Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-Function Analyses of a Caffeic Acid O-Methyltransferase from Perennial Ryegrass Reveal the Molecular Basis for Substrate Preference[W][OA]

Caffeic acid O-methyltransferase (COMT) is a key enzyme in the biosynthesis of monolignols, the building blocks of plant lignins. New crystallographic analyses of unliganded and product-bound forms of COMT detail (1) the closed conformational state that productively assembles reactant molecules within the enzyme’s active site and (2) the molecular bases for substrate preferences of the COMTs. Lignin forms from the polymerization of phenylpropanoid-derived building blocks (the monolignols), whose modification through hydroxylation and O-methylation modulates the chemical and physical properties of the lignin polymer. The enzyme caffeic acid O-methyltransferase (COMT) is central to lignin biosynthesis. It is often targeted in attempts to engineer the lignin composition of transgenic plants for improved forage digestibility, pulping efficiency, or utility in biofuel production. Despite intensive investigation, the structural determinants of the regiospecificity and substrate selectivity of COMT remain poorly defined. Reported here are x-ray crystallographic structures of perennial ryegrass (Lolium perenne) COMT (Lp OMT1) in open conformational state, apo- and holoenzyme forms and, most significantly, in a closed conformational state complexed with the products S-adenosyl-l-homocysteine and sinapaldehyde. The product-bound complex reveals the post-methyl-transfer organization of COMT’s catalytic groups with reactant molecules and the fully formed phenolic-ligand binding site. The core scaffold of the phenolic ligand forges a hydrogen-bonding network involving the 4-hydroxy group that anchors the aromatic ring and thereby permits only metahydroxyl groups to be positioned for transmethylation. While distal from the site of transmethylation, the propanoid tail substituent governs the kinetic preference of ryegrass COMT for aldehydes over alcohols and acids due to a single hydrogen bond donor for the C9 oxygenated moiety dictating the preference for an aldehyde.
IN-OPERANDO ELECTRON MICROSCOPY AND SPECTROSCOPY OF INTERFACES THROUGH GRAPHENE-BASED MEMBRANES

Title of dissertation: IN-OPERANDO ELECTRON MICROSCOPY AND SPECTROSCOPY OF INTERFACES THROUGH GRAPHENE-BASED MEMBRANES Alexander Yulaev, Doctor of Philosophy, 2017 Dissertation directed by: Professor Marina S. Leite, Department of Materials Science and Engineering, Institute for Research in Electronics and Applied Physics, UMD Doctor Andrei Kolmakov, Center for Nanoscale Science and Technology, NIST Electron microscopy and spectroscopy (EMS) techniques enable (near-) surface and interfacial characterization of a variety of materials, providing insights into chemical/electrochemical and morphological information with nanoscale spatial resolution. However, the experimental realization of EMS in liquid/gaseous samples becomes problematic due to their incompatibility with high vacuum (HV) conditions. To perform EMS under elevated pressure conditions, electron transparent membranes made of thin C, SiO2 or/and Si3N4 are implemented to isolate a liquid/gas sample from HV environment. Nevertheless, even a few ten nanometerthick membrane deteriorates signal quality due to significant electron scattering. The other challenge of EMS consists in inaccessibility to probe solid state interfaces, e.g. solid-state Li-ion batteries, which makes their operando characterization problematic, limiting the analysis to ex situ and postmortem examination. The first part of my thesis focuses on developing an experimental platform for operando characterization of liquid interfaces through electron transparent membranes made of graphene (Gr)/graphene oxide (GO). The second part is dedicated to probing Li-ion transport at solid-state-battery surfaces and interfaces using ultrathin carbon anodes. I demonstrated the capability of GO to encapsulate samples with different chemical, physical, and biological properties and characterized them using EMS methods. I proposed and tested a new CVD-Gr transfer method using anthracene as a sacrificial layer. Characterization of transferred Gr revealed the advantages of our route with respect to a standard polymer based approach. A novel platform made of an array of Gr-capped liquid filled microcapsules was developed, allowing for a wide field of view EMS. I showed the capability of conducting EMS analysis of liquid interfaces through Gr membranes using energy-dispersive X-ray spectroscopy, photoemission electron microscopy, and Auger electron spectroscopy. Using operando SEM and AES, I elucidated the role of oxidizing conditions and charging rate on Li plating morphology in all-solid-state Li-ion batteries with thin carbon anodes. Operando EMS characterization of Li-ion transport at battery interfaces with carbon or Gr anodes will provide valuable insights into safe all-solid-state Li-ion battery with enhanced performance. IN-OPERANDO ELECTRON MICROSCOPY AND SPECTROSCOPY OF INTERFACES THROUGH GRAPHENE-BASED MEMBRANES
Evidence from basic research for opioid combinations

