Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Streptococcus mutans polysaccharide synthesis by molecules targeting glycosyltransferase activity

Glycosyltransferase (Gtf) is one of the crucial virulence factors of Streptococcus mutans, a major etiological pathogen of dental caries. All the available evidence indicates that extracellular polysaccharide, particularly glucans produced by S. mutans Gtfs, contribute to the cariogenicity of dental biofilms. Therefore, inhibition of Gtf activity and the consequential polysaccharide synthesis may impair the virulence of cariogenic biofilms, which could be an alternative strategy to prevent the biofilm-related disease. Up to now, many Gtf inhibitors have been recognized in natural products, which remain the major and largely unexplored source of Gtf inhibitors. These include catechin-based polyphenols, flavonoids, proanthocyanidin oligomers, polymeric polyphenols, and some other plant-derived compounds. Metal ions, oxidizing agents, and some other synthetic compounds represent another source of Gtf inhibitors, with some novel molecules either discovered by structure-based virtual screening or synthesized based on key structures of known inhibitors as templates. Antibodies that inhibit one or more Gtfs have also been developed as topical agents. Although many agents have been shown to possess potent inhibitory activity against glucan synthesis by Gtfs, bacterial cell adherence, and caries development in animal models, much research remains to be performed to find out their mechanism of action, biological safety, cariostatic efficacies, and overall influence on the entire oral community. As a strategy to inhibit the virulence of cariogenic microbes rather than eradicate them from the microbial community, Gtf inhibition represents an approach of great potential to prevent dental caries.
Periodontitis as a potential risk factor for chronic obstructive pulmonary disease: a retrospective study.

AIMS AND OBJECTIVES A relationship between poor periodontal health and respiratory disease has been suggested by a number of recent studies. The present study was undertaken to evaluate potential association between respiratory diseases and periodontal health status and to co-relate the severity of periodontal disease with that of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS 150 patients of COPD (test group) and 50 Patients without COPD (control group) were recruited for the study. Information regarding patient's demographic and socioeconomic status and lifestyle (history of smoking) were considered in the study. Patients with COPD were grouped into mild, moderate and severe category on the basis of Spirometry. Periodontal health was assessed by measuring probing pocket depth, Clinical Attachment Loss (CAL) and Oral Hygiene Index (OHI). RESULTS The results showed that the subjects with COPD had significantly more mean CAL) and a higher mean OHI than those without COPD. The risk for COPD appeared to be significantly elevated when attachment loss was found to be severe. A trend was noted in that lung function appeared to diminish as the amount of attachment loss increased. CONCLUSION On the basis of the observed results of the study it can be concluded that the risk for COPD appeared to be significantly elevated when attachment loss was found to be severe. It is conceivable that oral interventions that improve oral health status may prove to lower the severity of lung infection in susceptible populations.
Polycomb Repressor Complex 2 in Genomic Instability and Cancer

Polycomb repressor complexes PRC1 and PRC2 regulate chromatin compaction and gene expression, and are widely recognized for their fundamental contributions to developmental processes. Herein, we summarize the existing evidence and molecular mechanisms linking PRC-mediated epigenetic aberrations to genomic instability and malignancy, with a particular focus on the role of deregulated PRC2 in tumor suppressor gene expression, the DNA damage response, and the fidelity of DNA replication. We also discuss some of the recent advances in the development of pharmacological and dietary interventions affecting PRC2, which point to promising applications for the prevention and management of human malignancies.
Smart: Support: Management Automated Reasoning Technology for Compaq Customer Service

Because of the increasingly competitive nature of the computer manufacturing industry, Compaq Computer Corporation has made some trend-setting changes in the way it does business. One of these changes is the extension of Compaq's call-logging system to include a problem-resolution component that assists customer support personnel in determining the resolution to a customer's questions and problems. Recently, Compaq extended its customer service to provide not only dealer support but also direct end user support; it is also accepting ownership of any Compaq customer's problems in a Banyan, Microsoft, Novell, or SCO UNIX operating environment. One of the tools that makes this feat possible is SMART (support management automated reasoning technology). SMART is part of a Compaq strategy to increase the effectiveness of the customer support staff and reduce overall cost to the organization by retaining problem-solving knowledge and making it available to the entire support staff at the point it is needed.
Hypersensitive Site 2 Specifies a Unique Function within the Human β-Globin Locus Control Region To Stimulate Globin Gene Transcription

