Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Water in Ligand Binding to Maltose-Binding Protein: Insight from a New Docking Protocol Based on the 3D-RISM-KH Molecular Theory of Solvation

Maltose-binding protein is a periplasmic binding protein responsible for transport of maltooligosaccarides through the periplasmic space of Gram-negative bacteria, as a part of the ABC transport system. The molecular mechanisms of the initial ligand binding and induced large scale motion of the protein's domains still remain elusive. In this study, we use a new docking protocol that combines a recently proposed explicit water placement algorithm based on the 3D-RISM-KH molecular theory of solvation and conventional docking software (AutoDock Vina) to explain the mechanisms of maltotriose binding to the apo-open state of a maltose-binding protein. We confirm the predictions of previous NMR spectroscopic experiments on binding modes of the ligand. We provide the molecular details on the binding mode that was not previously observed in the X-ray experiments. We show that this mode, which is defined by the fine balance between the protein-ligand direct interactions and solvation effects, can trigger the protein's domain motion resulting in the holo-closed structure of the maltose-binding protein with the maltotriose ligand in excellent agreement with the experimental data. We also discuss the role of water in blocking unfavorable binding sites and water-mediated interactions contributing to the stability of observable binding modes of maltotriose.
Autologous HSCT for advanced MS: is the glass half-empty or really half-full?

Sir, On the basis of persisting demyelination and axonal degeneration in brains of patients with progressive multiple sclerosis (MS), Metz et al. (2007) concluded that ‘autologous hematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration’. This was based on routine and immunohistochemical stains of brains from five patients who died at a median of 2 (range 0.5–18) months after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic stem cell transplantation (HSCT). Although this small series of autopsy cases contributed significant and interesting insights, the conclusion in the title would appear to be an overstatement of what is actually in evidence. In a ‘Scientific Commentary’ in response to Metz et al. , Martin (2007) also noted limitations in the study, including the small size of the series and that four of the five patients died early after the intervention. A general concern regarding the examination of biopsy or autopsy materials from patients to evaluate the effectiveness of therapeutic interventions has been that it provides only a single time point for each patient assessment. …
Phosphorylation of Nedd4‐2 by Sgk1 regulates epithelial Na+ channel cell surface expression

The epithelial Na+ channel (ENaC) plays an essential role in the regulation of whole body Na+ balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (α, β and γENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone‐induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4‐2 in a PY motif‐dependent manner and phosphorylates Nedd4‐2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4‐2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4‐2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone‐dependent regulation of ENaC.
Subcircuit Compact Model for Dopant-Segregated Schottky Gate-All-Around Si-Nanowire MOSFETs

In this paper, we demonstrate analytical device models and a unique subcircuit approach to physically and accurately model the dopant-segregated Schottky (DSS) gate-all-around (GAA) Si-nanowire (SiNW) MOSFETs. The direct current characteristics of the DSS GAA SiNW MOSFETs are investigated through numerical simulations and fabricated devices. Transport mechanisms are studied and explained with numerical devices from ambipolar thermionic tunneling to unipolar drift-diffusion and a combination of both as the dopant segregation doping and thickness are varied. The convex curvature in the Ids- Vds characteristics is accurately reproduced by the subcircuit compact model, and it is shown for the first time that such a unique gds-Vds characteristic in DSS devices is only feasible to be modeled by the subcircuit approach.
Serum LDH and exercise capacity in COPD

A 48-year-old man with rheumatoid arthritis (RA) was admitted with shortness of breath due to bronchospasm and hypoxaemia (Pao2 5.9 kPa (44 mm Hg)). He had no history of pulmonary disease or allergy/atopy. About 3 years before this admission he was treated with infliximab. He was switched from infliximab to etanercept because of its more convenient subcutaneous form of administration. He was switched from etanercept to adalimumab because his RA persistently flared on the former treatment. Three days before admission he had received adalimumab for the second time. Blood count showed a new eosinophilia of 0.8×109/l (normal range 0–0.4). He …
Dietary polyphenolic phytochemicals—promising cancer chemopreventive agents in humans? A review of their clinical properties

Epidemiological and preclinical evidence suggests that polyphenolic phytochemicals exemplified by epigallocatechin gallate from tea, curcumin from curry and soya isoflavones possess cancer chemopreventive properties. Whilst such naturally occurring polyphenols have been the subject of numerous mechanistic studies in cells, information on their clinical properties, which might help assess their promise as human cancer chemopreventive agents, is scarce. Therefore, we present a review of pilot studies and trials with a cancer chemoprevention‐related rationale, in which either healthy individuals or patients with premalignant conditions or cancer received polyphenolic phytochemicals. The review identifies trial design elements specifically applicable to polyphenolic phytochemicals. The available evidence for tea polyphenols tentatively supports their advancement into phase III clinical intervention trials aimed at the prevention of progression of prostate intraepithelial neoplasia, leukoplakia or premalignant cervical disease. In the case of curcumin and soya isoflavones more studies in premalignacies seem appropriate to optimise the nature and design of suitable phase III trials. The abundance of flavonoids and related polyphenols in the plant kingdom makes it possible that several hitherto uncharacterised agents with chemopreventive efficacy are still to be identified, which may constitute attractive alternatives to currently used chemopreventive drugs. © 2006 Wiley‐Liss, Inc.
Synthese von Zustands- und Ausgangsrückführungen für rekurrente Fuzzy-Systeme

