Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient safety and the next generation of HPV DNA tests.

The article by Kinney et al1 in the August 2010 issue of the Journal expressed concern about the approval by the US Food and Drug Administration (FDA) of the Cervista HPV HR (high-risk human papillomavirus) test (Third Wave Technologies, Madison, WI; now owned by Hologic, Bedford, MA) and questioned the safety of the device owing to the positivity rate seen in the study population for women 30 years and older with negative cytologic findings (NILM ≥30). The clinical cutoff for the Cervista HPV HR test was set in the same manner as for the only other FDA-approved HR-HPV test, Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD), by evaluating clinical sensitivity and specificity in the population with atypical squamous cells of undetermined significance (ASC-US). The rationale for this approach is that the ASC-US population, as a population with equivocal cytologic findings, provides an informative profile of how an HPV test performs in an intended-use population in which disease prevalence is sufficient for characterizing a clinical cutoff and disease end points can be readily assessed. A head-to-head comparison against the HC2 test was performed during review of the Cervista HPV HR device. This evaluation revealed equivalent clinical specificity for cervical intraepithelial neoplasia (CIN) 2 or worse for the 2 tests in the Cervista ASC-US data set, and the Cervista HPV HR test detected 100% of cases of CIN 3 or worse. In determining whether an in vitro diagnostic device is safe and effective, the FDA must consider whether the probable benefits of using the device outweigh the probable risks when the device is used in accordance with its approved labeling. Per current screening guidelines,2 the predominant use of HPV testing in the NILM ≥30 population is to extend cervical cancer screening intervals in HPV– women. In a worst-case scenario in …
MUNC13-4 Protein Regulates the Oxidative Response and Is Essential for Phagosomal Maturation and Bacterial Killing in Neutrophils*

Background: MUNC13-4 regulates vesicular trafficking, and its deficiency causes immunodeficiency in humans. Results: MUNC13-4 regulates ROS production, phagosomal maturation, and bacterial killing in neutrophils. Conclusion: MUNC13-4 is essential for the neutrophil-dependent innate immune response. Significance: This study identifies MUNC13-4 as a potential target for therapeutic intervention during bacterial infections. Neutrophils use diverse mechanisms to kill pathogens including phagocytosis, exocytosis, generation of reactive oxygen species (ROS), and neutrophil extracellular traps. These mechanisms rely on their ability to mobilize intracellular organelles and to deliver granular cargoes to specific cellular compartments or into the extracellular milieu, but the molecular mechanisms regulating vesicular trafficking in neutrophils are not well understood. MUNC13-4 is a RAB27A effector that coordinates exocytosis in hematopoietic cells, and its deficiency is associated with the human immunodeficiency familial hemophagocytic lymphohistiocytosis type 3. In this work, we have established an essential role for MUNC13-4 in selective vesicular trafficking, phagosomal maturation, and intracellular bacterial killing in neutrophils. Using neutrophils from munc13-4 knock-out (KO) mice, we show that MUNC13-4 is necessary for the regulation of p22phox-expressing granule trafficking to the plasma membrane and regulates extracellular ROS production. MUNC13-4 was also essential for the regulation of intracellular ROS production induced by Pseudomonas aeruginosa despite normal trafficking of p22phox-expressing vesicles toward the phagosome. Importantly, in the absence of MUNC13-4, phagosomal maturation was impaired as observed by the defective delivery of azurophilic granules and multivesicular bodies to the phagosome. Significantly, this mechanism was intact in RAB27A KO neutrophils. Intracellular bacterial killing was markedly impaired in MUNC13-4 KO neutrophils. MUNC13-4-deficient cells showed a significant increase in neutrophil extracellular trap formation but were unable to compensate for the impaired bacterial killing. Altogether, these findings characterize novel functions of MUNC13-4 in the innate immune response of the neutrophil and have direct implications for the understanding of immunodeficiencies in patients with MUNC13-4 deficiency.
Matematik öğretmenlerinin ders kitabı dışında kaynak kullanımları: nedenler, sonuçlar ve çıkarımlar

