Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnosis and Treatment of Sexual Dysfunctions in Late-Onset Hypogonadism

Testosterone is the principal androgen in the human male. The decline of testosterone with aging was recognized to be associated with a number of symptoms and signs that reduce the quality of life and that may even have severe, debilitating consequences. Clinically, late-onset hypogonadism (LOH) is diagnosed by use of biochemical and clinical measures. Despite published guidelines and recommendations, however, uncertainty surrounds the profile of clinical symptoms as well as the biochemical threshold of diagnosis. Clinicians should be aware of these shortcomings while adhering to the guidelines. Current treatment methods are centered on restoring testosterone to mid to lower levels of young men with natural testosterone replacements. Although recent studies have highlighted possible additional benefits involving improvement of systemic disorders, the goal of treatment is to improve sexual function, while observing for adverse effects in the prostate. Overall, the problem of LOH in debilitating the quality of life and well-being is real, and by following proper guidelines with attentiveness to the results of treatment trials, testosterone replacement therapy presents a safe and effective treatment option.
Role of evolutionary and ecological factors in the reproductive success and the spatial genetic structure of the temperate gorgonian Paramuricea clavata

Dispersal and mating features strongly influence the evolutionary dynamics and the spatial genetic structure (SGS) of marine populations. For the first time in a marine invertebrate, we examined individual reproductive success, by conducting larval paternity assignments after a natural spawning event, combined with a small-scale SGS analysis within a population of the gorgonian Paramuricea clavata. Thirty four percent of the larvae were sired by male colonies surrounding the brooding female colonies, revealing that the bulk of the mating was accomplished by males from outside the studied area. Male success increased with male height and decreased with increasing male to female distance. The parentage analyses, with a strong level of self-recruitment (25%), unveiled the occurrence of a complex family structure at a small spatial scale, consistent with the limited larval dispersal of this species. However, no evidence of small scale SGS was revealed despite this family structure. Furthermore, temporal genetic structure was not observed, which appears to be related to the rather large effective population size. The low level of inbreeding found suggests a pattern of random mating in this species, which disagrees with expectations that limited larval dispersal should lead to biparental inbreeding. Surface brooding and investment in sexual reproduction in P. clavata contribute to multiple paternity (on average 6.4 fathers were assigned per brood), which enhance genetic diversity of the brood. Several factors may have contributed to the lack of biparental inbreeding in our study such as (i) the lack of sperm limitation at a small scale, (ii) multiple paternity, and (iii) the large effective population size. Thus, our results indicate that limited larval dispersal and complex family structure do not necessarily lead to biparental inbreeding and SGS. In the framework of conservation purposes, our results suggested that colony size, proximity among colonies and the population size should be taken into consideration for restoration projects.
On Reducing the Effect of Covariate Factors in Gait Recognition: A Classifier Ensemble Method

Robust human gait recognition is challenging because of the presence of covariate factors such as carrying condition, clothing, walking surface, etc. In this paper, we model the effect of covariates as an unknown partial feature corruption problem. Since the locations of corruptions may differ for different query gaits, relevant features may become irrelevant when walking condition changes. In this case, it is difficult to train one fixed classifier that is robust to a large number of different covariates. To tackle this problem, we propose a classifier ensemble method based on the random subspace Method (RSM) and majority voting (MV). Its theoretical basis suggests it is insensitive to locations of corrupted features, and thus can generalize well to a large number of covariates. We also extend this method by proposing two strategies, i.e, local enhancing (LE) and hybrid decision-level fusion (HDF) to suppress the ratio of false votes to true votes (before MV). The performance of our approach is competitive against the most challenging covariates like clothing, walking surface, and elapsed time. We evaluate our method on the USF dataset and OU-ISIR-B dataset, and it has much higher performance than other state-of-the-art algorithms.
Fluctuations and Response in Financial Markets: The Subtle Nature of 'Random' Price Changes

