Miracle-dz/UniFAR-FTUs huggingface dataset:
Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence

Analysis of phosphorylated histone protein H2AX (γH2AX) foci is currently the most sensitive method to detect DNA double‐strand breaks (DSB). This protein modification has the potential to become an individual biomarker of cellular stress, especially in the diagnosis and monitoring of neoplastic diseases. To make γH2AX foci analysis available as a routine screening method, different software approaches for automated immunofluorescence pattern evaluation have recently been developed. In this study, we used novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescence images of γH2AX foci and compared the results with visual assessments. Dose‐ and time‐dependent γH2AX foci formation was investigated in human peripheral blood mononuclear cells (PBMCs) treated with the chemotherapeutic drug etoposide (ETP). Moreover, the AKLIDES system was used to analyze the impact of different immunomodulatory reagents on γH2AX foci formation in PBMCs. Apart from γH2AX foci counting the use of novel pattern recognition algorithms allowed the measurement of their fluorescence intensity and size, as well as the analysis of overlapping γH2AX foci. The comparison of automated and manual foci quantification showed overall a good correlation. After ETP exposure, a clear dose‐dependent increase of γH2AX foci formation was evident using the AKLIDES as well as Western blot analysis. Kinetic experiments on PBMCs incubated with 5 μM ETP demonstrated a peak in γH2AX foci formation after 4 to 8 h, while a removal of ETP resulted in a strong reduction of γH2AX foci after 1 to 4 h. In summary, this study demonstrated that the AKLIDES system can be used as an efficient automatic screening tool for γH2AX foci analysis by providing new evaluation features and facilitating the identification of drugs which induce or modulate DNA damage. © 2013 International Society for Advancement of Cytometry
Demonstration of Type IV Pilus Expression and a Twitching Phenotype by Haemophilus influenzae

ABSTRACT Haemophilus influenzae is considered a nonmotile organism that expresses neither flagella nor type IV pili, although H. influenzae strain Rd possesses a cryptic pilus locus. We demonstrate here that the homologous gene cluster pilABCD in an otitis media isolate of nontypeable H. influenzae strain 86-028NP encodes a surface appendage that is highly similar, structurally and functionally, to the well-characterized subgroup of bacterial pili known as type IV pili. This gene cluster includes a gene (pilA) that likely encodes the major subunit of the heretofore uncharacterized H. influenzae-expressed type IV pilus, a gene with homology to a type IV prepilin peptidase (pilD) as well as two additional uncharacterized genes (pilB and pilC). A second gene cluster (comABCDEF) was also identified by homology to other pil or type II secretion system genes. When grown in chemically defined medium at an alkaline pH, strain 86-028NP produces approximately 7-nm-diameter structures that are near polar in location. Importantly, these organisms exhibit twitching motility. A mutation in the pilA gene abolishes both expression of the pilus structure and the twitching phenotype, whereas a mutant lacking ComE, a Pseudomonas PilQ homologue, produced large appendages that appeared to be membrane bound and terminated in a slightly bulbous tip. These latter structures often showed a regular pattern of areas of constriction and expansion. The recognition that H. influenzae possesses a mechanism for twitching motility will likely profoundly influence our understanding of H. influenzae-induced diseases of the respiratory tract and their sequelae.
Possible Existence of Common Internalization Mechanisms among Arginine-rich Peptides*