Bu calismada, matematik ogretmenlerinin ders kitabi disinda kaynak kullanim durumlarinin belirlenmesi ve ogretmenleri kaynak kitap kullanimina iten nedenlerin incelenmesi amaclanmistir. Bu amac kapsaminda sekillenen calisma tarama modelinde betimsel bir arastirma olarak desenlenmistir. Calismaya 100 ortaokul matematik ogretmeni katilmistir. Katilimcilara acik uclu sorulardan olusan bir anket uygulanmistir. Anketten elde edilen veriler icerik analizine tabi tutularak cozumlenmistir. Yapilan analizler sonucunda katilimcilarin %80 gibi buyuk bir cogunlugunun ucretsiz olarak dagitilan ders kitabi disinda kaynak kitap kullandiklari belirlenmistir. Milli Egitim Bakanliginin kaynak kitap kullanilmamasi yonundeki duzenlemeleri, en azindan calismamiza katilan ogretmenler ozelinde, ders kitabi disinda kaynak kullanimini engelleyemedigi tespit edilmistir. Katilimci ogretmenler kendilerini ekstra kaynak kullanmaya iten sebepler bulundugunu; ders kitaplarinin hem soru bakimindan, hem konu anlatimi hem de ogrenci ozelligine uygunluk bakimindan beklentilerini karsilamadigini belirtmektedirler. Elde edilen bulgular ve ulasilan sonuclar, ders kitaplarinin hazirlanmasi ve secimi, ucretsiz dagitimi, kitaplarin kullanimi ve surecte ogretmenlerin ihtiyac duyacagi destek ve kitaplarin kullanimiyla birlikte ortaya cikan degisimin yonetimi konulari ekseninde tartisilmis ve bir takim onerilerde bulunulmustur.
Analysis of Salivary Gland Proteins of the Mosquito Anopheles darlingi (Diptera: Culicidae)

Abstract The salivary proteins of Anopheles darlingi Root, the principal vector of malaria in the Amazon Region, Brazil, were analyzed. Comparison of the protein profiles between adult males and females revealed that most of the polypeptides are present in both sexes, but female-specific polypeptides also were observed. SDS-PAGE analysis of sugar-fed female mosquitoes with ages varying from 1 to 10 d after adult emergence indicated that the proteins start to be accumulated in the first day of life and are present throughout the period analyzed. Analysis of blood-fed mosquitoes showed no differences in salivary proteins when compared with sugar fed ones, suggesting that there is no specific protein induced by blood. The protein profiles of the salivary glands dissected from wild-caught female mosquitoes from different geographical regions of Brazil were compared and some differences were observed.
The Golgi Protein ACBD3, an Interactor for Poliovirus Protein 3A, Modulates Poliovirus Replication

ABSTRACT We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence.
Association of FCRL3 Genotypes with Susceptibility of Iranian Patients to Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a complex disease, the hallmark of which is synovial joint inflammation. The substantial contribution from genetic factors in susceptibility to RA has been well-defined. The Fc receptor-like3 (FCRL3) gene is one of the genes that have recently shown a significant association with RA. To determine the possible role of FCRL3-169 C/T and FCRL3-110 A/G gene polymorphisms in the development of RA in Iranian patients, 320 RA patients and 302 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. No significant difference was found in genotype and allele frequencies of FCRL3-169 C/T between patients and controls. In contrast, at position ‐110 A/G, the frequency of the AA genotype and A allele was significantly decreased in RA patients compared to controls (p = 0.005). After Bonferroni correction for multiple testing, no significant correlations between FCRL3-169 C/T and ‐110 A/G polymorphism and laboratory and clinical features of the patients was observed. In conclusion, the results of this study showed a significant association between FCRL3-110 A/G polymorphism and susceptibility to RA.
Investigation of microstructured chitosans by coherent anti‐Stokes Raman microscopy

This work describes application of coherent anti‐Stokes Raman scattering (CARS) microscopy technique for analytical characterization of microstructured materials based on chitosan. We demonstrate that nitrogen–hydrogen vibration band in the high wavenumber region of CARS spectrum prevails over response from oxygen–hydrogen vibrations and can be used as a spectral marker of chitosan. The chemically selective imaging is experimentally demonstrated by applying CARS microscopy to discriminate between chitosan and polystyrene microparticles. CARS microscopy was shown to be a valuable tool for characterization of polluted chitosan fibre from utilized engine filter material. A possibility to observe foreign material pieces on the surface of the polluted chitosan fibre is demonstrated and discussed.
Phytochemicals as potential chemopreventive and chemotherapeutic agents in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is the fifth commonest malignancy worldwide and the incidence is rising. Surgery, including transplantation resection, is currently the most effective treatment for HCC; however, recurrence rates are high and long-term survival is poor. Identifying novel chemopreventive and chemotherapeutic agents and targeting them to patients at high risk of developing HCC or following curative treatment may go some way towards improving prognosis. This review examines current knowledge regarding the chemopreventive and chemotherapeutic potential of phytochemicals in heptocarcinogenesis. Both in-vitro and animal studies demonstrate that several phytochemicals, including curcumin, resveratrol, green tea catechins, oltipraz and silibinin, possess promising chemopreventive and chemotherapeutic properties. Despite this, very few clinical trials have been performed. Problems regarding validation of biomarkers, agent delivery, side effects and patient selection are barriers that need to be overcome to determine the potential of such agents in clinical practice.
A Wortmannin-sensitive Signal Transduction Pathway Is Involved in the Stimulation of Insulin Release by Vasoactive Intestinal Polypeptide and Pituitary Adenylate Cyclase-activating Polypeptide (*)

Vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide-27 (PACAP-27), and PACAP-38 stimulated insulin release with EC values of 0.15, 0.15, and 0.06 nM respectively, as expected for the VIP2/PACAP3 receptor subtype. Secretion was stimulated promptly and peaked at 6-10 min. At 30 min, the secretion rate was still 2-3-fold higher than the control rate. The peptides increased cyclic AMP and [Ca] transiently so that at 30 min they had returned to control values. Therefore, an additional signal is required to explain the prolonged stimulation of release. The prolonged effects, but not the acute effects of VIP and PACAP on insulin release were inhibited by low concentrations of wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor. While wortmannin inhibited PI 3-kinase activity in cell lysates, no activation by the peptides was seen. Therefore, the wortmannin-sensitive pathway is either dependent on basal PI 3-kinase activity, or another target for wortmannin is responsible for inhibition of the peptide-stimulated secretion. It is concluded that the acute stimulation of insulin release by VIP and PACAP is mediated by increased cyclic AMP and [Ca], whereas the sustained release is mediated by a novel wortmannin-sensitive pathway.
The Status of Women in Academic Anesthesiology: A Progress Report

BACKGROUND: The number of women in medicine has increased steadily in the last half century. In this study, we reassessed the status of women in academic anesthesiology departments in the United States in 2006. METHODS: Medical student, resident, and faculty rank gender data were obtained from the Association of American Medical Colleges. Data regarding the make-up and gender of anesthesia subspecialty society leadership, the editorial boards of Anesthesia & Analgesia and Anesthesiology, the awardees of anesthesia research grants, American Board of Anesthesiology examiners, and department chairs were obtained from websites, organization management personnel, and the Wood Library-Museum of Anesthesiology. Anesthesiology data were compared with composite data from medical school departments in other clinical specialties and to data from previous years, beginning in 1985. RESULTS: The percentage of medical school graduates, anesthesiology residents, and anesthesiology faculty members who are women has increased since 1985; however, the rate of increase in the percentage of women is significantly faster for medical school graduates compared with anesthesiology residents (P < 0.001) and faculty (P < 0.05). The percentage of women anesthesiology faculty members who were full professors in 2006 was 6.5% compared with 17.7% of men faculty (P < 0.001) and is not significantly different than in 1986 (P = 0.27). Fourteen percent of full anesthesiology professors were women and this does not differ from all clinical specialties combined (15%). Women comprised 12.7% of academic anesthesiology chairs and 10% of all medical school department chairs in 2006, significantly higher compared with 1993 (P < 0.05). Currently, 8% and 11% of editors and associate editors of Anesthesiology and Anesthesia & Analgesia are women, respectively. Eighteen percent of American Board of Anesthesiology oral board examiners in 2007 were women compared with 8% in 1985 (P < 0.05). The percentage of time in which women have served as anesthesiology society leaders was significantly greater during 1997–2006 compared with 1987–1996 (P < 0.001). The proportion of competitive research grants awarded to women has not changed over several decades. CONCLUSIONS: The status of women in academic anesthesiology in the first decade of the millennium has, by some measures, advanced compared with 20 yr ago. However, by other measures, there has been no change. The task ahead is to identify factors that discourage qualified women medical students, residents, and junior faculty members from pursuing careers in academic anesthesiology and advancing in academic rank.
Identifying Context Sources towards Context-aware Adapted Web Services

Context-awareness refers to the ability of services and applications to proactively adapt their behavior to the characteristics of the execution environment, such as weather conditions, location, etc., namely context. Web services as the most popular implementation of service-oriented applications are usually exploited in this field. During the development process of such services an interesting challenge lies in identifying reusable context properties or services that constitute potential context sources for the adaptation to context. In this paper a solution for this context source matchmaking is proposed. The identification is performed by matching the WSDL specifications participating either as business services or as context sources. The procedure is demonstrated through an evaluation exploiting descriptions from online service registries.
SYSTEMIC LUPUS ERYTHEMATOSUS: PROTOTYPE OF IMMUNE COMPLEX NEPHRITIS IN MAN

