Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of the Drug–Excipient Ratio in Matrix-Type-Controlled Release Systems: Computer Simulation Study

The main objective of this work is to study the drug release behavior from inert matrix systems by using computer simulation. This study allowed us to propose a new statistical method to evaluate the drug percolation threshold as a function of the exposed surface area of the device. The matrix system was simulated as a simple cubic lattice. The sites of the lattice were randomly occupied at various drug–excipient ratios. By simulating a diffusive process, the drug was delivered from the matrix system. The obtained release profiles were fitted to two different models: near the excipient percolation threshold, the square root of the time was well fitted, whereas close to (but above) the drug percolation threshold, the power law described accurately the release data. A relationship between the initial drug load and the amount of drug trapped inside the matrix system at infinite time was found. This relationship was conveniently described by an error function. Percolation thresholds in the matrix systems were determined from the latter relationship by using a nonlinear regression method. The assessment of percolation thresholds depends on the exposed surface area of the matrix systems. Moreover, estimated percolation thresholds were in agreement with the predicted values stated in the percolation theory.
Functional interaction of syntaxin and SNAP‐25 with voltage‐sensitive L‐ and N‐type Ca2+ channels.

We have used an electrophysiological assay to investigate the functional interaction of syntaxin 1A and SNAP‐25 with the class C, L‐type, and the class B, N‐type, voltage‐sensitive calcium channels. Co‐expression of syntaxin 1A with the pore‐forming subunits of the L‐ and N‐type channels in Xenopus oocytes generates a dramatic inhibition of inward currents (>60%) and modifies the rate of inactivation (tau) and steady‐state voltage dependence of inactivation. Syntaxin 1–267, which lacks the transmembrane region (TMR), and syntaxin 2 do not modify channel properties, suggesting that the syntaxin 1A interaction site resides predominantly in the TMR. Co‐expression of SNAP‐25 significantly modifies the gating properties of L‐ and N‐type channels and displays modest inhibition of current amplitude. Syntaxin 1A and SNAP‐25 combined restore the syntaxin‐inhibited N‐type inward current but not the reduced rate of inactivation. Hence, a distinct interaction of a putative syntaxin 1A‐SNAP‐25 complex with the channel is apparent, consistent with the formation of a synaptosomal SNAP receptors (SNAREs) complex. The in vivo functional reconstitution: (i) establishes the proximity of the SNAREs to calcium channels; (ii) provides new insight into a potential regulatory role for the two SNAREs in controlling calcium influx through N‐ and L‐type channels; and (iii) may suggest a pivotal role for calcium channels in the secretion process.
Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors

The properties of several multitargeted receptor tyrosine kinase inhibitors have been studied for their inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling. A structurally novel, multitargeted tyrosine kinase inhibitor (ABT-869), imatinib (STI571), and four compounds currently in clinical development (AG013736, BAY 43-9006, CHIR258, and SU11248) were tested for inhibition of CSF-1R signaling in both the enzymatic and cellular assays. ABT-869 showed potent CSF-1R inhibition in both the enzyme and cell-based assays (IC50s < 20 nmol/L). In contrast to a previous report, we have found that imatinib has activity against human CSF-1R in both assays at submicromolar concentrations. In enzyme assays, we have found that the inhibition of CSF-1R by both ABT-869 and imatinib are competitive with ATP, with Ki values of 3 and 120 nmol/L, respectively. SU11248 is a potent inhibitor of CSF-1R in the enzyme assay (IC50 = 7 nmol/L) and inhibits receptor phosphorylation in the cellular assay (IC50 = 61 nmol/L). AG013736 was also a potent inhibitor of CSF-1R in both assays (enzyme, IC50 = 16 nmol/L; cellular, IC50 = 21 nmol/L), whereas BAY 43-9006 is less potent in the enzyme assay (IC50 = 107 nmol/L) than in the cellular system (IC50 = 20 nmol/L). In contrast, we found that CHIR258 had less activity in the cellular assay (IC50 = 535 nmol/L) relative to its enzymatic potency (IC50 = 26 nmol/L). These results show the use of a cell-based assay to confirm the inhibitory activity of lead compounds and drug candidates, such as ABT-869, against the CSF-1R protein in situ. [Mol Cancer Ther 2006;5(4):1007–13]
Boceprevir: a novel nonstructural 3 (NS3) protease inhibitor for the treatment of chronic hepatitis C infection

