Miracle-dz/UniFAR-FTUs huggingface dataset:
Adamts-1 Is Essential for the Development and Function of the Urogenital System1

Abstract Successful ovulation and implantation processes play a crucial role in female fertility. Adamts-1, a matrix metalloproteinase with disintegrin and thrombospondin motifs, has been suggested to be regulated by the progesterone receptor in the hormonal pathway leading to ovulation. With the primary aim of investigating the role of Adamts-1 in female fertility, we generated Adamts-1 null mice. Forty-five percent of the newborn Adamts-1 null mice die, with death most likely caused by a kidney malformation that becomes apparent at birth. Surviving female null mice were subfertile, whereas males reproduced normally. Ovulation in null females was impaired because of mature oocytes remaining trapped in ovarian follicles. No uterine phenotype was apparent in Adamts-1 null animals. Embryo implantation occurred normally, the uteri were capable of undergoing decidualization, and no morphological changes were observed. These results demonstrate that a functional Adamts-1 is required for normal ovulation to occur, and hence the Adamts-1 gene plays an important role in female fertility, primarily during the tissue remodeling process of ovulation.
Evolutionary Indicators of Human Immunodeficiency Virus Type 1 Reservoirs and Compartments

ABSTRACT In vivo virologic compartments are cell types or tissues between which there is a restriction of virus flow, while virologic reservoirs are cell types or tissues in which there is a relative restriction of replication. The distinction between reservoirs and compartments is important because therapies that would be effective against a reservoir may not be effective against viruses produced by a given compartment, and vice versa. For example, the use of cytokines to “flush out” long-lived infected cells in patients on highly active antiretroviral therapy (T. W. Chun, D. Engel, M. M. Berrey, T. Shea, L. Corey, and A. S. Fauci, Proc. Natl. Acad. Sci. USA 95:8869-8873, 1998) may be successful for a latent reservoir but may not impact a compartment in which virus continues to replicate because of poor drug penetration. Here, we suggest phylogenetic criteria to illustrate, define, and differentiate between reservoirs and compartments. We then apply these criteria to the analysis of simulated and actual human immunodeficiency virus type 1 sequence data sets. We report that existing statistical methods work quite well at detecting viral compartments, and we learn from simulations that viral divergence from a calculated most recent common ancestor is a strong predictor of viral reservoirs.
Effectiveness of Subgingival Irrigation as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis: A Systematic Review.

AIM Subgingival applications of various chemotherapeutic agents have been used as an adjunct to nonsurgical periodontal treatment and preventive periodontal therapy. Their use in regular clinical practice, however, is less, perhaps due to concerns about clinical success or probably due to a lack of knowledge of their effectiveness or cost. The aim of this systematic review is to obtain overall quantitative estimate of effectiveness of subgingival irrigation (SI) in the treatment of chronic periodontitis. MATERIALS AND METHODS A literature search of electronic database was performed for articles published through December 31, 2014, followed by manual search of dental journals. Randomized controlled trails (RCTs) assessing the effect of SI as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis evaluated by changes in the clinical and microbiological outcomes were included. RESULTS This literature search yielded only two randomized, placebo-controlled studies that evaluated the efficacy of SI as an adjunct to SRP in patients with chronic periodontitis. The studies were methodologically not perfect (in terms of mediocre quality) with a risk of bias to come to any final conclusions to be reached. These studies didn't clearly mention about randomization, allocation concealment, blinding, dosage and formulation of irrigants, severity of periodontal disease, patient-centered outcomes and results data. CONCLUSION Due to insufficient evidence supporting the efficacy of SI as an adjunct to SRP in treating chronic periodontitis, more rigorous scientific research is required to assess the efficacy of SI as an adjunct to SRP in the treatment of periodontal diseases.
Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND Less than half of all patients with aggressive non-Hodgkin's lymphoma (NHL) are cured with standard chemotherapy. Therefore, it is important to distinguish between responders to standard treatment and non-responders who may benefit from an early change to a more effective therapy. This study was intended to assess the value of a midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) scan to predict clinical outcome in patients with aggressive NHL. PATIENTS AND METHODS Seventy newly diagnosed patients with aggressive NHL, who were treated with doxorubicin-containing chemotherapy, underwent a [(18)F]FDG-PET scan at midtreatment. Presence or absence of abnormal [(18)F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Multivariate analysis was performed to evaluate the effect of the International Prognostic Index (IPI) and early [(18)F]FDG-PET findings on PFS and OS. RESULTS At midtreatment, 33 patients showed persistent abnormal [(18)F]FDG uptake and none of these patients achieved a durable complete remission (CR), whereas 37 patients showed a negative scan; 31/37 remained in CR, with a median follow-up of 1107 days. Only 6/37 patients either achieved a partial response or relapsed. Comparison between groups indicated a statistically significant association between [(18)F]FDG-PET findings and PFS (P <1 x 10(-5)) and OS (P <1 x 10(-5)). In multivariate analysis, [(18)F]FDG-PET at midtreatment was a stronger prognostic factor for PFS (P <1 x 10(-7)) and OS (P <9 x 10(-6)) than the IPI (P <0.11 and P <0.03, respectively). CONCLUSIONS Early restaging [(18)F]FDG-PET may be used to tailor induction chemotherapy in patients with aggressive NHL.
The Effects of Pharmacologic Plasminogen Activator Inhibitor-1 Inhibition in Acute and Chronic Rejection in Murine Cardiac Allografts

