Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structure of the CCAAT Box/Enhancer-binding Protein β Activating Transcription Factor-4 Basic Leucine Zipper Heterodimer in the Absence of DNA*

The crystal structure of the heterodimer formed by the basic leucine zipper (bZIP) domains of activating transcription factor-4 (ATF4) and CCAAT box/enhancer-binding protein β (C/EBPβ), from two different bZIP transcription factor families, has been determined and refined to 2.6 Å. The structure shows that the heterodimer forms an asymmetric coiled-coil. Even in the absence of DNA, the basic region of ATF4 forms a continuous α-helix, but the basic region of C/EBPβ is disordered. Proteolysis, electrophoretic mobility shift assay, circular dichroism, and NMR analyses indicated that (i) the bZIP domain of ATF4 is a disordered monomer and forms a homodimer upon binding to the DNA target; (ii) the bZIP domain of ATF4 forms a heterodimer with the bZIP domain of C/EBPβ that binds the cAMP response element, but not CCAAT box DNA, with high affinity; and (iii) the basic region of ATF4 has a higher α-helical propensity than that of C/EBPβ. These results suggest that the degree of ordering of the basic region and the fork and the dimerization properties of the leucine zipper combine to distinguish the structurally similar bZIP domains of ATF4 and C/EBPβ with respect to DNA target sequence. This study provides insight into the mechanism by which dimeric bZIP transcription factors discriminate between closely related but distinct DNA targets.
Caspase pathway of elaidic acid (9t‐C18:1)‐induced apoptosis in human umbilical vein endothelial cells

Although TFAs (trans fatty acids) do have effects on many endothelial functions, systemic inflammation and immune disorders, only limited experimental evidence is available that TFAs participate in the pathogenesis of endothelial cell apoptosis. HUVEC (human umbilical vein endothelial cells) were grown in medium with elaidic acid (9t‐C18:1) at 50, 100, 200 and 400 μmol/l for 24 h. Apoptosis was measured by flow cytometry, and caspase 3, 8 and 9 activities by colorimetric assay and their mRNA expression by qRT‐PCR (quantitative real‐time PCR). Results showed that 9t‐C18:1 induced apoptosis of HUVEC in a dose‐dependent manner. The activities and mRNA expression of caspases 8, 9 and 3 were significantly increased compared with that of the control. Z‐IETD‐FMK and Z‐LEHD‐FMK inhibited the activation of caspase 3 and apoptosis induced by 9t‐C18:1. Also Z‐IETD‐FMK inhibited the activation of caspase 9. mRNA expressions of Bid and Smac (second mitochondria‐derived activator of caspase)/DIABLO [direct IAP (inhibitor of apoptosis)‐binding protein with low pI] were also significantly elevated. We conclude that 9t‐C18:1 induces apoptosis of HUVEC through activating caspases 8, 9 and 3. The death receptor pathway and the mitochondrial pathway both participated in the apoptosis course induced by 9t‐C18:1.
Latency-associated peptide prevents skin fibrosis in murine sclerodermatous graft-versus-host disease, a model for human scleroderma.

Murine sclerodermatous graft-versus-host disease (Scl GVHD), produced by transplanting B10.D2 bone marrow and spleen cells to lethally irradiated BALB/cJ mice, is a model for human scleroderma. Mice with Scl GVHD have skin thickening, lung fibrosis, cutaneous mononuclear cell infiltration, and upregulation of cutaneous transforming growth factor beta1 (TGF-beta1) and type I collagen mRNAs by day 21 after bone marrow transplantation. Elevated TGF-beta1 appears to be the critical cytokine driving fibrosis in Scl GVHD, which can be prevented with antibodies to TGF-beta administered early in disease. Here we demonstrate that we can also prevent skin thickening in mice with Scl GVHD with a naturally occurring antagonist to TGF-beta1, human latency-associated peptide (LAP). By quantitative real-time PCR analysis and immunostaining, LAP treatment also abrogates the upregulation of cutaneous TGF-beta1 and connective tissue growth factor mRNAs and type I collagen synthesis in Scl GVHD. In contrast to anti-TGF-beta antibodies, LAP at 4 ng total per mouse has no significant suppressive effect on cutaneous influx of T cells and monocytes or immune cell activation. LAP may be a potential new therapy in scleroderma and other TGF-beta-driven fibrosing disease that targets TGF-beta more specifically, without affecting systemic critical roles of TGF-beta on immune cell function.
Experimental Evaluation of Optimal Schedulers Based on Partitioned Proportionate Fairness

