Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of p53 and p21 in Cellular Defects and Tumorigenesis in Atm−/− Mice

ABSTRACT Disruption of the mouse Atm gene, whose human counterpart is consistently mutated in ataxia-telangiectasia (A-T) patients, creates an A-T mouse model exhibiting most of the A-T-related systematic and cellular defects. While ATM plays a major role in signaling the p53 response to DNA strand break damage, Atm−/−p53−/− mice develop lymphomas earlier than Atm−/− or p53−/− mice, indicating that mutations in these two genes lead to synergy in tumorigenesis. The cell cycle G1/S checkpoint is abolished in Atm−/−p53−/− mouse embryonic fibroblasts (MEFs) following γ-irradiation, suggesting that the partial G1 cell cycle arrest in Atm−/− cells following γ-irradiation is due to the residual p53 response in these cells. In addition, the Atm−/− p21−/− MEFs are more severely defective in their cell cycle G1 arrest following γ-irradiation than Atm−/− and p21−/−MEFs. The Atm−/− MEFs exhibit multiple cellular proliferative defects in culture, and an increased constitutive level of p21 in these cells might account for these cellular proliferation defects. Consistent with this notion, Atm−/−p21−/− MEFs proliferate similarly to wild-type MEFs and exhibit no premature senescence. These cellular proliferative defects are also rescued in Atm−/− p53−/− MEFs and little p21 can be detected in these cells, indicating that the abnormal p21 protein level in Atm−/− cells is also p53 dependent and leads to the cellular proliferative defects in these cells. However, the p21 mRNA level in Atm−/− MEFs is lower than that in Atm+/+ MEFs, suggesting that the higher level of constitutive p21 protein in Atm−/− MEFs is likely due to increased stability of the p21 protein.
Closed-loop control for a single-phase cascaded multilevel inverters operating with SHE-PWM

This paper presents the development of a control approach for single-phase cascaded multilevel inverters employing Selective Harmonic Elimination Pulse Width Modulation (SHE-PWM), a low-frequency modulation technique to reduce harmonic content by means of the elimination of low-order harmonics. After determining the switching angles for a range of modulation indexes, a closed-loop control strategy is proposed for regulating the peak current at the output. An alternative feedback strategy for this single-phase system is presented, which match the AC signal of output current to the DC input of the modulator. Simulation results validate the proposed control system for load and reference variations, while the elimination of desired harmonics is confirmed by spectral analysis over time.
Proxy-Reported Quality of Life and Family Impact for Children Followed Longitudinally by a Pediatric Palliative Care Team.

BACKGROUND One goal of pediatric palliative care is to maintain quality of life for children and their families. Quality-of-life investigations may be enhanced by considering clinically important metrics in addition to statistical significance. OBJECTIVE The purpose of this study was to longitudinally evaluate the effect of time on quality of life and family impact for pediatric palliative care patients across all diagnoses and ages. DESIGN This prospective quality-of-life study included administration of a 23-item PedsQL™ Measurement Model to evaluate for physical, emotional, social, and cognitive dimensions of the child's quality of life and a 36-item PedsQL Family Impact Module to assess for the familial impact at time of initial palliative care consultation, Month 6, and Month 12. SETTING/SUBJECTS All pediatric patients who received a palliative care consultation in our Midwestern free-standing children's hospital over a five-year period were included in the longitudinal study (n = 87). MEASUREMENTS Repeated measures ANOVA was used to investigate how proxy-reported quality of life and family impact changed with time with attentiveness to also follow trends in minimal clinically important difference (MCID) metrics. RESULTS The emotional domain showed a statistically significant positive trend over the first six months of palliative care involvement (p = 0.049), while the physical domain (p = 0.028) and daily activity (p = 0.039) showed a positive improvement for the full year. In using a standard of MCID, the physical, emotional, and cognitive domains improved in the quality-of-life scale and the communication, worry, and daily activity domains improved in the family impact scale over 12 months. CONCLUSIONS In considering quality-of-life analyses for pediatric palliative care programmatic improvements, providers may consider analyzing not only for statistical significance in collective data sets but also for clinically important difference over time.
Sex-specific association patterns in bonobos and chimpanzees reflect species differences in cooperation

