Miracle-dz/UniFAR-FTUs huggingface dataset:
Postnatal Age and Protein Tyrosine Phosphorylation at Synapses in the Developing Rat Brain

The relationship between postnatal age and protein tyrosine kinase activity in synaptosomes prepared from the rat forebrain was studied. Synaptosomal particulate and soluble fractions, as well as total homogenates, the cell soluble fraction, and P3, were prepared from rats ranging in postnatal age from 5 to 60 days and analyzed for (a) tyrosine kinase activity using polyglutamyltyrosine (4:1) as the substrate, (b) the presence of endogenous substrates for tyrosine phosphorylation using polyclonal antibodies specific for phosphotyrosine, and (c) levels of pp60src. Enzyme activity, expressed per milligram of protein, in the total homogenate, P3, and both the cell and synaptosomal soluble fractions was highest in the brains of young animals (postnatal days 5–10) and decreased thereafter to adult levels. In contrast, tyrosine kinase activity in the synaptosomal particulate fraction exhibited a unique biphasic developmental profile, increasing to maxima at postnatal days 10 and 20 before decreasing to adult values. Endogenous substrates for tyrosine phosphorylation were identified by incubating subcellular fractions with 2 mM ATP in the presence of sodium orthovanadate and probing nitrocellulose blots of proteins separated by gel electrophoresis with antiphosphotyrosine antibodies. Several phosphotyrosine‐containing proteins were detected in the synaptosomal particulate and P3 fractions, including proteins of Mr 180K, 145K, 120K, 100K, 77K, 68K, 62K, 54K, 52K, and 42K. In the cell soluble fraction a protein doublet of Mr 54/52K and a 120K protein were the major phosphotyrosine‐containing proteins. The 54/52K doublet was the major protein tyrosine kinase substrate in the synaptosomal soluble fraction. There was a general decrease in the immunostaining of phosphotyrosine‐containing proteins in the P3 fraction after postnatal day 10. In contrast, the tyrosine phosphorylation of several proteins in the synaptosomal particulate fraction increased to maximal levels during the third and fourth week after birth before declining to adult levels. Western blotting using monoclonal antibody 327, specific for pp60src, showed that pp60src levels decreased throughout development in both homogenate and P3 fractions. The concentration of pp60src in the synaptosomal particulate fraction and postsynaptic densities, in contrast, increased 80–100% during the third and fourth weeks before decreasing slowly to adult levels. The results indicate that the expression of tyrosine kinase and the phosphorylation of synaptic proteins on tyrosine residues at the developing synapse are transiently increased during the latter stages of synaptogenesis and suggest that the phosphorylation of proteins on tyrosine residues may be involved in the regulation of synapse formation.
Inhibition of Ca2+/Calmodulin-dependent Protein Kinase Blocks Morphological Differentiation of Plasmodium gallinaceum Zygotes to Ookinetes*

Once ingested by mosquitoes, malaria parasites undergo complex cellular changes. These include zygote formation, transformation of zygote to ookinete, and differentiation from ookinete to oocyst. Within the oocyst, the parasite multiplies into numerous sporozoites. Modulators of intracellular calcium homeostasis A23187, MAPTAM, and TMB-8 blocked ookinete development as did the calmodulin (CaM) antagonists W-7 and calmidazolium. Ca2+/CaM-dependent protein kinase inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN-92 did not have such effect. In vitro both zygote and ookinete extracts efficiently phosphorylated autocamtide-2, a classic CaM kinase substrate, which could be blocked by calmodulin antagonists W-7 and calmidazolium and CaM kinase inhibitor KN-93. These results demonstrated the presence of calmodulin-dependent CaM kinase activity in the parasite. KN-93-treated parasites, however, expressed the ookinete-specific enzyme chitinase and the ookinete surface antigen Pgs28 normally, suggesting that the morphologically untransformed parasites are biochemically mature ookinetes. In mosquitoes, KN-93-treated parasites did not develop as oocysts, while KN-92-treated parasites produced similar numbers of oocysts as controls. These data suggested that inPlasmodium gallinaceum morphological development of zygote to ookinete, but not its biochemical maturation, relies on Ca2+/CaM-dependent protein kinase activity and demonstrated that the morphological differentiation is essential for the further development of the parasite in infected blood-fed mosquitoes.
Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1/UAF1 Complex

