Miracle-dz/UniFAR-FTUs huggingface dataset:
Arrest, adaptation, and recovery following a chromosome double-strand break in Saccharomyces cerevisiae.

damage such as a double-strand break (DSB) of a chromosome causes eukaryotic cells to arrest cell cycle progression. Arrest provides a greater opportunity for cells to repair DNA damage prior to mitosis, which might cause cells to inherit chromosomes in which DNA repli-cation was not complete or in which broken chromosome segments, lacking a centromere, would be lost (Hartwell and Weinert 1989; Elledge 1996; Weinert 1998). DNA-damage-induced arrest is enforced by a network of checkpoint proteins that detect the damage and signal both the inhibition of mitosis and the induction of damage-in-ducible genes through a cascade of protein kinases, including Mec1p (a homolog of the mammalian ATM/ATR checkpoint kinases), Rad53p (whose human homolog is Cds1p), and Chk1p (homologous to human Chk1p) Lowndes and Murguia 2000). How these kinases are activated in response to DNA damage is not yet well understood. One putative DNA damage sensor involves both Rad24p and a complex of Rad17p, Mec3p, and Ddc1p (Kondo et al. 1999; Green et al. 2000). Another protein, Rad9p, is also required, independent of these other proteins (de la Torre-Ruiz et al. 1998). The ultimate targets of the damage signal cascade include Dun1p (Huang et al. 1998), a protein kinase that controls the induction of many damage-inducible genes; the Polo-like kinase Cdc5p (Shirayama et al. 1998) that regulates Cdc28p-cy-clin B kinase controlling both entry and exit from mito-sis; and Pds1p, an inhibitor of progression from metaphase to anaphase during mitosis (Cohen-Fix and Koshland 1999). Although much of the network of interacting proteins is conserved from yeast to mammals, damage-induced arrest in budding yeast appears to be different from damage-induced arrest in both mammalian cells and fission yeast, which block cell cycle progression at the transition from G 2 to M, primarily through regulating Cdk1–cyclin B kinase (Sanchez et al. 1999; Tinker-Kulberg and Morgan 1999). Many studies of DNA-damage-induced checkpoint responses have used genotoxic, DNA-modifying agents including UV lights and the alkylating chemical, methyl-methanesulfonate (MMS), or nucleotide depletion by hydroxyurea (HU). These treatments elicit a complicated cellular response, as they can create both single-or double stranded DNA breaks as well as interfere with the completion of DNA replication and even RNA transcription (S. Elledge, pers. comm.). To study a defined type of DNA damage, we and other investigators have made use of the site-specific HO endonuclease to create one or more DSBs at defined chromosomal locations. Using a galactose-inducible HO gene, it is …
Immunotoxicity of the organochlorine pesticide methoxychlor in female ICR, BALB/c, and C3H/He mice

Several types of pesticides, including organochlorines, are known to suppress or modulate immune responses. The present study evaluated the immunotoxicity of the organochlorine pesticide methoxychlor (MXC) in female BALB/c, C3H/He, and ICR mice. Mice were given oral MXC doses of 0, 30, 100, and 300 mg/kg each day for 7 consecutive days. On day 4, the mice also received an intravenous injection of sheep red blood cells (SRBC). The splenic plaque-forming cell (PFC) IgM response and the serum anti-SRBC IgM antibody titer were evaluated while splenic lymphocytes were counted by flow cytometry and the spleen underwent histopathological analysis. Significant decreases in IgM PFC responses were seen in BALB/c, C3H/He, and ICR mice that received MXC doses of 100 and 300 mg/kg. Similar changes in serum anti-SRBC IgM antibody titers occurred in three strain mice. Flow cytometric analysis revealed significantly decreased splenic T-cell (CD3+) populations in a dose dependent manner in BALB/c mice, and in the 300 mg/kg of MXC-treated group of C3H/He mice. Germinal center (GC) B-cell (CD19+PNA+) populations were significantly decreased in the 300 mg/kg of MXC-treated groups of all three mouse strains and in the 30 and 100 mg/kg of MXC-treated groups of BALB/c and C3H/He strain mice. Histopathological analysis revealed decreased cellularity of the periarteriolar lymphoid sheath (PALS; T-cell area) and decreased GC development in all three strains of mice treated with 300 mg/kg MXC. These results suggest that MXC has an immune-suppressive effect in mice, and that our protocol may be useful for rapidly detecting immunosuppression induced by environmental chemicals.
Computational Predictions of Volatile Anesthetic Interactions with the Microtubule Cytoskeleton: Implications for Side Effects of General Anesthesia