Basic peptides such as human immunodeficiency virus type 1 (HIV-1) Tat-(48–60) and DrosophilaAntennapedia-(43–58) have been reported to have a membrane permeability and a carrier function for intracellular protein delivery. We have shown that not only Tat-(48–60) but many arginine-rich peptides, including HIV-1 Rev-(34–50) and octaarginine (Arg8), efficiently translocated through the cell membranes and worked as protein carriers (Futaki, S., Suzuki, T., Ohashi, W., Yagami, T., Tanaka, S., Ueda, K., and Sugiura, Y. (2001) J. Biol. Chem. 276, 5836–5840). Quantification and time course analyses of the cellular uptake of the above peptides by mouse macrophage RAW264.7, human cervical carcinoma HeLa, and simian kidney COS-7 cells revealed that Rev-(34–50) and Arg8 had a comparable translocation efficiency to Tat-(48–60). Internalization of Tat-(48–60) and Rev-(34–50) was saturable and inhibited by the excess addition of the other peptide. Typical endocytosis and metabolic inhibitors had little effect on the internalization. The uptake of these peptides was significantly inhibited in the presence of heparan sulfate or chondroitin sulfates A, B, and C. Treatment of the cells with the anti-heparan sulfate antibody or heparinase III also lowered the translocation of these peptides. These results strongly suggest that the arginine-rich basic peptides share a certain part of the internalization pathway.
Tear changes in contact lens wearers following overnight eye closure.

PURPOSE Tear protein composition alters during eye closure, by becoming rich in secretory IgA (sIgA) and certain complement proteins. This may reflect altered ocular defense mechanisms during eye closure. Since overnight wear of contact lenses (CLs) is associated with an increased risk of corneal infection and inflammation, this study aimed to quantify tear protein changes with overnight soft CL wear. METHODS Non-stimulated tears were collected from 9 CL wearers prior to CL wear (baseline), after daily CL wear, and after 8 h sleep. Lenses were removed following wear and were extracted in 80% urea at 95 degrees C. Secretory IgA, complement C3 and C4, were measured using ELISA and total protein using the Pierce BCA assay. Assays were performed on tear samples and CL extracts. RESULTS Baseline tear protein concentrations were: 0 total tear protein (9.37 +/- 2.97 mg/mL), C3 (4.4 +/- 2.1 micrograms/mL), C4 (0.1 +/- 0.1 micrograms/mL), and sIgA (0.84 +/- 0.34 mg/mL). There were no differences in any protein levels between daily CL wear and no CL wear (p > 0.05). Following sleep, protein concentrations were: total tear protein (43.64 +/- 24.30 mg/mL), C3 (72.5 +/- 49.9 micrograms/mL), C4 (6.7 +/- 5.2 micrograms/mL), and sIgA (5.53 +/- 5.15 mg/mL). Total protein extracted from CLs after daily wear was 90 +/- 27 micrograms/CL and, after overnight wear, 152 +/- 24 micrograms/CL. Negligible levels of C3, C4 and sIgA were recovered from CL extracts. CONCLUSIONS Uncomplicated daily use of soft CLs does not appear to alter certain tear proteins compared with baseline levels. Uptake of these proteins by the CL does not appear to deplete the tear protein levels. Overnight levels of all tear proteins were increased, compared to daily CL wear.
Chronic hypoxia-induced cardiopulmonary changes in three rat strains: inhibition by the endothelin receptor antagonist SB 217242.

The cardiopulmonary profile of three different rat strains was compared after exposure to hypoxia (9% O2) for 0, 7, or 14 days. In Sprague-Dawley (SD), Wistar (W), and high altitude-sensitive (HAS) rats, pulmonary arterial pressure (PAP) rose 30, 58, and 85% respectively, after 7 days of hypoxia, and by 108, 116, and 167%, respectively, at 14 days compared to strain- and age-matched normoxic controls. Right ventricular hypertrophy (RVH), expressed as the ratio of right free wall/left wall + septum weight, in SD, W, and HAS was increased by 24, 53, and 48%, respectively, at 7 days, and by 51, 93, and 55% at 14 days compared to normoxic littermates. Histologically, marked medial thickening and luminal stenosis of small and medium-sized arteries were observed in all hypoxic rats, being most pronounced in the HAS rats at 14 days. Treatment of HAS rats with the ET receptor antagonist SB 217242 (3.6 or 10.8 mg/day i.p. by osmotic pump) significantly inhibited the hypoxia-induced increases in PAP (70-75% decrease). RVH was inhibited by 40% at the dose of 10.8 mg/day. Histologically, the SB 217242-treated rats had almost "normal" small and medium-sized arteries, comparable to those of the normoxic HAS controls. This study demonstrates an exaggerated PAP response to chronic hypoxia in HAS compared to SD and W rats. The inhibitory influence of SB 217242 on the functional and morphologic changes induced by hypoxia provides further evidence for a role for ET and the potential utility of ET receptor antagonists in the treatment of pulmonary hypertension.
Conceptual apraxia from lateralized lesions

