Miracle-dz/UniFAR-FTUs huggingface dataset:
Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination

Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.
Optimization of area under a delay constraint in digital filter synthesis using SAT-based integer linear programming

In this paper, we propose an exact algorithm for the problem of area optimization under a delay constraint in the synthesis of multiplierless FIR filters. To the best of our knowledge, the method presented in this paper is the only exact algorithm designed for this problem. We present the results of the algorithm on real-sized filter instances and compare with an improved version of a recently proposed exact algorithm designed for the minimization of area. We show that in many cases delay can be minimized without any area penalty. Additionally, we describe two approximate algorithms that can be applied to instances which cannot be solved, or take too long, with the exact algorithm. We show that these algorithms find similar solutions to the exact algorithm in less CPU time
Changes in Insulin Secretion and Insulin Sensitivity in Relation to the Glycemic Outcomes in Subjects With Impaired Glucose Tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1)

OBJECTIVE The Indian Diabetes Prevention Programme-1 (IDPP-1) showed that lifestyle modification (LSM) and metformin were effective for primary prevention of diabetes in subjects with impaired glucose tolerance (IGT). Among subjects followed up for 3 years (n = 502), risk reductions versus those for the control group were 28.5, 26.4, and 28.2% in LSM, metformin (MET), and LSM plus MET groups, respectively. In this analysis, the roles of changes in secretion and action of insulin in improving the outcome were studied. RESEARCH DESIGN AND METHODS For this analysis, 437 subjects (93 subjects with normoglycemia [NGT], 150 subjects with IGT, and 194 subjects with diabetes) were included. Measurements of anthropometry, plasma glucose, and plasma insulin at baseline and at follow-up were available for all of them. Indexes of insulin resistance (homeostasis model assessment of insulin resistance) and β-cell function (insulinogenic index [ΔI/G]: 30-min fasting insulin divided by 30-min glucose) were also analyzed in relation to the outcome. RESULTS Subjects with IGT showed a deterioration in β-cell function with time. Individuals with higher insulin resistance and/or low β-cell function at baseline had poor outcome on follow-up. In relation to no abnormalities, the highest incidence of diabetes occurred when both abnormalities coexisted (54.9 vs. 33.7%, χ2 = 7.53, P = 0.006). Individuals having abnormal insulin resistance (41.1%) or abnormal ΔI/G (51.2%, χ2 = 4.87, P = 0.027 vs. no abnormalities) had lower incidence. Normal β-cell function with improved insulin sensitivity facilitated reversal to NGT, whereas deterioration in both resulted in diabetes. The beneficial changes were better with intervention than in the control group. Intervention groups had higher rates of NGT and lower rates of diabetes. CONCLUSIONS In the IDPP-1 subjects, beneficial outcomes occurred because of improved insulin action and sensitivity caused by the intervention strategies.
Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy

Purpose: Epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) might be predictive for clinical response to EGFR inhibitor treatment. However, retrospective analyses of EGFR mutations in clinical trials have shown inconclusive results and the effect of EGFR sequencing in NSCLC is still controversial. Because the vast majority of EGFR mutations described have not been functionally characterized, simple correlation of mutational status and treatment response may not provide reliable information about the predictive value of EGFR mutations. Thus, we aimed to characterize a comprehensive panel of clinically observed EGFR mutations. Experimental Design and Results: A panel of 30 EGFR mutations was cloned and characterized for kinase activity and the ability to confer growth factor independence. Interestingly, 4 of 30 EGFR mutations showed no kinase activity even after ligand stimulation and were not able to confer growth factor independence. Ba/F3 cells expressing activating EGFR mutants were then used to test the efficacy of EGFR inhibitors in a cell proliferation assay. IC50 values were calculated for gefitinib, erlotinib, and AEE788. We show that the sensitivity of EGFR mutations toward different inhibitors varies significantly, thus establishing a comprehensive sensitivity profile for each inhibitor. Conclusions: EGFR mutations identified in NSCLC patients display distinct biological features. The variability in kinase activity, transforming potential, and sensitivity to EGFR inhibitors has to be considered in clinical studies aiming to correlate mutational status and drug response. The identification of comprehensive drug resistance profiles opens the opportunity to test alternative EGFR inhibitors in vitro.
Ethambutol induces impaired autophagic flux and apoptosis in the rat retina

