Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional regulation of FEN1 nuclease and its link to cancer

Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5′-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stalled replication fork rescue, telomere maintenance, long-patch base excision repair and apoptotic DNA fragmentation. Here, we summarize the distinct roles of the different nuclease activities of FEN1 in these pathways. Recent biochemical and genetic studies indicate that FEN1 interacts with more than 30 proteins and undergoes post-translational modifications. We discuss how FEN1 is regulated via these mechanisms. Moreover, FEN1 interacts with five distinct groups of DNA metabolic proteins, allowing the nuclease to be recruited to a specific DNA metabolic complex, such as the DNA replication machinery for RNA primer removal or the DNA degradosome for apoptotic DNA fragmentation. Some FEN1 interaction partners also stimulate FEN1 nuclease activities to further ensure efficient action in processing of different DNA structures. Post-translational modifications, on the other hand, may be critical to regulate protein–protein interactions and cellular localizations of FEN1. Lastly, we also review the biological significance of FEN1 as a tumor suppressor, with an emphasis on studies of human mutations and mouse models.
Nucleotide Bound to rab11a Controls Localization in Rod Cells But Not Interaction with Rhodopsin

Precise vectorial transport of rhodopsin is essential for rod photoreceptor health and function. Mutations that truncate or extend the C terminus of rhodopsin disrupt this transport, and lead to retinal degeneration and blindness in human patients and in mouse models. Here we show that such mutations disrupt the binding of rhodopsin to the small GTPase rab11a. The rhodopsin–rab11a interaction is a direct binding interaction that does not depend on the nucleotide binding state of rab11a. Expression of EGFP-rab11a fusion proteins in Xenopus laevis photoreceptors revealed that the nucleotide binding status of rab11a affects its subcellular localization, with GTP-locked mutants concentrated in the inner segment and GDP-locked mutants concentrated in the outer segment. shRNA-mediated knockdown of rab11a in rods led to shortened outer segments and retinal degeneration. Together, our results show the critical importance of direct rhodopsin–rab11a interactions for the formation and maintenance of vertebrate photoreceptors.
Impact of change readiness on commitment to technological change, focal, and discretionary behaviors

Purpose – Commitment to change (C2C), focal and discretionary behaviors are under-researched areas in the context of developing countries such as Pakistan. The purpose of this paper is to analyze the impact of change readiness on employee’s C2C, focal and discretionary behaviors when controlling for gender, qualification, experience, and marital status. In addition, the goal of this study is to determine whether the three-component model of Herscovitch and Meyer (2002) may also be applied in the private manufacturing companies of Karachi (Pakistan). Design/methodology/approach – A sample of 205 fulltime employees having administrative and managerial responsibilities in the manufacturing operations is drawn from the manufacturing companies of Karachi undergoing major technological change. Exploratory and confirmatory factor analyses are used to evaluate the reliability and validity of the measurement model. Besides, hypotheses are tested using structural equation modeling in AMOS version 22. Findings – The.
Converging Evidence for the Neuroanatomic Basis of Combinatorial Semantics in the Angular Gyrus

Human thought and language rely on the brain's ability to combine conceptual information. This fundamental process supports the construction of complex concepts from basic constituents. For example, both “jacket” and “plaid” can be represented as individual concepts, but they can also be integrated to form the more complex representation “plaid jacket. ” Although this process is central to the expression and comprehension of language, little is known about its neural basis. Here we present evidence for a neuroanatomic model of conceptual combination from three experiments. We predicted that the highly integrative region of heteromodal association cortex in the angular gyrus would be critical for conceptual combination, given its anatomic connectivity and its strong association with semantic memory in functional neuroimaging studies. Consistent with this hypothesis, we found that the process of combining concepts to form meaningful representations specifically modulates neural activity in the angular gyrus of healthy adults, independent of the modality of the semantic content integrated. We also found that individual differences in the structure of the angular gyrus in healthy adults are related to variability in behavioral performance on the conceptual combination task. Finally, in a group of patients with neurodegenerative disease, we found that the degree of atrophy in the angular gyrus is specifically related to impaired performance on combinatorial processing. These converging anatomic findings are consistent with a critical role for the angular gyrus in conceptual combination.
Natural Killer Cell Cytotoxicity and Immunosuppressive Cytokines (IL-10, TGF-β1) in Patients with Gastric Cancer