Background. Acute rejection and graft arterial disease (GAD) in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by inflammation and thrombus formation. Plasminogen activator inhibitor (PAI)-1 is critical in the inflammation and thrombus formation. However, little is known about the effect of PAI-1 in heart transplantation. Thus, the objective was to clarify the role of PAI-1 in the progression of cardiac rejection. Methods. Murine hearts were heterotopically transplanted using major mismatch combinations for evaluation of acute rejection and class II mismatch combinations for the GAD. We administered the specific PAI-1 inhibitor (IMD-1622) into murine recipients after cardiac allografts. Results. Nontreated allografts of the major mismatch group were acutely rejected, whereas the PAI-1 inhibitor prolonged their survival. Although severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated allografts of class II mismatch group on day 60, the PAI-1 inhibitor attenuated these changes. Conclusion. The PAI-1 inhibitor is potent for the suppression of both acute rejection and GAD.
CONTEMPORARY SOCIAL CONTRACT – SOCIAL LIBERALISM (NEW SOCIALISM)

My proposal of a contemporary social contract is a development of an outline of a program entitled, „The Social State versus Neoliberalism―. A contemporary social contract must employ positive elements of capitalism, such as workers' ownership of stocks, as well as of socialism, such as self-rule. The framework of the new social model arises from philosophical and sociological thinking of the society as a whole. Its central components could be articulated by economists, and political science can assess its political implementation. By considering Rousseau's Social Contract, I put forward criticisms of capitalist neoliberalism, which advocates deregulation of the market and enables a minority to enjoy great profits. I examine the foundations of its functioning-namely financial capital: a) Oligarchy of a few banks in collaboration with various corporations, especially oil companies, which employ false theories b) Unsupervised judgments of self-established agencies, especially those that determine creditworthiness c) Hidden rule of self-made technocratic associations. I conclude: In capitalism there is no democracy. A new socialism is needed to balance capitalism. In particular, we need market regulation in support of state and public institutions: a) Worker-owned stocks b) Partnerships between public and private c) Citizens' participation in governance. Concretely, the following actions are required on a local and global level: a) A call to resist the power of financial capital b) Abandoning the saying that the state, unlike the enterpreneur, is a poor governor c) Strengthening the secular state.
Telling It Like It Is: The Adaptive Function of Narratives in Coping With Loss in Later Life