The cytoskeleton is essential to cell morphology, cargo trafficking, and cell division. As the neuronal cytoskeleton is extremely complex, it is no wonder that a startling number of neurodegenerative disorders (including but not limited to Alzheimer’s disease, Parkinson’s disease and Huntington’s disease) share the common feature of a dysfunctional neuronal cytoskeleton. Recently, concern has been raised about a possible link between anesthesia, post-operative cognitive dysfunction, and the exacerbation of neurodegenerative disorders. Experimental investigations suggest that anesthetics bind to and affect cytoskeletal microtubules, and that anesthesia-related cognitive dysfunction involves microtubule instability, hyper-phosphorylation of the microtubule-associated protein tau, and tau separation from microtubules. However, exact mechanisms are yet to be identified. In this paper the interaction of anesthetics with the microtubule subunit protein tubulin is investigated using computer-modeling methods. Homology modeling, molecular dynamics simulations and surface geometry techniques were used to determine putative binding sites for volatile anesthetics on tubulin. This was followed by free energy based docking calculations for halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on the tubulin body, and C-terminal regions for specific tubulin isotypes. Locations of the putative binding sites, halothane binding energies and the relation to cytoskeleton function are reported in this paper.
Using RRNS Codes for Cluster Faults Tolerance in Hybrid Memories

Hybrid CMOS/non-CMOS memories, in short hybrid memories, have been lauded as future ultra-capacity data memories. Nonetheless, such memories are going to suffer from high degree of cluster faults, which impact their reliability. This paper proposes two modified Redundant Residue Number Systems (RRNS) based error correcting codes to tolerate cluster faults in hybrid memories, namely (i) Three Non-Redundant Moduli RRNS (3NRM-RRNS) and (ii) Two Non-Redundant Moduli RRNS (2NRM-RRNS). Experimental results and analysis show that 3NRM-RRNS and 2NRM-RRNS possess competitive error correction capability to that of Reed-Solomon (RS) and conventional RRNS (C-RRNS), but at lower cost (reduced code size, lower performance penalty). E.g., for 16-bit memory 2NRM-RRNS provides a bit-wise error correction capability up to t=41.5% using 41 bits codeword, whereas RS offers only up to t=33.3% using 48 bits and C-RRNS supports up to t=31.1% using 61 bits. In addition, 2NRM-RRNS is 5.6 times faster than C-RRNS in recovering a correct data, which in turn results in higher speed decoding performance.
Leveraging virtual business model innovation: a framework for designing business model development tools

This paper presents a framework for developing tool support for the design and management of new business models. Existing IT tools supporting the process of designing, innovating, and evaluating a company's business model are currently not leveraging the full potential of tool support, because they do not make use of theoretical and empirical knowledge around business model development. Against this backdrop, we analyze existing knowledge on business model design and management, resulting in a first systematization of the activities that are necessary for developing and managing new business models. In order to complement this knowledge and to identify the requirements for supporting these activities, a series of expert interviews is conducted. Based on the results of the interview series, a new business model development tool is created and evaluated. The learnings of this development process are then consolidated in a unified framework. This framework constitutes a new solution for systematically designing tool support for business model development and extends existing literature by highlighting the importance of collaboration between participants in a business model development project. It also provides designers of new business model development tool with an empirically based conceptualization to guide their efforts.
Topology optimization of magnetic actuator based on a level-set and a phase-field approach