Models of praxis have posited two major components, production and conceptual. Conceptual praxis disorders may occur in two domains: associative knowledge (tool-action associations such as hammer pound; tool-object associations such as hammer nail) and mechanical knowledge such as knowing the advantage that tools afford. Patients with Alzheimer's disease not only have conceptual apraxia (CA) but can dissociate CA from language deficits and from praxis production deficits (ideomotor apraxia). These findings suggests that knowledge about tools (action semantics) is independent of verbal semantics as well as movement representations. To learn if conceptual praxis knowledge is stored in one hemisphere (right or left) and if associative and mechanical conceptual praxis knowledge can be dissociated, we studied 29 right-handed subjects with unilateral strokes. Ten had left-hemisphere damage with no ideomotor apraxia. Eleven had left-hemisphere damage with ideomotor apraxia. There were eight right-hemisphere-damaged controls and 10 normal controls. These subjects were given tests for conceptual apraxia. There was a significant difference between groups, the left-hemisphere group with ideomotor apraxia being most impaired on both the associative and mechanical CA tests. There was a trend for associative and mechanical knowledge to be dissociated. Although conceptual praxis representations are stored in the left hemisphere, analysis of lesion sites did not reveal where in the left hemisphere they may be stored.
Squamous vulvar cancer: a clinically based individualization of treatment.

OBJECTIVE The aim of the study was to evaluate treatment results in 211 patients with previously untreated squamous cell vulvar cancer who were primary managed by surgery at the Gynecologic Oncology Unit of Alexandra Hospital, in terms of en bloc radical vulvectomy (N = 105), modified radical vulvectomy with three different incisions technique (N = 60), and radical hemivulvectomy (N = 46) with inguinofemoral lymphadenectomy. METHODS The surgical stage of disease, nodal status, lesion location and focality, marginal status, tumor size, physical and performance status, surgical modality used, and finally complications and recurrence rates were the analyzed factors for both survival and disease remission. RESULTS The overall 5-year survival was 70.1%. The 5-year survival for node-positive patients was 53.8% versus 79.7% for node-negative patients. Unifocal lesions had a 5-year survival of 76% compared with 50% of multifocal lesions. Posterolateral lesions had a better 5-year survival than that of anterior central lesions (79.5% vs 54. 4%). The marginal status of the surgical specimen was a significant predictor of both survival and recurrence. There was a significant difference in complications related to the en bloc radical vulvectomy in terms of wound breakdown, infection, and wound cellulitis. CONCLUSIONS Modified radical procedures are equally effective with the en bloc radical vulvectomy for the management of early (stage I/II) vulvar cancer. In advanced disease concervative surgery in an individualized approach could also effectively be applied.
Patterns of age‐dependent changes in the numbers of lymph follicles and germinal centres in somatic and mesenteric lymph nodes in growing C57Bl/6 mice

