Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (−/−) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP−/− mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (≥12 mo) BSP−/− mice. At 4 mo, BSP−/− mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP−/− versus WT bone marrow stromal cultures. BSP−/− hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP−/− mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN−/− mice.
Approximating the Sum of Correlated Lognormal or, Lognormal-Rice Random Variables

A simple and novel method is presented to approximate by the lognormal distribution the probability density function of the sum of correlated lognormal random variables. The method is also shown to work well for approximating the distribution of the sum of lognormal-Rice or Suzuki random variables by the lognormal distribution. The method is based on matching a low-order Gauss-Hermite approximation of the moment-generating function of the sum of random variables with that of a lognormal distribution at a small number of points. Compared with methods available in the literature such as the Fenton-Wilkinson method, Schwartz-Yeh method, and their extensions, the proposed method provides the parametric flexibility to address the inevitable trade-off that needs to be made in approximating different regions of the probability distribution function.
Dietary polyphenol intake and risk of type 2 diabetes in the Polish arm of the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study

Abstract This study aimed to test the association between dietary content of total and individual classes of polyphenols and incident cases of type 2 diabetes in Polish adults participating to the Health, Alcohol and Psychosocial factors In Eastern Europe study. At baseline, diet by 148-item FFQ and health information were collected from 5806 participants free of diabetes. Self-reported incident type 2 diabetes was ascertained at 2–4-year follow-up visit. OR and 95 % CI of type 2 diabetes comparing the various categories of polyphenol intake to the lowest one (reference category) and as 1 sd increase modelled as continuous variable were calculated by performing age-, energy-, and multivariate-adjusted logistic regression models. During the follow-up, 456 incident cases of type 2 diabetes occurred. When comparing extreme quartiles, intake of total polyphenol was inversely associated with the risk of type 2 diabetes (OR 0·43; 95 % CI 0·30, 0·61); 1 sd increase was associated with a reduced risk of diabetes (OR 0·68; 95 % CI 0·59, 0·79). Among the main classes of polyphenols, flavonoids, phenolic acids, and stilbenes were independent contributors to this association. Both subclasses of phenolic acids were associated with decreased risk of type 2 diabetes, whereas among subclasses of flavonoids, high intake of flavanols, flavanones, flavones and anthocyanins was significantly associated with decreased risk of type 2 diabetes. Total dietary polyphenols and some classes of dietary polyphenols were associated with lower risk of type 2 diabetes.
Biochemical and Molecular Action of Nutrients Garlic and Garlic-Derived Compounds Inhibit Human Squalene Monooxygenase 1

Although extracts of garlic inhibit cholesterol biosynthesis in cultured hepatocytes, the inhibitory components of garlic and the site or sites of inhibition in the cholesterol biosynthetic pathway have not been established. To elucidate potential mechanisms of inhibition, we examined the effect of fresh garlic extract and 16 water- or lipid-soluble compounds derived from garlic on puriﬁed recombinant human squalene monooxygenase. Squalene monooxygenase catalyzes the second and likely rate-limiting step in the downstream pathway for cholesterol biosynthesis. A 50% inhibitory concentration (IC 50 ) of squalene epoxidation was achieved with 1 g/L of fresh garlic extract; of the 16 garlic compounds tested, only selenocystine (IC 50 5 65 m mol/L), S -allylcysteine (IC 50 5 110 m mol/L), alliin (IC 50 5 120 m mol/L), diallyl trisulﬁde (IC 50 5 195 m mol/L), and diallyl disulﬁde (IC 50 5 400 m mol/L) substantially inhibited the enzyme. Kinetic analysis showed that the inhibition by garlic and by these compounds was slow and irreversible, suggestive of covalent binding to the enzyme; the ability of thiol-containing compounds such as glutathione and 2,3-dimercaptopropanol to prevent and reverse the inhibition indicated that the garlic compounds were reacting with sulfhydryl groups on the protein. Dithiols were better reversal agents than monothiols, further suggesting that these inhibitors bind to the proposed vicinal sulfhydryls present on this enzyme. These results indicate that squalene monooxygenase may be one of the target enzymes through which garlic inhibits cholesterol biosynthesis. J. Nutr. 131: 2001. selenium c selenocystine c squalene epoxidase
The Large, Oxygen-Rich Halos of Star-Forming Galaxies Are a Major Reservoir of Galactic Metals

