Miracle-dz/UniFAR-FTUs huggingface dataset:
Site and mechanics of failure in normal and dystrophin‐deficient skeletal muscle

Partial or complete tearing of skeletal muscle occurs both in acute muscle injury and in some pathological muscle conditions. Despite the impact of such tearing on normal muscle function, few studies have examined the site or mechanism of muscle injury at cellular or subcellular levels of organization. The present study determines the ultrastructural location and mechanical conditions of tensile failure in normal mouse extensor digitorum longus muscles. All of these muscles failed near a myotendinous junction (MTJ), but within the muscle fibers, in a transverse plane coincident with the edge of an A‐band. The breaking stress averaged 5.71 × 105 N/m2 for muscles stimulated tetanically during lengthening, and 5.01 × 105 N/m2 for unstimulated muscles. Breaking strain averaged 135%, and showed no dependence on the state of activation of the muscle. The energy absorbed by each muscle averaged 362.5 mJ/g in unstimulated muscle, and 613.2 mJ/g in the stimulated samples. In addition to the failure properties of normal muscle, the effect of dystrophin deficiency on the site and conditions of failure was determined using muscle from mdx mice, which lack dystrophin. The absence of dystrophin had no detectable effect on the stress, strain, or energy absorbed, regardless of the state of muscle activation. Unstimulated mdx muscle failed in the plane of an A‐band, but tetanic stimulation produced failure in the reticular lamina of the tendon, just external to the MTJ, in 75% of the fibers in the mdx muscles. Although dystrophin's cytoplasmic location makes it unlikely that this unique mode of failure is due directly to the absence of the protein, failure in the reticular lamina may result from a difference in load distribution that accompanies the response of mdx muscle to dystrophin deficiency. © 1995 John Wiley &Sons, Inc.
Extranodal NK/T‐cell lymphoma: diagnosis and treatment cues

Extranodal NK/T‐cell lymphoma, nasal type (ENKL) is mostly endemic to East Asia. It predominantly occurs in the nasal or paranasal areas and less frequently in the skin. Most of the tumours show NK‐cell, but rarely T‐cell, phenotypes. The Epstein–Barr virus (EBV) genome can be usually detected in lymphoma cells. Geographic localization of ENKL matches the endemic distribution of EBV, suggesting that EBV plays an important role in lymphomagenesis. Originally, NK‐cell and T‐cell types were believed to present the same clinicopathologic characteristics, but recent data suggest more aggressive characteristics for the NK‐cell phenotype. Although ENKL is sensitive to radiotherapy, it shows a poorer response to chemotherapeutic agents than other lymphomas due to expression of p‐glycoprotein. Therefore, new therapeutic approaches must be considered. Several new clinical trials are now being conducted in East Asia. Copyright © 2008 John Wiley & Sons, Ltd.
Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation1

Presentation of Ag by class II MHC is regulated by lysosomal proteases that not only destroy the class II invariant chain (Ii) chaperone but also generate the peptide Ag that is loaded onto the class II MHC dimer. We sought to determine the extent to which asparagine endopeptidase (AEP) influences human Ag and Ii processing. Our data confirm the constructive function of AEP in tetanus toxoid processing, but they are discordant with findings that suggest a destructive role for AEP in processing of the immunodominant myelin basic protein epitope. Furthermore, we observed no effect on invariant chain processing following AEP inhibition for several distinct allelic variants of human class II MHC products. We find that cysteine and aspartic proteases, as well as AEP, can act redundantly to initiate Ii processing. We detected considerable variation in lysosomal activity between different EBV-transformed B cell lines, but these differences do not result in altered regulation of invariant chain catabolism. We propose that, as for bound peptide Ag, the identity of the lysosomal enzyme that initiates invariant chain cleavage is dependent on the class II MHC allelic variants expressed.
Contribution REAL-TIME QUALITATIVE ULTRASOUND ELASTOGRAPHY OF CERVICAL LYMPH NODES IN ROUTINE CLINICAL PRACTICE : INTEROBSERVER AGREEMENTAND CORRELATION WITH MALIGNANCY