Zusammenfassung Als spezielle Klasse dynamischer Fuzzy-Systeme bieten rekurrente Fuzzy-Systeme die Möglichkeit, dynamische Prozesse anhand von Expertenwissen oder Messdaten zu modellieren. Dabei zeichnet sich die Regelbasis durch die Möglichkeit der linguistischen Interpretierbarkeit und somit der Transparenz aus. Dieser Artikel stellt Ansätze vor, mit denen sowohl (beobachterbasierte) Zustands- als auch Ausgangsrückführungen zur Stabilisierung bekannter Ruhelagen mit Hilfe bilinearer Matrixungleichungen ausgelegt werden können. Die sich ergebenden Regler sind dabei strukturell äquivalent zu Fuzzy-Reglern und können somit ebenfalls linguistisch interpretiert werden. Hinsichtlich der Ausgangsrückführungen wird gezeigt, dass sich bekannte Syntheseansätze aus der linearen Systemtheorie ebenfalls auf Ausgangsrückführungen für rekurrente Fuzzy-Systeme übertragen lassen.
An Electronic Commerce Recommendation Algorithm Joining Case-Based Reasoning and Collaborative Filtering

With the rapid development of network, information technology has provided an unprecedented amount of information resources. It has also led to the problem of information overload. Electronic commerce personalized recommender systems represent services that aim at predicting a customer's interest on information products available in the application domain, using customers' ratings on products. Peoples' experiences often do not enough to deal with the vast amount of available information. Thus, methods to help find products of electronic commerce have attracted much attention from both researchers and vendors. Collaborative filtering technology has proved to be one of the most effective for its simplicity in both theory and implementation. The paper gives an electronic commerce recommendation algorithm combining case-based reasoning and collaborative filtering. Firstly, it uses case-based reasoning to fill the vacant ratings. Then, it produces prediction collaborative filtering. The presented algorithm combining case-based reasoning and collaborative filtering can alleviate the sparsity issue.
Variation of Equilibrium Moisture Content of Heat-treated Couratari oblongifolia, Fraxinus excelsior, and Quercus rubra Wood

Heat treatment may result in variation of wood equilibrium moisture content (EMC). During this study, tauari (Couratari oblongifolia), ash (Fraxinus excelsior), and oak (Quercus rubra) woods were heat-treated at 190, 200, and 210oC for 3 hours and then put into a conditioning chamber with a temperature from 30 to 75oC and a relative humidity from 50 to 90%. The isothermal moisture adsorption curve was subsequently analyzed. Results indicated that the EMC of heat-treated wood was reduced by 23.4 to 37.4% compared to non-treated wood, but the EMC difference at different heat-treated temperatures for three hardwoods was quite small and the EMC of heat-treated wood was inversely proportional to their dry density.
NIACIN, AN OLD DRUG WITH NEW PERSPECTIVES FOR THE MANAGEMENT OF DYSLIPIDAEMIA

Abstract Niacin has been used for decades to treat dyslipidaemic disorders. Niacin is the most effective agent currently available for increasing levels of high-density lipoprotein. Moreover, significant improvements in cardiovascular outcomes in niacin treated patients have been demonstrated. However, tolerability concerns, particularly flushing, have limited its use in the past. Therefore, ER niacin, a prolonged-release formulation of niacin, has been developed with similar efficacy but a superior tolerability profile compared to the immediate-release formulations. Recent insights on niacin mechanisms of action have led to the development of a new agent called laropiprant. Laropiprant selectively blocks the binding of prostaglandin D2 to its receptor (DP1) in dermal capillaries, which mediates niacin-induced vasodilation. When co-administered with ER niacin, a marked reduction in ER niacin induced flushing is seen. The clinical use of niacin and the novel flush-reducing co-medication, will be discussed.
Therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back pain: cost utility analysis based on a randomized controlled trial