This paper aims at the development of a topology optimization method for magnetic actuator design using a levelset model that incorporates a fictitious interface energy model based on concepts in the phase-field method. The optimization problem is formulated for maximizing performance of a magnetic actuator with the ferromagnetic material constraint. The update scheme for implicit moving boundaries is developed based on the time evolutional equations. The proposed method is applied to the structural design of magnetic actuator and confirmed the effectiveness for achieving optimal configurations that deliver enhanced performance.
Stabilizing multi-channel slotted aloha for machine-type communications

In this paper, we consider a wireless cellular system with an unbounded population of machine-type users. The system provides a number of non-interfering slotted-time channels which users contend for when sending their uplink data packets. We propose a provably stable control procedure for the channel access probability in the sense that it maintains a finite number of unserviced users in the system. We also compare the proposed algorithm against the optimal multi-channel slotted Aloha to conclude that our solution demonstrates near-optimum performance.
Promoting problem-solving and reasoning during cooperative inquiry science

This paper reports on a study that was conducted on the effects of training students in specific strategic and meta-cognitive questioning strategies on the development of reasoning, problem-solving, and learning during cooperative inquiry-based science activities. The study was conducted in 18 sixth grade classrooms and involved 35 groups of students in three conditions: the cognitive questioning condition; the Philosophy for Children condition; and the comparison condition. The students were videotaped as they worked on a specific inquiry-science task once each term for two consecutive school terms. The results show that the students in all conditions demonstrated more helping discourses or discourses known to mediate learning than any other of the discourse categories. This outcome is encouraging because it is the helping discourses where students provide explanations, elaborations, and reasons that promote follow-up learning.
Exploring spatial patterns of mortality: the new atlas of United States mortality.

The National Center for Health Statistics, CDC, has produced an Atlas of United States Mortality which includes maps of rates for the leading causes of death in the United States for the period 1988-1992. As part of this project, many aspects of statistical mapping have been re-examined to maximize the atlas's effectiveness in conveying accurate mortality patterns to epidemiologists and public health practitioners. Because recent cognitive research demonstrated that no one map style is optimal for answering many different map questions, maps and graphs of several different mortality statistics are included for each cause of death. New mixed effects models were developed to provide predicted rates and improved variance estimates. Results from these models were smoothed using a weighted head-banging algorithm to produce maps of general spatial trends free of background noise. Maps of White female lung cancer rates from the new atlas are presented here to illustrate how this innovative combination of maps and graphs permits greater exploration of the underlying mortality data than is possible from previous single-map atlas designs. Published in 1999 by John Wiley & Sons, Ltd. This article is a U.S. Government work and is in the public domain in the United States.
The Functional Neuroanatomy of Thematic Role and Locative Relational Knowledge

Lexical-semantic investigations in cognitive neuroscience have focused on conceptual knowledge of concrete objects. By contrast, relational concepts have been largely ignored. We examined thematic role and locative knowledge in 14 left-hemisphere-damage patients. Relational concepts shift cognitive focus away from the object to the relationship between objects, calling into question the relevance of traditional sensory-functional accounts of semantics. If extraction of a relational structure is the critical cognitive process common to both thematic and locative knowledge, then damage to neural structures involved in such an extraction would impair both kinds of knowledge. If the nature of the relationship itself is critical, then functional neuroanatomical dissociations should occur. Using a new lesion analysis method, we found that damage to the lateral temporal cortex produced deficits in thematic role knowledge and damage to inferior fronto-parietal regions produced deficits in locative knowledge. In addition, we found that conceptual knowledge of thematic roles dissociates from its mapping onto language. These relational knowledge deficits were not accounted for by deficits in processing nouns or verbs or by a general deficit in making inferences. Our results are consistent with the hypothesis that manners of visual motion serve as a point of entry for thematic role knowledge and networks dedicated to eye gaze, whereas reaching and grasping serve as a point of entry for locative knowledge. Intermediary convergence zones that are topographically guided by these sensory-motor points of entry play a critical role in the semantics of relational concepts.
Cognitive therapy and behavioural coping in the management of work-related stress: An intervention study