Chronic hepatitis C infection is a leading cause of morbidity and mortality worldwide, with hepatitis C related cirrhosis being the most common indication for transplant and a major cause for the increase in hepatocellular carcinoma worldwide. Treatment for hepatitis C has consisted of nonspecific immunomodulatory therapies that stimulate the immune system and inhibit hepatitis C replication. Pegylated (peg-)interferon and ribavirin have been the standard of care with an overall sustained response rate of 40–50% in patients with genotype 1 infection, and 80% in genotype 2 or 3. Recently, direct-acting antiviral agents, including boceprevir, have demonstrated improved sustained response rates in patients with genotype 1 infection when given in combination with interferon and ribavirin. Boceprevir is a structurally novel hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor that has demonstrated robust antiviral activity in HCV replicons. Clinically, in phase II and III trials, boceprevir 800 mg three times daily with peginterferon and ribavirin has led to improved sustained response rates in genotype 1 infection treatment-naive patients, relapsers, partial responders, and null responders. Phase II data have demonstrated that ribavirin is essential for optimal boceprevir response. Moreover, phase II data have suggested that a 4-week peginterferon or ribavirin lead-in strategy may reduce relapse rates and provide crucial on-treatment data for treatment response with boceprevir addition. Side effects of boceprevir when added to peginterferon and ribavirin are similar to peginterferon and ribavirin, though higher rates of anemia have been noted, with an incremental increase in erythropoietin use. The addition of boceprevir represents a major advance in patients with genotype 1 infection who are treatment naïve.
Oral administration of tea saponins to relive oxidative stress and immune suppression in chickens

ABSTRACT The present study was designed to evaluate the effects of tea saponins on oxidative stress induced by cyclophosphamide in chickens. One hundred twenty chickens were randomly divided into 5 groups. Groups 3 to 4 received intramuscular injection of cyclophosphamide to induce oxidative stress and immunosuppression. After that, groups 2 and 4 were orally administered tea saponins in drinking water for 7 d. Then, groups 1 to 4 were immunized with a live, bivalent vaccine of Newcastle disease virus and infectious bronchitis virus. Blood samples were collected for analysis of oxidative parameters and specific antibody titers, and splenocytes were prepared for lymphocyte proliferative assay. The results showed that administration of tea saponins significantly increased total antioxidant capacity, total superoxide dismutase, catalase, glutathione peroxidase, glutathione, ascorbic acid, and &agr;‐tocopherol, and decreased malondialdehyde and protein carbonyl. Enhanced immune responses, such as lymphocyte proliferation induced by concanavalin A and lipopolysaccharides, and serum Newcastle disease virus‐ and infectious bronchitis virus‐specific antibodies were also observed in chickens injected with or without cyclophosphamide. In addition, no side effects were found in chickens throughout the study. Therefore, tea saponins may be a potential agent to improve imunosuppression induced by oxidative stress in chickens.
A role for protein kinase C in a form of metaplasticity that regulates the induction of long‐term potentiation at CA1 synapses of the adult rat hippocampus

The possibility that protein kinase C (PKC) is involved in the induction of N‐methyl‐ D‐aspartate (NMDA) receptor‐dependent long‐term potentiation (LTP) at CA1 synapses in the hippocampus has been the subject of considerable investigation. However, many of the conclusions have been drawn from the use of relatively nonspecific PKC inhibitors. In the present study we have examined the role of PKC in tetanus‐induced LTP of AMPA receptor‐mediated synaptic transmission in hippocampal slices obtained from adult rats. In particular, we have investigated the possible role of PKC in a molecular switch process that is triggered by the synaptic activation of metabotropic glutamate receptors and regulates the induction of LTP. We find that the three PKC inhibitors examined, chelerythrine, Ro‐31–8220 and Gö 6983, all block the setting of the molecular switch at concentrations consistent with inhibition of PKC. In contrast, these inhibitors are without affect on the induction of LTP, even when applied in very much higher concentrations. A PKA inhibitor, Rp‐cAMPS, had no effect on either process. We suggest that neither PKC nor PKA is required to induce LTP at this synapse. However, PKC is involved in the regulation of LTP induction, via the molecular switch process.
Plasma ESD Qualification Test Procedure of Alcatel Alenia Space Solar Array

The detrimental effects of spacecraft charging are well known, particularly when the charging leads to arcing on solar array and, consequently, to permanent power loss. Motivated by these concerns, Alcatel Alenia Space has undertaken several test campaigns to qualify solar array design and to investigate margins. This paper describes the state-of-the-art Alcatel Alenia Space solar array electrostatic discharge laboratory test setup and procedure. The primary discharges are created using a plasma source and negative polarization of the sample rear side. The required power to feed the arc can be delivered by a solar array simulator with low-capacitance power sources. The test sample is fully representative of a flight model
Kathryn Sikkink, Mixed Signals: U.S. Human Rights Policy and Latin America. Ithaca: Cornell University Press, 2004. Tables, figures, notes, index, 288 pp.; hardcover $29.95.

