition of the ROCK rescues CCM endothelial cell dysfunction, suggesting that the inhibition of RhoA-ROCK signaling may be a therapeutic strategy to prevent or arrest the progression of the CCM lesions.
A convenient chemical-microbial method for developing fluorinated pharmaceuticals (2013)

A significant proportion of pharmaceuticals are fluorinated and selecting the site of fluorine incorporation can be an important beneficial part a drug development process. Here we describe initial experiments aimed at the development of a general method of selecting optimum sites on pro-drug molecules for fluorination, so that metabolic stability may be improved. Several model biphenyl derivatives were transformed by the fungus Cunninghamella elegans and the bacterium Streptomyces griseus, both of which contain cytochromes P450 that mimic oxidation processes in vivo, so that the site of oxidation could be determined. Subsequently, fluorinated biphenyl derivatives were synthesised using appropriate Suzuki-Miyaura coupling reactions, positioning the fluorine atom at the pre-determined site of microbial oxidation; the fluorinated biphenyl derivatives were incubated with the microorganisms and the degree of oxidation assessed. Biphenyl-4-carboxylic acid was transformed completely to 4'-hydroxybiphenyl-4-carboxylic acid by C. elegans but, in contrast, the 4'-fluoro-analogue remained untransformed exemplifying the microbial oxidation - chemical fluorination concept. 2'-Fluoro- and 3'-fluoro-biphenyl-4-carboxylic acid were also transformed, but more slowly than the non-fluorinated biphenyl carboxylic acid derivative. Thus, it is possible to design compounds in an iterative fashion with a longer metabolic half-life by identifying the sites that are most easily oxidised by in vitro methods and subsequent fluorination without recourse to extensive animal studies.
Effects of high-amplitude low-frequency structural vibrations and machinery sound waves on ultrasonic guided wave propagation for health monitoring of composite aircraft primary structures (2020)

A reliable damage diagnostic by ultrasonic guided wave (GW) based structural health monitoring (SHM) can only be achieved if the physical interactions between wave propagation, the SHM system and environmental factors are fully understood. The purpose of this research was to gain knowledge about the effects of high-amplitude low-frequency structural vibrations (HA-LFV) and audible sound waves (SW) on ultrasonic GW propagation. Measurements were performed on a stiffened panel of a full-scale composite torsion box containing barely visible impact damage. Time-domain analysis of the filtered GW signals revealed that the main effect of HA-LFV was the presence of coherent noise. This was interpreted as the consequence of superposition of multiple dispersive wave groups produced by mode conversion at the moment of reflection on the corrugated panel surfaces during propagation. It was also observed that the coherent noise amplitude depends on the amplitude of the HA-LFV, and on the ratio between the HA-LFV frequency and the ultrasonic excitation frequency. These relationships can potentially be explored for the development of a HA-LFV compensation mechanism to enable in-service GW based damage diagnostics. In contrast, GW signals in the cases with audible SW present were almost unaffected. It was concluded that there is strong evidence supporting the hypothesis that ultrasonic GW propagation with HA-LFV effects can be analysed under the assumption of a permanently corrugated structure.
The structure and properties of ternary zinc phosphate glasses for optical applications (2014)

This dissertation focuses on the properties and structures of ternary zinc phosphate glasses that have recently been investigated as substrates for femto-second (fs) laser writing. Although these glasses have potential for use as optical substrates, their poor chemical properties limit their applications. In this work, ternary zinc phosphate glasses were studied to find compositions with enhanced chemical durability and the properties and structures of the investigated glasses are reported. Paper 1 and Paper 2 include the first systematic studies of the properties, structures of zinc aluminophosphate (ZAP) glasses and phase relationships in the ZnOAl2O3-P2O5 system, respectively. Adding alumina to a Zn-metaphosphate glass reduces dissolution rates in water by 4 orders of magnitude and increases the glass transition temperatures. The average Al coordination number can be predicted from a structural model that considers the number of non-bridging oxygens to coordinate metal cations, and this work is the first reported use of this model for a ternary phosphate glass. Paper 3 is the first systematic study of how the properties and structures of zinc magnesium polyphosphate glasses change when MgO replaces ZnO for compositions with fixed O/P ratios. The Mg 2+ and Zn 2+ ions have similar field strengths, but have much different effects on glass properties that are discussed in terms of relative polarizabilities (refractivities) and electron configurations of the Mg 2+ and Zn 2+ ions. In Paper 4, the creation of electronic defects in zinc phosphate glasses by exposure to ultraviolet and x-ray radiation is described. The nature of the defects formed is dependent on the glass composition and similar defects are created when these glasses are exposed to femto-second laser radiation.
Bi-directional PHEV battery charger based on normally-off GaN-on-Si multi-chip module (2014)

