Miracle-dz/UniFAR-FTUs huggingface dataset:
SNAREs Are Dominant Inhibitors of Membrane Fusion

Exocytosis in yeast requires the assembly of the secretory vesicle soluble N -ethylmaleimide–sensi-tive factor attachment protein receptor (v-SNARE) Sncp and the plasma membrane t-SNAREs Ssop and Sec9p into a SNARE complex. High-level expression of mutant Snc1 or Sso2 proteins that have a COOH-termi-nal geranylgeranylation signal instead of a transmembrane domain inhibits exocytosis at a stage after vesicle docking. The mutant SNARE proteins are membrane associated, correctly targeted, assemble into SNARE complexes, and do not interfere with the incorporation of wild-type SNARE proteins into complexes. Mutant SNARE complexes recruit GFP-Sec1p to sites of exocytosis and can be disassembled by the Sec18p ATPase. Heterotrimeric SNARE complexes assembled from both wild-type and mutant SNAREs are present in het-erogeneous higher-order complexes containing Sec1p that sediment at greater than 20S. Based on a structural analogy between geranylgeranylated SNAREs and the GPI-HA mutant inﬂuenza virus fusion protein, we propose that the mutant SNAREs are fusion proteins unable to catalyze fusion of the distal leaﬂets of the secretory vesicle and plasma membrane. In support of this model, the inverted cone–shaped lipid lysophosphati-dylcholine rescues secretion from SNARE mutant cells. This positive curvature reduces the activation energy for fusion of the stimulating completion of the exocytic reaction.
OPTH_A_271673 3781..3788

Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Purpose: To determine the characteristics of the patients who preferred using the eye drop guide (EDG) regularly and their opinions toward the guide in order to select the patients for prescribing the EDG appropriately. Patients and Methods: Fifty-seven glaucoma patients who completed the primary study, “The effect of ‘eye drop guide’ on the success rate of eye drop self-instillation in glaucoma patients”, were included. Patients’ instillation techniques, routine instillation or using the EDG, were chosen independently. After 4–6 months, they were interviewed about the frequency of EDG use and their rating scores toward the guide in 4 aspects including aiming aids, contamination prevention, reduction of drop waste, and ease of use. The differences in opinion scores between each frequency group and the factors associated with the regularity of EDG use were statistically analyzed. Results: Of fifty-seven patients completing the interview, 19.3% used the EDG everyday, while 45.6% had never used the EDG. The nonusers rated significantly lower scores in all aspects (p-value < 0.005). From multivariate analysis, the factors associated with the preference not to use the EDG were administering in supine position (p-value < 0.001, adjusted OR 34.866, 95% CI 4.974–244.412) and more than one eye drop use (p-value = 0.048, adjusted OR 5.280, 95% CI 1.018–27.396). Conclusion: The EDG should be selectively prescribed for the particular patients who had one medication and performed instillation in sitting or standing position. Although the regular EDG users tended to have positive opinions on the EDG, their long-term compliance with the guide was underinvestigated.
Educational options for children with medical

Schooling is known to influence a wide range of economic, social and psychological aspects of people’s life, but children with medical needs are subject to school failure more often than their healthy peers. The aim of this paper is to review different school options available to the paediatrics community for the education of children with medical needs. Hospital school, home tuition and mainstream school re-entry are examined. Critical aspects for each type of solution are discussed. The provision and stability of adequate educational opportunities for children with medical needs represents an important area of collaboration between doctors, educators and parents for the prevention of long-term consequences of illnesses and therapies.
An Exploratory Study on Solidity Guards and Ether Exchange Constructs

Ethereum is a blockchain platform that enables the use of smart contracts. Smart contracts will execute a set of instructions without an intermediary party when called upon. The possibility to make calls to another contract or exchange cryptocurrency allows for potential exploits to occur, most notable reentrancy. The Solidity language for coding smart contracts has syntactic constructs created to be safer alternatives, and guards to aid in securing code against exploits. In this paper, we collect a total of 26,799 verified Solidity smart contracts from Etherscan, to analyze the language constructs used in calling another contract or exchanging ether. We also analyze the usage of guards to make the code more secure. For instance, even though call is the unsafest function, it is still used by 50% of the contracts in our dataset. The safe method transfer is used by approximately one-third of contracts, and send is rarely used. We noticed that contracts using call have a higher average and median size in Lines of Code than normal. We also found an increased percentage of call contracts using more guards. Moreover, 97% of all contracts are using the require guard, with 23 uses of require on average per contract. This may be an indication that Solidity developers are using more guards to prevent exploits in their contracts
Asymptotics of Sequential Composite Hypothesis Testing Under Probabilistic Constraints