The Quasi-Partitioning Scheduling algorithm optimally solves the problem of scheduling a feasible set of independent implicit-deadline sporadic tasks on a symmetric multiprocessor. It iteratively combines bin-packing solutions to determine a feasible task-to-processor allocation, splitting task loads as needed along the way so that the excess computation on one processor is assigned to a paired processor. Though different in formulation, QPS belongs in the same family of schedulers as RUN, which achieve optimality using a relaxed (partitioned) version of proportionate fairness. Unlike RUN, QPS departs from the dual schedule equivalence, thus yielding a simpler implementation with less use of global data structures. One might therefore expect that QPS should outperform RUN in the general case. Surprisingly instead, our implementation of QPS on LITMUS^RT invalidates this conjecture, showing that the QPS offline decisions may have an important influence on run-time performance. In this work, we present an extensive comparison between RUN and QPS, looking at both the offline and the online phases, to highlight their relative strengths and weaknesses.
Contextual enhancements of knowledge management systems for user-centred provision through assistance systems

The work presented in this paper is an innovative approach to correlate user interactions with knowledge in collaborative environments for context sensitive knowledge enhancement. It premises that in a user-sensitive context the important information to use is coherent with the actions made by an individual as well as by the group. The presented approach shows how to utilise the monitored user interactions with existing (knowledge management) systems in a collaborative working environment to enrich and focus the enhancement of knowledge for individuals or group of individuals. The approach focuses on the implicit and explicit knowledge gathered through a feedback system that unobtrusively monitors the active and passive knowledge. The proposed process is supported by modular services which allow docking to various systems to monitor and analyse the user's interactions and support subsequent systems through monitored data. Successful application of the proposed solutions in a real-world PDM/PLM scenario is presented.
Online ensemble learning for security assessment in PMU based power system

This paper presents an online Adaboost algorithm for ensemble of support vector machines (SVM) for power system security assessment utilizing online measurement data obtained from Phasor Measurement Units (PMUs). Our proposed learning scheme consists of a strong learner and multiple weak learners. The weak learners are linear SVMs which are easy to implement and incrementally updated with low computation complexity. The strong learner compensates for inevitable classification errors of linear SVMs by using the boosting approach. Since the data is unbalanced, i.e., the number unsecured scenarios is much smaller than the number of secured scenarios, conventional online Adaboost may result in the high misdetection rate. Hence, we propose an online Adaboost algorithm that can adapt itself to the unbalanced online data. In addition, efficient tradeoff between misdetection (i.e., failing to detect unsecured samples) and false alarm (i.e., classifying secured samples wrongly) can be achieved by tuning a design parameter. Numerical results show that our proposed scheme can achieve high security assessment efficiency and accuracy, which is potential for the advanced security monitoring application in future smartgrid.
Emergence of Drug-Resistant Populations of Woodchuck Hepatitis Virus in Woodchucks Treated with the Antiviral Nucleoside Lamivudine

