gebhart/patrepeval huggingface dataset:
Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem-cell-based disease models (2018)

Synaptic dysfunction in CNS disorders is the outcome of perturbations in physiological synapse structure and function, and can be either the cause or the consequence in specific pathologies. Accumulating data in the field of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia and bipolar disorder, point to a neurodevelopmental origin of these pathologies. Due to a relatively early onset of behavioural and cognitive symptoms, it is generally acknowledged that mental illness initiates at the synapse level. On the other hand, synaptic dysfunction has been considered as an endpoint incident in neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's, mainly due to the considerably later onset of clinical symptoms and progressive appearance of cognitive deficits. This dichotomy has recently been challenged, particularly since the discovery of cell reprogramming technologies and the generation of induced pluripotent stem cells from patient somatic cells. The creation of 'disease-in-a-dish' models for multiple CNS pathologies has revealed unexpected commonalities in the molecular and cellular mechanisms operating in both developmental and degenerative conditions, most of which meet at the synapse level. In this review we discuss synaptic dysfunction in prototype neurodevelopmental and neurodegenerative diseases, emphasizing overlapping features of synaptopathy that have been suggested by studies using induced pluripotent stem-cell-based systems. These valuable disease models have highlighted a potential neurodevelopmental component in classical neurodegenerative diseases that is worth pursuing and investigating further. Moving from demonstration of correlation to understanding mechanistic causality forms the basis for developing novel therapeutics.
Stress-induced single-polarization single-mode fiber (1982)

The stress-induced birefringence in a single-mode optical fiber with an elliptical inner cladding or an elliptical core is calculated. Then the design of a fiber is proposed in which only one linearly polarized mode can propagate.
Inhibition of glycolysis in boar spermatozoa by alpha-chlorohydrin phosphate appears to be mediated by phosphatase activity (1995)

(R,S)-alpha-chlorohydrin-1-phosphate, previously shown to have no anti-glycolytic activity on mature boar sperm in vitro, is a substrate for acid and/or neutral phosphatase(s) that are associated with washed sperm. The high phosphatase activity hydrolyses the ester to alpha-chlorohydrin which undergoes oxidation to (S)-3-chlorolactaldehyde, a specific inhibitor of sperm glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase, thereby exhibiting an anti-glycolytic action.
Solution Structure and Molecular Determinants of Hemoglobin Binding of the First NEAT Domain of IsdB in<i>Staphylococcus aureus</i> (2014)

The human pathogen Staphylococcus aureus acquires heme iron from hemoglobin (Hb) via the action of a series of iron-regulated surface determinant (Isd) proteins. The cell wall anchored IsdB protein is recognized as the predominant Hb receptor, and is comprised of two NEAr transporter (NEAT) domains that act in concert to bind, extract, and transfer heme from Hb to downstream Isd proteins. Structural details of the NEAT 2 domain of IsdB have been investigated, but the molecular coordination between NEAT 2 and NEAT 1 to extract heme from hemoglobin has yet to be characterized. To obtain a more complete understanding of IsdB structure and function, we have solved the 3D solution structure of the NEAT 1 domain of IsdB (IsdB(N1)) spanning residues 125-272 of the full-length protein by NMR. The structure reveals a canonical NEAT domain fold and has particular structural similarity to the NEAT 1 and NEAT 2 domains of IsdH, which also interact with Hb. IsdB(N1) is also comprised of a short N-terminal helix, which has not been previously observed in other NEAT domain structures. Interestingly, the Hb binding region (loop 2 of IsdB(N1)) is disordered in solution. Analysis of Hb binding demonstrates that IsdB(N1) can bind metHb weakly and the affinity of this interaction is further increased by the presence of IsdB linker domain. IsdB(N1) loop 2 variants reveal that phenylalanine 164 (F164) of IsdB is necessary for Hb binding and rapid heme transfer from metHb to IsdB. Together, these findings provide a structural role for IsdB(N1) in enhancing the rate of extraction of metHb heme by the IsdB NEAT 2 domain.
The Signaling Adapters Fibroblast Growth Factor Receptor Substrate 2 and 3 Are Activated by the Thyroid TRK Oncoproteins (2003)

