Miracle-dz/UniFAR-FTUs huggingface dataset:
A Multi-Species Functional Embedding Integrating Sequence and Network Structure

A key challenge to transferring knowledge between species is that different species have fundamentally different genetic architectures. Initial computational approaches to transfer knowledge across species have relied on measures of heredity such as genetic homology, but these approaches suffer from limitations. First, only a small subset of genes have homologs, limiting the amount of knowledge that can be transferred, and second, genes change or repurpose functions, complicating the transfer of knowledge. Many approaches address this problem by expanding the notion of homology by leveraging high-throughput genomic and proteomic measurements, such as through network alignment. In this work, we take a new approach to transferring knowledge across species by expanding the notion of homology through explicit measures of functional similarity between proteins in different species. Specifically, our kernel-based method, HANDL (Homology Assessment across Networks using Diffusion and Landmarks), integrates sequence and network structure to create a functional embedding in which proteins from different species are embedded in the same vector space. We show that inner products in this space and the vectors themselves capture functional similarity across species, and are useful for a variety of functional tasks. We perform the first whole-genome method for predicting phenologs, generating many that were previously identified, but also predicting new phenologs supported from the biological literature. We also demonstrate the HANDL embedding captures pairwise gene function, in that gene pairs with synthetic lethal interactions are significantly separated in HANDL space, and the direction of separation is conserved across species. (Software for the HANDL algorithm is available at http://bit.ly/lrgr-handl.)
Physiological Basis of Transcranial Direct Current Stimulation

Since the rediscovery of transcranial direct current stimulation (tDCS) about 10 years ago, interest in tDCS has grown exponentially. A noninvasive stimulation technique that induces robust excitability changes within the stimulated cortex, tDCS is increasingly being used in proof-of-principle and stage IIa clinical trials in a wide range of neurological and psychiatric disorders. Alongside these clinical studies, detailed work has been performed to elucidate the mechanisms underlying the observed effects. In this review, the authors bring together the results from these pharmacological, neurophysiological, and imaging studies to describe their current knowledge of the physiological effects of tDCS. In addition, the theoretical framework for how tDCS affects motor learning is proposed.
Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46

Natural killer (NK) cells contribute to a variety of innate immune responses to viruses, tumors and allogeneic cells. However, our understanding of NK cell biology is severely limited by the lack of consensus phenotypic definition of these cells across species, by the lack of specific marker to visualize them in situ, and by the lack of a genetic model where NK cells may be selectively ablated. NKp46/CD335 is an Ig-like superfamily cell surface receptor involved in human NK cell activation. In addition to human, we show here that NKp46 is expressed by NK cells in all mouse strains analyzed, as well as in three common monkey species, prompting a unifying phenotypic definition of NK cells across species based on NKp46 cell surface expression. Mouse NKp46 triggers NK cell effector function and allows the detection of NK cells in situ. NKp46 expression parallels cell engagement into NK differentiation programs because it is detected on all NK cells from the immature CD122+NK1.1+DX5− stage and on a minute fraction of NK-like T cells, but not on CD1d-restricted NKT cells. Moreover, human NKp46 promoter drives NK cell selective expression both in vitro and in vivo. Using NKp46 promoter, we generated transgenic mice expressing EGFP and the diphtheria toxin (DT) receptor in NK cells. DT injection in these mice leads to a complete and selective NK cell ablation. This model paves a way for the in vivo characterization and preclinical assessment of NK cell biological function.
Airborne occupational allergic contact dermatitis from N,N‐bis[2‐bromo‐ethyl] aniline and N,N‐bis [2‐[(methylsulfonyl)‐oxy ]ethyl]aniline in a chemistry student