ABSTRACT Lamivudine [(−)-β-l-2′,3′-dideoxy-3′-thiacytidine] reduces woodchuck hepatitis virus (WHV) titers in the sera of chronically infected woodchucks by inhibiting viral DNA synthesis. However, after 6 to 12 months, WHV titers begin to increase toward pretreatment levels. Three WHV variants with mutations in the active site of the DNA polymerase gene are present at this time (W. S. Mason et al., Virology 245:18–32, 1998). We have asked if these mutant viruses were responsible for the lamivudine resistance and if their emergence caused an immediate rise in virus titers. Cell cultures studies implied that the mutants were resistant to lamivudine. Emergence of mutant WHV was not always associated, however, with an immediate rise in virus titers in the serum. One of the three types of mutant viruses became prominent in serum up to 7 months before titers in serum actually began to increase, at a time when wild-type virus was still predominant in the liver. The two other mutants did not show this behavior but were detected in serum and liver later, just at the time that virus titers began to rise. A factor linking all three mutants was that a similar duration of drug administration preceded the rise in titers, irrespective of which mutant ultimately prevailed. A simple explanation for these results is that the increase in virus titers following emergence of drug-resistant mutants can occur only as the preexisting wild-type virus is cleared from the hepatocyte population, allowing spread of the mutants. Thus, prolonged suppression of virus titers in the serum may sometimes be a measure of the stability of hepatocyte infection rather than of a successful therapeutic outcome.
Contour evolution scheme for variational image segmentation and smoothing

An algorithm, based on the Mumford-Shah (M-S) functional, for image contour segmentation and object smoothing in the presence of noise is proposed. However, in the proposed algorithm, contour length minimisation is not required and it is demonstrated that the M-S functional without contour length minimisation becomes an edge detector. Optimisation of this nonlinear functional is based on the method of calculus of variations, which is implemented by using the level set method. Fourier and Legendre's series are also employed to improve the segmentation performance of the proposed algorithm. The segmentation results clearly demonstrate the effectiveness of the proposed approach for images with low signal-to-noise ratios.
Approccio sostenibile al recupero dell'edilizia residenziale

L’attuale mercato italiano delle attivita sul costruito e le previsioni sul suo futuro conducono a riflessioni in merito allo scenario europeo che possano aiutare a meglio comprendere i comportamenti futuri nel nostro contesto nazionale. Il tema della riqualificazione degli edifici residenziali, realizzati con tecnologie non tradizionali, richiede in particolare sia una visione complessiva delle strategie da attuare per realizzare interventi consapevoli, sia una metodologia che conduca al raggiungimento di obiettivi coerenti con i concetti di sostenibilita. Il tema prioritario dei prossimi anni, o dei prossimi decenni, e confermato dall’andamento del mercato delle costruzioni: un piu razionale impiego delle risorse urbanistiche del settore residenziale esistente. In questa prospettiva assume particolare interesse il recupero dei tessuti residenziali realizzati con tecnologie industrializzate e prefabbricate che si presentano, nonostante il breve arco di tempo intercorso, in uno stato di degrado avanzato e che richiedono non solo una profonda riqualificazione a scala edilizia, ma anche il risanamento urbanistico delle aree, lo sviluppo delle infrastrutture e dei servizi connessi. Questo interesse e riconosciuto come aspetto imperante nei diversi contesti europei dove e possibile operare un significativo confronto con la situazione italiana in merito alle condizioni, alla diffusione e alle motivazioni che hanno portato nei trent’anni successivi al dopoguerra, seppur con scarti temporali trascurabili, alla produzione di gran parte degli edifici residenziali oggi esistenti. Gli orientamenti, sia teorici che operativi, per gli interventi si sviluppano soprattutto in relazione ad alcuni fenomeni manifestatisi negli ultimi decenni che, in sintesi, si possono cosi riassumere:
Replication of a cognitive behavioral therapy for chronic pain group protocol by therapists in training

