gebhart/patrepeval huggingface dataset:
Prion-like disorders: blurring the divide between transmissibility and infectivity (2010)

Prions are proteins that access self-templating amyloid forms, which confer phenotypic changes that can spread from individual to individual within or between species. These infectious phenotypes can be beneficial, as with yeast prions, or deleterious, as with mammalian prions that transmit spongiform encephalopathies. However, the ability to form self-templating amyloid is not unique to prion proteins. Diverse polypeptides that tend to populate intrinsically unfolded states also form self-templating amyloid conformers that are associated with devastating neurodegenerative disorders. Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins. Can these proteins and the neurodegenerative diseases to which they are linked become 'infectious' too? Here, we highlight advances that define the transmissibility of amyloid forms connected with Alzheimer's disease, Parkinson's disease and Huntington's disease. Collectively, these findings suggest that amyloid conformers can spread from cell to cell within the brains of afflicted individuals, thereby spreading the specific neurodegenerative phenotypes distinctive to the protein being converted to amyloid. Importantly, this transmissibility mandates a re-evaluation of emerging neuronal graft and stem-cell therapies. In this Commentary, we suggest how these treatments might be optimized to overcome the transmissible conformers that confer neurodegeneration.
Improving the beam quality in LMA fibers (2008)

The paper presents the results concerning with beam quality improvement by concurrently modifying the index and the doping profile in LMA fibers. Further, the mode effective area is maximized by providing a passive ring in the cladding. The influence of the index profile over the distribution of the optical power among various modes is presented. The aim is to favor the fundamental mode by concurrently rejecting the higher modes, i.e. generating a quality beam. Simulation results and manufacturer's tests led to a novel design which consists in providing a passive ring in the cladding. That was of great help in rejecting the higher-order modes, and it can be applied to a large range of LMA fibers. The cladding ring procedure is of interest for Liekki, and it is very likely that it would be put into production.
Model Studies for a Wave Riding Facility (1980)

Results of a model study for producing a stationary, oblique continuously breaking wave in a recirculating flume are reported. The wave is produced by placing a suitably shaped obstacle in the path of the flow issuing from a sluice gate. Attached to the downstream end of the obstacle is a turning vane which enables the flow to execute a 180 turn with minimum energy losses while remaining supercritical. The type of wave produced in the facility is demonstrated by a typical wave surface contour plot. Detailed pilot surveys of the flow are used to identify the main sources of power losses. These occur in the vicinity of the drive propellers and in the diffuser downstream. The studies indicate that it should be possible to produce a wave 1 m high in the facility which is presently under construction.
Proteinase inhibitors of bovine nasal cartilage (1978)

Extracts from bovine nasal cartilage with 1 M-guanidinium chloride were fractionated by ultrafiltration. Gel chromatography of the low-molecular-weight material resolved three distinct fractions with inhibitory activity against (a) collagenases (22000 mol.wt.), (b) thiol proteinases cathepsin B and papain (13000 mol.wt.), and (c) trypsin and other serine proteinases (7000 mol.wt.).
Screening of sulfate-reducing bacteria in colonoscopy samples from healthy and colitic human gut mucosa (2000)

A PCR-based approach combined with microbiological cultivation methods was employed to determine the occurrence of sulfate-reducing bacteria (SRB) in colon biopsy samples from ulcerative colitis patients and from non-colitic controls. The detection of mucosa-associated SRB was carried out by digoxigenin-dUTP-labelled PCR amplification, in liquid Postgate medium B and in a new liquid medium, termed VM medium I. Using Postgate medium B, the growth of SRB was confirmed in 92% of the colitic specimens and in 52% of non-colitic samples. However, PCR analysis and incubation in VM medium I detected SRB in 100% of biopsy material indicating ubiquitous presence of SRB in human colon mucosa.
Air-stable n-type organic thin-film transistor array and high gain complementary inverter on flexible substrate (2010)

Air-stable n-type organic thin-film transistor (TFT) arrays and a complementary inverter circuit were fabricated on a flexible substrate. A benzobis(thiadiazole) (BBT) derivative-based TFT showed excellent air- stability and performances such as an electron mobility of over 0.1 cm2/V s, a large ON/OFF ratio over 108 when combined with a cross-linkable olefin-type polymer gate dielectric. In addition, an organic complementary inverter that combined the BBT derivative and a pentacene TFT demonstrated a sharp switching behavior and a high gain of over 150. We attribute these excellent characteristics to a combination of the low-lying lowest unoccupied molecular orbital level of n-type semiconductor material and the low interface trap of the gate dielectric.
Hemispherical Resonator Gyro: Status Report and Test Results (1984)

The employment of Ring Laser Gyro (RLG) technology has been identified as an approach to provide a more accurate, highly reliable Attitude and Heading Reference System (AHRS) for helicopters. Based on this identification, a feasibility model RLG AHRS was interfaced with suitable flight test instrumentation to demonstrate its performance characteristics in flight profiles typical of Army tactical operations. In addition, the RLG AHRS was integrated with a doppler navigation system to demonstrate the improved overall navigation performance benefits achievable due to a more accurate heading input. The flight test results indicated that the RLG AHRS solves a number of the problems inherent in conventional spinning mass gyro strap-down references in high dynamic maneuvers.

