Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo three-dimensional characterization of the healthy human lamina cribrosa with adaptive optics spectral-domain optical coherence tomography.

PURPOSE To characterize the in vivo three-dimensional (3D) lamina cribrosa (LC) microarchitecture of healthy eyes using adaptive optics spectral-domain optical coherence tomography (AO-SDOCT). METHODS A multimodal retinal imaging system with a light source centered at 1050 nm and AO confocal scanning laser ophthalmoscopy was used in this study. One randomly selected eye from 18 healthy subjects was scanned in a 6° × 6° window centered on the LC. Subjects also underwent scanning with Cirrus HD-OCT. Lamina cribrosa microarchitecture was semiautomatically segmented and quantified for connective tissue volume fraction (CTVF), beam thickness, pore diameter, pore area, and pore aspect ratio. The LC was assessed in central and peripheral regions of equal areas and quadrants and with depth. A linear mixed effects model weighted by the fraction of visible LC was used to compare LC structure between regions. RESULTS The nasal quadrant was excluded due to poor visualization. The central sector showed greater CTVF and thicker beams as compared to the periphery (P < 0.01). Both superior and inferior quadrants showed greater CTVF, pore diameter, and pore mean area than the temporal quadrant (P < 0.05). Depth analysis showed that the anterior and posterior aspects of the LC contained smaller pores with greater density and thinner beams as compared to the middle third (P < 0.05). The anterior third also showed a greater CTVF than the middle third (P < 0.05). CONCLUSIONS In vivo analysis of healthy eyes using AO-SDOCT showed significant, albeit small, regional variation in LC microarchitecture by quadrant, radially, and with depth, which should be considered in further studies of the LC.
Outer Regions of the Cluster Gaseous Atmospheres

We present a systematic study of the hot gas distribution in the outer regions of regular clusters using ROSAT PSPC data. Outside the cooling flow region, the β-model describes the observed surface brightness closely, but not precisely. Between 0.3 and 1 virial radii, the profiles are characterized by a power law with slope, expressed in terms of the β-parameter, in the range β = 0.65-0.85. The values of β in this range of radii are typically larger by ≈0.05 than those derived from the global fit. There is a mild trend for the slope to increase with temperature, from ⟨β⟩ ≈ 0.68 for 3 keV clusters to ≈0.8 for 10 keV clusters; however, even at high temperatures there are clusters with flat gas profiles, β < 0.7. Our values of β at large radius are systematically higher, and the trend of β with temperature is weaker than was previously found; the most likely explanation is that earlier studies were affected by an incomplete exclusion of the central cooling flow regions. For our regular clusters, the gas distribution at large radii is quite close to spherically symmetric, and this is shown not to be an artifact of the sample selection. The gas density profiles are very similar when compared in units of the cluster virial radius. The radius of fixed mean gas overdensity 1000 (corresponding to the dark matter overdensity 200 for Ω = 0.2) shows a tight correlation with temperature, R ~ T0.5, as expected from the virial theorem for clusters with the universal gas fraction. At a given temperature, the rms scatter of the gas overdensity radius is only ≈7%, which translates into a 20% scatter of the gas mass fraction, including statistical scatter due to measurement uncertainties.
Diversity in insect axis formation: two orthodenticle genes and hunchback act in anterior patterning and influence dorsoventral organization in the honeybee (Apis mellifera)