We consider the sequential composite binary hypothesis testing problem in which one of the hypotheses is governed by a single distribution while the other is governed by a family of distributions whose parameters belong to a known set <inline-formula> <tex-math notation="LaTeX">$\Gamma $ </tex-math></inline-formula>. We would like to design a test to decide which hypothesis is in effect. Under the constraints that the probabilities that the length of the test, a stopping time, exceeds <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> are bounded by a certain threshold <inline-formula> <tex-math notation="LaTeX">$\epsilon $ </tex-math></inline-formula>, we obtain certain fundamental limits on the asymptotic behavior of the sequential test as <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> tends to infinity. Assuming that <inline-formula> <tex-math notation="LaTeX">$\Gamma $ </tex-math></inline-formula> is a convex and compact set, we obtain the set of all first-order error exponents for the problem. We also prove a strong converse. Additionally, we obtain the set of second-order error exponents under the assumption that the alphabet of the observations <inline-formula> <tex-math notation="LaTeX">$\mathcal {X}$ </tex-math></inline-formula> is finite. In the proof of second-order asymptotics, a main technical contribution is the derivation of a central limit-type result for a maximum of an uncountable set of log-likelihood ratios under suitable conditions. This result may be of independent interest. We also show that some important statistical models satisfy the conditions.
CPAA_A_288831 191..202

1Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, NY, USA; 2School of Medicine, University of Athens, Athens, Greece; 3School of Medicine, University of Crete, Heraklion, Greece; 4General Directorate of Public Health and Social Welfare, Attica Region, Athens, Greece; 5Cardiology Clinic, Cardiology Unlimited, PC, New York, NY, USA Abstract: The current era of preventive cardiology continues to emphasize on low-density lipoprotein cholesterol (LDL-C) reduction to alleviate the burden of atherosclerotic cardiovascular disease (ASCVD). In this regard, the pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme via monoclonal antibodies has emerged as a novel lipid-lowering therapy, leading to a marked reduction in circulating LDL-C levels and subsequent improvement of cardiovascular outcomes. As these agents are increasingly used in current clinical practice, mounting scientific and clinical evidence supports that PCSK9 inhibitors offer an excellent safety and tolerability profile with a low incidence of adverse events. Notably, the most frequently reported side effects are injection-site reactions. In contrast to statins, PCSK9 inhibitors do not appear to exert a detrimental effect on glycemic control or to increase the incidence of new-onset diabetes mellitus. Accumulating evidence also indicates that PCSK9 inhibitors are a safe, well-tolerated and effective therapeutic strategy for patients with statin intolerance. On the other hand, as PCSK9 inhibitors reduce LDL-C to unprecedented low levels, a large body of current research has examined the effects of their long-term administration on neurocognition and on levels of vitamin E and other fat-soluble vitamins, providing encouraging results. This review aims to present and discuss the current clinical and scientific evidence pertaining to the safety and tolerability of PCSK9 inhibitors.
A Sketch Is Worth a Thousand Words: Image Retrieval with Text and Sketch

We address the problem of retrieving images with both a sketch and a text query. We present TASK-former (Text And SKetch transformer), an end-to-end trainable model for image retrieval using a text description and a sketch as input. We argue that both input modalities complement each other in a manner that cannot be achieved easily by either one alone. TASK-former follows the late-fusion dual-encoder approach, similar to CLIP, which allows efficient and scalable retrieval since the retrieval set can be indexed independently of the queries. We empirically demonstrate that using an input sketch (even a poorly drawn one) in addition to text considerably increases retrieval recall compared to traditional text-based image retrieval. To evaluate our approach, we collect 5,000 hand-drawn sketches for images in the test set of the COCO dataset. The collected sketches are available a https://janesjanes.github. io/tsbir/.
Oxoreductase and Dehydrogenase Activities of the Human and Rat 11 (cid:98) -Hydroxysteroid Dehydrogenase Type 2 Enzyme*

