Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Physisporinus vitreus on wood properties of Norway spruce. Part 1: Aspects of delignification and surface hardness

Abstract The white rot fungus Physisporinus vitreus is currently tested for several biotechnological applications such as permeability improvement of refractory wood species or the optimization of the acoustic properties of wood for violins. The enzymatic activity of P. vitreus results in the degradation of pit membranes and simultaneous alterations of the tracheid cell wall structure in wood of Norway spruce [Picea abies (L.) Karst]. By this means, selective delignification and simultaneous degradation occur in the latewood tracheids at short incubation times. To study the delignification of individual cell wall layers in latewood tracheids, cellular UV-microspectrophotometry was applied to wood of Norway spruce that had been incubated for between 3 and 9 weeks. By means of this technique, the progressing delignification was demonstrated in the latewood tracheid secondary walls. Moreover, local delignification in close proximity to hyphal tunneling, cavities, and notches was evident. Additionally, the mechanical changes were measured (a) at the macroscopic level by Brinell hardness test and (b) at the cellular level by nanoindentation. Brinell hardness was significantly reduced with increasing incubation time which was attributed to the partial delignification. Unlike Brinell tests, results from nanoindentation tests did not show a clear effect of fungal activity because of the material heterogeneity and the high spatial resolution of this technique. The present study provides methodological approaches for the investigation of wood-fungus interactions and contributes to a better understanding of the characteristics of wood decay at the subcellular level caused by the white rot fungus P. vitreus. Moreover, it establishes the basis for a subsequent chemical analysis, for which the results will be the topic of a second paper in this series.
Low Double-Negative CD3+CD4−CD8− T Cells Are Associated with Incomplete Restoration of CD4+ T Cells and Higher Immune Activation in HIV-1 Immunological Non-Responders

Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3+CD4−CD8− T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4+ T cell count. The ART did not result in complete suppression of immune activation recorded by the percentage of CD38+HLA-DR+CD8+ T cells in INRs, and a strong inverse correlation was observed between DN T cells and immune activation. A low proportion of TGF-β1+DN T cells was found in INRs. Further mechanism study demonstrated that the level of TGF-β1-producing DN T cells and immune activation had a negative correlation after ART. Taken together, our study suggests that DN T cells control the immunological response in HIV-1-infected patients. These findings expand our understanding of the mechanism of immune reconstitution and could develop specific treatments to return the immune system to homeostasis following initiation of HIV-1 therapy.
Evidence That Vesicles Undergo Compound Fusion on the Synaptic Ribbon

The ribbon synapse can release a stream of transmitter quanta at very high rates. Although the ribbon tethers numerous vesicles near the presynaptic membrane, most of the tethered vesicles are held at a considerable distance from the plasma membrane. Therefore, it remains unclear how their contents are released. We evoked prolonged bouts of exocytosis from a retinal bipolar cell, fixed within seconds, and then studied the ribbons by electron microscopy. Vesicle density on ribbons was reduced by ∼50% compared with cells where exocytosis was blocked with intracellular ATP-γS. Large, irregularly shaped vesicles appeared on the ribbon in cells fixed during repetitive stimulation of exocytosis, and in some cases the large vesicles could be traced in adjacent sections to cisternae open to the medium. The large cisternal structures were attached to the ribbon by filaments similar to those that tether synaptic vesicles to the ribbon, and they occupied the base of the ribbon near the plasma membrane, where normal synaptic vesicles are found in resting cells. We suggest that the cisternae attached to ribbons represent synaptic vesicles that fused by compound exocytosis during strong repetitive stimulation and, thus, that vesicles tethered to the ribbon can empty their contents by fusing to other vesicles docked at the presynaptic membrane. Such compound fusion could explain the extremely high release rates and the multivesicular release reported for auditory and visual ribbon synapses.
Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif

Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins' interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions.
Scaling Biodiversity: Scaling species richness and distribution: uniting the species–area and species–energy relationships

