Miracle-dz/UniFAR-FTUs huggingface dataset:
Overlapping Binding Sites in Protein Phosphatase 2A for Association with Regulatory A and α-4 (mTap42) Subunits*

Diverse functions of protein Ser/Thr phosphatases depend on the distribution of the catalytic subunits among multiple regulatory subunits. In cells protein phosphatase 2A catalytic subunit (PP2Ac) mostly binds to a scaffold subunit (A subunit or PR65); however, PP2Ac alternatively binds to α-4, a subunit related to yeast Tap42 protein, which also associates with phosphatases PP4 or PP6. We mapped α-4 binding to PP2Ac to the helical domain, residues 19-165. We mutated selected residues and transiently expressed epitope-tagged PP2Ac to assay for association with A and α-4 subunits by co-precipitation. The disabling H118N mutation at the active site or the presence of the active site inhibitor microcystin-LR did not interfere with binding of PP2Ac to either the A subunit or α-4, showing that these are allosteric regulators. Positively charged side chains Lys41, Arg49, and Lys74 on the back surface of PP2Ac are unique to PP2Ac, compared with phosphatases PP4, PP6, and PP1. Substitution of one, two, or three of these residues with Ala produced a progressive loss of binding to the A subunit, with a corresponding increase in binding to α-4. Conversely, mutation of Glu42 in PP2Ac essentially eliminated PP2Ac binding to α-4, with an increase in binding to the A subunit. Reciprocal changes in binding because of mutations indicate competitive distribution of PP2Ac between these regulatory subunits and demonstrate that the mutated catalytic subunits retained a native conformation. Furthermore, neither the Lys41-Arg49-Lys74 nor Glu42 mutations affected the phosphatase-specific activity or binding to microcystin-agarose. Binding of PP2Ac to microcystin and to α-4 increased with temperature, consistent with an activation energy barrier for these interactions. Our results reveal that the A subunit and α-4 (mTap42) require charged residues in separate but overlapping surface regions to associate with the back side of PP2Ac and modulate phosphatase activity.
Rationale and development of multispecific antibody drugs

Bispecific antibodies (bsAbs) have been on the scene for decades and represent the next generation of antibody-based therapeutics. Unlike monospecific, monoclonal antibodies (mAbs), bsAbs can target two or more disease mechanisms as a single agent and can offer certain unique therapeutic strategies that are difficult to acheive with mAbs. The lessons learned during the past 35 years of mAb development and 25 years of bsAbs experience are shaping development of the next generation of bsAbs and multispecific antibody-based drugs. Recent improvements in manufacturability and drug-like properties of certain BsAb formats, and clinical success for a few BsAbs, are reviving this area. In this article, we discuss the potential limitations of the first-generation mAbs and opportunities to improve upon existing mAb drugs, factors driving the multispecific antibody field and the strengths, weaknesses and development status of representative multispecific antibody concepts.
Apparent heterogeneous responsiveness of human platelet rich plasma to catecholamines

The platelet-rich plasma (PRP) from 35 healthy Korean volunteers were challenged by four catecholamines and clonidine, which were known as α-adrenergic agonists. Wide individual variations were observed with the respect to the pattern and the degree of aggregation in response to each agent. They fall into five distinct groups; Group A (2.9%) was responsive to all five agonists; Group B (28.6%) aggregated in response to (−)-epinephrine, (−)-norepinephrine and epinine; Group C (37.1%) aggregated in response to (−)-epinephrine and (−)-norepinephrine; Group D (11.4%) aggregated only by (−)-epinephrine; Group E (20%) showed impaired responsiveness to all the α-agonists tested. All of the non-responding PRP were capable of induction of aggregation in response to (−)-epinephrine, (−)-norepinephrine and epinine in the presence of near-threshold concentration of collagen. Variations were also observed between groups with dopamine and clonidine. Dopamine and clonidine failed to induce secondary aggregation, even in the presence of low concentration of collagen, in most of the PRP preparations belonging to Groups D and E and only slight improvements were observed in the preparations belonging to groups B and C. The observation on heterogeneous responsiveness to catecholamines with PRP of Korean volunteers is quite different from the previous report with PRP of presumably mostly Caucasians.
The effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects.

Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5 micron triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings. (ABSTRACT TRUNCATED AT 250 WORDS)
esolving surface chemical states in XPS analysis of first row transition metals , xides and hydroxides : Sc , Ti , V , Cu and Zn ark

Chemical state X-ray photoelectron spectroscopic analysis of first row transition metals and their oxides and hydroxides is challenging due to the complexity of the 2p spectra resulting from peak asymmetries, complex multiplet splitting, shake-up and plasmon loss structure, and uncertain, overlapping binding energies. A review of current literature shows that all values necessary for reproducible, quantitative chemical state analysis are usually not provided. This paper reports a more consistent, practical and effective approach to curve-fitting the various chemical states in a variety of Sc, Ti, V, Cu and Zn metals, oxides and hydroxides. The curve-fitting procedures proposed are based on a combination of (1) standard spectra from quality reference samples, (2) a survey of appropriate literature databases and/or a compilation of the literature references, and (3) specific literature references where fitting procedures xides are available. Binding energies, full-width at half maximum (FWHM) values, spin-orbit splitting values, asymmetric peak-shape fitting parameters, and, for Cu and Zn, Auger parameters values are presented. The quantification procedure for Cu species details the use of the shake-up satellites for Cu(II)-containing compounds and the exact binding energies of the Cu(0) and Cu(I) peaks. The use of the modified Auger parameter for Cu and Zn species allows for corroborating evidence when there is uncertainty in the binding energy assignment. These procedures can remove uncertainties in analysis of surface states in , cata nano-particles, corrosion
T-cell co-stimulatory molecules: novel targets for the treatment of allergic airway disease

The first two articles in this series discussed the fundamental concept of T-cell co-stimulation as a key event in the induction of any immune response, in addition to reviewing the current data on the role of co-stimulatory molecules for the induction and progression of allergic airway diseases. Based on these considerations, this final edition will delineate and discuss novel strategies for the prevention and/or therapy of allergic diseases based upon the modulation of co-stimulation.
Tailbiting codes: Bounds and search results

Tailbiting trellis representations of linear block codes with an arbitrary sectionalization of the time axis are studied. The notations of regular and irregular tailbiting codes are introduced and their maximal state complexities are lower-bounded. The asymptotic behavior of the derived bound is investigated. Furthermore, for regular tailbiting codes the product state complexity is lower-bounded. Tables of new tailbiting trellis representations of linear block codes of rates 1/2, 1/3, and 1/4 are presented. Almost all found trellises are optimal in the sense of the new bound on the state complexity and for most codes with nonoptimal trellises there exist time-varying trellises which are optimal. Five of our newly found tailbiting codes are better than the previously known linear codes with the same parameters. Four of them are also superior to any previously known nonlinear code with the same parameters. Also, more than 40 other quasi-cyclic codes have been found that improve the parameter set of previously known quasi-cyclic codes.
Nosocomial klebsiellas: II. Transfer in a hospital ward

SUMMARY During a 6-month period an epidemiological survey of the carriage of Klebsiella was conducted in a hospital ward where no outbreak of nosocomial infection occurred. In this endemic situation the regular sampling of several sites on patients, members of the nursing staff, and the environment, and the biotyping of Klebsiella made it possible to analyse the patterns of transmission between sites. There was abundant evidence for striking transmission of Klebsiella between the throat, hands, and faeces of patients. Transmission between patients seemed to be mainly through hands. The role of nurses' hands in transmission was not evident from this survey, probably due to the relatively long interval (a week) between samplings. Through the hands of patients, wash stands and the surrounding floor were contaminated with Klebsiella. The biotyping of Klebsiella facilitated the epidemiological analysis of the results.
On Optimization Problems with Variational Inequality Constraints

This paper is devoted to a class of optimization problems that contain variational inequality or nonlinear complementarity constraints. Problems of this kind arise, for example, in game theory, bilevel programming, and the design of networks subject to equilibrium conditions. For such problems first-order necessary optimality conditions are derived and a numerical approach is proposed, based on nondifferentiable optimization techniques. This approach is illustrated by simple examples.
Visualization of the extracapsid coat in certain bluetongue-type viruses.

LECATSAS, G. & GORMAN, B. M. Visualization of the extracapsid coat in certain bluetonguetype viruses. Onderstepoort f . vet. Res. 39 (4) 193-196 (1972). Electron microscopic studies employing the negative staining technique have demonstrated an extracapsid coat in Corriparta, Eubenangee, D 'Aguilar, Warrego, Mitchell R, Walla! and M9! 71 viruses. These observations are substantiated by the fact that coated and uncoated virus particles exhibit different diameters. INTRODUCTION Verwoerd, Els, De Villiers & Huismans (1972) have demonstrated the presence of an extracapsid protein layer covering the bluetongue virus (BTV) nucleocapsid. A ccording to these workers the layer consists of two polypeptides. Negatively stained BTV from sucrose gradients invariably showed poorly defined surface detail whereas on certain caesium chloride gradients the particles were clearly defined as a result of the removal of the extracapsid protein layers. We report here the presence of the extracapsid protein coat in viruses isolated in Australia (Doherty, 1972) which have been shown by Schnagl & Holmes (1971) and Gorman, Goss, Sayers & Symons (1971) to have properties in common with viruses included in the g roup of bluetongue-type viruses (Verwoerd, 1970). In addition, similar results are recorded on an undescribed member of the group isolated locally from a horse and designated M9J71. MATERIAL AND METHODS Mouse brain-derived Corriparta (MRMI), Eubenangee (In1074), D'Aguilar (B8112), Warrego (Ch9935), Mitchell R (MRM10434) and Walla! (Ch12048) viruses were inoculated on to cultures of BHK 21 cells grown in Roux flasks in Eagle's medium, supplemented with 5% normal bovine serum. For virus growth serum was omitted. The local virus strain M9 /71, was adapted to and subsequently grown in BHK 21 cells for electron microscopic examination. Cells were pelleted at low speed, the medium poured off and the tube drained of medium by means of filter paper. A small portion of the pellet was then mixed with a small quantity of distilled water and the suspension so formed used for negative staining according to the following procedure. A drop of the suspension was mixed with a drop of 3% phosphotungstic acid (PTA) at pH 6 and then mixed using a Pasteur pipette. A drop of this mixture was then put on to a formvarcarbon coated grid, the excess fluid removed with filter paper and the grid allowed to dry. TABLE 1 Virus particle size (nm) by negative staining
The influence of surface free energy and surface roughness on early plaque formation. An in vivo study in man.