The 11 (cid:98) -hydroxysteroid dehydrogenase type 2 enzyme (11 (cid:98) HSD2) metabolizes glucocorticoids into their inactive 11-keto metabolites. Although the type 1 enzyme (11 (cid:98) HSD1) displays both oxidative and reductive activity, to date 11 (cid:98) HSD2 has been shown to have dehy- drogenase activity only. In this study we compared both dehydrogenase and reductase characteristics of the cloned rat 11 (cid:98) HSD1 and rat and human 11 (cid:98) HSD2 for three different 11-hydroxysteroid substrates, cortisol (F),corticosterone(B),anddexamethasone(Dex),andthecorrespond-ing11-ketometabolites,cortisone(E),11-dehydrocorticosterone(A),and11-dehydrodexamethasone(DH-Dex),respectively.Incellhomogenatesexpressingeithertheratorthehuman11 (cid:98) HSD2, the relative potency for the dehydrogenase reaction was B (cid:46) F (cid:46) Dex. Although there was no reduction of A or E, DH-Dex was readily converted to Dex with an equilibrium far on the side of the 11-hydroxy metabolite. DH-Dex reduction in homogenates was in- hibited by both glycyrrhetinic acid and carbenoxolone, with a 50% inhibition at 80 and 100 n M , respectively. In intact cells transfected with rat 11 (cid:98) HSD1, the equilibrium was on the reductase side for all substrates. Dehydrogenation of B or F was more potent with rat 11 (cid:98) HSD2thanwithrat11 (cid:98) HSD1.Therewasnodetectable11 (cid:98) HSD1 oxidation of Dex. These data indicate that both the cloned human and rat 11 (cid:98) HSD2 reduce DH-Dex and do this more readily than they oxidize Dex. Thus, 11 (cid:98) HSD2 seems also to be a bidirectional enzyme, although no reduction of the physiological compounds A and E was observed. ( Endocrinology 138: 2948–2952,
University of Southern Denmark Strength Training Improves Fatigue Resistance and Self-Rated Health in Workers with Chronic Pain

• You may download this work for personal use only. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying this open access version If you believe that this document breaches copyright please contact us providing details and we will investigate your claim. Please direct all enquiries to puresupport@bib.sdu. dk
Are Bred Vectors The Same As Lyapunov Vectors

The use of ensemble forecasting and data assimilation has made apparent the importance of local predictability properties of the atmosphere in space and in time (e.g., Toth and Kalnay, 1993, Molteni and Palmer, 1993). The “spaghetti” plots and other methods used to display operational ensemble products frequently show simultaneous high predictability in some areas and low predictability in others. The regional loss of predictability is an indication of the instability of the underlying flow, where small errors in the initial conditions (or imperfections in the model) grow to large amplitudes in finite times. The stability properties of evolving flows have been studied using Lyapunov vectors (e.g., Alligood et al, 1996, Ott, 1993, Kalnay, 2001), singular vectors (e.g., Lorenz, 1965, Farrell, 1988, Molteni and Palmer, 1993), and, more recently, with bred vectors (e.g., Szunyogh et al, 1997, Cai et al, 2001).
The Difficulty in Designing Shewhart X̄ and X Control Charts with Estimated Parameters

The performance of the Shewhart X̄ control chart with estimated in-control parameters has been discussed a number of times in the literature. Previous studies showed that at least 400/(n – 1) phase I samples, where n > 1 is the sample size, are required so that the chart performs on average as if the in-control process parameter values were known. This recommendation was based on the in-control expected average run length (ARL) performance. The reliance on the expected ARL metric, however, averages across the practitioner-to-practitioner variability. This variability occurs due to the different historical data sets practitioners use, which results in varying parameter estimates, control limits, and in-control ARL values. In our article, we show that taking this type of variability into consideration leads to far larger amounts of phase I data than what was previously recommended. This is to ensure low levels of variation in the in-control ARL values among practitioners. The standard deviation of the ARL (SDARL) metric is used to evaluate performance for various amounts of phase I data. We show that no realistic phase I sample size is sufficient to have confidence that the attained in-control ARL is close to the desired value. We additionally investigate the effect of different process standard deviation estimators on the X̄-chart performance, showing that it is best to use a biased estimator. We also study the design of the X-chart for the case n = 1, drawing similar conclusions regarding the amount of phase I data. An alternative approach to designing control charts is recommended.
Galactic Winds across the Gas-rich Merger Sequence. II. Lyα Emission and Highly Ionized O vi and N v Outflows in Ultraluminous Infrared Galaxies

