Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic survey of metabolic pathways in rice

A systematic proteomic analysis of rice (Oryza sativa) leaf, root, and seed tissue using two independent technologies, two-dimensional gel electrophoresis followed by tandem mass spectrometry and multidimensional protein identification technology, allowed the detection and identification of 2,528 unique proteins, which represents the most comprehensive proteome exploration to date. A comparative display of the expression patterns indicated that enzymes involved in central metabolic pathways are present in all tissues, whereas metabolic specialization is reflected in the occurrence of a tissue-specific enzyme complement. For example, tissue-specific and subcellular compartment-specific isoforms of ADP-glucose pyrophosphorylase were detected, thus providing proteomic confirmation of the presence of distinct regulatory mechanisms involved in the biosynthesis and breakdown of separate starch pools in different tissues. In addition, several previously characterized allergenic proteins were identified in the seed sample, indicating the potential of proteomic approaches to survey food samples with regard to the occurrence of allergens.
Small Molecule Structure Correctors Abolish Detrimental Effects of Apolipoprotein E4 in Cultured Neurons*

Background: Apolipoprotein E4 (apoE4), the major gene involved in Alzheimer disease, has a unique structure, intramolecular domain interaction, that is associated with neuropathology. Results: Potent small molecule structure correctors block apoE4 domain interaction and reverse apoE4 detrimental effects in cultured neurons. Conclusion: Structure correctors negate the detrimental effects of apoE4 in neurons. Significance: ApoE4 structure correctors could represent a therapeutic approach for treating apoE4-associated neuropathology. Apolipoprotein E4 (apoE4), the major genetic risk factor for late onset Alzheimer disease, assumes a pathological conformation, intramolecular domain interaction. ApoE4 domain interaction mediates the detrimental effects of apoE4, including decreased mitochondrial cytochrome c oxidase subunit 1 levels, reduced mitochondrial motility, and reduced neurite outgrowth in vitro. Mutant apoE4 (apoE4-R61T) lacks domain interaction, behaves like apoE3, and does not cause detrimental effects. To identify small molecules that inhibit domain interaction (i.e. structure correctors) and reverse the apoE4 detrimental effects, we established a high throughput cell-based FRET primary assay that determines apoE4 domain interaction and secondary cell- and function-based assays. Screening a ChemBridge library with the FRET assay identified CB9032258 (a phthalazinone derivative), which inhibits domain interaction in neuronal cells. In secondary functional assays, CB9032258 restored mitochondrial cytochrome c oxidase subunit 1 levels and rescued impairments of mitochondrial motility and neurite outgrowth in apoE4-expressing neuronal cells. These benefits were apoE4-specific and dose-dependent. Modifying CB9032258 yielded well defined structure-activity relationships and more active compounds with enhanced potencies in the FRET assay (IC50 of 23 and 116 nm, respectively). These compounds efficiently restored functional activities of apoE4-expressing cells in secondary assays. An EPR binding assay showed that the apoE4 structure correction resulted from direct interaction of a phthalazinone. With these data, a six-feature pharmacophore model was constructed for future drug design. Our results serve as a proof of concept that pharmacological intervention with apoE4 structure correctors negates apoE4 detrimental effects in neuronal cells and could be further developed as an Alzheimer disease therapeutic.
What Do British Historical Data Tell Us About Government Spending Multipliers?

British data from the early 1700s through World War I reflect the results of numerous high‐quality natural experiments of government spending. Britain frequently participated in wars, increasing military spending massively. Wartime distortions were relatively limited because the government generally adopted tax smoothing policy and rarely implemented interventions. Government spending multiplier estimates are low or negative and significantly below unity. This paper finds no evidence that the multiplier was higher in the slack state than in the normal state. (JEL E32, E62)
Temporomandibular disorders: evidence for significant overlap with psychopathology.

