Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Arsenic-Thiol Interactions in Metalloregulation of the ars Operon (*)

The ars operon of the Escherichia coli plasmid R773 that confers arsenical and antimonial resistance is negatively regulated by the ArsR repressor. ArsR residues Cys-32 and Cys-34 were previously identified as involved in induction by arsenite and antimonite, suggesting coordination between As(III) and the two cysteine thiolates. However, in small molecule thiolate-As(III) complexes, arsenic is frequently three-coordinate. A site-directed mutagenic approach was employed in a search for a third arsenic ligand. ArsR proteins with C32G, C34G, and C32G/C34G substitutions were active repressors, but were not inducible in vivo. In vitro, the altered repressor-ars DNA complexes could not be dissociated by inducers. Alteration of Cys-37 and Ser-43, residues located in or near the putative helix-turn-helix DNA-binding region of the protein, had no effect on the inducibility of the operon. While these results indicated that neither the thiolate of Cys-37 nor the hydroxyl oxygen of Ser-43 is required for induction, they did not eliminate either atom as a potential arsenic ligand. Another approach involved reaction with an alternative inducer, phenylarsine oxide, which can form only two coordinations. Phenylarsine oxide was shown to be as effective as or more effective than arsenite or antimonite in induction in vivo. In vitro, the organic arsenical was more effective than either arsenite or antimonite in dissociating the repressor-promoter complex. Thus, two ArsR-arsenic bonds are sufficient for induction. The interaction of ArsR proteins with As(III) was examined using a phenylarsine oxide affinity resin. ArsR proteins containing any two of the three cysteine residues Cys-32, Cys-34, and Cys-37 bound to the resin. Alteration of any two of the three resulted in loss of binding. Arsenic x-ray absorption spectroscopy of ArsR treated stoichiometrically with arsenite confirmed the average arsenic coordination as AsS. These results suggest that all three cysteine thiolates are arsenic ligands, but binding to only two, the Cys-32 and Cys-34 thiolates, is required to produce the conformational change that results in release of the repressor from the DNA and induction.
Kids R Us: Online Social Networking and the Potential for Empowerment

Our paper examines the dynamic of surveillance and empowerment from a theoretical perspective, identifies illustrative empirical examples, and perhaps most importantly investigates the practices that maximize the empowerment potential and minimize threats to that potential.In particular, we seek to understand the ways in which young people have adopted or adapted online media in order to deepen their social experiences, build community, and resist measures that seek to limit their online speech and access to information.We posit that there are four different models of the relationship between surveillance and empowerment in the context of young people on social networking sites (SNS). We introduce each of these with a discussion of the dynamic between surveillance and empowerment in each model and some representative examples.Finally, we explore whether there are particular conditions which permit empowerment to emerge in a surveillance environment.
Is Word Recognition Correlated With the Number of Surviving Spiral Ganglion Cells and Electrode Insertion Depth in Human Subjects With Cochlear Implants?

Objectives/Hypothesis: Speech perception scores using cochlear implants have ranged widely in all published series. The underlying determinants of success in word recognition are incompletely defined. Although it has been assumed that residual spiral ganglion cell population in the deaf ear may play a critical role, published data from temporal bone specimens from patients have not supported this hypothesis. The depth of insertion of a multichannel cochlear implant has also been suggested as a clinical variable that may be correlated with word recognition. In the current study these correlations were evaluated in 15 human subjects.
Piercing the Veil of Executive Turnover: Evidence from Downward Restatement Firms

Understanding the factors affecting executive turnover is particularly important, because it sheds light on to what extent such turnovers serves as an effective corporate monitoring and governance tool. Using hand-collected data to control firm-specific restatement characteristics, we examine how the likelihood of executive turnover is associated with other corporate governance variables for restatement firms. We find the likelihood of executive turnover increases with restatement severity, downward credit rating, large board size, and independent board members, but decreases with the dismissal of external auditors. Our results hold regardless whether the restatement is prompted by the company itself or other parties (e.g. auditors, regulators). In addition, our main evidence is more pronounced post – Sarbanes Oxley Act (SOX), consistent with the argument that board of directors use job termination more frequently to deal with management dereliction and to signal their commitment in enhancing corporate governance post-SOX. Our paper provides insights on intricacy among corporate governance schemes, and contributes to reconcile inconsistent conclusions in prior studies regarding the effect of restatement on executive turnovers.
A novel three-phase three-port UPS employing a single high-frequency isolation transformer

