Miracle-dz/UniFAR-FTUs huggingface dataset:
In‐vitro permeation of drugs into porcine hair follicles: is it quantitatively equivalent to permeation into human hair follicles?

It is already well‐established that the general permeability properties of porcine skin are close to those of human skin. However, very little is known with respect to drug absorption into hair follicles and the similarities if any between the two types of tissue. The aim of this study was to use the skin sandwich system to quantify follicular drug absorption into porcine hair follicles. To our knowledge, this is the first time that the skin sandwich has been extended to porcine tissue. For this purpose, seven different drugs — estradiol, corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and adenosine — exhibiting a wide range of log octanol‐water partition coefficients (log Ko/w), but comparable molecular weights, were chosen as candidate solutes. The results showed a parabolic profile with maximal follicular contribution occurring at intermediate log Ko/w values. Linear regression analysis indicated that the follicular contributions in porcine skin correlated well with previously published follicular contributions in human skin (r2 = 0.87). The novelty of this research is that we show that porcine tissue is a good surrogate for modelling human skin permeability within the specific context of quantifying drug absorption into hair follicles.
Spinal somatosensory conduction in diabetes

The velocity bf impulse conduction was compared in peripheral nerve, spinal cord, and supraspinal segment of the somatosensory pathway in 15 diabetic subjects (mean age, 34.3 ± 12.4 years) with little or no evidence of polyneuropathy, and in 15 age-matched normal controls. Motor and sensory conduction velocities (CVs) were slower in the diabetic subjects, and the latencies of F waves and somatosensory evoked potentials (SEPs) from arm and leg were longer (p <0.001 in each case), showing a relationship to duration of disease (0.51 <Irl <0.84, p <0.001 in each case). Indirect estimates of spinal somatosensory conduction velocity (SSCV) were slower in the diabetic subjects (39.4 ± 13.3 m/sec versus 54.2 ± 10.5 m/sec, p <0.001), but conduction in the supraspinal segment (cervical cord to cortex) was identical in the two groups (5.6 ± 1.3 m/sec versus 5.6 ± 0.8 m/sec, p <0.1). In relationship to peripheral nerve CV, the incidence of subnormal SSCV in the diabetic subjects could not be fully explained on the basis of: (1) a passive consequence of peripheral neuropathy, (2) a sensory distal axonopathy, or (3) a primary diabetic myelopathy. We conclude that 40% of diabetics have subclinical electro-physiologic dysfunction of the posterior columns of the spinal cord, which may contribute to the lower-extremity sensory symptoms that are so prevalent in this disorder.
Human Milk Oligosaccharides Inhibit the Adhesion to Caco-2 Cells of Diarrheal Pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris

Breast-fed children, compared with the bottle-fed ones, have a lower incidence of acute gastroenteritis due to the presence of several antiinfective factors in human milk. The aim of this work is to study the ability of human milk oligosaccharides to prevent infections related to some common pathogenic bacteria. Oligosaccharides of human milk were fractionated by gel-filtration and characterized by thin-layer chromatography and high-performance anion exchange chromatography. Fractions obtained contained, respectively, 1) acidic oligosaccharides, 2) neutral high-molecular-weight oligosaccharides, and 3) neutral low-molecular-weight oligosaccharides. Experiments were carried out to study the ability of oligosaccharides in inhibiting the adhesion of three intestinal microorganisms (enteropathogenic Escherichia coli serotype O119, Vibrio cholerae, and Salmonella fyris) to differentiated Caco-2 cells. The study showed that the acidic fraction had an antiadhesive effect on the all three pathogenic strains studied (with different degrees of inhibition). The neutral high-molecular-weight fraction significantly inhibited the adhesion of E. coli O119 and V. cholerae, but not that of S. fyris; the neutral low-molecular-weight fraction was effective toward E. coli O119 and S. fyris but not V. cholerae. Our results demonstrate that human milk oligosaccharides inhibit the adhesion to epithelial cells not only of common pathogens like E. coli but also for the first time of other aggressive bacteria as V. cholerae and S. fyris. Consequently, oligosaccharides are one of the important defensive factors contained in human milk against acute diarrheal infections of breast-fed infants.
Magnetic Shielding of a Cylindrical Shield in Nonlinear Hysteretic Material

