Miracle-dz/UniFAR-FTUs huggingface dataset:
Production of Papillomavirus‐Based Gene Transfer Vectors

Papillomaviruses are a diverse group of pathogens that infect the skin and mucosal tissues of humans and various animal species. The viral genome is a circular, double‐stranded DNA molecule ∼8‐kb in length. The non‐enveloped papillomavirus capsid is composed of a virally encoded major coat protein, L1, and a minor coat protein, L2. L1 and L2 co‐assemble when expressed in mammalian cells, and can promiscuously encapsidate essentially any <8‐kb plasmid present in the cell nucleus. In the last several years, there has been rapid development of techniques for intracellular production of papillomavirus‐based gene transfer vectors (also known as pseudoviruses). This unit outlines the production and propagative amplification of papillomaviral vectors. The system represents a highly tractable method for converting pre‐existing mammalian expression plasmids into infectious virus stocks. The resulting vectors have utility for in vitro, as well as in vivo gene delivery applications. Curr. Protoc. Cell Biol. 37:26.1. 1‐26.1. 19. © 2007 by John Wiley & Sons, Inc.
Influence of unhealthy food and beverage marketing on children's dietary intake and preference: a systematic review and meta‐analysis of randomized trials

Marketing of foods and beverages high in fat, sugar and salt are suggested to contribute to poor dietary behaviours in children and diet‐related diseases later in life. This systematic review and meta‐analysis of randomized trials aimed to assess the effects of unhealthy food and beverage marketing on dietary intake (grams or kilocalories) and dietary preference (preference score or percentage of participants who selected specific foods/beverages) among children 2 to 18 years of age.
Sensitivity of blood‐clotting factors and digestive enzymes to inhibition by organophosphorus pesticides

Organophosphorus pesticide toxicology is normally evaluated in relation to inhibition of cholinesterases (acetyl and butyryl), neuropathy target esterase, and carboxylesterases, with less attention given to other physiologically important hydrolases. This study considers the relative organophosphate sensitivities of the aforementioned serine hydrolases compared with purified blood‐clotting factors (thrombin, plasmin, and kallikrein) and digestive enzymes (α‐chymotrypsin, trypsin, and elastase), assayed under similar conditions. Inhibitors that we examined are organophosphorus insecticides or their activated metabolites (paraoxon, chlorpyrifos oxon, and profenofos) and other toxicants (phenyl saligenin cyclic phosphonate and tribufos) for comparison with values that are found in the literature for the fluorophosphonates (isoflurophate and sarin). Thrombin is the most sensitive blood‐clotting factor with IC‐50 values of 19 to 160 μM for tribufos, the cyclic phosphonate, isoflurophate, and profenofos; plasmin and kallikrein are less affected (IC‐50 >100 μM). α‐Chymotrypsin, trypsin, and elastase are most sensitive to the cyclic phosphonate (IC‐50 1.3–15 μM) and less so to isoflurophate, sarin, and profenofos (IC‐50 values from 3.6 to greater than 100 μM). The cholinesterases, carboxylesterase, and neuropathy target esterase are the most sensitive to inhibition with IC‐50 values for the insecticides of less than 0.001 to 0.6, 0.002 to 0.009, and 0.15 to 100 μM, respectively. The generally low potency of these organophosphates for blood‐clotting factors and digestive enzymes suggests that associated toxic effects are unlikely at sublethal doses. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 14: 51–56, 2000
The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVES We sought to provide an updated systematic review and meta-analysis of studies investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on systolic and diastolic blood pressure (SBP, DBP). METHODS Two independent investigators undertook a systematic search of the PubMed database (1980-2012) to identify randomized controlled trials comparing therapeutic PAP to sham-PAP, pill placebo, or standard care over at least one week in adult OSA patients without major comorbidities. The mean, variance, and sample size for diurnal and nocturnal SBP and DBP data were also extracted independently from each study. Random effects meta-analyses were conducted, followed by pre-specified subgroup and meta-regression analyses. RESULTS 32 studies were identified, with data available from 28 studies representing n = 1,948 patients. The weighted mean difference in diurnal SBP (-2.58 mm Hg, 95% CI -3.57 to -1.59 mm Hg) and DBP (-2.01 mm Hg, 95% CI -2.84 to -1.18 mm Hg) both significantly favored PAP treatment over control arms, with similar results seen in nocturnal readings. Statistically significant reductions in BP were seen in studies whose patients were younger, sleepier, had more severe OSA, and exhibited greater PAP adherence. Meta-regression indicated that the reductions in DBP with PAP were predicted by mean baseline BP (β = -0.22, p = 0.02) and Epworth Sleepiness Scale scores (β = -0.27, p = 0.04). CONCLUSIONS PAP treatment for OSA is associated with modest but significant reductions in diurnal and nocturnal SBP and DBP. Future research should be directed towards identifying subgroups likely to reap greater treatment benefits as well as other therapeutic benefits provided by PAP therapy.
The G Protein-coupled Receptor P2Y14 Influences Insulin Release and Smooth Muscle Function in Mice*