The timing of the first appearance of lymph follicles and germinal centres in various lymph nodes, and the ways in which numbers of these and IgM‐synthesising cells increase within the nodes, were investigated in male and female C57Bl/6N mice aged from 4 d to 16 wk. The lymphoid organs examined were the Peyer's patches, spleen, somatic (submandibular, deep cervical, brachial, axillary, inguinal and popliteal) and visceral (mesenteric and lumbar) lymph nodes. Primary follicles appeared in most somatic lymph nodes 6 d after birth. The number of follicles per node then increased rather sharply in larger lymph nodes and slowly in smaller nodes, up to 28 d of age, reaching a level which varied according to the location of the node. Thereafter, the number of follicles in the somatic lymph nodes increased only slightly to moderately, reaching a peak or plateau at 8–12 wk. In the mesenteric (ileocaecal) nodes, primary follicles first appeared at 12 d, then increased linearly during the suckling period and after weaning to reach a plateau at 8 wk of age. Germinal centres appeared in the submandibular and mesenteric nodes at 28 d and their numbers increased consistently in the latter, while remaining low in the former. The impact of possible ‘natural’ exogenous antigen stimulation of the various lymph nodes was estimated from the presence of IgM‐synthesising cells and germinal centres. Differences between the patterns of age‐dependent changes in the numbers of lymph follicles observed in the somatic and mesenteric lymph nodes during their ontogeny are discussed in relation to differences in the magnitude of the exogenous antigen stimulatory effect. We also found that the variations in the numbers of lymph follicles produced in somatic lymph nodes at different locations during the first 28 d after birth reflected differences in the dimensions of the body regions drained by a particular somatic lymph node at this stage of development.
The Global Diffusion of Markets and Democracy: The decision to privatize: economists and the construction of ideas and policies

Introduction Privatization is the distribution of state-owned assets to private owners. This distribution can happen by permitting spontaneous privatization, as frequently witnessed in Central and Eastern Europe; by giving or selling vouchers to the population to be redeemed for shares; or by sales through stock markets, private placements, or managerial buyouts. Privatization witnessed a global explosion in the 1980s and 1990s. Brune (2006) estimates that privatization revenues amounted to $1.3 trillion between 1985 and 2001, not including the mass privatization programs of the transition economies. Bortolotti, Fantini, and Siniscalco (2001) report that the global share of value added by state-owned enterprises fell from 9 percent to 6 percent in the 1978–1991 period. Privatization has been, in summary, of historic economic importance, reflecting a changed view of the state and its role in national economies. Why do countries decide to implement privatization programs at a given time? The orientation of political parties in power (Bortolotti, Fantini, and Siniscalco 2001), the legal orientation of an economy (La Porta et al . 1998), the speed of privatization (Lopez-de-Silanes et al . 1997), and concerns over budgetary control and international financial institutions (Brune, Garrett, and Kogut 2004) have been found to be consequential for the volume and value of privatization. This line of inquiry points to a more fundamental question: why should these factors matter now? Countries were in debt and had right-wing governments in previous decades without privatizing. These factors have fluctuated repeatedly over time.
Poor Performance of the Determine HIV-1/2 Ag/Ab Combo Fourth-Generation Rapid Test for Detection of Acute Infections in a National Household Survey in Swaziland

ABSTRACT Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and HIV antibodies (Ab) for early identification of acute infections, important for targeting prevention and reducing HIV transmission. In a nationally representative household survey in Swaziland, 18,172 adults, age 18 to 49 years, received home-based HIV rapid testing in 2010 and 2011. Of the 18,172 individuals, 5,822 (32.0%) were Ab positive (Ab+) by the Determine HIV-1/2 Ab/Ab combo test, and 5,789 (99.4%) of those were confirmed to be reactive in the Uni-Gold test. Determine combo identified 12 individuals as having acute infections (Ag+/Ab negative [Ab−]); however, none had detectable HIV-1 RNA and 8 of 12 remained HIV negative at their 6-week follow-up visit (4 were lost to follow-up). All RT-nonreactive samples were pooled and tested by nucleic acid amplification testing (NAAT) to identify acute infections. NAAT identified 13 (0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive, with RNA levels ranging from 300 to >10,000,000 copies/ml. However, none of them were Ag+ by Determine combo. Follow-up testing of 12 of the 13 NAAT-positive individuals at 6 months demonstrated 12 seroconversions (1 individual was lost to follow-up). Therefore, the Determine combo test had a sensitivity of 0% (95% confidence interval, 0 to 28) and positive predictive value of 0% for the detection of acute infections. The ability of the 4th-generation Determine combo to detect antigen was very poor in Swaziland. Thus, the Determine combo test does not add any value to the current testing algorithm; rather, it adds additional costs and complexity to HIV diagnosis. The detection of acute HIV infections may need to rely on other testing strategies.
The impact of isosorbide mononitrate on cervical ripening and labor induction in primiparous women with term pregnancy: A double-blind, randomized, controlled trial