The thyroid TRK oncogenes are generated by chromosomal rearrangements juxtaposing the neurotrophic tyrosine receptor kinase type 1 (NTRK1) tyrosine kinase domain to foreign activating sequences. TRK oncoproteins display a constitutive tyrosine kinase activity resulting in the capability to transform NIH3T3 cells. The TRK oncoproteins' signal transduction has been in part elucidated, and it involves several signal transducers activated by the NGF-stimulated NTRK1 receptor. In this paper, we investigate the role of FRS2 and FRS3, two related adapter proteins activated by fibroblast growth factor and NTRK1 receptors, in the signaling of the thyroid TRK-T1 and TRK-T3 oncogenes. By a combination of in vitro and in vivo assays, we demonstrate that both fibroblast growth factor receptor substrate (FRS)2 and FRS3 are recruited and activated by TRK-T1 and TRK-T3. Interaction studies using different TRK-T3 mutants indicate that FRS3 is recruited by the same tyrosine residue interacting with Shc and FRS2. Expression studies show different expression patterns of the FRS adapters in normal and tumor thyroid samples: FRS3 is expressed in both normal and thyroid tumor samples, whereas FRS2 is not expressed in normal thyroid but is differentially expressed in some tumors. Altogether, our data indicate that the FRS2 and FRS3 adapters may have a role in thyroid carcinogenesis triggered by TRK oncogenes.
TIMED Doppler Interferometer (TIDI) (2015)

The TIMED Doppler Interferometer (TIDI) is a Fabry-Perot interferometer designed to measure winds, temperatures, and constituents in the mesosphere and thermosphere (60-300 km) region of the atmosphere as part of the TIMED mission. TIDI is a limb viewer and observes emissions from OI 557.7 nm, OI 630.0 nm, OII 732.0 nm, O2(0-0), O2(0-1), Na D, OI 844.6 nm, and OH in the spectral region 550-900 nm. Wind measurement accuracies will approach 3 ms-1 in the mesosphere and 15 ms-1 in the thermosphere. The TIDI instrument has several novel features that allow high measurement accuracies in a modest-sized instrument. These include: an optical system that simultaneously feeds the views from four scanning telescopes which are pointed at ±45 ° and ±135 ° to the spacecraft velocity vector into a high-resolution interferometer, the first spaceflight application of the circle-to-line imaging optic (CLIO), and a high quantum efficiency, low noise CCD.
Displays develop a new flexibility (2006)

Flexible displays are of great interest especially for mobile applications. Currently, there are no active-matrix flexible displays on the market, even though research has been carried out continuously over several years. Here, we introduce flexible displays and the prototype devices that have been developed. Organic thin-film transistors have been fabricated on plastic substrates for display backplanes. We describe the performance of our transistors made using a self-organization process. Finally, a set of research goals are outlined.
Kurt-Ulrich Jäschke, Wilhelm der Eroberer. Sein doppelter Herrschaftsantritt im Jahre 1066 (1981)

Article Kurt-Ulrich Jäschke, Wilhelm der Eroberer. Sein doppelter Herrschaftsantritt im Jahre 1066 was published on August 1, 1981 in the journal Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Germanistische Abteilung (volume 98, issue 1).
Regularized thin-fiber model for nanofiber formation by centrifugal spinning (2014)

We propose a regularized thin-fiber (string) model that overcomes past numerical limitations and allows determination of the steady fiber velocity and diameter of a semi-infinite Newtonian viscous fiber emerging from a nozzle rotating about an axis in the presence of centrifugal, inertial, and viscous forces of arbitrary magnitudes. The results are controlled by two dimensionless groups, namely, the Rossby number Rb expressing the ratio of inertial to centrifugal forces and the Reynolds number Re, the ratio of inertial to viscous forces. We find that for Rb < 0.5 and Re < 1, regularization of the string-model equations is required to provide numerical stability, which we achieve. Solutions are thereby obtained in which viscosity reduces curvature in the fiber trajectory; these solutions asymptotically approach the inviscid solution at large distances along the spin line. Thus, long spin lines reach a diameter that is independent of viscosity, as long as the fiber is sufficiently long, a criterion that is made clear in the paper. At Rb > 0.5, regularization is not required, the curvature in fiber trajectory is increased by viscosity, and the solution at large distances along the spin line does not converge to the inviscid result. Regimes of behavior in the plane formed by Re and Rb are mapped out and example behavior is given for each regime.
Different functional states of fusion protein gB revealed on human cytomegalovirus by cryo electron tomography with Volta phase plate (2018)