In several group-living species, individuals' social preferences are thought to be influenced by cooperation. For some societies with fission–fusion dynamics, sex-specific association patterns reflect sex differences in cooperation in within- and between-group contexts. In our study, we investigated this hypothesis further by comparing sex-specific association patterns in two closely related species, chimpanzees and bonobos, which differ in the level of between-group competition and in the degree to which sex and kinship influence dyadic cooperation. Here, we used long-term party composition data collected on five chimpanzee and two bonobo communities and assessed, for each individual of 10 years and older, the sex of its top associate and of all conspecifics with whom it associated more frequently than expected by chance. We found clear species differences in association patterns. While in all chimpanzee communities males and females associated more with same-sex partners, in bonobos males and females tended to associate preferentially with females, but the female association preference for other females is lower than in chimpanzees. Our results also show that, for bonobos (but not for chimpanzees), association patterns were predominantly driven by mother–offspring relationships. These species differences in association patterns reflect the high levels of male–male cooperation in chimpanzees and of mother–son cooperation in bonobos. Finally, female chimpanzees showed intense association with a few other females, and male chimpanzees showed more uniform association across males. In bonobos, the most differentiated associations were from males towards females. Chimpanzee male association patterns mirror fundamental human male social traits and, as in humans, may have evolved as a response to strong between-group competition. The lack of such a pattern in a closely related species with a lower degree of between-group competition further supports this notion.
Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis

Background Recent years have seen marked improvements in end-of-life care, however concerns have been expressed that services are focused on the needs of patients with cancer. This review focuses on conversations about end-of-life care with frail and older people who have no main overriding diagnosis who are estimated to account for around 40% of deaths. Aim To investigate the attitudes of the public and healthcare professionals to advance care planning discussions with frail and older people. Design and setting Systematic literature review and narrative synthesis. Method Articles that related to frail or older individuals and either advance care plans or discussions on end-of-life care were included. Studies of specific conditions or that focused on prognosis, capacity, or resuscitation decisions were excluded. Results While a significant minority of frail older individuals would find them unwelcome, the majority would appreciate the chance to discuss end-of-life care, yet most do not have this opportunity. Attitudes to the timing of these discussions were variable, but most perceived the risk of leaving them too late. Most doctors believed it was their professional responsibility to initiate discussions, but felt limited by time pressures and the absence of a precipitating event. A wide range of barriers were identified including the reluctance of family members to discuss end-of-life care, the passive expectation that someone else would decide on an individual’s behalf, and significant uncertainty concerning future illness and decline. Conclusion The marked disparity between the majority of older individuals who would like the opportunity to discuss their end-of-life care and the minority that currently have this opportunity raises important questions if the wishes of this large group in society are to be respected. The challenge is to find effective ways of encouraging dialogue and choice within the constraints of the current healthcare systems and personal circumstances.
Runtime Memory Management in Many-core Systems

Author(s): Tajik, Hossein | Advisor(s): Dutt, Nikil | Abstract: With the number of cores on a chip continuing to increase, we are moving towards an era where many-core platforms will soon be ubiquitous. Efficient use of tens to hundreds of cores on a chip and their memory resources comes with unique challenges. Some of these major challenges include: 1) Data Coherency -- the need for coherency protocol and its induced overhead poses a major obstacle for scalability of many-core platforms. 2) Memory requirement variation -- concurrently running applications on a many-core platform have variable and different memory requirements, not only across different applications, but also within a single application; in this dynamic scenario, static analysis may not suffice to capture dynamic behaviors. 3) Scalability -- inefficiency of a central management makes distributed management a necessity for many-core platforms. To address all these issues, this dissertation proposes a comprehensive approach to manage available memory resources in many-core platforms equipped with Software Programmable Memories (SPMs). The main contributions of this dissertation are: 1) We introduce SPMPool: a scalable platform for sharing Software Programmable Memories. The SPMPool approach exploits underutilized memory resources by dynamically sharing SPM resources between applications running on different cores and adapts to the overall memory requirements of multiple applications that are concurrently executing on the many-core platform. 2) We propose different central and distributed management schemes for SPMPool and study the efficiency of auction-based mechanisms in solving the memory mapping problem. We also introduce a distributed auction-based scheme to manage the memory resources of platforms without central coordination. 3) We introduce offline and online memory phase detection methods in order to increase the adaptivity of memory management to the temporal changes in memory requirements of a single application. We also use memory phasic information to relax the need for static analysis of applications.We implemented a Java and Python based simulator for many-core platforms to investigate the efficacy of the proposed methods in this dissertation.The runtime memory management schemes proposed here enable better performance, power, and scalability for many-core systems.
Data-driven model order reduction via Loewner approach for fast frequency sweep in hybrid BI-FEM solution in large finite frequency selective surfaces