Axis formation is a key step in development, but studies indicate that genes involved in insect axis formation are relatively fast evolving. Orthodenticle genes have conserved roles, often with hunchback, in maternal anterior patterning in several insect species. We show that two orthodenticle genes, otd1 and otd2, and hunchback act as maternal anterior patterning genes in the honeybee (Apis mellifera) but, unlike other insects, act to pattern the majority of the anteroposterior axis. These genes regulate the expression domains of anterior, central and posterior gap genes and may directly regulate the anterior gap gene giant. We show otd1 and hunchback also influence dorsoventral patterning by regulating zerknült (zen) as they do in Tribolium, but that zen does not regulate the expression of honeybee gap genes. This suggests that interactions between anteroposterior and dorsal-ventral patterning are ancestral in holometabolous insects. Honeybee axis formation, and the function of the conserved anterior patterning gene orthodenticle, displays unique characters that indicate that, even when conserved genes pattern the axis, their regulatory interactions differ within orders of insects, consistent with relatively fast evolution in axis formation pathways.
Assessment of Sublethal Effects of Methoxyfenozide on Oriental Fruit Moth (Lepidoptera: Tortricidae)

Abstract Sublethal effects of the insect growth regulator methoxyfenozide were examined in oriental fruit moth, Grapholita molesta (Busck), in laboratory and field studies. In laboratory studies, oriental fruit moth larvae reared on diet amended with 0.1 ppm methoxyfenozide developed at the same rate as larvae reared on untreated diet, and paired moths reared as larvae from the same treated or untreated diets exhibited similar fecundity and fertility. Population growth differences over multiple generations were used to examine sublethal effects of methoxyfenozide on population dynamics in the field. Multiple single-tree cages were placed over apple (Malus spp.) trees treated with two applications of methoxyfenozide (70 g [AI]/ha) and nontreated trees. Cages were infested at a single time point with virgin male and female oriental fruit moth adults, and population growth was evaluated by egg counts, shoot infestation, fruit damage, and larval counts over a 12-wk period. Significantly fewer eggs, larvae, and damaged fruit were found on methoxyfenozide-treated compared with nontreated trees in 2001. Observed population differences may have been a result of direct mortality to eggs and larvae of the first generation rather than sublethal effects. In 2002, no differences were observed between treatments, but a heavy rain event shortly after the early infestation impacted the experiment. A late moth release treatment was tested in 2002 to examine the effects of residual methoxyfenozide 55 d after initial application. Significantly fewer eggs were found in the methoxyfenozide treatment compared with the control, but no differences existed among treatments in shoot infestation, percentage of damaged fruit, or larval populations. It was concluded direct mortality of eggs and larvae exposed to methoxyfenozide rather than sublethal effects were most important in reduction of subsequent generations.
Digoxin Use After Diagnosis of Colorectal Cancer and Survival: A Population-Based Cohort Study

Background: Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer–specific mortality. Methods: A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer–specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer–specific mortality. Results: Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer–specific mortality before adjustment (HR, 1.25; 95% CI, 1.07–1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91–1.34) and there was no evidence of a dose response. Conclusions: In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer–specific mortality with digoxin use after diagnosis. Impact: These results provide some reassurance that digoxin use is safe in colorectal cancer patients. Cancer Epidemiol Biomarkers Prev; 24(11); 1804–7. ©2015 AACR.
DNA barcode sequences used to identify Aedes (Stegomyia) albopictus (Diptera: Culicidae) in La Tebaida (Quindío, Colombia)

Aedes (Stegomyia) albopictus has been identified for the first time in the municipality of La Tebaida (Quindio department of Colombia), an area with active transmission of dengue fever by Ae. (Stegomyia) aegypti. Specimens of Ae. albopictus were detected in a tire used as an ovitrap in a remnant of bamboo plantation in a rural area of the municipality of La Tebaida; Ae. aegypti presented co-occurrence and both species were molecularly typed using cytochrome oxidase I (DNA barcode region). The first DNA barcode sequences were recorded for 13 Colombian specimens of Ae. albopictus, identifying an asiatic origin (Singapore) and demonstrating the utility of this method for molecular identification. These sequences can be used to identify genetic flow with other populations in Colombia, in ecological studies, and in studies of vector incrimination in outbreaks of emerging and re-emerging arbovirus in Colombia.
Significant Differences Characterise the Correlation Coefficients between Biocide and Antibiotic Susceptibility Profiles in Staphylococcus aureus

