Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Associates with Huntingtin Protein and Promotes Its Atypical Ubiquitination to Enhance Aggregate Formation*

Huntington disease (HD) is a neurodegenerative disorder caused by an expansion of polyglutamines in the first exon of huntingtin (HTT), which confers aggregation-promoting properties to amino-terminal fragments of the protein (N-HTT). Mutant N-HTT aggregates are enriched for ubiquitin and contain ubiquitin E3 ligases, thus suggesting a role for ubiquitination in aggregate formation. Here, we report that tumor necrosis factor receptor-associated factor 6 (TRAF6) binds to WT and polyQ-expanded N-HTT in vitro as well as to endogenous full-length proteins in mouse and human brain in vivo. Endogenous TRAF6 is recruited to cellular inclusions formed by mutant N-HTT. Transient overexpression of TRAF6 promotes WT and mutant N-HTT atypical ubiquitination with Lys6, Lys27, and Lys29 linkage formation. Both interaction and ubiquitination seem to be independent from polyQ length. In cultured cells, TRAF6 enhances mutant N-HTT aggregate formation, whereas it has no effect on WT N-HTT protein localization. Mutant N-HTT inclusions are enriched for ubiquitin staining only when TRAF6 and Lys6, Lys27, and Lys29 ubiquitin mutants are expressed. Finally, we show that TRAF6 is up-regulated in post-mortem brains from HD patients where it is found in the insoluble fraction. These results suggest that TRAF6 atypical ubiquitination warrants investigation in HD pathogenesis.
Extraordinary Hall-effect sensor in split-current design for readout of magnetic field-coupled logic devices

This work demonstrates a novel extraordinary Hall-effect sensor which is designed to probe the magnetization state of micron-scale Co/Pt dots. The applied split-current geometry is well-suited for the electrical readout of field-coupled computing structures realized by focused ion (FIB) techniques. The electrically measured hysteresis loop is in good agreement with SQUID measured hysteresis curves of identical layer stacks. Full reversal in a perpendicular field causes an approximately 0.1 percent change in the Hall-resistivity of the film. We argue that this sensor is scalable all the way down to probe single domain Co/Pt dots with lateral dimensions of 200 nm middot 200 mn.
[Optimization of genomic DNA extraction with magnetic bead- based semi-automatic system].

OBJECTIVE To develop a rapid and effective method for genomic DNA extraction with magnetic bead-based semi-automatic system. METHODS DNA was extracted from whole blood samples semi-automatically with nucleic acid automatic extraction system.The concentration and purity of samples was determined by UV-spectrophotometer. Orthogonal design was used to analyze the main effect of lysis time, blood volume, magnetic bead quantity and ethanol concentration on the DNA yield; also the 2-way interaction of these factors. RESULTS Lysis time, blood volume, magnetic bead quantity and ethanol concentration were associated with DNA yield (P<0.05), but no interaction existed. DNA yield was higher under the condition with 15 min of lysis time, 100 μl of blood volume, 80 μl of magnetic beads and 80 % of ethanol. A significant association was found between the magnetic bead quantity and DNA purity OD260/OD280 (P=0.008). Interaction of blood volume and lysis time also existed (P=0.013). DNA purity was better when the extracting condition was 40 μl of magnetic beads, 15 min of lysis time and 100 μl of blood volume. Magnetic beads and ethanol concentration were associated with DNA purity OD260/OD230 (P=0.017 and P<0.05), the result was better when magnetic beads was 40 μl and ethanol concentration was 80 %. CONCLUSION The results indicate that the optimized conditions with 40 μl magnetic beads will generate higher quality of genomic DNA from the whole blood samples.
A compact three-bit reconfigurable resonator consisting of lumped elements

A two-stage three-bit reconfigurable bandpass filter (BPF) using branch-line type resonators has been proposed to achieve low insertion loss. However, it employed transmission line resonators and has limitation for miniaturization. This paper proposes a three-bit reconfigurable resonator consisting of lumped elements. The circuit replaces the short stub with a LC resonant circuit, while open stubs are substituted with parallel capacitors. A prototype resonator was designed and fabricated with 1005-size chip components. It shows insertion loss of less than 1.1 dB, which is close to that for the transmission line type reconfigurable resonator. The circuit area occupied by the lumped elements is less than 40% comparing with the conventional configuration using transmission lines.
Placement of Debt in Formal Corporate Groups in Sweden