Cytotoxic activity of NK cells was estimated as related to IL-10 and TGF-β1 serum levels and Helicobacter pylori infection in gastric cancer patients. Moreover, we sought to determine whether human gastric adenocarcinoma cells in vitro release IL-10, TGF-β1 or factor(s) affecting NK cytotoxicity. The studies were conducted on 42 patients with gastric cancer (14 with I-II stage—group 1; 28 with III-IV stage—group 2) and on 20 healthy volunteers. The cytotoxicity was tested on NK cells isolated from peripheral blood. IL-10 and TGF-β1 levels were determined by ELISA. H. pylori was detected in cultures of gastric mucosa biopsies and in direct preparations. In 71.4% patients of group 1 NK cytotoxicity and IL-10 serum levels remained within a normal range while in 68% patients of group 2 a marked decrease was noted in cytotoxic function of NK cells, accompanied by increased levels of IL-10 in serum. In turn, in most patients of either group, independently of NK cytotoxicity and stage grouping in the patients, elevated serum levels of TGF-β1 were detected. Presence of H. pylori infection manifested no relationship with NK cytotoxicity, IL-10, or the TGF-β1 serum levels. In cultures of tumour cells presence of IL-10 and TGF-β1 was demonstrated. Nevertheless, supernatants of the cultures did not change cytotoxic activity of NK cells. Development of gastric carcinoma is accompanied by markedly decreased cytotoxic function of NK cells and by elevated IL-10 and TGF-β1 serum levels. Gastric carcinoma cells may release IL-10, the suppressive activity of which may in a secondary manner decrease NK cytotoxicity.
Elements of Crafts that Enhance Well-Being

Abstract The main goals of this study are to depict the elements reported to enhance well-being in the descriptions of craft-making participants and to describe the meanings behind crafting. The study is based on written narratives of 59 female textile craft makers aged 19 to 84. The analysis revealed that the elements that participants characterized as enhancing their well-being were the following: the raw materials, the artefacts, the sense of achievement, the possibilities for personal growth, the development of physical and cognitive skills, the control of one's body and feelings, and the social and cultural dimensions of craft. Craft as a meaningful leisure activity had positive effects on the craft makers' well-being by fostering the feelings of self-managing and empowerment.
Dynamic Hardware Development

Applications that leverage the dynamic partial reconfigurability of modern FPGAs are few, owing in large part to the lack of suitable tools and techniques to create them. While the trend in digital design is towards higher levels of design abstractions, forgoing hardware description languages in some cases for high-level languages, the development of a reconfigurable design requires developers to work at a low level and contend with many poorly documented architecture-specific aspects. This paper discusses the creation of a high-level development environment for reconfigurable designs that leverage an existing high-level synthesis tool to enable the design, simulation, and implementation of dynamically reconfigurable hardware solely from a specification written in C. Unlike previous attempts, this approach encompasses the entirety of design and implementation, enables self-re-configuration through an embedded controller, and inherently handles partial reconfiguration. Benchmarking numbers are provided, which validate the productivity enhancements this approach provides.
Timing and Specificity of the Cognitive Changes Induced by Interleukin-2 and Interferon-&agr; Treatments in Cancer Patients