Abstract According to the American Psychological Association (Division 12), there is strong, long-standing research support for cognitive behavioral therapy (CBT) to treat chronic pain. Furthermore, meta-analytic comparisons have shown CBT to be highly efficacious. However, not all researchers agree with this conclusion. The purpose of the current pilot study was to determine whether a CBT outpatient, group-based treatment facilitated by junior therapists benefited veterans who suffer from mixed idiopathic, chronic, noncancer pain, thus replicating results from effective CBT programs from the past. A sample of 46 veterans aged 33 to 81 years with chronic, noncancer pain who participated in an outpatient CBT pain group therapy protocol at a Midwestern Veterans Affairs Medical Center between November 3, 2009, and September 2, 2010 was evaluated. All participants completed a pre- and postintervention assessment. Paired-samples t tests were conducted to evaluate the impact of the program on veterans’ scores on assessment measures. No significant difference was found between the pre- and posttest primary outcome measures of pain intensity. A significant difference was established between the pre- and posttest secondary outcome measure of catastrophizing. However, there were no other significant differences found among the remaining pre- and posttest secondary outcome measures of pain interference, disability, and psychological distress. Training junior therapists on how to use CBT protocols may be enhanced by paying greater attention to what mechanisms are responsible for the desired outcomes among veterans with chronic pain.
Bit-Width Optimization by Divide-and-Conquer for Fixed-Point Digital Signal Processing Systems

This paper presents a novel approach to fractional bit-width optimization of fixed-point designs. We first propose a divide-and-conquer algorithm that can assign optimal fractional bit-widths to a special class of designs that does not have reconvergent paths starting from an internal signal. General designs are partitioned into designs of that special class and our algorithm is applied to each design. The algorithm recursively breaks down a given design into sub-designs and finds Pareto optimal solutions to each sub-design. Those solutions are merged to form Pareto optimal solutions to a larger design. In addition, two pruning methods based on area and error, respectively, are proposed, speeding up the algorithm. The optimization process is guided by static maximum absolute error analysis, and functional correctness is guaranteed for all possible input stimuli. Our approach is demonstrated in five case studies including polynomial approximation and RGB-to-YCbCr conversion, for which the divide-and-conquer algorithm produces the optimal solutions.
Interleukin‐2‐mediated Survival and Proliferative Signals are Uncoupled in T Lymphocytes that Fail to Divide after Activation1

T lymphocytes are heterogeneous with respect to their ability to proliferate following activation in vitro and in vivo. Approximately 30% of T lymphocytes fail to progress through the cell cycle, despite showing evidence of an activated state. The population of T lymphocytes that remains undivided during a primary stimulation has been shown to be refractory to restimulation via the TCR and fails to proliferate in response to IL‐2. In an in vitro model of T‐cell deletion following clonal expansion, we demonstrate that T lymphocytes that do not progress through the cell cycle during primary stimulation have a sevenfold greater survival advantage compared with T lymphocytes that have divided. Progression through multiple division cycles is associated with down‐regulation of Bcl‐2 during a postactivation period of growth factor withdrawal. However this alone does not account for diminished survival, as constitutive expression of a Bcl‐2 transgene did not restore survival to the levels seen in undivided cells. Engagement of the IL‐2 receptor on these undivided activated T lymphocytes leads to enhanced survival and up‐regulation of Bcl‐2 and Bcl‐xL. Surprisingly, while IL‐2 also induces phosphorylation of Akt, it does not initiate cell cycle progression in this population of primary undivided cells. Our data provide evidence that a T cell's survival capacity is linked to its proliferative behavior. Furthermore, our results provide the first report of a population of T cells, in which the IL‐2 receptor‐mediated signaling pathways leading to survival and proliferation are naturally uncoupled.
Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis.