Human cytomegalovirus (HCMV) enters host by glycoprotein B (gB)-mediated membrane fusion upon receptor-binding to gH/gL-related complexes, causing devastating diseases such as birth defects. Although an X-ray crystal structure of the recombinant gB ectodomain at postfusion conformation is available, the structures of prefusion gB and its complex with gH/gL on the viral envelope remain elusive. Here, we demonstrate the utility of cryo electron tomography (cryoET) with energy filtering and the cutting-edge technologies of Volta phase plate (VPP) and direct electron-counting detection to capture metastable prefusion viral fusion proteins and report the structures of glycoproteins in the native environment of HCMV virions. We established the validity of our approach by obtaining cryoET in situ structures of the vesicular stomatitis virus (VSV) glycoprotein G trimer (171 kD) in prefusion and postfusion conformations, which agree with the known crystal structures of purified G trimers in both conformations. The excellent contrast afforded by these technologies has enabled us to identify gB trimers (303kD) in two distinct conformations in HCMV tomograms and obtain their in situ structures at up to 21 Å resolution through subtomographic averaging. The predominant conformation (79%), which we designate as gB prefusion conformation, fashions a globular endodomain and a Christmas tree-shaped ectodomain, while the minority conformation (21%) has a columnar tree-shaped ectodomain that matches the crystal structure of the "postfusion" gB ectodomain. We also observed prefusion gB in complex with an "L"-shaped density attributed to the gH/gL complex. Integration of these structures of HCMV glycoproteins in multiple functional states and oligomeric forms with existing biochemical data and domain organization of other class III viral fusion proteins suggests that gH/gL receptor-binding triggers conformational changes of gB endodomain, which in turn triggers two essential steps to actuate virus-cell membrane fusion: exposure of gB fusion loops and unfurling of gB ectodomain.
End-to-End Object Encryption and Signatures for the Extensible Messaging and Presence Protocol (XMPP) (2014)

This document defines a method of end-to-end object encryption for the
Extensible Messaging and Presence Protocol (XMPP).
Efficacy and Safety of a Topical Diclofenac Solution (Pennsaid) in the Treatment of Primary Osteoarthritis of the Knee (2004)

Topical diclofenac is effective in the treatment of the symptoms of primary OA of the knee, with only minor local irritation and no significant systemic adverse events.
Singularities in a Relativistic Pulsar Wind (1998)

Abstract The nature of a singularity in a cool, gravitation-free axisymmetrical, relativistic, steady pulsar wind is further investigated, in line with the recent counter-argument of Ardavan (1995, hereafter A95) that the pure Alfvén ‘singularity’ has an equal importance to the Alfvén singularity if one defines the singularity via a quadratic form rather than using the ratio as adopted by Li & Melrose (1994). The pure Alfvénic point in A95 coincides with the proposed characteristic point through which a continuous wind will meet the star and infinity. However, we find that the critical point as implied in the quadratic form is in fact the intermediate point (Ardavan 1979), but not the pure Alfvénic point. Thus the analysis of A95 does not indicate any significance of the pure Alfvénic point. We also demonstrate that the intermediate point which appears in the quadratic form of A95 is not genuine.
Incoherent digital holographic adaptive optics (2012)