Objective Neuropsychological changes develop in patients treated by cytokine immunotherapy with interleukin-2 (IL-2) and interferon-&agr; (IFN-&agr;). However, the time course of appearance of these effects remains unclear, and their precise nature is still incompletely characterized. The objective of this study was to assess and characterize the early cognitive changes induced by IL-2 and IFN-&agr; in cancer patients at the end of the first week of treatment and to investigate the subsequent evolution of these changes. Methods The study was conducted in 47 cancer patients who received subcutaneous IL-2, administered alone (N = 17) or with IFN-&agr; (N = 7), or IFN-&agr; alone, administered subcutaneously at low doses (N = 7) or intravenously at high doses (N = 16). An automated battery of neuropsychological tests (Cambridge Neuropsychological Test Automated Battery) was used to measure reaction time, spatial working memory, and planning tasks. Cognitive tests were performed before treatment (day 1) and after 5 days (day 5) and 1 month of treatment. Results On day 5, patients treated with IL-2 alone had impaired spatial working memory and lower accuracy of planning abilities. In contrast, patients treated with IFN-&agr; did not show any impairment in performance accuracy in these tasks but showed longer latencies in the test of reaction time. Most of these early alterations persisted at the end of the first month of treatment without any obvious sign of worsening. Conclusions These findings suggest the existence of early differential neuropsychological changes in patients treated with IL-2 and IFN-&agr;.
Further evidence for favorable cost-effectiveness of elderly influenza vaccination

Vaccination represents the single most cost-effective strategy to avert influenza-related morbidity, mortality and economic consequences. This review presents an analysis of the pharmacoeconomic aspects of influenza vaccination of the elderly. The methodology of the analysis focuses on the main drivers of the pharmacoeconomic profile of elderly influenza vaccination, in particular the vaccine effectiveness in terms of prevention of hospitalization and mortality, the background incidence of hospitalization and death in unvaccinated individuals and the relative costing of the vaccine compared with the costs of a hospital in-patient day. The variation in outcomes between different studies could partly be explained by differences in the main drivers defined above. This review demonstrates that the pharmacoeconomic profile of elderly influenza vaccination is highly favorable. From the vast majority of studies it appears that financial benefits of elderly influenza vaccination surpass the costs and that, when this is not the case, cost–effectiveness in terms of net costs per life-year gained is acceptable.
CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis.

OBJECTIVE Most patients with idiopathic pulmonary fibrosis (IPF) show slowly progressive deterioration. However, accelerated deterioration also occurs in patient with IPF who have previously shown slowly progressive deterioration. The purpose of this study was to evaluate the CT findings of accelerated deterioration in patients with IPF. MATERIALS AND METHODS We evaluated the CT findings of 17 patients with IPF who fulfilled all the following criteria for accelerated deterioration of IPF: exacerbation of dyspnea within 1 month, new diffuse pulmonary opacities on chest radiography, a decrease in arterial oxygen tension (PaO2) of more than 10 mm Hg under similar conditions, and absence of apparent infectious agents and heart failure. Seven patients underwent sequential CT examination. Pathologic specimens were obtained from nine patients. RESULTS CT findings were classified as peripheral parenchymal opacification (n = 6), multifocal parenchymal opacification (n = 6), and diffuse parenchymal opacification (n = 5). Multifocal lesions developed diffusely in two of the seven patients who underwent sequential CT. These two patients both died. Three of the six patients with a multifocal pattern responded to corticosteroid therapy. All patients with a peripheral pattern showed various degrees of improvement following corticosteroid therapy. Multifocal and diffuse parenchymal opacification corresponded pathologically to acute diffuse alveolar damage. Peripheral parenchymal opacification corresponded pathologically to active fibroblastic foci. CONCLUSION CT patterns seen during periods of rapid deterioration in patients with IPF may allow predictions of prognosis and of response to treatment.
Organizational Innovativeness: Product Variation and Reorientation