Abstract Transactional models of stress emphasize the importance of cognitive appraisal of potential stressors in the determination of the stress response. This appraisal can be modified by the use of techniques normally associated with cognitive therapy. The contribution of a specifically cognitive component when intervening in work-related stress has not been well evaluated to date. This research seeks to determine the effectiveness of stress management training in the treatment of the work-related effects of stress by comparing the role of modifying dysfunctional cognitions with the teaching of appropriate behavioural coping strategies. Participants were allocated to one of two intervention conditions or to a waiting list control group. Those in the intervention conditions received group stress management either with the focus on delivering cognitive therapy techniques or with the focus on behavioural coping skills. Measures of general health were taken at the beginning and end of intervention and at 3-month follow-up. Participants in the cognitive therapy groups who were reporting symptoms of general ill-health at the start of the intervention showed a significant improvement at follow-up. Cognitive therapy appears to have been an effective intervention in work-related stress. Those in the behavioural group showed a smaller but still clinically effective improvement. Results are discussed in terms of methodological issues and implications for future research. It is suggested that changes in cognitive appraisal may need to be developed.
Key experiences in student teachers’ development

This study focuses on the question of why student teachers stay in teaching even after a profound ‘practice shock,’ i.e., a shock that in itself seems to characterize the complex and emotionally challenging first year of student teaching. Using a line drawing technique, the study investigates student teachers’ views of their first year of teaching by examining how they picture their development, their key experiences during that development, and the ways in which they coped with these experiences. The results suggest that most student teachers perceive their own development not as a steadily ascending line as is often suggested by research on the development of teachers’ professional identity. Instead, we now surmise that most student teachers view their development as a path with highs and lows that include transformative moments or periods. This relates to the idea of transformative learning and to theories on identity development that suggest people need a crisis for identity development to occur. During such a crisis, we saw that student teachers explicitly reconsidered their connections to teaching and that this reconsideration led to a regained motivation for teaching. It appeared that supervisors or mentor teachers played a significant role in first‐year (student) teachers’ regaining motivation for teaching.
Effect of perfusion pressure on force of contraction in thin papillary muscles and trabeculae from rat heart.

1. Increased coronary perfusion leads to increased myocardial contraction and oxygen consumption (Gregg's phenomenon) even when oxygen supply is presumably sufficient. Previous studies concerned whole hearts, however, in which local hypoxia may play a role. We developed techniques for internal perfusion of thin papillary muscles from rat heart. The influence of perfusion pressure on muscle contraction was studied. We investigated whether Gregg's phenomenon is due to (a) hypoxia, (b) stretch of the muscle fibres, or (c) increased contractility. 2. The effectiveness of the perfusion technique was demonstrated in four ways: (a) the diameter of the capillaries increased with perfusion pressure; (b) 14 +/‐ 4% (mean +/‐ S.D., n = 11) increase in muscle diameter was observed on a change of perfusion pressure from 0 to 50 cmH2O; (c) addition of India ink to the perfusate caused rapid staining of the entire muscle; (d) during internal perfusion and external superfusion peak force was mainly determined by the [Ca2+] in the internal perfusate. 3. An increase of perfusion pressure from 0 to 70 cmH2O induced 74 +/‐ 20% (mean +/‐ S.D., n = 11) increase in peak force of contraction. In the absence of internal perfusion peak force was not affected by approximately 50% reduction of the PO2 in the bathing solution (from 700 to 350 mmHg). Hence, oxygen supply was not a limiting factor, i.e. the effect of internal perfusion on force was not related to hypoxia. 4. Segment length was measured with markers attached to the surface of the muscle. Perfusion‐induced changes in segment length were negligible (‐0.2 +/‐ 1.5%, n = 11). Force‐length relationships at different perfusion pressures show that the perfusion‐induced increase in force was generally larger than the maximum increase in force that could be induced by stretch. Furthermore, the time course of stretch and perfusion effects on force was different. We conclude that Gregg's phenomenon is not related to changes in fibre length, i.e. the hypothesis of pressure‐induced stretch ('garden hose' effect) does not apply to papillary muscles. 5. The pressure‐induced changes in the force‐length relationship were similar to the changes obtained with interventions that increase contractility, such as increased [Ca2+]. 6. Since hypoxia and length effects were not involved, and the effect of perfusion pressure was similar to that of inotropic interventions, we conclude that Gregg's phenomenon is a change in contractility. Possible explanations include changes in the ionic composition or volume of the interstitium, and inotropic factors produced by the endothelium or intramyocardial neurons.
A vision lost? (Re)articulating an Arnoldian conception of education ‘in’ movement in physical education