We here report a 57-year-old Caucasian female patient with a history of DTH to several heparins, who was admitted as an inpatient for treatment of venous ulcers. In the light of her history, the glycosaminoglycan danaparoid (Orgaran) was chosen for prophylactic anticoagulation, which was necessary because of immobility and obesity. Two days after the initial injections, the patient developed erythematous plaques and disseminating papulovesicles at the injection sites (Fig. 1). Assuming DTH to danaparoid, anticoagulation was switched to the low molecular weight selective factor-Xa-inhibitor fondaparinux (Arixtra, Sanofi-Synthelabo, Berlin, Germany; 2.5mg subcutaneously per day), because recent reports document absence of in vitro cross-reactivity with antibodies to heparin-platelet factor 4; these may be associated with allergic heparin-induced skin reactions (2, 3). Fondaparinux was well tolerated throughout the treatment period of 2 weeks. A comprehensive series of skin allergy tests was initiated 6 weeks after clearance of the patient’s skin lesions using undiluted original drugs. Several heparins yielded positive i.c. test results at days 4–8 after injection of 0.1ml (undiluted drug, applied to the inner aspect of the lower left arm) with erythematous plaques developing at the injection sites (Table 1). A therapeutic dose of pentosan polysulfate was also injected subcutaneously, resulting in the formation of a similar lesion. In contrast, all skin tests with fondaparinux remained negative, and re-exposure 4 weeks after termination of the treatment was tolerated by the patient.
Low-dimensional Res2/C composite as effective hydrodesulfurization catalyst

Single-layer, ultrasmall ReS2 nanoplates embedded in amorphous carbon were synthesized from a hydrothermal treatment involving ammonium perrhenate, thiourea, tetraoctylammonium bromide, and further annealing. The rhenium disulfide, obtained as a low dimensional carbon composite (ReS2/C), was tested in the hydrodesulfurization of light hydrocarbons, using 3-methylthiophene as the model molecule, and showed enhanced catalytic activity in comparison with a sulfide CoMo/γ-Al2O3 catalyst. The ReS2/C composite was characterized by X-ray diffraction (XRD), Raman spectroscopy, N2 adsorption–desorption isotherms, scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). The improved catalytic performance of this ReS2/C composite may be ascribed to the presence of a non-stoichiometric sulfur species (ReS2−x), the absence of stacking along the c-axis, and the ultra-small basal planes, which offer a higher proportion of structural sulfur defects at the edge of the layers, known as a critical parameter for hydrodesulfurization catalytic processes.
Magnetic resonance angiography of collateral vessel growth in a rabbit femoral artery ligation model

Collateral vessel growth was visualized in a rabbit femoral artery ligation model by serial contrast‐enhanced magnetic resonance angiography (MRA) at 1.5 T in comparison with X‐ray angiography (XRA). XRA and MRA were performed directly after femoral artery ligation (day 0+) and after 7 and 21 days. XRA (in‐plane resolution, 0.3×0.3 mm) was performed with arterial catheterization for fast injection of iodinated contrast agent just proximal to the aortic bifurcation. MRA (in‐plane, 0.6×0.6 mm) was performed at 1.5 T with a five‐element phased‐array coil and slow injection of gadolinium‐based MR contrast agent into an ear vein. Collateral vessel scores on two‐dimensional XRA projections and on three‐dimensional digitally subtracted rotational MRA maximum intensity projections were obtained by two observers and compared. Collateral vessel counts and minimal detectable vessel diameters for MRA and XRA were combined in a computational flow model to interpret differences in spatial detection limits between imaging modalities in terms of flow. Collateral vessel scores were significantly higher in the ligated limb at day 7 (P < 0.05) and more so at day 21 (P < 0.001), in comparison with day 0+ or in the non‐ligated control limb on both XRA and MRA. Significantly more (smaller) vessels were visualized with XRA than with MRA, particularly on day 21 (P < 0.05). Inter‐observer agreement was high for both XRA (κ = 0.82) and MRA (κ = 0.78). The flow model showed that collateral vessels with diameters > 0.3 mm scored by XRA as well as MRA represent nearly 100% of the total blood flow, whereas smaller (0.1–0.3 mm diameter) vessels that can only be detected with XRA contribute little to the blood flow. Serial contrast‐enhanced MRA can non‐invasively visualize sub‐millimeter collateral vessels that represent nearly 100% of the restored blood flow, in a femoral artery ligation model. Copyright © 2006 John Wiley & Sons, Ltd.
Interior Carbonization Patterns as Evidence of Ritual Drink Preparation in Powell Plain and Ramey Incised Vessels