Introduction Two macroecological patterns of species richness are sufficiently common and occur across such a wide range of taxa and geographic realms that they can be regarded as universal. The first is an increase in the number of species with the area sampled, the species–area relationship (hereafter SAR). The other is the relationship between species richness and the availability of energy that can be turned into biomass – the species–energy relationship (hereafter SER). Both patterns have a long history of exploration (e.g. Arrhenius, 1921; Gleason, 1922; Preston, 1960; Wright, 1983; Williamson, 1988; Currie, 1991; Rosenzweig, 1995; Waide et al., 1999; Gaston, 2000; Hawkins et al., 2003). However, attempts to interpret them within one unifying framework, or at least to relate them to each other, have been surprisingly rare. The most notable exception has been Wright’s (1983) attempt to derive both patterns from the assumed relationship between total energy availability (defined as the product of available area and energy input per unit area) and population size. According to this theory, both area and energy positively affect species’ population abundances, which decreases probabilities of population extinction, and thus increases the total number of species that can coexist on a site. Then, species richness should increase with increasing area or increasing energy in the same way. Although this theory can be valid in island situations where the total number of species is determined by the rate of extinctions which are not balanced by immigration events (MacArthur & Wilson, 1967), the situation on the mainland is more complicated. The local occurrence of a species is given not only by the viability of this population itself, but by the broader spatial context (Rosenzweig,
Reactive Nonholonomic Trajectory Generation via Parametric Optimal Control

There are many situations for which a feasible nonholonomic motion plan must be generated immediately based on real-time perceptual information. Parametric trajectory representations limit computation because they reduce the search space for solutions (at the cost of potentially introducing suboptimality). The use of any parametric trajectory model converts the optimal control formulation into an equivalent nonlinear programming problem. In this paper, curvature polynomials of arbitrary order are used as the assumed form of solution. Polynomials sacrifice little in terms of spanning the set of feasible controls while permitting an expression of the general solution to the system dynamics in terms of decoupled quadratures. These quadratures are then readily linearized to express the necessary conditions for optimality. Resulting trajectories are convenient to manipulate and execute in vehicle controllers and they can be computed with a straightforward numerical procedure in real time.
New and emerging treatments for ulcerative colitis: a focus on vedolizumab

Ulcerative colitis (UC) is the most common form of chronic inflammatory bowel disease and lacks a curative pharmacological treatment. Traditional therapies, which include 5-aminosalicylates, corticosteroids and immunosuppressants, aim to induce and maintain remission. Biological therapy with anti-tumor necrosis factor-alpha agents has added to the range of available treatments. Vedolizumab belongs to a new class of agents (integrin antagonists) that inhibit leukocyte adhesion and aim to selectively inhibit the inflammatory pathway. This article reviews the emerging data on the use of vedolizumab for UC. Evidence to date supports its efficacy in inducing remission in UC, with no major safety concerns identified.
Haplotype Association between Haptoglobin (Hp2) and Hp Promoter SNP (A-61C) May Explain Previous Controversy of Haptoglobin and Malaria Protection

Background Malaria is one of the strongest recent selective pressures on the human genome, as evidenced by the high levels of varying haemoglobinopathies in human populations–despite the increased risk of mortality in the homozygous states. Previously, functional polymorphisms of Hp, coded by the co-dominant alleles Hp1 and Hp2, have been variously associated with several infectious diseases, including malaria susceptibility. Methodology/Principal Findings Risk of a clinical malarial episode over the course of a malarial transmission season was assessed using active surveillance in a cohort of Gambian children aged 10–72 months. We report for the first time that the major haplotype for the A-61C mutant allele in the promoter of haptoglobin (Hp)–an acute phase protein that clears haemoglobin released from haemolysis of red cells–is associated with protection from malarial infection in older children, (children aged ≥36 months, >500 parasites/ul and temperature >37.5°C; OR = 0.42; [95% CI 0.24–0.73] p = 0.002) (lr test for interaction, <36 vs ≥36 months, p = 0.014). Protection was also observed using two other definitions, including temperature >37.5°C, dipstick positive, plus clinical judgement of malaria blinded to dipstick result (all ages, OR = 0.48, [95% CI 0.30–0.78] p = 0.003; ≥36 months, OR = 0.31, [95% CI 0.15–0.62] p = 0.001). A similar level of protection was observed for the known protective genetic variant, sickle cell trait (HbAS). Conclusions/Significance We propose that previous conflicting results between Hp phenotypes/genotypes and malaria susceptibility may be explained by differing prevalence of the A-61C SNP in the populations studied, which we found to be highly associated with the Hp2 allele. We report the -61C allele to be associated with decreased Hp protein levels (independent of Hp phenotype), confirming in vitro studies. Decreased Hp expression may lead to increased oxidant stress and increased red cell turnover, and facilitate the development of acquired immunity, similar to a mechanism suggested for sickle cell trait.
The calcium-activated potassium channels of turtle hair cells