ABSTRACT The human β-globin locus control region (LCR) harbors both strong chromatin opening and enhancer activity when assayed in transgenic mice. To understand the contribution of individual DNase I hypersensitive sites (HS) to the function of the human β-globin LCR, we have mutated the core elements within the context of a yeast artificial chromosome (YAC) carrying the entire locus and then analyzed the effect of these mutations on the formation of LCR HS elements and expression of the genes in transgenic mice. In the present study, we examined the consequences of two different HS2 mutations. We first generated seven YAC transgenic lines bearing a deletion of the 375-bp core enhancer of HS2. Single-copy HS2 deletion mutants exhibited severely depressed HS site formation and expression of all of the human β-globin genes at every developmental stage, confirming that HS2 is a vital, integral component of the LCR. We also analyzed four transgenic lines in which the core element of HS2 was replaced by that of HS3 and found that while HS3 is able to restore the chromatin-opening activity of the LCR, it is not able to functionally replace HS2 in mediating high-level globin gene transcription. These results continue to support the hypothesis that HS2, HS3, and HS4 act as a single, integral unit to regulate human globin gene transcription as a holocomplex, but they can also be interpreted to say that formation of a DNase I hypersensitive holocomplex alone is not sufficient for mediating high-level globin gene transcription. We therefore propose that the core elements must productively interact with one another to generate a unique subdomain within the nucleoprotein holocomplex that interacts in a stage-specific manner with individual globin gene promoters.
Prevalence of factor H-binding protein variants and NadA among meningococcal group B isolates from the United States: implications for the development of a multicomponent group B vaccine.

BACKGROUND Two promising recombinant meningococcal protein vaccines are in development. One contains factor H-binding protein (fHBP) variants (v.) 1 and 2, whereas the other contains v.1 and 4 other antigens discovered by genome mining (5 component [5C]). Antibodies against fHBP are bactericidal against strains within a variant group. There are limited data on the prevalence of strains expressing different fHBP variants in the United States. METHODS A total of 143 group B isolates from patients hospitalized in the United States were tested for fHBP variant by quantitative polymerase chain reaction, for reactivity with 6 anti-fHBP monoclonal antibodies (MAb) by dot immunoblotting, and for susceptibility to bactericidal activity of mouse antisera. RESULTS fHBP v.1 isolates predominated in California (83%), whereas isolates expressing v.1 (53%) or v.2 (42%) were common in 9 other states. Isolates representative of 5 anti-fHBP MAb-binding phenotypes (70% of isolates) were highly susceptible to anti-fHBP v.1 or v.2 bactericidal activity, whereas 3 phenotypes were approximately 50% susceptible. Collectively, antibodies against the fHBP v.1 and v.2 vaccine and the 5C vaccine killed 76% and 83% of isolates, respectively. CONCLUSIONS Susceptibility to bactericidal activity can be predicted, in part, on the basis of fHBP phenotypes. Both vaccines have the potential to prevent most group B disease in the United States.
Subspace-based continuous-time identification of fractional order systems from non-uniformly sampled data

This work focuses on the identification of fractional commensurate order systems from non-uniformly sampled data. A novel scheme is proposed to solve such problem. In this scheme, the non-uniformly sampled data are first complemented by using fractional Laguerre generating functions. Then, the multivariable output error state space method is employed to identify the relevant system parameters. Moreover, an in-depth property analysis of the proposed scheme is provided. A numerical example is investigated to illustrate the effectiveness of the proposed method.
A prospective phase II trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients (p) with mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR).

