Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin D3 analogs and their 24‐Oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects

The seco‐steroid hormone, 1α,25 dihydroxyvitamin D3 (1α,25(OH)2D3) binds to a specific nuclear receptor that acts as a ligand‐inducible transcription factor. The resulting genomic effects include partial arrest in G0/G1 of the cell cycle and induction of differentiation; these effects have been observed in various types of cancer. Recently, we produced enzymatically the natural 24‐oxo metabolites of 1α,25(OH)2D3 and two of its potent synthetic analogs (1α,25‐(OH)2‐16‐ene‐D3 and 1α,25‐(OH)2‐20‐epi‐D3) using a rat kidney perfusion system. We have found that the 24‐oxo metabolites of both 1α,25(OH)2D3 and its analogs have either the same or greater antiproliferative activity against various cancer cells as their parental compounds. Notably, two cell lines (DU‐145 (prostate cancer) and MDA‐MB‐436 [breast cancer]) that were extremely resistant to the antiproliferative effects of vitamin D3 analogs displayed greater sensitivity towards the 24‐oxo metabolite of the vitamin D3 analog. Similarly, the 24‐oxo metabolites had the capacity to induce differentiation and apoptosis and to diminish the proportion of cells in S phase. Most interestingly, while the analog 1α,25(OH)2‐20‐epi‐D3 induced expression of BRCA1 in MCF‐7 breast cancer cells; its 24‐oxo metabolite dramatically suppressed BRAC1 expression. Thus, we have shown for the first time that the various biological activities produced by the hormone 1α,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1α,25(OH)2D3 and its natural 24‐oxo metabolites. J. Cell. Biochem. 66:413–425, 1997. © 1997 Wiley‐Liss, Inc.
Portfolio stress testing applied to commodity futures

In this article, we construct a portfolio of commodity futures which mimics the Dow Jones Commodity Index and perform an extensive stress testing exercise with a focus on hybrid scenarios. The increased volume of investments in commodities as financial instruments over the last decades underline the importance of a more thorough framework for stress testing of related portfolios. Our study is the first to show comparatively the marginal impact of the model choice for portfolio components versus the marginal role of tail dependence on the portfolio profit and loss in stress testing exercises. We model the distribution of returns of portfolio components with an asymmetric AR-GARCH model combined with Extreme Value Theory for extreme tails, and employ multivariate copula functions to model the time-varying joint dependence structure. Our study reveals that indeed, for a realistic stress test, a special attention should be given to the tail risk in individual commodity returns as well as to tail correlations. We also draw conclusions about parameter risk persistent in stress testing exercises. Finally yet importantly, in line with Basel IIIb, the study highlights the importance of using forward-looking hybrid and hypothetical scenarios over historical scenarios.
Prevalence of severe acute rotavirus gastroenteritis and intussusceptions in Ghanaian children under 5 years of age.

INTRODUCTION Vaccination is the most effective preventive strategy against rotavirus disease. Regional differences in prevalent rotavirus genotypes may affect vaccine efficacy. Pre-vaccine surveillance for burden of rotavirus disease, prevalent rotavirus genotypes, and association between rotavirus disease and intussusceptions helps in monitoring the impact of vaccination. METHODOLOGY A prospective study was conducted from January 2008 to December 2009 in children younger than five years hospitalized for longer than 24 hours with acute gastroenteritis. Data on confirmed cases of intussusception were collected retrospectively. Stools were tested by enzyme immunoassay, reverse-transcriptase polymerase chain reaction and nucleotide sequencing. RESULTS Acute gastroenteritis (AGE) caused 13.1% (2,147/16,348) of hospitalizations among children under five years. Stools were tested for 50.2% (1077/2147) of AGE cases. Of these, 49% (528/1077) were rotavirus positive. Rotavirus gastroenteritis, non-rotavirus gastroenteritis, and intussusceptions were most prevalent in children under 15 months [80.3%, 74% and 91% respectively]. Rotavirus was detected from more than 60% of acute gastroenteritis cases during peak months. The prevalence of intussusception showed no seasonal pattern. The peak ages of six to twelve months for acute gastroenteritis and five to eight months for intussusception overlapped. G1, G2 and mixed G/P genotypes were common in the isolated rotaviruses. CONCLUSION Rotavirus gastroenteritis causes significant morbidity in children younger than five years of age in Ghana. Although the peak age of rotavirus gastroenteritis and intussusceptions overlapped, there was no seasonal correlation between them. The high prevalence of mixed G/P genotypes in Ghanaian children may affect the effectiveness of vaccination.
Broadband infrared luminescence from Li2O-Al2O3-ZnO-SiO2 glasses doped with Bi2O3.