As the population ages, caregivers and health care providers need more insight into how people experience old age and their attitudes and emotions about growing older. It is particularly critical to understand how communication processes change and how older adults communicate their concerns and feelings. This article proposes that some discursive activities may play a crucial role in successfully adapting to, and coping with, loss in later life. Thus, this study explored how older adults reflect on and express themselves concerning recent experiences of loss. A sample of 41 residents of 2 independent-living retirement communities wrote in journals about a recent significant loss. Participants wrote about their losses during brief lab sessions over the course of 3 consecutive days. Each set of 3 journals was content-analyzed to measure the frequency with which the participants employed emotional expression, factual recounting, account giving, religious-account giving, humor, intensifiers, and referential statements. The analysis indicates that, overall, participants shifted from a primarily factual mode (what the loss was, how the loss occurred, etc.) to more of a focus on the impact of this loss on their lives (e.g., handling new tasks and expressions of emotions) over the 3 sessions. In addition, most participants offered accounts of their losses; that is, they attempted to find some meaning in the loss and integrate the loss into an overall framework for their lives. Many of these accounts focused on religion. Final sections of the article discuss the implications of journaling as a mechanism for effective coping with loss, as a useful tool for expressing emotions, and as a means for older adults' caregivers and health care providers to better adapt their supportive messages.
Structured lipids obtained by chemical and enzymatic interesterification from fish oil and palm kernel fat

Through the structured lipids is possible to obtain fatty acids which are used as nourishings or therapeutics on specific diseases or on abnormal metabolic conditions. They are also synthesized to improve or alter the physic and/or chemical characteristics of the triacylglycerols. The objective of this study was to obtain structured lipids by chemical and enzymatic interesterification from palm kernel fat and fish oil. The samples were analyzed for the solid fat content at the temperatures from 10 to 30 oC. A mathematical model of multiple regression of the quadratic type was applied. The solid fat content depended on the palm kernel fat and on the binary interactions between palm kernel fat and fish oil. The negative coefficients to the solid fat content showed an antagonic effect, which is characteristic of eutectic interactions between fats. The solid fat content after chemical and enzymatic interesterification was very similar.
Modeling and optimization techniques for digital video communication

This dissertation investigates the modeling and optimization of several problems that arise during compression or adaptation of both frame-based and object-based (structured) multimedia content. In particular, we address: (a) The optimal dynamic rate shaping (DRS) of Markov-1 sources. We present the first extensive experimental study on the various DRS algorithms (causally optimal, memoryless, and rate-based) both in their constrained and generalized forms. The study proves the computational viability of the DRS approach to transcoding and identifies a range of rate shaping ratios for which it is better than requantization, both complexity-wise as well as in performance. We substantiate the almost-optimal experimental performance of the memoryless algorithm by analyzing the behavior of the DRS problem assuming a first order Markovian source. (b) The modeling of object based audio-visual communication systems, such as MPEG-4, both at the server ( proxy) side for transcoding purposes and at the client end for adaptive play-out control. For the server-side problem, we suggest a way of modeling object-based scalability and some functionalities that it brings with it. Our goal in this study is to find algorithms that aid in semi-automating the selective addition/dropping of objects from a scene to provide content scalability. The ‘multiple choice knapsack problem (MCKP)’ is used to model objects encoded at different target bit rates. We discuss several efficient ways to choose objects optimally at the transcoded rate, and build on the above integer problem to impose logical inter-dependencies among objects. Experimental results are presented validating the efficiency and performance of these linear programming based algorithms. (c) The best possible intra and inter frame quantization. We use the MCKP formulation to study the intra-frame bit allocation problem as well, and suggest how to use the linear relaxation instead of the Lagrangian relaxation, dynamic programming or the marginal analysis approach. This method leads to a provable reduction in algorithmic complexity, is slightly more generic than the other ones and provides an alternate linear-programming duality based approach for a vast array of problems formulated in an Operational Rate-Distortion context. For the inter-frame quantization problem, we study the incremental improvement obtained by relaxing a so-called causality assumption and incorporate for dependencies explicitly in the model. (Abstract shortened by UMI.)
Experimental autoimmune uveoretinitis initiated by non‐phagocytic destruction of inner segments of photoreceptor cells by Mac‐1+ mononuclear cells