This paper summarizes the results of a larger study of innovativeness in product development (Normann, 1969). The objective of this study was to gain some understanding of how organizational structure influences innovativeness. The original study consisted of 13 case studies of product-development projects in 12 moderately large to large Swedish companies from various industries, such as food processing, packaging, pharmaceuticals, construction, electronics, and engineering. Two objectives guided the collection of data: (1) as accurate and complete a description as possible of the actual processes in product development; and (2) a description of the organizational context, including data on the formal organization, the communication system, the external environment, and so on. Respondents were encouraged to speak freely and to give their own perceptions of what had happened; however, an attempt was made to obtain data on various ideas suggested as important by current theory, particularly the approaches of March and Simon (1958) and Burns and Stalker (1961). Data were collected from documents and by long, unstructured interviews with top managers, including the company leaders and managers who had been actively participating in the project. All interviews were taped and typewritten. The material was then content analyzed in several stages. A comprehensive report on the data and the methodology guiding the analysis, as well as some initial theoretical development, can be found in Normann (1969). GENERAL CONCEPTS
Channel Capacity for Single Branch Receivers Operating in Generalized Fading Scenarios

In this paper, we provide closed-form expressions for the average channel capacity (ACC) of single branch receivers operating in generalized fading channels. The expressions are obtained in terms of the well-known Meijer's G-functions, which are easily implemented in the most popular computing softwares. For comparison purposes, the capacity of additive white Gaussian noise channels is depicted and, as expected, it outperforms those proposed here. In addition, it is shown that, for any given fading condition, the Nakagami-m ACC defines regions of capacity, appearing as either lower bound or upper bound in the generalized fading scenarios.
Treatment of Type I Endoleaks Using Transcatheter Embolization With Onyx

Purpose To report a single-center experience with transcatheter embolization of type I endoleaks using the liquid embolic agent Onyx, an ethylene vinyl alcohol copolymer. Methods Eight patients (4 men; mean age 74.8 years, range 63–86) with 10 type I endoleaks (6 abdominal and 4 thoracic) diagnosed 2 days to 9 years after endovascular repair were treated with Onyx embolization because cuff extension was precluded by an insufficient landing zone in 6 cases and an unsuitable aortic diameter in 2. Endoleaks were accessed with a 4-F diagnostic catheter and a coaxially introduced dimethylsulfoxide-compatible microcatheter. Onyx-34 was predominantly applied due to its high viscosity; patent side branches were coil embolized prior to Onyx delivery in 3 cases. Results Technical success of the procedure was achieved in all cases. The mean volume of Onyx used for abdominal endoleaks was 11.8 mL (range 3.0–25.5) and 19.4 mL (range 4.5–31.5) for thoracic endoleaks. The average duration of the procedure was 76.7 minutes (range 34.5–110.6), and the average radiation dose area product was 18.8 cGy*cm2 (range 10.6–55.8). Reperfusion of the endoleak was detected in one case 2 days after the procedure. A second case showed an occluded endoleak but a small trace of contrast between the aortic wall and the stent-graft. Non-target embolization was not found in any case. Mean follow-up was 13.2 months (range 8–24). The mean reduction in diameters for thoracic aneurysms after 6 and 12 months was 0.4 and 0.9 cm, respectively, and 0.6 and 1.2 cm, respectively, for abdominal aneurysms. Conclusion Transcatheter embolization of type I endoleaks using Onyx is a simple, safe, and sustainable treatment option with a high primary success rate for cases in which stent-graft extension is not possible. The benefit of additional coil embolization remains uncertain.
Methods of teaching medical trainees evidence‐based medicine: a systematic review

The principles of evidence‐based medicine (EBM) provide clinicians with the ability to identify, source, appraise and integrate research evidence into medical decision making. Despite the mantra of EBM encouraging the use of evidence to inform practice, there appears little evidence available on how best to teach EBM to medical trainees. A systematic review was performed to identify what type of educational method is most effective at increasing medical trainees' competency in EBM.
Diabetes Incidence and Long-Term Exposure to Air Pollution