The magnetic shielding efficiency of a cylindrical shield is studied starting from the experimentally determined hysteresis loops of the nonlinear shielding material. The magnetic transfer relation model is used in the frequency domain. This analytical model can be evaluated very fast, but works only for linear material. Therefore, the nonlinear shield is divided into a number of linear sublayers with constant complex permeability, which is modelled by an analytical complex function, fitted from the experimental hysteresis loops. The shielding factors are calculated by the analytical model as a function of the imposed field amplitude. They are validated by a finite element model and compared with measured shielding factors of cylindrical tubes. The correspondence is good for the three considered shields: a shield in aluminium (shielding by induced currents), a shield in Fe-Si steel (mainly shielding by flux shunting) and a multilayered shield in aluminium and Fe-Si steel
Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4

Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect. In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of β cells, and the putative signals involved. We demonstrated that AE, and especially 1 μg/mL of F2, decreased palmitate-induced apoptosis analyzed by flow cytometry. The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. The DPP-4 inhibitor linagliptin decreased the expression of caspase 3, suggesting that DPP-4 is critically involved in apoptotic signaling. Analysis of enzyme activity revealed that palmitate increased the activity of DPP4 nearly 2 folds, while F2 especially inhibited the activation. In addition, AMPK/mTOR, PI3K and mitochondrial pathways were regulated by AE, and this attenuated the palmitate-induced signaling cascades. In conclusion, AE is useful to prevent the exacerbation of β cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes.
Assessment of mammographic density before and after first full-term pregnancy

Mammographic density (MD) has consistently been found as one of the strongest breast cancer risk factors. In our study, both qualitative and quantitative density measurements were performed in a hospital-based group of premenopausal women before and after first full-term pregnancy providing an opportunity for direct evaluation of the effects of one pregnancy on MD. Mammograms were obtained from 23 women before and after first full-term pregnancy and from 28 nulliparous controls. MD was determined by a standard qualitative assessment method using the Breast Imaging Reporting and Data System, and a quantitative computer-based threshold method (0–100%). The mean age at mammography before and after pregnancy was 31 and 34 years, respectively, with a mean difference of 40 months between mammographies. The quantitative density assessment showed a significant reduction in relative MD after pregnancy of 12 percentage points (8.6–15.4), compared with 3.1 (0.0–6.2) in the nulliparous control group (P<0.001). A reduction in MD of more than 10% was seen in 52% of the patients, compared with 18% of the controls. The qualitative density assessment confirmed a reduction in MD after pregnancy by one Breast Imaging Reporting and Data System category (P=0.02). This longitudinal study showed that MD can be influenced by one full-term pregnancy. This effect was seen with both quantitative and qualitative assessment methods. It may be hypothesized that breast cancer risk reduction associated with pregnancy is mediated through a direct reduction of MD, and MD assessment might be incorporated in individualizing risk assessment and prevention.
Volatility of Secondary Market with Perspective to Brokers Role: An Empirical Study of Pakistan Stock Exchange

The objective of this study is to explore whether day trading is associated with volatility of stock prices or not. First, attempt is made to refer definitions of day traders given in prior researches. Common points in all these definitions are; the day trader try to complete cycle in same day and prefer low priced, volatile and large volume scrips. Day Trading is a common phenomenon in all over the world and legislators have imposed circuit breakers (Caps) to minimize the shocks of day trading. In Pakistan upper and lower caps are introduced too. Three types of indexes i.e. KSE 100, KSE All and KSE 30 are introduced by Karachi Stock Exchange (KSE). KSE 100 and KSE All indices are selected for the study sample period of the study is January 1, 2011 to December 31st, 2015. First, attempt is made to establish the fact that volatility in stock market exist. In this regard contemporary tools like Augmented Dickey Fuller Unit Root Test (ADF)Auto Regressive Conditional Heteroscedasticity (ARCH) and GARCH models are used. The results confirmed the volatility in the stocks. Then, trading behavior of investors is examined. The data includes price range from PKR 11.26 to PKR 12000 per scrip. Analysis exhibit that up to fifty percent trading is carried out in the scrips having price up to 100, and only 12.5% trading is done in the scrips that has price more than 1000. This trading behavior confirms that most of the investors are involved in day trading which is one of the reasons of stock market volatility.
Transformative Learning and Critical Thinking in Japanese Higher Education

