Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered microsatellites in incomplete-type intestinal metaplasia adjacent to primary gastric cancers.

AIM: To investigate the presence of genetic instability in precancerous lesions of the stomach. METHODS: Fifteen cases of sporadic gastric cancers with a background of intestinal metaplasia were studied by microsatellite assay at nine loci. Altered metaplastic mucosa was microdissected, reconstructed topographically, and examined immunohistochemically with an anti-p53 antibody, comparing its positive area with foci of microsatellite instability in each individual. RESULTS: Alterations at one or more loci were observed in seven of 15 cancers (46.7%) and four of 15 intestinal metaplasias (26.7%). Two cases of replication error positive phenotype had no microsatellite alterations in their metaplastic mucosa. All the microsatellite alterations in the metaplastic mucosa were restricted to incomplete-type intestinal metaplasia around the respective cancers. Moreover, in one case, an identical pattern of microsatellite alteration was detected in the cancer tissue and in the adjacent metaplastic mucosa, suggesting the sequential development of gastric cancer from intestinal metaplasia. Frequent alteration was found at the locus D1S191 (1q), indicating that this locus might be altered early in the development of intestinal-type gastric cancer. No significant association between microsatellite instability and p53 immunoreactivity was observed in the cases examined. CONCLUSION: These results indicate that microsatellite instability may be an early event in stomach carcinogenesis, especially in intestinal-type cancers.
Advances in Brief Childhood Hepatoblastomas Frequently Carry a Mutated Degradation Targeting Box of the b-Catenin Gene 1

Hepatoblastomas (HBs) are embryonal tumors affecting young children and representing the most frequent malignant liver tumors in childhood. The molecular pathogenesis of HB is poorly understood. Although most cases are sporadic, the incidence is highly elevated in patients with familial adenomatous polyposis coli. These patients carry germline mutations of the APC tumor suppressor gene. APC controls the degradation of the oncogene productb-catenin after its NH2-terminal phosphorylation on serine/threonine residues. APC, as well as b-catenin, has been found to be a central effector of the growth promoting winglesssignaling pathway in development. To find out if this pathway is involved in the pathogenesis of sporadic HBs, we examined 52 biopsies and three cell lines from sporadic HBs for mutations in the APC and b-catenin genes. Using single-strand conformational polymorphism analysis, deletion screening by PCR, and direct sequencing, we found a high frequency of b-catenin mutations in sporadic HBs (48%). The mutations affected exon 3 encoding the degradation targeting box of b-catenin leading to accumulation of intracytoplasmic and nuclearb-catenin protein. The high frequency of activating mutations in the b-cateningene indicates an important role in the pathogenesis of HB.
Causality between corruption and the level of GDP

Abstract Interaction between corruption and economic development is one of the most widely studied topics in the recent history of scientific research. Because of the strong influence of both these factors on the standard of living, we have tried to answer the following question: In what time frame is the interaction between these two factors most prominent? Taking into account the data of the level of corruption (as measured by the Corruption Perception Index (CPI) and economic development (as measured by the movement of GDP per year), in the time period from 1995 to 2011, we divided the research results into three time zones: zone 1 – which covers the time period of the first five years (short-term impacts), zone 2 – which covers the time period of the next five years (medium-term impacts), and finally zone 3 – which covers the time period of the last five years (long-term impacts). Based on the research results, we have come to conclusion that the strongest causality between these two factors are in zone 2, the so-called medium-term framework. The empirical findings of this article suggest that further research in this direction is necessary, if we take into account the fact that corruption is present in almost all countries of the world.
Percutaneous catheter ablation of arrhythmias in children.