Previous in vivo studies suggested that a high substratum surface free energy (s.f.e.) and an increased surface roughness facilitate the supragingival plaque accumulation. It is the aim of this clinical trial to explore the "relative" effect of a combination of these surface characteristics on plaque growth. 2 strips, one made of fluorethylenepropylene (FEP) and the other made of cellulose acetate (CA) (polymers with surface free energies of 20 and 58 erg/cm2, respectively) were stuck to the labial surface of the central incisors of 16 volunteers. Half the surface of each strip was smooth (Ra +/- 0.1 microns) and the other half was rough (Ra +/- 2.2 microns). The undisturbed plaque formation on these strips was followed over a period of 6 days. The plaque extension at day 3 and 6 was scored planimetrically from color slides. Finally, of 6 subjects samples were taken from the strips as well as from a neighbouring smooth tooth surface (s.f.e. 88 erg/cm2; Ra +/- 0.14 microns). These samples were analysed with a light microscope to score the proportion of coccoid cells, and small, medium, and large rods or fusiform bacteria. At day 3, a significant difference in plaque accumulation was only obtained when a rough surface was compared with a smooth surface. However, at day 6, significantly less plaque was recorded on FEP smooth (19.4%) when compared with CA smooth (39.5%). Between FEP rough (96.8%) and CA rough (98.2%), no significant difference appeared. (ABSTRACT TRUNCATED AT 250 WORDS)
Multi-finger knuckle recognition from video sequence: Extracting accurate multiple finger knuckle regions

This paper presents a multi-finger knuckle recognition system and proposes a finger knuckle region extraction algorithm from a video sequence. The use of video sequences makes it possible to achieve stable and robust finger knuckle region extraction, since the optimal image frame can be selected from a set of image frames to extract a region to be matched for each finger. Through a set of experiments, we demonstrate that the extraction rates of the proposed algorithm are 96.4%, 99.4%, 97.6% and 96.4% for index, middle, ring and little fingers, respectively, which are acceptable in practice. The result indicates that four fingers can be used for person authentication in most cases. We also demonstrate that the use of multiple finger knuckle regions exhibits efficient performance for person authentication.
Nelfinavir: A magic bullet to annihilate cancer cells

Commentary to: Nelfinavir induces the unfolded protein response in ovarian cancer cells, resulting in ER vacuolization, cell cycle retardation and apoptosis Ansgar Brüning, Petra Burger, Marianne Vogel, Martina Rahmeh, Andrea Gingelmaier, Klaus Friese, Miriam Lenhard, Alexander Burges
Of Guinea Pigs and Men – an Unusual Case of Jaundice

A 21-year-old male presented at the emergency room with jaundice, itching, dry cough, malaise and weight loss of 10 kg during the preceding four weeks. Eighteen months earlier, the patient had suffered an automobile accident leading to polytrauma. Serological markers for viral or other causes of hepatitis were absent. For suspected secondary sclerosing cholangitis, ultrasound and ERCP were performed but failed to reveal pathological findings. A liver biopsy showed cholestatic liver disease without signs of portal field-associated hepatitis. Hepato-biliary scintigraphy demonstrated hepatocellular dysfunction. The patient finally mentioned his guinea pig farm with around 50 animals, 20 of which had recently died for unknown reasons. The patient and three of his guinea pigs were subsequently tested for serological evidence of leptospirosis. IgG and IgM antibodies reacting with Leptospira interrogans were detected in the patient's serum, and all 3 guinea pigs were serologically positive for serovar Bratislava. Bacterial culture was not successful, and also PCR tests remained negative. The clinical symptoms quickly resolved after the initiation of antibiotic therapy with amoxicillin.
Ocular Safety of Intravitreal Injections of Age-Related Macular Degeneration Treatments in a Prospective Observational Cohort Study in Europe

