Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-grade serous carcinoma: molecular features and contemporary treatment strategies

Epithelial ovarian carcinoma consists of several subtypes, including high-grade and low-grade serous carcinoma. In the recent past, women with all subtypes of epithelial ovarian carcinoma have been treated similarly and are included in the same clinical trials. However, a distinction has emerged between the type I, low-grade tumors and the type 2, higher-grade epithelial malignancies. Low-grade serous carcinoma exhibits different molecular and clinical features from the other epithelial subtypes, as well as some degree of chemotherapy resistance. This review summarizes the genetic, molecular and clinical characteristics of low-grade serous disease and provides an appraisal of the management strategies
CAPPLAN: a decision‐support system for planning the pricing and sales effort policy of a salesforce

Describes the decision‐support system CAPPLAN which has been developed for firms which sell their products through a salesforce to industrial customers or wholesalers and retailers. Explains that in such situations, it is common practice to negotiate the price based on guidelines provided by the sales management. Details how CAPPLAN offers a jointly optimal differentiation of prices and allocation of calling effort across account groups subject to both a limited production capacity and working‐time capacity, and also provides a parametric optimization of prices and calling effort for varying levels of production capacity. Reports how the system has been applied at an industrial photo laboratory selling the development of film and the production of prints through retailers, resulting in a substantial improvement in profits.
Streptomycin, a Substance Exhibiting Antibiotic Activity Against Gram-Positive and Gram-Negative Bacteria.∗†

Summary A new antibacterial substance, designated as streptomycin, was isolated from two strains of an actinomyces related to an organism described as Actinomyces griseus. This substance resembles streptothricin in its solubility in water, mode of isolation and concentration from culture medium, its selective activity against gram-negative bacteria, and its limited toxicity to animals. However, the two substances differ in the nature of their respective bacteriostatic spectra as well as in their quantitative action upon different bacteria. It is suggested that one is dealing here with two closely related chemical compounds.
Development of an Adverse Drug Reaction Corpus from Consumer Health Posts for Psychiatric Medications

UWM-Adverse Drug Events Corpus (UWM-ADEC) is an annotated corpus that has been developed from consumer drug review posts in social media. In this corpus, we identified four types of Adverse Drug Reactions (ADRs) including physiological, psychological, cognitive, and functional problems. Additionally, we mapped the ADRs to corresponding concepts in Unified medical language Systems (UMLS). The quality of the corpus was measured using well-defined guidelines, double coding, high inter-annotator agreement, and final reviews by pharmacists and clinical terminologists. This corpus is a valuable source for research in the area of text mining and machine learning for ADRs identifications from consumer health posts, specifically for psychiatric medications.
Association between CCK-AR gene and schizophrenia with auditory hallucinations

Objective Previous studies on a possible association between CCK-AR polymorphisms and schizophrenia have been controversial. The aim of the present study was to assess a potential association between schizophrenic patients with auditory hallucinations and polymorphisms of the CCK-AR gene. Methods A set of single nucleotide polymorphisms mainly located in the regulatory region of the CCK-AR gene was analysed in a sample of 163 Diagnostic and statistical manual of mental disorders-IV-diagnosed schizophrenic patients and 162 healthy controls Results Significant differences in the genotype (P=0.011) and allele (P=0.0009) frequencies of the +121C/G SNP (located in the 5′ regulatory region) were found between patients and controls. The excess of the C allele in the patient group remained significant after Bonferroni correction (P=0.03). However, functional in vitro assays, did not reveal significant differences on gene expression between +121G and +121C alleles of this SNP. Further investigations revealed two risk haplotypes: +121C/+978A/+984T (P=0.01) and +121C/+978T/+984C (P=0.0091) as well as a protective haplotype: +121G/+978T/+984T (P=0.0001). Conclusion Our data support a possible role of the CCK-AR gene in the vulnerability to schizophrenia in patients with auditory hallucinations, and suggest remarkable allele heterogeneity.
Service Quality and Customers’ Willingness to Pay for Vehicle Repairs and Maintenance Services

