Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute, but reversible, kainic acid–induced DNA damage in hippocampal CA1 pyramidal cells of p53‐deficient mice

p53 plays an essential role in mediating apoptotic responses to cellular stress, especially DNA damage. In a kainic acid (KA)–induced seizure model in mice, hippocampal CA1 pyramidal cells undergo delayed neuronal death at day 3–4 following systemic KA administration. We previously demonstrated that CA1 neurons in p53−/− animals are protected from such apoptotic neuronal loss. However, extensive morphological damage associated with DNA strand breaks in CA1 neurons was found in a fraction of p53−/− animals at earlier time points (8 h to 2 days). No comparable acute damage was observed in wild‐type animals. Stereological counting confirmed that there was no significant loss of CA1 pyramidal cells in p53−/− animals at 7 days post‐KA injection. These results suggest that seizure‐induced DNA strand breaks are accumulated to a greater extent but do not lead to apoptosis in the absence of p53. In wild‐type animals, therefore, p53 appears to stimulate DNA repair and also mediate apoptosis in CA1 neurons in this excitotoxicity model. These results also reflect remarkable plasticity of neurons in recovery from injury.
Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects

Here, we investigate the role of RelB in the regulation of genes which were identified to be induced in an aryl hydrocarbon receptor (AhR)-dependent manner and critically involved in regulation of immune responses. We analyzed the expression of genes of the AhR gene battery, cytokines, and immune regulatory enzymes in bone marrow-derived macrophages (BMM) and thymus of B6 wildtype (wt) mice and RelB knockout (RelB−/−) mice after treatment with various AhR ligands. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced expression of indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2 was significantly repressed in thymus of RelB−/− mice but not in BMM derived from RelB−/− mice. Interestingly, the induced and basal expression of the cytokines interleukin (IL)-17A, IL-22, and CCL20 required the functional expression of RelB. The RelB-dependent expression of CCL20 was induced by the AhR ligands TCDD and 6-formylindolo[3,2-b]carbazole (FICZ), whereas indole-3-carbinol (I3C) suppressed CCL20 in lipopolysaccharide (LPS)-activated wt BMM. The LPS-induced expression of IL-6 and IL-10 was enhanced by TCDD and FICZ, whereas I3C significantly suppressed these cytokines in BMM. The exposure to FICZ led to higher increases of IL-17A and IL-22 mRNA compared to the effect of TCDD or I3C in thymus of wt mice. On the other hand, TCDD was the strongest inducer of CYP1A1, AhR Repressor (AhRR), and IDO2. In summary, these findings provide evidence for the important role of RelB in the transcriptional regulation of cytokines and enzymes induced by AhR ligands.
Behavioral dimensions of climate change: drivers, responses, barriers, and interventions

This overview describes the anthropogenic drivers of global climate change, reviews the behavioral and psychological responses to its impacts (including barriers to behavior change), considers behavior‐focused intervention strategies, and suggests future directions for research. In doing so, it demonstrates why and how behavioral science is crucial for confronting the complex challenges posed by global climate change. The human dimensions of climate change are discussed, followed by descriptions of key theoretical models for explaining and predicting climate‐relevant behavior, issues and distinctions in studying human behavior in response to global climate change, an account of psychological (as opposed to structural) adaptation and its behavioral sequelae, the many psychological barriers to behavior change in this context, and behavior‐focused intervention strategies. The overview concludes with suggestions for researchers interested in advancing knowledge about behavior change and psychological responses to climate change. When knowledge about human behavior, cognitions, and psychological adaptation is integrated with that produced by researchers in related social and natural science disciplines, the result will facilitate solutions to this massive shared challenge. WIREs Clim Change 2011, 2:801–827. doi: 10.1002/wcc.143
A Comparative Analysis of Content Delivery Network and Other Techniques for Web Content Delivery