A Diagno Hong E-mail Abstract—To evaluate real-time qualitative ultrasound (US) elastography for cervical lymphadenopathy in routine clinical practice, 74 nodes (37 malignant, 37 benign) in 74 patients undergoing sonography underwent US elastography prior to fine needle aspiration for cytology. Dynamic cine loops of elasticity imaging displayed using a chromatic-scale were qualitatively scored by three independent observers for the proportion of stiff areas from ES1-4 (soft to stiff). There was fair to good interobserver agreement as indicated by weighted kappa (k) statistic from 0.374 to 0.738. Median ES for benign and malignant nodes were 2 and 3 respectively. ES was higher in malignant nodes (p 5 0.0003–0.0049, Mann Whitney U tests) although areas under receiver operating characteristic curves (0.68–0.74) indicated suboptimal discrimination. The optimal discriminatory cut-off, ES . 2, achieved only 62.2% sensitivity, 83.8% specificity and 73% accuracy for malignancy. Improvements in reliability and accuracy of real-time qualitative ultrasound elastography are required for it to be adopted into routine clinical practice. (E-mail: aniltahuja@cuhk.edu.hk) 2010 World Federation for Ultrasound in Medicine & Biology.
MACHO Alert 95-30: First Real-Time Observation of Extended Source Effects in Gravitational Microlensing

We present analysis of MACHO Alert 95-30, a dramatic gravitational microlensing event toward the Galactic bulge whose peak magnification departs significantly from the standard point-source microlensing model. Alert 95-30 was observed in real time by the Global Microlensing Alert Network (GMAN), which obtained densely sampled photometric and spectroscopic data throughout the event. We interpret the light-curve "fine structure" as indicating transit of the lens across the extended face of the source star. This signifies resolution of a star several kiloparsecs distant. We find a lens angular impact parameter θmin/θsource = 0.715 ± 0.003. This information, along with the radius and distance of the source, provides an additional constraint on the lensing system. Spectroscopic and photometric data indicate the source is a M4 III star of radius 61 ± 12 R☉, located on the far side of the bulge at ~9 kpc. We derive a lens angular velocity, relative to the source, of 21.5 ± 2.9 km s-1 kpc-1, where the error is dominated by uncertainty in the angular size of the source star. Likelihood analysis yields a median lens mass of 0.67+ 2.53−0.46 M☉, located with 80% probability in the Galactic bulge at a distance of 6.93+ 1.56−2.25 kpc. If the lens is a main-sequence star, we can include constraints on the lens luminosity. This modifies our estimates to Mlens=0.53+ 0.52−0.35 M☉ and Dlens=6.57+ 0.99−2.25 kpc. Spectra taken during the event show that the absorption-line equivalent widths of Hα and the TiO bands near 6700 Å vary, as predicted for microlensing of an extended source. This is most likely due to center-to-limb variation in the stellar spectral lines. The observed spectral changes further support our microlensing interpretation. These data demonstrate the feasibility of using microlensing limb crossings as a tool to probe stellar atmospheres directly.
Multivariate Counting Processes: Copulas and Beyond

Multivariate stochastic processes with Poisson marginals are of interest in insurance and finance; they can be used to model the joint behaviour of several claim arrival processes, for example. We discuss various methods for the construction of such models, with particular emphasis on the use of copulas. An important class of multivariate counting processes with Poisson marginals arises if the events of a background Poisson process with constant intensity are moved forward in time by a random amount and possibly deleted; here we think of the events of the background process as triggering later claims in different categories. We discuss structural aspects of these models, their dependence properties together with stochastic order aspects, and also some related computational issues. Various actuarial applications are indicated.
Tone Perception in Sgaw Karen

Sgaw Karen has a complex tone system based on voice quality, f0 and duration. A perceptual study reveals that voice quality and duration are central to its patterns of tone contrast. F0-based identification cues are the presence of a low offset and of a falling contour. No evidence was found for the decompositionality of contours.
ToxR Antagonizes H-NS Regulation of Horizontally Acquired Genes to Drive Host Colonization

The virulence regulator ToxR initiates and coordinates gene expression needed by Vibrio cholerae to colonize the small intestine and cause disease. Despite its prominence in V. cholerae virulence, our understanding of the direct ToxR regulon is limited to four genes: toxT, ompT, ompU and ctxA. Here, we determine ToxR’s genome-wide DNA-binding profile and demonstrate that ToxR is a global regulator of both progenitor genome-encoded genes and horizontally acquired islands that encode V. cholerae’s major virulence factors and define pandemic lineages. We show that ToxR shares more than a third of its regulon with the histone-like nucleoid structuring protein H-NS, and antagonizes H-NS binding at shared binding locations. Importantly, we demonstrate that this regulatory interaction is the critical function of ToxR in V. cholerae colonization and biofilm formation. In the absence of H-NS, ToxR is no longer required for V. cholerae to colonize the infant mouse intestine or for robust biofilm formation. We further illustrate a dramatic difference in regulatory scope between ToxR and other prominent virulence regulators, despite similar predicted requirements for DNA binding. Our results suggest that factors in addition to primary DNA structure influence the ability of ToxR to recognize its target promoters.
Peak protein expression of IL-2 and IFN-gamma correlate with the peak rejection episode in a spontaneously tolerant model of rat liver transplantation.

