Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulation of protein conformational freedom as a function of pH: constant‐pH molecular dynamics using implicit titration

Solution pH is a determinant parameter on protein function and stability, and its inclusion in molecular dynamics simulations is attractive for studies at the molecular level. Current molecular dynamics simulations can consider pH only in a very limited way, through a somewhat arbitrary choice of a set of fixed charges on the titrable sites. Conversely, continuum electrostatic methods that explicitly treat pH effects assume a single protein conformation whose choice is not clearly defined. In this paper we describe a general method that combines both titration and conformational freedom. The method is based on a potential of mean force for implicit titration and combines both usual molecular dynamics and pH‐dependent calculations based on continuum methods. A simple implementation of the method, using a mean field approximation, is presented and applied to the bovine pancreatic trypsin inhibitor. We believe that this constant‐pH molecular dynamics method, by correctly sampling both charges and conformation, can become a valuable help in the understanding of the dependence of protein function and stability on pH. © 1997 Wiley‐Liss Inc.
Elementare Validität der KiL-Maße für fachdidaktisches Wissen und Fachwissen im schulischen Kontext von Lehramtsstudierenden der Mathematik

In der KiL-Studie (Messung professioneller Kompetenzen in mathematischen und naturwissenschaftlichen Lehramtsstudiengangen) wurde fachspezifisches Wissen von Lehramtsstudierenden als Fachwissen (FW), fachdidaktisches Wissen (FDW) und Fachwissen im schulischen Kontext (FWsK) konzeptualisiert und entsprechende Instrumente zur standardisierten Erhebung dieser Wissensbereiche entwickelt. In diesem Beitrag wird ausgehend von den quantitativen Befunden zur Struktur dieser Tests (N = 505) eine erganzende Interviewstudie vorgestellt. Diese untersucht die inhaltliche Validitat der beiden schulnahen Mase auf Aufgabenebene um ambivalente quantitative Befunde einordnen zu konnen. Dabei gelingt es aufzuzeigen wie Lehramtsstudierende (N = 18) auf unterschiedliches Wissen zur Losung der Aufgaben mit schulischem Bezug (FDW, FWsK) zuruckgreifen. 1. Zum Begriff der Validitat Die Validitat stellt ein wichtiges Gutekriterien fur Tests dar: „Ein Test gilt dann als valide (‚gultig‘), wenn er das Merkmal, das er messen soll, auch misst und nicht irgendein anderes. “ (Moosbrugger & Kelava 2008). In der Literatur finden sich verschiedene Aspekte die zur Validierung von Instrumenten beachtet werden sollten. In diesem Beitrag fokussieren wir auf die die Inhaltsvaliditat. Diese befasst sich ‐ aus im Folgenden noch zu erlauternden Grunden ‐ damit inwiefern theoretisch angenommene Wissensarten tatsachlich bei der Bearbeitung der Aufgaben eines Tests angewendet werden. 2. Konzeptualisierung des fachspezifischen Professionswissens in KiL Die KiL-Studie hat zum Ziel reliable und valide Testinstrumente zur Erfassung des professionellen Wissens von Lehramtsstudierenden, u. a. der Mathematik, zu entwickeln. Dabei unterscheidet die der Testentwicklung zugrundeliegende Konzeptualisierung des fachspezifischen Professionswissens von Lehrkraften nicht nur zwischen den von Shulman (1986) gepragten Komponenten Fachwissen (FW) und fachdidaktisches Wissen (FDW), sondern es wurde eine dritte Komponente eingefuhrt: das Fachwissen im schulischen Kontext (FWsK). In diesem Modell wird unter Fachwissen universitares mathematisches Fachwissen verstanden. Fachdidaktisches
Creating Wetlands: Primary Succession, Water Quality Changes and Self-Design over 15 Years

