Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapy for ventricular arrhythmias in structural heart disease: a multifaceted challenge

The unpredictable nature and potentially catastrophic consequences of ventricular arrhythmias (VAs) have obligated physicians to search for therapies to prevent sudden cardiac death (SCD). At present, a low left ventricular ejection fraction (LVEF) has been used as a risk factor to predict SCD in patients with structural heart disease and has been consistently adopted as the predominant, and sometimes sole, indication for implantable cardioverter defibrillator (ICD) therapy. Although the ICD remains the mainstay life‐saving therapy for SCD, it does not modify the underlying arrhythmic substrate and may be associated with adverse effects from perioperative and long‐term complications. Preventative pharmacological therapy has been associated with limited benefits, but anti‐arrhythmic medications have significant side effects profiles. Catheter ablation of VAs has greatly evolved over the last few decades. Substrate mapping in sinus rhythm has allowed haemodynamically unstable VAs to be successfully treated. Both LVEF as an indication for ICD therapy and electro‐anatomical mapping for substrate modification identify static components of underlying myocardial arrhythmogenicity. They do not take into account dynamic factors, such as the mechanisms of arrhythmia initiation and development of new anatomical or functional lines of block, leading to the initiation and maintenance of VAs. Dynamic factors are difficult to evaluate and consequently are not routinely used in clinical practice to guide treatment. However, progress in the treatment of VAs should consider and integrate dynamic factors with static components to fully characterize the myocardial arrhythmic substrate.
Slavery in Dutch South Africa

List of illustrations, map and figures List of tables Acknowledgements Abbreviations 1. The study of Cape slavery 2. The creation and growth of a slave society 3. Slave labour and the Cape economy 4. Slave trading 5. Slave demography 6. Prices and profits 7. Slave life and labour 8. Slave discipline and Company law 9. The slave response 10. Slavery and Cape society Notes Bibliography Index.
The Wider Benefits of Adult Learning: An Illustration of the Advantages of Multi‐method Research

This paper examines the advantages of combining quantitative and qualitative findings concerning the wider benefits of adult learning. The research issue is a broad one that was under‐researched when the projects were conducted. Quantitative and qualitative projects addressed different facets of this issue. Mostly, they were designed and conducted separately, and combined only at the stage of interpreting findings. We therefore refer to the project as multi rather than mixed method research. The advantages of combining methods in this research fall into the five categories presented as purposes of mixed methods research by Greene, Caracelli, and Graham (1989): initiation, triangulation, complementarity, development and expansion. I suggest that initiation, which refers to the new perspectives that are developed when researchers attempt to combine apparently contradictory quantitative and qualitative findings, is conceptually distinct from the other advantages. Unlike the other four advantages, it is not associated with particular and concrete outcomes, such as additional evidence for validity (triangulation), developing a fuller picture of the research issue (complementarity) or expanding the scope of the research (expansion), its design and implementation (development). Rather, initiation is a process through which the reconciliation of apparently contradictory findings leads to triangulation, complementarity, development and expansion. The ease with which findings from different methods are reconciled is a dimension that applies to multi‐method research, which is highlighted by initiation. It bears on the creativity and innovation associated with triangulation, complementarity, development and expansion.
Molecular Dynamics Simulations of Chemical Reactions for Use in Education

This paper reports a method of simulating chemical reaction kinetics by adding rule-based elementary reactions to a classical molecular dynamics simulation. The method can reproduce many important thermodynamic properties of chemical reactions, and can be used to build interactive software that runs on typical personal computers. Its capacity has many potential applications for learning the core ideas of chemistry.
p90RSK Targets the ERK5-CHIP Ubiquitin E3 Ligase Activity in Diabetic Hearts and Promotes Cardiac Apoptosis and Dysfunction

Rationale: Cardiomyocyte apoptosis is one of the key events in the development and progression of heart failure, and a crucial role for ICER (inducible cAMP early repressor) in this process has been previously reported. ERK5 is known to inhibit cardiac apoptosis after myocardial infarction (MI), especially in hyperglycemic states, via association with CHIP ubiquitin (Ub) ligase and subsequent upregulation of CHIP ligase activity, which induces ICER ubiquitination and subsequent protein degradation. The regulatory mechanism governing ERK5/CHIP interaction is unknown. Objective: We previously demonstrated increased p90RSK activation in the diabetic heart. As a logical extension of this work, we now investigate whether p90RSK activation inhibits ERK5-mediated CHIP activation, and subsequently increases ICER levels and apoptosis. Methods and Results: p90RSK activation inhibits ERK5/CHIP association and CHIP Ub ligase activity. p90RSK and CHIP share a common binding site in the ERK5 C-terminal domain (aa571–807). Overexpression of either p90RSK or an ERK5 fragment (aa571–807) inhibits ERK5/CHIP association, suggesting that p90RSK and CHIP competes for ERK5 binding and that p90RSK activation is critical for inhibiting ERK5/CHIP interaction. We also identified ERK5-S496 as being directly phosphorylated by p90RSK and demonstrated that an ERK5-S496A mutant significantly impairs Angiotensin II–mediated inhibition of CHIP activity and subsequent increase in ICER levels. In vivo, either cardiac-specific depletion of ERK5 or overexpression of p90RSK inhibits CHIP activity and accelerates cardiac apoptosis after MI—a phenomenon fully reversible by activating ERK5. Conclusions: These data suggest a role for p90RSK in inhibiting CHIP activity and promoting cardiac apoptosis through binding to and phosphorylation of ERK5-S496.
Proteasome-Mediated Reduction in Proapoptotic Molecule Bim Renders CD4+CD28null T Cells Resistant to Apoptosis in Acute Coronary Syndrome