Spontaneous orthotopic liver transplant (OLT) tolerance occurs uniformly between the inbred rat strains of DA (MHC haplotype RT1(a)) into PVG (RT1(c)) despite a fully allogeneic barrier. Animals transplanted in this combination do, however, undergo a rejection episode which appears to be self-limiting. In order to clarify this further we under took in situ measurements of the cytokines IL-2, IFN-gamma and TNF-alpha prior to, during and post rejection episode. The cytokine protein product was examined via immunoblotting assays and mRNA levels by RT-PCR. Comparisons were also made for syngeneic transplant combinations over the same time period. Peak protein expression of IL-2 and, to a lesser extent, IFN-gamma, occurred during the rejection episode between days 10 and 14. IFN-gamma was still present in syngeneic OLT on day 10 but was only present in allogeneic OLT on day 14. IL-2 was only detectable in allogeneic OLT on days 10 and 14. Transient increases in TNF-alpha occurred in allogeneic and syngeneic OLT with TNF-alpha levels falling by the peak rejection episode. Immunoblotting also confirmed the ability of hepatocytes to produce each of the cytokines studied. mRNA levels, by contrast, were maximal at days 1 and 10 for IL-2 and day 3 for IFN-gamma in allogeneic OLT when compared with syngeneic and non-transplanted controls. Earlier increases in IL-2 and IFN-gamma mRNA and time of peak protein expression do not correlate in this model. We therefore conclude that the measurement of peak mRNA levels alone are not enough to evaluate the rejection process especially since it is the cytokine protein products which have potential biological activity.
Estimating intergenerational schooling mobility on censored samples: consequences and remedies

In this paper we estimate the impact of parental schooling on child schooling, focus on the problem that children who are still in school constitute censored observations, and evaluate three solutions to it: replacement of observed with expected years of schooling, maximum likelihood approach, and elimination of all school-aged children. Using intergenerational data from the Wisconsin Longitudinal Study we test how the three correction methods deal with censored observations. The one that treats parental expectations as if they were realizations seems to fix the censoring problem quite well. Copyright (C) 2009 John Wiley & Sons, Ltd.
The MicroRNA390/TAS3 Pathway Mediates Symbiotic Nodulation and Lateral Root Growth1[OPEN]

miR390/TAS3 affect rhizobial infection, nodule proliferation, and the maintenance of a single-nodule meristem in addition to lateral root growth in Medicago truncatula. Legume roots form two types of postembryonic organs, lateral roots and symbiotic nodules. Nodule formation is the result of the interaction of legumes with rhizobia and requires the mitotic activation and differentiation of root cells as well as an independent, but coordinated, program that allows infection by rhizobia. MicroRNA390 (miR390) is an evolutionarily conserved microRNA that targets the Trans-Acting Short Interference RNA3 (TAS3) transcript. Cleavage of TAS3 by ARGONAUTE7 results in the production of trans-acting small interference RNAs, which target mRNAs encoding AUXIN RESPONSE FACTOR2 (ARF2), ARF3, and ARF4. Here, we show that activation of the miR390/TAS3 regulatory module by overexpression of miR390 in Medicago truncatula promotes lateral root growth but prevents nodule organogenesis, rhizobial infection, and the induction of two key nodulation genes, Nodulation Signaling Pathway1 (NSP1) and NSP2. Accordingly, inactivation of the miR390/TAS3 module, either by expression of a miR390 target mimicry construct or mutations in ARGONAUTE7, enhances nodulation and rhizobial infection, alters the spatial distribution of the nodules, and increases the percentage of nodules with multiple meristems. Our results revealed a key role of the miR390/TAS3 pathway in legumes as a modulator of lateral root organs, playing opposite roles in lateral root and nodule development.
Logarithmic temperature profiles in the bulk of turbulent Rayleigh–Bénard convection for a Prandtl number of 12.3

