Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variants in the receptor for advanced glycation end products (RAGE) gene were associated with circulating soluble RAGE level but not with renal function among Asians with type 2 diabetes: a genome-wide association study.

Background The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an important role in diabetic complications. We conducted genome-wide association study (GWAS) of sRAGE in Asian type 2 diabetes mellitus (T2DM) patient and validated the association in an independent cohort of T2DM. Methods GWAS for sRAGE was performed in 2058 T2DM patients. Associations between single-nucleotide polymorphisms (SNPs) and plasma sRAGE level were analyzed in an additive model using a linear mixed model. To validate the associations, we performed de novo genotyping in an independent cohort (n = 1984). We selected the top SNP for assessment with diabetic kidney disease (DKD). Results The strongest SNP, rs2070600C>T (P = 1.21 × 10-52), was a genotyped, missense SNP located on chromosome 6, corresponding to the RAGE (AGER) gene locus, the gene encoding RAGE. Conditioning analysis on rs2070600 revealed that rs2071288C>T was the top genotyped independent SNP (P = 8.36 × 10-10). Both SNPs were strongly and dose-dependently correlated with sRAGE level (TT = 399.6 pg/mL, CT = 737.0 pg/mL and CC = 967.0 pg/mL, P < 0.001 for rs2070600; TT = 687.9 pg/mL, CT = 737.6 pg/mL and CC = 904.7 pg/mL, P < 0.001 for rs2072188). Both SNPs were robustly replicated in the independent cohort, especially among Chinese patients (P = 9.02 × 10-72 for rs2070600; P = 1.13 × 10-9 for rs2071288). Log-transformed sRAGE was associated with DKD after adjustment for age, gender and ethnicity in pooled cohorts [odds ratio 2.536 (95% confidence interval 1.864-3.450), P < 0.001]. However, we did not observe any significant association between rs2070600 and DKD. Conclusions Common variants in RAGE are strongly associated with plasma sRAGE level, which is associated with DKD. However, we did not find a causal link between sRAGE and renal function by Mendelian randomization.
Constitutive relations for tin-based-solder joints

The authors present extensive data on 62Sn36Pb2Ag, 60Sn40Pb, 96.5Sn3. 5Ag, 97Pb3Sn, and 95Pb5Sn solders. All of the data were collected on actual soldered assemblies to properly account for the effects of grain size and intermetallic compound distribution. Tensile and shear loading were employed in the strain rate range between 10/sup -7/ and 10/sup -1/ s/sup -1/ and temperature range between 25 and 135 degrees C. It is noted that all of the data can be fit to the same general form of constitutive relations, i.e. only the constants depend on the solder alloy. The derived constitutive relations are used to predict solder joint response under thermal cycling. Based on the calculated hysteresis loops, it is apparent that each solder will have a different acceleration factor between field use cycling and accelerated test cycling. <<ETX>>
Colloidal Nanocrystal Quantum Dots for High-Efficiency Optoelectronic Conversions

