Miracle-dz/UniFAR-FTUs huggingface dataset:
On k-NN Method with Preprocessing

The objective of this study is to introduce a new model of data classification based on preliminary reduction of the training set of examples (preprocessing) in order to facilitate the use of nearest neighbours (NN) techniques in near real-time applications. This study accordingly addresses the issue of minimising the computational resource requirements of NN techniques, memory as well as time. The approach proposed in the paper is a modification of the classical k-Nearest Neighbours (k-NN) method and the k-NN method with local metric induction. Generally, the k-NN method with local metric induction in comparison with the classical k-NN method gives better results in the classification of new examples. Nevertheless, for the large data sets the k-NN method with local metric induction is less time effective than the classical one. The time/space efficiency of classifying algorithms based on these two methods depends not only on a given metric but also on the size of training data. In the paper, we present three methods of preliminary reduction of the training set of examples. All reduction methods decrease the size of a given experimental data preserving the relatively high classification accuracy. Results of experiments conducted on well known data sets, demonstrate the potential benefits of such reduction methods.
Up‐regulation of survivin by AKT and hypoxia‐inducible factor 1α contributes to cisplatin resistance in gastric cancer

This study investigated the contribution of survivin and its upstream regulators, AKT and hypoxia‐inducible factor 1α (HIF–1α), to the resistance of gastric cancer cells to cisplatin (CDDP). We found that over‐expression of survivin increased the resistance of SGC7901 and BGC823 gastric cancer cells to CDDP. Its over‐expression abrogated CDDP‐induced inhibition of cell proliferation and CDDP‐induced cell apoptosis. In contrast, down‐regulation of survivin expression using small hairpin RNA (shRNA) vectors and the small‐molecule inhibitor YM155, or inhibition of survivin function using a recombinant cell‐permeable dominant‐negative survivin protein (dNSur9), promoted CDDP‐induced apoptosis. CDDP‐resistant sub‐lines generated from the parental SGC7901 and BGC823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF–1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (pAKT). Specific inhibition of AKT reduced the expression of HIF–1α and survivin, whereas specific inhibition or depletion of HIF–1α reduced survivin expression but had no effect on the expression of phosphorylated AKT. The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF–1α enhanced the sensitivity of CDDP‐resistant cells to CDDP. Specific inhibition of survivin, AKT and HIF‐1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up‐regulation of survivin by AKT and HIF–1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.
Structure-Based Prediction of the Nonspecific Binding of Drugs to Hepatic Microsomes

For the accurate prediction of in vivo hepatic clearance or drug–drug interaction potential through in vitro microsomal metabolic data, it is essential to evaluate the fraction unbound in hepatic microsomal incubation media. Here, a structure-based in silico predictive model of the nonspecific binding (fumic, fraction unbound in hepatic microsomes) for 86 drugs was successfully developed based on seven selected molecular descriptors. The R2 of the predicted and observed log((1 − fumic)/fumic) for the training set (n = 64) and test set (n = 22) were 0.82 and 0.85, respectively. The average fold error (AFE, calculated by fumic rather than log((1 − fumic)/fumic)) of the in silico model was 1.33 (n = 86). The predictive capability of fumic for neutral drugs compared well to that for basic compounds (R2 = 0.82, AFE = 1.18 and fold error values were all below 2, except for felodipine and progesterone) in our model. This model appears to perform better for neutral compounds when compared to models previously published in the literature. Therefore, this in silico model may be used as an additional tool to estimate fumic and for predicting in vivo hepatic clearance and inhibition potential from in vitro hepatic microsomal studies.
Anti-Ro/SSA antibodies in rheumatoid arthritis: clinical and immunologic associations.