A three-phase PWM rectifier and a three-phase PWM inverter are coupled via two four-quadrant full-bridge converter cells and a high-frequency isolation transformer. By employing a third transformer winding and further full-bridge cell battery energy storage is incorporated into the power transfer between rectifier and inverter resulting in a three-port UPS concept. The phase shift control of the power flow between the ports is analyzed for square-wave operation of the full-bridge cells. Furthermore, the utilization of the degrees of freedom of the system control, i.e. the extension to duty cycle control for optimizing the system behavior is discussed and control laws ensuring minimum overall system losses are derived. Finally, a control-oriented converter model is proposed and the decoupled control of the power flow of the ports is treated briefly. All theoretical considerations are verified by simulations using PSIM.
Mechanism of protein phosphatase-2Aregulating phosphorylation of amyloid precursor proteosome and Aβ generation.

OBJECTIVE To discuss whether PP-2A influences the phosphorylation level at APP threonine 668 locus thus regulating Aβ secretion. METHOD In the experiment, 24 hours after N2a cells of stably transfected human APP (N2a/APP) were treated with okadaic acid (OA) or DES (C6-ceramide) (N2a/APP), an injection of OA cerebral stereotactic was administered to a SD rat in the hippocampal region, or PP-2A overexpressed plasmids was transfected transiently, the aggregate levels of APP phosphorylated APP, and APP-CTF were detected through immunoblotting and the activity of PP-2A and secretase was also detected using a reagent kit. RESULT The phosphorylation level of APP was significantly increased after the PP-2A activity was inhibited by OA. DES activated PP-2A or over-expressed PP-2A was able to reduce the phosphorylation level of APP. Either can inhibit PP and reduce the phosphorylation level of APP. The level of phosphorylated APP was increased significantly after the SD rat was injected with OA through the hippocampal region. The activity of β- and γ-secretases in N2a/APP cells significantly increased after OA treatment whereas the α-secretase activity had no significant changes; the Aβ level increased. CONCLUSION We discovered that PP-2A was capable of regulating the Aβ level by regulating APP phosphorylation level and β and γ-secretase activity(Fig. 5, Ref. 30).
Extremely high levels of melanoma in Tauranga, New Zealand: Possible causes and comparisons with Australia and the northern hemisphere

The objective of the study was to determine the incidence of melanoma in the Tauranga region of New Zealand, to compare these findings within Australasia and the northern hemisphere, and to understand the causes of the relatively high rates in Tauranga. Data were obtained from retrospective review of histology reports from the public and private health systems in greater Tauranga (Tauranga and Western Bay of Plenty Districts). Primary cutaneous melanomas (including both invasive and in situ melanomas) reported during 2003 were included. Age‐standardized melanoma rates were calculated for the entire population as well as for the non‐Maori population of the region, identified from the 2001 New Zealand Census. The age‐standardized incidence of invasive melanoma in the non‐Maori population of the greater Tauranga region was 79/100 000. The age‐standardized rate for the entire population was 70/100 000. The rate of in situ disease was 78/100 000 for non‐Maori and 72/100 000 for the entire population. The Tauranga region of New Zealand has an exceptionally high incidence of invasive and in situ melanomas. This is likely related to environmental, geographical and societal factors, including relatively high levels of UV exacerbated in recent times by ozone depletion, relatively cool summer temperatures which encourage outdoor exposure, and relatively fair skin colouring.
Using Sentiment Analysis to track reaction to the Global Game Jam Theme

In this paper, we examine the Global Game Jam Theme and the reaction of the 'jammers' to the release. The Theme is one of the main drivers for creative aspect of the Game Jam, it sets the tone of the games that are developed at the Jam. This paper introduces an experiment which uses 'sentiment analysis' to gauge the positive or negative reaction to the theme over the last 7 years of the Global Game Jam. The results of this study show that the 2012 theme had the the highest sentiment. Finally, we suggest that the 'sentiment analysis' or 'context analysis' could be used to gather data sets for other studies such as development practices.
What are Best Practices for Retaining Employees During Mergers and Acquisitions

The purpose of this report is to guide decision makers at this company, by offering the most recent theories and practices regarding talent retention programs. Recently mergers and acquisitions have become a major part of global business. During the M&A, it is important to manage the organizational and human resource issues. Our team focused on gathering real business cases. Then we highlight some suggestions from the best practices to create successful M&A. It is our intent that the research findings in this report will help to enlighten and inform the company’s leaders to guide the effective human management program centered on key talent, ultimately leading to organizational success.
On-Chip Process Variation Detection Using Slew-Rate Monitoring Circuit

