Miracle-dz/UniFAR-FTUs huggingface dataset:
The evolving role of the orphan nuclear receptor ftz‐f1, a pair‐rule segmentation gene

Segmentation is a critical developmental process that occurs by different mechanisms in diverse taxa. In insects, there are three common modes of embryogenesis—short‐, intermediate‐, and long‐germ development—which differ in the number of segments specified at the blastoderm stage. While genes involved in segmentation have been extensively studied in the long‐germ insect Drosophila melanogaster (Dm), it has been found that their expression and function in segmentation in short‐ and intermediate‐germ insects often differ. Drosophila ftz‐f1 encodes an orphan nuclear receptor that functions as a maternally expressed pair‐rule segmentation gene, responsible for the formation of alternate body segments during Drosophila embryogenesis. Here we investigated the expression and function of ftz‐f1 in the short‐germ beetle, Tribolium castaneum (Tc). We found that Tc‐ftz‐f1 is expressed in stripes in Tribolium embryos. These stripes overlap alternate Tc‐Engrailed (Tc‐En) stripes, indicative of a pair‐rule expression pattern. To test whether Tc‐ftz‐f1 has pair‐rule function, we utilized embryonic RNAi, injecting double‐stranded RNA corresponding to Tc‐ftz‐f1 coding or non‐coding regions into early Tribolium embryos. Knockdown of Tc‐ftz‐f1 produced pair‐rule segmentation defects, evidenced by loss of expression of alternate En stripes. In addition, a later role for Tc‐ftz‐f1 in cuticle formation was revealed. These results identify a new pair‐rule gene in Tribolium and suggest that its role in segmentation may be shared among holometabolous insects. Interestingly, while Tc‐ftz‐f1 is expressed in pair‐rule stripes, the gene is ubiquitously expressed in Drosophila embryos. Thus, the pair‐rule function of ftz‐f1 is conserved despite differences in expression patterns of ftz‐f1 genes in different lineages. This suggests that ftz‐f1 expression changed after the divergence of lineages leading to extant beetles and flies, likely due to differences in cis‐regulatory sequences. We propose that the dependence of Dm‐Ftz‐F1 on interaction with the homeodomain protein Ftz which is expressed in stripes in Drosophila, loosened constraints on Dm‐ftz‐f1 expression, allowing for ubiquitous expression of this pair‐rule gene in Drosophila.
Dynamic Contrast-Enhanced Ultrasound Parametric Maps to Evaluate Intratumoral Vascularization

ObjectivesThe purposes of this study were to assess the reliability of parametric maps from dynamic contrast-enhanced ultrasound (DCE-US) to reflect the heterogeneous distribution of intratumoral vascularization and to predict the tissue features linked to vasculature. This study was designed to compare DCE-US parametric maps with histologic vascularity measurements. Materials and MethodsDynamic contrast-enhanced ultrasound was performed on 17 melanoma-bearing nude mice after a 0.1-mL bolus injection of SonoVue (Bracco SPA, Milan, Italy). The parametric maps were developed from raw linear data to extract pixelwise 2 semiquantitative parameters related to perfusion and blood volume, namely, area under the curve (AUC) and peak intensity (PI). The mathematical method to fit the time-intensity curve for each pixel was a polynomial model used in clinical routine and patented by the team. Regions of interest (ROIs) were drawn on DCE-US parametric maps for whole tumors and for several local areas of 15 mm2 within each tumor (iROI), the latter reflecting the heterogeneity of intratumoral blood volume. As the criterion standard correlation, microvessel densities (MVDs) were determined for both ROI categories. In detail, for all iROI of 15 mm2, MVD and maturity were divided separately for vessels of 0 to 10 &mgr;m, 10 to 40 &mgr;m, and greater than 40 &mgr;m in diameter, and the results were correlated with the ultrasound findings. ResultsAmong the 17 studied mice, a total of 64 iROIs were analyzed. For the whole-tumor ROI set, AUC and PI values significantly correlated with MVD (rAUC = 0.52 [P = 0.0408] and rPI = 0.70 [P = 0.0026]). In the case of multiple iROI, a strong linear correlation was observed between the DCE-US parameters and the density of vessels ranging in their diameter from 0 to 10 &mgr;m (rAUC = 0.68 [P < 0.0001]; rPI = 0.63 [P < 0.0001]), 10 to 40 &mgr;m (rAUC = 0.98 [P = 0.0003]; rPI = 0.98 [P = 0.0004]), and greater than 40 &mgr;m (rAUC = 0.86 [P = 0.0120]; rPI = 0.92 [P = 0.0034]), respectively. However, the DCE-US parameter values of perfusion and blood volume were not significantly different according to the diameters (AUC: P = 0.1731; PI: P = 0.2918) and maturity of blood vessels. ConclusionsParametric maps of DCE-US can be reliably established from raw linear data and reflect the heterogeneous histological measures of vascularization within tumors. In contrast, the values of DCE-US parametric maps (AUC, PI) do not allow deduction of heterogeneous tissue features such as the diameters and maturity of vascular networks.
Indoor particulate matter of outdoor origin: importance of size-dependent removal mechanisms.