Monodispersed colloidal quantum dots (QDs) synthesized by low-cost solution methods have many attractive properties, including high wavelength tunability, efficient luminescence, narrow emission bandwidth, and strong broadband absorption. They therefore offer a new class of materials for efficient optoelectronic conversions in various devices, including light-emitting diodes (LEDs), photodetectors, and thin-film solar cells. Despite the recent rapid progress, the development of QD-based devices is still in its infancy. For instance, both the external quantum efficiency of QD-LEDs and power conversion efficiency of QD solar cells reported in the literature are only a few percent, far below those of state-of-the-art inorganic and organic semiconductor devices. The performance of QD-based devices is largely limited by the insulating and bulky organic ligands of QDs, which are necessary for colloidal synthesis, but create large interparticle spacing and interfacial energy barriers, impeding charge transport and injection as well as exciton dissociation and energy transfer. This work aims to enhance the energy conversion efficiencies in QD-based optoelectronic devices through surface modification of QDs and device structure optimization, which can enable efficient electronic coupling and energy transfer between QDs and surrounding materials. First, an in-house capability of colloidal QD synthesis by the hot-injection method was developed. High-quality CdSe, CdS and CdTe core QDs with sharp excitonic absorption features and narrow PL bandwidths were synthesized. Growing a ZnS shell surrounding the CdSe core QDs via the SILAR method increased the photoluminescence quantum yield (PL QY) from 10% to ~50%. Furthermore, the ZnS shell was replaced by a graded CdS/Zn0.5Cd0. 5S/ZnS multishell, leading to reduced interfacial defects and an improved PL QY ~65%. Second, CdSe and CdSe/ZnS QDs with inorganic metal chalcogenide ligands (SnS44-) were synthesized by an organic-to-inorganic ligand exchange process. The SnS4 ligands significantly enhanced the inter-QD electronic coupling in QD solids, but caused a substantial reduction in the PL efficiency. Finally, the applicability of CdSe QDs with organic and inorganic ligands for optoelectronic applications is evaluated through detailed optical, electrical and optoelectronic characterization. LEDs based on a QDs/organic materials hybrid structure were fabricated and characterized. The best result was obtained from the LEDs based on organically-capped CdSe/ZnS QDs with a layer of blue phosphorescent FIrpic dyes as efficient exciton harvesters and energy donors. Precise control of the concentration of the donors and their distance from the QD layer led to complete exciton energy transfer and efficiency enhancement by a factor of 2.5. Meanwhile, the SnS4-capped QDs were found to retain strong excitonic absorption. Under a 150 W Xe lamp illumination, the photocurrent response of an ITO/QDs/Al structure increased by several orders of magnitude after the ligand exchange. These findings bode…
New Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Catalyzed by Benzotriazolium-Based Ionic Liquids under Solvent-Free Conditions

An efficient synthesis of novel 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) and their derivatives, using Brønsted acidic ionic liquid [C2O2BBTA][TFA] as a catalyst, from the condensation of aryl aldehyde, β-ketoester and urea was described. Reactions proceeded smoothly for 40 min under solvent-free conditions and gave the desirable products with good to excellent yields (up to 99%). The catalyst could be easily recycled and reused with similar eﬃcacies for at least six cycles.
Evaluation of genotype MTBDRplus line probe assay in detection of rifampicin and isoniazid resistance in comparison to solid culture drug susceptibility testing in a tertiary care centre of western Uttar Pradesh

Background: Isoniazid (INH) and rifampicin (Rif) are the key first-line antituberculosis drugs, and resistance to these drugs i.e., multi-drug-resistant tuberculosis (MDR-TB), is likely to result in treatment failure and poor clinical outcomes. India has the highest burden of TB and MDR-TB in the world, disproportionately high even for India's population. The GenoType® MTBDRplus molecular method allows rapid detection of Rif and INH resistance. Aim: The present study was done to compare the performance of line probe assay test (GenoType® MTBDRplus) with solid culture method for an early diagnosis of MDR-TB. Methods: Totally 1503 sputum samples of MDR-TB suspects were subjected to fluorescent microscopy. Decontamination was done by N-acetyl-L-cysteine and sodium hydroxide method. Fluorescent microscopy-positive samples were subjected to GenoType® MTBDRplus (HAIN Lifescience) assay. Sixty-two random samples were compared with phenotypic drug susceptibility testing (DST) (1% proportion method) using solid culture method by Lowenstein–Jensen media. Results: The sensitivity, specificity, positive predictive value and negative predictive value for detection of resistance to Rif were 94.74%, 95.35%, 90% and 97.62% and to INH were 92.00%, 91.89%, 88.46% and 94.44%, respectively, in comparison with the phenotypic DST. Conclusion: GenoType® MTBDRplus has good sensitivity and specificity in detecting MDR-TB cases with a significantly lesser turnaround time as compared to conventional DST method and simultaneous detection of Rif and INH resistance. This technique saves several weeks of time required for culture and DST.
Retrodeformation of fossil specimens based on 3D bilateral semi-landmarks: Implementation in the R package “Morpho”