OBJECTIVE To assess the prevalence of anti-Ro/SSA in RA and to analyse clinical and serological features of anti-Ro/SSA positive patients with RA. METHODS 195 consecutive patients affected by RA were studied by counterimmunoelectrophoresis and ELISA for the detection of anti-Ro/SSA antibodies. Anti-Ro were found in 12 patients, with a prevalence of 6%. These 12 patients were pooled with other 15 patients known to have anti-Ro/SSA antibodies and RA, in order to evaluate their clinical and laboratory features. RESULTS Anti-Ro positive patients showed a common pattern of joint involvement at onset and a comparable progression of disease compared to anti-Ro negative subjects. In addition, extra-articular manifestations (such as xerophthalmia, xerostomia, scleritis, oral ulcers and amyloidosis) and peculiar autoantibody profile (hypergammaglobulinemia, anti-dsDNA and AMA) were found significantly associated to anti-Ro/SSA positivity. Even though DMARDs withdrawals were more frequently detected in anti-Ro/SSA patients, especially when using gold salts, no statistical difference between the two groups was detected. In addition, anti-TNFalpha treatment did not cause further progression of autoimmunity neither on laboratory nor on clinical ground. CONCLUSION Anti-Ro/SSA can be detected in about 6% of patients affected by RA. These patients presented a peculiar clinical picture characterised by extra-articular manifestations some of which are known to be anti-Ro/SSA correlated, while others are more disease-specific (amyloidosis, episcleritis). Anti-Ro/SSA are significantly associated with other autoantibodies not specific for RA such as anti-dsDNA and AMA. Treatment with anti-TNF drugs did not cause further progression of autoimmunity neither on laboratory nor on clinical ground.
Guidelines for the management of hemophilia

Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.
Outcomes of Adrenalectomy in Patients with Unilateral Primary Aldosteronism: A Review

Abstract Aldosterone hypersecretion in primary aldosteronism is unilateral (aldosterone producing adenoma and primary unilateral hyperplasia) or bilateral (idiopathic adrenal hyperplasia). Laparoscopic adrenalectomy is nowadays the preferred approach to treat patients with unilateral primary aldosteronism. We review the outcomes of this intervention in recently published series. Laparoscopic adrenalectomy has a morbidity of 5–14%, mortality below 1%, and a mean hospital stay around 3 days. It generally results in the normalization of aldosterone secretion and in a large decrease of blood pressure and antihypertensive medication, but normotension without treatment is only achieved in 42% of all cases. Normotension following adrenalectomy is more likely in young and lean women with recent low grade hypertension than in obese men with long-standing high grade hypertension or a family history of hypertension. However, individual prediction of the blood pressure outcome is not accurate and predictors of hypertension cure should not be used to select patients for surgery. Age, associated health conditions and preferences of the patient are more relevant to this end.
Endoscopic Treatment of Vesicoureteral Reflux with Polydimethylsiloxane in Adults: Do Location and Appearance of the Ureteric Orifice Have a Role in the Success Rates?

Introduction: Low success rate for high grade reflux and anatomical abnormality of ureteric orifices continues to be the most important dilemma of the endoscopic treatment of vesicoureteral reflux (VUR). The aim of this study was to evaluate the efficacy of endoscopic polydimethylsiloxane injection in adults with VUR concerning reflux severity and the status of the ureteric orifice. Materials and Methods: Fifty-three ureters (34 patients) were treated with endoscopic polydimethylsiloxane injection. The grade of VUR was I, II, III, IV and V in 2, 13, 25, 10 and 3 ureters, respectively.Any endoscopic characteristics of ‘golf hole’, broad appearance or lateral placement of ureteric orifices were classified as complex appearance ureters (CAU). Patients with persistent reflux were considered for second and third injections with the same material. Success was determined as no reflux. Results: The total success rate was 100, 92.30, 92, 80 and 66.66% for grade I, II, III, IV and V reflux after the third injection, respectively. The cure rates of ureters with normal appearance were 100, 88.88, 90, 100 and 100% for grade I, II, III, IV and V reflux. The cure rates of CAU were 100% for both grade II and III, 60% for grade IV and 50% for grade V reflux. The injected volumes per renal unit ranged between 0.2 and 3.2 ml (mean 1.05 ml). Conclusions: Although there are disadvantages in the usage of higher volumes of injectable material for successful results and difficulty in subureteral injection both in high grade reflux and complex anatomical situations in adults when compared to children, our results indicate that endoscopic treatment of VUR is an effective therapy for adults.
IMMP 7-1 The Inhibitory Effect of Selenomethionine and Sodium Selenite on a Human Cholangiocyte MMNK 1 Cell Line