ABSTRACT Ethambutol (EMB), an effective first-line antituberculosis agent, can cause serious visual impairment or irreversible vision loss in a significant number of patients. However, the mechanism underlying this ocular cytotoxicity remains to be elucidated. In this study, we found that there were statistically significant dose- and time-dependent increases in the number of cytoplasmic vacuoles and the level of cell death in EMB-treated RGC-5 cells (retinal ganglion cells). The protein kinase C (PKC)δ inhibitor rottlerin markedly reduced the EMB-induced activation of caspase-3 and the subsequent apoptosis of RGC-5 cells. Western blot analysis revealed that the expression levels of class III PI3K, Beclin-1, p62 and LC3-II were upregulated, and LC3 immunostaining results showed activation of the early phase and inhibition of the late stage of autophagy in retinas of the EMB-intraperitoneal (IP)-injected rat model. We further demonstrated that exposure to EMB induces autophagosome accumulation, which results from the impaired autophagic flux that is mediated by a PKCδ-dependent pathway, inhibits the PI3K/Akt/mTOR signaling pathway and leads to apoptotic death in retina neuronal cells. These results indicate that autophagy dysregulation in retinal neuronal cells might play a substantial role in EMB-induced optic neuroretinopathy. Summary: This study provides the first evidence that EMB induces autophagosome accumulation, which results from the impaired autophagic flux that is mediated by a PKCδ-dependent pathway, and leads to apoptotic death in retina neuronal cells.
African Traditional Religion and Christian Faith

Contemporary writings of those knowledgeable about the growing numerical strength of Christian adherents in Africa are shot through with optimism about the future of Christianity there. In fact, it is being predicted that by the year A.D. 2000 the Christian population in Africa would have increased from its present ninety-seven million to three hundred fifty-one million. 1 While this writer shares in that optimism, it must be stressed that the future of Christianity in Africa is tied up with a better understanding of the nature of African traditional religion. Such an understanding has been made imperative by the wind of political change that is blowing through Africa. Besides this, the re-examination of the nature of African traditional religion will enrich Christianity and contribute a deepening of the doctrine of die cosmic Christ to which most theologians have hitherto paid only a lip service.
The Effect of Awareness of Success or Failure

The main idea of the experiment was to determine what would be the difference in gain made by two groups of fourth-grade arithmetic pupils one of which was made aware of success or failure. The one group used for the purpose of maintaining or reviewing previously learned skills in arithmetic a series of mixed fundamental drill 1mits which contained no reference to standards of work, and hence no provision for a child or class to keep an objective record of growth (or lack of it) in power over arithmetic. The other group used exactly the same material and under comparable conditions, with this exception: on each drill unit there appeared a set of standards similar to the sample shown here.
Paraoxonase-1 Is Not a Major Determinant of Stent Thrombosis in a Taiwanese Population

Background Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of CYP (CYP 2C19*2, CYP 2C19*3, and CYP 2C19*17), ABCB1 (ABCB1 3435C>T, ABCB1 129T>C, and ABCB1 2677G>T/A), and PON1 (PON1 Q192R, PON1 L55M, and PON1 108C>T) on the development of stent thrombosis (ST) in patients receiving clopidogrel after percutaneous coronary intervention (PCI). Methods and Results We evaluated the incidence of ST (0.64%) in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions). The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of CYP 2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263–9.544; P = 0.031). However, genetic variations in PON1 and ABCB1 showed no significant association with ST. Conclusion We conclude that in a Taiwanese population, PON1 Q192R genotype is not associated with ST development after PCI. However, the presence of CYP 2C19*2 allele is a risk factor for ST development after PCI.
Compilation of published signal sequences.