Using Trades and Quotes data from the Paris stock market, we show that the random walk nature of traded prices results from a very delicate interplay between two opposite tendencies: long-range correlated market orders that lead to super-diffusion (or persistence), and mean reverting limit orders that lead to sub-diffusion (or anti-persistence). We define and study a model where the price, at any instant, is the result of the impact of all past trades, mediated by a non constant `propagator' in time that describes the response of the market to a single trade. Within this model, the market is shown to be, in a precise sense, at a critical point, where the price is purely diffusive and the average response function almost constant. We find empirically, and discuss theoretically, a fluctuation-response relation. We also discuss the fraction of truly informed market orders, that correctly anticipate short term moves, and find that it is quite small.
Parameter identification using memetic algorithms for fuzzy systems

In recent years, fuzzy modelling has become very popular because of its ability to assign meaningful linguistic labels to fuzzy sets in the rule base. However, in order to achieve better performance in fuzzy modelling, parameter identification often needs to be performed. In this paper, we address this optimization problem using memetic algorithms (MAs) for Sugeno and Yasukawa's (SY) qualitative (fuzzy) model. MAs are essentially variants of Genetic Algorithms incorporated with local search methods (or memes) that could better improve the search control accuracy. In addressing the parameter identification problem, MAs are utilized to perform search exploitation within the neighbourhood of the prior knowledge extracted via the Improved SY fuzzy modelling approach. The use of MAs in performing parameter identification is examined empirically, and found to produce better solutions attributable to the extraction and proper use of prior knowledge.
Contrasting the direct radiative effect and direct radiative forcing of aerosols

Abstract. The direct radiative effect (DRE) of aerosols, which is the instantaneous radiative impact of all atmospheric particles on the Earth's energy balance, is sometimes confused with the direct radiative forcing (DRF), which is the change in DRE from pre-industrial to present-day (not including climate feedbacks). In this study we couple a global chemical transport model (GEOS-Chem) with a radiative transfer model (RRTMG) to contrast these concepts. We estimate a global mean all-sky aerosol DRF of −0.36 Wm−2 and a DRE of −1.83 Wm−2 for 2010. Therefore, natural sources of aerosol (here including fire) affect the global energy balance over four times more than do present-day anthropogenic aerosols. If global anthropogenic emissions of aerosols and their precursors continue to decline as projected in recent scenarios due to effective pollution emission controls, the DRF will shrink (−0.22 Wm−2 for 2100). Secondary metrics, like DRE, that quantify temporal changes in both natural and anthropogenic aerosol burdens are therefore needed to quantify the total effect of aerosols on climate.
Long‐term follow‐up of imatinib plus combination chemotherapy in patients with newly diagnosed Philadelphia chromosome‐positive acute lymphoblastic leukemia

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty‐two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5‐year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5‐year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P < 0.0001), and overall survival (P = 0.002). During the initial phase of treatment of patients with Ph+ ALL, it is important to maintain imatinib dose intensity. Am. J. Hematol. 90:1013–1020, 2015. © 2015 Wiley Periodicals, Inc.
Properties and topography of the major integral plasma membrane protein of a unicellular organism

The cellular distribution, membrane orientation, and biochemical properties of the two major NaOH-insoluble (integral) plasma membrane proteins of Euglena are detailed. We present evidence which suggests that these two polypeptides (Mr 68 and 39 kD) are dimer and monomer of the same protein: (a) Antibodies directed against either the 68- or the 39-kD polypeptide bind to both 68- and 39-kD bands in Western blots. (b) Trypsin digests of the 68- and 39-kD polypeptides yield similar peptide fragments. (c) The 68- and 39-kD polypeptides interconvert during successive electrophoresis runs in the presence of SDS and beta- mercaptoethanol. (d) The 39-kD band is the only major integral membrane protein evident after isoelectric focusing in acrylamide gels. The apparent shift from 68 to 39 kD in focusing gels has been duplicated in denaturing SDS gels by adding ampholyte solutions directly to the protein samples. The membrane orientation of the 39-kD protein and its 68-kD dimer has been assessed by radioiodination in situ using intact cells or purified plasma membranes. Putative monomers and dimers are labeled only when the cytoplasmic side of the membrane is exposed. These results together with trypsin digestion data suggest that the 39- kD protein and its dimer have an asymmetric membrane orientation with a substantial cytoplasmic domain but with no detectable extracellular region. Immunolabeling of sectioned cells indicates that the plasma membrane is the only cellular membrane with significant amounts of 39- kD protein. No major 68- or 39-kD polypeptide bands are evident in SDS acrylamide gels or immunoblots of electrophoresed whole flagella or preparations enriched in flagellar membrane vesicles, nor is there a detectable shift in any flagellar polypeptide in the presence of ampholyte solutions. These findings are considered with respect to the well-known internal crystalline organization of the euglenoid plasma membrane and to the potential for these proteins to serve as anchors for membrane skeletal proteins.
Binding of actin to liver cell membranes: the state of membrane-bound actin