Data were analyzed for 277 acute and chronic temporomandibular disorder (TMD) patients to determine if there was a relationship between psychological and physical diagnoses. A significant (p < .01) relationship existed among the following: combined past or current mood disorder-personality disorder and muscle disorder; combined current mood, anxiety, or substance use disorder-personality disorder and muscle disorder; and combined current anxiety disorder-personality disorder and muscle disorder. This study further confirmed other research that has found that significant psychopathology exists in TMD. More important, this psychopathology appears to be linked primarily to muscle disorders, as opposed to disc or joint disorders, within the rubric of TMD.
A strategy for the construction of double-stranded DNA microcircles with circumferences less than 50 bp.

A procedure for the construction of double-stranded DNA microcircles is described that overcomes the natural limits of established circularization procedures. The assembly strategy needs only three components, i.e. two synthetic oligonucleotides containing any sequence of interest and T4 DNA ligase. All components can be provided in large quantities and only two enzymatic reaction steps are required. Such microcircles can serve as a model for topologically fixed and highly bent DNA molecules and the amounts needed for X-ray crystallography, n.m. r. spectroscopy or drug binding studies can readily be produced. The construction of a 42 base pair double-stranded DNA microcircle is presented, by far the smallest double-stranded DNA circle yet described either in vivo or in vitro.
The role of granulocyte transfusions in neutropenic patients

The precise role for donor granulocyte infusions remains to be delineated, partly because of the lack of defined clinical trials. The aim of this article is to summarize the studies undertaken so far and highlight the logistical problems associated with undertaking future studies. We also aim to provide a practical guide to the application of this therapeutic approach.
Factors associated with refractory renal disease in patients with systemic lupus erythematosus: the role of patient nonadherence.

OBJECTIVE To assess the prevalence and underlying reasons for the development of chronic renal insufficiency (CRI) in patients with systemic lupus erythematosus (SLE) seen over a 3-year period in our lupus clinic, in particular to determine the frequency and types of patient-dependent factors that were associated with nonadherence when it occurred. METHODS We determined the frequency and types of patient-dependent factors that were associated with the development of CRI in patients with SLE. CRI was defined as a serum creatinine level > or = 200 mumol/l for at least 6 months. RESULTS Of the 462 patients followed at the lupus clinic between 1995 and 1998, 17 patients developed CRI. Patient-related factors were deemed to be the major reason for the development of CRI in 5 of these. Three of the 5 patients were nonwhite, and the 2 patients who were white were new immigrants. All 5 patients were reluctant to take high-dose corticosteroids because of potential adverse effects. Financial problems contributed to nonadherence in 2 cases. Two patients refused to continue steroids and immunosuppressive therapy and chose to use "alternative" medications as their sole therapy. Of these 5 patients, 3 are now on long-term renal replacement therapy, 1 has died, and 1 patient continues to be followed with a serum creatinine level of 250 mumol/l. CONCLUSION There is a need for an educational program based on patients' cultural background in order to enhance patients' understanding of the aims, risks, and benefits of therapy in SLE.
Detecting outliers in irregularly distributed spatial data sets by locally adaptive and robust statistical analysis and GIS

In this paper, we propose a new method for detecting outliers in an irregularly distributed spatial data set. Our method has two desirable properties. First, it is functionally effective due to the introduction of sensitive outlier indices and locally adaptive and robust statistical criteria. Second, it is computationally efficient because of the use of super-block based spatial data sorting and searching scheme. Our method has been implemented using the C programming language and integrated with the Arc/Info GIS system. The integration leads to a powerful exploratory data analysis tool for checking and analysing anomalous values in a GIS environment. Local outliers can be automatically labeled with our method, subject to some user-defined parameters. Outliers represent anomalous or suspicious values in a statistical sense, which may not necessarily be erroneous values. Instead of being simply discarded, statistical outliers should be investigated further using prior qualitative knowledge or in association with other GIS data layers.
Impaired Orthostatic Blood Pressure Recovery Is Associated with Unexplained and Injurious Falls

Cardiovascular disorders are recognized as important modifiable risk factors for falls. However, the association between falls and orthostatic hypotension (OH) remains ambivalent, particularly because of poor measurement methods of previous studies. The goal was to determine for the first time to what extent OH (and variants) are risk factors for incident falls, unexplained falls (UF), injurious falls (IF) and syncope using dynamic blood pressure (BP) measurements in a population study.
Volatility Premium and Term Structure of China Blue-Chip Index Options