EAU in mice is a model of human posterior uveitis. EAU is a Th1‐dependent disease that has been assumed to target the neural retina and related tissues; however, in situ effector cells and the target have not yet been clearly demonstrated. In the present study, we induced EAU in B10R mice by immunizing them with human interphotoreceptor retinoid‐binding protein peptide 161–180. Histological examinations revealed that EAU occurred approximately 11 days after the immunization and reached a peak on day 14. Retinae from normal or EAU mice were treated with proteases to obtain mono‐dispersed cells. The mono‐dispersed cells thus obtained were separated into three to four fractions by discontinuous Percoll density‐gradient (e.g. PBS/40/60) centrifugation. In normal mice, 94% of the total cells were recovered in two fractions (i.e. PBS/40 and pellet); and these fractions mainly contained inner and outer segments and cell bodies of photoreceptor cells and RPE cells, respectively. In EAU mice, additional cells (i.e. inflammatory cells) were obtained at the 40/60 interface. Electron microscopic examination showed that tissue damage during EAU was initiated by non‐phagocytic destruction of inner segments by Mac‐1+ mononuclear cells on day 11, followed by phagocytic activity of macrophages against outer segments and RPE cells on day 14. In vitro culturing of normal retinal cells with EAU infiltrates suggested the involvement of TNF‐α and NO in the tissue damage. These results indicate that EAU was initiated by non‐phagocytic destruction of inner segments of photoreceptor cells by Mac‐1+ mononuclear cells.
MORC3, a Component of PML Nuclear Bodies, Has a Role in Restricting Herpes Simplex Virus 1 and Human Cytomegalovirus

ABSTRACT We previously reported that MORC3, a protein associated with promyelocytic leukemia nuclear bodies (PML NBs), is a target of herpes simplex virus 1 (HSV-1) ICP0-mediated degradation (E. Sloan, et al., PLoS Pathog 11:e1005059, 2015, http://dx.doi.org/10.1371/journal.ppat.1005059). Since it is well known that certain other components of the PML NB complex play an important role during an intrinsic immune response to HSV-1 and are also degraded or inactivated by ICP0, here we further investigate the role of MORC3 during HSV-1 infection. We demonstrate that MORC3 has antiviral activity during HSV-1 infection and that this antiviral role is counteracted by ICP0. In addition, MORC3's antiviral role extends to wild-type (wt) human cytomegalovirus (HCMV) infection, as its plaque-forming efficiency increased in MORC3-depleted cells. We found that MORC3 is recruited to sites associated with HSV-1 genomes after their entry into the nucleus of an infected cell, and in wt infections this is followed by its association with ICP0 foci prior to its degradation. The RING finger domain of ICP0 was required for degradation of MORC3, and we confirmed that no other HSV-1 protein is required for the loss of MORC3. We also found that MORC3 is required for fully efficient recruitment of PML, Sp100, hDaxx, and γH2AX to sites associated with HSV-1 genomes entering the host cell nucleus. This study further unravels the intricate ways in which HSV-1 has evolved to counteract the host immune response and reveals a novel function for MORC3 during the host intrinsic immune response. IMPORTANCE Herpesviruses have devised ways to manipulate the host intrinsic immune response to promote their own survival and persistence within the human population. One way in which this is achieved is through degradation or functional inactivation of PML NB proteins, which are recruited to viral genomes in order to repress viral transcription. Because MORC3 associates with PML NBs in uninfected cells and is a target for HSV-1-mediated degradation, we investigated the role of MORC3 during HSV-1 infection. We found that MORC3 is also recruited to viral HSV-1 genomes, and importantly it contributes to the fully efficient recruitment of PML, hDaxx, Sp100, and γH2AX to these sites. Depletion of MORC3 resulted in an increase in ICP0-null HSV-1 and wt HCMV replication and plaque formation; therefore, this study reveals that MORC3 is an antiviral factor which plays an important role during HSV-1 and HCMV infection.
Trends in Stroke-Related Mortality in the ABC Region, São Paulo, Brazil: An Ecological Study Between 1997 and 2012