Background: The relevance of the widely expressed GPCR P2Y14 is only partially understood. Results: Analysis of P2Y14-KO mice revealed decreased gastrointestinal emptying, reduced glucose tolerance, and insulin release. Conclusion: P2Y14 function is required for proper intestine emptying and adequate glucose response. Significance: P2Y14 plays a role in smooth muscle function and maintaining energy homeostasis by influencing insulin release. UDP sugars were identified as extracellular signaling molecules, assigning a new function to these compounds in addition to their well defined role in intracellular substrate metabolism and storage. Previously regarded as an orphan receptor, the G protein-coupled receptor P2Y14 (GPR105) was found to bind extracellular UDP and UDP sugars. Little is known about the physiological functions of this G protein-coupled receptor. To study its physiological role, we used a gene-deficient mouse strain expressing the bacterial LacZ reporter gene to monitor the physiological expression pattern of P2Y14. We found that P2Y14 is mainly expressed in pancreas and salivary glands and in subpopulations of smooth muscle cells of the gastrointestinal tract, blood vessels, lung, and uterus. Among other phenotypical differences, knock-out mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. An unchanged insulin tolerance suggested altered pancreatic islet function. Transcriptome analysis of pancreatic islets showed that P2Y14 deficiency significantly changed expression of components involved in insulin secretion. Insulin secretion tests revealed a reduced insulin release from P2Y14-deficient islets, highlighting P2Y14 as a new modulator of proper insulin secretion.
Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

Abstract Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.
Evaluation of collagen in connective tissue walls of odontogenic cysts--a histochemical study.

BACKGROUND The purpose of this study was to evaluate the nature of collagen in the connective tissue walls of odontogenic cysts, like the odontogenic keratocyst (OKC), dentigerous cyst and radicular cyst using picrosirius red stained sections. Furthermore, it was intended to assess if the capsular connective tissue can affect the nature of overlying epithelium, thus emphasizing the role of epithelial-mesenchymal interactions in biological behaviour of the cysts. MATERIALS AND METHOD The material for the study included 51 formalin-fixed paraffin-embedded tissue blocks (15 odontogenic keratocyst, 15 dentigerous cysts, 15 radicular cysts and four normal mucosa and two dental follicular tissue as controls), retrieved from the Department of Oral Pathology and Microbiology, MCODS, Manipal. Tissue blocks were sectioned at 5-μm thickness, stained with picrosirius red stain and observed with polarization and light microscopy. RESULTS Few sections of OKC and dentigerous cyst exhibited greenish-yellow birefringence in sub-epithelial region, whereas others showed a yellowish-orange birefringence under polarization microscopy. Most radicular cysts had yellowish-orange to orange birefringence. Shift in colour in case OKC and dentigerous cyst was attributed to the presence of inflammation in those sections. These regions also exhibited either a change in phenotype or thickness of overlying epithelium. CONCLUSION This technique can be used to study the nature of collagen fibres in odontogenic cyst walls. Further studies with an increased sample size and using various epithelial and mesenchymal markers and ssDNA antibodies should be carried out to confirm the effect of epithelial-mesenchymal interactions on the nature of epithelium of odontogenic cysts.
Social Health Insurance and the Use of Formal and Informal Care in Developing Countries: Evidence from Ghana’s National Health Insurance Scheme

Abstract This paper studies the relationship between the use of formal and informal health care in a developing country setting by examining the introduction of a social health insurance scheme in Ghana. We estimate the effects of gaining coverage on changes in care seeking behaviour and show how these effects differ by age and wealth status. District-level differences in the implementation of the insurance scheme provide exogenous variation in access to insurance and allow us to address issues with selection into coverage. Results indicate that insurance access strongly increased use of formal care and reduced out-of-pocket expenditures on health services.
High-Risk Human Papillomavirus Reactivation in Human Immunodeficiency Virus–Infected Women: Risk Factors for Cervical Viral Shedding