While transformative learning (Mezirow, 1991) appears to have little uptake in Japanese higher education, we argue that a focus on ‘critical thinking’ (as taught as a component of formal courses or as the focus of a course of learning itself) may provide a means by which the more challenging aspects of transformative learning might receive greater attention. Given that transformational learning may be difficult to engender in formal educational contexts, and particularly so in Japan, we suggest that a connection between the ‘critical reflection’ of transformative learning can be made with aspects of critical thinking as it is often presented in formal teaching contexts. Moreover, we argue this may be afforded by the growing institutional commitments to the internationalization of higher education in Japan that often incorporate the delivery of critical thinking courses and the promotion of discourses that trade heavily on the importance of critical thinking for graduates. We provide a brief review and critique of transformational learning, consider the linkages between transformative learning and critical thinking with a particular focus critical refl ection, and provide some brief consideration of how aspects of transformational learning can be incorporated pragmatically in Japanese higher education contexts.
Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis*

Objective:To determine serum concentrations of thrombomodulin, the marker of endothelial injury, in patients with sepsis-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome and to investigate the independent association between this marker and the development of disseminated intravascular coagulation, multiple organ dysfunction syndrome, and mortality. Design:A prospective cohort study. Setting:A 37-bed intensive care unit of a tertiary care hospital. Patients:One hundred consecutive patients with sepsis. Interventions:Serum thrombomodulin concentrations and the development of disseminated intravascular coagulation and multiple organ dysfunction syndrome were determined in patients on days 1 and 3 of sepsis. These data were used to determine an association between day 1 thrombomodulin concentrations and development of disseminated intravascular coagulation, multiple organ dysfunction syndrome, and mortality during intensive care unit stay. These connections were determined by the Cox proportional hazards model and plotting of receiver operating characteristic curves. Measurements and Main Results:Day 1 serum concentrations of thrombomodulin were higher in patients with disseminated intravascular coagulation (11.1 ± 1.0 vs. 5.3 ± 0.5 ng/mL; p < .0001) or multiple organ dysfunction syndrome (10.3 ± 0.7 vs. 4.3 ± 0.4 ng/mL; p < .0001) than those without, respectively. In patients with resolved disseminated intravascular coagulation (4.9 ± 0.5 vs. 8.9 ± 0.9 ng/mL, day 3 vs. day 1, p = .005) or multiple organ dysfunction syndrome (6.3 ± 1.4 vs. 12.0 ± 1.6 ng/mL, day 3 vs. day 1, p < .0001) on day 3 of sepsis, day 3 levels of thrombomodulin were down from day 1. Thrombomodulin concentration independently predicted the development of disseminated intravascular coagulation (hazard ratio 1.13, p < .0001), multiple organ dysfunction syndrome (hazard ratio 1.12, p < .0001), and mortality (hazard ratio 1.19, p < .0001) during intensive care unit stay. The area under the receiver operating characteristic curve showed that day 1 serum thrombomodulin levels had good discriminative power in predicting the development of disseminated intravascular coagulation (0.811), multiple organ dysfunction syndrome (0.896), and mortality (0.803) during intensive care unit stay. Conclusions:Endothelial cell injury is critical in the progression from disseminated intravascular coagulation to multiple organ dysfunction syndrome and subsequent mortality in septic patients. Serum concentrations of thrombomodulin may be used in monitoring disseminated intravascular coagulation and multiple organ dysfunction syndrome in these patients.
CSE1L Links cAMP/PKA and Ras/ERK pathways and regulates the expressions and phosphorylations of ERK1/2, CREB, and MITF in melanoma cells

The Ras/ERK (extracellular signal‐regulated protein kinase) and cAMP/PKA (protein kinase A) pathways are essential for the transcriptional activities of CREB (cAMP response element binding protein) and MITF (microphthalmia‐associated transcription factor) in melanogenesis and the progression of melanoma. However, the interaction between Ras/ERK and cAMP/PKA pathways in the melanogenesis and progression of melanoma is not fully known. Here, we report that CSE1L (chromosome segregation 1‐like protein) regulates cAMP/PKA‐induced CREB and MITF expressions as well as Ras‐induced ERK1/2 phosphorylation. IBMX, a cAMP/PKA activator, treatment induced CSE1L phosphorylation and augmented Ras‐induced ERK1/2 phosphorylation. CSE1L knockdown by CSE1L shRNA expression vectors inhibited Ras‐induced ERK1/2 phosphorylation and melanogenesis in melanoma cells. CSE1L overexpression increased phospho‐CREB expression; CSE1L knockdown also inhibited Ras‐induced phospho‐CREB, MITF, and tyrosinase expressions, regardless of the presence of IBMX. This study identifies CSE1L links and controls the Ras/ERK and cAMP/PKA pathways in the melanogenesis of melanoma cells. Melanomas frequently develop drug resistance via paradoxical activation of Ras/Raf/MEK/ERK or alternatively activated Ras/ERK and cAMP/PKA pathways. Thus CSE1L may be a potential target for treating melanomas that harbor Ras mutations or are resistant to drugs targeting Raf/MEK/ERK. © 2015 Wiley Periodicals, Inc.
Long term comparison of some shock attentuating insoles