The limited liability of group affiliated firms provides the group with an option of partial liquidation which has positive effects on the survival of groups. The option of partial liquidation also has a negative effect on the incentives of the parent firm (and ultimately the controlling shareholders). It exacerbates the asset substitution problem. Lenders being aware of this problem can be expected to require higher interest rates from group affiliated firms. One way, however, for the parent firm to commit to not taking advantage of partial liquidation is by placing more debt at the top of the group. I investigate the placement of debt in formal corporate groups in which the parent firms have very high ownership stakes in their subsidiaries. I argue that such firms have very high incentive to place debt strategically. I find the parent firms in my sample do indeed have higher leverage than their subsidiaries. The difference is not very large, however. Closer inspection reveals that the complexity and transparency of the group are very important influences on how debt is placed within groups. The size of the group and the amount of intra-group debt within the group are substantial negative influences on subsidiary debt. This is taken as indication that lenders in this situation face reduced transparency and cannot be sure where the funds they lend end up within the group.
Evaluation of the Effect of Acetyl L-Carnitine on Experimental Cisplatin Nephrotoxicity

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.
The Syndication Network and Deal Flow of Venture Capital Firms

This paper analyzes the positions that Venture Capital firms hold in a syndication network and determines the effect that network positions have on generating deal flow quantity and quality. Using data on syndicated investments in the German venture capital market and data on the deal flow of the firms, we show that those firms that hold network positions characterized by network openness have a higher deal flow quantity and quality.
Data-driven models for statistical testing: measurements, estimates and residuals

This paper is the second of a three paper series on statistical analysis of deep-submicron semiconductor test data. The subjects of this paper are the models and methods for computing healthy die estimates of the test response. Production data are used to demonstrate the ideas in this paper. The conceptual skeleton for the analysis is the computed difference between the measurement and a data-driven model of the healthy response. Uni-variate and multi-variate estimates are used to show the potential of the concept. Within the framework of estimating healthy response it is shown that significant reductions of distribution variance can be obtained with a corresponding improvement in outlier detection
Low Physical Activity Accentuates the Effect of the FTO rs9939609 Polymorphism on Body Fat Accumulation

OBJECTIVE—Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined. RESEARCH DESIGN AND METHODS—The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS—In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06–1.20], P = 9 × 10−5). This association was abolished when adjusting for BMI (1.06 [0.97–1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13–1.24], P = 1 × 10−12) and obesity (1.27 [1.20–1.34], P = 2 × 10−16). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 ± 0.3 kg/m2 increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS—We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.
Effects of chewing gum and time-on-task on alertness and attention

Abstract Rationale Chewing gum has been shown to reliably increase subjective alertness whereas the effects on attention are more variable. It has been suggested that chewing gum only enhances attention when the person has been performing a task for some time. Objectives The current research aimed to investigate if time-on-task trends enhancing effects of chewing gum could be observed in alertness and attention during and following chewing. Methods Study 1 used tests of reported mood, including reported mood, and tests of attention (categoric search, focussed attention, simple reaction time, and vigilance). These tasks were performed shortly after the start of chewing. Study 2 examined effects of previous and current chewing on reported alertness and the attention tests. Results Study 1 showed that chewing gum increased reported alertness and hedonic tone and improved performance on the categoric search task. Chewing gum maintained reported alertness across sessions in study 2. In the first experimental session of study 2 gum improved categoric search performance, and during the second session gum broadened focus of attention and quickened vigilance reaction time. This effect on vigilance reaction time was moderated by time-on-task, with an initial negative effect being replaced by a positive effect. Discussion The results confirm the robust effect of chewing gum on reported alertness and show that changes in the effects of chewing gum on attention require further investigation. Future research may also determine underlying mechanisms for an alerting effect.
PRIVATIZATION OF TRANSIT SERVICES BETWEEN SUBURBAN COMMUNITIES IN THE DETROIT METROPOLITAN AREA: A MARKETING APPROACH. FINAL REPORT