The human deubiquitinase USP1 plays important roles in cancer-related processes, such as the DNA damage response, and the maintenance of the undifferentiated state of osteosarcoma cells. USP1 deubiquitinase activity is critically regulated by its interaction with the WD40 repeat-containing protein UAF1. Inhibiting the function of the USP1/UAF1 complex sensitizes cancer cells to chemotherapy, suggesting that this complex is a relevant anticancer target. Intriguingly, whereas UAF1 has been reported to locate in the cytoplasm, USP1 is a nuclear protein, although the sequence motifs that mediate its nuclear import have not been functionally characterized. Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1/UAF1 complex. Using a cellular relocation assay based on these results, we map the UAF1-binding site to a highly conserved 100 amino acid motif in USP1. Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs. Importantly, our findings have practical implications for the development of USP1-directed therapies. First, the UAF1-interacting region of USP1 identified here might be targeted to disrupt the USP1/UAF1 interaction with therapeutic purposes. On the other hand, we describe a cellular relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1/UAF1 complex.
Modeling the functional relationship network at the splice isoform level through heterogeneous data integration

Functional relationship networks, which reveal the collaborative roles between genes, have significantly accelerated our understanding of gene functions and phenotypic relevance. However, establishing such networks for alternatively spliced isoforms remains a difficult, unaddressed problem due to the lack of systematic functional annotations at the isoform level, which renders most supervised learning methods difficult to be applied to isoforms. Here we describe a novel multiple instance learning-based probabilistic approach that integrates large-scale, heterogeneous genomic datasets, including RNA-seq, exon array, protein docking and pseudo-amino acid composition, for modeling a global functional relationship network at the isoform level in the mouse. Using this approach, we formulate a gene pair as a set of isoform pairs of potentially different properties. Through simulation and cross-validation studies, we showed the superior accuracy of our algorithm in revealing the isoform-level functional relationships. The local networks reveal functional diversity of the isoforms of the same gene, as demonstrated by both large-scale analyses and experimental and literature evidence for the disparate functions revealed for the isoforms of Ptbp1 and Anxa6 by our network. Our work can assist the understanding of the diversity of functions achieved by alternative splicing of a limited set of genes in mammalian genomes, and may shift the current gene-centered network prediction paradigm to the isoform level. Author summary Proteins carry out their functions through interacting with each other. Such interactions can be achieved through direct physical interactions, genetic interactions, or co-regulation. To summarize these interactions, researches have established functional relationship networks, in which each gene is represented as a node and the connections between the nodes represent how likely two genes work in the same biological process. Currently, these networks are established at the gene level only, while each gene, in mammalian systems, can be alternatively spliced into multiple isoforms that may have drastically different interaction partners. This information can be mined through integrating data that provide isoform-level information, such as RNA-seq and protein docking scores predicted from amino acid sequences. In this study, we developed a novel algorithm to integrate such data for predicting isoform-level functional relationship networks, which allows us to investigate the collaborative roles between genes at a high resolution.
Metrics for Cyber Robustness

Cyber robustness measures how long an ICT system can resist to attackers that compose attacks to escalate their privileges till reaching their goals. This paper proposes three metrics to evaluate this ability. The basic one is the security stress that considers the probability that an attacker reaches a predefined goal in a time interval. The relation between the interval size and the probability evaluates the overall robustness. This metric is the starting point to define two metrics that evaluate cyber robustness through the financial impact. We approximate the security stress using the output of the Haruspex suite. The suite tools forecast how a system is attacked by simulating the interaction between the system and some attackers. The output of the suite supports both the computation of the metrics and the design of more robust versions. Lastly, we apply the metrics to compare three versions of an industrial control system.
The Health IT Regional Extension Center Program: evolution and lessons for health care transformation.