Web content delivery is based on client-server model. In this model, all the web requests for specific contents are serviced by a single web server as the requested contents reside only on one server. Therefore, with the increasing reliance on the web, the load on the web servers is increasing, thus causing scalability, reliability and performance issues for the web service providers. Various techniques have been implemented to handle these issues and improve the Quality of Service of the web content delivery to end-users such as clustering of servers, client-side caching, proxy server caching, mirroring of servers, multihoming and Content Delivery Network (CDN). This paper gives an analytical and comparative look on these approaches. It also compares CDN with other distributed systems such as grid, cloud and peer-to-peer computing.
Effect of vacuum drying on blackcurrant ’ s antioxidant components

Fresh consumption of black currant is not typical, it is mainly distributed as processed food (concentrate, jam, frozen, dried powder etc.) For these reasons effect of preservation technologies on changes of valuable components has primarily importance. Aim of present study was to investigate changes of antioxidant compounds and antioxidant activity of black currant during vacuum drying at different temperature levels (40-50-60°C). As for control atmospheric drying at 60°C was also performed. Black currant (Ribes nigrum L.) var. Titania grown in Hungary in 2010 was used for the experiments. Samples were dried at three temperature levels (40-50-60°C at 10 mbar) as long as they reached a wet content lesser than 10%. Vacuum drying was performed by an industrial Memmert V 200 vacuum dryer. As a control, atmospheric drying was performed at 60°C using an atmospheric dryer. During drying process the dry material content, total polyphenol, total anthocyanin, ascorbic acid content and antioxidant activity were determined. Statistical evaluation was performed using Statistica 9. Software. Antioxidant compounds and antioxidant activity of black currant were affected by drying temperature (4050-60°C) and pressure (60°C 10 mbar and 1000 mbar). 50°C vacuum drying proved to be the optimal for preserve antioxidant compounds among the dehydration methods investigated. Based on our results it was concluded that drying temperature affects drying duration, rate of wet decrease and amount of antioxidant compounds. Drying temperature at 50°C proved to be the optimum. Black currant products made by moderate drying technology are suited for production of functional food products (for example: mueslies, teamixes, sauces with fruit pieces, jams etc.) due to their high antioxidant content.
Overshootless repetitive control

Repetitive control (RC) is a widely used effective approach for periodic reference tracking and periodic disturbance rejection. In this paper, its use for periodic disturbance rejection and piecewise constant reference tracking is analyzed in a continuous-time framework. First, two previously proposed repetitive control structures, namely the basic repetitive controller and the current iteration repetitive controller, are studied. We first show that they do not provide a satisfying piecewise constant reference tracking performance, either because of a nonzero steady state error or because of large overshoots. Then a new structure, named the overshootless repetitive controller, is proposed to provide the same suitable periodic disturbance rejection capability as the current iteration repetitive controller while providing better transients.
Transient introduction of human telomerase mRNA improves hallmarks of progeria cells

Hutchinson–Gilford progeria syndrome (HGPS) is characterized by accelerated senescence due to a de novo mutation in the LMNA gene. The mutation produces an abnormal lamin A protein called progerin that lacks the splice site necessary to remove a farnesylated domain. Subsequently, progerin accumulates in the nuclear envelope, disrupting nuclear architecture, chromatin organization, and gene expression. These alterations are often associated with rapid telomere erosion and cellular aging. Here, we further characterize the cellular and molecular abnormalities in HGPS cells and report a significant reversal of some of these abnormalities by introduction of in vitro transcribed and purified human telomerase (hTERT) mRNA. There is intra‐individual heterogeneity of expression of telomere‐associated proteins DNA PKcs/Ku70/Ku80, with low‐expressing cells having shorter telomeres. In addition, the loss of the heterochromatin marker H3K9me3 in progeria is associated with accelerated telomere erosion. In HGPS cell lines characterized by short telomeres, transient transfections with hTERT mRNA increase telomere length, increase expression of telomere‐associated proteins, increase proliferative capacity and cellular lifespan, and reverse manifestations of cellular senescence as assessed by β‐galactosidase expression and secretion of inflammatory cytokines. Unexpectedly, mRNA hTERT also improves nuclear morphology. In combination with the farnesyltransferase inhibitor (FTI) lonafarnib, hTERT mRNA promotes HGPS cell proliferation. Our findings demonstrate transient expression of human telomerase in combination with FTIs could represent an improved therapeutic approach for HGPS.
Device-Measured Desk-Based Occupational Sitting Patterns and Stress (Hair Cortisol and Perceived Stress)