Previous work has shown that actin binds specifically and saturably to liver membranes stripped of endogenous actin (Tranter, M. P., S. P. Sugrue, and M. A. Schwartz. 1989. J. Cell Biol. 109:2833-2840). Scatchard plots of equilibrium binding data were linear, indicating that binding is not cooperative, as would be expected for F- or G- actin. To determine the state of membrane-bound actin, we have analyzed the binding of F- and G-actin to liver cell membranes. G-actin in low salt depolymerization buffer and EF-actin, a derivative that polymerizes very poorly in solution, bind to liver cell membranes as well as untreated actin in polymerization buffer. Phalloidin-stabilized F-actin binds, but to a lesser extent. The binding of F- and G-actins are mutually competitive and are inhibited by ATP, suggesting that both forms of actin bind to the same sites. For untreated actin in polymerization buffer, the time course of binding is biphasic, with an initial rapid component which is followed by a plateau phase, then a second, slower component. The binding kinetics of pure F-actin and pure G-actin are both monophasic and match the fast and slower components, respectively, of untreated actin. In the reconstituted system, membrane- bound actin does not stain with rhodamine-phalloidin, nor are actin filaments detected by EM. Distinct regions of amorphous material, however, are visible, which stain with an anti-actin antibody. The exact nature of this material has yet to be determined. A model of actin binding is presented.
Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary. We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi‐likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population‐average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.
Diffuse iris melanoma: Report of a case with review of the literature

Diffuse iris melanoma is an uncommon variant of anterior uveal melanoma. It is characterized by heterochromia and unilateral glaucoma secondary to angle invasion, and can be difficult to diagnose. We present a patient who had been managed for left-sided raised intraocular pressure with latanoprost eye drops for 12-months and pigmentary changes were subsequently noted. On referral to the Ocular Oncology Unit, Sydney, iris melanoma was suspected and confirmed on iridectomy, and the eye was eventually enucleated.
Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G1‐modulated P53 activity

Hepatitis B virus (HBV) causes chronic infection in about 350 million people worldwide. Given the important role of the most abundant liver‐specific microRNA, miR‐122, in hepatic function and liver pathology, here we investigated the potential role and mechanism of miR‐122 in regulating HBV replication. We found that miR‐122 expression in liver was significantly down‐regulated in patients with HBV infection compared with healthy controls, and the miR‐122 levels were negatively correlated with intrahepatic viral load and hepatic necroinflammation. The depletion of endogenous miR‐122 by its antisense inhibitor led to enhanced HBV replication, whereas overexpression of miR‐122 by transfection of mimic or its expression vector inhibited viral production. We next identified cyclin G1 as an miR‐122 target from multiple candidate target genes that are involved in the regulation of HBV replication. Overexpression and knockdown studies both showed that cyclin G1 regulated viral replication in HBV transfected cells. We also observed that cyclin G1 expression was up‐regulated in HBV‐infected patients, and cyclin G1 levels were inversely associated with miR‐122 expression in liver tissues. Using coimmunoprecipitation, a luciferase reporter system, and electrophoretic mobility shift assay, we further demonstrated that cyclin G1 specifically interacted with p53, and this interaction blocked the specific binding of p53 to HBV enhancer elements and simultaneously abrogated p53‐mediated inhibition of HBV transcription. Finally, we show that miR‐122 suppressed HBV replication in p53 wildtype cells but not in null isogenic cells. Conclusion: miR‐122 down‐regulates its target cyclin G1, and thus interrupts the interaction between cyclin G1 and p53 and abrogates p53‐mediated inhibition of HBV replication. Our work shows that miR‐122 down‐regulation induced by HBV infection can impact HBV replication and possibly contribute to viral persistence and carcinogenesis. (HEPATOLOGY 2012;)
Collection-limited theory interprets the extraordinary response of single semiconductor organic solar cells