The need for efficient and accurate detection schemes to mitigate the impact of process variations on the parametric yield of integrated circuits has increased in the nm design era. In this paper, a new variation detection technique is presented that uses slew as a metric along with delay to determine the mismatch between the drive strengths of NMOS and PMOS devices. The importance of considering both of these metrics is illustrated and a new slew-rate monitoring circuit is presented for measuring slew of a signal from the critical path of a circuit. Design considerations, simulation results and characteristics of the slew-rate monitor circuitry in a 45 nm SOI technology are presented, and a sensitivity of 1 MHz/ps is achieved. This scheme can detect the threshold voltage variation in the order of mV, with a sensitivity of 0.95 MHz/mV.
Phospholipid Hydroperoxides Are Substrates for Non-selenium Glutathione Peroxidase*

This study investigated phospholipid hydroperoxides as substrates for non-selenium GSH peroxidase (NSGPx), an enzyme also called 1-Cys peroxiredoxin. Recombinant human NSGPx expressed in Escherichia coli from a human cDNA clone (HA0683) showed GSH peroxidase activity withsn-2-linolenoyl- orsn-2-arachidonoyl-phosphatidylcholine hydroperoxides as substrate; NADPH or thioredoxin could not substitute for GSH. Activity did not saturate with GSH, and kinetics were compatible with a ping-pong mechanism; kinetic constants (mM−1min−1) were k 1 = 1–3 × 105 and k 2 = 4–11 × 104. In the presence of 0.36 mm GSH, apparentK m was 120–130 μm and apparentV max was 1.5–1.6 μmol/min/mg of protein. Assays with H2O2 and organic hydroperoxides as substrate indicated activity similar to that with phospholipid hydroperoxides. Maximal enzymatic activity was at pH 7–8. Activity with phospholipid hydroperoxide substrate was inhibited noncompetitively by mercaptosuccinate with K i 4 μm. The enzyme had no GSH S-transferase activity. Bovine cDNA encoding NSGPx, isolated from a lung expression library using a polymerase chain reaction probe, showed >95% similarity to previously published human, rat, and mouse sequences and does not contain the TGA stop codon, which is translated as selenocysteine in selenium-containing peroxidases. The molecular mass of bovine NSGPx deduced from the cDNA is 25,047 Da. These results identify a new GSH peroxidase that is not a selenoenzyme and can reduce phospholipid hydroperoxides. Thus, this enzyme may be an important component of cellular antioxidant defense systems.
Translational Insights Into Peroxisome Proliferator-Activated Receptors in Experimental Acute Pancreatitis

Abstract Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas frequently associated with metabolic causes, contributing factors, or consequences, including hypertriglyceridemia, obesity, and disorders of intermediary metabolism, respectively. To date, there is no specific therapy for this disease. Future optimal therapy should correct both inflammatory and metabolic components of the disease. Peroxisome proliferator-activated receptors (PPARs) are lipid-sensing nuclear receptors that control inflammatory and metabolic pathways via ligand-dependent and ligand-independent mechanisms. There are 3 known subtypes, PPAR-&agr;, PPAR-&bgr;/&dgr;, and PPAR-&ggr;, which are differentially expressed in various tissues. The PPARs interact closely with other transcription factors such as nuclear factor &kgr;B and signal tranducers and activators of transcription that have pivotal roles in the pathobiology of AP. In this comprehensive review, we summarize the role of PPARs in AP, highlighting important in vitro and in vivo experimental findings. Finally, we propose future research directions as well as potential translational use of PPAR agonists in the treatment of AP.
Purification and Properties of Wild-type and Exonuclease-deficient DNA Polymerase II from Escherichia coli(*)

Wild-type DNA polymerase II (pol II) and an exonuclease-deficient pol II mutant (D155A/E157A) have been overexpressed and purified in high yield from Escherichia coli. Wild-type pol II exhibits a high proofreading 3′-exonuclease to polymerase ratio, similar in magnitude to that observed for bacteriophage T4 DNA polymerase. While copying a 250-nucleotide region of the lacZα gene, the fidelity of wild-type pol II is high, with error rates for single-base substitution and frameshift errors being ≤10. In contrast, the pol II exonuclease-deficient mutant generated a variety of base substitution and single base frameshift errors, as well as deletions between both perfect and imperfect directly repeated sequences separated by a few to hundreds of nucleotides. Error rates for the pol II exonuclease-deficient mutant were from ≥13- to ≥240-fold higher than for wild-type pol II, depending on the type of error considered. These data suggest that from 90 to >99% of base substitutions, frameshifts, and large deletions are efficiently proofread by the enzyme. The results of these experiments together with recent in vivo studies suggest an important role for pol II in the fidelity of DNA synthesis in cells.
Internet security games as a pedagogic tool for teaching network security