Cholangiocarcinoma (CCA) is a malignant tumor arisen from bile duct epithelial cells. Liver fluke (Opisthorchis viverrini) infection is considered as a main cause of CCA in Northeast Thailand. Low Se intake has been found to be associated with the high risk of several cancers. The chemotherapeutic and chemopreventive potentials of several selenium compounds have been studied and proved in many cancers, which draw our attention on the selenium supplements on CCA. This study aimed to demonstrate the inhibitory effect of 2 selenium compounds, selenomethionine (SeMet) and sodium selenite, on cell viability and migration of a human immortal cholangiocyte MMNK1 cell line using sulforhodamine B assay and wound healing assay, respectively. Our results showed that selenium compounds suppressed the cell viability of MMNK1 but they did not affect cell migration. Our data suggest for the role of selenium compounds in CCA chemoprevention.
Output feedback passification of saturated switched systems

ABSTRACT This paper addresses the passivity and feedback passification of the saturated switched systems. A switching law and output feedback controllers are designed such that the corresponding closed-loop systems are with the passivity and disturbance tolerance capacity. The switching law satisfies a maximal dwell time (DT) condition, which avoids too high switching frequency. More importantly, under the switching law, the storage function is allowed to be increased during the DT and then decreased due to the drop of itself at the mixed time/state-dependent switching instants. This releases the performance requirement of existing results where the storage function must be non-increasing all the time. Finally, the existence of the upper bound of DT and output feedback controllers is guaranteed by solving some linear matrix inequalities. Two examples are given to show the effectiveness of the proposed method.
The influence of sex hormones upon hepatic lesions produced by 2-acetaminofluorene.

The carcinogenic action of 2-acetaminofluorene has been described by Wilson, De Eds and Cox (14) and by Bielschowsky (1). This compound is particularly interesting because of the fact that, when fed to stock albino rats (14) and to descendants of Wistar rats (1), it produced a greater variety of tumors than most known carcinogens. Bielschowsky (2) reported the development of benign and malignant tumors of the thyroid in rats following simultaneous administration of 2-acetaminofluorene and the antithyroid drug, allylthiourea, the carcinogen alone being without influence upon the normal gland. Adenomas of the thyroid, but not malignant tumors, have been observed in rats fed allylthiourea (3), brassica seed (5) and thiouracil (10) for long periods of time. This observation of the susceptibility of the stimulated goitrous thyroid to the tumor-producing action of the carcinogen suggested that it might be interesting to investigate the influence in this connection of other agents that stimulate growth of specific tissues. Androgenic and estrogenic hormones were chosen for this purpose.
Effect of Customer Satisfaction on Performance of the Hotel Industry in the Western Tourism Circuit of Kenya

The hotel industry is one of the fastest growth sectors of the global economies; its significant contribution is seen to be on an upward trend, as evidenced even here in Kenya where international hotel chains are opening its branches to reap the market rewards from this competitive industry. The purpose of this research project was to find out the effect of customer satisfaction in this industry. The researcher employed descriptive research design, simple random sampling was used, questionnaire as the research instrument was used for data collection, and descriptive statistics was used in analyzing data. Presentation of data was done through use of bar graphs, pie chart and frequency tables. The research findings showed, hotels strive to meet the expectations of the hotel customers through provision of excellent services in pursuit of customer satisfaction, and the customers appreciate this by becoming not only regular, but also loyal clients’, hence good performance of the hotel. The hotel industry in western tourism circuit of Kenya has low performance as compared to what other tourism regions has, yet the tourism circuit has unique and great potential to offer. These research findings suggested some appropriate hotel strategies that may enhance customer satisfaction Key Words : Customer, customer satisfaction, hotel performance
Reversible Oxidation of ERK-directed Protein Phosphatases Drives Oxidative Toxicity in Neurons*