Background: Stress and poor mental health are significant issues in the workplace and are a major cause of absenteeism and reduced productivity. Understanding what might contribute towards employee stress is important for managing mental health in this setting. Physical activity has been shown to be beneficial to stress but less research has addressed the potential negative impact of sedentary behaviour such as sitting. Therefore, the aim of this study was to assess the relationship between device-measured occupational desk-based sitting patterns and stress (hair cortisol levels (HCL), as a marker of chronic stress and self-reported perceived stress (PS)). Methods: Employees were recruited from four workplaces located in Central Scotland with large numbers of desk-based occupations. Seventy-seven participants provided desk-based sitting pattern data (desk-based sitting time/day and desk-based sit-to-stand transitions/day), a hair sample and self-reported perceived stress. HCL were measured using enzyme-linked immunosorbent assay and PS using the Cohen Self-Perceived Stress Scale. Linear regression models were used to test associations between desk-based sitting time/day, desk-based sit-to-stand transitions/day, HCL and PS. Results: There were no associations between any of the desk-based sitting measures and either HCL or PS. Conclusions: Desk-based sitting patterns in the workplace may not be related to stress when using HCL as a biomarker of chronic stress or PS. The relationship between sitting patterns and stress therefore requires further investigation.
Recognition Inthe-Wild : Unified Model for Multi-Modal Sensors and Multi-Label Classification

Automatic recognition of behavioral context (location, activities, body-posture etc.) can serve health monitoring, aging care, and many other domains. Recognizing context in-the-wild is challenging because of great variability in behavioral patterns, and it requires a complex mapping from sensor features to predicted labels. Data collected in-the-wild may be unbalanced and incomplete, with cases of missing labels or missing sensors. We propose using the multiple layer perceptron (MLP) as a multi-task model for context recognition. Based on features from multi-modal sensors, the model simultaneously predicts many diverse context labels. We analyze the advantages of the model’s hidden layers, which are shared among all sensors and all labels, and provide insight to the behavioral patterns that these hidden layers may capture. We demonstrate how recognition of new labels can be improved when utilizing a model that was trained for an initial set of labels, and show how to train the model to withstand missing sensors. We evaluate context recognition on the previously published ExtraSensory Dataset, which was collected in-the-wild. Compared to previously suggested models, the MLP improves recognition, even with fewer parameters than a linear model. The ability to train a good model using data that has incomplete, unbalanced labeling and missing sensors encourages further research with uncontrolled, in-the-wild behavior.
Is Optogenetic Activation of Vglut1-Positive Aβ Low-Threshold Mechanoreceptors Sufficient to Induce Tactile Allodynia in Mice after Nerve Injury?

Mechanical allodynia is a cardinal feature of pathological pain. Recent work has demonstrated the necessity of Aβ-low-threshold mechanoreceptors (Aβ-LTMRs) for mechanical allodynia-like behaviors in mice, but it remains unclear whether these neurons are sufficient to produce pain under pathological conditions. We generated a transgenic mouse in which channelrhodopsin-2 (ChR2) is conditionally expressed in vesicular glutamate transporter 1 (Vglut1) sensory neurons (Vglut1-ChR2), which is a heterogeneous population of large-sized sensory neurons with features consistent with Aβ-LTMRs. In naive male Vglut1-ChR2 mice, transdermal hindpaw photostimulation evoked withdrawal behaviors in an intensity- and frequency-dependent manner, which were abolished by local anesthetic and selective A-fiber blockade. Surprisingly, male Vglut1-ChR2 mice did not show significant differences in light-evoked behaviors or real-time aversion after nerve injury despite marked hypersensitivity to punctate mechanical stimuli. We conclude that optogenetic activation of cutaneous Vglut1-ChR2 neurons alone is not sufficient to produce pain-like behaviors in neuropathic mice. SIGNIFICANCE STATEMENT Mechanical allodynia, in which innocuous touch is perceived as pain, is a common feature of pathological pain. To test the contribution of low-threshold mechanoreceptors (LTMRs) to nerve-injury-induced mechanical allodynia, we generated and characterized a new transgenic mouse (Vglut1-ChR2) to optogenetically activate cutaneous vesicular glutamate transporter 1 (Vglut1)-positive LTMRs. Using this mouse, we found that light-evoked behaviors were unchanged by nerve injury, which suggests that activation of Vglut1-positive LTMRs alone is not sufficient to produce pain. The Vglut1-ChR2 mouse will be broadly useful for the study of touch, pain, and itch.
Molecular cloning of a DNA fragment from human chromosome 14(14q11) involved in T‐cell malignancies.