A data-driven model order reduction technique for fast frequency sweep in computationally intensive full-wave solution in large finite frequency selective surfaces is detailed. A hybrid Boundary Integral-Finite Element Domain Decomposition Method is addressed to accurately predict the electromagnetic behavior of these structures. A reduced-order model is built up by means of output data provided by the electromagnetic solver, which is used as a black box as regards the model order reduction process. A Loewner matrix approach is taken into account to provide a tangential interpolation to S parameter output data. As a result, a dynamical system representation fitting the simulation data is obtained, and further electromagnetic insight can be earned from this system representation.
Beyond social support: Self-care confidence is key for adherence in patients with heart failure

Background: Adherence to treatment is crucial to improve outcomes in patients with heart failure. Good social support is associated with better adherence, but the mechanism for this association has not been well-explored. Aims: The aim of this secondary analysis was to examine whether self-care confidence mediates the relationship between social support and treatment adherence in heart failure patients hospitalized with acute exacerbation. Methods: A total of 157 inpatients with heart failure (63.5±13 years, 73% New York Heart Association class III/IV) were recruited from two hospitals located in urban areas in the USA. Participants completed the Self-Care of Heart Failure Index, the Multidimensional Perceived Social Support Scale, and the Medical Outcomes Study Specific Adherence Scale. A series of regression models were used to determine the mediation relationship. Results: Controlling for marital status and hospital site, social support was associated with adherence (p=0.03). When self-confidence was included in the model, the effect of social support became non-significant, indicating full mediation of the relationship between social support and adherence by self-care confidence. The indirect effect (0.04) of social support on adherence through self-confidence was significant (95% confidence interval: 0.01–0.09). Conclusion: Heart failure self-care confidence mediated the relationship between social support and treatment adherence. Thus interventions targeting patients’ self-care confidence is essential to maximize patients’ treatment adherence.
Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms.

In a nine-week double-blind crossover comparison of dextroamphetamine, levoamphetamine (Cydril), and placebo with 11 hyperkinetic children, effects were assessed by an established teacher rating scale, a parent rating scale, and a new tool, weekly quantification of parent-selected target symptoms. Both active drugs were significantly more effective than placebo. Dextroamphetamine seemed consistently superior to levoamphetamine, though not to a significant degree (on this size sample). Levoamphetamine seemed "slower starting," requiring three weeks to show significant benefit on target symptoms, whereas dextroamphetamine showed nearly its maximum benefit the first week. Levoamphetamine seemed better for hyperactivity and aggressiveness than for inattentiveness, whereas dextroamphetamine seemed equally beneficial for all three. These data are consistent with the possibility that therapeutic effects of amphetamine on hyperkinetic children are mediated, at least in some, by dopaminergic systems.
Three‐dimensional reconstruction of the myofiber pattern in the fetal and neonatal mouse heart

A methodology for three‐dimensional reconstruction from serial sections and interactive computer graphics is described briefly. This methodology was applied to study the morphogenesis of the cardiac myofiber pattern in the fetal and neonatal mouse heart (ventricles). Few organized in‐plane myofibers were found in the myocardial wall before 12 days postconception, but many fibers were observed in the very numerous trabeculae at all times up to birth. However, beginning at about 12 days, the number of fibers in the myocardial wall increases rapidly: these are seen predominantly in the transverse plane. The neonatal mouse heart, especially the left ventricle, resembles a small adult muscular artery. But the global myofiber pattern in the mouse heart at these stages appears to be more complex than might be inferred from earlier studies of the local myofiber pattern at a few sites in the ventricles of a few species of adult mammals. In particular, the pattern in and adjacent to the interventricular septum appears quite complex.
Management of Scientific Documents and Visualization of Citation Relationships using Weighted Key Scientific Terms

Effective management and visualization of scientific and research documents can greatly assist researchers by improving understanding of relationships (e.g. citations) between the documents. This paper presents work on the management and visualization of large corpuses of scientific papers in order to help researchers explore their citation relationships. Term selection and weighting are used for mining citation relationships by identifying the most relevant. To this end, we present a variation of the TF-IDF scheme, which uses external domain resources as references to calculate the term weighting in a particular domain; document weighting is taken into account in the calculation of term weighting from a group of citations. A simple hierarchical word weighting method is also presented. The work is supported by an underlying architecture for document management using NoSQL databases and employs a simple visualization interface.
Relationships at work in a networked business incubator: the case of H-Farm

