Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic expression of the platelet-specific integrin, αIIbβ3, in a murine model for Glanzmann thrombasthenia

Integrins mediate the adhesion of cells to each other and to the extracellular matrix during development, immunity, metastasis, thrombosis, and wound healing. Molecular defects in either the α- or β-subunit can disrupt integrin synthesis, assembly, and/or binding to adhesive ligands. This is exemplified by the bleeding disorder, Glanzmann thrombasthenia (GT), where abnormalities of the platelet-specific integrin, αIIbβ3, prevent platelet aggregation following vascular injury. We previously used a retrovirus vector containing a cDNA cassette encoding human integrin β3 to restore integrin αIIbβ3 on the surface of megakaryocytes derived from peripheral blood stem cells of GT patients. In the present study, bone marrow from β3-deficient (β3–/–) mice was transduced with the ITGβ3-cassette to investigate whether the platelet progeny could establish hemostasis in vivo. A lentivirus transfer vector equipped with the human ITGA2B gene promoter confined transgene expression to the platelet lineage. Human β3 formed a stable complex with murine αIIb, effectively restoring platelet function. Mice expressing significant levels of αIIbβ3 on circulating platelets exhibited improved bleeding times. Intravenous immunoglobulin effectively diminished platelet clearance in animals that developed an antibody response to αIIbβ3. These results indicate the feasibility of targeting platelets with genetic therapies for better management of patients with inherited bleeding disorders.
The Physical Foundation of Human Mind and a New Theory of Investment

This paper consists of two parts. In the first part, we develop a new information theory, in which it is not a coincidence that information and physical entropy share the same mathematical formula. It is an adaptation of mind to help search for resources. We then show that psychological patterns either reflect the constraints of physical laws or are evolutionary adaptations to efficiently process information and to increase the chance of survival in the environment of our evolutionary past. In the second part, we demonstrate that the new information theory provides the foundation to understand market behavior. One fundamental result from the information theory is that information is costly. In general, information with higher value is more costly. Another fundamental result from the information theory is that the amount of information one can receive is the amount of information generated minus equivocation. The level of equivocation, which is the measure of information asymmetry, is determined by the correlation between the source of information and the receiver of information. In general, how much information one can receive depends on the background knowledge of the receiver. The difference in cost different investors are willing to pay for information and the difference in background knowledge about a particular information causes the heterogeneity in information processing by the investment public, which is the main reason of the price and volume patterns observed in the market. Many assumptions in some of the recent models on behavioral finance can be derived naturally from this theory.
A Stress Singularity Approach for the Prediction of Fatigue Crack Initiation in Adhesive Bonds. Part 1: Theory

Abstract Since crack initiation in adhesive bonds tends to occur near the interface corners where the stress fields are singular, we define a fatigue initiation criterion using stress singularity parameter, Q (a generalized stress intensity factor) and the singular eigenvalue, λ. Hattori et al., successfully used a generalized stress intensity factor to characterize the static strength of bimaterial interfaces. We show that this criterion is only appropriate for situations in which the adhesive contact angle is no larger than 90° and the modulus ratio (adhesive to adherend) is smaller than 0.1. Fortunately, these conditions are often met in real joints, permitting the use of a single eigenvalue approach. We then extend this criterion to the case of fatigue arising from mechanical, thermal, or hygroscopic cycling. In preparation for Part 2 (experimental), the special case of an epoxy wedge on a flat aluminum substrate is considered. The singularity is analyzed both analytically and numerically. The scale o.
Effects of electrical leakage currents on MEMS reliability and performance