INTRODUCTION The process by which proteins are transported across membranes was presented as a detailed hypothesis, the 'signal hypothesis' in 1975 (1) and subsequently in revised forms (2,3). An essential feature is the presence of a polypeptide of 20-40 amino acids, predominantly hydrophobic, at the amino terminus of secreted proteins. This binds to the endoplasmic reticulum and transport Is initiated before translation is complete. Despite some contradictory evidence (e.g. 4-6) the essentials of the signal hypothesis have been widely accepted and have been extended to include proteins which become integrated into membranes (3,7) and bacterial systems (8). The current hypothesis requires that the signal peptide must be transient. However, a number of secreted and membrane-bound proteins have now been shown to have N-terminal sequences which resemble the transient peptides, but which are not cleaved. It has been shown that these sequences can function as signals for translocation into the rough endoplasmic reticulum (9,10). Therefore, they have been included in this compilation. Proteins which are transferred across two membrane bilayers into mitochondria and chloroplasts have also now been found to have transient amino terminal regions (-3,11,12). A major difference In the transport of these proteins is that it occurs post-translationally and it is clear that their signals are quite different.
Algebraic techniques for enumerating self-avoiding walks on the square lattice

The authors describe a new algebraic technique for enumerating self-avoiding walks on the rectangular lattice. The computational complexity of enumerating walks of N steps is of order 3N/4 times a polynomial in N, and so the approach is greatly superior to direct counting techniques. They have enumerated walks of up to 39 steps. As a consequence, they are able to accurately estimate the critical point, critical exponent, and critical amplitude.
Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC)

Abstract Objective: To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950–1975 (at age 20), 1960–1985 (at age 30) and 1970–1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time. Setting: The EPIC project. Subjects: In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries. Results: Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950–1975, 1960–1985 and 1970–1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption. Conclusion: The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.
Time Talk by Korean Young Learners of English

The present study is designed to test how Korean-speaking young learners of English make the aspectual distinctions and how they talk about the past events. An experiment was conducted on 65 learners of English in grade 3 and 7 returnees, asking them to describe 19 film clips in English and Korean. The results demonstrated that the classroom young learners showed biased distribution in the use of tense and aspect morphology in English: They used the progressive -ing predominantly on activity verbs and past forms primarily on achievement verbs. Regarding viewpoint distinctions for the given events, they were guided by inherent lexical aspect of verbs rather than actual situational properties of the events, and failed to distinguish between different viewpoints, apparently not knowing the meaning or function of the progressive -ing. A comparison across the Korean task and the English task revealed that the use of tense-aspect morphology is universal in that progressive forms are used mostly for activities and past forms primarily for achievements, but language-dependent in that the same events of accomplishments are described differently in L1 and L2. This is interpreted as evidence that the development of the interlanguage system is autonomous of the mother tongue.
Tivantinib for the treatment of hepatocellular carcinoma

ABSTRACT Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with a poor prognosis due to late diagnosis in the majority of cases. Physicians are frequently confronted with patients who are not eligible for curative or locoregional treatments any more. In this scenario, the multi-tyrosine kinase inhibitor sorafenib remains the only systemic first-line treatment option providing modest survival benefit compared to placebo with significant but for most patients acceptable adverse effects. Areas covered: Tivantinib was the first antiproliferative agent to be been applied in a phase III trial based on receptor overexpression analyses after disease progression on sorafenib. While phase I and II trials with tivantinib in second line showed encouraging results, a recent press release announced that the METIV-HCC phase III study of tivantinib in HCC did not meet its primary endpoint of improving overall survival. Expert commentary: Evidence for antiangiogenetic therapy inducing tumor hypoxia leading to overexpression of proliferative genes, including cMET, underlines the potential of tivantinib as second-line treatment. However, as the mechanism of action of tivantinib through cMET inhibition has recently been questioned by several groups, identification of alternative proliferative markers or targets is mandatory.
A STUDY OF NON-COMMUNICABLE MORBIDITY PATTERN IN GERIATRIC PATIENTS ATTENDING A REFERRAL RAILWAY HOSPITAL IN ALLAHABAD, UTTAR PRADESH