The succession of vegetation, soil development, water quality changes, and carbon and nitrogen dynamics are summarized in this article for a pair of 1-hectare flow-through-created riverine wetlands for their first 15 years. Wetland plant richness increased from 13 originally planted species to 116 species overall after 15 years, with most of the increase occurring in the first 5 years. The planted wetland had a higher plant community diversity index for 15 years, whereas the unplanted wetland was more productive. Wetland soils turned hydric within a few years; soil organic carbon doubled in 10 years and almost tripled in 15 years. Nutrient removal was similar in the two wetlands in most years, with a trend of decreased removal over 15 years for phosphorus. Denitrification accounted for a small percentage of the nitrogen reduction in the wetlands. The wetlands were effective carbon sinks with retention rates of 1800–2700 kilograms of carbon per hectare per year, higher than in comparable reference wetlands and more commonly studied boreal peatlands. Methane emission rates are low enough to create little concern that the wetlands are net sources of climate change radiative forcing. Planting appears to have influenced carbon accumulation, methane emissions, and macrophyte community diversity.
Hidden mechanism for mode locking solid-state lasers by use of a slow off-resonant saturable absorber.

We describe a hidden mechanism for stable mode locking of solid-state lasers that uses a slow saturable absorber. The physical origin of this novel mechanism is attributed to the transformation of the saturable-absorber-induced self-frequency shift into a fast nonlinear loss because the absorption line is off resonance. Based on the exact solution of the governing steady-state equation, we investigate in detail the dependence of the pulse parameters on the laser control parameters in connection with the stability region of the solution.
Price and Quality Competition with Boundedly Rational Consumers

We consider a market model with n rational rms (doctors) and a continuum of boundedly rational consumers (patients). Following Spiegler (2006a), we assume that patients are not familiar with the market and rely on anecdotes. We analyze the price setting game played by doctors with given, dierent healing qualities. Doctors know their own quality, as well as the qualities of their competitors. We nd a unique equilibrium in mixed strategies. All doctors, no matter how bad, make positive prots that are typically considerably higher than their maxmin payos. In order to analyze welfare, we introduce a pre-stage where doctors choose qualities. Even though a better quality comes for free, doctors mainly oer mediocre qualities in all SPNE. If the highest possible quality is high enough, welfare strictly decreases in the number of doctors.
Morphology, molecular genetics and multidisciplinary management: soft tissue pathology in 2014 and beyond.

This special edition of Pathology focuses on a relatively uncommon but nonetheless fascinating branch of pathology. Soft tissue tumours (with the exception of lipoma) are collectively infrequent and, comprising over 50 distinct histotypes, individually rare. Whilst sarcoma accounts for only around 2% 1 of cancers worldwide, these tumours result in significant mortality and morbidity, both during treatment and in longterm survivors following radical treatment (the latter disproportionately so in the paediatric population, in whom second malignancies are a real threat). Occurring in all age groups and anatomical locations, soft tissue tumours will come across the desk of most surgical pathologists from time to time, but because of their relative rarity and the sometimes bewildering array of diagnostic possibilities, they are often challenging for those whose experience in this area is limited. Some guidance in the pathology reporting of soft tissue sarcoma has been offered by the Royal College of Pathologists of Australasia (RCPA), under the umbrella of the Structured Pathology Reporting project (now part of the International Collaboration on Cancer Reporting, ICCR). The first edition of the protocol for soft tissue tumour resections was published in 2011 and can be accessed online; the evidence on which those recommendations were based was previously canvassed in this journal. Ongoing efforts to integrate morphological, immunohistochemical and molecular genetic information result in more-orless constant revision and reclassification of these tumours, including the characterisation of new entities (such as the recently described epithelioid inflammatory myofibroblastic sarcoma) and the disappearance of old ones (such as MFH); reclassification of lesions (such as myofibroma, now classified as a pericytic/perivascular lesion); recognition that apparently separate entities may be related, and that hybrids may occur (such as giant cell fibroblastoma and dermatofibrosarcoma protruberans, or haemosiderotic fibrolipomatous tumour and myxoinflammatory fibroblastic sarcoma); and recognition that lesions previously thought to be reactive (such as nodular fasciitis) may in fact be neoplastic. In this issue Vickie Jo and Chris Fletcher summarise the significant changes in the recently published 4th edition of the WHO classification, including new immunohistochemical markers which may assist with diagnosis, as well as elaborating new information which has come to light since that classification appeared (highlighting soft tissue pathology as a rapidly evolving area, and perhaps providing some hints as to likely changes that will appear in the 5th edition! ). Many of these conceptual advances have occurred in light of molecular genetic analyses which have enhanced our understanding of sarcomagenesis. But a word of caution is offered by Cristina Antonescu and Paola dal Cin, who discuss the increasing recognition of
Characterization of emissions of biogenic atmospheric hydrogen sulfide