of the privatization reforms were adopted and implemented. Without the Chile case, the number of full-scale reforms in both education and health sectors is not as representative of this type of reform. In addition, it is likely that the interests and frameworks used by the various authors of the case studies influenced their findings and limited the strength of comparative analysis. For instance, reviewing the two Mexico cases, one sees a very different vision of Mexican politics emerging in education and in health, only some of which is due to the difference of the sectors. However, there are inevitable trade-offs in putting together such a complex volume, and the editors and authors have provided a major contribution to a literature that has been in need of strong empirical work and a systematic approach to gleaning generalizations from complex and differing processes. This volume presents a wealth of information and advice for policymakers, reformers, consultants, and academics; a great source for good thinking about how to change policy in order to make significant changes in health and education systems. It is a rare compendium that merits careful reading and review. It suggests that policy reform is complex and that there is room for experimentation. Its generalizations and conclusions are guides to thinking but, as the authors acknowledge, not the last word in the complex world of political possibilities.
A feedback strategy to improve the entropy of a chaos-based random bit generator

In this paper, the guidelines to design a true random bit generator (TRBG) circuit with a predefined minimum entropy are discussed. The approach is proposed for a TRBG based on a one-dimensional piecewise-linear chaotic map; it does not require bit throughput reduction, and it is suitable for the development of integrated TRBG circuits. In particular, the proposed design strategy is based on a feedback control procedure that allows to dynamically change the system parameters for the correction of the circuit "nonidealities" (e.g., the circuit offsets). The correction algorithm does not require a direct measurement of the system "nonidealities" or of the effective value of the map parameters, but only a dynamic estimation of these quantities based on the observation of the TRBG output. The design approach is validated by a hardware prototype implemented on a field-programmable analog array. The results of the NIST FIPS 140-2 test suite, the DIEHARD test suite, and the Coron's Universal test, applied to the TRBG output sequences before and after a simple post processing without throughput reduction, are reported and discussed.
A Field Investigation of Bacillus anthracis Contamination of U.S. Department of Agriculture and Other Washington, D.C., Buildings during the Anthrax Attack of October 2001

ABSTRACT In response to a bioterrorism attack in the Washington, D.C., area in October 2001, a mobile laboratory (ML) was set up in the city to conduct rapid molecular tests on environmental samples for the presence of Bacillus anthracis spores and to route samples for further culture analysis. The ML contained class I laminar-flow hoods, a portable autoclave, two portable real-time PCR devices (Ruggedized Advanced Pathogen Identification Device [RAPID]), and miscellaneous supplies and equipment to process samples. Envelopes and swab and air samples collected from 30 locations in the metropolitan area once every three days were subjected to visual examination and DNA extraction, followed by real-time PCR using freeze-dried, fluorescent-probe-based reagents. Surface swabs and air samples were also cultured for B. anthracis at the National Veterinary Service Laboratory (NVSL) in Ames, Iowa. From 24 October 2001 to 15 September 2002, 2,092 pieces of mail were examined, 405 real-time PCR assays were performed (comprising 4,639 samples), and at the NVSL 6,275 samples were subjected to over 18,000 platings. None of the PCR assays on DNA extracted from swab and air samples were positive, but viable spores were cultured from surface swabs taken from six locations in the metropolitan area in October, November, and December 2001 and February, March, and May 2002. DNA extracted from these suspected B. anthracis colonies was positive by real-time and conventional PCRs for the lethal factor, pXO1, and for capA and vrr genes; sequence analysis of the latter amplicons indicated >99% homology with the Ames, vollum, B6273-93, C93022281, and W-21 strains of B. anthracis, suggesting they arose from cross-contamination during the attack through the mail. The RAPID-based PCR analysis provided fast confirmation of suspect colonies from an overnight incubation on agar plates.
Use of transdermal fentanyl without prior opioid stabilization in patients with cancer pain

SUMMARY Objective: To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare the effects on patients according to whether they had previously received strong opioids, weak opioids or non-opioid analgesia. Methods: Cancer patients requiring strong analgesia were recruited into an open-label, multicentre study, conducted in eight countries. Patients received transdermal fentanyl treatment for 28days. Pain severity, overall satisfaction with pain control, convenience of use of patches and treatment preferences were recorded daily. Results: Of the 292 participants, 135 had previously received a strong opioid, 84 had previously received a weak opioid and 73 had received no regular opioids. Thirty-eight patients did not complete the study, mainly due to adverse events. For all groups the proportion of patients with ‘good to excellent’ pain control increased after transdermal fentanyl treatment. Transdermal fentanyl was well tolerated, with the most common treatment-related adverse events being nausea, vomiting and constipation. The percentage of strong-opioid-tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly in the strong-opioid-naïve groups. Most patients rated the convenience of the patches as ‘good to excellent’, and most preferred transdermal fentanyl to their previous therapy. Conclusions: Transdermal fentanyl is an effective and well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously received opioids. Previous guidelines have often advocated initial dose finding with short-acting opioids but this study demonstrates that such a complex titration and conversion schedule may not be necessary, and that treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous analgesic therapy fails to provide adequate relief.
Ergonomics in Dentistry