7020 Background: The EGFR TK inhibitor erlotinib is a standard treatment in previously treated NSCLC p. Recently, EGFR gene mutations have been reported to be a predictor of efficacy of this and related compounds. This phase II trial evaluated the efficacy and safety of erlotinib in untreated p with advanced NSCLC and mutated EGFR. METHODS Eligibility criteria included stage IIIB-IV chemotherapy-naive p with confirmed NSCLC and mutated EGFR, PS 0-2, age ≥ 18 years, adequate organ functions, measurable disease and written informed consent. DNA was extracted by laser capture microdissection. Exon 19 deletions were examined by Genscan and the L858R and T790M mutations with a TaqMan assay. Mutations were confirmed by sequencing. Erlotinib was given orally at 150 mg per day. RESULTS From March to December 2005, 37 (12.5%) of 297 tumors screened were found to have mutations in the TK domain of the EGFR gene (25 deletions; 11 L858R; no T790M). Median age: 68 years; 12 males, 25 females; histology: 28 adenocarcinoma, 4 BAC, 4 large cell carcinoma; 9 smokers. Response has been evaluated in 21 p so far: complete response, 6 p; partial response, 13 p; progressive disease, 2 p; overall response rate, 90% (95% CI:70%-90%). Responses occurred in 100% of tumors with exon 19 deletions and in 75% of those with L858R. All responses are ongoing (up to ≥8 months) and all but one p are still alive. Toxicity profile was predictable (mild to moderate rash, diarrhea, asthenia and emesis). No drug related severe adverse events occurred. CONCLUSIONS Single-agent erlotinib produces a high response rate in previously untreated p with advanced NSCLC and mutated EGFR. In-frame deletions in exon 19 seem particularly predictive for response in this setting. [Table: see text].
High‐Risk Early‐Stage Ovarian Cancer Randomized Clinical Trial Comparing Cisplatin Plus Cyclophosphamide versus Whole Abdominal Radiotherapy

From 1985 to 1989 70 patients with high-risk FIGO Stage I-II ovarian carcinoma entered a randomized trial comparing chemotherapy (CT: cisplatin 50 mg/m2 + cyclophosphamide 600 mg/nr day 1 every 28 days for 6 courses) versus whole abdominal radiotherapy (WAR) given according to the open-field technique (43.2 Gy/24 fractions to the pelvis and 30.2 Gy to the upper abdomen). Protocol violations occurred in 8 patients randomized to WAR who received CT because of their own and/or physician's decision. Since protocol compliance was poor and accrual low the study was prematurely closed. Treatment-related toxicity for patients receiving CT was mild and tolerable, consisting chiefly of controllable grade 3 emesis (71%). Grade 3–4 diarrhea was experienced by 28% of patients treated with WAR: severe enteritis requiring hospitalization was observed in 2 patients. Late bowel obstruction requiring surgery was observed in I patient. At a median follow-up of 60 months, 21 patients died and 23 relapsed. Five-year survival was 71% and 53% (p =.16), while relapse- free survival was 14% and 50% (p =.07) for CT and WAR, respectively. Although no firm conclusion can be drawn from the present study, a short-term CT. including cisplatin, appears a safe treatment in comparison to WAR.
Tangled Webs: Evidence of Cross-Talk Between c-Raf-1 and Akt

The apparent cross-communication that can occur between different cell signaling pathways indicates that some signaling mechanisms may be more complex than originally envisaged. Jun et al. discuss recent studies suggesting that two signaling pathways that can be activated by the same growth factor receptor, the Ras-Raf pathway and the phosphatidylinositol 3-kinase (PI3K)–Akt (protein kinase B) pathway, can integrate with each other to generate a particular response, depending on the cell type and the stage of cell differentiation.
High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer.