A major factor determining the electrical resonant frequency of turtle cochlear hair cells is the time course of the Ca-activated K current (Art, J. J., and R. Fettiplace. 1987. Journal of Physiology. 385:207- 242). We have examined the notion that this time course is dictated by the K channel kinetics by recording single Ca-activated K channels in inside-out patches from isolated cells. A hair cell's resonant frequency was estimated from its known correlation with the dimensions of the hair bundle. All cells possess BK channels with a similar unit conductance of approximately 320 pS but with different mean open times of 0.25-12 ms. The time constant of relaxation of the average single- channel current at -50 mV in 4 microM Ca varied between cells from 0.4 to 13 ms and was correlated with the hair bundle height. The magnitude and voltage dependence of the time constant agree with the expected behavior of the macroscopic K(Ca) current, whose speed may thus be limited by the channel kinetics. All BK channels had similar sensitivities to Ca which produced half-maximal activation for a concentration of approximately 2 microM at +50 mV and 12 microM at -50 mV. We estimate from the voltage dependence of the whole-cell K(Ca) current that the BK channels may be fully activated at -35 mV by a rise in intracellular Ca to 50 microM. BK channels were occasionally observed to switch between slow and fast gating modes which raises the possibility that the range of kinetics of BK channels observed in different hair cells reflects a common channel protein whose kinetics are regulated by an unidentified intracellular factor. Membrane patches also contained 30 pS SK channels which were approximately 5 times more Ca-sensitive than BK channels at -50 mV. The SK channels may underlie the inhibitory synaptic potential produced in hair cells by efferent stimulation.
Brittle fracture due to an array of microcracks

The method of distributed dislocations is used to analyse the response of an infinite elastic solid containing a single periodic array of inclined curved cracks. Uniform remote loading is applied to the body, and the cracks are of arbitrary but identical shapes. Expressions are derived for the stress intensity factors at each crack tip, the crack displacement profile and the extra compliance of the body due to the presence of the cracks. For an array of straight cracks, the stress intensity factors, and the extra compliance are found as a function of crack orientation and spacing. Using this framework, we examine brittle fracture by the development of a periodic array of cracks in a solid which suffers all combinations of remote proportional loading. The solution for remote shear is explored in detail. The various types of response are summarized in a fracture map, and are compared with experimental observations for polymers and rocks.
Artificial Control of Nitrate Respiration through the lac Promoter Permits the Assessment of Oxygen-Mediated Posttranslational Regulation of the nar Operon in Pseudomonas aeruginosa

ABSTRACT In this study, oxygen and nitrate regulation of transcription and subsequent protein expression of the unique narK1K2GHJI respiratory operon of Pseudomonas aeruginosa were investigated. Under the control of PLAC, P. aeruginosa was able to transcribe nar and subsequently express methyl viologen-linked nitrate reductase activity under aerobic conditions without nitrate. Modulation of PLAC through the LacI repressor enabled us to assess both transcriptional and posttranslational regulation by oxygen during physiological whole-cell nitrate reduction.
Toward accurate prediction of pKa values for internal protein residues: The importance of conformational relaxation and desolvation energy

