Miracle-dz/UniFAR-FTUs huggingface dataset:
Monoclonal antibody-induced ErbB3 receptor internalization and degradation inhibits growth and migration of human melanoma cells

Members of the ErbB receptor family are targets of a growing numbers of small molecules and monoclonal antibodies inhibitors currently under development for the treatment of cancer. Although historical efforts have been directed against ErbB1 (EGFR) and ErbB2 (HER2/neu), emerging evidences have pointed to ErbB3 as a key node in the activation of proliferation/survival pathways from the ErbB receptor family and have fueled enthusiasm toward the clinical development of anti-ErbB3 agents. In this study, we have evaluated the potential therapeutic efficacy of a set of three recently generated anti-human ErbB3 monoclonals, A2, A3 and A4, in human primary melanoma cells. We show that in melanoma cells expressing ErbB1, ErbB3 and ErbB4 but not ErbB2 receptor ligands activate the PI3K/AKT pathway, and this leads to increased cell proliferation and migration. While antibodies A3 and A4 are able to potently inhibit ligand-induced signaling, proliferation and migration, antibody A2 is unable to exert this effect. In attempt to understand the mechanism of action and the basis of this different behavior, we demonstrate, through a series of combined approaches, that antibody efficacy strongly correlates with antibody-induced receptor internalization, degradation and inhibition of receptor recycling to the cell surface. Finally, fine epitope mapping studies through a peptide array show that inhibiting vs. non-inhibiting antibodies have a dramatically different mode of binding to the to the receptor extracellular domain. Our study confirms the key role of ErbB3 and points to exploitation of novel combination therapies for treatment of malignant melanoma.
Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial.

BACKGROUND We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder (ADHD) over a longer period than has been reported in previous studies of central stimulants in this condition. METHODS Sixty-two children, aged 6 to 11 years, meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design, randomized, double-blind, placebo-controlled study of amphetamine treatment. Treatment was not restricted to children with "pure" ADHD, ie, some had comorbid diagnoses. In the amphetamine group, children received active treatment for 15 months. RESULTS Amphetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children--Revised. Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group. Adverse effects were few and relatively mild. CONCLUSION The results of this long-term, placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment.
Realistic estimation of power penalty through a probabilistic framework in a WDM receiver with component crosstalk

In this work, the performance degradation in a Wavelength Division Multiplexing (WDM) receiver system is analyzed in terms of power penalty considering the presence of multiple component crosstalk sources. In conventional way, power penalty is calculated considering the presence of all crosstalk sources simultaneously (i.e. worst case) which is not reality in practice and leads to unrealistic estimation. Here a probabilistic approach is adopted which considers all possible probabilistic appearances of the interfering channels and their realistic impact while calculating Bit Error Rate (BER) and penalty. Power penalty considering the presence of signal-crosstalk beat noise is formulated and the effect of the variation of number of interfering channels and crosstalk level are studied for a fixed thermal noise and photocurrent setting of the receiver. In addition the obtained results are compared with the existing worst case analysis model.
p 53 therapy in a patient with Li-Fraumeni syndrome

Li-Fraumeni syndrome is an autosomal dominant disorder that greatly increases the risk of developing multiple types of cancer. The majority of Li-Fraumeni syndrome families contain germ-line mutations in the p53 tumor suppressor gene. We describe treatment of a refractory, progressive Li-Fraumeni syndrome embryonal carcinoma with a p53 therapy (Advexin) targeted to the underlying molecular defect of this syndrome. p53 treatment resulted in complete and durable remission of the injected lesion by fluorodeoxyglucose-positron emission tomography scans with improvement of tumor-related symptoms. With respect to molecular markers, the patient’s tumor had abnormal p53 and expressed coxsackie adenovirus receptors with a low HDM2 and bcl-2 profile conducive for adenoviral p53 activity. p53 treatment resulted in the induction of cell cycle arrest and apoptosis documented by p21 and cleaved caspase-3 detection. Increased adenoviral antibody titers after repeated therapy did not inhibit adenoviral p53 activity or result in pathologic sequelae. Relationships between these clinical, radiographic, and molecular markers may prove useful in guiding future application of p53 tumor suppressor therapy. [Mol Cancer Ther 2007;6(5):1478–82]
Pathways to the First Contact with Specialist Mental Health Care

