Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay between β1-Integrin and Rho Signaling Regulates Differential Scattering and Motility of Pancreatic Cancer Cells by Snail and Slug Proteins*

Background: This study was designed to compare the role of Snail and Slug in pancreatic cancer. Results: Snail and Slug have differential effects on three-dimensional scattering, motility, adhesion, and Rho signaling. Conclusion: Snail, but not Slug, promotes motility and scattering in three-dimensional collagen of pancreatic cancer cells. Significance: Understanding how Snail and Slug modulate pancreatic cancer progression may identify therapeutic targets for this deadly disease. The Snail family of transcription factors has been implicated in pancreatic cancer progression. We recently showed that Snail (Snai1) promotes membrane-type 1 matrix metalloproteinase (MT1-MMP)- and ERK1/2-dependent scattering of pancreatic cancer cells in three-dimensional type I collagen. In this study, we examine the role of Slug (Snai2) in regulating pancreatic cancer cell scattering in three-dimensional type I collagen. Although Slug increased MT1-MMP expression and ERK1/2 activity, Slug-expressing cells failed to scatter in three-dimensional collagen. Moreover, in contrast to Snail-expressing cells, Slug-expressing cells did not demonstrate increased collagen I binding, collagen I-driven motility, or α2β1-integrin expression. Significantly, inhibiting β1-integrin function decreased migration and scattering of Snail-expressing cells in three-dimensional collagen. As Rho GTPases have been implicated in invasion and migration, we also analyzed the contribution of Rac1 and Rho signaling to the differential migration and scattering of pancreatic cancer cells. Snail-induced migration and scattering were attenuated by Rac1 inhibition. In contrast, inhibiting Rho-associated kinase ROCK1/2 increased migration and scattering of Slug-expressing cells in three-dimensional collagen and thus phenocopied the effects of Snail in pancreatic cancer cells. Additionally, the increased migration and scattering in three-dimensional collagen of Slug-expressing cells following ROCK1/2 inhibition was dependent on β1-integrin function. Overall, these results demonstrate differential effects of Snail and Slug in pancreatic cancer and identify the interplay between Rho signaling and β1-integrin that functions to regulate the differential scattering and migration of Snail- and Slug-expressing pancreatic cancer cells.
[Knowledge and Self Efficacy Related with HIV Prevention among Chilean Women].

OBJECTIVE To assess the relationship between knowledge and self efficacy associated to HIV/AIDS in women from Chile with social disadvantages. METHODOLOGY Correlation study that uses the baseline assessment of the "Testing an HIV and AIDS intervention in Chilean women" study, carried out between 2006 and 2008, with a sample of 496 women between 18 and 49 years old, in 2 neighborhoods of Santiago de Chile. Participants answered a structured survey conducted by trained interviewers. The survey included questions about sociodemographic information, risk behaviors and a self-efficacy knowledge scale among others. RESULTS The average age was 32.3±9.1 years, 72.2% live with their partner and 42.7% have completed high school education. The mean score of HIV infection knowledge was 8.9±2.5, while the mean score for the three scales used to measure self-efficacy were: "Peer rules" =9.8±3.6, "Risk reduction intentions =12.2±3.6 and "Self Efficacy Form"=20.2±4.7. HIV knowledge had a weak positive correlation with the "Risk reduction intentions" scale (r=0.19; p<0.0001) and the "Self Efficacy Form" scale (r=0.34; p<0.0001), however there was no correlation with the "Safe sex peer rules" (r=0.13;p=0.78). CONCLUSION There is a weak positive correlation between the HIV/AIDS related knowledge and self-efficacy among Chilean with social disadvantages.
The P450–1 gene of Gibberella fujikuroi encodes a multifunctional enzyme in gibberellin biosynthesis