ABSTRACT Ergonomics is much broader than preventing work‑related musculoskeletal disorders. The successful application of ergo‑ nomics assures high productivity, avoidance of illnesses and injuries, and increased satisfaction among workers. Unsuc‑ cessful application, on the other hand, can lead to work‑related musculoskeletal disorders (MSDs). This article sets forth broad important background information on ergonomics so that the dental practitioner can have a general awareness of ergonomic risk factors as well as some basis for understanding the ongo‑ ing dialogue about ergonomics, its diagnosis, treatment, and regulation. This article provides alternatives to be considered by the practitioner in light of the practitioner's own circumstances, experiences and goals. A practitioner wishing to improve his or her work environment, for whatever reason, may wish to follow an incremental approach to such efforts, as is briefy discussed here. How to cite this article: Gupta A, Bhat M, Mohammed T, Bansal N, Gupta G. Ergonomics in Dentistry. Int J Clin Pediatr Dent 2014;7(1):30-34.
RING Domain Mutations Uncouple TRIM5α Restriction of HIV-1 from Inhibition of Reverse Transcription and Acceleration of Uncoating

ABSTRACT Rhesus TRIM5α (TRIM5αrh) is a cytosolic protein that potently restricts HIV-1 at an early postentry stage, prior to reverse transcription. The ability of TRIM5αrh to block HIV-1 infection has been correlated with a decrease of pelletable HIV-1 capsid during infection. To genetically dissect the ability of TRIM5α to block reverse transcription, we studied a set of TRIM5αrh RING domain mutants that potently restrict HIV-1 but allow the occurrence of reverse transcription. These TRIM5αrh RING variants blocked HIV-1 infection after reverse transcription but prior to integration, as suggested by the routing of nuclear viral DNA to circularization in the form of 2-long terminal repeat (2-LTR) circles. The folding of RING domain variants was similar to that of the wild type, as evaluated by nuclear magnetic resonance. RING domain changes that allowed the occurrence of reverse transcription were impaired in their ability to decrease the amount of pelletable capsid compared with wild-type TRIM5α. Similar effects of this particular group of mutations were observed with human TRIM5α inhibition of N-tropic murine leukemia virus (N-MLV). Interestingly, TRIM5αrh RING domain variants also prevented the degradation of TRIM5αrh that occurs following cell entry of HIV-1. These data correlated the block of reverse transcription with the ability of TRIM5α to accelerate uncoating. Collectively, these results suggest that TRIM5αrh blocks HIV-1 reverse transcription by inducing premature viral uncoating in target cells.
Social Change Model of Leadership Development: A 4-Year Program

The social change model (SCM) of leadership development defines all students as potential leaders. Service acts as a powerful means for developing leadership skills within our students. After the 20th anniversary celebration by the International Leadership Association of the SCM, the authors wanted to illustrate how practice can inform research as they applied the model to a 4-year leadership program. The President’s Leadership Fellows is a 4-year program where all students have an opportunity to develop into leaders through classroom and cocurricular leadership experiences. Students actively participate in individual and group activities designed to experience social change and leadership theory on a practical, personal level. The students can then identify with the key elements of the SCM framework. This article outlines this leadership program and how it can help inform further research from practice.
Have Mobile Devices Changed Working Patterns in the 21st Century? A Time-diary Analysis of Work Extension in the UK

It is commonly claimed that ubiquitous connectivity erodes the boundaries that once separated work from other aspects of life. Mobile devices in particular enable people to perform work-related activities anytime anywhere. Surprisingly, however, we know little about how people nationwide organise their daily working time over a period that has witnessed rapid technological change. Using the United Kingdom Time Use Surveys 2000 and 2015, covering this period of technological change, we studied work extension practices, and the links between work extension, total work hours and subjective time pressure. We found a significant, though small, increase in work extension, and evidence that it was significantly associated with time pressure in 2015, but not in 2000. Additionally, work extension increased total work hours, which was concentrated entirely in time working with a mobile device. We discuss our results in light of some taken-for-granted narratives about mobile devices allowing work to colonise life.
The Joint Effect of Audit Quality and Legal Regimes on the Use of Real Earnings Management: International Evidence

This study investigates whether and how a firm's real earnings management (REM) is influenced by the strength of a country's legal regime and the presence of a Big 4 auditor. In a cross-country examination using data from 22 countries, we find that REM increases in countries with stronger legal regimes as firms switch from accrual-based earnings management (AEM) to REM. The presence of a Big 4 auditor reduces REM (as well as AEM) and attenuates the positive relation between legal regime strength and REM. Our results suggest that higher-quality auditors limit client firms’ use of REM, especially in countries with a strong legal regime. This article is protected by copyright. All rights reserved.