Objective: To examine the pathways to mental health care followed by patients presenting for the first time to community- and hospital-based services and the degree to which individual characteristics, cultural background, illness type, severity and service-related variables influence the time and pathways taken to reach care. Method: One hundred and forty-six consecutive Australian-born, Asian and Arabicspeaking patients making their first lifetime contact with mental health services in two area health regions were included. Symptom severity was assessed using the Health of the Nations Outcome Scales. Illness explanatory models, social support, English-language proficiency and acculturation were also assessed. Results: An average of three professional consultations were made prior to first contact with public mental health services. Family physicians occupied a pivotal role in the helpseeking pathway with 53% of patients consulting a general practitioner. The median time taken to reach specialist mental health services was 6 months, with significantly shorter time for patients with psychotic disorders. Individual variables such as gender, social support, ethnicity and English flency were not associated with delays in receiving public mental health care. Ethnicity was associated with lower utilization of allied health professionals. Conclusions: The data suggest that social and cultural factors influence the range of professionals consulted by those with a mental illness but do not delay their presentation to public mental health services.
The role of cement in the long term performance and premature failure of Charnley low friction arthroplasties.

A number of polyethylene acetabular cups (59) and femoral stems (38) of Charnley hip prostheses were obtained following revision surgery and examined by scanning electron microscopy. In many cases, acrylic cement particles were embedded in the articulating surface of the cups. These particles caused surface pitting. The appearance of the articulating surfaces suggested that some cement had been present from the time of arthroplasty. In other cups there was evidence of cement ingress during the service life. Failure to use sufficient cement at arthroplasty resulted in cavities on the backs of the cups. Many femoral heads had become scratched in vivo. the surface roughness increasing from an initial value less than 0.02 pm Ra to a value on removal of 0.07 pm Ra. The increased roughness increases the amount of wear in the polyethylene sockets. Laboratory tests show that retrieved acrylic cement particles will scratch stainless steel, and it is our conclusion that entrapped cement will damage both components of the prosthesis and may cause premature failure.
Power electronics laboratory education: The JUST experience

Power electronics has become increasingly important as more applications are electrified. Application range from personnel mobile electronics, to home appliance, transportation and renewable energy systems to name a few. Advances in power semiconductors technology combined with demand for higher efficiency, faster, compact systems has revolutionized the industry, and created a high demand for power electronic engineers. In this paper, an overview of power electronics laboratory education, teaching methodology and student evaluation at Jordan University of Science & Technology (JUST) will be presented.
In vitro evaluation of the determinants of bactericidal activity of ampicillin dosing regimens against Escherichia coli

An in vitro flow model was used to examine the influence of peak concentration (Cmax), the area under the antibiotic concentration-time curve (AUC), the magnitude of AUC above the MIC, and the aggregate time the antibiotic concentration exceeds the MIC (TMIC) on the bactericidal effect of ampicillin against Escherichia coli ATCC 12407. Bacteria in the log phase were exposed to therapeutically realistic drug regimens. Ampicillin concentration and bacterial density (CFU per milliliter) were measured over time. Four parameters reflecting bactericidal activity were quantitated: difference between initial and minimum and initial and final bacterial densities, area under the bacterial density-time curve, and a fourth parameter, sigma, which is a function of these three. Multiple regression analysis confirmed AUC as the major factor in predicting bactericidal activity. An AUC of greater than 70 micrograms.h/ml correlated with the lack of emergence of resistance.
Incidence of Dementia in a Community-Dwelling Brazilian Population

The authors report the incidence of dementia in a community-dwelling Brazilian population. In 1997, 1656 individuals aged 65 years or more, the majority being of very low educational level, were screened at their homes in Catanduva, Brazil, and dementia was diagnosed in 118 cases. The remaining 1538 individuals were rescreened 3.25 years later applying a health questionnaire, the Mini-Mental State Examination (MMSE) and the Pfeffer Functional Activities Questionnaire (PFAQ). According to PFAQ and MMSE scores, selected subjects were submitted to clinical, neurologic, and cognitive evaluations. The subjects diagnosed with dementia underwent laboratory tests and brain computed tomography. A total of 1119 individuals were rescreened and 50 incident cases of dementia (28 with Alzheimer disease [AD]) were identified. The incidence rate of dementia was 13.8 and of AD was 7.7 per 1000 person-years for individuals aged 65 years or older. The incidence rates of dementia almost doubled with every 5 years of age. There was no difference according to gender, but women had a higher incidence of dementia, predominantly AD, in very old age. There was a trend for higher incidence of dementia in illiterates (p = 0.07), but multivariate analysis disclosed significant association only between age and higher incidence of dementia. The incidence rates of dementia in this Brazilian community are comparable to those reported in Western and Asian studies.
The State of BIM-Based Quantity Take-Off Implementation Among Commercial General Contractors