The emission rate measurements of H 2 S into the atmosphere from coastal marine sediments were made by the use of an emission flux reactor (chamber) technique under deaerated (gaseous N 2 ) and aerated (ambient air) conditions. The emission rates of H 2 S varied over a wide range (>0.05 to < 100 gS m -2 yr -1 ) . The emission of H 2 S was inversely related to the stage of tidal hydrology, with incoming and outgoing tidal hydrostatic pressure affecting the gaseous release at the locale. The diurnal studies showed an enhancement in the emission rates at night; however the emission rate of H 2 S is unaffected by increasing light intensity (between 100 and 90,000 lux) at constant temperature. The emission rates of H 2 S are greater in the deaerated chamber than in the aerated chamber. The measured marine fluxes of ~0.1 gS m -2 yr -1 seem to agree well with those derived from global marine sulfur budgets. DOI: 10.1111/j.1600-0889.1986. tb00091.x
High power handling RF MEMS design and technology

RF microelectromechanical (MEMS) switches are usually limited in term of power handling. Self actuation and electro migration constitute indeed the main failure mechanisms related to medium and high RF power. To overcome these malfunctions, an original MEMS topology based on the use of two bridge levels is proposed in this paper. Both appropriate design and technology have been developed in order to enhance power capabilities of MEMS switches. A power handling of 8W in cold switching has finally been reached.
A Priori Anisotropic Mesh Adaptation on Implicitly Defined Surfaces

Mesh adaptation on surfaces demands particular care due to the important role played by the surface fitting. We propose an adaptive procedure based on a new error analysis which combines a rigorous anisotropic estimator for the $L^1$-norm of the interpolation error with an anisotropic heuristic control of the geometric error. We resort to a metric-based adaptive algorithm which employs local operations to modify the initial mesh according to the information provided by the error analysis. An extensive numerical validation corroborates the robustness of the error analysis as well as of the adaptive procedure.
What Wrapped Perichondrial and Periosteal Grafts Offer as Regenerators of New Tissue

The major goals in contour restoration procedures are to re-establish the desired contour with the use of resilient and durable materials that can be easily found and harvested. Cartilage grafts are commonly used for these purposes though they often possess a problem of donor site morbidity and shortage of quantity. The neo-cartilage formation capacities of both perichondrium and periosteum are well-known. We aimed to optimize both the amount and quality of the newly forming tissue from perichondrial and periosteal grafts. For this purpose the grafts were wrapped on themselves. Placement of oxidized regenerated cellulose (ORC) within graft layers was performed in two groups with the aim of giving support to the regenerating tissue, and increasing the connective tissue formation within the graft layers. Three-month-old New Zealand white rabbits were used. Group 1 ear perichondrial, and Group 2 calvarium periosteal grafts of 1.4 × 2.4 cm were harvested, folded on themselves, and sutured at the edges to create closed pockets. 0.8 × 0.8 cm sized ORC sheets were placed inside the pockets before wrapping in Group 3 perichondrial and Group 4 periosteal grafts. 0.2-mL autogenous blood was injected in each pocket. All grafts were transplanted under the abdominal muscle fascia, and harvested after 6 weeks. Volumes and weights of wrapped perichondrial grafts were higher than their periosteal counterparts either with or without the inclusion of ORC. Grafts with ORC (Groups 3 and 4) were heavier than the grafts lacking ORC (Groups 1 and 2), in a statistically significant manner (P ≤ 0.01). Histologically, the inclusion of ORC in both perichondrial and periosteal grafts resulted in an increased amount of fibrosis, yet did not preclude neo-cartilage formation.
Kinetics and the Mechanism of Interaction of the Endoplasmic Reticulum Chaperone, Calreticulin, with Monoglucosylated (Glc1Man9GlcNAc2) Substrate*