A high frequency, high efficiency bi-directional battery charger for Plug-in Hybrid Electric Vehicle (PHEV) is built with high voltage normally-off GaN-on-Si HFETs. The battery charger topology consists of a 500 kHz Full Bridge (FB) AD/DC stage and a 500 kHz Dual Active Bridge (DAB) DC/DC stage. The system functionality is verified and measured efficiency is 97% for the AC/DC stage and 97.2% for the DC/DC stage, which leads to a total efficiency 94.2%. By doing sinusoidal charging, the DC link capacitance can be reduced to much less than one third but efficiency will drop to 92.0%.
Methicillin resistant<i>Staphylococcus aureus</i>(MRSA) in the intensive care unit (2002)

Methicillin resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. MRSA strains are endemic in many American and European hospitals and account for 29%-35% of all clinical isolates. Recent studies have documented the increased costs associated with MRSA infection, as well as the importance of colonisation pressure. Surveillance strategies have been proposed especially in high risk areas such as the intensive care unit. Pneumonia and bacteraemia account for the majority of MRSA serious clinical infections, but intra-abdominal infections, osteomyelitis, toxic shock syndrome, food poisoning, and deep tissue infections are also important clinical diseases. The traditional antibiotic therapy for MRSA is a glycopeptide, vancomycin. New antibiotics have been recently released that add to the armamentarium for therapy against MRSA and include linezolid, and quinupristin/dalfopristin, but cost, side effects, and resistance may limit their long term usefulness.
Security and Efficiency Analysis of One Time Password Techniques (2016)

As a result of the rapid growth of available services provided via Internet, as well as multiple accounts a person owns, reliable user authentication schemes are mandatory for security purposes. OTP systems have prevailed as the best viable solution for security over sensitive information and pose an interesting field for research. Although, OTP schemes enhance authentication's security through various algorithmic customizations and extensions, certain compromises should be made; especially since excessively tolerable to vulnerability systems tend to have high computational and storage needs. In order to minimize the risk of a non-authenticated user having access to sensitive data, depending on the use, OTP system's architecture differs; as its tolerance towards already known attack methods. In this paper, the most widely accepted and promising OTP schemes are described and evaluated in terms of resistance against security attacks and in terms of computational intensity (performance efficiency). The results showed that there is a correlation between the security level, the computational efficiency and the storage needs of an OTP system.
Low power multi-channel capacitive touch sensing unit using capacitor to time conversion method (2012)

This paper presents a multi-channel capacitive touch sensing unit for SoC applications. This unit includes a simple common processing unit and switch array to detect the touch sensing input by capacitive-time(C-T) conversion method. This touch sensor ASIC is designed based on the Capacitive-Time(C-T) conversion method to have advantages of small current and chip area, and the minimum resolution of the unit is 41 fF per count with the built-in sensing oscillator, LDO regulator and I2C for no additional external components. This unit is implemented in 0.18 um CMOS process with dual supply voltage of 1.8 V and 3.3 V. The total power consumption of the unit is 60 uA and the area is 0.26 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Feasibility of cross-protective vaccination against flaviviruses of the Japanese encephalitis serocomplex (2012)