The State of BIM-Based Quantity Take-Off Implementation Among Commercial General Contractors Morgan Christian Tagg School of Technology, BYU Master of Science Building Information Modeling (BIM) plays an important role in today’s construction industry. Models are tools that help stakeholders communicate, visualize building geometry, perform trade coordination and clash detection among others. A less popular aspect of BIM that shows high potential is the quantity take-off (QTO) feature. Yet, its implementation among commercial general contractors (GC) has not received as much attention. The purpose of this study was to identify how the BIM QTO features were being implemented among commercial general contractors, what challenges they faced and how they worked to overcome those challenges. Through a three-step process including semi structured interviews with estimators, preconstruction, BIM and Virtual Design Construction (VDC) managers, valuable insights on the BIM QTO implementation state among general contractors were gathered and analyzed. Links between BIM QTO benefits, project design phases and delivery methods, software, training, leadership and jurisdictions were discussed. The data indicated that BIM QTO’s benefits were best leveraged through early general contractor involvement, the adequate contract framework, trained BIM QTO estimators, and early and strategic communication between owners, designers and estimators. The conditions for increased efficiency were discussed along with the solutions to the common BIM-based QTO challenges.
Determinants of emotional regulation among marketing staff in the Jordanian banking sector

This study empirically verifies the determinants of emotional regulation as observed among marketing staff in the Jordanian banking sector. In particular, it examines the relationship between participants’ cognitive flexibility capabilities, their levels of response inhibition and their levels of mindfulness on the degree of emotional regulation they exhibited. Data was collected from a sample of 120 respondents who were administered four standardized survey questionnaires. Multiple linear regression was used to analyze the data, and results show no significant relationship between cognitive flexibility, inhibition levels, and a combination of both factors on emotional regulation. However, it found that mindfulness had a low but significant and positive relationship with emotional regulation.
Towards Neutral Distribution Taxes and Vanishing Tax Effects in the European Union

The European Union (EU) has no explicit common income tax law. Nevertheless, Court of Justice decisions have driven EU member states to adopt more similar corporate tax systems, and thus, to align the tax treatment of corporate profit distributions - dividends and capital gains. This paper empirically analyzes the influence of the tax preferences of individual and corporate shareholders for the two corporate distribution types - dividends or capital gains - from 1990 to 2012. In the first years of the observation period, European tax systems have provided opposing tax advantages, where individual shareholders have preferred capital gains and corporate shareholders have preferred dividends. To account for these differences depending on the firm's shareholder structure, we derive firm-specific tax preferences for profit distributions. Our empirical analysis reveals that - in line with current literature - the firm-specific tax preferences indeed affect dividend payments. Moreover, we show that in contrast to our detailed study, a simplified approach to measure tax effects on distributions overestimates this influence. In subsequent years, as European Court of Justice decisions have indirectly aligned EU corporate tax systems, we find that tax preferences have converged to a great extent with the tendency to equal tax treatment of dividends and capital gains for both - individual and corporate - shareholder groups. In line with this development, we find that the association of tax preferences and distribution policies vanishes in the last years of the observation period. Our study implies that the EU common regulatory framework, even in the absence of explicit law, can affect corporate distribution decisions and foster neutral taxation of dividends and capital gains across EU member states.
In pursuit of the high‐resolution structure of nicotinic acetylcholine receptors

The nicotinic acetylcholine receptor (nAChR) has been studied extensively for well over four decades because of its important physiological roles and medical relevance. A large body of data from biochemical and biophysical studies are now available. The structural information, which is needed to integrate existing data to address the mechanism and function of nAChRs, started to emerge in recent years. Structural studies of acetylcholine binding proteins (AChBPs) have greatly facilitated the study of nAChRs. The recently determined crystal structures of the prokaryotic homologues of nAChRs will probably have similar impact over time. However, a direct structural model of nAChRs at high resolution will be important for mechanistic studies and drug development. Here we will review some of the recent efforts in this area and use the high‐resolution structure of the extracellular domains of nAChR α1 to illustrate the potential insights one may gain at higher resolution.
Biophysical and Ultrastructural Characterization of Adeno-Associated Virus Capsid Uncoating and Genome Release

ABSTRACT We describe biophysical and ultrastructural differences in genome release from adeno-associated virus (AAV) capsids packaging wild-type DNA, recombinant single-stranded DNA (ssDNA), or dimeric, self-complementary DNA (scDNA) genomes. Atomic force microscopy and electron microscopy (EM) revealed that AAV particles release packaged genomes and undergo marked changes in capsid morphology upon heating in physiological buffer (pH 7.2). When different AAV capsids packaging ss/scDNA varying in length from 72 to 123% of wild-type DNA (3.4 to 5.8 kb) were incrementally heated, the proportion of uncoated AAV capsids decreased with genome length as observed by EM. Genome release was further characterized by a fluorimetric assay, which demonstrated that acidic pH and high osmotic pressure suppress genome release from AAV particles. In addition, fluorimetric analysis corroborated an inverse correlation between packaged genome length and the temperature needed to induce uncoating. Surprisingly, scAAV vectors required significantly higher temperatures to uncoat than their ssDNA-packaging counterparts. However, externalization of VP1 N termini appears to be unaffected by packaged genome length or self-complementarity. Further analysis by tungsten-shadowing EM revealed striking differences in the morphologies of ssDNA and scDNA genomes upon release from intact capsids. Computational modeling and molecular dynamics simulations suggest that the unusual thermal stability of scAAV vectors might arise from partial base pairing and optimal organization of packaged scDNA. Our work further defines the biophysical mechanisms underlying adeno-associated virus uncoating and genome release.
Urinary Incontinence in Pregnant Women: Prevalence, Associated Factors, and Its Effects on Health-Related Quality of Life