Abstract We report measurements of logarithmic temperature profiles $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\varTheta (z,r) = A(r)\times \ln (z/L) + B(r)$ in the bulk of turbulent Rayleigh–Bénard convection (here $\varTheta $ is a scaled and time-averaged local temperature in the fluid, $ z$ is the vertical and $r$ the radial position, and $L$ is the sample height). Two samples had aspect ratios $\varGamma \equiv D/L = 1.00$ and 0.50 (where $D=190\ \mathrm{mm}$ is the diameter). The fluid was a fluorocarbon with a Prandtl number of $\mathit{Pr} = 12.3$ . The measurements covered the Rayleigh-number range $2\times 10^{10} \lesssim \mathit{Ra} \lesssim 2\times 10^{11}$ for $\varGamma = 1.00$ and $3\times 10^{11} \lesssim \mathit{Ra} \lesssim 2\times 10^{12}$ for $\varGamma = 0.50$ . In contradistinction to what had been found for $\varGamma = 0.50$ and $\mathit{Pr} = 0.78$ by Ahlers et al. (Phys. Rev. Lett., vol. 109, 2012, art. 114501; J. Fluid Mech., 2014, in press), the measurements revealed no $\mathit{Ra}$ dependence of the amplitude $A(r)$ of the logarithmic term. Within the experimental resolution, the amplitude was also found to be independent of $\varGamma $ . It varied with $r$ in a manner consistent with the function $A(\xi ) = A_1/\sqrt{2\xi - \xi ^2}$ , where $\xi \equiv (R-r)/R$ with $R=D/2$ and $A_1 \simeq 0.0016$ . The results for $A(r)$ are smaller than those obtained from experiments and direct numerical simulations (Ahlers et al., Phys. Rev. Lett., vol. 109, 2012, art. 114501) at similar values of $\mathit{Ra}$ for $\mathit{Pr} = 0.7$ and $\varGamma = \frac{1}{2}$ by a factor that depended slightly upon $\mathit{Ra}$ but was close to $2$ .
Voltage-dependent Ca2+ currents contribute to spontaneous Ca2+ waves in rabbit corpus cavernosum myocytes.

INTRODUCTION Corpus cavernosum myocytes generate spontaneous tone that contributes to penile detumescence. It is essential to elucidate how tone is generated to fully understand the processes involved in erection. Tissue experiments have shown that blockers of voltage-dependent Ca2+ channels (VDCCs) reduce tone. However, there is also a widespread belief that these channels are poorly expressed in this tissue. Furthermore, it is unclear how VDCC would interact with recently described intracellular Ca2+ waves, which initiate contractions. AIMS (i) To directly examine VDCC currents in freshly isolated corpus cavernosum myocytes; and (ii) to study the relationship between VDCC and intracellular Ca2+ waves. MAIN OUTCOME MEASURES VDCC and cytosolic Ca2+ were measured using patch clamp and confocal microscopy. Methods. Male New Zealand white rabbits were euthanized and corpus cavernosum myocytes dispersed enzymatically for patch clamp recording and confocal Ca2+ imaging (using fluo-4AM). RESULTS Isolated myocytes developed robust VDCC that could be separated into two components. One activated at -45 mV, reversed at +40 mV, inactivated with a V(1/2) of -27 mV and was enhanced by Ba2+. This component was blocked with nifedipine, but not Ni2+ or mibefradil. The other component inactivated with a V(1/2) of -87 mV, was unchanged in Ba2+, and was blocked by Ni2+ or mibefradil, but not nifedipine. Even though Ni2+ had no effect on intracellular Ca2+ waves, nifedipine blocked them, although localized Ca2+ events remained. CONCLUSIONS At least two VDCC are expressed in rabbit corpus cavernousum myocytes. One may be designated L-type Ca2+ current, whereas the other is a putative T-type current. The L-current facilitates conversion of local Ca2+ events into global Ca2+ waves, whereas the putative T-current plays little part in this process. These results provide a new basis for understanding the role of L-type Ca2+ current in generating detumescent tone in the corpus cavernosum.
Characterization of Buriti (Mauritia flexuosa L.) oil by absorption and emission spectroscopies

Amostras de oleo obtido do fruto do Buriti (Mauritia flexuosa L.) foram caracterizadas por espectroscopia de absorcao e emissao. O espectro de absorcao foi obtido no intervalo de 300 a 2000 nm, enquanto o espectro de emissao foi analisado entre 400 e 800 nm, onde observamos varias bandas. Para melhor entender a complexidade destes espectros, tambem obtivemos os espectros de absorcao e emissao dos componentes majoritarios do oleo de Buriti. Correlacionando estes dados, apresentamos uma discussao sobre a origem das bandas observadas.
Stable Cooperative Solutions for the Iterated Prisoner's Dilemma