Research question: What types of non-communicable geriatric cases attend the Railway referral hospital in Allahabad, Uttar Pradesh? Objectives: 1) To identify the various morbidities in the geriatric population attending the OPD of the selected hospital. 2) To observe the sex-wise difference of such morbidities among the studied subjects. Study design: Hospital-based cross-sectional study. Study location: the North Central Railway Hospital of Allahabad. Study duration: 1 year (from March, 2010 to February, 2011). Material and method: Medical record analysis, clinical history taking and examination using a pretested questionnaire. Results: Total 467 respondents were included in the study (235 males and 232 females). Three-fourth of the subjects rated their health status as either ‘mostly’ or ‘somewhat’ healthy. Nearly 62% had vision abnormality while 15.2% suffered from impaired hearing. Respiratory (43.5%) and musculoskeletal symptoms were among the most commonly observed morbidities. Diabetes mellitus and overactive bladder syndrome were significantly commoner among males while respiratory complaints, osteoarthritis, rheumatoid arthritis and low back ache were more common in females as compared to males. Discharge per vaginum was the most common gynecological problem noted (41.4% of all female patients). Conclusion: The study identifies the common morbidities in geriatric hospital attendees and underscores the need for appropriate resource allocation and arrangements.
MR imaging predictors of local control of glottic squamous cell carcinoma treated with radiation alone.

PURPOSE To retrospectively evaluate the prognostic significance of magnetic resonance (MR) imaging-determined tumor parameters, especially the presence of cartilage invasion, regarding local control of glottic squamous cell carcinoma treated with radiation therapy (RT) alone. MATERIALS AND METHODS The study was performed with the approval of our institutional review board; direct patient consent was waived. Pretreatment MR images of 118 patients aged 41-86 years (110 men, eight women) with glottic carcinoma treated with RT alone were reviewed for tumor involvement of specific laryngeal anatomic subsites (including laryngeal cartilage), tumor volume, and extralaryngeal tumor spread; these findings were compared with local control. Local control was defined as absence of a recurrence at the primary site for 2 years. Statistical significance of differences between curves for local control estimated with the Kaplan-Meier method was tested with log-rank test. RESULTS Results of univariate analysis showed all MR imaging-determined parameters to be significant predictors of local control rate, compared with clinical parameters where T classification and vocal cord mobility were the only significant parameters associated with local control. Multivariate analysis (Cox regression model) of clinical and radiologic parameters revealed that hypopharyngeal extension (P=.04) and intermediate T2 signal intensity (SI) in cartilage similar to tumor SI (P<.001) were independent prognostic factors with regard to local control. CONCLUSION Intermediate T2 SI in cartilage, which may suggest cartilage invasion, and hypopharyngeal extension of tumor, predict greater likelihood of local failure, whereas high T2 SI, which may suggest inflammatory tissue in cartilage, predicts lower likelihood of local failure.
Utility of the Type D Scale 16 and Voice Handicap Index to Assist Voice Care in Student Teachers and Teachers

An epidemiological cross-sectional survey study was performed among female student teachers and teachers for primary education, using a general questionnaire, the Type D Scale 16 (DS16) and Voice Handicap Index (VHI). Type D personality is the combination of high ‘negative affectivity’ and high ‘social inhibition’, and the DS16 has been considered to be a reliable and valid measure of these two stable personality traits. The objectives of the study were to assess the VHI of type D subjects in comparison to non-type-D subjects, to explore the utility of the DS16 and the VHI to assess whether subjects with a type D personality were more handicapped due to their voice complaints, and whether they behaved differently in seeking voice care. It was investigated whether subjects of the type D group in comparison to the non-type-D group had a voice handicap even when they did not report voice complaints. The type D group did not report more voice complaints than the non-type-D group. However, the type D group had higher VHI scores compared to the non-type-D group. Furthermore, significantly more type D subjects had a VHI score greater than the 75th percentile than the non-type-D subjects, and they sought less voice care than the non-type-D subjects. Also among subjects who reported voice complaints, the type D group sought less care than the non-type-D group. Even among the subjects who did not report voice complaints, significantly more type D than non-type-D subjects had VHI scores higher than the 75th percentile. The findings indicated that type D subjects were apparently more bothered by their voice than the non-type-D subjects (high VHI scores); however, they did not report more voice complaints, and they also sought less voice care. The DS16 used along with the VHI was useful to identify subjects of the type D trait with a voice handicap. This enables specific voice care, encompassing not only physical, but also psychosocial aspects of vocal health.