Purpose:Estimate the incidence of pertinent ocular adverse events (POAEs) related to intravitreal (IVT)injections for age-related macular degeneration (AMD) treatments in Europe. Methods:Ophthalmologists prospectively followed patients, who received IVT injection treatment for AMD including Macugen ® , Lucentis ® , and Avastin ® at ophthalmic clinical centers in Europe, and determined outcomes of interest as clinically appropriate up to two years. Main outcomesincluded endophthalmitis, retinal detachment, vitreous hemorrhage, retinal tear, traumatic cataract, and increased intraocular pressure (IOP). Results: 501 patients from 69 sites in 13 countries were enrolled.The mean age was 73.6 years. Most patients received monotherapy (80.4%), were white (97.4%), and never smoked (65.3%). The total number of IVT injections for AMD treatment was 3,754 among those patients. The incidence of POAEs was low overall (0 to 1.28% per injection, 0 to 6.6% per patient). Increased IOP was the most frequently reported POAE. There was a positive association between the incidence of increased IOP and the number of injections received.Endophthalmitis was not reported. Conclusions: The incidence of POAEs related to IVT injections in this study was low and similar to that reported in the literature.
Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone.

BACKGROUND In two randomized phase III trials (MM-009 and MM-010), lenalidomide plus dexamethasone significantly prolonged time to progression and overall survival (OS) in patients with relapsed/refractory multiple myeloma compared with dexamethasone alone. In both trials the treatment was continued until disease progression or unacceptable toxicity. We conducted a subanalysis to determine if continuing therapy after achieving≥partial response (PR) improved survival. PATIENTS AND METHODS Data were collected on 212 patients who were treated with lenalidomide plus dexamethasone and achieved≥PR. Kaplan-Meier survival estimates were compared between patients on continued treatment versus patients discontinuing therapy because of adverse events, withdrawal of consent, or other reasons. Time-dependent multivariate regression analyses were used to determine the benefit of continuing treatment with lenalidomide. RESULTS A total of 174 patients received continued treatment until disease progression or death, and 38 patients discontinued therapy without progression. There was a trend toward longer median OS in patients who continued therapy (50.9 months vs. 35.0 months; P=.0594). When controlling for the number of previous antimyeloma therapies, β2-microglobulin levels, and Durie-Salmon stage (which adversely affected survival in these patients), continued lenalidomide treatment (HR, 0.137; 95% CI, 0.045-0.417; P=.0005) or each additional cycle of lenalidomide (HR, 0.921; 95% CI, 0.886-0.957; P<.0001) were both associated with longer survival. CONCLUSION Continued lenalidomide treatment until disease progression after achievement of ≥PR is associated with a significant survival advantage when controlling for patient characteristics. These findings should be confirmed in a prospectively designed trial.
Semi-supervised Chinese contextual polarity classification with automatic feature selection

Common approaches to the tasks of sentiment analysis start with a list of words with prior polarities, which are context-free. However, a word can exhibit different polarities in different contexts, which are termed as contextual polarities. In this paper, viewing polarities of words as properties of word senses, we treat the Chinese contextual polarity classification as word sense disambiguation (WSD), and manually labeled a Chinese dataset for training and testing. Due to the insufficiency of labeled data, semi-supervised methods are adopted; to find the effective features for the contextual polarity classification, two automatic feature selection algorithms are proposed. We combine the semi-supervised methods with automatic feature selection algorithms in order to utilize the strengths of both. The experimental results show that the semi-supervised methods, automatic feature selection, and the combination of both help to improve the Chinese contextual polarity classification above a supervised baseline model.
Energy harvesting from ambient light using PVDF with highly conductive and transparent silver nanowire/PEDOT:PSS hybride electrodes

In this study, we investigate the conversion of light-induced thermal energy to electrical energy by exploiting the piezo- and pyroelectric effect of polyvinylidene fluoride (PVDF). Due to the transparency, high conductivity, surface coverage and a facile and scalable deposition process, spray-coated silver nanowire (AgNW) and PEDOT:PSS hybrid films are used as transparent top and bottom electrodes. By adding ethylene glycol, a high boiling point solvent, the conductivity of the PEDOT:PSS films is increased by 5 orders of magnitude, up to 1816 S/cm. For an illuminated area of 8 cm⁁2 and a temperature variation of 5.7 °C, the power output of the PVDF foil reaches 413 nW at a voltage of 4.3 V and a current of 96 nA. These values compare well to the state-of-the-art performance of pyroelectric harvesters based on PVDF. As a possible application, we propose the use of this material system for a self-powered light and temperature sensor node.