This research investigates the suitability of online security games as a pedagogic tool, for teaching network security in an educational framework. Based on the advanced challenges they provide, we have selected security games offered by Next Generation Security. Our research is based on network security principles, a core module in MSc Network Security at Anglia Polytechnic University. We compare two cohorts; both were given lectures and laboratory sessions. Only for the second group laboratory sessions were conducted by means of security games. We consider the game usage and views expressed by lecturers and students, to assess whether this method can be usefully incorporated in teaching specific sections of information security. Online and offline course feedback and interviews are used to assess the student experience. Quantitative and qualitative data gathered from this empirical study is analysed to derive conclusions. Advantages, discontents and educational concerns of this method are discussed. Deviation from current learning paradigms is addressed, in relation to the use of pure Internet based tools
Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate.

OBJECTIVE Depressed men commonly have erectile dysfunction, and men with erectile dysfunction are frequently depressed. Since the etiologic and modulatory relationships between depression and erectile dysfunction have been poorly characterized, a 12-week, randomized, double-blind, placebo-controlled trial was conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment in men with erectile dysfunction and mild-to-moderate comorbid depressive illness. METHOD Men (N=152, mean age=56 years) with erectile dysfunction for > or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean at baseline=16.9) were randomly assigned to flexible-dose treatment with sildenafil citrate or matching placebo. Interviewer-rated and self-report instruments were used to assess changes in sexual function, depressive symptoms, and quality of life. Conservative criteria were used to classify erectile dysfunction treatment response and nonresponse. RESULTS Sildenafil was strongly associated with erectile dysfunction treatment response. Fifty-eight men met the conservative criteria for response (48 given sildenafil, 10 given placebo), and 78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of 10.6 and 2.3 in Hamilton depression scale scores were seen in treatment responders and nonresponders, respectively; 76% of treatment responders showed a > or =50% decline in Hamilton depression scale score versus 14% of nonresponders. Quality of life was similarly improved in treatment responders. CONCLUSIONS Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life.
Synthesis of a novel hepatitis C virus protein by ribosomal frameshift

Hepatitis C virus (HCV) is an important human pathogen that affects ∼100 million people worldwide. Its RNA genome codes for a polyprotein, which is cleaved by viral and cellular proteases to produce at least 10 mature viral protein products. We report here the discovery of a novel HCV protein synthesized by ribosomal frameshift. This protein, which we named the F protein, is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frameshift into the −2/+1 reading frame. This ribosomal frameshift requires only codons 8–14 of the core protein‐coding sequence, and the shift junction is located at or near codon 11. An F protein analog synthesized in vitro reacted with the sera of HCV patients but not with the sera of hepatitis B patients, indicating the expression of the F protein during natural HCV infection. This unexpected finding may open new avenues for the development of anti‐HCV drugs.
[Chemical constituents from the fruits of Areca catechu].

OBJECTIVE To investigate the chemical constituents of the fruits of Areca catechu. METHODS The chemical constituents were isolated by silica gel, RP-18 and Sephadex LH-20 column chromatographies. Their structures were determined by chemical and spectroscopic methods. RESULTS Thirteen compounds were isolated from the 95% ethanol extract of the fruits of Areca catechu. Their structures were identified as isorhamnetin (1), quercetin (2), liquiritigenin (3), 5,7,4'-trihydroxy-3',5'-dimethoxyflavanone (4), (+)-catechin (5), resveratrol (6), ferulic acid (7), vanillic acid (8), 5,8-epidioxiergosta-6,22-dien-3beta-ol (9), stigmasta-4-en-3-one (10), beta-sitosterol (11), cycloartenol (12), and de-O-methyllasiodiplodin (13), respectively. CONCLUSION Compounds 2-4,6,7,9,10, 12,13 are isolated from this plant for the first time.
Failure of Vancomycin Continuous Infusion against Experimental Endocarditis Due to Vancomycin-Intermediate Staphylococcus aureus

ABSTRACT Continuous infusion of vancomycin was evaluated against experimental endocarditis due to heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA. Animals were infected with hVISA PC1 (vancomycin MIC, 2 mg/liter) or VISA PC3 (vancomycin MIC, 8 mg/liter) and treated for 5 days with constant serum levels of 20 or 40 mg/liter. Vancomycin continuous infusion was unsuccessful, as 20 mg/liter was barely active against PC1 (6 of 13 sterile vegetations) and 40 mg/liter failed against PC3 (2 of 9 sterile vegetations).