Background— The number of CD4+CD28null (CD28null) T cells, a unique subset of T lymphocytes with proinflammatory and cell-lytic phenotype, increases markedly in patients with acute coronary syndrome (ACS). ACS patients harboring high numbers of CD28null T cells have increased risk of recurrent severe acute coronary events and unfavorable prognosis. The mechanisms that govern the increase in CD28null T cells in ACS remain elusive. We investigated whether apoptosis pathways regulating T-cell homeostasis are perturbed in CD28null T cells in ACS. Methods and Results— We found that CD28null T cells in ACS were resistant to apoptosis induction via Fas-ligation or ceramide. This was attributable to a dramatic reduction in proapoptotic molecules Bim, Bax, and Fas in CD28null T cells, whereas antiapoptotic molecules Bcl-2 and Bcl-xL were similar in CD28null and CD28+ T cells. We also show that Bim is phosphorylated in CD28null T cells and degraded by the proteasome. Moreover, we demonstrate for the first time that proteasomal inhibition restores the apoptosis sensitivity of CD28null T cells in ACS. Conclusions— We show that CD28null T cells in ACS harbor marked defects in molecules that regulate T-cell apoptosis, which tips the balance in favor of antiapoptotic signals and endows these cells with resistance to apoptosis. We demonstrate that the inhibition of proteasomal activity allows CD28null T cells to regain sensitivity to apoptosis. A better understanding of the molecular switches that control the apoptosis sensitivity of CD28null T cells may reveal novel strategies for targeted elimination of these T cells in ACS patients.
SEQUENCE ANALYSIS AND MOLECULAR CHARACTERIZATION OF A NITROCATECHOL DIOXYGENASE GENE FROM Pseudomonas putida

A Pseudomonas putida capable of degrading polychlorinated biphenyl was also found to transform 4-nitrocatechol to 3-nitro-2-hydroxy-6-oxo-hexa-2,4-dienoic acid (NHODA). Crude cell extract of this bacterium exhibited an enzyme (nitrocatechol dioxygenase, Ndo) activity catalyzing this transformation. The gene encoding Ndo was cloned in E. coli. The cloned gene (ndo) expressed in E. coli had enzyme activity that degraded not only 4-nitrocatechol but also 4-chlorocatechol, 4-methylcatechol, 2,3-dihydroxybiphenyl, and 4′-chloro-2,3-dihydroxybiphenyl. Nucleotide sequence analysis of the cloned ndo exhibited an open reading frame of 939 base pairs. This sequence can encode a 313 amino acids protein of approximately molecular weight of 35 kd, which was confirmed by in vitro transcription and translation assay and SDS-PAGE analysis. A putative ribosomal binding site (GAGGAGA) was present 7 base pairs upstream from the AUG start codon and a promotor site homologous to E. coli ‘−10’ and ‘−35’ regulatory region was located at ‘−123’ and ‘−174’ area of our clone with sequences of TTGAAG and GTGACA, respectively. The deduced amino acid sequence showed 69% homology with Cdo from Burkholderia cepacia AAI. A unique insertion of 21 amino acids was found towards the N-terminal of the Ndo. Expression of ndo in strain OU83 was repressed in presence of 3-chlorobenzoic acid as judged by the decrease in the expression of ndo specific transcript.
Young “netizens” creating public citizenship in cyberspace