Adverse human health effects have been observed to correlate with levels of outdoor particulate matter (PM), even though most human exposure to PM of outdoor origin occurs indoors. In this study, we apply a model and empirical data to explore the indoor PM levels of outdoor origin for two major building types: offices and residences. Typical ventilation rates for each building type are obtained from the literature. Published data are combined with theoretical analyses to develop representative particle penetration coefficients, deposition loss rates, and ventilation-system filter efficiencies for a broad particle size range (i.e., 0.001-10 microm). We apply archetypal outdoor number, surface area, and mass PM size distributions for both urban and rural airsheds. We also use data on mass-weighted size distributions for specific chemical constituents of PM: sulfate and elemental carbon. Predictions of the size-resolved indoor proportion of outdoor particles (IPOP) for various conditions and ambient particle distributions are then computed. The IPOP depends strongly on the ambient particle size distribution, building type and operational parameters, and PM metric. We conclude that an accurate determination of exposure to particles of ambient origin requires explicit consideration of how removal processes in buildings vary with particle size.
Orthostatic Hypotension, Hypotension and Cognitive Status: Early Comorbid Markers of Primary Dementia?

Objective: Few studies have explored the relationship between orthostatic hypotension (OH) and cognition. The aim of this study was to examine the association of OH with cognitive impairment and decline in a cohort of Chinese elderly, and its effect modification by blood pressure (BP) status at baseline. Method: Among 2,321 community-living older adults, free of cardiovascular disease and stroke, baseline BP measurements were used to determine the presence of OH and categorize participants as hypotensives, normotensives or hypertensives. The Mini-Mental State Examination (MMSE) was used to assess cognitive impairment (MMSE score <24). Cognitive decline (decrease in MMSE score by ≧1) was assessed from 1 to 2 years of follow-up for 1,347 participants without baseline cognitive impairment. Results: Mean age of the subjects was 65.5 years and 381 (16.6%) showed OH. OH was not associated with cognitive impairment overall. However, among hypotensives, OH increased the odds of cognitive impairment (OR = 4.1, 95% CI = 1.11–15.1), while hypertensives with OH showed reduced odds of cognitive impairment (OR = 0.48, 95% CI = 0.26–0.90). Among cognitively intact participants, OH was not associated with cognitive decline overall or in BP subgroups. Conclusion: The increased risk of cognitive impairment in hypotensives with OH suggests that hypotension with OH may be an early comorbid marker of a primary incipient dementia.
'Patient satisfaction': knowledge for ruling hospital reform--an institutional ethnography.

Driven by funding restraint, Canadian health-care has undergone over a decade of significant reform. Hospitals are being restructured, as text-based practices of accountability bring a new business-orientation into hospital and clinical management. New forms of knowledge, generated through records of various sorts, are a necessary resource for managing care in the new environment. This paper's research uses Canadian sociologist Dorothy E. Smith's institutional ethnographic methodology to critically analyse one instance of text-based management. I analyse information about 'patient satisfaction' as it is generated through a patient survey (in which I was implicated through my involvement with a hospitalized family member). Subsequently, I have studied the management environment into which that information would be entered. I argue that in the instance analysed, the information becomes part of a dominant consumer oriented healthcare discourse that subordinates concerns about 'what actually happened' as a professional caregiver would have known it. On this basis, I contend that this sort of taken-for-granted approach to making decisions about quality care in hospitals may be seriously, even dangerously, flawed.
Stability study of stavudine-loaded O-palmitoyl-anchored carbohydrate-coated liposomes