Introduction: Single opioid analgesics are modestly effective in reducing pain but have a narrow therapeutic index and frequently produce intolerable side effects. Adjuvant analgesics are often used to improve the opioid therapeutic index. Basic science research has accumulated evidence that opioid combinations in animal models and in vitro have potential to improve the therapeutic index of opioids and/or prevent opioid tolerance. Areas covered: Opioid receptor pharmacology is reviewed including receptor genetics and downstream signaling. Receptor functional selectivity and ligand biased responses are discussed in relationship to opioid pharmacodynamics, signal modulation and synergy. The accumulated bench research over the past decade, in particular, provides a rationale for considering clinical trials of opioid combinations. These combinations include both selective agonist–agonist or agonist–antagonist pairs which are reviewed. Expert opinion: The use of opioid antagonists (naloxone and naltrexone), oxycodone, fentanyl and methadone with morphine improves analgesia in animal models and blunts physical dependence and conditioned place preference (a marker for psychological dependence). Sequential or simultaneous dosing schedules, dose levels or ratios need to be explored further. Pain phenotype may be an important factor predicting responses to combinations such that trial design will need to take this into account. Side effects will need to be monitored closely as little is known about the influence of opioid combinations on side effects.
Modeling of North Pacific Climate Variability Forced by Oceanic Heat Flux Anomalies.

Abstract Potential predictability of low-frequency climate changes in the North Pacific depends on two main factors. The first is the sensitivity of the atmosphere to ocean-induced anomalies at the sea surface in midlatitudes. The second is the degree of teleconnectivity of the tropical low-frequency variability to midlatitudes. In contrast to the traditional approach of prescribing sea surface temperature (SST) anomalies, the response of a coupled atmospheric general circulation (CCM3)–mixed layer ocean model to oceanic perturbations of the mixed layer heat budget is examined. Since positive oceanic heat flux perturbations partially increase SST anomalies (locally), and partially are vented directly into the atmosphere, expressing boundary forcing on the atmosphere by prescribing upper-ocean heat flux anomalies allows for better understanding of the physical mechanism of low-frequency variability in midlatitudes. In the framework of this approach SST is considered to be a part of the adjustment of the co.
Angular-dependent interatomic potential for the binary Ni–Cr system

A new interatomic potential has been developed for the Ni–Cr system in the angular-dependent potential (ADP) format by fitting the potential parameters to a set of experimental and first-principles data. The ADP potential reproduces a wide range of properties of both elements as well as binary alloys with reasonable accuracy, including thermal and mechanical properties, defects, melting points of Ni and Cr, and the Ni–Cr phase diagram. The potential can be used for atomistic simulations of solidification, mechanical behavior and microstructure of the Ni-based and Cr-based phases as well as two-phase alloys.
The role of drag in insect hovering

SUMMARY Studies of insect flight have focused on aerodynamic lift, both in quasi-steady and unsteady regimes. This is partly influenced by the choice of hovering motions along a horizontal stroke plane, where aerodynamic drag makes no contribution to the vertical force. In contrast, some of the best hoverers– dragonflies and hoverflies – employ inclined stroke planes, where the drag in the down- and upstrokes does not cancel each other. Here, computation of an idealized dragonfly wing motion shows that a dragonfly uses drag to support about three quarters of its weight. This can explain an anomalous factor of four in previous estimates of dragonfly lift coefficients, where drag was assumed to be small. To investigate force generation and energy cost of hovering flight using different combination of lift and drag, I study a family of wing motion parameterized by the inclined angle of the stroke plane. The lift-to-drag ratio is no longer a measure of efficiency, except in the case of horizontal stroke plane. In addition, because the flow is highly stalled, lift and drag are of comparable magnitude, and the aerodynamic efficiency is roughly the same up to an inclined angle about 60°, which curiously agrees with the angle observed in dragonfly flight. Finally, the lessons from this special family of wing motion suggests a strategy for improving efficiency of normal hovering, and a unifying view of different wing motions employed by insects.
Persistent complex bereavement disorder in caregivers of terminally ill patients undergoing supportive-expressive treatment: a pilot study