Electrostatically driven MEMS devices commonly operate with electric fields as high at 10/sup 8/ V/m applied across the dielectric between electrodes. Even with the best mechanical design, the electrical design of these devices has a large impact both on performance (e.g., speed and stability) and on reliability (e.g., corrosion and dielectric or gas breakdown). In this paper, we discuss the reliability and performance implications of leakage currents in the bulk and on the surface of the dielectric insulating the drive (or sense) electrodes from one another. Anodic oxidation of poly-silicon electrodes can occur very rapidly in samples that are not hermetically packaged. The accelerating factors are presented along with an efficient early-warning scheme. The relationship between leakage currents and the accumulation of quasistatic charge in dielectrics are discussed, along with several techniques to mitigate charging and the associated drift in electrostatically actuated or sensed MEMS devices. Two key parameters are shown to be the electrode geometry and the conductivity of the dielectric. Electrical breakdown in submicron gaps is presented as a function of packaging gas and electrode spacing. We discuss the tradeoffs involved in choosing gap geometries and dielectric properties that balance performance and reliability.
Functional Domain Mapping of the Clathrin-associated Adaptor Medium Chains μ1 and μ2*

The clathrin-associated adaptors AP-1 and AP-2 are heterotetrameric complexes involved in the recognition of sorting signals present within the cytosolic domain of integral membrane proteins. The medium chains of these complexes, μ1 and μ2, have been implicated in two types of interaction: assembly with the β1 and β2 chains of the corresponding complexes and recognition of tyrosine-based sorting signals. In this study, we report the results of a structure-function analysis of the μ1 and μ2 chains aimed at identifying regions of the molecules that are responsible for each of the two interactions. Analyses using the yeast two-hybrid system and proteolytic digestion experiments suggest that μ1 and μ2 have a bipartite structure, with the amino-terminal one-third (residues 1–145 of μ1 and μ2) being involved in assembly with the β chains and the carboxyl-terminal two-thirds (residues 147–423 of μ1 and 164–435 of μ2) binding tyrosine-based sorting signals. These observations support a model in which the amino-terminal one-third of μ2 is embedded within the core of the AP-2 complex, while the carboxyl-terminal two-thirds of the protein are exposed to the medium, placing this region in a position to interact with tyrosine-based sorting signals.
Increasing children's social competence through games, an exploratory study

We describe the design and evaluation of Playground Architect, a multi-player game designed to help shy children gain social confidence. The game is played by a small group of children around an interactive tabletop surface using a tangible user interface. The game was evaluated with 32 children (mean age 9.5). All players enjoyed the game. Shy children enjoyed being in charge and were quite talkative during play. Interviews with teachers show that some shy children behaved notably more outgoing. These results illustrate the potential of socially educational games.
Predicting Functional Recovery after Acute Ankle Sprain

Introduction Ankle sprains are among the most common acute musculoskeletal conditions presenting to primary care. Their clinical course is variable but there are limited recommendations on prognostic factors. Our primary aim was to identify clinical predictors of short and medium term functional recovery after ankle sprain. Methods A secondary analysis of data from adult participants (N = 85) with an acute ankle sprain, enrolled in a randomized controlled trial was undertaken. The predictive value of variables (age, BMI, gender, injury mechanism, previous injury, weight-bearing status, medial joint line pain, pain during weight-bearing dorsiflexion and lateral hop test) recorded at baseline and at 4 weeks post injury were investigated for their prognostic ability. Recovery was determined from measures of subjective ankle function at short (4 weeks) and medium term (4 months) follow ups. Multivariate stepwise linear regression analyses were undertaken to evaluate the association between the aforementioned variables and functional recovery. Results Greater age, greater injury grade and weight-bearing status at baseline were associated with lower function at 4 weeks post injury (p<0.01; adjusted R square=0.34). Greater age, weight-bearing status at baseline and non-inversion injury mechanisms were associated with lower function at 4 months (p<0.01; adjusted R square=0.20). Pain on medial palpation and pain on dorsiflexion at 4 weeks were the most valuable prognostic indicators of function at 4 months (p< 0.01; adjusted R square=0.49). Conclusion The results of the present study provide further evidence that ankle sprains have a variable clinical course. Age, injury grade, mechanism and weight-bearing status at baseline provide some prognostic information for short and medium term recovery. Clinical assessment variables at 4 weeks were the strongest predictors of recovery, explaining 50% of the variance in ankle function at 4 months. Further prospective research is required to highlight the factors that best inform the expected convalescent period, and risk of recurrence.
The Posttranslocational Chaperone Lipoprotein PrsA Is Involved in both Glycopeptide and Oxacillin Resistance in Staphylococcus aureus