Abstract Powell Plain and Ramey Incised jars are considered to be hallmarks of the Mississippian period at Cahokia, but the actual function of the vessels has not been adequately addressed. This study sought to determine the typical use of both vessel types as indicated by carbonization present on the interior and exterior of the vessel surfaces. Traces of carbonization were identified, and distinct patterns were correlated with cooking behavior. Interior carbonization patterns were the most telling, indicating the preparation of beverages or medicines using a cooking process called “decoction. ” In combination with the ceremonial nature of the vessels, the jars with discernible use-alteration evidence indicate that both vessel types were employed almost exclusively for the purpose of ritual drink preparation.
Value-Risk Tradeoffs and Managerial Incentives

Moral hazard theory posits that managerial risk aversion imposes agency costs on shareholders, and firms respond by providing risk-taking incentives to mitigate these costs. An underlying assumption in this literature is that increasing shareholder value requires increasing risk, yet there is limited empirical evidence supporting this assumption or the role of such risk-return tradeoffs in incentive compensation design. Using measures based on the firm’s stock price, I find that shareholder value increases with risk, consistent with managerial risk aversion reducing shareholder value. I also find that firms implement compensation contracts with stronger risk-taking incentives when potential risk-related agency costs are more severe, particularly among firms where value increases with idiosyncratic rather than systematic risk and whose managers are more risk-averse. Overall, these results are consistent with firms designing executive compensation contracts to help manage risk-related agency costs. Additional findings highlight how the incentive effects of equity-based compensation depend on firms’ risk-return tradeoffs, providing one explanation for conflicting results in prior literature regarding how managers’ stock holdings affect their investment decisions.
Synthesis, Anti‐MRSA, and Anti‐VRE Activity of Hemin Conjugates with Amino Acids and Branched Peptides

The increasing prevalence of antibiotic‐resistant bacterial strains has necessitated the synthesis of novel antibacterial agents. It was previously shown that naturally occurring metalloporphyrin hemin possesses dark antibacterial activity against Gram‐positive bacteria. To improve hemin antibacterial activity, we synthesized a number of hemin conjugates with amino acids and branched peptides. Arginine‐containing hemin conjugates demonstrated high antibacterial activity against Gram‐positive bacteria including methicillin‐ and vancomycin‐resistant strains in vitro. Most of the synthesized conjugates showed low toxicity against human erythrocytes and leukocytes.
Stability and function of a putative microtubule-organizing center in the human parasite Toxoplasma gondii

The organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here, we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and discovered that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 (ΔkinesinAΔapr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live ΔkinesinAΔapr1 parasites, and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and to invade host cells, as well as decreased secretion of effectors important for these processes. Together, the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.
Photoprotective properties of 20(S)-protopanaxatriol, an aglycone of ginseng saponins: Protection from ultraviolet-B radiation-induced oxidative stress in human epidermal keratinocytes.

Ginsenosides are responsible for diverse pharmacological properties ascribed to ginseng, a plant used in traditional medicine. Ginsenosides are classified into three categories: Protopanaxadiol, protopanaxatriol (PPT) and oleanolic acid. As an aglycone of PPT-type ginsenosides, PPT exists in two stereoisomeric forms, 20(S)-PPT and 20(R)‑PPT. The 20(S)‑PPT stereoisomer is a major metabolic product of PPT‑type ginsenosides produced in the gastrointestinal tract. In the present study, 20(S)-PPT suppressed the elevation of reactive oxygen species in HaCaT cells following irradiation with ultraviolet (UV)‑B. In addition, 20(S)‑PPT inhibited UV‑B‑induced gelatinase activities of matrix metalloproteinase-2 and -9 in HaCaT cells, and suppressed UV‑B‑induced expression and secretion of these proteins. Accordingly, 20(S)‑PPT restored the total glutathione levels in UV‑B‑irradiated keratinocytes. Taken together, these data indicated that 20(S)‑PPT may possess photoprotective properties that combat the effects of UV‑B radiation.
Adherence to hand hygiene guidelines - significance of measuring fidelity.