Calreticulin is a lectin-like molecular chaperone of the endoplasmic reticulum in eukaryotes. Its interaction withN-glycosylated polypeptides is mediated by the glycan, Glc1Man9GlcNAc2, present on the target glycoproteins. In this work, binding of monoglucosyl IgG (chicken) substrate to calreticulin has been studied using real time association kinetics of the interaction with the biosensor based on surface plasmon resonance (SPR). By SPR, accurate association and dissociation rate constants were determined, and these yielded a micromolar association constant. The nature of reaction was unaffected by immobilization of either of the reactants. The Scatchard analysis values for K a agreed well with the one obtained by the ratiok 1/k −1.The interaction was completely inhibited by free oligosaccharide, Glc1Man9GlcNAc2, whereas Man9GlcNAc2 did not bind to the calreticulin-substrate complex, attesting to the exquisite specificity of this interaction. The binding of calreticulin to IgG was used for the development of immunoassay and the relative affinity of the lectin-substrate association was indirectly measured. The values are in agreement with those obtained with SPR. Although the reactions are several orders of magnitude slower than the diffusion controlled processes, the data are qualitatively and quantitatively consistent with single-step bimolecular association and dissociation reaction. Analyses of the activation parameters indicate that reaction is enthalpically driven and does not involve a highly ordered transition state. Based on these data, the mechanism of its chaperone activity is briefly discussed.
Economical training sets for linear ID3 learning

Our work is in machine learning, a subfield of artificial intelligence. We describe a variant of Quinlan's ID3 algorithm (1986) which is attuned to the situation that every feature's value-set is linearly ordered and finite. We then seek economical training sets, that is, ones which are small in size but result in learned decision trees of high accuracy. Our search focuses on geometric properties of the target concept, such as its extreme points, edges, faces, and surface. We categorize all concepts into three classes, from simplest to most general, and for each class we identify certain training sets, some quite small, others less so, which result in highly accurate learning of the concepts in that class. Some of our results are rigorously provable (but the proofs do not appear here), for other results our evidence is empirical. <<ETX>>
Müller cell‐derived VEGF is a significant contributor to retinal neovascularization

Vascular endothelial growth factor (VEGF‐A) is a major pathogenic factor and a therapeutic target for age‐related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Despite intensive effort in the field, the cellular mechanisms of VEGF action remain virtually uninvestigated. This situation makes it difficult to design cellular target‐based therapeutics for these diseases. In light of the recent finding that VEGF is a potential neurotrophic factor, revealing the cellular mechanisms of VEGF action becomes necessary to preserve its beneficial effect and inhibit its pathological function in long‐term anti‐VEGF therapeutics for ocular vascular diseases. We therefore generated conditional VEGF knockout mice with an inducible Cre/lox system and determined the significance of Müller cell‐derived VEGF in retinal development and maintenance and ischaemia‐induced neovascularizartion and vascular leakage. Retinal development in the conditional VEGF knockout mice was analysed by examining retinal and choroidal vasculatures and retinal morphology and function. Ischaemia‐induced retinal neovascularization and vascular leakage in the conditional VEGF knockout mice were analysed with fluorescein angiography, quantification of proliferative neovascular cells, immunohistochemistry, and immunoblotting using an oxygen‐induced retinopathy model. Our results demonstrated that disruption of Müller cell‐derived VEGF resulted in no apparent defects in retinal and choroidal vasculatures and retinal morphology and function, significant inhibition of the ischaemia‐induced retinal neovascularization and vascular leakage, and attenuation of the ischaemia‐induced breakdown of the blood‐retina barrier. These results suggest that the retinal Müller cell‐derived VEGF is a major contributor to ischaemia‐induced retinal vascular leakage and pre‐retinal and intra‐retinal neovascularization. The observation that a significant, but not complete, reduction of VEGF in the retina does not cause detectable retinal degeneration suggests that appropriate doses of anti‐VEGF agents may be important to the safe treatment of retinal vascular diseases. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Malignant transformation of oral leukoplakia: a systematic review of observational studies.