The broadband emission in the 1.2~1.6mum region from Li2O-Al2O3-ZnO-SiO2 ( LAZS ) glass codoped with 0.01mol. %Cr2O3 and 1.0mol. %Bi2O3 when pumped by the 808nm laser at room temperature is not initiated from Cr4+ ions, but from bismuth, which is remarkably different from the results reported by Batchelor et al. The broad ~1300nm emission from Bi2O3-containing LAZS glasses possesses a FWHM ( Full Width at Half Maximum ) more than 250nm and a fluorescent lifetime longer than 500mus when excited by the 808nm laser. These glasses might have the potential applications in the broadly tunable lasers and the broadband fiber amplifiers.
Quality improvement guidelines for the treatment of acute pain and cancer pain. American Pain Society Quality of Care Committee.

OBJECTIVE To develop quality improvement (QI) guidelines and programs to improve treatment outcomes for patients with acute pain and cancer pain. PARTICIPANTS Twenty-four members of the American Pain Society (APS) participated in preparing the statement, including 15 nurses (oncology, general medical-surgical nursing, pediatrics, and QI research), seven physicians (clinical pharmacology, neurology, anesthesiology, radiation oncology, and physiatry), one psychologist, and one statistician. Participants were self-selected from the 3000 members of the APS, which supported the process and held annual open committee meetings and scientific symposia beginning in 1988. EVIDENCE MEDLINE was searched (1980 to 1995) to identify all articles on pain assessment, treatment of acute pain or cancer pain, and QI or education related to pain. CONSENSUS PROCESS Following panel discussions, one member (M.B.M.) prepared successive drafts and circulated them to the panel and APS membership for comments. After publication of a prototype version in 1991, 14 panelists carried out formal studies of implementation of the guidelines at three medical centers. This article was prepared based on this research, a new literature review, and suggestions from 50 pain clinicians and researchers. CONCLUSIONS Quality improvement programs to improve treatment of acute pain and cancer pain should include five key elements: (1) Assuring that a report of unrelieved pain raises a "red flag" that attracts clinicians' attention; (2) making information about analgesics convenient where orders are written; (3) promising patients responsive analgesic care and urging them to communicate pain; (4) implementing policies and safeguards for the use of modern analgesic technologies; and (5) coordinating and assessing implementation of these measures. Several short-term studies suggest that this QI approach may improve patient satisfaction and facilitate recognition of institutional obstacles to optimal pain treatment, but it is not a panacea for undertreated pain. By making the magnitude of the problem apparent and committing the institution to change, pain treatment QI programs can provide a foundation for a multifaceted approach that includes education of clinicians and patients, design of informational tools to minimize errors in prescribing, and improved coordination of the process of assessing and treating pain.
In Vitro Cell Death Discrimination and Screening Method by Simple and Cost-Effective Viability Analysis