The paper includes a description of the RLG AHRS, flight test instrumentation, data recording, data reduction and display systems. Of particular note is the use of a standard time division multiplex data bus which interfaced all elements of the flight test configuration.
Model based engineering of Pichia pastoris central metabolism enhances recombinant protein production (2014)

The production of recombinant proteins is frequently enhanced at the levels of transcription, codon usage, protein folding and secretion. Overproduction of heterologous proteins, however, also directly affects the primary metabolism of the producing cells. By incorporation of the production of a heterologous protein into a genome scale metabolic model of the yeast Pichia pastoris, the effects of overproduction were simulated and gene targets for deletion or overexpression for enhanced productivity were predicted. Overexpression targets were localized in the pentose phosphate pathway and the TCA cycle, while knockout targets were found in several branch points of glycolysis. Five out of 9 tested targets led to an enhanced production of cytosolic human superoxide dismutase (hSOD). Expression of bacterial β-glucuronidase could be enhanced as well by most of the same genetic modifications. Beneficial mutations were mainly related to reduction of the NADP/H pool and the deletion of fermentative pathways. Overexpression of the hSOD gene itself had a strong impact on intracellular fluxes, most of which changed in the same direction as predicted by the model. In vivo fluxes changed in the same direction as predicted to improve hSOD production. Genome scale metabolic modeling is shown to predict overexpression and deletion mutants which enhance recombinant protein production with high accuracy.
Collagen fiber orientations in human secondary osteons (1977)

Scanning electron microscopy studies of decalcified human secondary osteons were conducted to determine correlations in fiber orientations in these osteons with their appearance under crossed polaroids. Using a new sample preparation technique, osteons were prepared to expose many of their lamellar interfaces. By studying many such samples, it was concluded that osteons which appear 'dark' under crossed polaroids contain fibers with orientations having little or no transverse component, whereas 'bright' osteons possess fiber orientations with transverse and longitudinal components. 'Intermediate' osteons have been found to contain fiber orientations richer in longitudinal component than in transverse.
A focal domain of extreme demethylation within D4Z4 in FSHD2 (2013)

These data challenge the simple view that FSHD is caused by a broad "opening" of D4Z4 and lead us to postulate that the region of focal demethylation is the site of action of the key D4Z4 chromatin regulatory factors that go awry in FSHD.
A Textbook of Exodontia: Exodontia. Oral Surgery and Anesthesia. (1931)

In this edition the author has incorporated all the important results of recent studies in the field of general and local anesthesia. He gives a detailed description of the various local anesthetics together with their physiologic action, method of preparation and injection, and the after-effects. The book deals largely with clinical work. Excellently executed drawings from life, showing the position of the patient and the operator, for every type of exodontia, will be of great value both to the student and to the general practitioner. Those who desire a more detailed description of the pathology and technic for the removal of impacted mandibular third molars may consult the same author's book on "Impacted Third Mandibular Molars." This volume is a practical manual on exodontia, and does not include the pathology and treatment of the diseases of the mouth, except for one chapter on cysts of the jaws. The book is
Total synthesis of the racemic 3-methyl analogue of the antitumour agent acivicin (1989)

The racemic 3-methyl analogue (19a) of acivicin (1) has been synthesized by a stereorandom route starting with acetonitrile oxide (3) and a novel vinylglycine precursor, ethyl 2-acetoxybut-3-enoate (9). The diastereoisomeric alcohols (11a,b) and azides (14a,b) were separated and used for the synthesis of the individual diastereoisomers of compounds (10), (12), and (15)–(19). The erythro- and threo-diastereoisomers were identified on the basis of their 1H and 13C n.m.r. spectra.
Nanotube-Based Colorimetric Probe for Ultrasensitive Detection of Ataxia Telangiectasia Mutated Protein (2011)