AIMS AND OBJECTIVES The aim was to evaluate the usability of fidelity measures in compliance evaluation of hand hygiene. BACKGROUND Adherence to hand hygiene guidelines is important in terms of patient safety. Compliance measures seldom describe how exactly the guidelines are followed. DESIGN AND METHODS A cross-sectional observation study in a university hospital setting was conducted. Direct observation by trained staff was performed using a standardised observation form supplemented by fidelity criteria. A total of 830 occasions were observed in 13 units. Descriptive statistics (frequency, mean, percentages and range) were used as well as compliance rate by using a standard web-based tool. In addition, the binomial standard normal deviate test was conducted for comparing different methods used in evaluation of hand hygiene and in comparison between professional groups. RESULTS Measuring fidelity to guidelines was revealed to be useful in uncovering gaps in hand hygiene practices. The main gap related to too short duration of hand rubbing. Thus, although compliance with hand hygiene guidelines measured using a standard web-based tool was satisfactory, the degree of how exactly the guidelines were followed seemed to be critical. CONCLUSIONS Combining the measurement of fidelity to guidelines with the compliance rate is beneficial in revealing inconsistency between optimal and actual hand hygiene behaviour. RELEVANCE TO CLINICAL PRACTICE Evaluating fidelity measures is useful in terms of revealing the gaps between optimal and actual performance in hand hygiene. Fidelity measures are suitable in different healthcare contexts and easy to measure according to the relevant indicators of fidelity, such as the length of hand rubbing. Knowing the gap facilitates improvements in clinical practice.
Mapping of the vaccinia virus thymidine kinase gene by marker rescue and by cell-free translation of selected mRNA.

A selective plaque assay that uses thymidine kinase (TK)-deficient human 143 cells was developed to titer mixtures of TK(+) and TK(-) vaccinia virus. With this assay it could be shown that methotrexate-resistant TK(+) virus was formed in cells coinfected with TK(-) virus and wild-type virus DNA. By substituting vaccinia DNA fragments cloned in plasmids for virion DNA, this marker rescue system provided the basis for mapping the TK gene. Of the 15 HindIII fragments, only J could rescue five independently derived TK(-) mutants. This 5000-base-pair (bp) fragment maps approximately 80,000 bp from the left-end of the 180,000-bp vaccinia genome. Marker rescue could be detected with 18 ng or less of plasmid and was proportionate to DNA concentration. The resistance to methotrexate of the TK(+) recombinants was shown to be due to TK synthesis. Evidence that the HindIII J fragment contains the structural TK gene and not a regulatory element was demonstrated by the synthesis of active TK in a cell-free system programmed with mRNA selected by hybridization to the plasmid. Previous studies [Belle-Isle, H. , Venkatesan, S. & Moss, B. (1981) Virology 112, 306-317] indicated that mRNAs coding for three immediate early polypeptides with molecular weights of 41,000, 21,000, and 17,000 map within HindIII J. The mapping of the easily selectable vaccinia virus TK gene now opens the way to genetic manipulations that should increase our understanding of vaccinia virus gene expression and facilitate the use of vaccinia virus as an efficient cloning vector for foreign genes.
Readmission After Ileostomy Creation: Retrospective Review of a Common and Significant Event