Observations with the Hubble Space Telescope show that halos of ionized gas are common around star-forming galaxies. The circumgalactic medium (CGM) is fed by galaxy outflows and accretion of intergalactic gas, but its mass, heavy element enrichment, and relation to galaxy properties are poorly constrained by observations. In a survey of the outskirts of 42 galaxies with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope, we detected ubiquitous, large (150-kiloparsec) halos of ionized oxygen surrounding star-forming galaxies; we found much less ionized oxygen around galaxies with little or no star formation. This ionized CGM contains a substantial mass of heavy elements and gas, perhaps far exceeding the reservoirs of gas in the galaxies themselves. Our data indicate that it is a basic component of nearly all star-forming galaxies that is removed or transformed during the quenching of star formation and the transition to passive evolution.
On answering why-not questions in reverse skyline queries

This paper aims at answering the so called why-not questions in reverse skyline queries. A reverse skyline query retrieves all data points whose dynamic skylines contain the query point. We outline the benefit and the semantics of answering why-not questions in reverse skyline queries. In connection with this, we show how to modify the why-not point and the query point to include the why-not point in the reverse skyline of the query point. We then show, how a query point can be positioned safely anywhere within a region (i.e., called safe region) without losing any of the existing reverse skyline points. We also show how to answer why-not questions considering the safe region of the query point. Our approach efficiently combines both query point and data point modification techniques to produce meaningful answers. Experimental results also demonstrate that our approach can produce high quality explanations for why-not questions in reverse skyline queries.
Managing infertility with the follitropin alfa prefilled pen injector – patient considerations

Gonadotropin treatment has been used in fertility treatment since the 1930s. First, preparations coming from animals were injected, then, gonadotropins prepared from the pituitary glands of human cadavers. A great step was achieved with the introduction of human menopausal gonadotropin extracted from the urine of postmenopausal women. When cases of Creutzfeld-Jacob disease were recognized after the use of human pituitary-derived hormone injections, urinary gonadotropins were increasingly purified and then produced by the use of recombinant DNA technology. Recombinant gonadotropins were characterized by the extreme high specificity and the nearly 100% purity. This allows for follitropin alfa, the first recombinant-human follicle stimulating hormone (r-hFSH) approved, to be quantified and filled by mass, with a small variance of only ±2% and no more with a bioassay with a variance of 45%. With recombinant preparations, it is also possible to cover the tremendous growing demand for gonadotropins. Ovarian stimulation has become a self-injecting procedure for the patients. Accurate and easy-to-use injection devices which minimize pain, difficulty, and stress are essential for patient compliance. So, two pen injectors adapted from the well-known insulin pen were introduced in fertility treatment, one as a multiple-use device rechargeable with premixed, prefilled cartridges with r-hFSH (follitropin β) and the other a disposable, prefilled drug delivery system with a liquid formulation of follitropin alfa filled by mass. The efficacy in comparison to the quite more cumbersome handling with ampoules and syringes has been proven very quickly. In several studies, it has been shown that patients had a preference to the prefilled follitropin alfa pen due to the faster preparation and were more confident of accurate dosing. The follitropin alfa (filled by mass [FbM]) prefilled pen is a move toward better quality of treatment and also better quality of life for the women within the stressful period of fertility treatment.
Ecstasy-induced toxicity in rat liver.

BACKGROUND/AIMS The aim of the present study was to examine the effects of single and repeated administration of 3,4-methylenedioxyme-thamphetamine (MDMA, "ecstasy") on rat liver. METHODS Animals were given an acute (20 mg/kg) and repeated (20 mg/kg, b.i.d., for 4 consecutive days) intraperitoneal dose of MDMA, and at various times after administration the hepatic and serum determinations were made. RESULTS The effect of acute MDMA administration included increased triglyceride and cholesterol levels and an increase in all enzyme activities 6 h post administration. The toxic effect of MDMA was also observed in other hepatic processes. Glycogen content showed a marked decrease, which was accompanied by a decrease in serum glucose levels. No significant changes in lipid peroxidation and hepatic GSH content were observed. In contrast, multiple MDMA administration produced some evidence of oxidative stress, namely, increased MDA content and decreased GSH content, a small decrease in liver glycogen at 3 h recovering 6 h post dose, no effect on blood glucose and increased AST and ALP activities but no effects on ALT activity. Seven days after the last MDMA injection a tendency towards recovery was shown. CONCLUSION Our results show that the liver toxicity caused by MDMA administration involves several mechanisms.
GSK3β Activity Modifies the Localization and Function of Presenilin 1*