There is a growing concern by regulatory authorities for the selection of antibiotic resistance caused by the use of biocidal products. We aimed to complete the detailed information on large surveys by investigating the relationship between biocide and antibiotic susceptibility profiles of a large number of Staphylococcus aureus isolates using four biocides and antibiotics commonly used in clinical practice. The minimal inhibitory concentration (MIC) for most clinically-relevant antibiotics was determined according to the standardized methodology for over 1600 clinical S. aureus isolates and compared to susceptibility profiles of benzalkonium chloride, chlorhexidine, triclosan, and sodium hypochlorite. The relationship between antibiotic and biocide susceptibility profiles was evaluated using non-linear correlations. The main outcome evidenced was an absence of any strong or moderate statistically significant correlation when susceptibilities of either triclosan or sodium hypochlorite were compared for any of the tested antibiotics. On the other hand, correlation coefficients for MICs of benzalkonium chloride and chlorhexidine were calculated above 0.4 for susceptibility to quinolones, beta-lactams, and also macrolides. Our data do not support any selective pressure for association between biocides and antibiotics resistance and furthermore do not allow for a defined risk evaluation for some of the compounds. Importantly, our data clearly indicate that there does not involve any risk of selection for antibiotic resistance for the compounds triclosan and sodium hypochlorite. These data hence infer that biocide selection for antibiotic resistance has had so far a less significant impact than feared.
Predictors of Self‐Reported Adherence and Plasma HIV Concentrations in Patients on Multidrug Antiretroviral Regimens

Background: Adherence to prescribed medications is a central feature of good clinical HIV care, but little is known about the factors associated with multidrug antiretroviral adherence, or about how such adherence is related to plasma HIV suppression. Methods: We collected data from 133 HIV‐infected adults receiving antiretroviral therapy. Study subjects completed customized adherence self‐report instruments and provided blood samples to measure plasma HIV‐1 RNA concentrations and CD4+ lymphocyte counts. Regression models were used to determine the independent predictors of antiretroviral adherence and plasma HIV concentration, and the relationships between the two. Results: Adherence was poor (average, <80% antiretrovirals/day) in 28% (95% confidence interval [CI], 20%‐36%), fair (80%‐99% per day) in 23% (95% CI, 15%‐30%), and excellent (100% per day) in 50% (95% CI, 41%‐58%) of study subjects. Mean decreases in HIV‐1 concentration from highest‐ever levels were 1.3, 1.6, and 2.0 log10 copies/ml in these three groups, respectively (χ2; p < .02). Two‐stage least squares regression demonstrated a ‐1.3 log difference in viral load associated with each category improvement in adherence. In multivariate models, confidence in medication‐taking ability, or perceived self‐efficacy, and convenience of the medication regimen, or “fit” with routine and daily activities, were also associated with greater medication adherence (odds ratios [OR] 5.3; 95% CI, 2.4‐11.8. and 9.0; 95% CI, 1.8‐45.3, respectively). The latter was also independently associated with a lower plasma HIV concentration (p < .02). Conclusions: Nonadherence to combination antiretroviral medications is common and is associated with increased levels of plasma HIV. Programs and clinical efforts to improve medication taking should strive to integrate medications better into patients' daily routines and to improve patients' confidence in their ability to take medications correctly.
Efficacy of nonsurgical periodontal therapy on glycaemic control in type II diabetic patients: a randomized controlled clinical trial