Background: Stroke is the second leading cause of death and the third leading cause of physical disability in the world, with a high burden of morbidity and mortality, but it has been shown a reduction in mortality worldwide over the past two decades, especially in regions with higher income. Objective: The study analyzed the temporal trend and the factors associated with stroke-related mortality in the cities that make up the ABC region of São Paulo (Santo André, São Bernardo do Campo, São Caetano do Sul, Diadema, Mauá, Ribeirão Pires, and Rio Grande da Serra), in comparison to data from the capital city of São Paulo, in the state of São Paulo, Brazil. Method: This was an ecological study conducted in 2017 using data from 1997 to 2012. Data were collected in 2017 from the Department of Informatics of the Brazilian Unified National Health System (DATASUS), where the Mortality Information System (SIM/SUS) was accessed. Linear regression analysis was used to estimate the temporal trend of stroke-related mortality according to sex, stroke subtypes, and regions. The confidence level adopted was 95%. Results: There was a reduction in the mortality rates stratified according to sex, age groups above 15 years, and subtypes of stroke. Mortality from hemorrhagic and non-specified stroke decreased in all regions. However, a significant reduction in ischemic stroke-related mortality was observed only in the ABC region and in Brazil. Conclusion: The ABC region showed greater mortality due to stroke in males, the age group above 49 years, and non-specified stroke between 1997 and 2012.
Combination of Hyperband and Bayesian Optimization for Hyperparameter Optimization in Deep Learning

Deep learning has achieved impressive results on many problems. However, it requires high degree of expertise or a lot of experience to tune well the hyperparameters, and such manual tuning process is likely to be biased. Moreover, it is not practical to try out as many different hyperparameter configurations in deep learning as in other machine learning scenarios, because evaluating each single hyperparameter configuration in deep learning would mean training a deep neural network, which usually takes quite long time. Hyperband algorithm achieves state-of-the-art performance on various hyperparameter optimization problems in the field of deep learning. However, Hyperband algorithm does not utilize history information of previous explored hyperparameter configurations, thus the solution found is suboptimal. We propose to combine Hyperband algorithm with Bayesian optimization (which does not ignore history when sampling next trial configuration). Experimental results show that our combination approach is superior to other hyperparameter optimization approaches including Hyperband algorithm.
Subversion of Cell Signaling Pathways by Hepatitis C Virus Nonstructural 5A Protein via Interaction with Grb2 and P85 Phosphatidylinositol 3-Kinase

ABSTRACT Hepatitis C virus (HCV) sets up a persistent infection in patients that likely involves a complex virus-host interaction. We previously found that the HCV nonstructural 5A (NS5A) protein interacts with growth factor receptor-binding protein 2 (Grb2) adaptor protein and inhibits the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by epidermal growth factor (EGF). In the present study, we extended this analysis and investigated the specificity of the Grb2-NS5A interaction and whether the subversion of mitogenic signaling involves additional pathways. NS5A containing mutations within the C-terminal proline-rich motif neither bound Grb2 nor inhibited ERK1/2 activation by EGF, demonstrating that NS5A-Grb2 binding and downstream effects were due to direct interactions. Interestingly, NS5A could also form a complex with the Grb2-associated binder 1 (Gab1) protein in an EGF treatment-dependent manner. However, the NS5A-Gab1 association, which appeared indirect, was not mediated by direct NS5A-Grb2 interaction but was likely dependent on direct NS5A interaction with the p85 subunit of phosphatidylinositol 3-kinase (PI3K). The in vivo association of NS5A with p85 PI3K required the N-terminal, but not the C-terminal, region of NS5A. The downstream effects of the NS5A-p85 PI3K interaction included increased tyrosine phosphorylation of p85 PI3K in response to EGF. Consistent with this observation and the antiapoptotic properties of NS5A, we also detected enhanced tyrosine phosphorylation of the downstream AKT protein kinase and increased serine phosphorylation of BAD, a proapoptotic factor and an AKT substrate, in the presence of NS5A. These results collectively suggest a model in which NS5A interacts with Grb2 to inhibit mitogenic signaling while simultaneously promoting the PI3K-AKT cell survival pathway by interaction with p85 PI3K, which may represent a crucial step in HCV persistence and pathogenesis.