Objective: To evaluate causes and predictors of readmission after new ileostomy creation. Background: New ileostomates have been reported to have higher readmission rates compared with other surgical patients, but data on predictors are limited. Methods: A total of 1114 records at 2 associated hospitals were reviewed to identify adults undergoing their first ileostomy. Primary outcome was readmission within 60 days of surgery. Multiple logistic regression was used to identify independent predictors; area under the receiver-operator characteristic curves (AUC) were used to evaluate age-stratified models in secondary analysis. Results: In all, 407 patients underwent new ileostomy; 58% had cancer, 31% IBD; 49% underwent LAR, 27% colectomy, and 14% proctocolectomy. Median length of stay was 8 days. Among the patients, 39% returned to hospital, and 28% were readmitted (n = 113) at a median of 12 days postdischarge. The most common causes of readmission were dehydration (42%), intraperitoneal infections (33%), and extraperitoneal infections (29%). Dehydration was associated with later, longer, and repeated readmission. Independent significant predictors of readmission were Clavien-Dindo complication grade 3 to 4 [odds ratio (OR) 6.7], Charlson comorbidity index (OR 1.4 per point), and loop stoma (OR 2.2); longer length of stay (OR 0.5) and age 65 years or older (OR 0.4) were protective. Cohort stratification above or below age 65 revealed that older patient readmissions were more predictable (AUC 0.84) with more preventable causes, whereas younger patient readmissions were difficult to predict or prevent (AUC 0.65). Conclusions: Readmissions are most commonly caused by dehydration, and are predicted by serious complications, comorbidity burden, loop stoma, shorter length of stay, and age. Readmissions in older patients are easier to predict, representing an important target for improvement.
Fusion Pore Dynamics and Insulin Granule Exocytosis in the Pancreatic Islet

Insulin secretion from intact mouse pancreatic islets was investigated with two-photon excitation imaging. Insulin granule exocytosis occurred mainly toward the interstitial space, away from blood vessels. The fusion pore was unusually stable with a lifetime of 1.8 seconds. Opening of the 1.4-nanometer-diameter pore was preceded by unrestricted lateral diffusion of lipids along the inner wall of the pore, supporting the idea that this structure is composed of membrane lipids. When the pore dilated to 12 nanometers, the granules rapidly flattened and discharged their contents. Thus, our methodology reveals fusion pore dynamics in intact tissues at nanometer resolution.
Na 1 /H 1 exchange in mosquito Malpighian tubules

Petzel, D. H. Na 1 /H 1 exchange in mosquito Malpighian tubules. Am 279: R1996–R2003, 2000. — Fluid secretion and intracellular pH were measured in isolated mosquito Malpighian tubules to determine the presence of Na 1 /H 1 exchange. Rates of ﬂuid secretion by individual Malpighian tubules in vitro were inhibited by 78% of control in the presence of 100 m M 5-( N -ethyl- n -isopropyl)-amiloride (EIPA), a speciﬁc inhibitor of Na 1 /H 1 exchange. Steady-state intracellular pH was measured microﬂuorometrically by using 2 9 ,7 9 -bis(2-carboxy-ethyl)-5(6)-carboxyﬂuorescein in individual Malpighian tubules. Bathing the Malpighian tubules in 0 mM extracellular Na 1 or in the presence of 100 m M EIPA reduced the steady-state intracellular pH by 0.5 pH units. Stimulation of the Na 1 /H 1 exchanger by using the NH 4 Cl pulse technique resulted in a rate of recovery from the NH 4 Cl-induced acute acid load of 8.7 6 1.0 3 10 2 3 pH/s. The rates of recovery of intracellular pH after the acute acid load in the absence of extracellular Na 1 or in the presence of 100 m M EIPA were 0.7 6 0.6 and 2 0.3 6 0.3 3 10 2 3 pH/s, respectively. These results indicate that mosquito Malpighian tubules possess a Na 1 /H 1 exchanger. ;
New advances in the pharmacological management of chronic heart failure

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. β-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents - all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).