Recent studies have shown that the genes of the gibberellin (GA) biosynthesis pathway in the fungus Gibberella fujikuroi are organized in a cluster of at least seven genes. P450–1 is one of four cytochrome P450 monooxygenase genes in this cluster. Disruption of the P450–1 gene in the GA-producing wild-type strain IMI 58289 led to total loss of GA production. Analysis of the P450–1-disrupted mutants indicated that GA biosynthesis was blocked immediately after ent-kaurenoic acid. The function of the P450–1 gene product was investigated further by inserting the gene into mutants of G. fujikuroi that lack the entire GA gene cluster; the gene was highly expressed under GA production conditions in the absence of the other GA-biosynthesis genes. Cultures of transformants containing P450–1 converted ent-[14C]kaurenoic acid efficiently into [14C]GA14, indicating that P450–1 catalyzes four sequential steps in the GA-biosynthetic pathway: 7β-hydroxylation, contraction of ring B by oxidation at C-6, 3β-hydroxylation, and oxidation at C-7. The GA precursors ent-7α-hydroxy[14C]kaurenoic acid, [14C]GA12-aldehyde, and [14C]GA12 were also converted to [14C]GA14. In addition, there is an indication that P450–1 may also be involved in the formation of the kaurenolides and fujenoic acids, which are by-products of GA biosynthesis in G. fujikuroi. Thus, P450–1 displays remarkable multifunctionality and may be responsible for the formation of 12 products.
Laser Doppler Imaging of Activation-Flow Coupling in the Rat Somatosensory Cortex

Activation-flow coupling (AFC) provides a physiological basis for mapping cerebral activation using cerebral blood flow (CBF) as a surrogate marker for neuronal function. Laser Doppler offers a minimally invasive approach for measuring changes in cerebral blood flow but the spatial resolution of this technique is limited by the number of individual probes that can be used. Recently, laser Doppler imaging (LDI) scanners, which use computer-driven optics to scan and measure LD changes in two dimensions, have successfully measured flow changes in the exposed cortex of animals. Here we demonstrate the use of an LDI device through a thinned skull to determine the spatiotemporal characteristics of AFC in alpha-chloralose anesthetized rats in response to electrical forepaw stimulation. The spatial and temporal characteristics of the AFC response measured by LDI are in agreement with prior results obtained using a single LD probe. These results suggest a promising role for LDI in the characterization of the spatiotemporal characteristics of AFC in animal models and possibly for intraoperative monitoring in the human brain.
A 1.4Mpixel CMOS image sensor with multiple row-rescan based data sampling for optical camera communication

A 1.4Mpixel CMOS image sensor (CIS) with multiple row-rescan (MRR) based data sampling for optical camera communication (OCC) is presented. The CIS achieves a data sampling rate at a row-scan rate of 51kS/s even with a frame rate of 30fps, a pixel size of 2.2mm × 2.2mm by multiply rescanning the rows at a modulated LED spot. The detectable minimum LED size projected onto the CIS becomes 13.2mm × 13.2mm. The MRR could be a practical solution for IEEE 802.15. SG7a OCC.
Potent and Selective Inhibition of Tat-Dependent HIV-1 Replication in Chronically Infected Cells by a Novel Naphthalene Derivative JTK-101

In search for effective human immunodeficiency virus type 1 (HIV-1) transcription inhibitors, we have evaluated more than 100,000 compounds for their inhibitory effects on HIV-1 long terminal repeat (LTR)-driven reporter gene expression, and identified a novel naphthalene derivative, JTK-101. This compound could suppress tumour necrosis factor (TNF)-α-induced HIV-1 production in latently infected OM-10.1 cells at nanomolar concentrations. JTK-101 could also potently inhibit constitutive HIV-1 production in MOTL-4/IIIB. However, the antiviral activity of JTK-101 was found to be much weaker in acutely infected cells and the chronically infected cells U937/IIIB cells than in OM-10.1 and MOLT-4/IIIB cells. JTK-101 selectively suppressed TNF-α-induced HIV-1 mRNA synthesis in OM-10.1 cells in a dose-dependent fashion. JTK-101 modestly inhibited TNF-α-induced HIV-1 LTR-driven reporter gene expression, but potently inhibited Tat-induced gene expression. Immunoblot analysis revealed that low-level expression of the Tat cofactors CDK9 and cyclin T1 might contribute to the diminished antiviral activity in U937/IIIB cells. Furthermore, JTK-101 could not inhibit HIV-1 replication in chronically infected monocytes/macrophages, in which CDK9 and cyclin T1 were undetectable. These results suggest that JTK-101 exerts its anti-HIV-1 activity through the inhibition of known or unknown Tat cofactors, presumably CDK9/cyclin T1.
Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas

Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre‐treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly‐diagnosed malignant glioma were examined with MRI and three‐dimensional proton (1H) MRSI. Thirty‐nine patients (22 grade 3 and 17 glioblastoma multiforme, GBM) were studied prior to surgery, and 33 GBM patients were studied after surgery but prior to treatment with radiation and chemotherapy. Signal intensities of choline (Cho), creatine (Cr), N‐acetyl aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Recursive partitioning methods were applied to parameters that included age, histological grade, MRI and MRSI variables to generate survival trees. Patients were grouped into high and low risk categories and the corresponding Kaplan–Meier curves were plotted for comparison between groups. The parameters that were selected by recursive partitioning as being predictive of poor outcome were older age, larger contrast enhancement, higher Cho‐to‐Cr, higher Cho‐to‐NAA, higher LL and lower Cr‐to‐NAA abnormalities. The survival functions were significantly different between the sub‐groups of patients obtained from the survival tree for both pre‐surgery and post‐surgery data. The results of this study suggest that pre‐treatment MRI and three‐dimensional 1H‐MRSI provide information that predicts outcome for patients with malignant gliomas and have drawn attention to variables that should be examined prospectively in future studies using these techniques. Copyright © 2004 John Wiley & Sons, Ltd.
On Neighbourhood Matching for Texture‐by‐Numbers

Texture‐by‐Numbers is an attractive texture synthesis framework, because it is able to cope with non‐homogeneous texture exemplars, and provides the user with intuitive creative control over the outcome of the synthesis process. Like many other exemplar‐based texture synthesis methods, its basic underlying mechanism is neighbourhood matching. In this paper we review a number of commonly used neighbourhood matching acceleration techniques, compare and analyse their performance in the specific context of Texture‐by‐Numbers (as opposed to ordinary unconstrained texture synthesis). Our study indicates that the standard approaches are not optimally suited for the Texture‐by‐Numbers framework, often producing visually inferior results compared to searching for the exact L2nearest neighbour. We then show that performing Texture‐by‐Number using the Texture Optimization framework in conjunction with an efficient FFT‐based search is able to produce good results in reasonable running times and with a minimal memory overhead.
Volatility Forecasting with the Multifractal Model of Asset Returns

This paper presents an empirical application of the Multifractal Model of Asset Returns (MMAR) to intraday stock prices, with a goal of generating accurate volatility forecasts. Intraday stock volatility exhibits long tails, persistence, and strong evidence of moment scaling. This allows us to apply the MMAR. A forecasting method for the MMAR is implemented through Monte Carlo simulation, and this forecasting method is compared to Generalized Autoregressive Conditional Heteroskedasticity (GARCH) alternatives over several testing samples. The MMAR significantly outperformed the GARCH models. This suggests that the framework of multifractality has a large potential for further development and application within finance.
RAPID DECREASES IN DONOR-SPECIFIC CYTOTOXIC T LYMPHOCYTE PRECURSOR FREQUENCIES AND GRAFT OUTCOME AFTER LIVER AND LUNG TRANSPLANTATION 1

Background. A decrease in donor-specific T cell precursor frequencies as seen late, one or more years, after transplantation is assumed to reflect transplantation tolerance, a condition important for long term acceptance of the allograft. However, such late decreases also occur in recipients that developed chronic transplant dysfunction questioning its relevance in transplantation tolerance. We investigated whether early, i.e., the first 6 months, decreases in donor-specific T cell precursor frequencies reflect transplantation tolerance and predict graft outcome after liver and lung transplantation. Methods. Donor and third party specific cytotoxic (CTLp) and helper T lymphocyte precursor (HTLp) frequencies were analyzed in pretransplant and 1 (or 2) and 6-month blood samples taken from liver and lung recipients and were correlated with graft outcome. Results. In liver allograft recipients with good graft function (n=7), mean donor-specific CTLp frequencies decreased as early as 1 month after transplantation and remained low thereafter. In contrast, mean CTLp frequencies did not decrease in liver allograft recipients with chronic transplant dysfunction (n=6). In lung allograft recipients, donor-specific CTLp frequencies remained relatively high and frequencies were not different between recipients without (n=6) or with (n=6) chronic transplant dysfunction. Donor-specific HTLp frequencies did not change significantly after liver or lung transplantation and did not differ between recipients without or with chronic transplant dysfunction. Conclusions. An early decrease in donor-specific CTLp correlates with good graft outcome after liver transplantation. Such rapid decreases in alloreactivity do not occur after lung transplantation illustrating the unique capacity of liver allografts to induce transplantation tolerance.
Age-period-cohort and cultural engagement