Abstract Background: The proposal of persistent complex bereavement disorder (PCBD) in the DSM-V increased the interest on the impact of grief on the psychological health. Aims: Investigating the time course of psychological symptoms, emotional and social abilities in caregivers (undergoing or not to supportive-expressive treatment) of terminally ill cancer patients from 1 months before loss to 14 months after it. Method: Thirty-three of 60 caregivers were assessed by PG-12, HAM-A, HAM-D, TAS-20 and ASQ, at the admission in Hospice, and after 3, 10 and 14 months from the loss. Twelve caregivers adhered to follow a supportive-expressive treatment and 21 caregivers did not. Results: PG-12, anxiety, and depression scores decreased in both groups over time. The score of difficulty in identifying emotions and confidence with closeness decreased significantly only in the treated-group. PG-12 score at T0 was able to predict the DSM V diagnosis of PCBD at T3. Conclusions: Findings showed a decrease of the anxiety, depression, security in the attachment style and an increase of the ability to identify emotions during the first year after loss in caregivers of terminally ill cancer patients. Pre-loss assessment of prolonged grief risk seems useful to predict the diagnosis of PCBD 1 year after loss.
Early Paternal Deprivation Alters Levels of Hippocampal Brain-Derived Neurotrophic Factor and Glucocorticoid Receptor and Serum Corticosterone and Adrenocorticotropin in a Sex-Specific Way in Socially Monogamous Mandarin Voles

In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels.
Ameliorative effect of Elaeocarpus ganitrus on gentamicin-induced nephrotoxicity in rats

Objectives: The present study was designed to evaluate the ameliorative effect of Elaeocarpus ganitrus on gentamicin (GM)-induced nephrotoxicity in rats. Materials and Methods: E. ganitrus (100, 200, and 400 mg/kg body weight) was administered orally to male Wistar rats. GM (100 mg/kg) was used to induce nephrotoxicity. Study parameters include serum albumin, creatinine, blood urea nitrogen (BUN), uric acid, creatinine, and albuminuria. Total protein in serum, antioxidant enzymes activities, phagocytic index, and neutrophil adhesion assays were performed to determine oxidative stress and immunomodulatory action of E. ganitrus. Results: The results revealed that coadministration of E. ganitrus significantly reduced the elevated level of serum creatinine, BUN, uric acid, and albuminuria with considerable increase in the serum albumin and urine creatinine. Furthermore, E. ganitrus noticeably increased serum total protein and antioxidant enzyme levels with significant alteration in phagocytic index and neutrophil adhesion assay when compared with GM-treated group in a dose-dependent manner. Conclusion: The present study revealed that ethanolic extract of E. ganitrus seeds has immunomodulatory and nephroprotective activity.
Can two-sided messages increase the helpfulness of online reviews?

Purpose – Online reviews are increasingly available for a wide range of products and services. Several studies have demonstrated the benefits of the presence of customer reviews to an online retailer, but the issue of what makes online reviews helpful to a consumer in the process of making a purchase decision remains uninvestigated. The paper aims to discuss this issue. Design/methodology/approach – Given the strategic potential of online reviews, this study drew on past research to develop a conceptual understanding of the components of helpfulness and to further empirically test the model using actual online review data from iPeen.com in Taiwan. A content analysis of 989 reviews across four products identified the interplay effects of review sidedness, reviewer’s expertise, and product type on the helpfulness of an online review. Findings – For search goods, consumers consider two-sided reviews to be more helpful than one-sided reviews when the reviewers are experts in writing such articles, whereas the.
A Case of 36-Year-Old Woman With Recurrent Hypoglycemia Due to Insulinoma With Cytokeratin-19 Expression: A Marker of Poor Prognosis

lipase elevation and IBD activity index or C-reactive protein (a marker of inflammation). Proposed explanations for this asymptomatic hyperlipasemia included latent extraintestinal involvement of the pancreas, extrapancreatic release of lipase from the inflamed bowel, and intestinal reabsorption of released lipase in the inflamed bowel. Autoimmune pancreatitis (AIP) can also complicate IBD, with AIP conferring a 12to 15-fold increased risk for IBDwhen compared with the general population. It is possible that in a subgroup of patients with increased IgG4 in colonic mucosal specimens, the colitis may be an extrapancreatic manifestation of AIP mimicking IBD. Notably, in our patient population, IgG4 was only examined in 1 patient and was normal, making AIP an unlikely explanation for hyperlipasemia in that patient. Another possible explanation of hyperlipasemia is macrolipasemia, a complex of lipase with other proteins, usually immunoglobulins. None of the patients in our cohort were studied for macrolipasemia; therefore, it is unclear whether this etiology is contributing to hyperlipasemia in this setting. In our population of pediatric patients with IBD, we have shown that hyperlipasemia is a relatively common finding (20% of patients). We have also observed the difficulties of accurately diagnosing acute pancreatitis in the setting of pediatric IBD, given the overlap of symptoms in both conditions. On the basis of our observations, we conclude that hyperlipasemia may most often be a nonspecific complication of pediatric IBD. Therefore, we recommend careful consideration when diagnosing pancreatitis in pediatric patients with IBD. Magnetic resonance imaging as the most sensitive diagnostic modality considerations for autoimmune pancreatitis and macrolipasemia may aid the final conclusions and the selection of therapeutic interventions.
Institute for Mathematical Physics Diffeomorphism Covariant Star Products and Noncommutative Gravity Diffeomorphism Covariant Star Products and Noncommutative Gravity