The purpose of this study was to evaluate the physicochemical stability of carbohydrate-anchored liposomes. In the present study, carbohydrate (galactose, fucose, and mannose) was palmitoylated and anchored on the surface of positively charged liposomes (PL). The stabilities of plain neutral liposomes (NL), PL, and O-palmitoyl carbohydrate-anchored liposomes were determined. The effects of storage conditions (4°C±2°C, 25°C±2°C/60%±5% relative humidity [RH], or 40°C±2°C/75%±5% RH for a period of 10, 20, and 30 days) were observed on the vesicle size, shape, zeta potential, drug content, and in vitro ligand agglutination assay by keeping the liposomal formulations in sealed ambercolored vials (10-mL capacity) after flushing with nitrogen. The stability of liposomal formulations was found to be temperature dependent. All the liposomal formulations were found to be stable at 4°C±2°C up to 1 month. Storage at 25°C±2°C/60%±5% RH and 40°C±2°C/75%±5% RH adversely affected uncoated liposomal formulations. Carbohydrate coating of the liposomes could enhance the stability of liposomes at 25°C±2°C/60%±5% RH and 40°C±2°C/75%±5% RH.
CCN1 Suppresses Pulmonary Vascular Smooth Muscle Contraction in Response to Hypoxia

Pulmonary vasoconstriction and increased vascular resistance are common features in pulmonary hypertension (PH). One of the contributing factors in the development of pulmonary vasoconstriction is increased pulmonary artery smooth muscle cell (PASMC) contraction. Here we report that CCN1, an extracellular matrix molecule, suppressed PASMC contraction in response to hypoxia. CCN1 (Cyr61), discovered in past decade, belongs to the Cyr61-CTGF-Nov (CCN) family. It carries a variety of cellular functions, including angiogenesis and cell adhesion, death, and proliferation. Hypoxia robustly upregulated the expression of CCN1 in the pulmonary vessels and lung parenchyma. Given that CCN1 is a secreted protein and functions in a paracine manner, we examined the potential effects of CCN1 on the adjacent smooth muscle cells. Interestingly, bioactive recombinant CCN1 significantly suppressed hypoxia-induced contraction in human PASMCs in vitro. Consistently, in the in vivo functional studies, administration of bioactive CCN1 protein significantly decreased right ventricular pressure in three different PH animal models. Mechanistically, protein kinase A–pathway inhibitors abolished the effects of CCN1 in suppressing PASMC contraction. Furthermore, CCN1-inhibited smooth muscle contraction was independent of the known vasodilators, such as nitric oxide. Taken together, our studies indicated a novel cellular function of CCN1, potentially regulating the pathogenesis of PH.
Terminal Oxidase Diversity and Function in “Metallosphaera yellowstonensis”: Gene Expression and Protein Modeling Suggest Mechanisms of Fe(II) Oxidation in the Sulfolobales

ABSTRACT “Metallosphaera yellowstonensis” is a thermoacidophilic archaeon isolated from Yellowstone National Park that is capable of autotrophic growth using Fe(II), elemental S, or pyrite as electron donors. Analysis of the draft genome sequence from M. yellowstonensis strain MK1 revealed seven different copies of heme copper oxidases (subunit I) in a total of five different terminal oxidase complexes, including doxBCEF, foxABCDEFGHIJ, soxABC, and the soxM supercomplex, as well as a novel hypothetical two-protein doxB-like polyferredoxin complex. Other genes found in M. yellowstonensis with possible roles in S and or Fe cycling include a thiosulfate oxidase (tqoAB), a sulfite oxidase (som), a cbsA cytochrome b 558/566, several small blue copper proteins, and a novel gene sequence coding for a putative multicopper oxidase (Mco). Results from gene expression studies, including reverse transcriptase (RT) quantitative PCR (qPCR) of cultures grown autotrophically on either Fe(II), pyrite, or elemental S showed that the fox gene cluster and mco are highly expressed under conditions where Fe(II) is an electron donor. Metagenome sequence and gene expression studies of Fe-oxide mats confirmed the importance of fox genes (e.g., foxA and foxC) and mco under Fe(II)-oxidizing conditions. Protein modeling of FoxC suggests a novel lysine-lysine or lysine-arginine heme B binding domain, indicating that it is likely the cytochrome component of a heterodimer complex with foxG as a ferredoxin subunit. Analysis of mco shows that it encodes a novel multicopper blue protein with two plastocyanin type I copper domains that may play a role in the transfer of electrons within the Fox protein complex. An understanding of metabolic pathways involved in aerobic iron and sulfur oxidation in Sulfolobales has broad implications for understanding the evolution and niche diversification of these thermophiles as well as practical applications in fields such as bioleaching of trace metals from pyritic ores.
Relative involvement of Shc tyrosine 239/240 and tyrosine 317 on insulin induced mitogenic signaling in rat1 fibroblasts expressing insulin receptors.