ABSTRACT Understanding in detail the factors which permit Staphylococcus aureus to counteract cell wall-active antibiotics is a prerequisite to elaborating effective strategies to prolong the usefulness of these drugs and define new targets for pharmacological intervention. Methicillin-resistant S. aureus (MRSA) strains are major pathogens of hospital-acquired and community-acquired infections and are most often treated with glycopeptides (vancomycin and teicoplanin) because of their resistance to most penicillins and a limited arsenal of clinically proven alternatives. In this study, we examined PrsA, a lipid-anchored protein of the parvulin PPIase family (peptidyl-prolyl cis/trans isomerase) found ubiquitously in all Gram-positive species, in which it assists posttranslocational folding at the outer surface of the cytoplasmic membrane. We show by both genetic and biochemical assays that prsA is directly regulated by the VraRS two-component sentinel system of cell wall stress. Disruption of prsA is tolerated by S. aureus, and its loss results in no detectable overt macroscopic changes in cell wall architecture or growth rate under nonstressed growth conditions. Disruption of prsA leads, however, to notable alterations in the sensitivity to glycopeptides and dramatically decreases the resistance of COL (MRSA) to oxacillin. Quantitative transcriptional analysis reveals that prsA and vraR are coordinately upregulated in a panel of stable laboratory and clinical glycopeptide-intermediate S. aureus (GISA) strains compared to their susceptible parents. Collectively, our results point to a role for prsA as a facultative facilitator of protein secretion or extracellular folding and provide a framework for understanding why prsA is a key element of the VraRS-mediated cell wall stress response.
The Synaptic Organization of the Brain

Introduction to synaptic circuits, Gordon M.Shepherd and Christof Koch membrane properties and neurotransmitter actions, David A.McCormick peripheral ganglia, Paul R.Adams and Christof Koch spinal cord - ventral horn, Robert E.Burke olfactory bulb, Gordon M.Shepherd, and Charles A.Greer retina, Peter Sterling cerebellum, Rodolfo R.Llinas and Kerry D.Walton thalamus, S.Murray Sherman and Christof Koch basal ganglia, Charles J.Wilson olfactory cortex, Lewis B.Haberly hippocampus, Thomas H.Brown and Anthony M.Zador neocortex, Rodney J.Douglas and Kevan A.C. Martin Gordon M.Shepherd. Appendix: Dendretic electrotonus and synaptic integration.
Relevance of IGF-I, IGFBP-3, and IGFBP-2 Measurements during GH Treatment of GH-Deficient and Non-GH-Deficient Children and Adolescents

Background: Little information is available on the relevance of parameters representing the insulin-like growth factor (IGF) system with regard to growth hormone (GH) treatment during childhood. In adults, high IGF-I levels were found to be associated with side effects and long-term risks. Aim/Method: Our aim was to monitor the serum levels of IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP-2 during long-term GH treatment of 156 patients with GH deficiency (GHD) and of 153 non-GHD patients. We determined the extent to which the IGF parameters exceed the normal ranges and identified those parameters which are predictive of 1st-year growth. Results: In prepubertal GHD children, the levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 exceeded the 95th centile of the reference values for this age group in 2.3, 0.3, and 7.9% of the cases, respectively, whereas in prepubertal non-GHD children, the same parameters exceeded the 95th reference centile in 20.1, 3.5, and 32.2%, respectively. In pubertal GHD children IGF-I, IGFBP-3, and IGF-I/IGFBP-3 levels exceeded the 95th reference centile in 11.1, 1.5, and 15.4%, respectively. In pubertal non-GHD children, these levels also exceeded the 95th centile in 26.7, 7.0, and 41.4%, respectively. In both GHD and non-GHD groups, however, some patients had IGF parameters which were below the reference values. Our analysis showed that, in both groups, in addition to maximum GH, all IGF parameters (IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio, IGFBP-2 or derivatives) significantly extend the scope of a calculated model for predicting 1st-year height velocity. Conclusion: For reasons of safety and optimization of GH therapy, it is essential to follow up IGF-I, IGFBP-3, and IGFBP-2 levels regularly during childhood.
Cooperative Spectrum Sensing with Noisy Hard Decision Transmissions