Background/Aims: For in vitro cytotoxicity testing, discrimination of apoptosis and necrosis represents valuable information. Viability analysis performed at two different time points post treatment could serve such a purpose because the dynamics of metabolic activity of apoptotic and necrotic cells is different, i.e. a more rapid decline of cellular metabolism during necrosis whereas cellular metabolism is maintained during the entire execution phase of apoptosis. This study describes a straightforward approach to distinguish apoptosis and necrosis. Methods: A431 human epidermoid carcinoma cells were treated with different concentrations/doses of actinomycin D (Act-D), 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), Ro 31-8220, H2O2 and photodynamic treatment (PDT). The resazurin viability signal was recorded at 2 and 24 hrs post treatment. Apoptosis and necrosis were verified by measuring caspase 3/7 and membrane integrity. Results: Calculation of the difference curve between the 2 and 24 hrs resazurin signals yields the following information: a positive difference signal indicates apoptosis (i.e. high metabolic activity at early time points and low signal at 24 hrs post treatment) while an early reduction of the viability signal indicates necrosis. For all treatments, this dose-dependent sequence of cellular responses could be confirmed by independent assays. Conclusion: Simple and cost-effective viability analysis provides reliable information about the dose ranges of a cytotoxic agent where apoptosis or necrosis occurs. This may serve as a starting point for further in-depth characterisation of cytotoxic treatments.
Synthesis and Antimycobacterial Activity of Novel Amino Alcohols Containing Central Core of the Anti‐HIV Drugs Lopinavir and Ritonavir

Eleven new amino alcohol derivatives have been synthesized from reactions of lopinavir intermediate and heteroaromatic aldehyde in good yields. These compounds, the antiretrovirals (lopinavir and ritonavir) and lopinavir key intermediate were evaluated as antibacterial agents against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and their activity expressed as the minimum inhibitory concentration (MIC) in μm. Ten amino alcohols evaluated displayed significant activity (MIC between 6.15 and 108.4 μm) when compared to first‐line drug ethambutol (MIC = 15.9 μm). Three of them showed more activity than ethambutol (MIC = 6.15; 6.21 and 13.4 μm). The appreciable activity of these compounds can be considered an important finding for the rational design of new leads for anti‐TB compounds.
Economic performance and efficiency determinants of crop-producing farms in Norway

Purpose The purpose of this paper is to explore the economic performance of Norwegian crop farms using a stochastic frontier analysis. Design/methodology/approach The analysis was based on a translog cost function and unbalanced farm-level panel data for 1991–2013 from 455 Norwegian farms specialized in crop production in eastern and central regions of Norway. Findings The results of the analysis show that the mean efficiency was about 78–81 percent. Farm management practices and socioeconomic factors were shown to significantly affect the economic performance of Norwegian crop farms. Research limitations/implications Farmers are getting different types of support from the government and the study does not account for the different effects of different kinds of subsidy on cost efficiency. Different subsidies might have different effects on farm performance. To get more informative and useful results, it would be necessary to repeat the analysis with less aggregated data on subsidy payments. Practical implications One implication for farmers (and their advisers) is that many of them are less efficient than the estimated benchmark (best performing farms). Thus, those lagging behind the best performing farms need to look at the way they are operating and to seek out ways to save costs or increase crop production. Perhaps there are things for lagging farmers to learn from their more productive farming neighbors. For instance, those farmers not practicing crop rotation might be well advised to try that practice. Social implications For both taxpayers and consumers, one implication is that the contributions they pay that go to subsidize farmers appear to bring some benefits in terms of more efficient production that, in turn, increase the supply of some foods so possibly making food prices more affordable. Originality/value Unlike previous performance studies in the literature, the authors estimated farm-level economic performance accounting for the contribution of both an important farm management practice and selected socioeconomic factors. Good farm management practices, captured through crop rotation, land tenure, government support and off-farm activities were found to have made a positive and statistically significant contribution to reducing the cost of production on crop-producing farms in the Central and Eastern regions of Norway.
Pharmacogenomics of long-acting β2-agonists