PURPOSE E-cadherin (E-cad) and its associated intracellular molecules, catenins, are critical for intercellular epithelial adhesion and are often expressed in non-small-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to investigate the expression of cadherins and catenins and their prognostic significance in NSCLC. PATIENTS AND METHODS Tumor tissue samples from 193 patients with stages I to III NSCLC were obtained from the University of Colorado Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in triplicate for the TMAs, and slides were stained by immunohistochemistry with antibodies against E-cad, N-cadherin, alpha (alpha)-, beta (beta)-, and gamma (gamma)-catenin, p120, p27, and adenomatous polyposis coli (APC) gene product. Clinical data were collected by the tumor registries. Patients were followed for a median period of 51 months (range, 18 to 100 months). RESULTS Absent or severely reduced membranous expression for E-cad, alpha-, beta-, and gamma-catenin, and p120 were observed in 10%, 17%, 8%, 31%, and 61% of the cases, respectively. Tumor cell dedifferentiation correlated with reduced expression for E-cad, beta-catenin, gamma-catenin, and p120 in squamous cell carcinomas but not in adenocarcinomas. There was an inverse correlation between nodal metastasis and expression of E-cad and gamma-catenin. Besides the traditional clinical prognostic variables, E-cad and alpha-, beta-, and gamma-catenin expression were of positive prognostic value in univariate survival analyses. In multivariate analysis, E-cad expression was the only independent prognostic factor for survival in addition to age, node status, tumor status, and pathologic surgical margins. CONCLUSION Reduced expression of E-cad and catenins is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.
Magnetic resonance imaging and laboratory aids in the diagnosis of multiple sclerosis

This editorial concerns the role of magnetic resonance imaging (MRI) and other diagnostic aids in the differential diagnosis of multiple sclerosis (MS). The diagnosis of MS is basically a clinical one. No laboratory finding is diagnostic. A number of diseases (old and newly recognized) can have features that suggest MS, and the clinician must be wary of malung the diagnosis of MS unless these disorders can be clearly excluded. The clinical diagnosis of MS has long depended on the ability of the physician to demonstrate the occurrence of white matter lesions in both time and space that cannot be explained on another basis. Schumacher and colleagues {l) gave an excellent exposition of this principle, which served for many years as the standard diagnostic guide for MS. In addition to showing dissemination of white matter lesions in time and space, one must take into consideration that the risk for MS is higher in the following groups than in the general population:
Purification and some properties of a novel heat-stable cis-toluene dihydrodiol dehydrogenase.

cis-Toluene dihydrodiol dehydrogenase was purified 200-fold from cells of a thermotolerant Bacillus species grown with toluene as the sole source of carbon and energy. The purified enzyme preparation was remarkably heat-stable and exhibited a half-life of 100 min at 80 degrees C, the temperature optimum. The activation energy of the reaction was 36 kJ.mol-1. Isoelectric focusing indicated that the pI of the native enzyme was 6.4 and that of the denatured enzyme 6.5. Although the pH optimum was 9.8, the enzyme was most stable at pH 8. The Mr of the enzyme was approx. 172,000 as determined by gel filtration and 166,000 by polyacrylamide-gel electrophoresis. The enzyme was composed of six apparently identical subunits with Mr values of 29,500. Kinetic analysis revealed that the Km for cis-toluene dihydrodiol was 92 microM and for NAD+ was 80 microM. The apparent Km values for cis-benzene dihydrodiol and cis-naphthalene dihydrodiol were 330 microM and 51 microM respectively. The enzyme was inhibited by mercurials but was unaffected by metal-ion chelators. Steady-state kinetics and product-inhibition patterns suggested that the enzyme mechanism was ordered Bi Bi.
The Translocated Salmonella Effector Proteins SseF and SseG Interact and Are Required To Establish an Intracellular Replication Niche

ABSTRACT The facultative intracellular pathogen Salmonella enterica causes a variety of diseases, including gastroenteritis and typhoid fever. Inside epithelial cells, Salmonella replicates in vacuoles, which localize in the perinuclear area in close proximity to the Golgi apparatus. Among the effector proteins translocated by the Salmonella pathogenicity island 2-encoded type III secretion system, SifA and SseG have been shown necessary but not sufficient to ensure the intracellular positioning of Salmonella vacuoles. Hence, we have investigated the involvement of other secreted effector proteins in this process. Here we show that SseF interacts functionally and physically with SseG but not SifA and is also required for the perinuclear localization of Salmonella vacuoles. The observations show that the intracellular positioning of Salmonella vacuoles is a complex phenomenon resulting from the combined action of several effector proteins.
Mass spectrometric detection of CYP450 adducts following oxidative desulfuration of methyl parathion