Shc is phosphorylated on Tyr-239/240 and/or Tyr-317, which serves as a docking site for Grb2. To clarify the relative involvement of Shc Tyr-239/240 and Tyr-317 in insulin-induced mitogenesis, we generated expression vectors for Y317F (1F)-Shc, Y239/240F (2F)-Shc, and Y239/240/317F (3F)-Shc, and stably transfected them into Rat1 fibroblasts expressing insulin receptors (HIRc). Insulin-induced Shc phosphorylation and subsequent association with Grb2 was enhanced in wild-type (WT)-Shc cell. In contrast, insulin-stimulated Shc phosphorylation and Shc.Grb2 association were significantly decreased in 1F-Shc and 3F-Shc cells, while these were only slightly affected and almost comparable in 2F cells compared with those in parental HIRc cells. The kinetics of MAP kinase activation closely paralleled the kinetics of Shc phosphorylation and Shc.Grb2 association. Thus, insulin stimulation of MAP kinase activation occurred more rapidly in WT-Shc cells, and the activation was delayed in 1F-Shc and 3F-Shc cells, while it was comparable in 2F-Shc cells compared with that in HIRc cells. Furthermore, WT-Shc cells displayed enhanced sensitivity to insulin stimulation of thymidine incorporation. Importantly, the sensitivity was significantly decreased in 1F-Shc and 3F-Shc cells, while it was almost comparable in 2F-Shc cells compared with that in HIRc cells. These results indicate that Shc Tyr-317 is more predominant insulin-induced phosphorylation site than Tyr-239/240 for coupling with Grb2 leading to MAP kinase activation and mitogenesis in Rat1 fibroblasts.
Percutaneous Radiofrequency Ablation of Sonographically Unidentifiable Liver Tumors

Objective: The purpose of this study was to evaluate the safety and feasibility of a real-time integrated system with computed tomography (CT) and sonographic images for radiofrequency (RF) ablation of hepatic malignancies poorly defined on B-mode sonography, and to clarify the suitable phase of CT images for using this virtual sonography. Methods: Between September 2004 and December 2004, 12 patients with 16 hepatocellular carcinomas and two metastatic lesions arising from colorectal adenocarcinoma (n = 1) and rectal carcinoid (n = 1) were treated. The maximum diameter of nodules ranged from 1.0 to 2.5 cm (mean ± SD; 1.5 ± 0.6 cm) on CT images. Results: Complete tumor necrosis was achieved in a single session in 19 lesions (90%), while a second session was required for the remaining two lesions (10%). Portal phase multi-planar reconstruction images were displayed under a suitable position corresponding to the ultrasound images in 9 patients (HCC = 7, metastasis = 2), and arterial phase multi-planar reconstruction images were displayed in the 3 remaining patients with hepatocellular carcinoma. Conclusion: Percutaneous RF ablation guidance using virtual sonography is an effective treatment for patients with hepatic malignancies. The portal phase of CT images may be the most suitable to indicate the 3-dimensional relationship between the liver vasculature and tumors on virtual sonography.
Contribution à l'analyse de l'écoulement tridimensionnel instable s'établissant à l'intérieur de cavités cylindriques

L'etude developpee au cours de cette these a pour objectif l'analyse de la phase d'etablissement d'ecoulements en cavites fermees pour des valeurs du nombre de reynolds moderees (re = 1000, 2000 et 3200). Une attention particuliere est accordee a la comprehension des mecanismes physiques a l'origine de la formation et du developpement des cellules tourbillonnaires de section droite, des perturbations tridimensionnelles et de l'instabilite. Differentes formes et longueurs de cavites ont ete considerees. Les resultats topologiques et cinematiques obtenus completent ceux de la litterature et constituent une nouvelle base de donnees pour de futures etudes numeriques. Nous avons notamment montre que les cavites fermees, bien que generalement considerees comme des configurations elementaires, sont le siege d'une structure 3d tres riche sujette a l'influence de tres petites perturbations de la geometrie. Des simulations experimentales et numeriques des ecoulements ont ete conduites. Pour les experiences, l'ecoulement, genere par la translation a vitesse constante d'une cavite le long d'une paroi fixe (couvercle), est enregistre, au cours du temps, par l'intermediaire d'un appareil photographique lie au repere de la cavite. Les structures tourbillonnaires sont mises en evidence au moyen de deux techniques complementaires de visualisation, la technique des traceurs solides et celle de l'electrolyse de l'etain. Les simulations numeriques ont ete realisees avec le code proust developpe par l'equipe turbomachine du laboratoire de mecanique des fluides et d'acoustique de l'ecole centrale de lyon. La methode de calcul est basee sur la resolution des equations de navier-stokes ecrites sous forme conservative et integrees en espace dans le cadre d'une formulation volumes finis.
Lipopolysaccharide Induces Both a Primary and a Secondary Phase of Sensitization in the Developing Rat Brain