Purpose Diabetes and periodontal disease are two common diseases with high prevalence rates. Recent evidence has shown a bidirectional relationship between diabetes and periodontitis. The aim of this study was to investigate the effects of nonsurgical periodontal therapy on glycemic control in type 2 diabetes mellitus patients. Methods Sixty subjects aged 35-45 years with blood sugar controlled by oral hypoglycaemic agents were randomly divided equally among 3 groups: group A (scaling, mouthwash, and brushing), group B (mouthwash and brushing), and group C (brushing only). Glycated haemoglobin (HbA1c), fasting blood sugar (FBS), probing pocket depth (PPD), gingival index (GI), plaque index (PI), and the relevant drug history were recorded at baseline and after 3 months of intervention. Comparison of the mean difference among the variables was performed by parametric and nonparametric tests, which were further evaluated using multiple regression analysis. Results The mean differences between the PPD, FBS, HbA1c, GI, and PI in groups A and B were found to be statistically significant (P<0.001). Multiple regression analysis in group A showed that out of all the independent variables, GI and frequency of drug administration independently (b=0.3761 and b=0.598) showed a significantly greater impact on HbA1c (R2=0.832, P<0.05). Conclusions Nonsurgical periodontal therapy can effectively decrease HbA1c levels in type 2 diabetes mellitus patients on medication.
Productive infection of primary murine astrocytes, lymphocytes, and macrophages by human immunodeficiency virus type 1 in culture

A mouse model of human immunodeficiency virus type 1 (HIV-1) infection would be extremely valuable for evaluation of therapies and vaccines; however, multiple blocks to productive infection of NIH 3T3 and other mouse cell lines have been reported. The authors investigated the replication of HIV-1 in primary mouse astrocytes, lymphocytes, and macrophages in culture by infection with intact HIV-1 pseudotyped with the vesicular stomatitis virus G envelope glycoprotein (VSV-G) or with the envelope glycoprotein of amphotropic murine leukemia virus. Astrocytes, lymphocytes, and macrophages were susceptible to productive infection as variously assayed by detection of p24 and Tat proteins, viral protease-mediated processing of Gag, appropriately spliced viral RNA, and infectious progeny virus. As expected, NIH 3T3 cells were not susceptible to productive infection by VSV/NL4. Susceptibility mapped neither to the Fv locus nor to a possible polymorphism in cyclin T1. This study indicates that there are no intrinsic intracellular barriers to HIV-1 replication in primary mouse cells when virus entry is efficient.
In Search of Simplicity: A Self-Organizing Group Communication Overlay

Group communication primitives have broad utility as building blocks for distributed applications. The challenge is to create and maintain the distributed structures that support these primitives while accounting for volatile end-nodes and variable network characteristics. Most solutions proposed to date rely on complex algorithms or global information, thus limiting the scale of deployments and acceptance outside the academic realm. This article introduces a low-complexity, self-organizing solution for maintaining multicast trees, that we refer to as UMM (unstructured multi-source multicast). UMM uses traditional distributed systems techniques: layering, soft-state, and passive data collection to adapt to the dynamics of the physical network and maintain data dissemination trees. The result is a simple, adaptive system with lower overheads than more complex alternatives. We have implemented UMM and evaluated it on up to 1024-node emulated ModelNet networks and on the PlanetLab testbed. Extensive experimental evaluations and quantitative comparisons with alternative solutions demonstrate VMM's low overhead, efficient network usage, and ability to quickly adapt to network changes and to recover from failures.
A numerical model simulating reactive transport and evolution of fracture permeability

A numerical model is presented to describe the evolution of fracture aperture (and related permeability) mediated by the competing chemical processes of pressure solution and free‐face dissolution/precipitation; pressure (dis)solution and precipitation effect net‐reduction in aperture and free‐face dissolution effects net‐increase. These processes are incorporated to examine coupled thermo‐hydro‐mechano‐chemo responses during a flow‐through experiment, and applied to reckon the effect of forced fluid injection within rock fractures at geothermal and petroleum sites. The model accommodates advection‐dominant transport systems by employing the Lagrangian–Eulerian method. This enables changes in aperture and solute concentration within a fracture to be followed with time for arbitrary driving effective stresses, fluid and rock temperatures, and fluid flow rates. This allows a systematic evaluation of evolving linked mechanical and chemical processes. Changes in fracture aperture and solute concentration tracked within a well‐constrained flow‐through test completed on a natural fracture in novaculite (Earth Planet. Sci. Lett. 2006, in press) are compared with the distributed parameter model. These results show relatively good agreement, excepting an enigmatic abrupt reduction in fracture aperture in the early experimental period, suggesting that other mechanisms such as mechanical creep and clogging induced by unanticipated local precipitation need to be quantified and incorporated. The model is applied to examine the evolution in fracture permeability for different inlet conditions, including localized (rather than distributed) injection. Predictions show the evolution of preferential flow paths driven by dissolution, and also define the sense of permeability evolution at field scale. Copyright © 2006 John Wiley & Sons, Ltd.
DA-Complex Assembly Activity Required for VP16C Transcriptional Activation