BACKGROUND Normal human skin harbors a single epidermal dendritic cell (DC) population, the CD1a(+++)CD11b(-) Langerhans cells. In many chronic inflammatory skin diseases, the epidermal DC pool bears a second population, the CD1a(+)CD11b(+++) inflammatory dendritic epidermal cells (IDECs). Immunophenotypic, ultrastructural, and functional aspects of IDECs have been investigated in chronic untreated skin lesions of intrinsic and extrinsic atopic dermatitis (AD), contact dermatitis (CD), and psoriasis, but little is known about freshly induced early skin lesions. OBJECTIVE We sought to characterize enumerative and immunophenotypic changes in the epidermal DC pool during the development of eczematous skin lesions. METHODS The atopy patch test with aeroallergens and food-protein allergens and a conventional patch test with standard-series haptens were performed as models for early skin lesions of extrinsic and intrinsic AD and CD, respectively. After 72 hours, epidermal cell suspensions were prepared, analyzed in a standardized flow cytometric technique, and compared with the results obtained from chronic lesions. RESULTS The migration of IDECs into the epidermis occurs within 72 hours and is thus an early event. It continues in chronic AD, but not in chronic CD, lesions. The specific upregulation of FcepsilonRI, especially on IDECs, occurs later during formation of extrinsic but not intrinsic AD lesions. LCs were negative for Cd36 in patch test lesions, whereas in chronic skin lesions, LCs expressed Cd36. CONCLUSION The DC alteration during skin lesion formation can be subdivided into early and late events, with the influx of IDECs as an early event and the alteration of the DC phenotype as a late event.
Thermal energy harvesting from human warmth for wireless body area network in medical healthcare system

In the medical healthcare system, wireless body area network (WBAN) is used to monitor the fall event of a patient by sensing his/her body state orientation (stand or fall posture). However, for a conventional WBAN, the only way to communicate with the doctors' computers or hospital's servers is through the local gateway. Hence, the reliability of the WBAN is greatly dependent on the life span of the gateway. In this paper, a selective gateway method based on the residual energy of the sensor nodes has been proposed. By changing the gateway, the lifetime of the WBAN can be extended. To further increase the lifetime of the WBAN, a thermal energy harvesting system has been proposed to harvest heat energy from human warmth. Energy harvested using the thermoelectric generator (TEG) is stored in an energy storage device until sufficient energy is available. Based on the experimental test results obtained, the accumulated energy is around 1.369 mJ to power the loads comprising of sensor, RF transmitter and its associated electronic circuits. The sensed information is transmitted in 5 digital words of 12-bit data across a transmission period of 120 msec. The receiver platform displays the patient identification number and sounds out an alarm buzzer for aid if a fall event is detected.
Postoperative recovery: a concept analysis.

AIM This paper presents a concept analysis of the phenomenon of postoperative recovery. BACKGROUND Each year, millions of patients throughout the world undergo surgical procedures. Although postoperative recovery is commonly used as an outcome of surgery, it is difficult to identify a standard definition. METHOD Walker and Avant's concept analysis approach was used. Literature retrieved from MEDLINE and CINAHL databases for English language papers published from 1982 to 2005 was used for the analysis. FINDINGS The theoretical definition developed points out that postoperative recovery is an energy-requiring process of returning to normality and wholeness. It is defined by comparative standards, achieved by regaining control over physical, psychological, social and habitual functions, and results in a return to preoperative level of independence/dependency in activities of daily living and optimum level of psychological well-being. CONCLUSION The concept of postoperative recovery lacks clarity, both in its meaning in relation to postoperative recovery to healthcare professionals in their care for surgical patients, and in the understanding of what researchers in this area really intend to investigate. The theoretical definition we have developed may be useful but needs to be further explored.
Winners and Losers in Flexible Labor Markets: The Fate of Women with Chronic Illness in Contrasting Policy Environments—Sweden and Britain

This study compares employment rates among men and women with and without chronic illness in the contrasting policy environments of Britain and Sweden, through analysis of household surveys for 1979–1995. Professional and managerial groups were winners in both countries, including during recession. By the 1990s, employment rates for healthy Swedish women were uniformly high across the social groups and almost comparable with those of their male counterparts; rates for women and men with a chronic illness were also comparable, albeit at a lower overall rate. The greatest losers were male and female unskilled manual workers in Britain. British women with a chronic illness in the 1990s had less than half the employment rates of healthy women. Such social inequalities were much smaller and less consistent in Sweden, where the impact of illness was softened for all social groups. In Britain, workless men tended to be classed as unemployed or permanently sick, while workless women were more likely to be classed as looking after home/family. Lesser differences were seen in Sweden. No evidence was found to support the hypothesis that women in general, and the less skilled and sick in particular, would be the winners in a more flexible, less regulated labor market—quite the reverse.