OBJECTIVE Animal and cross-sectional epidemiological studies suggest a link between air pollution and diabetes, whereas the limited prospective data show mixed results. We studied the association between long-term exposure to traffic-related air pollution and incidence of diabetes. RESEARCH DESIGN AND METHODS We followed 57,053 participants of the Danish Diet, Cancer, and Health cohort in the Danish National Diabetes Register between baseline (1993–1997) and 27 June 2006. We estimated the mean levels of nitrogen dioxide (NO2) at the residential addresses of the cohort participants since 1971 and modeled the association between NO2 and diabetes incidence with a Cox regression model, separately for two definitions of diabetes: all cases and a more strict definition where unconfirmed cases were excluded. RESULTS Over a mean follow-up of 9.7 years of 51,818 eligible subjects, there were 4,040 (7.8%) incident diabetes cases in total and 2,877 (5.5%) with confirmed diagnoses. Air pollution was not associated with all diabetes cases (hazard ratio 1.00 [95% CI 0.97–1.04] per interquartile range of 4.9 μg/m3 mean NO2 levels since 1971), but a borderline statistically significant association was detected with confirmed cases of diabetes (1.04 [1.00–1.08]). Among confirmed diabetes cases, effects were significantly enhanced in nonsmokers (1.12 [1.05–1.20]) and physically active people (1.10 [1.03–1.16]). CONCLUSIONS Long-term exposure to traffic-related air pollution may contribute to the development of diabetes, especially in individuals with a healthy lifestyle, nonsmokers, and physically active individuals.
Relationships among metalinguistic awareness, cognitive development, verbal abilities and biliteracy in first grade early French immersion students

The purpose of the current study was to investigate the relation of language and cognitive factors to biliteracy development among EFI first grade children. Variables of interest included phonological awareness, print awareness, level of operativity, English/French verbal ability, and influences in the home environment (e.g. socioeconomic status, parent's level of education, time spent on reading activities). A battery of language, cognitive and reading tests was administered in Fall and again in Spring of the first grade to sixty-eight preliterate Anglophone children. A parent questionnaire yielded information pertaining to socioeconomic status, and reading related leizure activities in the home. A teacher questionnaire provided details which described the various classroom environments of the children in the study. Results of correlational analyses indicate that phonological and print awareness both form a significant, positive relationship with French and English reading. Level of operativity and level of English verbal ability did not correlate significandy with any measure of reading. The pattern of correlations between French verbal ability tasks and French/English reading was inconsistent. Four of the six French verbal measures correlated significantly, but weakly with French reading and only one measure formed a significant positive correlation with English reading. Analyses of scatterplots which showed the relation of phonological abilities to
Randomised clinical trial of Hydrofiber dressing with silver versus povidone–iodine gauze in the management of open surgical and traumatic wounds

This prospective, randomised clinical trial compared pain, comfort, exudate management, wound healing and safety with Hydrofiber® dressing with ionic silver (Hydrofiber Ag dressing) and with povidone–iodine gauze for the treatment of open surgical and traumatic wounds. Patients were treated with Hydrofiber Ag dressing or povidone–iodine gauze for up to 2 weeks. Pain severity was measured with a 10‐cm visual analogue scale (VAS). Other parameters were assessed clinically with various scales. Pain VAS scores decreased during dressing removal in both groups, and decreased while the dressing was in place in the Hydrofiber Ag dressing group (n = 35) but not in the povidone–iodine gauze group (n = 32). Pain VAS scores were similar between treatment groups. At final evaluation, Hydrofiber Ag dressing was significantly better than povidone–iodine gauze for overall ability to manage pain (P < 0·001), overall comfort (P ≤ 0·001), wound trauma on dressing removal (P = 0·001), exudate handling (P < 0·001) and ease of use (P ≤ 0·001). Rates of complete healing at study completion were 23% for Hydrofiber Ag dressing and 9% for povidone–iodine gauze (P = ns). No adverse events were reported with Hydrofiber Ag dressing; one subject discontinued povidone–iodine gauze due to adverse skin reaction. Hydrofiber Ag dressing supported wound healing and reduced overall pain compared with povidone–iodine gauze in the treatment of open surgical wounds requiring an antimicrobial dressing.