We have developed a nanotube-based colorimetric probe using multiwalled carbon nanotubes (MWNTs), anti-immunoglobulin G (anti-IgG), and horseradish peroxidase (HRP). The probe was used as an alternative to conventional colorimetric conjugates to obtain amplified signals in a sandwich-type immunoassay for ataxia telangiectasia mutated (ATM), a potential biomarker for radiation doses and cancers. Results show that the MWNT-based probe colorimetry was 5000 times more sensitive than a conventional ELISA, while its concentration range was 10,000 times wider than that of the latter. Its limit of detection (LOD) was 0.2 fg/mL (54 aM, ~32 molecules in 1 μL samples). Control experiments showed that detection of ATM molecules at the picogram-level could still be achieved in samples that contained protein makers present at more than 100 times the ATM concentration, demonstrating the high specificity of the technique. The MWNT-based probe also has the potential to become a universal probe for colorimetric assays of most protein markers because it can recognize the associated rabbit polyclonal antibodies.
Enhanced susceptibility to suicidal death of erythrocytes from transgenic mice overexpressing erythropoietin (2007)

Eryptosis, a suicidal death of mature erythrocytes, is characterized by decrease of cell volume, cell membrane blebbing, and breakdown of cell membrane asymmetry with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increased cytosolic Ca(2+) activity, which could result from activation of Ca(2+)-permeable cation channels. Ca(2+) triggers phosphatidylserine exposure and activates Ca(2+)-sensitive K(+) channels, leading to cellular K(+) loss and cell shrinkage. The cation channels and thus eryptosis are stimulated by Cl(-) removal and inhibited by erythropoietin. The present experiments explored eryptosis in transgenic mice overexpressing erythropoietin (tg6). Erythrocytes were drawn from tg6 mice and their wild-type littermates (WT). Phosphatidylserine exposure was estimated from annexin binding and cell volume from forward scatter in fluorescence-activated cell sorting (FACS) analysis. The percentage of annexin binding was significantly larger and forward scatter significantly smaller in tg6 than in WT erythrocytes. Transgenic erythrocytes were significantly more resistant to osmotic lysis than WT erythrocytes. Cl(-) removal and exposure to the Ca(2+) ionophore ionomycin (1 microM) increased annexin binding and decreased forward scatter, effects larger in tg6 than in WT erythrocytes. The K(+) ionophore valinomycin (10 nM) triggered eryptosis in both tg6 and WT erythrocytes and abrogated differences between genotypes. An increase of extracellular K(+) concentration to 125 mM blunted the difference between tg6 and WT erythrocytes. Fluo-3 fluorescence reflecting cytosolic Ca(2+) activity was larger in tg6 than in WT erythrocytes. In conclusion, circulating erythrocytes from tg6 mice are sensitized to triggers of eryptosis but more resistant to osmotic lysis, properties at least partially due to enhanced Ca(2+) entry and increased K(+) channel activity.
Speech enhancement using a ternary-decision based filter (2002)

A new speech enhancement scheme based on a generalized Wiener filter formulation is proposed. A ternary-valued parameter is derived empirically based on the likelihood of the input signal vector being classified as speech. This parameter controls the Wiener filter coefficient in order to obtain an improved speech spectral estimate. This "ternary-decision" concept renders a logical compromise between the simple, hard, "binary speech/noise decision" filtering and the elaborate "soft-decision" filtering approaches in terms of practicality and performance. An important feature in our scheme is that we exploit the interframe spectral relationship to reinforce the assessment of the likelihood of weak speech components. This feature prevents many weak formants from being disproportionally attenuated as in most previous schemes. Other important features of our scheme include a novel speech/noise classifier and a robust noise median amplitude tracker, both of which make the estimate of noise spectrum more reliable. A preliminary evaluation of this new scheme is reported here.
Effect of Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs on Gene Expression of Mesenchymal Stem Cells (2012)

We have previously shown that mesenchymal stem cells (MSCs) from patients with osteoarthritis (OA) constitutively express type X collagen, a marker of late-stage chondrocyte hypertrophy, osteogenic marker genes, including alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), and chondrogenesis marker gene aggrecan (ACAN). As patients with arthritis often take nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (Acet), the purpose of the study was to assess whether these drugs can affect the gene expression of human MSCs. MSCs isolated from the bone marrow of patients with OA or normal donors were cultured without (control) or with Acet or NSAIDs, which include ibuprofen, diclofenac (Dic), naproxen, and celebrex. After 3 days of culture, the expression of type X collagen alpha 1 (COL10A1), ACAN, COL1A1, as well as ALP, BSP, OC, and Runt-related transcription factor 2 was analyzed by real-time reverse transcription (RT)-polymerase chain reaction. The results showed that COL10A1 and the osteogenic and chondrogenic marker genes can be regulated by NSAIDs and Acet in normal MSCs. In contrast, Acet did not significantly affect COL10A1 expression in OA MSCs, while Dic is the only drug that had no significant effect on all markers in normal MSCs. The upregulation of COL10A1 in normal MCSs by Acet and Npx may explain why stem cells from patients with OA express COL10A1 constitutively. This knowledge may help in designing better strategies for stem cell differentiation into chondrocyte-like cells, from this source, with Dic being a viable option for treating OA pain, with an eye toward preventing the potential to enhance calcification in the repair of cartilage and degenerated intervertebral discs.
Protein design: from computer models to artificial intelligence (2017)