Background Related to escalating health care costs and the questionable effectiveness of multiple interventions including lumbar facet joint interventions, cost effectiveness or cost utility analysis has become the cornerstone of evidence-based medicine influencing coverage decisions. Methods Cost utility of therapeutic lumbar facet joint nerve blocks in managing chronic low back pain was performed utilizing data from a randomized, double-blind, controlled trial with a 2-year follow-up, with direct payment data from 2016. Based on the data from surgical interventions, utilizing the lowest proportion of direct procedural costs of 60%, total cost utility per quality adjusted life year (QALY) was determined by multiplying the derived direct cost at 1.67. Results Patients in this trial on average received 5.6 ± 2.6 procedures over a period of 2 years, with average relief over a period of 2 years of 82.8 ± 29.6 weeks with 19 ± 18.77 weeks of improvement per procedure. Procedural cost for one-year improvement in quality of life showed USD $2,654.08. Estimated total costs, including indirect costs and drugs with multiplication of direct costs at 1.67, showed a cost of USD $4,432 per QALY. Conclusions The analysis of therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back pain shows clinical effectiveness and cost utility at USD $2,654.08 for the direct costs of the procedures, and USD $4,432 for the estimated overall cost per one year of QALY, in chronic persistent low back pain non-responsive to conservative management.
Classification d'objets 3D par extraction aléatoire de sous-parties discriminantes pour l'étude du sous-sol en prospection pétrolière

Dans cet article, nous proposons une nouvelle approche de classification d'objets 3D inspiree des Time Series Shapelets de Lexiang Ye (2009). L'idee est d'utiliser des sous-surfaces discriminantes pour la classification concernee afin de prendre en compte la nature locale des elements pertinents. Cela permet a l'utilisateur d'avoir connaissance des sous-parties qui ont ete utiles pour determiner l'appartenance d'un objet a une classe. Les resultats obtenus confirment l'interet de la selection aleatoire de caracteristiques candidates pour la pre-selection d'attributs en classification supervisee.
The orb web during the life of Argiope aurantia (Lucas).

Changes in size, quantity, and regularity of detail were followed in the orb webs of Argiope aurantia Lucas for 8 laboratory-born females reared under controlled environmental conditions. Mesh width and the number of radii decreased steadily from the 3rd month of life to death. Thread length and area of web reached peaks around the time of the last molt and sexual maturation, and decreased thereafter. Leg length, weight, and molt, while related to web characteristics, do not account entirely for changes in dimensions. Furthermore, after several months under similarly controlled conditions, 6 females that had been caught outdoors built unusually large webs. The characteristic changes of Argiope aurantia webs in the laboratory appear to reflect not only physiological maturation and declinc, but may be related to early experience with the efficiency of the web as a trap.
Sporangium-Specific Gene Expression in the Oomycete Phytopathogen Phytophthora infestans

ABSTRACT The oomycete genus Phytophthora includes many of the world's most destructive plant pathogens, which are generally disseminated by asexual sporangia. To identify factors relevant to the biology of these propagules, genes induced in sporangia of the potato late blight pathogen Phytophthora infestans were isolated using cDNA macroarrays. Of ∼1,900 genes known to be expressed in sporangia, 61 were up-regulated >5-fold in sporangia versus hyphae based on the arrays, including 17 that were induced> 100-fold. A subset were also activated by starvation and in a nonsporulating mutant. mRNAs of some genes declined in abundance after germination, while others persisted through the germinated zoospore cyst stage. Functions were predicted for about three-quarters of the genes, including potential regulators (protein kinases and phosphatases, transcription factors, and G-protein subunits), transporters, and metabolic enzymes. Predominant among the last were several dehydrogenases, especially a highly expressed sorbitol dehydrogenase that accounted for 3% of the mRNA. Sorbitol dehydrogenase activity also rose during sporulation and several stress treatments, paralleling the expression of the gene. Another interesting metabolic enzyme resembled creatine kinases, which previously were reported only in animals and trypanosomes. These results provide insight into the transcriptional and cellular processes occurring in sporangia and identify potential targets for crop protection strategies.
The societal costs of alcohol misuse in Australia

It is well documented that alcohol-related problems compromise individual and social health, and wellbeing. The individual harms are numerous, including premature death, loss of enjoyment and loss of social utility through fear of crime and victimisation. The misuse of alcohol, particularly among those most at risk in our community, presents a major challenge for all levels of government. In this paper, a study is presented that provides a better national-level estimate of the costs of alcohol-related problems in Australia. Despite taking a conservative estimate, the aggregate of a range of societal costs substantially outweighs the tax revenue for the Commonwealth generated from the sale of alcohol. Results of this study provide evidence to policymakers regarding costs to the criminal justice system, costs to the health system, costs resulting from lost productivity and costs related to alcohol-related road accidents. Such evidence will provide an understanding of the economic tradeoffs that are present when making decisions that affect all Australians. Proposals are provided in the conclusion for a greater investment in prevention, based on the sound evaluation of prevention and diversion strategies by comparison with treatment options, in order to ensure better investments for the nation.
Good Figures