Presenilin 1, a causative gene product of familial Alzheimer disease, has been reported to be localized mainly in the endoplasmic reticulum and Golgi membranes. However, endogenous Presenilin 1 also localizes at the plasma membrane as a biologically active molecule. Presenilin 1 interacts with N-cadherin/β-catenin to form a trimeric complex at the synaptic site through its loop domain, whose serine residues (serine 353 and 357) can be phosphorylated by glycogen synthase kinase 3β. Here, we demonstrate that cell-surface expression of Presenilin 1/γ-secretase is enhanced by N-cadherin-based cell-cell contact. Physical interaction between Presenilin 1 and N-cadherin/β-catenin plays an important role in this process. Glycogen synthase kinase 3β-mediated phosphorylation of Presenilin 1 reduces its binding to N-cadherin, thereby down-regulating its cell-surface expression. Moreover, reduction of the Presenilin 1·N-cadherin·β-catenin complex formation leads to an impaired activation of contact-mediated phosphatidylinositol 3-kinase/Akt cell survival signaling. Furthermore, phosphorylation of Presenilin 1 hinders ϵ-cleavage of N-cadherin, whereas ϵ-cleavage of APP remained unchanged. This is the first report that clarifies the regulatory mechanism of Presenilin 1/γ-secretase with respect to its subcellular distribution and its differential substrate cleavage. Because the cleavage of various membrane proteins by Presenilin 1/γ-cleavage is involved in cellular signaling, glycogen synthase kinase 3β-mediated phosphorylation of Presenilin 1 should be deeply associated with signaling functions. Our findings indicate that the abnormal activation of glycogen synthase kinase 3β can reduce neuronal viability and synaptic plasticity via modulating Presenilin 1/N-cadherin/β-catenin interaction and thus have important implications in the pathophysiology of Alzheimer disease.
No . 15 / 01 Worker Flows and the Impact of Labour Transitions on Earnings in Uganda by

The paper examines the flow of workers between employment states, the role of education in these transitions and the impact of the transitions on earnings. It uses panel data for three waves (2005/06, 2009/10 and 2010/11) of household surveys in Uganda. Using the Markov chain process, we estimate transition probability matrices and find bi-directional transitions between formal and informal employment but with a higher tendency of workers to transition from formal to informal than in the opposite direction. When we investigate the relation between education and transitions using probit models, we find the transition from informal to formal increases with education but the movement from formal to informal employment and switching from not working to working declines with education. We further investigate the impact of the transitions on the worker’s welfare by estimating wage equations and find evidence for a decline in monthly wages for workers moving from formal to informal employment and a wage gain for workers moving in the reverse direction. We suggest that transitions from informal to formal employment are induced by higher wage offers, while transitions in the opposite direction are more likely to be due to losing a job. JEL Classification: J23, J40, O17, O55,
MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.

Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware. net.
Enhancement of security against zero dynamics attack via generalized hold

Zero dynamics attack is lethal to cyber-physical systems in the sense that it is stealthy and there is no way to detect it. Fortunately, if the given continuous-time physical system is of minimum phase, the effect of the attack is negligible even if it is not detected. However, the situation becomes unfavorable again if one uses digital control by sampling the sensor measurement and using the zero-order-hold for actuation because of the ‘sampling zeros. ’ When the continuous-time system has relative degree greater than two and the sampling period is small, the sampled-data system must have unstable zeros (even if the continuous-time system is of minimum phase), so that the cyber-physical system becomes vulnerable to ‘sampling zero dynamics attack. ’ In this paper, we begin with its demonstration by a few examples. Then, we present an idea to protect the system by allocating those discrete-time zeros into stable ones. This idea is realized by employing the so-called ‘generalized hold’ which replaces the zero-order-hold.
The Antisense Transcriptomes of Human Cells

Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the plus or minus strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here, we describe a technique that can be used to (i) identify the DNA strand of origin for any particular RNA transcript, and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was nonrandom across the genome, and differed among cell types. Antisense transcripts thus appear to be a pervasive feature of human cells, which suggests that they are a fundamental component of gene regulation.
Overall Survival of Elderly Patients Having Surgery for Colorectal Cancer Is Comparable to Younger Patients: Results from a South Asian Population