Data indicate that bacterial products in combination with other antenatal or postnatal exposures increase the risk of perinatal brain injury. We have previously shown that administration of lipopolysaccharide (LPS) 4 h before hypoxia-ischemia (HI) increases brain injury in 7-d-old rats. The mechanisms behind such sensitization are unclear, but contrasts against a preconditioning effect of LPS given 1–3 d before ischemia in adult animals. To investigate how the effects of LPS depend on the time interval between administration and HI in the developing brain, we evaluated the effect of varying time interval (2–72 h) between LPS and HI, the duration of HI (20 or 50 min), and age of the rat pups (postnatal d 4 or 7). Outcome was assessed by brain injury scoring of specific regions. We found that LPS reduced brain injury (by 78%) when administered 24 h before 50 min of HI. However, when LPS was administered 6 h before either 20 or 50 min of HI, brain injury was increased by 2026% and 137%, respectively. Even LPS given 72 h before HI increased injury, both when LPS was administered at postnatal d 4 (by 446%) and 7 (by 77%). In conclusion, LPS enhanced vulnerability in the developing brain both in the acute (4–6 h) and the chronic (72 h) phase after administration, whereas an intermediate interval between LPS and HI had the opposite effect. The long-term sensitizing effect of LPS has not been previously described.
Acute flank pain: comparison of non-contrast-enhanced CT and intravenous urography.

PURPOSE To compare non-contrast-enhanced computed tomography (CT) and intravenous urography (IVU) in the evaluation of patients who present with acute flank pain and in whom ureteric obstruction is suspected. MATERIALS AND METHODS The findings at non-contrast-enhanced CT and IVU in 20 patients with acute flank pain were compared for the presence or absence of ureteric obstruction and delineation of ureteric stones. RESULTS Twelve of the 20 patients had non-contrast-enhanced CT and IVU findings consistent with ureteric obstruction. Of these 12 patients, five had a ureteric stone that was demonstrated on both non-contrast-enhanced CT scans and IVU radiographs, six had a stone that was depicted on non-contrast-enhanced CT scans only, and in one patient a stone could not be delineated definitively on either non-contrast-enhanced CT scans or IVU radiographs. Eight patients had findings at non-contrast-enhanced CT and IVU consistent with the absence of obstruction. CONCLUSION Non-contrast-enhanced CT is more effective than IVU in precisely identifying ureteric stones and is equally effective as IVU in the determination of the presence or absence of ureteric obstruction.
High HIV incidence among MSM prescribed postexposure prophylaxis, 2000–2009: indications for ongoing sexual risk behaviour

Objective:To determine (trends in) HIV incidence among MSM\ who have recently had postexposure prophylaxis (PEP) prescribed in Amsterdam, compared with MSM participating in the Amsterdam Cohort Studies (ACS). Design and methods:We used data from MSM who were prescribed PEP in Amsterdam between 2000 and 2009, who were HIV-negative at the time of PEP prescription and had follow-up HIV testing 3 and/or 6 months after PEP prescription (n = 395). For comparison, cohort data from MSM participating in the ACS in the same period were used (n = 782). Poisson log-linear regression analyses were performed to model trends in HIV incidence and identify differences in HIV incidence between both cohorts at different time points. Results:Between 2000 and 2009, among MSM who were prescribed PEP, an overall HIV incidence of 6.4 [95% confidence interval (CI) 3.4–11.2] per 100 person-years was found, compared with an HIV incidence of 1.6 (95% CI 1.3–2.1) per 100 person-years among MSM participating in the ACS (P < 0.01). In both cohorts, an increasing trend in HIV incidence over time was observed [incidence rate ratio (IRRpercalendaryear) 1.3 (95% CI 0.9–1.7) and 1.1 (95% CI 1.0–1.2) among MSM prescribed PEP and MSM of the ACS, respectively]. The difference in HIV incidence between both cohorts was most evident in more recent years [IRRPEPversusACS in 2009 4.8 (95% CI 2.0–11.5)]. Conclusion:Particularly in more recent years, MSM recently prescribed PEP had a higher HIV incidence compared with MSM participating in the ACS, indicating ongoing sexual risk behaviour.