Introduction: Long-acting β2-agonists are an effective class of drugs, when combined with inhaled corticosteroids, for reducing symptoms and exacerbations in patients with asthma that is not adequately controlled by inhaled corticosteroids alone. However, because this class of drugs has been associated with severe adverse events, including hospitalization and death in small numbers of patients, efforts to identify a pharmacogenetic profile for patients at risk has been diligently investigated. Areas covered: The PubMed search engine of the National Library of Medicine was used to identify English-language and non-English language articles published from 1947 to March 2015 pertinent to asthma, pharmacogenomics, and long-acting β2-agonists. Keywords and topics included: asthma, asthma control, long-acting β2-agonists, salmeterol, formoterol, pharmacogenetics, and pharmacogenomics. This strategy was also used for the Cochrane Library Database and CINAHL. Reference types were randomized controlled trials, reviews, and editorials. Additional publications were culled from reference lists. The publications were reviewed by the authors and those most relevant were used to support the topics covered in this review. Expert opinion: Children, who carry the ADRB2 Arg16Arg genotype, may be at greater risk than adults for severe adverse events. Rare ADRB2 variants appear to provide better clues for identifying the at-risk population of asthmatics.
Standardizing the Technical Tender Process in the Construction Industry

Abstract At the time of writing this paper, 15 construction companies in South Africa were fined a total of R1.46bn for bid rigging. This underlines the need to change the way tenders are adjudicated. This study investigated the possibility of standardising the technical tender process in the South African construction industry. A standardised technical questionnaire submitted with the tender documentation, including the relevant scoring matrix would ensure consistency and transparency in tendering across the industry. The study found overwhelming evidence that a standardised technical tender process is possible. Clients are the key to making this system work because they need to give the consultants sufficient time to prepare tender documents. Clients must agree up front with the consultants on the scoring matrix weightings and consultants should participate in both the financial and technical adjudication. Over time, the standardization of the technical tender process will help bidders understand their shortfalls and take corrective action.
Measurement of forces generated during distraction of growing-rods in early onset scoliosis.

AIM To measure the forces applied during distraction of growing-rods in early onset scoliosis (EOS), aimed at developing a motorized elongation device. METHODS A consecutive series of measurements were carried out to analyze the forces applied by the surgeon during distraction of single growing-rods in 10 patients affected by EOS (mean age 8.3 years; range 6 to 10 years) undergoing the first distraction 6 months following implantation of the rods. For each measurement, output from the transducer of a dedicated pair of distraction calipers was recorded at zero load status and at every 1 mm of distraction, up to a maximum of 12 mm for each of the two connected rods. RESULTS Twenty measurements were obtained showing a linear increase of the load with increasing distraction, with a mean peak force of 485 N at 12 mm distraction and a single reading over 500 N. We did not observe bone fractures or ligament disruptions during or after rod elongations. There was one case of superficial wound infection in the cohort. CONCLUSION The safe peak force carrying capacity of a motorized device for distraction of growing-rods is 500N.
Long-term promoter activity during herpes simplex virus latency

The ability to direct foreign gene expression from the herpes simplex virus type 1 (HSV-1) genome during an acute or latent infection is a subject of increasing importance in the utilization of HSV vectors for gene therapy. Little is known about the types of transcription factors present in neurons or about whether different neuronal populations within a ganglion vary in their complement of these factors. With respect to HSV-1 latency, it is not known how or why the latency-associated transcript (LAT) promoter is able to function continually during latency while all other viral promoters are inactive. To further studies of these two phenomena, we constructed seven recombinant viruses with various promoter constructs driving expression of the lacZ reporter gene. Each construct was inserted into HSV-1 at the glycoprotein C locus, and recombinant viruses were evaluated for the ability to express beta-galactosidase during acute and latent viral infections in murine dorsal root ganglia. During acute infection of murine dorsal root ganglia, the activities of the promoters varied over a wide range. Constructs containing the murine metallothionein promoter (MT1), the phosphoglycerate kinase promoter, the Moloney murine leukemia virus long terminal repeat (LTR), or the region upstream of and including the HSV LAT core promoter (LAT) were active during the acute but not the latent phase of infection. The addition of transcription factor binding sites present in the upstream LAT region to the MT1 and LTR promoters (LAT-MT1 and LAT-LTR, respectively) significantly increased acute-phase expression. Despite these high initial rates of transcription, of all the promoter constructs only LAT-LTR was able to remain transcriptionally active after the establishment of a latent state. Thus, the Moloney murine leukemia virus LTR provides a DNA element which functions to prevent promoter inactivation during latency. An analogous HSV long-term-expression element is evidently not present in the upstream LAT promoter, indicating that the HSV long-term-expression function is provided by a region outside of that which gives high-level neuronal expression during the acute phase of infection.
ELECTROCARDIOGRAM REFERENCE VALUES FOR THE BUZZARD IN SPAIN