Proton uptake or release controls many important biological processes, such as energy transduction, virus replication, and catalysis. Accurate pKa prediction informs about proton pathways, thereby revealing detailed acid‐base mechanisms. Physics‐based methods in the framework of molecular dynamics simulations not only offer pKa predictions but also inform about the physical origins of pKa shifts and provide details of ionization‐induced conformational relaxation and large‐scale transitions. One such method is the recently developed continuous constant pH molecular dynamics (CPHMD) method, which has been shown to be an accurate and robust pKa prediction tool for naturally occurring titratable residues. To further examine the accuracy and limitations of CPHMD, we blindly predicted the pKa values for 87 titratable residues introduced in various hydrophobic regions of staphylococcal nuclease and variants. The predictions gave a root‐mean‐square deviation of 1.69 pK units from experiment, and there were only two pKa's with errors greater than 3.5 pK units. Analysis of the conformational fluctuation of titrating side‐chains in the context of the errors of calculated pKa values indicate that explicit treatment of conformational flexibility and the associated dielectric relaxation gives CPHMD a distinct advantage. Analysis of the sources of errors suggests that more accurate pKa predictions can be obtained for the most deeply buried residues by improving the accuracy in calculating desolvation energies. Furthermore, it is found that the generalized Born implicit‐solvent model underlying the current CPHMD implementation slightly distorts the local conformational environment such that the inclusion of an explicit‐solvent representation may offer improvement of accuracy. Proteins 2011. © 2011 Wiley‐Liss, Inc.
Finite Bisimulation of Reactive Untimed Infinite State Systems Modeled as Automata With Variables

Some discrete-event systems such as software are typically infinite state systems, and a commonly used technique for performing formal analysis such as automated verification is based on their finite abstractions. In this paper, we consider a model for reactive untimed infinite state systems called input-output extended finite automaton (I/O-EFA), which is an automaton extended with discrete variables such as inputs, outputs, and data. Using I/O-EFA as a model many value-passing processes can be represented by finite graphs. We study the problem of finding a finite abstraction that is bisimilar to a given I/O-EFA. We present a sufficient condition under which the underlying transition system of an I/O-EFA admits a finite bisimilar quotient. We then identify a class of I/O-EFAs for which a partition satisfying our sufficient condition can be constructed by inspecting the structure of the given I/O-EFA. We also identify a lower bound abstraction (that is coarser than any finite bisimilar abstraction), and present an iterative refinement algorithm whose termination guarantees the existence of a finite bisimilar abstraction. The results are illustrated through examples that model reactive software.
A constraint-based approach to table structure derivation

This paper presents an approach to deriving an abstractgeometric model of a table from a physical representation.The technique developed uses a graph of constraints betweencells which must be satisfied in order to determinetheir relative horizontal and vertical position. The methodis evaluated with a test set of tables drawn from US Securitiesand Exchange Commission (SEC) filings.
Large deviations analysis of consensus+innovations detection in random networks

We study the large deviations performance of consensus+innovations distributed detection over random networks, where each sensor, at each time k, weight averages its decision variable with its neighbors decision variables (consensus), and accounts for its new observation (innovation). Sensor observations are independent identically distributed (i.i.d.) both in time and space, but have generic (non Gaussian) distributions. The underlying network is random, described by a sequence of i.i. d. stochastic, symmetric weight matrices W(k); we measure the corresponding speed of consensus by |logr|, where r is the second largest eigenvalue of the second moment of W(k). We show that distributed detection exhibits a phase transition behavior with respect to | logr|: when |logr| is above a threshold, distributed detection is equivalent to the optimal centralized detector, i.e., has the error exponent equal to the Chernoff information. We explicitly quantify the optimality threshold for | log r| as a function of the log-moment generating function Λ0(·) of a sensor's log-likelihood ratio. When below the threshold, we analytically find the achievable error exponent as a function of r and Λ0(·). Finally, we illustrate by an example the dependence of the optimality threshold on the type of the sensor observations distribution.
NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus

Accurate chromosome segregation in meiosis requires dynamic changes in chromatin organization. In Drosophila melanogaster, upon completion of recombination, meiotic chromosomes form a single, compact cluster called the karyosome in an enlarged oocyte nucleus. This clustering is also found in humans; however, the mechanisms underlying karyosome formation are not understood. In this study, we report that phosphorylation of barrier to autointegration factor (BAF) by the conserved kinase nucleosomal histone kinase-1 (NHK-1; Drosophila Vrk1) has a critical function in karyosome formation. We find that the noncatalytic domain of NHK-1 is crucial for its kinase activity toward BAF, a protein that acts as a linker between chromatin and the nuclear envelope. A reduction of NHK-1 or expression of nonphosphorylatable BAF results in ectopic association of chromosomes with the nuclear envelope in oocytes. We propose that BAF phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear envelope, allowing karyosome formation in oocytes. These data provide the first mechanistic insight into how the karyosome forms.