Introduction There has been a continuous debate on whether elderly patients with colorectal cancer (CRC) fair worse. The aim of this study is to assess the thirty-day mortality (TDM) and overall survival (OS) of elderly patients undergoing surgery for CRC. Method OS between two groups (≥70 versus <70 years) having surgery for CRC was analyzed. Demographics, tumour characteristics, and serological markers were considered as independent factors. Multivariable analysis was done using the Cox proportional hazard model. We also compared overall survival in the elderly versus those <60 and <50 years. Results 477 patients, 160 elderly (55% male; median age 75, range 70–89) and 317 younger patients (49% male; median age 55, range 16 to 69), were studied. Overall survival in CRC patients ≥70 is comparable to <70 (P = 0.45) and <60 years (P = 0.08). Poor OS was observed in the ≥70 versus <50 years (P = 0.03). TDM in the elderly was poor (P < 0.05). Postoperative cardiac complication was the only determinant affecting survival in the elderly (P = 0.01). Conclusion OS in elderly CRC patients having surgery is not worse compared to <70 and <60 years although the TDM was higher. Postoperative cardiac complications significantly affected OS in those ≥70 compared to those <50 years. Chronological age alone should not negatively influence surgical decision-making in the elderly.
Erratum: Detection of six novel FBN1 mutations in British patients affected by Marfan syndrome

Marfan syndrome (MFS), an autosomal dominant disorder of the extracellular matrix, is due to mutations in fibrillin‐1 (FBN1) gene. Investigations carried out in the last decade, unveiled the unpredictability of the site of the mutation, which could be anywhere in the gene. FBN1 mutations have been reported in a spectrum of diseases related to MFS, with no clear evidence for a phenotype‐genotype correlation. In this paper we analysed 10 British patients affected by MFS and we were able to characterise five novel missense mutations (C474W, C1402Y, G1987R, C2153Y, G2536R), one novel frameshift mutation (7926delC), one already described mutation (P1424A) and one FBN1 variant (P1148A) classified as a polymorphism in the Asian population. Four out of the five novel missense mutations involved either cysteines or an amino acid conserved in the domain structure. The mutation yield in this study is calculated at 80.0% (8/10), thus indicating that SSCA is a reliable and cost‐effective technique for the screening of such a large gene. Our results suggest that this method is reliable to search for FBN1 mutations and that FBN1 screening could be a helpful tool to confirm and possibly anticipate the clinical diagnosis in familial cases. © 2001 Wiley‐Liss, Inc.
Marine Traffic Safety Diagnostic Scheme in Korea

Abstract: According to the Marine Traffic Safety Law, revised in 2009, Marine Traffic Safety Diagnostic Scheme is introduced to secure the safe navigation, prevent the marine accident and to maximize the efficiency of the port operation. The diagnostic system aims to investigate, measure and evaluate the effect of the various development project such as the construction of bridge over navigable waterway, and of piers in port and etc. Then the diagnostic results should be reflected on the project designed for the safe navigation. This paper introduces the Marine Traffic Safety Diagnostic Scheme includes the diagnostic process, evaluation items, diagnostic criteria, registration criteria of the diagnostic agent and the standards of written diagnostic report. This paper also discusses various marine traffic safety evaluation model including ES model & IWRAP model which is the most important part of the system.
“Cogent Religious Instruction”: A Response to the Phenomenon of Radical Islamist Terrorism in Australia

Over the past 15 years, 47 Muslim Australians have been convicted for terrorism offences. Australian courts have determined that these acts were motivated by the offenders’ “Islamic” religious beliefs and that interpretations of Quranic verses concerning jihad, in relation to shariah, caliphate, will of God and religious duty contributed to the commission of these crimes. This paper argues that these ideas, derived from certain classical-era Islamic jurisprudence and modern Islamist thought, contradict other classical-era interpretations and, arguably, the original teachings of Islam in the time of the Prophet Muhammad. In response to the call for “cogent religious instruction” to combat the phenomenon of radical Islamist terrorism, this paper outlines a deradicalization program that addresses late 20th- and early 21st-century time-period effects: (1) ideological politicization associated with Islamist jihadism; (2) religious extremism associated with Salafism; and (3) radicalization associated with grievances arising from Western military interventions in Muslim-majority countries. The paper offers a counter narrative, based on a contextualized reading of the Quran and recent research on the authentication of the Covenants of the Prophet Muhammad. It further contends that cogent religious instruction must enhance critical-thinking skills and provide evidence-based knowledge in order to undermine radical Islamist extremism and promote peaceful coexistence.