Significance We demonstrate that, instead of the charge generation mechanism, charge collection can readily explain the bottleneck toward higher efficiency single organic semiconductor based OPVs (SS-OPVs). This change in archetype has the potential to transform the design rules for materials used in OPV devices and would inspire searches for a completely different set of polymers for OPV cells. Furthermore, we believe that our findings will broaden the understanding of the physics of charge transport and the impact of charged defect states in organic electronic devices. Hence, this work should have deep and immediate impact on the chemists, materials scientists, and device physicists in the field and would be of broad interest to the organic electronics community. The bulk heterojunction (BHJ) organic photovoltaic (OPV) architecture has dominated the literature due to its ability to be implemented in devices with relatively high efficiency values. However, a simpler device architecture based on a single organic semiconductor (SS-OPV) offers several advantages: it obviates the need to control the highly system-dependent nanoscale BHJ morphology, and therefore, would allow the use of broader range of organic semiconductors. Unfortunately, the photocurrent in standard SS-OPV devices is typically very low, which generally is attributed to inefficient charge separation of the photogenerated excitons. Here we show that the short-circuit current density from SS-OPV devices can be enhanced significantly (∼100-fold) through the use of inverted device configurations, relative to a standard OPV device architecture. This result suggests that charge generation may not be the performance bottleneck in OPV device operation. Instead, poor charge collection, caused by defect-induced electric field screening, is most likely the primary performance bottleneck in regular-geometry SS-OPV cells. We justify this hypothesis by: (i) detailed numerical simulations, (ii) electrical characterization experiments of functional SS-OPV devices using multiple polymers as active layer materials, and (iii) impedance spectroscopy measurements. Furthermore, we show that the collection-limited photocurrent theory consistently interprets typical characteristics of regular SS-OPV devices. These insights should encourage the design and OPV implementation of high-purity, high-mobility polymers, and other soft materials that have shown promise in organic field-effect transistor applications, but have not performed well in BHJ OPV devices, wherein they adopt less-than-ideal nanostructures when blended with electron-accepting materials.
Early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in the KIKO mouse model of Friedreich ataxia

ABSTRACT Friedreich ataxia (FRDA), the most common recessive inherited ataxia, results from deficiency of frataxin, a small mitochondrial protein crucial for iron-sulphur cluster formation and ATP production. Frataxin deficiency is associated with mitochondrial dysfunction in FRDA patients and animal models; however, early mitochondrial pathology in FRDA cerebellum remains elusive. Using frataxin knock-in/knockout (KIKO) mice and KIKO mice carrying the mitoDendra transgene, we show early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in this FRDA model. At asymptomatic stages, the levels of PGC-1α (PPARGC1A), the mitochondrial biogenesis master regulator, are significantly decreased in cerebellar homogenates of KIKO mice compared with age-matched controls. Similarly, the levels of the PGC-1α downstream effectors, NRF1 and Tfam, are significantly decreased, suggesting early impaired cerebellar mitochondrial biogenesis pathways. Early mitochondrial deficiency is further supported by significant reduction of the mitochondrial markers GRP75 (HSPA9) and mitofusin-1 in the cerebellar cortex. Moreover, the numbers of Dendra-labeled mitochondria are significantly decreased in cerebellar cortex, confirming asymptomatic cerebellar mitochondrial biogenesis deficits. Functionally, complex I and II enzyme activities are significantly reduced in isolated mitochondria and tissue homogenates from asymptomatic KIKO cerebella. Structurally, levels of the complex I core subunit NUDFB8 and complex II subunits SDHA and SDHB are significantly lower than those in age-matched controls. These results demonstrate complex I and II deficiency in KIKO cerebellum, consistent with defects identified in FRDA patient tissues. Thus, our findings identify early cerebellar mitochondrial biogenesis deficits as a potential mediator of cerebellar dysfunction and ataxia, thereby providing a potential therapeutic target for early intervention of FRDA. Summary: Our findings identify early cerebellar mitochondrial biogenesis deficits as a potential mediator of cerebellar dysfunction and ataxia, and indicate a potential therapeutic target for early intervention of Friedreich ataxia.