OBJECTIVE Assess the Regional Extension Center (REC) program's progress toward its goal of supporting over 100,000 providers in small, rural, and underserved practices to achieve meaningful use (MU) of an electronic health record (EHR). DATA SOURCES/STUDY SETTING Data collected January 2010 through June 2013 via monitoring and evaluation of the 4-year REC program. STUDY DESIGN Descriptive study of 62 REC programs. DATA COLLECTION/EXTRACTION METHODS Primary data collected from RECs were merged with nine other datasets, and descriptive statistics of progress by practice setting and penetration of targeted providers were calculated. PRINCIPAL FINDINGS RECs recruited almost 134,000 primary care providers (PCPs), or 44 percent of the nation's PCPs; 86 percent of these were using an EHR with advanced functionality and almost half (48 percent) have demonstrated MU. Eighty-three percent of Federally Qualified Health Centers and 78 percent of the nation's Critical Access Hospitals were participating with an REC. CONCLUSIONS RECs have made substantial progress in assisting PCPs with adoption and MU of EHRs. This infrastructure supports small practices, community health centers, and rural and public hospitals to use technology for care delivery transformation and improvement.
A History Mechanism for Visual Data Mining

A major challenge of current visualization and visual data mining (VDM) frameworks is to support users in the orientation in complex visual mining scenarios. An important aspect to increase user support and user orientation is to use a history mechanism that, first of all, provides un- and redoing functionality. In this paper, we present a new approach to include such history functionality into a VDM framework. Therefore, we introduce the theoretical background, outline design and implementation aspects of a history management unit, and conclude with a discussion showing the usefulness of our history management in a VDM framework
The Influence of Small Quantities of Oxygen in the Structure, Microstructure, Hardness, Elasticity Modulus and Cytocompatibility of Ti-Zr Alloys for Dental Applications

The mechanical properties of Ti alloys are changed significantly with the addition of interstitial elements, such as oxygen. Because oxygen is a strong stabilizer of the α phase and has an effect on hardening in a solid solution, it has aroused great interest in the biomedical area. In this paper, Ti-Zr alloys were subjected to a doping process with small amounts of oxygen. The influence of interstitial oxygen in the structure, microstructure and some selected mechanical properties of interest for use as biomaterial and biocompatibility of the alloys were analyzed. The results showed that in the range of 0.02 wt% to 0.04 wt%, oxygen has no influence on the structure, microstructure or biocompatibility of the studied alloys, but causes hardening of the alloys, increasing the values of the microhardness and causing variation in the elasticity modulus values.
The Impact of Employer-Provided Health Insurance on Dynamic Employment Transitions

We estimate the impact of employer-provided health insurance (EPHI) on the job mobility of males over time using a dynamic empirical model that accounts for unobserved heterogeneity. Previous studies of job-lock reach different conclusions about possible distortions in labor mobility stemming from an employment-based health insurance system: a few authors find no evidence of job-lock, while most find reductions in the mobility of insured workers of between 20 and 40%. WE use data from the National Longitudinal Survey of Youth which describes the health insurance an individual holds, as well as whether he is offered insurance by his employer. This additional information allows us to model the latent individual characteristics that are correlated with the offer of EPHI, the acceptance of EPHI, and employment transitions. Our results provide an estimate of job-lock unbiased through correlation with positive job characteristics and individual specific turnover propensity. We find no evidence of job-lock among married males, and produce small estimates of job-lock among unmarried males of between 10 and 15%.
ROBUST ADAPTIVE BEAMFORMING USING A FULLY DATA-DEPENDENT LOADING TECHNIQUE