A crucial question for cultural sociologists is how patterns of taste and cultural practice vary across time (Reeves 2014, Jaeger and Katz-Gerro 2010). Does cultural engagement increase with age (Scherger 2009)? Have there been historical shifts in the nature of cultural capital? Has snobbery declined over time? Despite this interest, the relationship between time and taste remains under-examined. Understanding this association requires that researchers attend to three distinct dimensions of time: age (how old people are when data collection occurs), period (when data collection occurs), and cohort (the year or period in which people were born) (Yang et al. 2008). Differences between age-period-cohort (APC) effects are described in this fictional dialogue, adapted from Suzuki (2012: 452):
Prevalence and calf-level risk factors for failure of passive transfer in dairy calves in New Zealand

Abstract AIM To determine the prevalence of failure of passive transfer (FPT) in dairy calves in New Zealand and to assess a range of potential calf-level risk factors for their association with FPT. METHOD Between July and September 2015, 107 dairy farms in nine regions across New Zealand were visited on three occasions: before 20% of cows had calved, when ∼50% of cows had calved, and when the last 10–20% of cows were calving. Farms were randomly selected from the client list of participating veterinary practices. On each farm, blood samples were collected from 10–20 calves between 24 hours and 8 days old and concentrations of total protein (TP) in serum determined. Calf identification, date of birth, dam’s age and breed, details of colostrum feeding and the farmer’s health assessment of the calf on arrival at the calf rearing facility were recorded. Concentrations of TP in serum ≤52 g/L were used to define FPT. RESULTS Of 3,819 calves sampled, 1,263 (33 (95% CI=31.6–34.6)%) were diagnosed with FPT, and the prevalence within farms ranged from 5–83%. Calf-level risk factors that were associated with increased odds of FPT were increasing age of dam (OR=1.12; 95% CI=1.08–1.16), calves recorded as unhealthy compared to healthy upon arrival at the calf rearing facility (OR=2.59; 95% CI=1.60–4.19), calves sampled on farms in Otago (OR=2.85; 95% CI=1.42–5.74) and Southland (OR 2.31; 95% CI=1.15–4.67) compared to the Far North, and calves sampled in the middle compared to the early calving period (OR=1.24; 95% CI=1.03–1.51). CONCLUSION On the farms visited FPT was diagnosed in one third of dairy calves. Calf-level risk factors for FPT included age of dam, health status of calf, region, and time of the calving period. Further investigations are required to establish why these are associated with increased odds of FPT. CLINICAL RELEVANCE These results provide a baseline for benchmarking, which, alongside the reported calf-level risk factors, can be used by veterinarians to improve colostrum management.
A Review of the Pharmacologic and Pharmacokinetic Aspects of Rosuvastatin

Rosuvastatin is a new HMG‐CoA reductase inhibitor with unique pharmacologic and pharmacokinetic properties. It has additional HMG‐CoA reductase enzyme‐binding interactions that cause tighter binding, has substantial active transport into hepatocytes, and has the lowest (LDL) for sterol synthesis in hepatocytes. Rosuvastatin 10 mg and 80 mg dosages have superior low‐density lipoprotein (LDL) cholesterol‐lowering efficacy as compared to atorvastatin 10 mg and 80 mg. Rosuvastatin 10 mg has also been shown to have superior LDL reductions to 20 mg of both simvastatin and pravastatin. This agent can raise high‐density lipoprotein (HDL) 8% to 12% and lower triglycerides by 10% to 35%. Rosuvastatin is a hydrophilic agent with poor penetration in extrahepatic tissue such as human umbilical vein endothelial cells and fibroblasts. It also has a low potential for cytochrome P450 drug interactions and can be dosed in the morning or night. In conclusion, rosuvastatin is an agent with molecular alterations that provide it with unique pharmacologic and pharmacokinetic effects. As such, it is a novel and unique HMG‐CoA reductase inhibitor for the treatment of hyperlipidemia.
Adaptive Designs for Dose-Finding Studies Based on Sigmoid E max Model