This paper is the second in a series aimed at examining the gaseous environments of z ≤ 0.3 quasars and ultraluminous infrared galaxies (ULIRGs) as a function of AGN/host galaxy properties across the merger sequence. This second paper focuses on the Lyα emission and O vi 1032, 1038 and N v 1238, 1243 absorption features, tracers of highly ionized gas outflows, in ULIRGs observed with HST/COS. Lyα emission is detected in 15 out of 19 ULIRGs, and 12 of the 14 clear Lyα detections show emission with blueshifted velocity centroids and/or wings. The equivalent widths of the Lyα emission increase with increasing AGN luminosities and AGN bolometric fractions. The blueshifts of the Lyα emission correlate positively with those of the [O iii] λ5007 emission, where the latter traces the ionized gas outflows. The Lyα escape fractions tend to be slightly larger in objects with stronger AGN and larger outflow velocities, but they do not correlate with nebular line reddening. Among the 12 ULIRGs with good continuum signal-to-noise ratios, O vi and/or N v absorption features are robustly detected in six of them, all of which are blueshifted, indicative of outflows. In the combined ULIRG + quasar sample, the outflows are more frequently detected in the X-ray weak or absorbed sources. The absorption equivalent widths, velocities, and velocity dispersions of the outflows are also higher in the X-ray weak sources. No other strong correlations are visible between the properties of the outflows and those of the AGN or host galaxies.
r-process Viable Outflows are Suppressed in Global Alpha-viscosity Models of Collapsar Disks

Collapsar disks have been proposed to be rich factories of heavy elements, but the major question of whether their outflows are neutron rich and could therefore represent significant sites of the rapid neutron-capture (r-) process or dominated by iron-group elements remains unresolved. We present the first global models of collapsars that start from a stellar progenitor and self-consistently describe the evolution of the disk, its composition, and its outflows in response to the imploding stellar mantle, using energy-dependent M1 neutrino transport and an α-viscosity to approximate turbulent angular-momentum transport. We find that a neutron-rich, neutrino-dominated accretion flow (NDAF) is established only marginally—either for short times or relatively low viscosities—because the disk tends to disintegrate into an advective disk already at relatively high mass-accretion rates, launching powerful outflows but preventing it from developing a hot, dense, and therefore neutron-rich core. Viscous outflows disrupt the star within ∼100 s with explosion energies close to that of hypernovae. If viscosity is ignored, a stable NDAF with disk mass of about 1 M ☉ is formed but is unable to release neutron-rich ejecta, while it produces a relatively mild explosion powered by a neutrino-driven wind blown off its surface. With ejecta electron fractions close to 0.5, all models presumably produce large amounts of 56Ni. Our results suggest that collapsar models based on the α-viscosity are inefficient r-process sites and that genuinely magnetohydrodynamic effects may be required to generate neutron-rich outflows. A relatively weak effective viscosity generated by magnetohydrodynamic turbulence would improve the prospects for obtaining neutron-rich ejecta.
Land pollution by illegal dumps in the Tashkent region

The problem of the emergence of illegal dumps in rural areas is considered in the article on the example of the Tashkent region of the Republic of Uzbekistan. It was revealed that the sizes of illegal disposal fields vary from 1.0 to 18,895 m2, there are dumps for building materials from construction sites, agricultural, household waste, as well as mixed landfills. The continuity of the layer of illegal dumps ranges from 60 to 100%. The roadsides also present long stretched illegal dumps with a continuity of the waste layer from 10 to 42%. For a full-scale assessment of the location, size and composition of illegal dumps, it is recommended to develop a GIS monitoring system.
Soluble receptor activator of nuclear factor (RANKL)/osteoprotegerin (OPG) ratio predicts survival in multiple myeloma. Proposal for a novel prognostic index.