Widely dispersed travel patterns in metropolitan centers and increasing operating expenses along with serious financial problems to public transportation agencies generated this research study. The purpose of this research was to develop a testing procedure for privatizing transit services between suburban centers in large metropolitan cities. The Detroit metro area was selected as the case study site for this proposed methodology since it represented the changing urban structures and dispersed travel patterns of contemporary metropolitan areas in the U.S. Basically, the research approach centered around 4 major elements: Market identification; Assessing private provider interest; Matching markets with providers; and Development of operating plans. A methodology incorporating these 4 elements was developed, documented and applied to the Detroit suburban area, focusing mainly on travel demands between suburban communities in the three-county Detroit metro area. The research analysis resulted in a total of 53 candidate markets, and narrowed down to 14 potential markets by two independent priority ranking procedures. Matching of provider interest with merged multiple markets resulted in the identification of 5 viable sectors where privatizing transit services appeared feasible. This report provides a list of references, the Private Provider Survey, and numerous charts ranging from revenue and operating expenses, to worktrips, ridership and population, to market groups, service rankings, growth factor data, farebox revenue data and other.
Assessing Intimate Partner Violence in Health Care Settings Leads to Women's Receipt of Interventions and Improved Health

Objective. This study investigated whether disclosure of violence to health care providers and the receipt of interventions relate to women's exit from an abusive relationship and to their improved health. Methods. A volunteer sample of 132 women outpatients who described intimate partner violence during the preceding year were recruited from multiple hospital departments and community agencies in suburban and urban metropolitan Boston. Through in-person interviews, women provided information on demographics, past year exposure to violence, past year receipt of interventions, and whether they disclosed partner violence to their health care provider. They also described their past month health status with the 12-Item Short-Form Health Survey and further questions. Results. Of the 132 women, 44% had exited the abusive relationship. Among those who were no longer with their partner, 55% received a domestic violence intervention (e.g. advocacy, shelter, restraining order), compared with 37% of those who remained with their partner. Talking to their health care provider about the abuse increased women's likelihood of using an intervention (odds ratio [OR]=3.9). Those who received interventions were more likely to subsequently exit (OR=2.6) and women no longer with the abuser reported better physical health based on SF-12 summary scores (p=0.05) than women who stayed. Conclusions. Health care providers may make positive contributions to women's access to intimate partner violence services. Intimate partner violence interventions relate to women's reduced exposure to violence and better health.
Properties of a unique form of the murine amphotropic leukemia virus receptor expressed on hamster cells

Identification and cloning of the receptors for amphotropic murine leukemia virus (A-MuLV) and gibbon ape leukemia virus (GaLV) have both enabled the determination of the normal function of these virus receptors in cells and initiated experimental examination of how these receptors interact with their respective viruses. GaLV and A-MuLV have distinct host ranges and use different receptors to infect human cells. It was therefore surprising to find that the human GaLV and A-MuLV receptors were not only structurally similar but performed similar cellular functions (B. O'Hara, S. V. Johann, H. P. Klinger, D. G. Blair, H. Rubinson, K. J. Dunn, P. Sass, S. M. Vitek, and T. Robbins, Cell Growth Differ. 1:119-127, 1990; M. van Zeijl, S. V. Johann, E. Closs, J. Cunningham, R. Eddy, T. B. Shows, and B. O'Hara, Proc. Natl. Acad. Sci. USA 91:1168-1172, 1994; M. P. Kavanaugh, D. G. Miller, W. Zhang, W. Law, S. L. Kozak, D. Kabat, and A. D. Miller, Proc. Natl. Acad. Sci. USA 91:7071-7075, 1994; and Z. Olah, C. Lehel, W. B. Anderson, M. V. Eiden, and C. A. Wilson, J. Biol. Chem., in press). We have now determined that the murine retrovirus 10A1 can use both the human GaLV receptor and the human A-MuLV receptor to infect cells. Furthermore, we have cloned and functionally characterized a unique form of the amphotropic receptor homolog expressed in E36 hamster cells. This receptor (EAR) can serve as both a GaLV receptor and an A-MuLV receptor, and it therefore differs from the receptors expressed in human cells, which function exclusively as either GaLV or A-MuLV receptors.
Can finite‐frequency effects be accounted for in ray theory surface wave tomography?

