Miracle-dz/UniFAR-FTUs huggingface dataset:
Myocardial Smad4 Is Essential for Cardiogenesis in Mouse Embryos

Congenital heart diseases are the most commonly observed human birth defects and are the leading cause of infant morbidity and mortality. Accumulating evidence indicates that transforming growth factor-&bgr;/bone morphogenetic protein signaling pathways play critical roles during cardiogenesis. Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of transforming growth factor-&bgr;/bone morphogenetic protein signaling. The aim of this work was to investigate the roles of Smad4 during heart development. To overcome the early embryonic lethality of Smad4−/− mice, we specifically disrupted Smad4 in the myocardium using a Cre/loxP system. We show that myocardial-specific inactivation of Smad4 caused heart failure and embryonic lethality at midgestation. Histological analysis revealed that mutant mice displayed a hypocellular myocardial wall defect, which is likely the primary cause for heart failure. Both decreased cell proliferation and increased apoptosis contributed to the myocardial wall defect in mutant mice. Data presented in this article contradict a previous report showing that Smad4 is dispensable for heart development. Our further molecular characterization showed that expression of Nmyc and its downstream targets, including cyclin D1, cyclin D2, and Id2, were downregulated in mutant embryos. Reporter analysis indicated that the transcriptional activity of the 351-bp Nmyc promoter can be positively regulated by bone morphogenetic protein stimulation and negatively regulated by transforming growth factor-&bgr; stimulation. Chromatin immunoprecipitation analysis revealed that the Nmyc promoter can form a complex with Smad4, suggesting that Nmyc is a direct downstream target of Smad4. In conclusion, this study provides the first mouse model showing that Smad4 plays essential roles during cardiogenesis.
Is Code Still Moving Around? Looking Back at a Decade of Code Mobility

In the mid-nineties, mobile code was on the rise and, in particular, there was a growing interest in autonomously moving code components, called mobile agents. In 1997, we published a paper that introduced the concept of mobile code paradigms, which are design patterns that involve code mobility. The paradigms highlighted the locations of code, resources, and execution as first-class abstractions. This characterization proved useful to frame mobile code designs and technologies, and also as a basis for a quantitative analysis of applications built with them. Ten years later, things have changed considerably. In this paper we present our view of how mobile code evolved and discuss which paradigms succeeded or failed in supporting effectively distributed applications.
Technological progresses in monoclonal antibody production systems

Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large‐scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the optimization of cell culture productivity in normal bioreactors appears as a better strategy. This review describes the main technological progresses made with this intent, presenting the advantages and limitations of each production system, as well as suggestions for improvements. New and upgraded bioreactors have emerged both for adherent and suspension cell culture, with disposable reactors attracting increased interest in the last years. Furthermore, the strategies and technologies used to control culture parameters are in constant evolution, aiming at the on‐line multiparameter monitoring and considering now parameters not seen as relevant for process optimization in the past. All progresses being made have as primary goal the development of highly productive and economic mAb manufacturing processes that will allow the rapid introduction of the product in the biopharmaceutical market at more accessible prices. © 2010 American Institute of Chemical Engineers Biotechnol. Prog. , 2010
Social Problems in Major League Baseball: Revisiting and Expanding Talamini’s Analysis Twenty Years Later

The purpose of this research was to review, revisit, and expand Talamini’s social problems within Major League Baseball (MLB). Talamini’s categories, which include gambling, player/managerial violence, spectator violence, cheating, crime, and greed are reviewed and applied to social problems in MLB since the original publication in 1987. In order to better understand social problems and deviant behavior within MLB, the original categories are related to specific deviance theories to better understand causation of deviance. Theories are then organized by Shoemaker’s proposed integrated model, which organizes causes of deviance on the structural, social-psychological, and psychological levels. Relating Talamini’s social problems categories to sociology of deviance theories, and then organized by Shoemaker’s proposed integrated model aids in better explaining MLB deviance. Recommendations are made to sport management practitioners, students, and scholars regarding how to ameliorate the aforementioned social problems.
The gradient of Gurken, a long-range morphogen, is directly regulated by Cbl-mediated endocytosis