Electrocardiographic reference values were established on apparently healthy buzzards (Buteo buteo) in Lugo (Spain) from March 1997 to June 1999. All birds were anesthetized with isofluorane and placed in dorsal recumbence. The standard and augmented unipolar limb leads electrocardiograms were recorded in 65 buzzards. The wave forms were analyzed in lead II at 50 mm/sec and at 1 cm = 1 mV to determine P, PR, QRS, T and QT durations and P, QRS and T amplitudes. The polarity of each wave form was tabulated in all leads. The mean electrical axis (MEA) for the frontal plane was calculated using leads II and III. The mean heart rate was 325.2 ± 52.9 beats/min. In lead II, the P wave was positive, the dominant pattern of QRS complex was QS and the T wave was always positive. The average value of the MEA was −99.2 ± 7.7°. Establishment of normal electrocardiogram (EKG) values will facilitate a better understanding of EKG changes seen in many diseases of these birds.
Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type

The increased application of nanoparticles (NPs) is increasing the risk of their release into the environment. Although many toxicity studies have been conducted, the environmental risk is difficult to estimate, because uptake mechanisms are often not determined in toxicity studies. In the present study, the authors review dominant uptake mechanisms of NPs in cells, as well as the effect of NP properties, experimental conditions, and cell type on NP uptake. Knowledge of NP uptake is crucial for risk assessment and is essential to predict the behavior of NPs based on their physical–chemical properties. Important uptake mechanisms for eukaryotic cells are macropinocytosis, receptor‐mediated endocytosis, and phagocytosis in specialized mammalian cells. The studies reviewed demonstrate that uptake into nonphagocytic cells depends strongly on NP size, with an uptake optimum at an NP diameter of approximately 50 nm. Increasing surface charges, either positive or negative, have been shown to increase particle uptake in comparison with uncharged NPs. Another important factor is the degree of (homo‐) aggregation. Results regarding shape have been ambiguous. Difficulties in the production of NPs, with 1 property changed at a time, call for a full characterization of NP properties. Only then will it be possible to draw conclusions as to which property affected the uptake. Environ Toxicol Chem 2014;33:481–492. © 2013 SETAC
The effect of Tehran metro rail system on residential property values: A comparative analysis between high-income and low-income neighbourhoods

Estimating the effect of rail transit on residential property values has resulted in mixed findings. Some researchers report positive effects on property values while others are negative or insignificant. The current paper argues that the impact of rail transit on property values depends on contextual factors which can influence magnitude and direction of the impact and cause variation in the findings. Tehran’s Metro Rail System is chosen because the neighbourhoods served by the metro to the north side and south side of the city are dramatically different in terms of economic, social and physical circumstances. A comparative analysis of six of Tehran’s metro stations is conducted between the high-income neighbourhoods, which are located primarily on the city’s north side, and lower-income neighbourhoods on the south side to determine the effects of proximity to metro stations on residential property values. The paper uses a mixed-method sequential explanatory design based on a before-and-after estimation strategy, which includes trend analysis, difference-in-differences model and qualitative impact assessment methods. The results show that there are large increases in premiums for residential properties near the lower-income neighbourhoods, the south side parts of the Tehran Metro Rail System, while a negative treatment effect for residential properties lying close to the northern stations in the high-income neighbourhoods. The qualitative survey also suggests that the impact of metro station is affected by a number of contextual factors, including the need for public transportation, land-use planning and management, socio-cultural effect and possible nuisance effects.