This paper deals with adaptive array beamforming in the presence of errors due to steering vector mismatch and flnite sample efiect. Diagonal loading (DL) is one of the widely used techniques for dealing with these errors. However, the main drawback of DL techniques is that there is not an easy and reliable manner to determine the required loading factor. Recently, serval DL approaches proposed the so-called automatic scheme on computing the required loading factor. In this paper, we propose a fully data-dependent loading to overcome the di-culties. The novelty is that the proposed method does not require any additional sophisticated scheme to choose the required loading. The loading factor can be completely obtained from the received array data. Analytical formulas for evaluating the performance of the proposed method under random steering vector error are further derived. Simulation results are provided to conflrm the validity of the proposed method and make comparison with the existing DL methods.
The road less traveled

Phagosomes containing the bacterial pathogen Legionella pneumophila are transported to the ER after macrophage internalization. To modulate phagosome transport, Legionella use a specialized secretion system that injects bacterial proteins into eukaryotic cells. This review will focus on recent studies that have identified bacterial proteins and host processes that play a concerted role in transporting Legionella to the ER.
Enhancing Flexibility in Service Oriented Enterprise Application Integration through Semantic Web Technologies

As business processes become more and more involved with computer- and data-operations, interdependencies arise. Business processes are designed around the IT-infrastructure and applications and hardware solutions are modified to satisfy business processes. The domain of enterprise application integration (EAI) seeks to enable an organization to integrate its existing applications and to incorporate new applications and technologies into an existing IT infrastructure. Due to the complexities of most EAI scenarios, modifications to an existing solution may result in a new solution which, while syntactically correct, may differ enough on the semantic level that data or sub-processes become nonsensical for existing processes and applications. While existing technologies serve their function very well on the syntactic level, the problem remains on the semantic level. The thesis poses the following question: Can semantic web technologies be used to enhance the flexibility of service oriented enterprise application integration? The analysis performed in the thesis is based on an existing EAI framework. This framework works in practice, but challenges are faced when new systems or data are added to the integrated processes. Based on the analysis performed in this thesis, a new prototype framework is developed. It was found that representing the integrated data domain as ontologies provide a common vocabulary and understanding of data across (and beyond) the enterprise. This reduces risks by providing a degree of transparency in an otherwise hard to understand data model. More importantly, many of the high-risk manual tasks such as service- and data-mapping and message routing may be automated by allowing the integration middleware to reason on the data it transmits. Automatic reasoning is made possible primarily through the incorporation of semantically enriched data. To summarize, it was found that using semantics in EAI scenarios provides multiple benefits and significantly increases flexibility and the ability to adapt.
Psychopathy, the Machiavellian, and Anomie

In their extensive investigation Christie and Geis ( 1) report that no significant correlations had been found between Machiavellianism and subscales of the MMPI, with the implication that general psychopathology is uncorrelated with this measure. Smith, however, has argued ( 4 ) that common descriptors of che psychopath ( 2 ) resemble those of the Machiavel and thus measures of these behaviors should share common variance. Examples of overlapping descriptors would be: poverty of affect, manipulative style, unconcern with traditional morality, and low ideological commitment ( 1 ) . Also tendencies reflecting components of anomie, e.g., cynicism, low interpersonal trust, and external locus of control run through descriptions of both constructs ( 1, 2 ) . The presenc study compared a volunteer group of 66 American college students (19 female, 47 male; Ma, 25.6 yr.) on Christie and Geis' Mach IV scale, MMPI Psychopathic Deviate scale and Factor I (16 items) of Elrnore's Social Feeling Index, a measure of anomie (3) . High scores are said to reflect an absence of feelings of progress, of self-fulfillment, and of self-worth ( 3 ) . The Pearson correlations among all three measures were statistically significant: Mach IV and Psychopathic Deviate scale = . 25 ($ < .05), Mach IV and Social Feeling = . 34 ( f l < .01), the MMPI scale and Social Feeling = -50 ($ < .01). Thus psychopathy as measured by the MMPI scale does share significant variance with Machiavellianism for this group, and both measures relate strongly to anomie. These significant correlations support Smith's view (4) that psychopathy and Machiavellianism are converging dimensions. Further the belief ( 1 ) that the Machiavel is more or less "rational" complements Smith's view that, racher than being pathologically antisocial, the psychopath is merely the logical extreme in cultures which reward competition, material success, and maintenance of a "good image. "
The random access hierarchy