We present a series of synthetic tests showing that regional surface wave tomographies with a dense path coverage of the target region can be safely conducted under ray theory because the shortcomings of ray theory in considering finite‐frequency effects can be counterbalanced by a physically‐based regularization of the inversion. In particular, we show that with ray theory applied under the above conditions, it is possible to detect heterogeneities with length scales smaller than the wavelength of the data set.
New Challenges for Performance Management: Exploratory Evidence on Organisational Responses to Identity Fraud

Available evidence indicates that identity fraud is a significant risk to organisations. Despite this, a lack of research exists on the role of performance measurement and costing systems in supporting organisational responses to this problem. This paper presents exploratory evidence on the challenges for performance measurement and costing systems if organisational responses to the identity fraud problem are to prove effective.
Molecular Crosstalk between HIV-1 Integration and Host Proteins – Implications for Therapeutics

The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS), which is one of the leading causes of infectious disease-related mortality worldwide (UNAIDS, 2010). An HIV infection is a chronic disease. While there is no regimen to eradicate the HIV from an infected person, there are more than 20 drugs approved for the treatment of HIV infection, the majority of which target viral reverse transcriptase (RT) and protease (PR). In addition to the development of chemotherapeutic agents such as RT and PR inhibitors (RTI and PI), the advent of the combination therapy of different classes of antiviral drugs, the highly active antiretroviral therapy (HAART), has brought a significant decrease in the morbidity and mortality associated with HIV infections for over a decade. Nowadays, HAART is a standard treatment for HIV infection and AIDS (Palella et al., 1998). However, despite the successful suppression of HIV RNA detected in plasma over prolonged periods of time and a dramatic decrease in patient mortality, HAART is still facing problems, including the emergence of drug resistant viruses and serious side effects in treated individuals. In addition, current treatments only suppress the HIV replication, and eradication of virus from the body cannot be achieved. Therefore, considerable efforts have been made to develop novel anti-HIV drugs that exhibit entirely distinct mechanisms of action. To date, three additional classes of inhibitors have been approved by the US Food and Drug Administration (FDA) as oral antiHIV agents: a fusion inhibitor blocking the fusion step of the viral and cellular membranes, an entry inhibitor targeting coreceptor binding by the virus, and an integrase (IN) inhibitor blocking the integration step of viral DNA. Although many promising inhibitors against HIV replication have arisen over recent years, the current approach in anti-HIV chemotherapy is mostly based on competitive agents targeting the active sites of viral enzymes or the binding pockets of cellular receptors. One of the drawbacks of existing drugs, particularly the antivirals exhibiting allosteric effects, is the rapid emergence of mutant HIV strains resistant to the drugs due to the innately high mutational rate in of viral enzymes. On the other hand, it is becoming increasingly clear that protein-protein interactions (PPIs) could also serve as attractive targets of drugs for human
Palliative care clinical research networks, a requirement for evidence-based palliative care: time for coordinated action.

ACOMPREHENSIVE RESEARCH NETWORK is critical to facilitate the clinical studies needed to improve our evidence base in palliative care. Such a network should have the capacity to review and respond to varied research requests ranging from practice surveys and quality projects to authoritative randomized controlled trials, with infrastructure to meet approved protocols efficiently and effectively. Participating sites should represent varied skills, demographics, practice patterns, and health delivery systems to be able to match study sites to the needs of the particular research study and broadly represent the populations for whom we provide care. Palliative care still lacks such a research network, limiting our capacity to complete studies, rigorously test our interventions, and ensure generalizability of study findings. As a first step, we must develop an understanding of current capacity within potential study sites, in terms of organizational ability to conduct research and translate research into practice, as well as identify opportunities to increase this capacity.
Improved plasma culture system for production of erythrocytic colonies in vitro: quantitative assay method for CFU-E.

An improved plasma culture system is described for the production of erythrocytic colonies by mammalian adult hemopoietic cells in vitro under the influence of erythropoietin. The concentration of fetal calf serum in the medium used for dilution of the cells was critical for erythrocytic colony formation when low numbers of cells were plated. Optimal concentrations were found for plasma, fetal calf serum, bovine serum albumin, and L-asparagine in the culture medium, and the colony-forming efficiency was shown to depend on the concentration of erythropoietin. With erythropoietin at plateau concentration, the number of erythrocytic colonies produced was directly proportional to the number of bone marrow or spleen cells plated, over a wide range of cell concentrations. Colony numbers per culture conformed to a Poisson distribution. Thus, the improved plasma culture system may be used for the quantitative assay of CFU-E. The method is rapid (2 days), reliable, convenient, and inexpensive. Since the improved plasma culture system also supports granulocytic colony formation by bone marrow cells in the presence of conditioned medium (CSA), and the number of granulocytic colonies produced is proportional to the number of cells plated, the same hemopoietic cell suspensions can be simultaneously assayed for CFU-E and CFU-C under virtually identical conditions.