`̀ It is generally admitted that the foundations of our present knowledge of visual perception were laid in the laboratories of the gestalt psychologists _ . More specifically, from its beginnings gestalt psychology had a kinship to art. Art pervades the writings of MaxWertheimer,Wolfgang Ko« hler, and Kurt Koffka. Here and there the arts are explicitly mentioned, but what counts more is that the spirit underlying the reasoning of these men makes the artist feel at home. Indeed, something like an artistic vision of reality was needed to remind scientists that most natural phenomena are not described adequately if they are analyzed piece by piece. That a whole cannot be attained by the accretion of isolated parts was not something the artist had to be told. '' (Arnheim 1974, pages 4 ^ 5)
Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth*

Caveolae are plasma membrane-attached vesicular organelles. Caveolin-1, a 21–24-kDa integral membrane protein, is a principal component of caveolae membranes in vivo. Both caveolae and caveolin are most abundantly expressed in terminally differentiated cells: adipocytes, endothelial cells, and muscle cells. Conversely, caveolin-1 mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes such as v-abl and H-ras(G12V); caveolae are absent from these cell lines. However, its remains unknown whether down-regulation of caveolin-1 protein and caveolae organelles contributes to their transformed phenotype. Here, we have expressed caveolin-1 in oncogenically transformed cells under the control of an inducible-expression system. Regulated induction of caveolin-1 expression was monitored by Western blot analysis and immunofluorescence microscopy. Our results indicate that caveolin-1 protein is expressed well using this system and correctly localizes to the plasma membrane. Induction of caveolin-1 expression in v-Abl-transformed and H-Ras (G12V)-transformed NIH 3T3 cells abrogated the anchorage-independent growth of these cells in soft agar and resulted in the de novo formation of caveolae as seen by transmission electron microscopy. Consistent with its antagonism of Ras-mediated cell transformation, caveolin-1 expression dramatically inhibited both Ras/MAPK-mediated and basal transcriptional activation of a mitogen-sensitive promoter. Using an established system to detect apoptotic cell death, it appears that the effects of caveolin-1 may, in part, be attributed to its ability to initiate apoptosis in rapidly dividing cells. In addition, we find that caveolin-1 expression levels are reversibly down-regulated by two distinct oncogenic stimuli. Taken together, our results indicate that down-regulation of caveolin-1 expression and caveolae organelles may be critical to maintaining the transformed phenotype in certain cell populations.
Action of sympathomimetic drugs on the bronchial circulation of the horse

In the quietly standing horse I.V. administration of adrenaline decreased, and of dobutamine increased, bronchial artery flow. These changes paralleled changes in arterial pressure. With phenylephrine and noradrenaline bronchial artery flow decreased while arterial pressure increased, indicating active vasoconstriction in the bronchial circulation. With clenbuterol an increase in bronchial artery flow was accompanied by a decrease in systemic blood pressure, indicating bronchial arterial vasodilatation. We conclude that alpha‐constrictor and beta 2‐dilator receptors are present in the bronchial artery bed and that stimulation of these receptors could explain changes in flow seen in the horse during exercise and anaesthesia.
Indication for preoperative localization of small peripheral pulmonary nodules in thoracoscopic surgery.

OBJECTIVE Widespread clinical use of helical computed tomography has improved the detection rate for small peripheral pulmonary nodules. As a result, use of thoracoscopic surgery to confirm the diagnosis of small peripheral pulmonary nodules has become more important than ever before. However, if small peripheral pulmonary nodules are too small or located too deeply to detect thoracoscopically, it is necessary to mark the small peripheral pulmonary nodules preoperatively. The purpose of this study was to determine indications for preoperative hookwire marking in thoracoscopic resection of small peripheral pulmonary nodules. METHODS A total of 120 patients underwent thoracoscopic pulmonary resection in our institute from 1999 to 2001. Small peripheral pulmonary nodules were marked preoperatively in 61 of these patients by means of percutaneous placement of a hookwire under computed tomographic guidance. The hookwire-marked small peripheral pulmonary nodules either were smaller than 10 mm or were located more than 10 mm below the pleural surface. RESULTS Although 9 of the hookwire-marked small peripheral pulmonary nodules were easily identified during thoracoscopy, the other 52 small peripheral pulmonary nodules could not have been identified during thoracoscopy without the hookwire marking. Of the 59 small peripheral pulmonary nodules that were not hookwire marked, 7 required conversion to thoracotomy to locate the nodules. Small peripheral pulmonary nodules from both groups were examined and assigned to either an undetectable or detectable group. Discriminant function analysis indicated that a linear function (ie, depth = 0.836 x size - 2.811) could be used to differentiate between undetectable and detectable small peripheral pulmonary nodules, and preoperative hookwire marking for small peripheral pulmonary nodules should be considered for nodules in the region above those. CONCLUSION The results suggest that this formula might serve as an indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic resection.