To be considered fast, algorithms for operations on large data structures should operate in polylog time, i.e., with the number of steps bounded by a polynomial in log(N) where N is the size of the data structure. Example: an ordered list of reasonably short strings can be searched in log2 (N) time via binary search. To measure the time and space complexity of such operations, the usual Turing machine with its serial-access input tape is replaced by a random access model. To compare such problems and define completeness, the appropriate relation is loglog reducibility: the relation generated by random-access transducers whose work tapes have length at most log(log(N)). The surprise is that instead of being a refinement of the standard log space, polynomial time, polynomial space, . hierarchy, the complexity classes for these random-access Turing machines form a distinct parallel hierarchy, namely, polylog time, polylog space, exppolylog time, . Propositional truth evaluation, context-free language recognition and searching a linked list are complete for polylog space. Searching ordered lists and searching unordered lists are complete for polylog time and nondeterministic polylog time respectively. In the serial-access hierarchy, log-space reducibility is not fine enough to classify polylog-time problems and there can be no complete problems for polylog space even with polynomial-time Turing reducibility
The Adjustment Process of Patients with Amyotrophic Lateral Sclerosis

Abstract Purpose: The purpose of this study was to describe the adjustment process of patients with Amyotrophic Lateral Sclerosis(ALS). Method: The data were collected from May 2007 to February 2008 through individual in-depth interviews with 4 ALS patients. The data collection and analysis were performed according to grounded theory methodology, as suggested by Strauss and Corbin. Results: ‘Accepting the sick role’ was the central phenomenon, which was derived from ‘perceiving an intial symptom’. Therefore, the adjustment pattern was represented by using the different strategies, which were ‘raising hope’ and ‘hoping to dye comfortably’. For taking a view of the future, ALS patients adopted the strategies of ‘living positively’, ‘being treated hardly’, ‘joining in the experience’, ‘depending on the absolute being’, ‘recognizing the dying process’. Conclusion: This study provides guidance for the development of nursing interventions for patients with ALS. Key words : Amyotrophic Lateral Sclerosis(ALS), Adjustment process, Grounded theory methodology
Cynical Hostility, Powerful others Control Expectancies, and Patient Adherence in Hemodialysis

Objective The present study examined the joint role of cynical hostility and powerful others health locus of control expectancies in predicting regimen adherence in a sample of center hemodialysis patients. Method: Forty-eight hemodialysis patients completed the Cook-Medley Hostility (Ho) Scale and the Powerful Others Health Locus of Control (PHLC) scale. Adherence to the fluid-restriction and phosphorus reduction components of the treatment regimen was assessed by examining patients' interdialysis session weight gains and serum phosphorus (P) levels. Results: In a hierarchical regression analysis, higher hostility was associated with significantly higher serum P levels indicating poorer dietary and medication adherence. The main effect for hostility was qualified by the interaction of hostility and PHLC. This pattern indicated that the deleterious effect of hostility on adherence was most pronounced among patients possessing the expectancy that positive health outcomes are not strongly contingent on the actions or advice of powerful others (eg, health care providers). Similar analyses failed to show significant effects for hostility or PHLC in the prediction of interdialytic weight gain. Conclusions: The present findings suggest that jointly assessing hostility and health-related expectancies may be useful in identifying chronically ill patients who are potentially at risk for difficulties in performing a prescribed regimen.