Collaborating with universities in Hong Kong, Finland, the United Kingdom and Australia the research project outlined in this paper takes up one of the key initial findings related to the importance of children's online spaces away from school. The project brings together complementary strengths from each partner nation to assist our mutual need to understand the worlds of our young “netizens” – the new public citizens of cyberspace. Differing in social and cultural context, each setting is recognised as a strong contributor to understanding the competencies of young people's digital expertise. We work from the shared view that the arrival of Web 2.0 and 3.0 social networking tools is educationally challenging and demands futuristic thinking for sustainable education and social connectivity globally. Our research aim is to use a common research design to discover how young people are behaving in the new online spaces; what guides their decision-making; and what, if any, common values appear to emerge when results between countries are compared. Locally derived knowledge gained from samples of 12-year-olds will be subjected to cross-cultural comparisons and validation. In doing so, we make some assumptions about the homogenising process that shared global networks may be fostering. Bringing together these contributions will strengthen the decision-making process and provide new knowledge about meaning making, agency and citizenship for the twenty-first-century e-democracy. This paper reports on the conceptual process underlying the research and the research design.
Shear strength in one- and two-way slabs according to the critical shear crack theory

Currently, there is no generally-accepted theory giving a physical explanation of the shear strength in one- and two-way slabs. Furthermore, for members without transverse reinforcement, shear strength is estimated in most codes of practice following empirical or semi-empirical approaches. In this paper, the fundamentals of the Critical Shear Crack Theory (CSCT) are introduced. This theory, based on a mechanical model, is shown to provide a unified approach for one- and two-way shear in slabs, leading to simple design expressions for estimating the strength and deformation capacity of such members. The paper also details a code-like formulation based on this theory and developed for the Swiss code for structural concrete. Comparisons of the theory to a wide range of test data are finally presented.
Sentence comprehension in competing speech: Dichotic sentence-word priming reveals hemispheric differences in auditory semantic processing

This study examined the effects of competing speech on auditory semantic comprehension using a dichotic sentence-word priming paradigm. Lexical decision performance for target words presented in spoken sentences was compared in strongly and weakly biasing semantic contexts. Targets were either congruent or incongruent with the sentential bias. Sentences were presented to one auditory channel (right or left), either in isolation or with competing speech produced by a single talker of the same gender presented simultaneously. The competing speech signal was either presented in the same auditory channel as the sentence context, or in a different auditory channel, and was either meaningful (played forward) or unintelligible (time-reversed). Biasing contexts presented in isolation facilitated responses to congruent targets and inhibited responses to incongruent targets, relative to a neutral baseline. Facilitation priming was reduced or eliminated by competing speech presented in the same auditory channel, supporting previous findings that semantic activation is highly sensitive to the intelligibility of the context signal. Competing speech presented in a different auditory channel affected facilitation priming differentially depending upon ear of presentation, suggesting hemispheric differences in the processing of the attended and competing signals. Results were consistent with previous claims of a right ear advantage for meaningful speech, as well as with visual word recognition findings implicating the left hemisphere in the generation of semantic predictions and the right hemisphere in the integration of newly encountered words into the sentence-level meaning. Unlike facilitation priming, inhibition was relatively robust to the energetic and informational masking effects of competing speech and was not influenced by the strength of the contextual bias or the meaningfulness of the competing signal, supporting a two-process model of sentence priming in which inhibition reflects later-stage, expectancy-driven strategic processes that may benefit from perceptual reanalysis after initial semantic activation.
Queering the Workplace

Despite many advances toward equity in society, gay, lesbian, and bisexual (GLB) individuals remain subjected to many stereotypes and experience negative consequences resulting from a dominant heterosexual environment, which includes significant obstacles that inhibit opportunities and participation in the workplace. As a start to addressing these issues, this conceptual article begins by providing an overview of the experiences of GLB people in the workplace, focusing on forms of discrimination, its impacts on GLB people, and coping mechanisms employed to mitigate stress. Though the literature supporting this endeavor is largely derived from the United States, an examination of extant literature suggests that experiences of GLB Canadians are similar. This paper concludes by encouraging employers to foster expansive learning environments as a means of promoting full participation for GLB individuals in the workplace.
High Degree of NCAM Diversity Generated by Alternative RNA Splicing in Brain and Muscle

The neural cell adhesion molecules (NCAMs) are cell surface glycoproteins involved in vertebrate cell contact formation. Several NCAM mRNA types are generated from a single primary transcript by alternative splicing and differential polyadenylation. In this presentation we analyse sequence heterogeneities within NCAM transcripts detected in the junctions of exons 7/8, 12/13 and 13/14. The highest degree of evolutionary conservation is observed in the 30‐nucleotide insertion (π) between exons 7 and 8, coding for an identical peptide sequence in the mouse, rat and chicken. The most complex splicing pattern is found between exons 12 and 13, called splice site a. Three alternative exons of 15, 48 and 42 nucleotides can be inserted in various combinations, which may also contain the additional trinucleotide AAG. In mouse muscle cell lines, differential ‘extra exon’ and AAG usage in splice site α creates up to 16 NCAM diversity forms, some (if not all) of which are also expressed in mouse brain. Additional microdiversity is generated by the insertion of an alternative AAG trinucleotide in exon junction 13/14. If all combinations of splicing patterns identified so far were to occur and to be translated, there could be up to 192 different NCAM proteins.
Dynamics of serial position change in probe-recognition task