The effect of one years general use on the performance of four shock attentuating insoles is reported. Testing was carried out using the JP Biomechanics Shock Meter on twelve volunteers on a timed oval course at eight intervals during the year. The results show that two of the insoles perform well (Viscolas and PPT) although deterioration does occur after 6-9 months use; the other two insoles (Plastazote and Gait Aid) perform poorly. It is suggested that manufacturers provide some information to the user or supplier regarding the effective life of their products.
Argonaute-1 binds transcriptional enhancers and controls constitutive and alternative splicing in human cells

Significance Argonaute proteins are well characterized factors in posttranscriptional gene silencing, the process by which small RNAs trigger mRNA degradation or inhibit translation in the cytoplasm. We report here that Argonaute proteins also play important roles in the nucleus. Our genome-wide analysis reveals that Argonaute-1 (AGO-1) binds preferentially to active transcriptional enhancers and that this association is mediated by the RNAs that are transcribed from these enhancers (eRNAs). Moreover, the interaction of AGO-1 with enhancers does not seem to regulate transcription of the neighboring genes but of alternative and constitutive splicing. These results contribute to the understanding of the complex regulation of gene expression in eukaryotic cells. The roles of Argonaute proteins in cytoplasmic microRNA and RNAi pathways are well established. However, their implication in small RNA-mediated transcriptional gene silencing in the mammalian cell nucleus is less understood. We have recently shown that intronic siRNAs cause chromatin modifications that inhibit RNA polymerase II elongation and modulate alternative splicing in an Argonaute-1 (AGO1)-dependent manner. Here we used chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to investigate the genome-wide distribution of AGO1 nuclear targets. Unexpectedly, we found that about 80% of AGO1 clusters are associated with cell-type-specific transcriptional enhancers, most of them (73%) overlapping active enhancers. This association seems to be mediated by long, rather than short, enhancer RNAs and to be more prominent in intragenic, rather than intergenic, enhancers. Paradoxically, crossing ChIP-seq with RNA-seq data upon AGO1 depletion revealed that enhancer-bound AGO1 is not linked to the global regulation of gene transcription but to the control of constitutive and alternative splicing, which was confirmed by an individual gene analysis explaining how AGO1 controls inclusion levels of the cassette exon 107 in the SYNE2 gene.
A new switching strategy for field oriented control of motor driver using multi-dimensional feedback quantization modulation

This work proposes a new switching strategy for field oriented control of a motor driver to minimize the power of filtered error induced by finite bit resolution of the gating signal. It is shown that the conventional space vector pulse width modulation (SVPWM) is a special case of the proposed general switching strategy which has infinite bit resolution within one input period. Another special case, multi-dimensional feedback quantization modulator: MDFQM, is proposed and compared with SVPWM. The experiments in this study compared mean-square-error of motor speed, switching number of the three-phase voltage source inverter, and current waveforms. The experimental results show that MDFQM can reduce the switching number as well as the heat dissipation of the power transistors.
Increase in early polyethylene wear after sterilization with ethylene oxideRadiostereometric analyses of 201 total hips

We evaluated polyethylene wear by measuring femoral head penetration in 201 THA (median age 62 (31-81) years, 117 women) extracted from 5 randomized studies aimed to assess various fixation principles. There were 30 cemented all-polyethylene Lubinus cups sterilized by gamma irradiation in a reduced oxygen environment, 65 porous-coated Trilogy cups with liners gamma-sterilized in inert gas. Moreover, 37 cemented cups were sterilized with ethylene oxide (Reflection all-poly) and 69 porous-coated cups had liners sterilized in ethylene oxide (Reflection). 28 mm femoral heads were used in all cups. The patients were followed with repeated radiostereometric measurements (RSA) up to 2 years. The activity level of the patients was evaluated by a questionnaire. After 2 years, cups with polyethylene sterilized in EtO had almost twice the proximal and 3D penetration rates, as compared with gamma-sterilized polyethylene. The penetration did not differ between the gamma-irradiated designs. Using stepwise linear regression analysis, we found that the type of sterilization, age and weight were the most important predictors and that they determined the direction of the proximal penetration rate. Activity score, male gender and proximal migration of the cup had little effect. The accelerated wear observed with the EtO-sterilized polyethylene causes concerns about long-term problems and especially in younger patients.