This work adds to the previous literature on networked business incubators (NBIs) by exploring the complex network of relationships originated from a NBI. In particular, social ties (cooperative relations between individuals) and business ties (formal linkages between organizations) are investigated. The analytical framework developed here is empirically illustrated through a case study research on a leading Italian private NBI called H-Farm. Primary data collection was conducted during the period MayÐSeptember 2012 by means of face-to-face in-depth interviews and a survey. Data are elaborated through social network analysis tools. The results highlight the co-presence and interaction of social and business ties, which build up a vital environment nurturing an entrepreneurial ecosystem. Community-based relationships and an influential incubator management are crucial for sustaining incubatees in product and business development activities.
Identical transcriptional control of the divergently transcribed prtP and prtM genes that are required for proteinase production in lactococcus lactis SK11

We have investigated transcriptional regulation of the divergently transcribed genes required for proteinase production (prtP and prtM) of Lactococcus lactis SK11. Their promoters partially overlap and are arranged in a face-to-face configuration. The medium-dependent activities of both prtP and prtM promoters were analyzed by quantitative primer extension studies and beta-glucuronidase assays with L. lactis MG1363 cells harboring transcriptional gene fusions of each promoter with the promoterless beta-glucuronidase gene (gusA) from Escherichia coli. High-level production of prtP- or prtM-specific mRNAs was found after the growth of cells in media with low peptide concentrations, while increases in peptide concentrations resulted in an approximately eightfold decrease in mRNA production. Furthermore, prtP and prtM promoters exhibited similar efficiencies under different growth conditions. Deletion analysis of the prt promoter region showed that all the information needed for full activity and regulation of the prtP and prtM promoters is retained within a 90-bp region which includes both transcription initiation sites. An inverted repeat sequence positioned around the prtP and prtM transcription initiation sites was disrupted by either deletion or insertion of a small DNA sequence to analyze their effects on the activities of both prtP and prtM promoters. The mutations affected the activities of these promoters only marginally at low peptide concentrations but resulted in 1.5- to 5-fold derepression at high peptide concentrations. These results indicate that the expression of both prtM and prtP genes is controlled in an identical manner via a control mechanism capable of repressing transcription initiation at high peptide concentrations.
Pour une modélisation surfaciste de la flexion. Le cas de la conjugaison du français

Les descriptions de la morphologie flexionnelle des langues sont naturellement basees sur l’observation detaillee de l’ensemble des proprietes connues des systemes en question mais quelle part de ces connaissances est accessible aux locuteurs ? Dans ce travail nous proposons une approche resolument basee sur des connaissances accessibles illustree sur la conjugaison du francais. Le modele propose ici vise a repondre a la question du remplissage des paradigmes (Paradigm Cell Filling Problem : Ackerman et al., 2009) a partir des connaissances lexicales presentes dans un lexique-echantillon et de l’inference de connaissances flexionnelles dans le cadre de la theorie de l’information (Shannon, 1948). Notre analyse est basee sur l’observation classique que un paradigme flexionnel est un ensemble de formes toutes mutuellement reliees par des analogies. A partir de ce point, nous proposons un mecanisme de construction des connaissances flexionnelles et de remplissage des paradigmes.
The Bacillus subtilis Acyl Lipid Desaturase Is a Δ5 Desaturase

ABSTRACT Bacillus subtilis was recently reported to synthesize unsaturated fatty acids (UFAs) with a double bond at positions Δ5, Δ7, and Δ9 (M. H. Weber, W. Klein, L. Muller, U. M. Niess, and M. A. Marahiel, Mol. Microbiol. 39:1321-1329, 2001). Since this finding would have considerable importance in the double-bond positional specificity displayed by the B. subtilis acyl lipid desaturase, we have attempted to confirm this observation. We report that the double bond of UFAs synthesized by B. subtilis is located exclusively at the Δ5 position, regardless of the growth temperature and the length chain of the fatty acids.
An immunoinformatics approach to define T cell epitopes from polyketide and non‐ribosomal peptide synthesis proteins of Mycobacterium tuberculosis as potential vaccine candidates

The role of polyketide and non‐ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty‐one proteins from polyketide and non‐ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides. All possible overlapping nanomeric peptide sequences from 41 small molecule metabolic proteins were generated through in silico and analyzed for their ability to bind to 33 alleles belonging to A, B, and C loci of HLA class I molecule. Polyketide and non‐ribosomal protein analyses revealed that 20% of generated peptides were predicted to bind HLA with halftime of dissociation T1/2 ≥ 100 minutes, and 77% of them were mono‐allelic in their binding. The structural bases for recognition of nanomers by different HLA molecules were studied by structural modeling of HLA class I‐peptide complexes. Pathogen peptides that could mimic as self‐peptides or partially self‐peptides in the host were excluded using a comparative study with the human proteome; thus, subunit or DNA vaccines will have more chance of success.