An adaptive optical system based on incoherent digital holography is described. Theoretical and experimental studies show that wavefront sensing and compensation can be achieved by numerical processing of digital holograms of incoherent objects and a guide star, thereby dispensing with the hardware components of conventional adaptive optics systems, such as lenslet arrays and deformable mirrors. The incoherent digital holographic adaptive optics (IDHAO) process is seen to be robust and effective under various ranges of parameters, such as aberration type and strength. Furthermore, low and noisy image signals can be extracted by IDHAO to yield high-quality images with good contrast and resolution, both for point-like and continuous extended objects, illuminated with common incoherent light. Potential applications in astronomical and other imaging systems appear plausible.
Everolimus for stent-based intracoronary applications. (2004)

Everolimus, a novel proliferation signal inhibitor initially developed for the prevention of allograft rejection after organ transplantation, is a potent anti-proliferative and immunosuppressive agent. Compared to sirolimus, everolimus absorbs to local tissue more rapidly and possesses longer cellular residence time and activity. The stent-based intracoronary elution of everolimus was first investigated by BioSensors International using a bioabsorbable-PLA-polymer-coated S-Stent for drug delivery. Following preclinical animal studies that demonstrated excellent safety and efficacy of this device, the clinical FUTURE trial program was initiated. FUTURE I and II were designed to demonstrate safety and feasibility of the everolimus-eluting stent in a small patient population with focal de novo coronary lesions. At follow-up, an acceptable safety profile without evidence of stent thrombosis or late stent malapposition was observed. Moreover, these studies revealed a remarkable reduction of neointimal proliferation with everolimus-eluting stent implantation versus procedures utilizing bare-metal stents. Guidant Corporation licensed the exclusive rights to both the S-Stent and the bioabsorbable drug delivery platform. Guidant will conduct two pivotal trials (FUTURE III and IV) in order to demonstrate the efficacy of this stent design. FUTURE IV will make a non-inferiority comparison between everolimus and the already-approved drug eluting stent systems. Given the pooled results of FUTURE I and II, there is already some evidence suggesting that the everolimus-eluting stent is as potent a suppressor of reactive neointimal ingrowth as the sirolimus-eluting CYPHERTM stent. The everolimus-eluting coronary stent might shortly be established as a new and promising contender in the field of drug eluting stents for treatment of coronary heart disease.
Microsecond ferrite microwave switch (1957)

A novel ferrite structure in rectangular waveguide utilizing a new mode conversion technique has been highly successful as an on-off microwave ferrite switch. The unit provides 25 db of pulsed attenuation with only 0.5 db insertion loss. The VSWR is less than 1.15 and the RF rise and fall times are less than 1/10 microsecond. Less than 30 ampere turns of magnetomotive force are required to drive the unit from a small compact low voltage driving circuit. Theory, general design consideration, developmental problems, optimization procedures and component characteristics will be discussed.
Host regulation by the aphid parasitoid <i>Aphidius ervi</i>: the role of teratocytes (2000)

Abstract The biochemical profile and metabolism of Acyrthosiphon pisum (Harris) (Homoptera, Aphididae) are markedly altered and redirected in response to parasitization by the endophagous braconid Aphidius ervi Haliday (Hymenoptera, Braconidae). In the present study, the role played in the host regulation process by teratocytes, cells deriving from the dissociation of the embryonic membrane of the parasitoid, is taken into consideration. The protein synthesis activity of these cells of embryonic origin is analysed in vitro and an essential characterization of those proteins de novo synthesized and released in the incubation medium is provided. Teratocytes, obtained by dissecting parasitized host aphids, 3, 4 and 5 days after parasitoid oviposition, were incubated in vitro and, at the end of the incubation period, were separated from the medium for SDS‐PAGE analysis of both cellular and secreted proteins. Various cellular proteins were more abundant as the time between parasitization and teratocyte collection increased. Furthermore, two proteins, showing an approximate molecular mass of 15 kD (p15) and 45 kD (p45) respectively, were abundantly secreted in the incubation medium by 5 day‐old teratocytes. Incubations in presence of 35 S radiolabelled amino acids indicated that p15 and p45 are both synthesized by A. ervi teratocytes. The amino acid composition of these two proteins was similar to that reported for other insect proteins with a demonstrated nutritional function. The p45 protein was found to be glycosylated. A tentative physiological model describing the host regulation role played by different parasitoid‐derived factors is proposed.
Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX‐1 (2006)

PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes.
Analysis of electrical and optical characteristics of InGaSb PIN photodiodes (2012)

This study represents an analysis of electrical and optical characteristics of InGaSb PIN photodiodes. The electrical characteristics are analysed by depicting a model of zero-bias resistance–area product (R0A) of such photodiodes. The effects of dislocation and temperature on R0A are also included in the model. Different optoelectronic properties of the material are extracted by fitting the obtained models with experimental data. The extracted dislocation density is 6.67×108 cm−2, which is close to the measured value of 2.4(±0.2)×108 cm−2. Through the dislocation and temperature-dependent modelling, maximum R0A is found to be 1.85 Ω cm2 at 139 K. Experimental data obtained at 300 and 363 K are fitted with theoretical model. The optical properties are analysed by the modelling of responsivity, quantum efficiency and detectivity. Cutoff wavelength is found to be 2271 nm, which is within ±5 nm of the experimentally obtained data. The present analysis gives a photodiode responsivity is 0.47 A/W, quantum efficiency is 28.86% and detectivity is 1.53×109 cm Hz1/2/W1 at a particular wavelength of λ=2.0 µm, which are agreeable to the experimentally obtained data.
Diagnosis and Detection of Drug-Resistant Strains of M. tuberculosis (1995)

Although tuberculosis (TB) continues to affect an estimated 10% to 50% of the world population, with three million tuberculosis-related deaths annually, the disease had been widely believed to be controlled in the United States. Improved nutrition, higher standards of living for the poor, and the post-World War II discoveries of antituberculosis antibiotics dramatically decreased the incidence of active disease. The rate of decline in incidence in the U.S. had been approximately 6% per year, reaching an all-time low of only 22,000 reported cases in 1984.1,2 This decline in diagnosed disease was the foundation for the forecast that complete eradication of tuberculosis could be achieved in the United States by the end of the 20th century.

However, beginning in the 1960s, responsibility for managing remaining tuberculosis cases shifted from specialized hospital units to less-well-equipped outpatient settings. Medical school teaching of tuberculosis-related issues declined, and research funding for the disease was dramatically reduced.2 In the 1980s, large-scale immigration from regions endemic for tuberculosis introduced new cases into the U.S., and the increase in homelessness and AIDS in American cities has created a dangerous and self-perpetuating pocket of disease in two populations that are particularly at risk. Finally, the ease with which the organism can spread within institutionalized populations has made outbreaks of tuberculosis common in prisons, nursing homes, and hospitals.

As a result of these many factors, a deadly resurgence of this ancient scourge is taking place, with an estimated 10 to 15 million Americans currently infected by tuberculosis.1 Two recent studies from San Francisco and New York revealed startling findings about the nature of the latest epidemic.3,4 Using DNA fingerprinting to evaluate the relative contribution of recent infection to the overall incidence of TB, these studies found that at least 33% of current cases can …
Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges (2009)

Female sexual dysfunction (FSD) is a prevalent problem, afflicting approximately 40% of women and there are few treatment options. FSD is more typical as women age and is a progressive and widespread condition. Common symptoms associated with FSD include diminished vaginal lubrication, pain and discomfort upon intercourse, decreased sense of arousal and difficulty in achieving orgasm. Only a small percentage of women seek medical attention. In comparison to the overwhelming research and treatment for erectile dysfunction in males, specifically with the development of phosphodiesterase type 5 inhibitors, significantly less has been explored regarding FSD and treatment is primarily limited to psychological therapy. Several cardiovascular diseases have been linked with FSD including atherosclerosis, peripheral arterial disease and hypertension, all of which are also pathological conditions associated with aging and erectile dysfunction in men. Using animal models, we have expanded our understanding of FSD, however a tremendous amount is still to be learned in order to properly treat women suffering from FSD. The aim of this review is to provide the most current knowledge on FSD, advances in basic science addressing this dysfunction, and explore developing therapeutic options.