To isolate DNA segments specific to chromosome band 14q11, which has been implicated in a number of human T‐cell malignancies, a genomic DNA library was prepared from a variant cell subline of the human lymphoblastic KE37 cell line. This subline (KE37‐R) bears a t(8;14) (q24;q11) translocation, and the breakpoint on the resulting chromosome 8q+ has been located at the 3′ end of the third c‐myc exon. Three molecular clones were isolated by screening the library with a c‐myc exon 3 probe, and one of them (lambda K40) was analyzed in detail. It contains a 15‐kb insert consisting of 4.5 kb of sequence from chromosome 8 (e.g., downstream of c‐myc exon 3) and sequences from chromosome 14. The origin of these latter sequences was established by hybridizing DNA from chromosomes sorted by flow cytometry to a lambda K40 subclone containing only chromosome 14 presumptive sequences and by Southern blot analysis of rodent X human somatic hybrid cell DNA with the same probe. No cross‐hybridization was found between the lambda K40 clone and a cDNA clone for the alpha chain T‐cell receptor gene which is also located in 14q11. A preliminary survey of DNAs from human T‐cell malignancies with a probe corresponding to chromosome 14 sequences of lambda K40 clone revealed for some of them restriction patterns different from those of the germ line DNA. The fact that the rearrangement observed in a leukemic patient was not found in DNA from lymphocytes obtained during remission excluded any polymorphism. (ABSTRACT TRUNCATED AT 250 WORDS)
Applying Graph Theory to Examine the Dynamics of Student Discussions in Small-Group Learning

Group work in science, technology, engineering, and mathematics courses is an effective means of improving student outcomes, and many different factors can influence the dynamics of student discussions and, ultimately, the success of collaboration. The substance and dynamics of group discussions are commonly examined using qualitative methods such as discourse analysis. To complement existing work in the literature, we developed a quantitative methodology that uses graph theory to map the progression of talk-turns of discussions within a group. We observed groups of students working with peer facilitators to solve problems in biological sciences, with three iterations of data collection and two major refinements of graph theory calculations. Results include general behaviors based on the turns in which different individuals talk and graph theory parameters to quantify group characteristics. To demonstrate the potential utility of the methodology, we present case studies with distinct patterns: a centralized group in which the peer facilitator behaves like an authority figure, a decentralized group in which most students talk their fair share of turns, and a larger group with subgroups that have implications for equity, diversity, and inclusion. Together, these results demonstrate that our adaptation of graph theory is a viable quantitative methodology to examine group discussions.
Trust* : extending the reach of trust in distributed systems