Oxidative stress links diverse neuropathological conditions that include stroke, Parkinson's disease, and Alzheimer's disease and has been modeled in vitro with various paradigms that lead to neuronal cell death following the increased accumulation of reactive oxygen species. For example, immortalized neurons and immature primary cortical neurons undergo cell death in response to depletion of the antioxidant glutathione, which can be elicited by administration of glutamate at high concentrations. We have demonstrated previously that this glutamate-induced oxidative toxicity requires activation of the mitogen-activated protein kinase member ERK1/2, but the mechanisms by which this activation takes place in oxidatively stressed neurons are still not fully known. In this study, we demonstrate that during oxidative stress, ERK-directed phosphatases of both the serine/threonine- and tyrosine-directed classes are selectively and reversibly inhibited via a mechanism that is dependent upon the oxidation of cysteine thiols. Furthermore, the impact of ERK-directed phosphatases on ERK1/2 activation and oxidative toxicity in neurons was tested in a neuronal cell line and in primary cortical cultures. Overexpression of the highly ERK-specific phosphatase MKP3 and its catalytic mutant, MKP3 C293S, were neuroprotective in transiently transfected HT22 cells and primary neurons. The neuroprotective effect of the MKP3 C293S mutant, which enhances ERK1/2 phosphorylation but blocks its nuclear translocation, demonstrates the necessity for active ERK1/2 nuclear localization for oxidative toxicity in neurons. Together, these data implicate the inhibition of endogenous ERK-directed phosphatases as a mechanism that leads to aberrant ERK1/2 activation and nuclear accumulation during oxidative toxicity in neurons.
Activity‐dependent reconfiguration of the effective dendritic field of motoneurons

A neuron in vivo receives a continuous bombardment of synaptic inputs that modify the integrative properties of dendritic arborizations by changing the specific membrane resistance (Rm). To address the mechanisms by which the synaptic background activity transforms the charge transfer effectiveness (Tx) of a dendritic arborization, the authors simulated a neuron at rest and a highly excited neuron. After in vivo identification of the motoneurons recorded and stained intracellularly, the motoneuron arborizations were reconstructed at high spatial resolution. The neuronal model was constrained by the geometric data describing the numerized arborization. The electrotonic structure and Tx were computed under different Rm values to mimic a highly excited neuron (1 kOhm.cm2) and a neuron at rest (100 kOhm.cm2). The authors found that the shape and the size of the effective dendritic fields varied in the function of Rm. In the highly excited neuron, the effective dendritic field was reduced spatially by switching off most of the distal dendritic branches, which were disconnected functionally from the somata. At rest, the entire dendritic field was highly efficient in transferring current to the somata, but there was a lack of spatial discrimination. Because the large motoneurons are more sensitive to variations in the upper range of Rm, they switch off their distal dendrites before the small motoneurons. Thus, the same anatomic structure that shrinks or expands according to the background synaptic activity can select the types of its synaptic inputs. The results of this study demonstrate that these reconfigurations of the effective dendritic field of the motoneurons are activity‐dependent and geometry‐dependent. J. Comp. Neurol. 422:18–34, 2000. © 2000 Wiley‐Liss, Inc.
Political clientelism and the media: southern Europe and Latin America in comparative perspective

This article explores the relationship between political clientelism and the development of media systems in southern Europe and Latin America, considering the cases of Greece, Italy, Spain, Portugal, Mexico, Colombia and Brazil. Common characteristics of the media systems in these countries include low newspaper circulation, a tendency towards political instrumentalization of the media, limited development of journalism as a differentiated and autonomous profession, and regulatory agencies that are at the same time party-politicized and relatively weak. We argue that these media-system characteristics must be understood in relation to a broader history of political clientelism - though a number of forces, including commercialization of media industries and globalization, have tended in recent years to undermine clientelistic relationships.
Tissue microarray design and construction for scientific, industrial and diagnostic use