BACKGROUND Supraventricular tachycardias (SVTs) are the most common arrhythmias in children, with Wolff-Parkinson-White (WPW) syndrome the most prevalent entity. Percutaneous catheter ablation is now the standard of care for SVT in pediatric patients, although specific techniques are required due to their age. OBJECTIVE To evaluate the results of percutaneous catheter ablation of arrhythmias in children at our institution. METHODS This was a retrospective study of the clinical records of patients aged 18 years who underwent electrophysiologic study and ablation between January 2002 and December 2006. The following variables were evaluated: demographic data, type of arrhythmia, associated structural heart disease, type of energy used, immediate and late success rate and incidence of complications. RESULTS During this period, 101 procedures were performed in 97 patients aged < or = 18 years. The mean age of the patients was 15.9 +/- 2.5 years (range: 7.7-18 years), and fifty-five (56.7%) were male. The arrhythmias treated were, in decreasing order of frequency: WPW syndrome (58.4%), atrioventricular reentrant tachycardia (25.7%), atrial tachycardia (5.9%), right ventricular outflow tract (RVOT) tachycardia (5%), ventricular tachycardia (2%), atrial fibrillation (2%) and frequent extrasystoles originating in the left atrium (1%). There was associated structural heart disease in six patients. Cryoablation was performed in four cases (parahisian accessory pathways in three and anterolateral accessory pathway in one). The immediate success rate was 94.1%. The six unsuccessful cases corresponded to five with parahisian accessory pathways (the procedure was not completed due to very high risk of inducing complete atrioventricular block [AVB]) and one case of RVOT tachycardia associated with arrhythmogenic right ventricular dysplasia. There were complications in two procedures (2%): one case of right bundle branch block and one of ventricular tachycardia requiring electrical cardioversion. The mean follow-up was 17.6 months. In 87.1% of cases there was clinical and ECG success on long-term followup. Three patients (3%) required repeat procedures, and were asymptomatic in later follow-up. CONCLUSION Percutaneous catheter ablation of arrhythmias in children proved to be a safe and effective treatment.
Imaging extrasynaptic glutamate dynamics in the brain

Glutamate is the major neurotransmitter in the brain, mediating point-to-point transmission across the synaptic cleft in excitatory synapses. Using a glutamate imaging method with fluorescent indicators, we show that synaptic activity generates extrasynaptic glutamate dynamics in the vicinity of active synapses. These glutamate dynamics had magnitudes and durations sufficient to activate extrasynaptic glutamate receptors in brain slices. We also observed crosstalk between synapses—i.e., summation of glutamate released from neighboring synapses. Furthermore, we successfully observed that sensory input from the extremities induced extrasynaptic glutamate dynamics within the appropriate sensory area of the cerebral cortex in vivo. Thus, the present study clarifies the spatiotemporal features of extrasynaptic glutamate dynamics, and opens up an avenue to directly visualizing synaptic activity in live animals.
Seasonal Changes Drive Short-Term Selection for Fitness Traits in the Wheat Pathogen Zymoseptoria tritici

ABSTRACT In a cross-infection experiment, we investigated how seasonal changes can affect adaptation patterns in a Zymoseptoria tritici population. The fitness of isolates sampled on wheat leaves at the beginning and at the end of a field epidemic was assessed under environmental conditions (temperature and host stage) to which the local pathogen population was successively exposed. Isolates of the final population were more aggressive, and showed greater sporulation intensity under winter conditions and a shorter latency period (earlier sporulation) under spring conditions, than isolates of the initial population. These differences, complemented by lower between-genotype variability in the final population, exhibited an adaptation pattern with three striking features: (i) the pathogen responded synchronously to temperature and host stage conditions; (ii) the adaptation concerned two key fitness traits; (iii) adaptation to one trait (greater sporulation intensity) was expressed under winter conditions while, subsequently, adaptation to the other trait (shorter latency period) was expressed under spring conditions. This can be interpreted as the result of short-term selection, driven by abiotic and biotic factors. This case study cannot yet be generalized but suggests that seasonality may play an important role in shaping the variability of fitness traits. These results further raise the question of possible counterselection during the interepidemic period. While we did not find any trade-off between clonal multiplication on leaves during the epidemic period and clonal spore production on debris, we suggest that final populations could be counterselected by an Allee effect, mitigating the potential impact of seasonal selection on long-term dynamics.
Design of On-Chip Transformer With Various Coil Widths to Achieve Minimal Metal Resistance

A layout design algorithm of a variable-width transformer is proposed to minimize metal resistance in this letter. The proposed algorithm can rapidly design metal widths in each coil of a planar transformer for a given chip area. Two on-chip transformers with identical self-inductance are fabricated to verify the proposed algorithm in 90-nm CMOS technology. Measurement results demonstrate the improvement of metal resistance approximates to the value of 11.6%. Results of this study provide an effective algorithm to design a minimal-loss transformer for radio frequency integrated circuit applications.
Efficacy of low dose intravenous immunoglobulins in children with toxic epidermal necrolysis: an open uncontrolled study.

BACKGROUND High dose intravenous immunoglobulins (IVIG) have emerged as a promising new therapy for treating the rare but potentially fatal drug reaction toxic epidermal necrolysis (TEN). Experimental in vitro studies support the view that IVIG can block the fas-fas ligand mediated apoptosis in TEN. METHODS Ten pediatric patients of TEN were treated with IVIG (0.05 - 0.1 gm/kg/day) along with antibiotics and supportive care. RESULTS Patients with 67% of mean body surface area of involvement showed an average of 2.1 days for arrest of progression of lesions and 8.1 days for complete reepithelization. There was no mortality. CONCLUSIONS Low dose IVIG appears to be a safe and effective treatment for TEN in children. Randomized trials are needed to further evaluate the efficacy of IVIG and compare it with other therapeutic modalities.
Multiple sclerosis unaffected by azathioprine in pilot study.