For the iterated Prisoner's Dilemma, there exist Markov strategies which solve the problem when we restrict attention to the long term average payoff. When used by both players these assure the cooperative payoff for each of them. Neither player can benefit by moving unilaterally any other strategy, i.e. these are Nash equilibria. In addition, if a player uses instead an alternative which decreases the opponent's payoff below the cooperative level, then his own payoff is decreased as well. Thus, if we limit attention to the long term payoff, these \emph{good strategies} effectively stabilize cooperative behavior. We characterize these good strategies and analyze their role in evolutionary dynamics.
Role of Multidrug Resistance Protein 1 (MRP1) and Glutathione S-Transferase A1-1 in Alkylating Agent Resistance

We investigated the role of phase II (conjugation) and phase III (efflux) detoxification of the anticancer drugs melphalan (MLP) and chlorambucil (CHB). Although both drugs are substrates of Alpha-class glutathioneS-transferases (GST) and the monoglutathionyl conjugates formed in these enzymatic reactions are transported by MRP1, we found that GSTA1-1 and MRP1 acted in synergy to confer resistance to CHB but not to MLP (Morrow, C. S., Smitherman, P. K., Diah, S. K., Schneider, E., and Townsend, A. J. (1998) J. Biol. Chem. 273, 20114–20120). To explain this selectivity of MRP1/GST-mediated resistance, we report results of side-by-side experiments comparing the kinetics of MLP- versusCHB-glutathione conjugate: formation, product inhibition of GSTA1-1 catalysis, and transport by MRP1. The monoglutathionyl conjugate of CHB, CHB-SG, is a very strong competitive inhibitor of GSTA1-1 (K i 0.14 μm) that is >30-fold more potent than that of the corresponding conjugate of MLP, MLP-SG (K i 4.7 μm). The efficiency of GSTA1-1-mediated monoglutathionyl conjugate formation is more than 4-fold higher for CHB than MLP. Lastly, both CHB-SG and MLP-SG are efficiently transported by MRP1 with similarV max although the K m for CHB-SG (0.37 μm) is significantly lower than for MLP-SG (1.1 μm). These results indicate that MRP1 is required for GSTA1-1-mediated resistance to CHB in order to relieve potent product inhibition of the enzyme by intracellular CHB-SG formed. The kinetic properties of MRP1 are well suited to eliminate CHB-SG at pharmacologically relevant concentrations. For MLP detoxification, where product inhibition of GSTA1-1 is less important, GSTA1-1 does not confer resistance because of the relatively poorer catalytic efficiency of MLP-SG formation. Similar analyses can be useful for predicting the pharmacological and toxicological consequences of MRP and GST expression on cellular sensitivity to various other electrophilic xenobiotics.
Venture Capital Finance: A Security Design Approach

This paper provides a theory of venture capital financing based on the complementarity between the financing and advising roles of venture capitalists. We examine the interaction between the staging of investment, that characterizes young firms with a high growth potential, and the double-sided moral hazard problem arising from the managerial contributions of entrepreneurs and venture capitalists. The optimal contractual arrangements have features that resemble the securities actually employed in venture capital financing. In particular, we identify an incentive-related insurance motive for making the initial financier bear the start-up's downside risk, as well as a financing motive for protecting him against dilution. This can explain the widespread use of convertible preferred stock.
Bioimpedance Measurement: Modeling of Coplanar Electrodes and Impedance Characterization

In many bioimpedance measurements, coplanar electrodes have to be used because the conventional parallel-plate configuration is either impossible or not preferred. Despite the widely use, the effect of the electrode geometry on the measurement, and the physical process of electrode-electrolyte interface impedance have not been well studied. In this work, we designed a type of fingers-like coplanar electrode and described the impedane measurement method for different test objects, which included various biologically relevant solution, blood and excised tissue. For best understanding interface characteristics of those objects, we adopted electrochemical impedance models to analyze the physical processes, and compared the electrical properties of these objects by amptitude-frequency plots in the frequency range of 100 Hz to 10 MHz. The results show that the impedance measurement method is effective, and fingers-like coplanar electrode can be used for bioimpedance measurement.