Building trust is a common requirement in distributed environments especially since many transactions now occur on a person-to-person basis. Examples range from e-commerce on the Internet to peer-to-peer and grid resource sharing. Many solutions to the problem of requiring trust among unknown entities rely on the use of a reputation metric to assess the risk of a potential transaction. However, such reputation systems require (often implicitly) that trust is transitive which can be a problematic assumption. This dissertation proposes a novel mechanism which we call trust*. The trust* model uses guarantees to extend local trust between unknown end-points. Trust* can be used as a substitution for end-to-end trust. Principals provide guarantees within existing (local) trust relationships to build a chain of localised agreements between the unknown end-points. The guarantees are backed by local micropayments to provide deterrents and incentives. Trust* relationships can be composed transitively, and the guarantees reduce the risk for the trusting party when doing so. This is because a guarantee is only ever provided locally by a directly trusted principal. Thus, trust management can be reduced to a locally solved problem. This work aims to develop a new technique for assessing and reducing the risk involved in trusting others in a distributed environment. The thesis of this dissertation is that an electronic analogue of real-world guarantees, is a useful and interesting way to provide these assurances. We develop an extension of the notion of trust, which we call trust*, which is built upon local guarantees, and which provides a novel conceptual framework for analysing and reasoning about a wide variety of trust-related problems in distributed systems. We present the concept of trust* and apply it to a number of application sce-
Antimicrobial resistance among salmonella isolates from hospitals in Rome

Summary The susceptibility to antimicrobial agents of 569 salmonella isolates collected in 1977–8 from patients in hospitals in Rome was tested. Fifty-nine per cent of all isolates were resistant to one or more antimicrobials. Resistance was most common to sulphathiazole, tetracycline, streptomycin, whereas colistin, gentamicin, tobramycin, trimethoprim-sulphamethoxazole and nalidixic acid were the most active in vitro. Multiple resistance was most frequently found in strains of Salmonella wien and S. typhimurium (94% and 38% respectively). A significant change in the resistance pattern of S. wien was observed between 1977 and 1978, with a significant increase of susceptibility to some antimicrobials in 1978. Twenty-one R-plasmids transmissible to E. coli K12 were derived from 46 resistant strains of S. typhimurum.
Autologous Freeze-Dried, Platelet-Rich Plasma Carrying Icariin Enhances Bone-Tendon Healing in a Rabbit Model

Background: Tendon-bone interface (TBI) injuries are common in sports activities. Owing to the limited regenerative ability of the TBI, its functional healing remains a difficulty in clinical practice. Icariin (ICA) provides strong stimulation for osteogenesis. Platelet-rich plasma (PRP) can be used as a carrier for bioactive molecules, although its ability to provide sustained release for such molecules needs improvement. Hypothesis: Freeze-dried PRP (FD-PRP) as a carrier for ICA can provide sustained release of ICA into the tendon-bone (T-B) healing site, thus accelerating T-B healing. Study Design: Controlled laboratory study. Methods: A total of 84 New Zealand rabbits with partial patellectomy in the hindlimb were randomly allocated into 3 different treatments: ICA incorporated with FD-PRP (ICA/FD-PRP), FD-PRP alone (FD-PRP), or saline control (CTL). The rabbit patella–patellar tendon (PP) interfaces were postoperatively harvested at postoperative week 8 or 16 for gross, radiological, histological, and mechanical evaluations. Results: Our results showed that FD-PRP can act as a carrier for sustained release of ICA into the T-B healing site. Macroscopically, no signs of infection or osteoarthritis were shown in the regenerated PP interfaces, and the area of cartilaginous metaplasia in the FD-PRP and ICA/FD-PRP groups at postoperative week 16 was significantly larger than that of the CTL group (P < .05 for all). Radiologically, micro–computed tomography showed that new bone which formed at the healing site in the ICA/FD-PRP group was significantly increased, remodeled, and mineralized in comparison with the CTL group (P < .05 for all). Histologically, the ICA/FD-PRP group exhibited a significant native PP interface, as shown by the enlargement and remodeling of new bone, well-organized collagen fibers, and robust production of proteoglycans in the regenerated fibrocartilage. The mechanical strength of the regenerated PP interface was significantly improved in the ICA/FD-PRP group. Significantly higher failure load and stiffness were shown in the ICA/FD-PRP group compared with the CTL and FD-PRP groups, respectively (P < .05 for all). Conclusion: FD-PRP is a suitable sustained-release carrier for ICA, and ICA/FD-PRP can provide sustained release of ICA into the T-B healing site, thus effectively accelerating T-B healing. Clinical Relevance: Findings of this study demonstrate the feasibility of using FD-PRP as a carrier for ICA to improve T-B healing and provide a foundation for future clinical application.