Background: The most favorable method for cervical ripening is not fully agreed upon by practitioners; however, vaginal administration of isosorbide mononitrate (IMN) is considered a low-risk method of labor induction for pregnant women at full term. Our study was designed to assess the effect of IMN on cervical ripening and labor induction among primiparous women in Iran. Materials and Methods: A randomized, double-blind, placebo-controlled trial was conducted on 90 primiparous women with Bishop score ≤ 5, term pregnancy, and no sign of labor. The women were allocated into two groups to receive either a 40 mg (2 × 20 mg) IMN tablet vaginally (n = 45) or placebo (n = 45) at 0 and 12 h. If uterine contractions were not present after 24 h, women were sent to the labor section for induction of labor. Bishop score, reason for induction, duration of active, second, and third phase of labor, and mode of delivery were assessed. Results: There was a significant difference between the IMN group and the controls with respect to the Bishop score (4.92 vs. 4.03, P = 0.0.01), induction to active phase interval (387.6 vs. 520.4 min, P = 0.03), the length of induction (350 vs. 446 min, P = 0.03), and the drug administration to delivery interval (33.9 vs. 36.2 h, P = 0.03). The major side effect of IMN was headache, which responded to analgesia. Conclusions: IMN can be an effective alternative drug for cervical ripening and could decrease the labor interval. Further studies are necessary to fully address the benefits of IMN, especially in pregnancies of gestational age greater than 42 weeks.
Managing menu innovation in a saturated market: An empirical evidence from the Chain restaurants in Malaysia

This paper presents the empirical results of a recently concluded research study about managing menu innovation in a consumer market that has reached to its saturation level. Such market condition resulting in increased competition and, therefore, a need for increased innovation is essential. In this study, an investigation was carried in substantiating the effect of market saturation toward the relationship between innovation orientations and new menu innovation process. The region of Klang Valley was chosen as the study setting for its dynamic and matured consumer foodservice market. In this investigation, the theoretical conceptualization and the empirical validation of the proposed menu innovation process as a second-order hierarchical model along with the moderating variable of market saturation as first-order constructs were first advanced using both Statistical Package for Social Science (SPSS version 19) and partial least squares. Empirically, the measurement and structural models of this study confirmed adequate estimations based on partial least squares path modeling parameters. In line with the strength of partial least squares to explain complex relationships, the use of path modeling has made it possible to advance the theoretical contribution to this study. The results show that the moderating effect of market saturation on the link between the exogenous and endogenous variables found to have a medium effect size (f2 = 0.289) and significant at ρ < 0.05). The findings point to managerial challenges in shaping competition as evidence of radical innovations is still being pursued, although slightly weaken. This study, apart from its contribution to the model development of menu innovation process, has meaningful implications for restaurateurs to stay afloat in such a market condition.
Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000‐2015 period (the GEHEP 005 study)

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000‐2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla‐Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV‐infected patients with the following characteristics: median age 51 years (IQR, 44‐58), 67.9% male, 19.1% HIV‐coinfected, 23.5% HBV‐coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono‐infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.
Putative cholinergic projections from the nucleus isthmi and the nucleus reticularis mesencephali to the optic tectum in the goldfish (Carassius auratus)

The nucleus isthmi of fish and amphibians has reciprocal connections with the optic tectum, and biochemical studies suggest that it may provide a major cholinergic input to the tectum. In goldfish, we have combined immunohistochemical staining for choline acetyltransferase with retrograde labeling of nucleus isthmi neurons after tectal injections of horseradish peroxidase.