UNLABELLED The aim of this systematic review was to ascertain the malignant transformation rate of oral leukoplakia and the associated risk factors. METHOD Published literature was searched through several search engines from 1960 to the end of December 2013. The inclusion criteria included 'leukoplakia', 'pre-cancer', 'malignant transformation', 'follow-up' and 'outcome'. Two reviewers extracted the data independently and also assessed the quality of evidence. RESULTS The search strategy resulted in 1032 abstracts or full-text articles, of which 24 met the inclusion criteria. There was much variation in the definitions used by the various authors in their original reports to define oral leukoplakia or in the criteria used to recruit their patients for follow-up. The estimated overall (mean) malignant transformation rate for the total population described in these 24 studies amounts to 3.5% (405/11423), with a wide range between 0.13% and 34.0%. Based on the evidence presented, the features that stand out as significant determinants contributing to malignant potential of OL include advanced age, female sex, leukoplakia exceeding 200 mm(2) , non-homogeneous type (eg. erythroleukoplakia) and the higher grades of dysplasia. CONCLUSION The review indicates that drawing meaningful evidence-based conclusions are difficult from retrospective studies of this nature. However, many of the determinants exposed in the review require further investigation by well-designed prospective studies.
Comparative study of RT23 and Merieux tuberculin tested among healthy volunteers.

SETTING Several studies have indicated considerable variability in the biological results of different tuberculin preparations in different geographical areas or even within a single region. OBJECTIVE To compare the biological potency of two different tuberculins. DESIGN We performed simultaneous testing with RT23 and Merieux tuberculin in a group of 546 Police Academy students in Athens to compare reactions to both tuberculins. The students were divided into three groups according to their year of training; the participants in each group were tested using the Mantoux method simultaneously with the two tuberculins in different concentrations. RESULTS Using a 10 mm cut-off point for a positive tuberculin skin test, positive reactions to RT23 and Merieux were highly correlated. No statistically significant difference was established. The results indicated significant superiority of the size of the reaction with RT23 tuberculin (P = 0.014). CONCLUSIONS Both tuberculins appear to have equivalent potency, with RT23 more frequently producing reactions of larger sizes.
Psoralen plus ultraviolet‐A‐bath photochemotherapy as an adjunct treatment modality in cutaneous chronic graft versus host disease

Background: Cutaneous chronic graft versus host disease (GVHD) is a severe complication following allogeneic stem cell (PBSCT) and bone marrow transplantation (BMT). Immunosuppressive therapy consists of prednisone, cyclosporine‐A, azathioprine or mycophenolate mofetil (MMF). Treatment of patients refractory to immunosuppression represents a major problem.
Outer Retinal Tubulation

Results: Branching tubules were identified in the outer retina of 54 patients with age-related macular degeneration and in 9 patients with other diagnoses. The tubules appeared as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 40 to 140 μm high and 40 to 2260 μm wide. Morphologic features ranged from single straight or branching tubules to complex cavitary networks, usually overlying areas of pigment epithelial alteration or subretinal fibrosis. The tubules generally remained stable over time. In a retinal practice specializing in advanced age-related macular degeneration, these structures were identified in 60 of 248 patients (24.2%) seen during a 3-month period.
EVALUATION OF THE BLOOD‐AQUEOUS BARRIER AFTER VITREOUS REPLACEMENT WITH PERFLUOROPROPANE GAS AND LIQUID SILICONE

Fluorophotometric measurements of blood–aqueous barrier permeability after intravitreal injection of perfluoropropane gas in rabbit eyes revealed fluorescein leakage immediately after injection; 3 days later, recovery of barrier integrity had begun to occur and 7 days and 14 days after gas injection, when the gas bubble was still in the eye, anterior chamber fluorescein concentrations were normal. Similarly, in eyes undergoing vitrectomy and injection of silicone liquid or vitrectomy only, anterior chamber fluorescein levels were elevated 3 days and 1 week after surgery. Nevertheless, normal barrier integrity was reestablished in both the silicone-filled eyes and the vitrectomized eyes after 1 week. Since there was no difference between the group injected with silicone and the group that underwent vitrectomy only with respect to anterior chamber fluorescein concentration at any of the times studied, it is concluded that the temporary disruption of the blood-aqueous barrier is associated with the surgical procedure rather than the presence of silicone liquid in the vitreous cavity.