ABSTRACT One class of transcriptional activation domains stimulates the concerted binding of TFIIA and TFIID to promoter DNA. To test whether this DA-complex assembly activity contributes significantly to the overall mechanism of activation in vivo, we analyzed mutants of the 38-amino-acid residue VP16C activation subdomain from herpes simplex virus. An excellent correlation was observed between the in vivo activation function of these mutants and their in vitro DA-complex assembly activity. Mutants severely defective for in vivo activation also showed reduced in vitro binding to native TFIIA. No significant correlation between in vivo activation function and in vitro binding to human TATA binding protein, human TFIIB, or Drosophila melanogaster TAFII40 was observed for this set of VP16C mutants. These results argue that the ability of VP16C to increase the rate and extent of DA-complex assembly makes a significant contribution to the overall mechanism of transcriptional activation in vivo.
Probing the structure of complex macromolecular interactions by homolog specificity scanning: the P1 and P7 plasmid partition systems

The P1 plasmid partition locus, P1 par, actively distributes plasmid copies to Escherichia coli daughter cells. It encodes two DNA sites and two proteins, ParA and ParB. Plasmid P7 uses a similar system, but the key macromolecular interactions are species specific. Homolog specificity scanning (HSS) exploits such specificities to map critical contact points between component macromolecules. The ParA protein contacts the par operon operator for operon autoregulation, and the ParB contacts the parS partition site during partition. Here, we refine the mapping of these contacts and extend the use of HSS to map protein–protein contacts. We found that ParB participates in autoregulation at the operator site by making a specific contact with ParA. Similarly, ParA acts in partition by making a specific contact with ParB bound at parS. Both these interactions involve contacts between a C‐terminal region of ParA and the extreme N‐terminus of ParB. As a single type of ParA–ParB complex appears to be involved in recognizing both DNA sites, the operator and the parS sites may both be occupied by a single protein complex during partition. The general HSS strategy may aid in solving the three‐dimensional structures of large complexes of macromolecules.
Short Term Evolution of a Highly Transmissible Methicillin-Resistant Staphylococcus aureus Clone (ST228) in a Tertiary Care Hospital

Staphylococcus aureus is recognized as one of the major human pathogens and is by far one of the most common nosocomial organisms. The genetic basis for the emergence of highly epidemic strains remains mysterious. Studying the microevolution of the different clones of S. aureus is essential for identifying the forces driving pathogen emergence and spread. The aim of the present study was to determine the genetic changes characterizing a lineage belonging to the South German clone (ST228) that spread over ten years in a tertiary care hospital in Switzerland. For this reason, we compared the whole genome of eight isolates recovered between 2001 and 2008 at the Lausanne hospital. The genetic comparison of these isolates revealed that their genomes are extremely closely related. Yet, a few more important genetic changes, such as the replacement of a plasmid, the loss of large fragments of DNA, or the insertion of transposases, were observed. These transfers of mobile genetic elements shaped the evolution of the ST228 lineage that spread within the Lausanne hospital. Nevertheless, although the strains analyzed differed in their dynamics, we have not been able to link a particular genetic element with spreading success. Finally, the present study showed that new sequencing technologies improve considerably the quality and quantity of information obtained for a single strain; but this information is still difficult to interpret and important investments are required for the technology to become accessible for routine investigations.