Interaction between receptor activator and RANK/osteoprotegerin (OPG) plays a dominant role in osteoclast activation and possibly in plasma cell survival in multiple myeloma (MM). We measured soluble RANKL (sRANKL), OPG, and bone remodelling markers in 121 newly diagnosed MM patients to evaluate their role in bone disease and survival. Serum levels of sRANKL were elevated in patients with MM and correlated with bone disease. The ratio sRANKL/OPG was also increased and correlated with markers of bone resorption, osteolytic lesions, and markers of disease activity. The ratio sRANKL/OPG, CRP and (cid:2) 2 -microglobulin were the only independent prognostic factors predicting survival in multivariate analysis. We have generated a prognostic index based on these factors, which divides our patients into three risk groups. The low-risk group had a 96% probability of survival at five years while the intermediate-risk and the high- risk groups had probabilities of survival of 52% and 0% respectively. Not only do these results confirm for the first time in humans the importance of the sRANKL/OPG in the development of bone disease but they also highlight the role of this pathway in the biology of plasma cell growth as reflected by its influence on survival.
Approximate H∞ identification using partial sum operators in a disc algebra basis

H/sub /spl infin// system identification using a basis in the disc algebra is presented. The approximate model is represented by a partial sum with respect to this basis. The identification problem is to estimate the expansion coefficients of this partial sum. Since the constructed basis functions cannot be represented analytically, they are approximated in order to arrive at a model in a suitable form. An algorithm is presented which calculates the model parameters from the frequency domain data set.
Effect of Rehabilitation on Sleep Quality after Ablation for Atrial Fibrillation Data from a Randomized Trial

Background: Low sleep quality is common in patients with atrial fibrillation (AF). Positive effects of cardiac rehabilitation on patients treated for AF with ablation have been found, but whether cardiac rehabilitation affects sleep quality is unknown. The objectives of this study were to investigate (1) differences in sleep quality between cardiac rehabilitation and usual care groups and (2) whether other factors could affect sleep quality. Methods: From the randomized CopenHeart RFA trial, 210 patients treated for AF with ablation were included. A rehabilitation program consisting of physical exercise and psychoeducational consultations was tested. Sleep quality was measured with the Pittsburg Sleep Quality Index (PSQI) questionnaire before intervention and at the end of intervention. Anxiety, depression, and European Heart Rhythm Association scores were assessed. Results: No difference between groups in sleep quality was found (PSQI global mean [SD] score, 6.60 [3.61] points for the cardiac rehabilitation group [n = 83] and 6.08 [3.60] points for the usual care group [n = 90]; P = .34), althoughimprovements insleepqualitywerenotedinbothgroups. Sleeplatency, duration, andefficiencywere significant by type of AF at 1 month. Anxiety, depression, and higher European Heart Rhythm Association scores at 4 months were associated with a higher PSQI global mean score at the end of intervention. Conclusion: The rehabilitation program showed no effect on sleep quality. A large proportion of patients reported poor sleep quality, and patients reporting anxiety, depression, or AF symptoms described worse sleep quality compared with patients who did not experience anxiety, depression, or AF symptoms. More research in the field is warranted.
Steady-state solutions of the Euler equations in two dimensions. II - Local analysis of limiting V-states

Steady-state solutions of the 2D incompressible Euler equations (which we call V-states) are studied analytically. That is, a local expansion is done in the neighborhood of any point on the boundary of a V-state (which consists of piecewise constant regions of vorticity). The analytical results contained in paper I by Wu, Overman, and Zabusky are proven. In particular, the limiting V-states for the numerically calculated translating and rotating V-states have $90^\circ$ corners and not cusps. It is also proven that at a point which lies on the boundary of only one region and at which the tangent angle has a jump discontinuity then the difference in tangent angles can only be $90^\circ$ (a corner) or $180^\circ$ (a cusp). The analytical behavior of doubly and triply connected rotating V-states is also investigated.