PURPOSE: The purpose of this study was to determine the prevalence of and risk factors for urinary incontinence (UI) during pregnancy and to evaluate its effect on health-related quality of life. DESIGN: Descriptive, cross-sectional study. SUBJECTS AND SETTING: The sample of the study comprised 287 pregnant women attending an outpatient clinic located in a research and training hospital in Ankara, Turkey. METHODS: Data were collected using an investigator-developed questionnaire that included 2 validated instruments, the International Consultation on Incontinence Questionnaire Short Form and Incontinence Quality of Life scale. RESULTS: The prevalence of UI in the study population was 21.3% (n = 61). Cumulative scores in pregnant women who “always” experienced UI and those who expressed a “large amount” of UI were lower than women with milder UI. Logistic regression analysis found associations between UI and age in years (odds ratio [OR] = 3.833; 95% confidence interval [CI], 1.763-8.332), parity (OR = 2.539; 95% CI, 1.135-5.675), third trimester versus first trimester (OR = 3.206; 95% CI, 1.178-8.725), and prior use of hormonal contraceptives (OR = 0.209; 95% CI, 0.085-0.513). CONCLUSIONS: Urinary incontinence is prevalent among pregnant women. Age, parity, and gestational week were associated with an increased likelihood of UI during pregnancy. Prior use of contraceptive hormones was associated with a reduced risk of UI during pregnancy.
Impedance Measurement of a Dipole Above a Periodically Structured Reflective Surface

The impedance of a horizontal dipole antenna placed closely above a periodically structured reflective surface was determined. In order to characterize the antenna directly at its feed point, a measurement technique is suggested where the influence of the feed network is eliminated. Implications of the reflective surface on the dipole impedance are discussed in detail. Furthermore, the radiation pattern and the total efficiency of a low-profile dipole are investigated quantitatively.
Exploring the Uncertainties in Cancer Risk Assessment Using the Integrated Probabilistic Risk Assessment (IPRA) Approach

Current methods for cancer risk assessment result in single values, without any quantitative information on the uncertainties in these values. Therefore, single risk values could easily be overinterpreted. In this study, we discuss a full probabilistic cancer risk assessment approach in which all the generally recognized uncertainties in both exposure and hazard assessment are quantitatively characterized and probabilistically evaluated, resulting in a confidence interval for the final risk estimate. The methodology is applied to three example chemicals (aflatoxin, N‐nitrosodimethylamine, and methyleugenol). These examples illustrate that the uncertainty in a cancer risk estimate may be huge, making single value estimates of cancer risk meaningless. Further, a risk based on linear extrapolation tends to be lower than the upper 95% confidence limit of a probabilistic risk estimate, and in that sense it is not conservative. Our conceptual analysis showed that there are two possible basic approaches for cancer risk assessment, depending on the interpretation of the dose‐incidence data measured in animals. However, it remains unclear which of the two interpretations is the more adequate one, adding an additional uncertainty to the already huge confidence intervals for cancer risk estimates.
Climate Change Disclosures in the Annual Reports: Evidence from Bangladesh

This study examines the nature and extent of climate change disclosures in the corporate annual reports of the listed companies in Dhaka Stock Exchange, Bangladesh. For this purpose, annual reports related to the year 2014 of the sample 88 listed companies have been scrutinized. In regard to this study, content analysis approach has been conducted considering thirteen different disclosure issues regarding climate change. Our analysis provides the comprehension of below average climate change disclosure practices by the Bangladeshi companies, though 58 percent companies have reported at least one issue on climate change and global warming. ‘Energy saving & efficiency’ and ‘water management & pollution’ are mostly reported issues that are industry specific requirements in some case. From the viewpoint of industry, Banking industry and Cement industry have started to report some issues related to the climate change, where 4 industries out of selected 17 industries have not provided any climate change disclosure. Disseminating climate change disclosure within 10 sentences by most of the reported companies manifests the desideratum of in-depth disclosure practices.