This study assesses customer perception, customer expectation of service quality and their willingness to pay for vehicle repairs and maintenance services among patrons of small scale auto mechanics services in the Kumasi metropolis. Many organisations view service quality as only a support mechanism, rather than a viable competitive strategy. The SERVQUAL model was used to determine how customer expectation and perception of service quality influence the willingness to pay for auto mechanical services. A descriptive design was used and data was collected from two hundred (200) customers within the Kumasi Metropolis using questionnaire design. The data was analysed using SPSS. It was found that all the determinants of service quality (SERVQUAL); tangibility, reliability, responsiveness, assurance and empathy have a relationship with willingness to pay. However, customers’ perceptions of service quality offered by mechanical service industry did not meet their expectations (all gaps scores recorded negative except one). For the purpose of expanding knowledge in the field of the small scale auto mechanic industry future researchers should investigate into the factors influencing service quality in the small scale auto mechanics that engage in vehicle repairs and maintenance; service quality and customer satisfaction, how they are measured in terms of customer Willingness-To-Pay for vehicle repairs and maintenance services. Original Research Article Kankam-Kwarteng et al.; JSRR, 10(5): 1-11, 2016; Article no.JSRR. 24918 2
The Effects of Auditor Dismissals and Resignations on Audit Fees: Evidence Based on SEC Disclosures Under Sarbanes-Oxley

This paper assesses the effects of auditor dismissals and resignations on audit fees and, in particular, whether companies pay more or less for their audits around these events. We also test the hypotheses that the fee discount around a dismissal can be explained by the benefits of auditor incumbency and the fee premium around a resignation varies in relation to the additional audit effort and litigation risk of the incoming auditor. We base our study on a comprehensive sample of audit fee disclosures made by SEC registrants during fiscal years 2000 to 2004, so that our study period includes auditor changes before and after the Sarbanes-Oxley (SOX) legislation. For dismissals, we find that not only does the successor auditor discount fees, and in a way that supports our discounting hypothesis, but also that fees are discounted one year before the auditor change by the incumbent auditor, consistent with the view that the threat of a dismissal may influence fees. For resignations, fees are higher one year before and after the event indicating that both the incumbent and incoming auditor charge a premium around a resignation, possibly because the new auditor needs to cope with greater than normal litigation risk and/or audit effort. SOX appears not to have affected discounting around a dismissal, but the fee premium around a resignation increases following the legislation, consistent with our resignation hypothesis. We also find that non-audit fees are discounted around a dismissal, and this result too appears to be unchanged by SOX.
Methylation of H3 Lysine 4 at Euchromatin Promotes Sir3p Association with Heterochromatin*

Set1p methylates lysine 4 of histone H3 and can activate transcription by recruiting the chromatin-remodeling factor Isw1p. In addition, Lys-4-methylated H3 is required for maintenance of silencing at the telomeres, rDNA, and HML locus in Saccharomyces cerevisiae. The molecular mechanism underlying the role of Set1p in silencing is not known. Here we report that euchromatic methylation of H3 Lys-4 is necessary to maintain silencing at specific heterochromatic sites. Inactivation of Set1p catalytic activity or mutation of H3 Lys-4 leads to decreased binding of the silent information regulator Sir3p at heterochromatic sites. Concomitantly, there is an increase in the amount of Sir3p bound to genes located in subtelomeric regions. Consistent with this result is the finding that in vitro, Sir3p preferentially binds histone H3 tails when methylation is absent at H3 Lys-4, a situation found in heterochromatin. The inability of Sir3p to bind methylated H3 Lys-4 tails suggests a model whereby H3 Lys-4 methylation prevents Sir3p association at euchromatic sites and therefore concentrates Sir3p at unmodified, heterochromatic regions of the genome.
Dual sustained release delivery system for multiple route therapy of an antiviral drug

Abstract Context: The first successful molecule against herpes infections was Acyclovir, which competes with new generations in the market, with its potential activity. The major physicochemical constraints and pharmacokinetics of Acyclovir such as low solubility, poor permeability, less half-life, high dose has initiated many researchers to develop diverse modified release dosage forms. Objective: The objective of this work was to design polymeric nanoparticles of Acyclovir and then incorporate the drug-loaded nanoparticles within an in situ gelling system to provide dual sustained release effect, whereby the duration of action and bioavailability through different routes of administration could be improved. Materials and methods: The formulation was designed through 32 factorial design, first developing the nanoparticles using Polycaprolactone and Pluronic F127 by Solvent evaporation process, followed by dispersion of the suspended nanoparticles into thermosensitive in situ gelling system of Pluronic F127 with Carbopol. Results and discussion: The characterization of the nanoparticles and its sol-gel system performed through zeta sizer, SEM, XRD, TG-DSC, FTIR and rheology helped to optimize the formulation. The drug release could be sustained to 60% and 30% at eight hours, for the nanoparticles and their in situ gel systems, respectively, with non-Fickian diffusion mechanism of drug release. The test for % cell viability with NIH3T3 cell line revealed low level of toxicity for the nanoparticles. Conclusion: The statistical significance obtained for the trail formulations experimentally proved its suitability for this dosage form design to achieve desired level of drug release.
The adaptation of megavoltage cone beam CT for use in standard radiotherapy treatment planning