In two seminal texts, Meaning in movement, sport and physical education and Education, movement and the curriculum, Arnold articulated ‘… the place of movement in the curriculum’. The concepts of ‘about’, ‘through’ and ‘in’ movement are in theory how Arnold holistically conceptualised the practice of physical education. The importance and desire to revisit Arnold's work reflects that (1) several international curriculum documents, at both junior and senior level, are premised on Arnoldian dimensions; (2) it possesses more currency in curriculum theory than ‘other’ holistic frameworks or models; (3) its use as a framework in physical education curriculum documents may not be as intended given the ways in which Arnold's work has variously been (re)interpreted and (re)presented over the years; and (4) not all dimensions (in particular education ‘in’ movement) are well understood nor fully conceptualised or contextualised. On the basis of the above rationales, the purpose is to examine and critique plausible shortcomings to the currently underemphasised and least understood concept of education ‘in’ movement as it primarily pertains to physical education curriculum theorisation, development and ultimately pedagogy. I contend that Arnold's education ‘in’ movement is more than mere participation in movement, physical activity and sport or as others have suggested education ‘through’ the physical. Drawing on the literature from diverse fields (e.g. philosophy, phenomenology), I will further develop the argument that engagement in these activities alone does not adequately reflect Arnold's conceptualisation of education ‘in’ movement and that opportunity for development of knowledge and understanding on multiple levels (pre-conscious, conscious) is a pre-requisite for individuals to develop deeper meaning and understanding about their engagement as agents within movement. This article, therefore, highlights how Arnold's vision has been ‘lost’, and proposes a re(articulated) and re(emphasised) vision that complements contemporary physical education curriculum theory.
Diagnosing PTSD: Lessons From Neuropsychology

Problematic diagnostic issues related to neurocognitive conditions have been well documented in research using neuropsychological instruments. However, due to the nature of differing assessment methods, these issues have not been as clearly established in the diagnostic assessment of psychiatric disorders that rely on self-report. Nonetheless, they appear relevant. This article summarizes diagnostic-related lessons learned based on clinical neuropsychological research and how they are applicable to the practice of diagnosing psychiatric conditions, post-traumatic stress disorder (PTSD) in particular. Ignoring these lessons raises serious risk for misdiagnosis, inappropriate treatment and services, and iatrogenic illness.
Evaluating lotteries, risks, and risk‐mitigation programs

Two experiments were designed to explore the existence of systematic differences in risk perceptions and risk attitudes between Chinese and US participants. The first experiment involved ranking monetary lotteries using measures of perceived riskiness and willingness to pay (WTP). Several simple heuristics were evaluated to predict perceived riskiness and WTP. Using WTP responses, Cumulative Prospect Theory functions were determined for participants from both countries. The second experiment involved ranking multi‐attribute real‐world risks and associated risk‐mitigation programs using measures of concern and preference, respectively. Compared to their US counterparts, Chinese participants are found to be less risk averse, more concerned about risks with higher catastrophic potential, and more in favor of risk‐mitigation programs with greater scope of benefit. The results also reveal higher within‐group agreement by Chinese participants for all tasks. For both national groups, the within‐group agreement was highest when ranking risk‐mitigation programs, but lowest when ranking lotteries with negative expected value. The implications of cross‐cultural versus cross‐task variation are discussed.