ABSTRACT This article constructs China VIX with ETFs option data from SSE, HKEx, and CBOE, and investigates the corresponding volatility premiums and volatility term structures. We find that China’s volatility premiums exist in all the three markets with a specific pattern during and after the market crash, and they are highly similar and correlated. This pattern shows that volatility premiums are significantly negative during market crash and quickly rise to a large positive number after the crash, and then slowly decay until next crisis. Moreover, it suggests that investors should short volatility after market collapse rather than long it like most market participants did in the past. Despite the three volatility term structures show that implied volatilities generally decrease with the increasing of terms and rise sharply near the maturity dates, there is no such obvious pattern in the volatility term structure of SSE 50 ETF options due to the extremely imperfection of China’s option market.
ILr1β production is dependent on the activation of purinergic receptors and NLRP3 pathway in human macrophages

The Nod‐like receptor family protein 3 (NLRP3)‐inflammasome pathway is known to be activated by danger signals such as monosodium urate (MSU). We investigated the role of P2 purinergic receptors in the activation of NLRP3‐inflammasome pathway after MSU treatment of primary human monocyte‐derived macrophages (MDMs). After initial stimulation with a low concentration of LPS (0.1 μg/ml), a 6 h treatment with MSU crystals (250, 500, and 1000 μg/ml) induced the MDMs to release IL‐1β, IL‐1α, and IL‐6 in a dose‐dependent manner. Moreover, the caspase 1 inhibitor Z‐YVAD‐FMK and the cathepsin B inhibitor CA‐074Me reduced production of IL‐1β in a dose‐dependent manner after LPS + MSU treatment We used real‐time reverse transcription‐quantitative PCR to show that treatment with LPS and MSU (500 μg/ml) induced significantly greater expression of NLRP3 and IL‐1β than after treatment with LPS. We also found that MSU treatment induced P2X purinergic receptor 7 (P2X7R) mRNA and protein expression. Furthermore, addition of the P2X7 purinergic receptor antagonist A‐740003 significantly impeded IL‐1β production and pro‐IL‐1β cleavage after treatment with LPS + MSU. Remarkably, RNA silencing of P2X7R (but not P2X4R) inhibited the release of IL‐1β and other M1 macrophage cytokines (such as IL‐1α, IL‐6, and TNF‐α) from MDMs stimulated with LPS + MSU. Taken as a whole, our results show that P2 purinergic receptors and the NLRP3 inflammasome pathway are involved in the secretion of IL‐1β from MSU‐stimulated human macrophages. This pathway may constitute a novel therapeutic target for controlling the inflammatory process in several associated pathologies. —Gicquel, T. , Robert, S. , Loyer, P., Victoni, T. , Bodin, A. , Ribault, C. , Gleonnec, F. , Couillin, I. , Boichot, E. , Lagente, V. IL‐1β production is dependent on the activation of purinergic receptors and NLRP3 pathway in human macrophages. FASEB J. 29, 4162‐4173 (2015). www.fasebj. org
Nutrient density score of typical Indonesian foods and dietary formulation using linear programming

Abstract Objective The present research aimed to analyse the nutrient density (ND), nutrient adequacy score (NAS) and energy density (ED) of Indonesian foods and to formulate a balanced diet using linear programming. Design Data on typical Indonesian diets were obtained from the Indonesian Socio-Economic Survey 2008. ND was investigated for 122 Indonesian foods. NAS was calculated for single nutrients such as Fe, Zn and vitamin A. Correlation analysis was performed between ND and ED, as well as between monthly expenditure class and food consumption pattern in Indonesia. Linear programming calculations were performed using the software POM-QM for Windows version 3. Setting Republic of Indonesia, 2008. Subjects Public households (n 68 800). Results Vegetables had the highest ND of the food groups, followed by animal-based foods, fruits and staple foods. Based on NAS, the top ten food items for each food group were identified. Most of the staple foods had high ED and contributed towards daily energy fulfillment, followed by animal-based foods, vegetables and fruits. Commodities with high ND tended to have low ED. Linear programming could be used to formulate a balanced diet. In contrast to staple foods, purchases of fruit, vegetables and animal-based foods increased with the rise of monthly expenditure. Conclusions People should select food items based on ND and NAS to alleviate micronutrient deficiencies in Indonesia. Dietary formulation calculated using linear programming to achieve RDA levels for micronutrients could be recommended for different age groups of the Indonesian population.
Induction of human tumor‐loaded dendritic cells