Cytochrome P450 (CYP)‐mediated desulfuration of methyl parathion results in mechanism‐based inhibition of the enzyme. Although previous data suggest that reactive sulfur is released and binds to the apoprotein, the identities of neither the adduct(s) nor the affected amino acid(s) have been clearly determined. In this study, nanospray tandem mass spectroscopy was used to analyze peptide digests of CYP resolved by SDS–PAGE from liver microsomes of male rats following incubation in the absence or presence of methyl parathion. Oxidative desulfuration was confirmed by measurement of methyl paraoxon, and inhibition of specific CYP isozymes was determined by measurement of testosterone hydroxylation. Total CYP content was quantified spectrophotometrically. Incubation of microsomes with methyl parathion decreased CYP content by 58%. This effect was not associated with a comparable increase in absorbance at 420 nm, suggesting the displacement of heme from the apoprotein. Rates of testosterone 2β‐ and 6β‐hydroxylation, respectively, were reduced to 8 and 2%, implicating CYP3A and CYP2C11 in the oxidative desulfuration of methyl parathion. Mass spectrometric analysis identified 96 amu adducts to cysteines 64 and 378 of CYP3A1. In addition, a peptide containing cysteine 433 that coordinates with heme was possibly modified as it was detected in control, but not methyl parathion samples. A comparison of rat CYP3A1 with human CYP3A4 suggests that cysteines 64 and 378 reside along the substrate channel, remote from the active site. Alteration of these residues might modulate substrate entry to the binding pocket of the enzyme. Copyright © 2012 John Wiley & Sons, Ltd.
A Meta-Analysis of the Neuropsychological Effects of Adjuvant Chemotherapy Treatment in Women Treated for Breast Cancer

ABSTRACT Given the improvement in mortality rates associated with breast cancer, the importance of understanding the long-term neuropsychological consequences of chemotherapy is becoming increasingly vital. This study applies meta-analytic techniques to the scant literature on the relationship between contemporary adjuvant chemotherapy treatment for breast cancer and cognitive dysfunction as examined through neuropsychological indices. Seven studies (involving more than 300 participants) were selected from over 200 potential articles, based on three inclusion criteria: presence of breast cancer, administration of chemotherapy treatment, and use of neuropsychological tests. From these, nine treatment-control comparisons were used to generate 129 Hedge's d effect sizes across the cognitive domains of simple attention, working memory short- and long-term memory, speed of processing, language, spatial abilities, and motor function. Small to medium cumulative effect sizes, showing diminished cognitive function for chemotherapy treatment groups compared to control groups, were obtained for each of the eight cognitive domains. Overall, these results suggest that women who undergo adjuvant chemotherapy as treatment for breast cancer may experience subtle yet consequential cognitive decline.
Translational methods and computational complexity

This paper investigates the computational complexity of binary sequences as measured by the rapidity of their generation by multitape Turing machines. A "translational" method which escapes some of the limitations of earlier approaches leads to a refinement of the established hierarchy. The previous complexity classes are shown to possess certain translational properties. An related hierarchy of complexity classes of monotonic functions is examined
Receiving electronics for intra-oral ultrasound probe

In this paper, we present the receiving electronics used in an intra-oral ultrasound probe which can be integrated with a PC or microcontroller based system to form a portable ultrasound imaging system. In general, this probe will house the transmitting circuitry, the transducers and the receiving electronics of an ultrasound imaging system. The receiving electronics, made up of the pre-amplifier arrays and beamformer will be presented here, with the focus on the pre-amplifier arrays, which has been successfully implemented. The pre-amplifier condition the echoes signals by amplifying and preventing noise interferences. It also acts as the impedance converter between the transducer and beamforming stage. This is performed at centre frequency of 20 MHz whilst driving loads equivalent to coaxial cables. The beamformer uses delay/storage elements to align the amplified echoes signals in time before summing them for processing. Analog storage elements will be utilised together with digital control signals for this ASIC.