The asymmetric localization of gurken mRNA and post-translational sorting mechanisms are responsible for the polar distribution of Gurken protein in Drosophila. However, endocytosis of Egfr, the receptor for Gurken in the follicle cells, also plays a role in shaping the extracellular gradient of the Gurken morphogen. Previously, we have found that mutation in the Cbl gene caused elevated Egfr signaling along the dorsoventral axis, and resulted in dorsalization phenotypes in embryos and egg shells. Here, we report that overexpression of the Cbl long isoform significantly changed Gurken distribution. Using an HRP-Gurken fusion protein, we demonstrate that internalization of the Gurken-Egfr complex depends on the activity of Cbl. Increased levels of CblL promote the internalization of this complex, leading to the reduction of free ligands. The Gurken-Egfr complex trafficks through the Rab5/Rab7 associated endocytic pathway to the lysosomal degradation compartment for signaling termination. We observe endocytic Gurken not only in the dorsal but also in the ventral follicle cells, which is, to our knowledge, the first visualization of Gurken on the ventral side of egg chambers. Our results show that Gurken travels towards the lateral/posterior of the egg chamber in the absence of Cbl, suggesting that Cbl actively regulates Gurken distribution through promoting endocytosis and subsequent degradation.
Women and Politics: The Pursuit of Equality

WOMEN AND POLITICS examines the pursuit of gender equality from two viewpoints: the legal equality doctrine, which emphasizes gender neutrality, and the fairness doctrine, which recognizes differences between men and women. The text's in-depth analysis and clear presentation of theory and history helps students to think critically about gender and about the challenges faced by women today and in the past. Extensive coverage of diversity among women and consistent attention to the intersections of race, class, and gender are integral to the text's two-viewpoints theme.
Evaluation of the porcine intestinal collagen layer as a biomaterial.

The submucosal layer of the small intestine has been investigated as a source of collagenous tissue with the potential to be used as a biomaterial because of its inherent strength and biocompatibility. In this study we utilized a novel method for processing the tissue to generate an acellular intestinal collagen layer (ICL). This nondetergent, nonenzymatic chemical cleaning protocol removes cells and cellular debris without damaging the native collagen structure. Multilayer laminates of ICL crosslinked with a water-soluble carbodiimide (EDC) were evaluated as a tissue repair material in a rabbit abdominal hernia model. The ICL laminates provided the requisite physical properties and did not lead to adhesion formation. No immune response to the porcine collagen was detectable, and this material did not show any calcification in either the rabbit model or in the juvenile rat model.
Parasitic aware routing methodology based on higher order RLCK moment metrics

In the multi-GHz frequency domain, inductive and capacitive parasitics of interconnects can cause significant 'ringing' or overdamping, which may lead to false switching or increased delay. Routing techniques which rely on wire length reduction or coupling capacitance minimization are unable to obtain the best routing solution. In this paper, the inductive and capacitive interactions of the wires are introduced through a 'moment' based cost function. This higher order RLCK moment metric guides the routing process of long wires, ensuring that the chosen solution has the best trade-off between ringing and delay under a monotone signal response. Another significant departure from existing routing methodologies is to account for the signal direction in the nets which may increase or decrease the effective inductive and capacitive parasitics.
Printed Slot and Wire Antennas: A Review

The first part of this paper focuses on printed slot antennas. Starting with discussions of a narrow modified slot and a wide slot fed by a microstrip line, we proceed to a topic of generation of a circularly polarized beam. In addition, a rectangular slot antenna fed by a coplanar waveguide is described. The modification of a rectangular slot into an elliptical slot for enhancing the bandwidth is also presented. The second part of this paper covers wire antennas, first presenting the theoretical treatment and then the radiation characteristics of various configurations. It is described that a multiloop antenna exhibits multiband characteristics; a spiral antenna has wideband characteristics with the help of resistive material; and a helical element, having only the region, radiates a circularly polarized wave. An inverted F-antenna (IFA) backed by an electromagnetic band gap (EBG) reflector and a composite helical and spiral (CHES) antenna are then presented, both radiating a tilted beam. Next, a curl antenna array that has an unrivaled aperture efficiency of more than 90% is introduced.
Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate.