The use of a diffeomorphism covariant star product enables us to construct diffeomorphism invariant gravities on noncommutative symplectic manifolds without twisting the symmetries. As an example, we construct noncommutative deformations of all two-dimensional dilaton gravity models thus overcoming some difficulties of earlier approaches. One of such models appears to be integrable. We find all classical solutions of this model and discuss their properties.
Annexin A1: Novel roles in skeletal muscle biology

Annexin A1 (ANXA1, lipocortin‐1) is the first characterized member of the annexin superfamily of proteins, so called since their main property is to bind (i.e., to annex) to cellular membranes in a Ca2+‐dependent manner. ANXA1 has been involved in a broad range of molecular and cellular processes, including anti‐inflammatory signalling, kinase activities in signal transduction, maintenance of cytoskeleton and extracellular matrix integrity, tissue growth, apoptosis, and differentiation. New insights show that endogenous ANXA1 positively modulates myoblast cell differentiation by promoting migration of satellite cells and, consequently, skeletal muscle differentiation. This suggests that ANXA1 may contribute to the regeneration of skeletal muscle tissue and may have therapeutic implications with respect to the development of ANXA1 mimetics. J. Cell. Physiol. 227: 3007–3015, 2012. © 2011 Wiley Periodicals, Inc.
Drug treatment of depression: reflections on the evidence

Guidelines are readily available for the treatment of depression, and more recent ones are explicitly evidence-based. Their core messages vary little but they tend to minimise uncertainties and gloss over difficult areas. This article examines three areas of uncertainty: the thresholds of severity and, for milder depression, the duration of illness for which antidepressants are more effective than placebo; the next step in drug treatment when a patient has failed to respond adequately to a first antidepressant; and how long continuing on antidepressants should be recommended in relation to individual patients’ needs. It is concluded that the uncertainties in relation to treating individual patients are a combination of lack of evidence and individual patient factors but there is also an intrinsic uncertainty that will continue to require good clinical judgement.
Improvement of parametric stability margin under pole assignment

The improvement of the parametric stability margin of state space uncertain systems via a maximization formulation under the constraints of pole assignment is investigated. The class of systems considered is where the uncertainty may be modeled as the, possibly nonlinear, variation of a parameter appearing in the entries of the system and input matrices. The continuity and differentiability properties of the stability margin are discussed. A gradient-based approach is presented for the improvement of the stability margin and a compact formula to compute the gradient is provided. Numerical examples are used to demonstrate the effectiveness of the approach.
Validity of haptic cues and its effect on priming visual spatial attention

This study investigated cross-modal links in attention between haptics and vision. A visual change-detection task was used as a measure of visual attention. Haptic taps on the back was used to prompt the user the visual quadrant within which changes occurred. The location of the haptic cues was consistent with the quadrant of the visual changes on either 80% or 20% of the trials. Ten subjects were randomly assigned to the two test conditions. The subjects were informed of the validity of the haptic cues before the experiments. We measured the effectiveness of haptic cues in terms of the changes in detection times in the visual task. Our results indicated that for the subjects in the 80% validity group, detection times decreased significantly with valid haptic cues, and increased significantly with invalid haptic cues. For the subjects in the 20% validity group, however, the results were less consistent. Some of the subjects benefited from haptic cues, while others managed to ignore the (mostly invalid) haptic cues. These results are interpreted as evidence that the use of haptic cues to reorient a person's visual spatial attention is natural and intuitive when the validity of the haptic cues is high. It is also concluded that the observed cross-modal attentional links between haptics and vision may involve a voluntary shift in attention as supposed to a purely involuntary mechanism.
An analysis of culture as a tourism commodity.

The notion of culture has been the object of multidisciplinary studies attempting, with difficulty, to define this polyhedral social concept expressed in symbolic representations. Culture has a significant role in tourism functioning as an internationally promoted commodity, a role that has often been the subject of debates among academics concerned about the vilification of culture’s primary social role. This article analyzes the complexity of the concept of culture in combination with the characteristics of a product, as conceived in marketing, focusing on the levels of product theory from Kotler and Armstrong. The research is based on secondary data analysis in the discussion. This incorporates culture’s symbolic representations, its tangibility and intangibility, its multiplicity of interpretations and meanings, the ambiguous status of ownership by the buyer and its versatility to satisfy consumers’ needs while functioning as a unit of identification for a society. As a product culture presents a unique configuration with a construct of four different dimensions highlighting the need for special consideration in culture’s marketing process. The research could also be considered as a platform for future investigations on the subject and as supporting material in education. Key words: Cultu