Potential areas where megavoltage computed tomography (MVCT) could be used are second- and third-phase treatment planning in 3D conformal radiotherapy and IMRT, adaptive radiation therapy, single fraction palliative treatment and for the treatment of patients with metal prostheses. A feasibility study was done on using MV cone beam CT (CBCT) images generated by proprietary 3D reconstruction software based on the FDK algorithm for megavoltage treatment planning. The reconstructed images were converted to a DICOM file set. The pixel values of megavoltage cone beam computed tomography (MV CBCT) were rescaled to those of kV CT for use with a treatment planning system. A calibration phantom was designed and developed for verification of geometric accuracy and CT number calibration. The distance measured between two marker points on the CBCT image and the physical dimension on the phantom were in good agreement. Point dose verification for a 10 cm × 10 cm beam at a gantry angle of 0° and SAD of 100 cm were performed for a 6 MV beam for both kV and MV CBCT images. The point doses were found to vary between ±6.1% of the dose calculated from the kV CT image. The isodose curves for 6 MV for both kV CT and MV CBCT images were within 2% and 3 mm distance-to-agreement. A plan with three beams was performed on MV CBCT, simulating a treatment plan for cancer of the pituitary. The distribution obtained was compared with those corresponding to that obtained using the kV CT. This study has shown that treatment planning with MV cone beam CT images is feasible.
Social Engineering-Based Attacks-Model and New Zealand Perspective

The objective of this research was to present and demonstrate the major aspects and underlying constructs of social engineering. An in-depth literature review was carried out resulting in the construction of a conceptual model of social engineering attacks. A case study was undertaken to understand the phenomenon with New Zealand-based IT practitioners to contribute insightful opinions. On this basis an improved model of social engineering-based attacks was formulated.
On-membrane digestion of beta-casein for determination of phosphorylation sites by matrix-assisted laser desorption/ionization quadrupole/time-of-flight mass spectrometry.

This article discusses the features of a newly developed matrix-assisted laser desorption/ionization quadrupole/time-of-flight (MALDI-QqTOF) mass spectrometer that is useful in the analysis of phosphorylated peptides. Aliquots of beta-casein, a commonly used phosphorylated protein standard, were digested with trypsin directly on a non-porous polyurethane membrane used as sample support in MALDI-QqTOF mass spectrometry (MS) experiments. Although a complete peptide map was obtained, it was difficult to obtain sequence information for some of the tryptic fragments, in particular T1-2, which bears four phosphate groups and is thus difficult to ionize in positive mode. This article focuses on the sequencing of this particular fragment by comparing MS/MS spectra obtained using different precursor ions. These precursors associated with T1-2 were [M + H](+), [M + H](2+), and [M + H - nH(3)PO(4)](+) ions. Typically, phosphorylated ions showed facile unimolecular losses of phosphoric acid moieties, and produced limited backbone fragmentation. The abundance of [M + H](2+) ions of T1-2 in the full mass spectrum was low relative to that of [M + H](+). [M + H - 4H(3)PO(4)](+) ions as MS/MS precursors underwent backbone fragmentations, with phosphoserine residues transformed into dehydroalanines or serines. Unusual b + 18 u fragments were observed, although only for segments with previously phosphorylated serines. These partly interfered with c-ions, and were noticeable due to overlapping isotopic envelopes. It was possible to establish the sequence of phosphorylated tryptic fragment T1-2 and the location of phosphate groups using the mass of dehydroalanine residues (69 Da) and b + 18 u fragments as markers. All MS and MS/MS spectra obtained with fully phosphorylated beta-casein were compared with spectra acquired with dephosphorylated beta-casein obtained commercially. These comparisons helped assess the spectral differences caused by the presence of phosphate groups. Also, they highlighted the potential usefulness of conducting dephosphorylation directly on the probe prior to MALDI analysis in future studies.
mTOR activates the VPS 34 – UVRAG complex to regulate autolysosomal tubulation and cell survival

Lysosomes are essential organelles that function to degrade and recycle unwanted, damaged and toxic biological components. Lysosomes also act as signalling platforms in activating the nutrientsensing kinase mTOR. mTOR regulates cellular growth, but it also helps to maintain lysosome identity by initiating lysosomal tubulation through a process termed autophagosome-lysosome reformation (ALR). Here we identify a lysosomal pool of phosphatidylinositol 3-phosphate that, when depleted by specific inhibition of the class III phosphoinositide 3-kinase VPS34, results in prolonged lysosomal tubulation. This tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34. Loss of these phosphorylation sites reduced VPS34 lipid kinase activity and resulted in an increase in number and length of lysosomal tubules. In cells in which phosphorylation at these UVRAG sites is disrupted, the result of impaired lysosomal tubulation alongside ALR activation is massive cell death. Our data imply that ALR is critical for cell survival under nutrient stress and that VPS34 is an essential regulatory element in this process.
Networks in Technology Commercialization