OBJECTIVE: To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human papillomavirus (HPV) cervical infection in human immunodeficiency virus (HIV)-infected and HIV-uninfected women. METHODS: Data from 898 women in the HIV Epidemiology Research Study (HERS) were used to evaluate cervical HPV latency and reactivation. Prior exposure to HPV types (16, 18, 31, 35, and 45) was determined by serologic testing at enrollment, and cervical shedding of HPV was detected by polymerase chain reaction at 6-month intervals. Human papillomavirus cervical shedding and sexual history were used to estimate rates of reactivation and recurrence. Repeated measures survival analysis was used to estimate hazard ratios and 95% confidence intervals for reactivation and recurrence. Rates of total HPV shedding (recurrence and reactivation) during follow-up were assessed by HIV status and rate ratios were calculated. RESULTS: Reactivation of latent HPV infections was observed in HIV-infected women, but few reactivation events were identified in HIV-uninfected women. Factors consistently associated with reactivation in HIV-infected women included CD4 count less than 200/mm3 and age younger than 35 years. Women infected with HIV had 1.8 to 8.2 times higher rates of viral shedding (reactivation plus recurrence) compared with HIV-uninfected women. CONCLUSION: Women with a history of cervical HPV infection may be at risk of reactivation of latent viral infection even in the absence of sexual activity, and this risk is higher in women with HIV infection. LEVEL OF EVIDENCE: II
Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity

The C-type lectin receptor Dectin-2 can trigger the leukotriene C4 synthase–dependent generation of cysteinyl leukotrienes and the caspase-associated recruitment domain 9– and NF-κB–dependent generation of cytokines, such as IL-23, IL-6, and TNF-α, to promote Th2 and Th17 immunity, respectively. Dectin-2 activation also elicits the type 2 cytokine IL-33, but the mechanism by which Dectin-2 induces these diverse innate mediators is poorly understood. In this study, we identify a common upstream requirement for PI3Kδ activity for the generation of each Dectin-2–dependent mediator elicited by the house dust mite species, Dermatophagoides farinae, using both pharmacologic inhibition and small interfering RNA knockdown of PI3Kδ in bone marrow–derived dendritic cells. PI3Kδ activity depends on spleen tyrosine kinase (Syk) and regulates the activity of protein kinase Cδ, indicating that PI3Kδ is a proximal Syk-dependent signaling intermediate. Inhibition of PI3Kδ also reduces cysteinyl leukotrienes and cytokines elicited by Dectin-2 cross-linking, confirming the importance of this molecule in Dectin-2 signaling. Using an adoptive transfer model, we demonstrate that inhibition of PI3Kδ profoundly reduces the capacity of bone marrow–derived dendritic cells to sensitize recipient mice for Th2 and Th17 pulmonary inflammation in response to D. farinae. Furthermore, administration of a PI3Kδ inhibitor during the sensitization of wild-type mice prevents the generation of D. farinae–induced pulmonary inflammation. These results demonstrate that PI3Kδ regulates Dectin-2 signaling and its dendritic cell function.
Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis

Objective: To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). Methods: This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients’ mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. Results: We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. Conclusions: We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.
Lithium Augmentation of Venlafaxine in Adolescent Major Depression

Objective: Studies on the pharmacotherapy of adolescent major depression are limited but suggest that the illness is often resistant to drug treatment. We aim to report the use of lithium augmentation of venlafaxine in two teenagers with major depression. Clinical picture: Two 16–year-olds with major depression are described. Treatment: In both patients, the treatment involved trials of a selective serotonin re-uptake inhibitor, venlafaxine, and psychotherapy preceded lithium augmentation of venlafaxine. The trial of venlafaxine alone had been short in one patient. Outcome: Combining lithium and venlafaxine was rapidly followed by marked improvement in mood and function. Conclusions: Augmentation of antidepressants should be considered in young depressed patients who fail to respond to adequate trials of new antidepressants alone.
Utility and limitations of intraductal ultrasonography in distinguishing longitudinal cancer extension along the bile duct from inflammatory wall thickening