Serological cross-reactivity providing cross-protective immunity between antigenically related viruses is a cornerstone of vaccination. It was the immunological basis for the first human vaccine against smallpox introduced more than 200 years ago, and continues to underpin modern vaccine development as has recently been shown for human papillomavirus vaccines, which confer cross-protection against other oncogenic papillomavirus types not present in the vaccine. Here, we review the feasibility of cross-protective vaccination against an antigenic group of clinically important viruses belonging to the Japanese encephalitis serocomplex in the Flaviviridae family. We will discuss evidence suggesting that 'new generation' flavivirus vaccines may provide effective cross-protective immunity against heterologous Japanese encephalitis serocomplex viruses, and appraise potential risks associated with cross-reactive vaccine immunity. The review will also focus on the structural and mechanistic basis for cross-protective immunity among this group of flaviviruses, which is predominantly mediated by antibodies against a single viral surface protein.
Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment. (1993)

The platelet GP Ib-IX receptor supports platelet adhesion and activation by binding to vWf in the exposed subendothelial matrix. An abnormal GP Ib-IX complex exists in platelet-type or pseudo-von Willebrand disease and has a characteristic increased affinity for soluble vWf resulting in impaired hemostatic function due to the removal of larger vWf multimers from the circulation. Genetic studies within an afflicted family have demonstrated that the disease is linked to a Gly233-->Val amino acid substitution within the alpha-subunit of the oligomeric GP Ib-IX complex (Miller, J.L., D. Cunningham, V.A. Lyle, and C. L. Finch. 1991. Proc. Natl. Acad. Sci. USA. 88:4761-4765). To evaluate the functional consequences of this mutation, we constructed a recombinant analogue of the alpha-subunit of GP Ib containing Val233. Experiments comparing molecules with either Gly233 or Val233 revealed that the Val substitution generates a molecule with increased affinity for vWf. The recombinant fragment reproduces the functional abnormality of the GP Ib-IX complex in platelet-type von Willebrand disease, thus establishing the molecular basis of the bleeding disorder within this family. Moreover, it becomes apparent that structural elements responsible for the regulation of hemostasis through modulation of vWf affinity for platelets reside within the alpha-subunit of the GP Ib-IX complex.
Contactless, photoinitiated snap-through in azobenzene-functionalized polymers (2013)

Photomechanical effects in polymeric materials and composites transduce light into mechanical work. The ability to control the intensity, polarization, placement, and duration of light irradiation is a distinctive and potentially useful tool to tailor the location, magnitude, and directionality of photogenerated mechanical work. Unfortunately, the work generated from photoresponsive materials is often slow and yields very small power densities, which diminish their potential use in applications. Here, we investigate photoinitiated snap-through in bistable arches formed from samples composed of azobenzene-functionalized polymers (both amorphous polyimides and liquid crystal polymer networks) and report orders-of-magnitude enhancement in actuation rates (approaching 10(2) mm/s) and powers (as much as 1 kW/m(3)). The contactless, ultra-fast actuation is observed at irradiation intensities <<100 mW/cm(2). Due to the bistability and symmetry of the snap-through, reversible and bidirectional actuation is demonstrated. A model is developed to elucidate the underlying mechanics of the snap-through, specifically focusing on isolating the role of sample geometry, mechanical properties of the materials, and photomechanical strain. Using light to trigger contactless, ultrafast actuation in an otherwise passive structure is a potentially versatile tool to use in mechanical design at the micro-, meso-, and millimeter scales as actuators, as well as switches that can be triggered from large standoff distances, impulse generators for microvehicles, microfluidic valves and mixers in laboratory-on-chip devices, and adaptive optical elements.
Association analysis for NMDA receptor subunit 2B (GRIN2B) genetic variants and psychopathology and clozapine response in schizophrenia (2001)