Most individuals with cystic fibrosis (CF) carry one or two mutations that result in a maturation defect of the full-length protein. One such mutation, deltaF508, results in a mutant membrane glycoprotein that fails to progress to the apical membrane, where the wild-type protein normally functions as a cyclic AMP-regulated chloride channel. 4-Phenylbutyrate (Buphenyl), an orally bioavailable short chain fatty acid, modulates heat shock protein expression and restores maturation of the deltaF508 protein in vitro and in vivo. We performed a randomized, double-blind, placebo-controlled, dose-escalation and safety study of Buphenyl in 19 adults with CF (homozygous deltaF508) to test the hypothesis that Buphenyl would be safe, well-tolerated, and associated with an increase in chloride transport in nasal epithelia. Three dose levels (20, 30, or 40 g divided t.i.d.) of drug or placebo were given for 1 week. Serial measurements of chloride transport by nasal potential difference (NPD) testing and metabolic safety testing were performed. A maximum tolerated dose of 20 g was defined based on minimal adverse reactions, the safety profile, and a statistically significant induction of chloride transport that was maximal by day 3. This short-term phase I/II study demonstrates proof of principle that modulation of deltaF508 CFTR biosynthesis and trafficking is a viable therapeutic approach for cystic fibrosis.
Conceptualization: On Theory and Theorizing Using Grounded Theory

This article explores the use of grounded theory to generate conceptualizations of emergent social patterns in research data. The naming of patterns and their abstraction across time, place and people, are discussed. The constant comparative method employed in grounded data analysis is offered as a developmental tool for enhancing researchers' abilities to conceptualize and form emergent theories. Conceptual levels, descriptions, power and flawed approaches to analysis are explored at length.
N-Acetylcysteine as a Treatment for Addiction

Jennifer E. Murray1,2,*, Jerome Lacoste3 and David Belin2,4 1Department of Experimental Psychology, University of Cambridge, Cambridge, 2INSERM European Associated Laboratory, Psychobiology of Compulsive Habits, 3Unite de Recherche Clinique Intersectorielle, Centre Hospitalier Henri-Laborit, Poitiers, 4INSERM U1084 LNEC & Universite de Poitiers, AVENIR Team Psychobiology of Compulsive Disorders, Poitiers, 1,2UK 2,3,4France
Pilot Study of a 10-Week Multidisciplinary Tai Chi Intervention in Sedentary Obese Women

Objective: Alternative approaches to weight control and physical activity are increasingly needed. Numerous factors influence weight management, including the choice of physical exercise. No study has previously examined the therapeutic effect of a multidisciplinary weight management program incorporating Tai Chi (TC) exercises among sedentary obese women. Design: Randomized intervention trial with blinded medical provider. Setting: In day hospital consultations. Participants: Twenty-one obese women. Intervention: All subjects participated in a 10-week weight management program that was part of usual care and included a hypocaloric balanced diet, a weekly physician/psychologist/dietician group session, and an exercise program. For the exercise component, subjects were randomized to either a 2-hour weekly session of TC or a conventional structured exercise program. Main Outcome Measures: Changes in weight, body composition, heart rate, blood pressure, mobility scores, mood, Three Factor Eating Questionnaire scores, and General Self-Efficacy. Results: The TC arm improved in resting systolic blood pressure, chair rise test, mood, and reduced percent of fat at week 10 and at 6 months follow-up. General self-efficacy was enhanced in both groups and maintained at 30 weeks. Conclusion: The observed benefits over a 30-week period of a multidisciplinary weight management program incorporating TC exercises on physical functioning mood and dietary restraint need further understanding of how sedentary obese women adhere to physical activity like TC or other alternative exercises.
Sparse Learning via Iterative Minimization With Application to MIMO Radar Imaging

Through waveform diversity, multiple-input multiple-output (MIMO) radar can provide higher resolution, improved sensitivity, and increased parameter identifiability compared to more traditional phased-array radar schemes. Existing methods for target estimation, however, often fail to provide accurate MIMO angle-range-Doppler images when there are only a few data snapshots available. Sparse signal recovery algorithms, including many l1-norm based approaches, can offer improved estimation in that case. In this paper, we present a regularized minimization approach to sparse signal recovery. Sparse learning via iterative minimization (SLIM) follows an lq-norm constraint (for 0 <; q ≤ 1), and can thus be used to provide more accurate estimates compared to the l1-norm based approaches. We herein compare SLIM, through imaging examples and examination of computational complexity, to several well-known sparse methods, including the widely used CoSaMP approach. We show that SLIM provides superior performance for sparse MIMO radar imaging applications at a low computational cost. Furthermore, we will show that the user parameter q can be automatically determined by incorporating the Bayesian information criterion.
Formal verification guided automatic design error diagnosis and correction of complex processors