AbstractBackground:We wanted to distinguish wall thickening caused by cancer extension from that caused by inflammation after placing a biliary catheter on intraductal ultrasonography (IDUS). Methods: We studied 51 patients with biliary tract malignancies who had undergone placement of biliary drainage catheters before IDUS. IDUS was performed from a transhepatic (n = 34) or transpapillary (n = 17) route with a thin-caliber ultrasonic probe (2.0 mm in diameter, 20-MHz frequency). At the hepatic side of the tumor, the thickness, asymmetry, outer margin, inner margin, and internal echoes of the bile duct wall were reviewed prospectively and correlated with the histologic findings of the surgically resected specimens in all cases. Results: When IDUS showed wall thickening in a semicircular fashion, notched outer margin, rigid inner margin, papillary inner margin, and heterogeneous internal echoes, each finding had a positive predictive value for diagnosing cancer extension (100%, 100%, 83%, 100%, and 90%, respectively). When these factors were used as the diagnostic criteria of cancer extension, IDUS accurately demonstrated suitable surgical margins in 76% of all patients and 71% of patients with bile duct carcinoma. Conclusion: Wall thickening in a semicircular fashion, notched outer margin, rigid or papillary inner margin, and heterogeneous internal echoes are specific for cancer extension. However, surgical margins can be inaccurately assessed in some patients.
DOES FINANCIAL STATEMENT PUBLICATION EFFECT STOCK PRICE OF LQ-45 AT JAKARTA STOCK EXCHANGE

This article is purposed to know empirically wheather there is difference between stock price before and after the publicizing of financial statement of LQ-45 companies, listing at Jakarta Stock Exchange. Sample and data used in this analysis is all LQ-45 companies and 10 days stock price before and after financial statements are published. The finding shows that six variables such as return on equity, return on investment, price book value, price earning ratio, quick ratio and current ratio have significant and insignificant relationship toward stock price. According to the estimation can be concluded that all of those variables influence stock price 99.5% and however, most investor at Jakarta Stock Exchange are not consider to fundamental and internal factors in decision making process to buy or to sell a stock. Jel Classification: Keywords: Financial Statement, LQ-45 Stock Price
Structural determinants of processing and secretion of the Haemophilus influenzae Hap protein

Haemophilus influenzae elaborates a surface protein called Hap, which is associated with the capacity for intimate interaction with cultured epithelial cells. Expression of hap results in the production of three protein species: outer membrane proteins of approximately 155 kDa and 45 kDa and an extracellular protein of approximately 110 kDa. The 155 kDa protein corresponds to full‐length mature Hap (without the signal sequence), and the 110 kDa extracellular protein represents the N‐terminal portion of mature Hap (designated Haps). In the present study, we examined the mechanism of processing and secretion of Hap. Site‐directed mutagenesis suggested that Hap is a serine protease that undergoes autoproteolytic cleavage to generate the 110 kDa extracellular protein and the 45 kDa outer membrane protein. Biochemical analysis confirmed this conclusion and established that cleavage occurs on the bacterial cell surface. Determination of N‐terminal amino acid sequence and mutagenesis studies revealed that the 45 kDa protein corresponds to the C‐terminal portion of Hap, starting at N1037. Analysis of the secondary structure of this protein (designated Hapβ) predicted formation of a β‐barrel with an N‐terminal transmembrane α‐helix followed by 14 transmembrane β‐strands. Additional analysis revealed that the final β‐strand contains an amino acid motif common to other β‐barrel outer membrane proteins. Upon deletion of this entire C‐terminal consensus motif, Hap could no longer be detected in the outer membrane, and secretion of Haps was abolished. Deletion or complete alteration of the final three amino acid residues had a similar but less dramatic effect, suggesting that this terminal tripeptide is particularly important for outer membrane localization and/or stability of the protein. In contrast, isolated point mutations that disrupted the amphipathic nature of the consensus motif or eliminated the C‐terminal tryptophan had no effect on outer membrane localization of Hap or secretion of Haps. These results provide insight into a growing family of Gram‐negative bacterial exoproteins that are secreted by an IgA1 protease‐like mechanism; in addition, they contribute to a better understanding of the structural determinants of targeting of β‐barrel proteins to the bacterial outer membrane.
Cartel Stability by a Margin

We study cartel stability when firms maintain collusion only if it is more profitable than competition by a sufficiently large margin. Accounting for an (endogenous) cartel margin suggests new unambiguous comparative statics of changes in market characteristics on the scope for stable cartels. The margin increases their effect on the gain from collusion, relative to the gain from deviation. More specifically, we find that when there is a (small) cartel margin, both lower industry marginal cost and less product differentiation can increase cartel stability. The common conjecture that collusion is more prevalent in homogeneous goods and low cost industries–which has no basis in existing cartel theory–is canonically true when firms require even only a small cartel margin. Implications for competition policy include a focus in enforcement on standardized product-low input cost industries. In merger control, efficiencies may increase the risk of coordinated effects.
Time-Delay Systems: Design of Delay-Free and Low-Order Observers

This note provides a comprehensive treatment on the design of functional observers for linear systems having a time-varying delay in the state variables. The designed observers possess attractive features of being low-order and delay-free and hence they are cost effective and easy to implement. Existence conditions are derived and a design procedure for finding low-order observers is given.