A preferred anti‐cancer vaccine would be tumor‐specific, simple to rapidly construct and safe to administer. It would permit immunization against a spectrum of the tumor's distinctive antigens, without requiring their prior identification. Toward these goals, we describe a modification of standard extracorporeal photopheresis (ECP) which initiates, within a single day, both monocyte‐to‐dendritic cell (DC) differentiation and malignant cell apoptosis. The transition of monocytes to immature DCs was identified by the expression of cytoplasmic CD83 and membrane CD36 in the absence of membrane CD14 staining, as well as induction of membrane CD83 expression. Differentiating DCs were avidly phagocytic and engulfed apoptotic malignant T cells. Differentiating DCs were capable of stimulating significant proliferation of normal alloreactive lymphocyte responders, indicting increased expression of membrane MHC class II molecules. This approach provides a clinically practical means of developing tumor‐loaded cells that have initiated the transition to DCs without the requirement of exogenous cytokines, excessive cellular manipulation or isolation. Construction of DC vaccines using this methodology can be generalized to other diseases and may offer a novel approach for improved cancer immunotherapy. © 2001 Wiley‐Liss, Inc.
Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study

ABSTRACT Aim: The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin ± oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice. Methods: This was a large, multi-national, multi-centre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA1c < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5–10, 10–20 or ≥ 20 years) stratified by prior therapy. Results: After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA1c decreased ~ 2.2%-points versus ~ 1.6%-points, FPG decreased ~ 4.5 mmol/L versus ~ 2.9 mmol/L and PPPG decreased ~ 6.8 mmol/L versus ~ 5.0 mmol/L. Target HbA1c was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period. Conclusions: According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.
Linagliptin for the treatment of type 2 diabetes (pharmacokinetic evaluation)

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). The novel compound linagliptin has important different pharmacokinetic (PK) properties, when compared with previously commercialized DPP-4 inhibitors, which may offer some advantages in clinical practice. Linagliptin has a unique PK/pharmacodynamic (PD) profile and is the first DPP-4 inhibitor with a nonrenal elimination route. Therefore, it can be administered in patients with renal impairment without dose adjustment or monitoring of renal function. The drug has a low potential for drug–drug interactions (DDIs) and no clinically relevant ones were reported so far. Areas covered: An extensive literature search was performed to analyse primarily PK and secondarily PD characteristics of linagliptin in both healthy volunteers and patients with T2DM (treated with linagliptin as monotherapy or combined therapy). Updated information about linagliptin PK either after single administration (large dose range) or after chronic administration (steady state) were also included. A special focus has been put on DDIs and on PK/PD of linagliptin in patients with renal impairment. Expert opinion: Head-to-head comparative studies and/or increased clinical experience with DPP-4 inhibitors will determine the clinical advantage, if any, of one agent over another.
The Moderating Role of Top Management Team Diversity in Strategic Change in a Multicultural Context

This paper analyses the influence of corporate governance diversity on corporate strategic changes in an international multicultural context with a view to overcoming the deficiencies of previous studies. The results achieved may reveal to what extent diversity in the composition of a top management team provides a clear picture of the internal complexity that arises in the strategy decision&#8208;making process. In order to fill the gap in the literature, and given the nested structure of the dataset, a multi&#8208;level econometric model is applied which reveals the clear interaction effects among the TMT diversity dimensions on the corporate strategic change.
Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions1