It is known that a syndrome resembling schizophrenia is produced by the N-methyl-d-aspartate receptor antagonists. It has also been demonstrated that the level of an ionotropic N-methyl-d-aspartate 2B subunit (GRIN2B) of the glutamate receptor tends to increase after subchronic administration of clozapine, suggesting that GRIN2B may play an active role in the pathogenesis of schizophrenia and the function of clozapine medication. We studied 100 schizophrenic patients, investigating the associations for the GRIN2B genetic variants, and psychiatric symptoms and clozapine response. No significant differences were demonstrated comparing these three groups in terms of the baseline Brief Psychiatric Rating Scale (BPRS) score (P = 0.441). The percentage of patients scoring within 20% of baseline BPRS after clozapine treatment was similar for the three genotype groups (P = 0.132). A marginally higher mean clozapine dosage was revealed, however, for patients bearing the 2664C/C genotype (P = 0.013). Although replication of this research is required to confirm the results, an association for the GRIN2B C2664T polymorphism and clozapine treatment is suggested from our findings, which may assist in the prediction of optimal dosage for schizophrenic patients.
Mechanical Comparison of Two Suture Constructs For Extra‐Capsular Stifle Stabilization (2011)

NLL construct is mechanically superior to OF construct.
Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels (2007)

Many inhibitory neurotransmitters in the brain activate Kir3 channels by stimulating pertussis toxin (PTX)-sensitive G-protein-coupled receptors. Here, we investigated the regulation of native muscarinic receptors and Kir3 channels expressed in NGF-differentiated PC12 cells, which are similar to sympathetic neurons. Quantitative reverse transcription-PCR and immunocytochemistry revealed that NGF treatment significantly upregulated mRNA and protein for m2 muscarinic receptors, PTX-sensitive G alpha(o) G-proteins, and Kir3.2c channels. Surprisingly, these upregulated muscarinic receptor/Kir3 signaling complexes were functionally silent. Ectopic expression of m2 muscarinic receptors or Kir3.2c channels was unable to produce muscarinic receptor-activated Kir3 currents with oxotremorine. Remarkably, pretreatment with muscarinic (m2/m4) receptor antagonists resulted in robust oxotremorine-activated Kir3 currents. Thus, sustained cholinergic stimulation of natively expressed m2/m4 muscarinic receptors controlled cell surface expression and functional coupling of both receptors and Kir3 channels. This new pathway for controlling Kir3 signaling could help limit the potential harmful effects of excessive Kir3 activity in the brain.
On the interlimb coordination and synchronization during gait (2011)

Human locomotion is based on the finely tuned coordination of the two legs. For this research, we studied the contribution of interlimb pathways for coordinating and synchronizing the legs' motion in the case where body weight is externally supported and vestibular feedback is limited. The experiments were conducted using a novel device intended for gait therapy: the MIT-Skywalker. The subject's body weight was supported by an underneath saddle-like seat, and a chest harness was used to provide stabilization of the torso. Two neurologically healthy individuals were asked to walk on the MIT-Skywalker, while one side of its split belt treadmill was unexpectedly dropped during the perturbed leg stance phase. Leg kinematics are reported as well as the effect of the timing of perturbation on the unperturbed leg. Presented here are the phase-response curves (PRCs) for both legs. We found that unilateral perturbations evoked responses at the contralateral limb, while the timing of the activation played a significant role in those responses.
Cancer marker-free enrichment and direct mutation detection in rare cancer cells by combining multi-property isolation and microfluidic concentration (2019)

Genetic analysis, rather than simply counting the number of circulating tumor cells (CTCs), which are rare cancer cells in peripheral blood, has great potential for non-invasive biopsy or "liquid biopsy." However, a practical problem in conventional enrichment of CTCs is that the isolated target cells are mixed with numerous residual leukocytes, and are suspended in a large volume. Hence, further isolation (i.e., cytokeratin (CK)-positive cell picking) or DNA purification is required for downstream genetic analysis after isolation. Here, we propose a novel cancer marker-free method of CTC enrichment by size-based Filtration and Immunomagnetic Negative selection followed by Dielectrophoretic concentration (CTC-FIND) for direct detection of genetic mutations in rare cancer cells suspended in whole blood. A combination of two independent isolation methods based on physical (filtration) and biochemical properties (immunomagnetic negative selection) in CTC-FIND allowed highly efficient cancer marker-free purification (5.1-log depletion of leukocytes). The isolated cells were trapped and concentrated using a microfluidic step-channel device using dielectrophoresis for discrimination and downstream genetic analysis. The feasibility of cancer marker-free enrichment by CTC-FIND was successfully demonstrated by directly detecting mutations in various cancer cells with a very high sensitivity of 1 cell per mL, including EpCAM and CK-negative cells, which were used to spike 8 mL of whole blood. Thus, CTC-FIND can be used with liquid biopsy to detect genetic mutations in wide-ranging CTC subsets, independent of cancer cell-specific marker expression.
Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models (2015)