Azathioprine (2.0 to 4.7 mg/kg/day) was administered to 15 multiple sclerosis patients for an average of 15 months. The conditions of five of six patients who had chronic progressive courses prior to administration of azathioprine continued to deteriorate. Four of six patients who had a remitting and exacerbating course had six exacerbations in a total of 78 months of treatment, an average of one exacerbation per 13 months. Evidence of varying degrees of immune suppression occurred in approximately half the patients. Neither the type nor degree of suppression, nor the dose of azathioprine required to depress the patients' peripheral white blood cell count to 4,000/cu mm bore any relationship to their clinical course. We see no evidence for beneficial effect of azathioprine administered to multiple sclerosis patients in doses ordinarily regarded as immunosuppressive.
Evaluation of a Newly Developed GenoArray Human Papillomavirus (HPV) Genotyping Assay and Comparison with the Roche Linear Array HPV Genotyping Assay

ABSTRACT Persistent infection with high-risk types of human papillomavirus (HPV) is a necessary step in the development of cervical cancer. The incorporation of HPV detection into cervical screening programs may improve the ability to identify women at risk of cervical cancer. We recently evaluated the performance characteristics of a newly developed HPV detection assay, the GenoArray (GA) genotyping assay, for the detection of HPV infections by comparing it with the commercial Roche Linear Array (LA) HPV genotyping assay. The GA assay has an analytical sensitivity for the detection of HPV types 16 (HPV-16) and HPV-18 of as few as 10 to 50 copies, and its reproducibility is adequate. The GA and LA assays showed no significant difference in the rates of detection of genotypes detected by both HPV genotyping assays and oncogenic genotypes, and the interassay agreement was excellent. The GA and LA assays revealed either concordant or compatible genotyping results for 97.5% of the samples and discordant results for only eight (2.5%) samples. Compatible results were also observed for the detection of single or multiple HPV infections and the detection of most of the genotypes. The GA assay also demonstrated good clinical performance characteristics when the comparisons were carried out with clinical subgroups of samples from patients with normal cytologies, low-grade or high-grade squamous intraepithelial lesions, and cancers. Therefore, the GA assay appears to be highly sensitive and specific for the genotyping of HPV. It has the advantage that it specifically detects HPV-52, which overcomes a limitation of the LA assay, and hence, it has potential value for use for genotyping, especially in regions where HPV-52 has a high prevalence.
On Relay Selection and Subcarrier Assignment for Multiuser Cooperative OFDMA Networks With QoS Guarantees

This paper investigates quality of service (QoS)-aware relay selection and subcarrier assignment in multiuser OFDMA relay networks. In contrast to some existing works, which solve the sum-rate maximization problem directly, we first simplify it by exploiting the structure of the optimal solution and then consider the simplified problem from the perspectives of both primal and dual optimality. To characterize the optimal sum-rate performance, we solve the simplified problem optimally by the branch-and-cut method. In addition to the sum-rate maximization problem, we demonstrate that its two variants, namely, the worst-user rate maximization problem and the mixed rate maximization problem, can be also similarly simplified and then solved optimally by the branch-and-cut method. The optimal method serving as the benchmark is particularly suitable for problems of moderate scale. Furthermore, we study the simplified sum-rate maximization problem comprehensively from a dual perspective and propose three types of subgradient methods for the dual problem. The dual subgradient methods obtaining near-optimal solutions can be implemented in a distributed manner and thus are quite suitable for high-dimensional problems. To provide more in-depth analysis, we further consider the scenario in which subcarrier pairing is incorporated and suggest the natural generalization from the one-source-node case to the multiple-source-node case. Finally, two groups of simulations are conducted to validate the optimality of the branch-and-cut method and the effectiveness of the dual subgradient methods.
Identification of Ribosome-binding Protein p34 as an Intracellular Protein That Binds Acidic Fibroblast Growth Factor*