Serological studies, immunofluorescence studies, and immunochemical assays of glomerular eluates indicate that several antigen-antibody systems may be involved in the pathogenesis of the tissue lesions of SLE. The NDNA-anti-NDNA system appears to be operative in most patients with active SLE. In addition, antibodies to SDNA are found with considerable frequency in SLE sera and glomerular eluates. It is not known if these antibodies fix to NDNA which has been denatured after deposition in glomeruli or if SDNA-anti-DNA complexes are deposited initially. NDNA antigen has been demonstrated in both serum and glomerular deposits, and SDNA determinants have also been found in glomerular deposits. In addition, there is evidence that rheumatoid factor contributes to the immune complex deposition in certain patients either by fixing to preformed immune complexes or as part of an independent γ-globulin-anti-γ-globulin system. It is anticipated that the definition of these immune systems, and the assessment of their relative toxicity will provide insight into underlying etiologic factors as well as provide a sound basis for therapy in this form of glomerulonephritis.
Dynamic redox control of NF-κB through glutaredoxin-regulated S-glutathionylation of inhibitory κB kinase β

The transcription factor NF-κB, a central regulator of immunity, is subject to regulation by redox changes. We now report that cysteine-179 of the inhibitory κB kinase (IKK) β-subunit of the IKK signalosome is a central target for oxidative inactivation by means of S-glutathionylation. S-glutathionylation of IKK-β Cys-179 is reversed by glutaredoxin (GRX), which restores kinase activity. Conversely, GRX1 knockdown sensitizes cells to oxidative inactivation of IKK-β and dampens TNF-α-induced IKK and NF-κB activation. Primary tracheal epithelial cells from Glrx1-deficient mice display reduced NF-κB DNA binding, RelA nuclear translocation, and MIP-2 (macrophage inflammatory protein 2) and keratinocyte-derived chemokine production in response to LPS. Collectively, these findings demonstrate the physiological relevance of the S-glutathionylation–GRX redox module in controlling the magnitude of activation of the NF-κB pathway.
A novel ZVS DC/DC converter for high power applications

This paper presents a novel zero voltage switch (ZVS) pulse-width modulation (PWM) DC/DC converter for high power, high output voltage applications. By using two active switches in the secondary side of a transformer, the proposed converter achieves not only ZVS of the active switches in the entire load ranges but also soft commutation of the output rectifier diodes. The proposed topology has simple structure and control strategy. Simulation results and experimental results of a 2.8 kW 200 kHz DC/DC converter are presented.
Asymptotic behavior of elliptic problems in perforated domains with nonlinear boundary conditions

In this paper, we apply the periodic unfolding method in perforated domains introduced by Cioranescu et al. (Portu- gal. Math. 63(4) (2006), 467-496) to a class of elliptic problems with nonlinear conditions on the boundary of the holes. A new compactness result will play a major role in the homogenization process and provides correctors without using any extension operator.
Enamel Tissue Engineering 281 Enamel Tissue Engineering

Dental scientists are eagerly embracing regenerative medicine using tissue engineering technology. Enamel, one component of teeth, is the hardest tissue in the body. It cannot regenerate by itself, because it is formed by a layer of ameloblasts that is lost by the time the tooth crown has completely formed. Although the enamel is spent during lifetime, it is vulnerable to wear, damage, and decay. For these reasons, the development of a technique that produces artificially-grown enamel using culture and transplantation techniques is strongly desired. In this chapter we report a new technique for culturing enamel organ epithelial cells that have the capacity to produce enamel. After completion of the formation of the tooth crown, which is composed of an enamel-dentin complex, tooth root formation begins. Generally, no new ameloblasts or enamel is generated from the enamel organ epithelial cells after the tooth root is formed. Epithelial cell rests of Malassez, derived from Hertwig’s epithelial root sheath fragments, are located in the periodontal ligament, and recently we reported that these cells are also capable of enamel production using the same technique. Dental epithelial cells including enamel organ epithelial cells and epithelial cell rests of Malassez can continue to proliferate when they are subcultured on top of feeder layer cells. These subcultured cells were placed onto collagen sponge scaffolds along with dental pulp cells and the constructs were transferred into the abdominal cavities of rats. When removed after 4 weeks, enamel production was observed in the scaffolds. The key finding of this study is that even after multiple divisions, the cells retained the capacity to produce enamel. Now that dental epithelial cells can be generated by a culture and transplantation system, the next step will be to combine the tissue-engineered enamel with the injured enamel in original teeth.
Integrin alpha(v)beta(3) is involved in stimulated migration of vascular adventitial fibroblasts by basic fibroblast growth factor but not platelet-derived growth factor.

We examined the effects of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) on the migration of vascular adventitial fibroblasts (VAFs) isolated from rat aortic adventitiae. Both bFGF and PDGF significantly stimulated VAF migration in vitro. An antibody to rat beta(3) integrin reduced bFGF-stimulated migration in a dose dependent manner. Moreover, VAF migration was inhibited in the presence of cyclic RGD (cRGD) peptide. However, PDGF-directed migration was blocked only by equivalent cRGD peptide but not by antibody to beta(3) integrin. These data suggest that alpha(v)beta(3) integrin mediates VAF migration stimulated by bFGF and that chemoattractant directed migration may be through distinct integrins.