This article examines technology commercialization as networked processes. It presents a longitudinal analysis of a technological invention called intelligent paper over a period of 13 years in 1997–2009. In the analysis, six technology commercialization phases are identified and the roles of various actors in each phase are depicted. The study shows how the processes of technology development and commercialization intertwine and shape each other. The study contributes to literature on commercialization of innovation by presenting an empirical case study where the processes of technology development and commercialization are complex and continuously evolving processes.
A series compensation enabled ZVS range enhancement of a dual active bridge converter for wide range load conditions

A novel ZVS range control technique using an auxiliary series transformer for a Dual Active Bridge (DAB) DC-DC converter is proposed. The auxiliary transformer fed with an additional H-bridge at the secondary, adds a phase-controlled voltage in series with the main converter voltage either at the primary or secondary. This addition helps to control the reactive power flowing through the main converters of the DAB. Hence the power-factor of the main converters can be controlled in such a way that the DAB can maintain ZVS even at light loads. Also it operates at minimum reactive power at higher loads while it still operates in ZVS and thus results in higher efficiency on both extremes. The series transformer carries dominantly reactive power since the compensation angle is most often near quadrature. For medium/high power DAB, the cost and additional losses associated with the series circuit can be neglected due to significant efficiency improvement. The external inductor can be eliminated by using a series transformer designed with enough leakage inductance hence saving the additional magnetic cost. The proposed technique is validated with simulations followed by experiment on a hardware implementation. The technique is also simulated for a medium voltage DAB system with actual switching and magnetic data to bring out the efficiency improvements.
Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients.

PURPOSE Detection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome. PATIENTS AND METHODS qRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (beta1-->4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3). RESULTS Fifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P <.0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of > or = one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P =.0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1). CONCLUSION Molecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.
Intestinal stem cell growth and differentiation on a tubular scaffold with evaluation in small and large animals.

AIMS To investigate the growth and differentiation of intestinal stem cells on a novel tubular scaffold in vitro and in vivo. MATERIALS & METHODS Intestinal progenitor cells from mice or humans were cultured with myofibroblasts, macrophages and/or bacteria, and evaluated in mice via omental implantation. Mucosal regeneration was evaluated in dogs after rectal mucosectomy followed by scaffold implantation. RESULTS Intestinal progenitor cells differentiated into crypt-villi structures on the scaffold. Differentiation and scaffold coverage was enhanced by coculture with myofibroblasts, macrophages and probiotic bacteria, while the implanted scaffolds enhanced mucosal regeneration in the dog rectum. CONCLUSION Intestinal stem cell growth and differentiation on a novel tubular scaffold is enhanced through addition of cellular and microbial components, as validated in mice and dogs.
HOMOGENEITY ANALYSIS OF TURKISH CLIMATE DATA

The climate data is a long-term time series correlated naturally. If there are any artificial effects not originated from the climate, analysis results can be ambiguous. Thereby, the detection of such effects, called inhomogeneity, becomes crucial. In previous studies, this investigation has been conducted under the unrealistic independence assumption considering only mean shifts. In this study, homogeneity analysis is applied to Turkish precipitation data by using (non)parametric methods designed for correlated data or for handling variance as well mean shifts. These are Friedman test, CUSUM and Shewart charts. Then, findings are compared to that of SNHT obtained in another study. Results show that CUSUM chart is a good method for the homogeneity analysis.
Are Collagen Fibrils in the Developing Avian Cornea Composed of Two Different Collagen Types?

In the avian corneal stroma, the collagen is organized in orthogonal lamellae, each of which is composed of numerous striated collagen fibrils of uniform, thin (25 nm) diameter. ’. ’ This is true for both the epithelially derived primary stroma of the early embryo, and the mesenchymally derived secondary stroma of the more mature embryo and adult. In most other connective tissues, such as the adjacent sclera, the diameters of the collagen fibrils are thicker and more variable. It has been suggested that thin, uniform diameter fibrils are requisite for corneal transparency; a sequella of severe corneal injury may be the local deposition of large, randomly oriented collagen fibrils resulting in an opaque scar. The collagen fibril, then, is a major functional unit of the corneal stroma, as well as of the stromal matrices of other organs. These units form by a process of “molecular morphogenesis” termed fibrillogenesis. ’ In this process, individual collagen molecules or their procollagen precursors become assembled into supramolecular structures having the proper diameters, lengths, and spatial relationships to each other. How is this assembly achieved and controlled? Results from molecular self-assembly and