Relationship between practice and serial position effects was investigated, in order to obtain more evidence for underlying short-term memory processes. The investigated relationship is termed the dynamics of serial position change. To address this issue, the present study investigated mean latency, errors, and performed Ex-Gaussian convolution analysis. In six-block trials the probe-recognition task was used in the so-called fast experimental procedure. The serial position effect was significant in all six blocks. Both primacy and recency effects were detected, with primacy located in the first two blocks, producing a non-linear serial position effect. Although the serial position function became linear from the third block on, the convolution analysis revealed a non-linear change of the normal distribution parameter, suggesting special status of the last two serial positions. Further, separation of convolution parameters for serial position and practice was observed, suggesting different underlying mechanisms. In order to account for these findings, a strategy shift mechanism is suggested, rather then a mechanism based on changing the manner of memory scanning. Its influence is primarily located at the very beginning of the experimental session. The pattern of results of errors regarding the dynamics of serial position change closely paralleled those on reaction times. Several models of short-term memory were evaluated in order to account for these findings.
Teaching Children to Add by Counting-On With One-Handed Finger Patterns

Three experiments report classroom instruction derived from cognitive research and focused on moving children across two developmental transitions: from counting-all to counting-on with entities present for the second addend and from the latter to counting-on as a number-word sequence solution procedure to solve symbolic single-digit addition problems. For the second transition, a new particularly efficient method of keeping track of number words counted-on was taught: counting-on with one-handed finger patterns. Classroom teachers were able to teach both kinds of transitions to most first and second graders, even to first graders below average in mathematics. Many first graders spontaneously transferred counting-on with finger patterns to the solution of addition word problems; some required instruction to do so. Most children were readily able to extend counting-on with finger patterns to counting up with finger patterns for subtraction. Counting-on with finger patterns was procedurally efficient enough.
Involvement of Quinolinate Phosphoribosyl Transferase in Promotion of Potato Growth by a Burkholderia Strain

ABSTRACT Burkholderia sp. strain PsJN stimulates root growth of potato explants compared to uninoculated controls under gnotobiotic conditions. In order to determine the mechanism by which this growth stimulation occurs, we used Tn5 mutagenesis to produce a mutant, H41, which exhibited no growth-promoting activity but was able to colonize potato plants as well as the wild-type strain. The gene associated with the loss of growth promotion in H41 was shown to exhibit 65% identity at the amino acid level to the nadC gene encoding quinolinate phosphoribosyltransferase (QAPRTase) in Ralstonia solanacearum. Complementation of H41 with QAPRTase restored growth promotion of potato explants by this mutant. Expression of the gene identified in Escherichia coli yielded a protein with QAPRTase activities that catalyzed the de novo formation of nicotinic acid mononucleotide (NaMN). Two other genes involved in the same enzymatic pathway, nadA and nadB, were physically linked to nadC. The nadA gene was cotranscribed with nadC as an operon in wild-type strain PsJN, while the nadB gene was located downstream of the nadA-nadC operon. Growth promotion by H41 was fully restored by addition of NaMN to the tissue culture medium. These data suggested that QAPRTase may play a role in the signal pathway for promotion of plant growth by PsJN.
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1

Designer Anti-HIV Developing a protective HIV vaccine remains a top global health priority. One strategy to identify potential vaccine candidates is to isolate broadly neutralizing antibodies from infected individuals and then attempt to elicit the same antibody response through vaccination (see the Perspective by Burton and Weiss). Wu et al. (p. 856, published online 8 July) now report the identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike. Zhou et al. (p. 811, published online 8 July) analyzed the crystal structure for one of these antibodies, VRC01, in complex with an HIV-1 gp120. VRC01 focuses its binding onto a conformationally invariant domain that is the site of initial CD4 attachment, which allows the antibody to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. The epitopes recognized by these antibodies suggest potential immunogens that can inform vaccine design. A human antibody achieves broad neutralization by binding the viral site of recognition for the primary host receptor, CD4. Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1–infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1–infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
Deaf in my own way: Identity, learning and narratives

Abstract This article describes the development of identity in deaf persons. It examines how deaf people learn to live under special conditions. Data is based on conversations (interviews) with 22 deaf persons. A discussion, grounded in narrative theory, of how the development of self-identity is closely related to interactions with deaf and hearing people is presented. Further it seems that experiences from interactions with hearing persons play a significant role. Within a frame of a dialogical perspective on learning, a model is presented for the development of how a deaf person relates to him/herself and to other deaf and hearing persons. The author is the hearing son of sign lingual, deaf parents. For more than 20 years he has been working within the field of deaf education, as a teacher and as a principal. The research project was conducted when the author was a research fellow at the Department of Special Needs Education at the University of Oslo, Norway.