In this paper we present a method to automatically debug and correct design errors of modern microprocessors. Given a golden sequential model of the processor and the erroneous cycle-accurate model of superscalar out-of-order processors, we employ a multiplexer-based method, which has been used for RTL/gate-level designs, to formally identify the candidate locations for the errors/bugs along with a counter example to guide the error correction mechanism. By analyzing the design and the generated candidate locations and the corresponding counter example, we automatically generate a set of potential solutions to correct the error. Finally, the potential solutions are formally verified against the golden model until the error is corrected. To show the effectiveness of our method, we have chosen a complex out-of-order superscalar processor with timing error recovery mechanisms as our case study. We have injected a number of bugs in the processor model and could successfully find the bugs and also their corresponding fixes.
Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.
Location of active transmission sites of Schistosoma japonicum in lake and marshland regions in China

SUMMARY Schistosomiasis control in China has, in general, been very successful during the past several decades. However, the rebounding of the epidemic situation in some areas in recent years raises concerns about a sustainable control strategy of which locating active transmission sites (ATS) is a necessary first step. This study presents a systematic approach for locating schistosomiasis ATS by combining the approaches of identifying high risk regions for schisotosmiasis and extracting snail habitats. Environmental, topographical, and human behavioural factors were included in the model. Four significant high-risk regions were detected and 6 ATS were located. We used the normalized difference water index (NDWI) combined with the normalized difference vegetation index (NDVI) to extract snail habitats, and the pointwise ‘P-value surface’ approach to test statistical significance of predicted disease risk. We found complicated non-linear relationships between predictors and schistosomiasis risk, which might result in serious biases if data were not properly treated. We also found that the associations were related to spatial scales, indicating that a well-designed series of studies were needed to relate the disease risk with predictors across various study scales. Our approach provides a useful tool, especially in the field of vector-borne or environment-related diseases.
Brain Networks Supporting Execution of Mathematical Skills versus Acquisition of New Mathematical Competence

This fMRI study examines how students extend their mathematical competence. Students solved a set of algebra-like problems. These problems included Regular Problems that have a known solution technique and Exception Problems that but did not have a known technique. Two distinct networks of activity were uncovered. There was a Cognitive Network that was mainly active during the solution of problems and showed little difference between Regular Problems and Exception Problems. There was also a Metacognitive Network that was more engaged during a reflection period after the solution and was much more engaged for Exception Problems than Regular Problems. The Cognitive Network overlaps with prefrontal and parietal regions identified in the ACT-R theory of algebra problem solving and regions identified in the triple-code theory as involved in basic mathematical cognition. The Metacognitive Network included angular gyrus, middle temporal gyrus, and anterior prefrontal regions. This network is mainly engaged by the need to modify the solution procedure and not by the difficulty of the problem. Only the Metacognitive Network decreased with practice on the Exception Problems. Activity in the Cognitive Network during the solution of an Exception Problem predicted both success on that problem and future mastery. Activity in the angular gyrus and middle temporal gyrus during feedback on errors predicted future mastery.
A 1 Electrical Phenomena on the Moon and Mars

The Moon and Mars represent intriguing and divergent case studies where natural electrical processes may occur in environments beyond our more familiar terrestrial experience. The windy, Aeolian environment of Mars likely produces substantial electrical activity via the tribo-electrification of individual dust grains that occurs during atmospheric disturbances. While there may be some analogies between atmospheric electrical processes on the Earth and Mars, the highly rarefied, dry Martian atmosphere imposes unique conditions that govern the charging and discharge dynamics of particulates. In contrast to the windswept surface of Mars, the Moon is a small airless body whose surface is directly exposed to variable space plasmas and solar irradiation. Measurements during the Apollo missions, together with more recent data from orbital spacecraft, indicate that there are active and dynamic charging processes occurring on and near the lunar surface. One possible consequence of dynamic lunar electrical activity may be the levitation and perhaps large scale transport of lunar dust. For both the Moon and Mars we only have indirect evidence at best for the existence of electrical activity of any real global consequence. This paper is a brief, semi-tutorial review that discusses the background and history behind these investigations, highlights key ongoing research, and describes future efforts that will help resolve the fundamental, outstanding questions that remain.