We tested in B6 mice whether the local expansion of CD4 T cells producing proinflammatory cytokines including IL-17 (Th17 cells) in the colonic lamina propria (cLP) depends on the commensal microflora. High numbers of CD4 Th17 cells were found in the lamina propria of the ileum and colon but not the duodenum, jejunum, mesenteric lymph nodes, spleen, or liver of specific pathogen-free (SPF) mice. The microflora is required for the accumulation of cytokine (IL-17, IFN-γ, TNF-α, IL-10)-producing CD4 T cells in the cLP because only low numbers of cytokine-producing cLP CD4 T cells were found in syngeneic (age- and sex-matched) germfree mice. The fraction of cLP Th17 cells was higher in (type I and type II) IFN- but not IL-4- or IL-12p40-deficient SPF congenics. cLP CD4 Th17 cells produce IL-17 but not IFN-γ, TNF-α, IL-4, or IL-10. cLP CD4 Th17 cells accumulate locally in colitis induced by adoptive transfer of IFN-γ+/+ or IFN-γ−/− CD4 T cells into congenic SPF (but not germfree) RAG−/− hosts. In this colitis model, cLP CD4 T cells that “spontaneously” produce IL-17 progressively increase in number in the inflamed cLP, and increasing serum IL-17 levels appear as the disease progresses. Commensal bacteria-driven, local expansion of cLP CD4 Th17 cells may contribute to the pathogenesis of this inflammatory bowel disease.
Sodium‐magnesium antiport in Retzius neurones of the leech Hirudo medicinalis.

1. Intracellular free magnesium ([Mg2+]i) and sodium ([Na+]i) concentrations were measured in Retzius neurones of the leech Hirudo medicinalis using ion‐sensitive microelectrodes. 2. The mean steady‐state values for [Mg2+]i and [Na+]i were 0.46 mM (pMg, 3.34 +/‐ 0.23; range, 0.1‐1.2 mM; n = 32) and 8.95 mM (pNa, 2.05 +/‐ 0.15; range, 5.1‐15.5 mM, n = 21), respectively, at a mean membrane potential (Em) of ‐35.6 +/‐ 6.1 mV (n = 32). Thus, [Mg2+]i is far below the value calculated for a passive distribution (16.9 mM) but close to the equilibrium value calculated for a hypothetical 1 Na(+)‐1 Mg2+ antiport (0.41 mM). 3. Simultaneous measurements of [Mg2+]i, [Na+]i and Em in Retzius neurones showed that an increase in the extracellular Mg2+ concentration ([Mg2+]o) resulted in an increase in [Mg2+]i, a parallel decrease in [Na+]i and a membrane depolarization, while a decrease in [Mg2+]o had opposite effects. These results are compatible with calculations based on a 1 Na(+)‐1 Mg2+ antiport. 4. Na+ efflux at high [Mg2+]o still occurred when the Na(+)‐K+ pump was inhibited by the application of ouabain or in K(+)‐free solutions. This efflux was blocked by amiloride. 5. In the absence of extracellular Na+ ([Na+]o), no Mg2+ influx occurred. Mg2+ influx at high [Mg2+]o was even lower than in the presence of [Na+]o. Mg2+ efflux was blocked in the absence of [Na+]o. 6. The rate of Mg2+ extrusion was reduced by lowering [Na+]o, even if the Na+ gradient across the membrane remained almost unchanged. 7. Mg2+ efflux was blocked by amiloride (half‐maximal effect at 0.25 mM amiloride; Hill coefficient, 1.3) but not by 5‐(N‐ethyl‐N‐isopropyl)‐amiloride (EIPA). 8. No changes in intracellular Ca2+ and pH (pHi) could be detected when [Mg2+]o was varied between 1 and 30 mM. 9. Changing pHi by up to 0.4 pH units had no effect on [Mg2+]i. 10. The results suggest the presence of an electrogenic 1 Na(+)‐1 Mg2+ antiport in leech Retzius neurones. This antiport can be reversed and is inhibited by low extracellular and/or intracellular Na+ and by amiloride.