With the aim of identifying new intracellular binding partners for acidic fibroblast growth factor (aFGF), proteins from U2OS human osteosarcoma cells were adsorbed to immobilized aFGF. One of the adsorbed proteins is a member of the leucine-rich repeat protein family termed ribosome-binding protein p34 (p34). This protein has previously been localized to endoplasmic reticulum membranes and is thought to span the membrane with the N terminus on the cytosolic side. Confocal microscopy of cells transfected with Myc-p34 confirmed the endoplasmic reticulum localization, and Northern blotting determined p34 mRNA to be present in a multitude of different tissues. Cross-linking experiments indicated that the protein is present in the cell as a dimer. In vitro translated p34 was found to interact with maltose-binding protein-aFGF through its cytosolic coiled-coil domain. The interaction between aFGF and p34 was further characterized by surface plasmon resonance, giving aK D of 1.4 ± 0.3 μm. Even though p34 interacted with mitogenic aFGF, it bound poorly to the non-mitogenic aFGF(K132E) mutant, indicating a possible involvement of p34 in intracellular signaling by aFGF.
Developmental systems and psychopathology

Efforts to understand the etiology of adult mental disorders by studying children has produced unanticipated changes in our understanding of pathology, individual development, and the role of social context. Among these are the blurring of the division between mental illness and mental health, the need to attend to patterns of adaptation rather than personality traits, and the powerful influences of the social world on individual development. Current developmental views place deviancy in the dynamic relation between individuals and their contexts. At another level, when we view the history of developmental psychopathology, dialectical developmental processes are evident as we trace how patterns of adaptation of researchers, expressed in theoretical models and empirical paradigms, increasingly have come to match the complexities of human mental health and illness.
Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics

Abstract 1. We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2. Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3. Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4. Using the fluorescent probe 5 (and 6)-carboxy-2′,7′-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5. These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones.
The effect of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis.

BACKGROUND Low-dose doxycycline (LDD) is recognized to have non-antimicrobial properties that can therapeutically modulate the host response. The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of LDD in combination with non-surgical periodontal therapy, compared to non-surgical periodontal therapy alone, on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels and clinical parameters over a 12-month period in patients with chronic periodontitis. METHODS GCF samples were collected, and clinical parameters including probing depth (PD), clinical attachment level, gingival index (GI), and plaque index were recorded. Thirty chronic periodontitis patients were randomized either to a low-dose doxycycline (LDD) or placebo group. The LDD group received low-dose doxycycline (20 mg) b.i. d. for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i. d. for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, all clinical measurements and GCF sampling were repeated. GCF MMP-8 levels were determined by a time-resolved immunofluorescence assay. Intragroup comparisons were tested by the Friedman test followed by Wilcoxon signed-rank test to analyze significance of changes over time. The Mann-Whitney test was used to determine differences between the LDD and placebo groups. RESULTS Significant improvements were observed in all clinical parameters in both groups over the 12-month period (P < 0.0125). The LDD group showed a significantly greater reduction in mean PD scores at 9 and 12 months and in mean GI scores at all time points than the placebo group (P < 0.05). From baseline to 12 months, GCF MMP-8 levels were significantly reduced in both groups (P < 0.0125). The GCF MMP-8 level in the LDD group was significantly lower than that of the placebo group at 6 months (P < 0.05). CONCLUSIONS The present results indicate that low-dose doxycycline therapy in combination with scaling and root planing can reduce GCF MMP-8 levels and improve clinical periodontal parameters in patients with chronic periodontitis. These results provide additional information about the usefulness of low-dose doxycycline therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease. The effectiveness and course of low-dose doxycycline therapy can be monitored conveniently by assessing GCF MMP-8 levels.
Experimental and Analytical Analysis of Sorting Algorithms Error Criticality for HPC and Large Servers Applications

In this paper, we investigate neutron-induced errors in three implementations of sort algorithms (QuickSort, MergeSort, and RadixSort) executed on modern graphics processing units designed for high-performance computing and large server applications. We measure the radiation-induced error rate of sort algorithms taking advantage of the neutron beam available at the Los Alamos Neutron Science Center facility. We also analyze output error criticality by identifying specific output error patterns. We found that radiation can cause wrong elements to appear in the sorted array, misalign values as well as application crashes or system hangs. This paper presents results showing that the criticality of the radiation-induced output error pattern depends on the application. Additionally, an extensive fault-injection campaign has been performed. This campaign allows for better understanding of the observed phenomena. We take advantage of SASS-assembly Intrumentator Fault Injector developed by NVIDIA, which can inject faults into all the user-accessible architectural state. Comparing fault-injection results with radiation experiments data provides an understanding that not all the output errors observed under radiation can be replicated in fault injection. However, fault injection is useful in identifying possible root causes of the output errors observed in radiation testing. Finally, we take advantage of our experimental and analytical study to design efficient experimentally tuned hardening strategies. We detect the error patterns that are critical to the final application and find the more efficient way to detect them. With an overhead as low as 16% of the execution time, we are able to reduce the output error rate of sort of about one order of magnitude.