Context: In 2013 the high throughput technology known as Tissue Micro Array (TMA) will be fifteen years old. Its elements (design, construction and analysis) are intuitive and the core histopathology technique is unsophisticated, which may be a reason why has eluded a rigorous scientific scrutiny. The source of errors, particularly in specimen identification and how to control for it is unreported. Formal validation of the accuracy of segmenting (also known as de-arraying) hundreds of samples, pairing with the sample data is lacking. Aims: We wanted to address these issues in order to bring the technique to recognized standards of quality in TMA use for research, diagnostics and industrial purposes. Results: We systematically addressed the sources of error and used barcode-driven data input throughout the whole process including matching the design with a TMA virtual image and segmenting that image back to individual cases, together with the associated data. In addition we demonstrate on mathematical grounds that a TMA design, when superimposed onto the corresponding whole slide image, validates on each and every sample the correspondence between the image and patient′s data. Conclusions: High throughput use of the TMA technology is a safe and efficient method for research, diagnosis and industrial use if all sources of errors are identified and addressed.
Effects of external tetraethylammonium ions and quinine on delayed rectifying K+ channels in mouse pancreatic beta‐cells.

1. The whole‐cell and outside‐out patch configurations of the patch‐clamp technique were used to study the mechanisms of block produced by external tetraethylammonium ions (TEA+) and quinine on delayed rectifying K+ channels in mouse pancreatic beta‐cells. 2. In whole‐cell recordings, TEA+ blocks the delayed outward current (which reflects the activity of delayed rectifying K+ channels by greater than 85%) in a concentration‐dependent manner. The block appeared to be 1:1 with a Kd of approximately 1.4 mM at a membrane potential of 0 mV. The value of Kd varied with the membrane potential and there was an e‐fold increase for a 70 mV depolarization. 3. Single‐channel recordings revealed that delayed rectifying K+ channels have a unitary conductance of 8.5 pS ([K+]1 = 155 mM; [K+]o = 5.6 mM) and a single‐channel K+ permeability of 2.8 X 10(‐14) cm3 s‐1. 4. First latency histograms of channel openings during voltage pulses from ‐70 to 0 mV peaked after 4 ms. A reaction scheme involving two closed states adequately but not perfectly described the distribution of the first latencies. The openings of the channels were grouped in bursts and the distribution of the closed times required two exponentials with time constants of 2.0 and 13 ms, respectively. The distribution of the open times could be described by a single exponential with a time constant of 25 ms. 5. Channel block produced by TEA+ (1 mM) was associated with a 40% decrease of the single‐channel current amplitudes and a reduction in single‐channel K+ permeability to 1.9 X 10(‐14) cm3 s‐1 but did not measurably affect the single‐channel kinetics suggesting that the blocking reaction is very rapid. 6. Quinine blocked the whole‐cell delayed outward current in a concentration‐dependent manner. Half‐maximal inhibition was attained at approximately 4 microM and the binding appeared to be 2:1. 7. Single‐channel recordings indicated that the inhibition produced by quinine (10 microM) resulted from a decrease in the duration of the openings to a mean value of 6.7 ms. The time constants for the distribution of the closures were increased by approximately 30%. Quinine did not affect the amplitude of the openings. The rate constant of the blocking reaction (kB) was 15 mM‐1 ms‐1 at 0 mV.
Dipole Antenna Above EBG Substrate for Local SAR Reduction

This letter investigates the performance of a dipole antenna above an electromagnetic band-gap (EBG) substrate to realize a low specific absorption rate (SAR) antenna. The frequency band considered is 3.5 GHz, which is assigned to fourth-generation mobile communications. One of the motivations for this proposal is that the size of the EBG substrate can be small enough for a handset. The dipole antenna above the EBG substrate was found to reduce the local SAR in a cubic head model by 84% as compared to the local SAR of a perfect electric conductor. The radiation efficiency was also improved by 10%. These results were also confirmed for a realistic head model.