We propose an adaptive procedure for dose-finding in clinical trials when the primary efficacy endpoint is continuous. We model the mean of the efficacy endpoint, given the dose, as a four-parameter logistic function. The efficacy endpoint at each dose is distributed according to either a normal or a gamma distribution. We consider the cases of fixed variance and fixed coefficient of variation assuming them to be both known and unknown. The analytic formulae for the Fisher information matrix are obtained, which are used to build the locally and adaptive D -optimal designs.
Rodent Habenulo–Interpeduncular Pathway Expresses a Large Variety of Uncommon nAChR Subtypes, But Only the α3β4* and α3β3β4* Subtypes Mediate Acetylcholine Release

Recent studies suggest that the neuronal nicotinic receptors (nAChRs) present in the habenulo–interpeduncular (Hb–IPn) system can modulate the reinforcing effect of addictive drugs and the anxiolytic effect of nicotine. Hb and IPn neurons express mRNAs for most nAChR subunits, thus making it difficult to establish the subunit composition of functional receptors. We used immunoprecipitation and immunopurification studies performed in rat and wild-type (+/+) and β2 knock-out (−/−) mice to establish that the Hb and IPn contain significant β2* and β4* populations of nAChR receptors (each of which is heterogeneous). The β4* nAChR are more highly expressed in the IPn. We also identified novel native subtypes (α2β2*, α4β3β2*, α3β3β4*, α6β3β4*). Our studies on IPn synaptosomes obtained from +/+ and α2, α4, α5, α6, α7, β2, β3, and β4−/− mice show that only the α3β4 and α3β3β4 subtypes facilitate acetylcholine (ACh) release. Ligand binding, immunoprecipitation, and Western blotting studies in β3−/− mice showed that, in the IPn of these mice, there is a concomitant reduction of ACh release and α3β4* receptors, whereas the receptor number remains the same in the Hb. We suggest that, in habenular cholinergic neurons, the β3 subunit may be important for transporting the α3β4* subtype from the medial habenula to the IPn. Overall, these studies highlight the presence of a wealth of uncommon nAChR subtypes in the Hb–IPn system and identify α3β4 and α3β3β4, transported from the Hb and highly enriched in the IPn, as the subtypes modulating ACh release in the IPn.
Iron depletion before HCV antiviral therapy: A pilot, randomized, controlled trial

It is not known whether iron depletion before pegylated IFN or combination treatment improves sustained virological response (SVR) rate in patients with chronic hepatitis C, despite its use in clinical practice in this setting. We aimed to investigate whether blood letting improves the efficacy (SVR) and tolerability of PEG‐IFNα2b + Ribavirin in chronic hepatitis C patients. Patients with chronic hepatitis C and ferritin >100 ng/mL were randomized to: (1) repeated phlebotomies to obtain a ferritin level <50 ng/mL followed by pegylated‐Interferon α2b + ribavirin (active arm); or (2) pegylated‐Interferon α2b + ribavirin (control arm). Primary endpoint was SVR rate, secondary endpoint was frequency of clinical and laboratory grade 3–4 adverse events. Thirty‐three patients were enrolled in the study (19 in active arm, 14 in control arm). The 19 patients in the active arm underwent a median of 5 phlebotomies (range: 1–9) to achieve the targeted ferritin (<50 ng/mL). Phlebotomies significantly reduced ferritin, iron, transferrin saturation, aspartate aminotransferase, alanine aminotransferase, and hemoglobin levels. Platelet count significantly increased, whereas HCV‐RNA levels remained unchanged. After antiviral therapy overall SVR was 31.6% in active arm and 21.4% in control arm (P = 0.698). Considering only the 18 patients who were naive to antiviral therapy, SVR was 60% in active arm versus 25% in control arm (P = 0.188). Tolerability, drug dose reduction or withdrawal were similar in the two arms. In conclusion phlebotomies do not increase the overall efficacy of antiviral therapy. However, the strong trend to higher SVR in naive patients undergoing phlebotomies warrants further investigation. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.