Most critical component of the cognitive radio paradigm is spectrum sensing and accordingly, detection of primary users. Recently proposed cooperative spectrum sensing methods do not consider errors occurring during the transmission of local cognitive radio decisions to the cognitive base station. However, perfect communication is clearly not the case in realistic cooperative spectrum sensing scenarios and might lead to misleading performance result interpretations. In this paper, we extend the simple cooperative spectrum sensing communication model to admit transmission imperfections. Specifically, we consider the case where the local hard cognitive radio decisions that are based on any local detection scheme are corrupted by additive noise during transmission from cognitive radios to cognitive base station. Utilizing this extended cooperative spectrum sensing model, we present the complex optimal and a practical and effective suboptimal detector that is capable of operating with any local cognitive radio detection scheme: Two-step detector. We present simulation results investigating the performance of the proposed detectors and the effect of parameters of interest such as number of cognitive radios and signal to noise ratio. Moreover, we provide comparisons between non-cooperative and cooperative spectrum sensing performances revealing some cases where non-cooperative scheme is more effective.
Stability and change in low self-esteem: the role of psychosocial factors

Synopsis Low self-esteem, defined as negative evaluation of self (NES), has been shown to play a significant role in the development of depression at a case level (Brown et al. 1986). This study investigated the stability of this risk factor in 102 women over a 7-year period and examined psychosocial factors that might influence change. At the end of the 7 years about half of those originally identified as having NES no longer had it, but very few moved in the reverse direction to NES. Level of depressive symptomatology also decreased but this was not a sufficient explanation for the substantial improvement in self-esteem. Life changes that involved an improvement in the quality of close relationships or an increase in work status appeared to be the most important factors in positive NES change. Ratings made at the time of first contact of environmental difficulties and positive evaluation of self (measured independently of NES) were related to positive NES change, but only via their link with positive life changes occurring in the 7-year follow-up period.
Transmission of human papillomavirus type 11 infection by desquamated cornified cells.

While much is known about the human papillomavirus (HPV) productive cycle, the mechanisms of virion transmission from person to person are poorly understood. The keratinocyte is the target cell of HPV infection. As keratinocytes differentiate, nuclei are lost and the cornified cell envelope develops. Layers of these desquamated cornified cells (DCCs) are continuously shed from the stratum corneum. Release of HPV requires the cornified cell envelope, a normally very durable structure, to break apart, liberating the contents of the cell. In differentiated keratinocytes infected with HPV 11, the cornified cell envelope is abnormally thin and fragile. In this study, DCCs from HPV 11-infected genital epithelium were used to investigate the mechanisms of viral transmission. First, HPV 11-infected tissue was examined for the presence of virions by transmission electron microscopy. Virions were observed in the nuclei of differentiated keratinocytes. In addition, virions were detected in the cytoplasm of DCCs that had undergone nuclear dissolution. Rarely, virions were observed outside of cells. Next, infectivity of intact and ruptured DCCs was tested in an assay performed in the athymic mouse xenograft system. High-titer cesium chloride gradient-purified HPV 11 virions infected 100% of recovered xenografts. Using intact DCCs derived from HPV 11-infected tissue, 62.5% of recovered xenografts were infected. To test the effects of mechanical stress on infectivity, DCCs were ruptured by sonication and used in the infectivity assay. The infectivity rate increased to 90%. We conclude that DCCs serve as vehicles for efficient, concentrated delivery of virions in HPV 11 infection.
Nutritional Factors in Ovarian Cancer Survival

Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. Because symptoms tend be nonspecific, early detection is difficult, and most ovarian cancers are diagnosed at an advanced stage when the prognosis is poor. Nonetheless, there is clinical evidence that even given the same tumor characteristics (histologic type, stage, and grade), some cases experience much better survival than others. This has led to extensive research on molecular prognostic factors to enable more efficient and targeted therapeutic regimens. However, little is known about the impact that lifestyle factors, such as diet or physical activity, may have in the prognosis of ovarian cancer, whether on disease-free survival or on the response to and complications from treatment. The role of obesity on ovarian cancer survival is unclear. Obesity may delay diagnosis, hinder optimal surgical and cytotoxic treatment, and cause postoperative complications. As overweight and obesity rates reach epidemic proportions, the impact of body mass index in the clinical management of ovarian cancer is increasingly significant, whereas current evidence of its impact is limited and inconclusive.
The Effects of Disease-Induced Juvenile Mortality on the Transient and Asymptotic Population Dynamics of Chinook Salmon (Oncorhynchus tshawytscha)

The effects of an increased disease mortality rate on the transient and asymptotic dynamics of Chinook salmon (Oncorhynchus tshawytscha) were investigated. Disease-induced mortality of juvenile salmon has become a serious concern in recent years. However, the overall effects of disease mortality on the asymptotic and transient dynamics of adult spawning abundance are still largely unknown. We explored various scenarios with regard to the density-dependent process, the distribution of survivorship over the juvenile phase, the disease mortality rate, and the infusion of stray hatchery fish. Our results suggest that the sensitivity to the disease mortality rate of the equilibrium adult spawning abundance and resilience (asymptotic return rate toward this equilibrium following a small perturbation) varied widely and differently depending on the scenario. The resilience and coefficient of variation of adult spawning abundance following a large perturbation were consistent with each other under the scenarios investigated. We conclude that the increase in disease mortality likely has an effect on fishery yield under a fluctuating environment, not only because the mean equilibrium adult spawning abundance has likely been reduced, but also because the resilience has likely decreased and the variance in adult spawning abundance has likely increased. We also infer the importance of incorporating finer-scale spatiotemporal information into population models and demonstrate a means for doing so within a matrix population modeling framework.
A Machine Learning Approach for Developing Test Oracles for Testing Scientific Software

Absence of test oracles is the grand challenge for testing complex scientific software. Metamorphic testing is the novel technique for developing test oracles on metamorphic relations. Although it is easy to find metamorphic relations based on general guidelines and domain knowledge, the ones that can adequately test the software are difficult to be developed. This paper introduces a machine learning approach for iteratively developing metamorphic relations. The approach develops initial metamorphic relations and tests first, and then the relations and tests are refined through mining the initial test execution and evaluation results with machine learning algorithms. The approach and its effectiveness are illustrated through testing an open source discrete dipole approximation program. Keywords-metamorphic testing, metamorphic relation, test oracle, scientific software, machine learning.
A data-driven analysis of student efforts and improvements on a SPOC experiment

In recent years, Massive Open Online Courses (MOOCs) increasingly attract the attention from all circles. MOOCs provide students with abundant learning resources, which are also utilized by colleges to improve the effect of teaching. Moreover, Small Private Online Course (SPOC) and flipped classroom have been proved to be effective in some STEM courses. In this paper, we conduct a SPOC experiment on Data Structures and Algorithms. We leverage both online and offline data to analyze the efforts and improvements of students, including comparing test scores between different classes, collecting student information from questionnaires and exploring the online learning behaviors of students. We also discuss and explain our findings according to the experience which we get from the teaching experience.