ADAMTS13 metalloprotease cleaves von Willebrand factor (VWF), thereby inhibiting platelet aggregation and arterial thrombosis. An inability to cleave ultralarge VWF resulting from hereditary or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Plasma exchange is the most effective initial therapy for TTP to date. Here, we report characterization of transgenic mice expressing recombinant human ADAMTS13 (rADAMTS13) in platelets and its efficacy in inhibiting arterial thrombosis and preventing hereditary and acquired antibody-mediated TTP in murine models. Western blotting and fluorescent resonance energy transfer assay detect full-length rADAMTS13 protein and its proteolytic activity, respectively, in transgenic (Adamts13(-/-)Plt(A13)), but not in wild-type and Adamts13(-/-), platelets. The expressed rADAMTS13 is released on stimulation with thrombin and collagen, but less with 2MesADP. Platelet-delivered rADAMTS13 is able to inhibit arterial thrombosis after vascular injury and prevent the onset and progression of Shigatoxin-2 or recombinant murine VWF-induced TTP syndrome in mice despite a lack of plasma ADAMTS13 activity resulting from the ADAMTS13 gene deletion or the antibody-mediated inhibition of plasma ADAMTS13 activity. These findings provide a proof of concept that platelet-delivered ADAMTS13 may be explored as a novel treatment of arterial thrombotic disorders, including hereditary and acquired TTP, in the presence of anti-ADAMTS13 autoantibodies.
DEVELOPMENT OF HIGH DENSITY FIBER REINFORCED SILICON CARBIDE FCVI COMPOSITES (1991)

Silicon carbide continuous fiber reinforced composites are prepared by Forced flow thermal gradient Chemical Vapor Infiltration. In order to obtain high density and homogeneous ceramic composites the effects of time and thermal gradient across the preform are studied during infiltration. Cross sections of the infiltrated composites are studied with the aid of optical microscopy and image analysis. This manuscript gives an impression of the experimental composite densities and density gradients achieved and critical aspects that play a role in the infiltration process.
The Bacillus BioBrick Box: generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis (2013)

Our genetic toolbox contains three compatible empty integration vectors, two reporter vectors and a set of six promoters, two of them inducible. Furthermore, five different epitope tags offer convenient protein handling and detection. All parts adhere to the BioBrick standard and hence enable standardized work with B. subtilis. We believe that our well-documented and carefully evaluated Bacillus BioBrick Box represents a very useful genetic tool kit, not only for the iGEM competition but any other BioBrick-based project in B. subtilis.
Characterization of the genomic structure and expression of the mouse Apex2 gene (2003)

We isolated a mouse cDNA encoding APEX2 protein and demonstrated that APEX2 binds to PCNA. The level of Apex2 mRNA was high in the thymus, bone marrow, spleen, and kidney in adult mice. Apex2 consists of six exons and is flanked on the 3' end by Alas2 on X chromosome 63.0. Furthermore, Apex2 is flanked on the 5' end by a novel gene with a 106-bp intergenic sequence. We disrupted Apex2 in embryonic stem cells derived from a male mouse, and a 55-kDa APEX2 protein was detected in the nuclei of Apex2(+) but not Apex2-disrupted cells. Immunoelectron microscopy revealed that APEX2 is also localized in the mitochondria of Apex2(+) cells. In serum-stimulated BALB/c 3T3 cells, the level of Apex2 mRNA was transiently increased and the level of APEX2 reached a maximum in the late S phase, thus indicating that APEX2 may participate in postreplicative base excision repair.