The rational design of novel biomolecules with desired functional properties is one of the most fascinating challenges in science, with implications at the fundamental and practical levels. From the fundamental point of view, the design of proteins able to support nonnatural reactivities represents the decisive test on our understanding of the molecular mechanisms through which biomolecules operate. From the practical point of view, new designs may open the way to applications in a wide variety of fields, ranging from health to life science, and from catalysis to material sciences. During the past decades, we have witnessed an amazing transition in the application of computational methods to protein and enzyme design, from simple fold prediction to ab initio structural design. Herein, we review key areas and fundamental aspects of research in the design of protein structures, interactions, and reactivities. We also provide our perspective on the exciting range of developments that are made possible by the integration of innovations in hardware, software, and theory, while keeping an eye on the applications, challenges, and opportunities that can open up in many different domains of science. WIREs Comput Mol Sci 2017, 7:e1318. doi: 10.1002/wcms.1318 This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods
[The deontological aspects of the legal regulation of the activities of military medical commissions]. (1992)

Practically, the questions of deontology are not working out in the sphere of military medical rating (expertise). Finally this fact leads to methodical errors, defects in medical examinations, and thus to a considerable number of requests and complaints. The authors examine the basic questions of deontology from the point of view of the following aspects: collegiality, obligation to render the verdict on medical examination in the presence of examinee, medical secrecy and strict legal regulation of this norm, deontological questions in drawing up, filling in, storing and giving out medical rating documents.
Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia (1992)

A rapid and physiologically relevant hyperthermia-based induction procedure has been utilized to develop an in vivo model of induced herpes simplex virus (HSV) reactivation in outbred Swiss Webster mice. This procedure was found to efficiently reactivate latent virus from both trigeminal and lumbosacral ganglia. Examination of the time between hyperthermia and virus production demonstrated that detectable levels of infectious virus were present in ganglia as soon as 14 h posttreatment, with peak percent recoveries at 24 h. These data indicated that the switch from latent to active viral gene transcription occurred rapidly following treatment. Immunohistochemical staining for HSV type 1 antigens revealed rare antigen-positive ganglionic neurons 24 h postinduction. HSV antigens were not detected in any other cell type, and lateral spread of the infection was not observed. This is the first report of the detection of HSV antigens in vivo following induced reactivation in the intact nervous system and demonstrates that the neuron is the site of infectious virus production. In addition, our data strongly suggest that at least some neurons in which HSV antigens are detected during reactivation do not survive. Because the temporal and spatial characteristics of HSV reactivation have been clearly defined, this model is uniquely suited for the molecular dissection of the reactivation process.
High resolution estimation of the time of arrival for GSM location (2002)

Location services in cellular systems have become more and more important. One of the reasons is the Federal Communications Commission's (FCC) requirement to determine the position of a mobile user within an root-mean-square accuracy of 125 meters. A number of location techniques are based on the estimation of the time of arrival (TOA) or the time difference of arrival (TDOA) of the line-of-sight (LOS) signal component. However, due to multipath propagation and the limited bandwidth available in GSM or in other narrowband systems, an accurate TOA-estimation using conventional methods is hardly achievable. In this paper TOA-estimations using the modified-least-squares-Prony (MLS-Prony) and the Root-MUSIC techniques are presented. Moreover, the performance of both techniques is evaluated through simulations of a GSM transmission over different multipath channels.
Cost-per-Click Pricing for Display Advertising (2014)

Display advertising is a $25 billion business with a promising upward revenue trend. In this paper, we consider an online display advertising setting in which a web publisher posts display ads on its website and charges based on the cost-per-click pricing scheme while promising to deliver a certain number of clicks to the ads posted. The publisher is faced with uncertain demand for advertising slots and uncertain traffic to its website as well as uncertain click behavior of visitors. We formulate the problem as a novel queueing system, where the slots correspond to service channels with the service rate of each server inversely related to the number of active servers. We obtain the closed-form solution for the steady-state probabilities of the number of ads in the publisher's system. We determine the publisher's optimal price to charge per click and show that it can increase in the number of advertising slots and the number of promised clicks. We show that the common heuristic used by many web publishers to convert between the cost-per-click and cost-per-impression pricing schemes using the so-called click-through-rate can be misleading because it may incur substantial revenue loss to web publishers. We provide an alternative explanation for the phenomenon observed by several publishers that the click-through-rate tends to drop when they switch from the cost-per-click to cost-per-impression pricing scheme.