Many fossil specimens exhibit deformations caused by taphonomic processes. Due to these deformations, even important specimens have to be excluded from morphometric analyses, impoverishing an already poor paleontological record. Techniques to retrodeform and virtually restore damaged (i.e. deformed) specimens are available, but these methods genenerally imply the use of a sparse set of bilateral landmarks, ignoring the fact that the distribution and amount of control points directly affects the result of the retrodeformation. We propose a method developed in the R environment and available in the R-package “Morpho” that, in addition to the landmark configurations, also allows using a set of semi-landmarks homogeneously distributed along curves and on surfaces. We evaluated the outcome of the retrodeformation, regarding the number of semi-landmarks used and its robustness against asymmetric noise, based on simulations using a virtually deformed gorilla cranium. Finally, we applied the method to a well-known Neanderthal cranium that exhibits signs of taphonomically induced asymmetry.
A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

Low-carbohydrate, high-fat diets (ketogenic diets) might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF) is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR), tumor-bearing (TB), and ketogenic formula (KF) groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.
Expression of a carotenoid‐modifying gene and evolution of red coloration in weaverbirds (Ploceidae)

Red carotenoid colours in birds are widely assumed to be sexually selected quality indicators, but this rests on a very incomplete understanding of genetic mechanisms and honesty‐mediating costs. Recent progress was made by the implication of the gene CYP2J19 as an avian carotenoid ketolase, catalysing the synthesis of red C4‐ketocarotenoids from yellow dietary precursors, and potentially a major mechanism behind red coloration in birds. Here, we investigate the role of CYP2J19 in the spectacular colour diversification of African weaverbirds (Ploceidae), represented by five genera and 16 species: eight red, seven yellow and one without carotenoid coloration. All species had a single copy of CYP2J19, unlike the duplication found in the zebra finch, with high expression in the retina, confirming its function in colouring red oil droplets. Expression was weak or undetected in skin and follicles of pigment‐depositing feather buds, as well as in beaks and tarsi, including those of the red‐billed quelea. In contrast, the hepatic (liver) expression of CYP2J19 was consistently higher (>14‐fold) in seven species with C4‐ketocarotenoid coloration than in species without (including one red species), an association strongly supported by a phylogenetic comparative analysis. The results suggest a critical role of the candidate ketolase, CYP2J19, in the evolution of red C4‐ketocarotenoid colour variation in ploceids. As ancestral state reconstruction suggests that ketocarotenoid coloration has evolved twice in this group (once in Euplectes and once in the Quelea/Foudia clade), we argue that while CYP2J19 has retained its ancestral role in the retina, it has likely been co‐opted for red coloration independently in the two lineages, via increased hepatic expression.
Exploiting the control power of SDN during the transition from IP to SDN networks

The emerging software‐defined networking (SDN) paradigm introduces new opportunities to improve network performance due to the flexibility and programmability provided by a logically centralized element named controller. However, a rapid adoption of the full SDN architecture is difficult in the short term due to economic and technical reasons. This paper faces the SDN nodes replacement problem during the transition from traditional IP networks to fully deployed SDN networks. Six different replacement methods are proposed to select the most appropriate set of traditional IP nodes to be upgraded to SDN‐enabled switches at a particular transition stage. To show the effectiveness of the proposed methods, they have been applied on an optimization problem currently studied by the research community: the power consumption problem. An integer linear programming formulation is presented to solve it and a genetic algorithm is evaluated through simulations on realistic network topologies. Results highlight that energy‐efficiency in hybrid IP/SDN networks can be significantly improved by only replacing a reduced number of IP nodes.
The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated‐recombinant arginase I BCT‐100

Arginine is a semi‐essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT‐100, a pegylated (PEG) recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT‐100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone. Against ALL xenografts, BCT‐100 leads to a reduction in ALL engraftment and a prolongation of survival. ALL blasts express the arginine transporter CAT‐1, yet the majority of blasts are arginine auxotrophic due to deficiency in either argininosuccinate synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous upregulation or retroviral transduced increases in ASS or OTC may promote ALL survival under moderately low arginine conditions, expression of these enzymes cannot prevent BCT‐100 cytotoxicity at arginine depleting doses. RNA‐sequencing of ALL blasts and supporting stromal cells treated with BCT‐100 identifies a number of candidate pathways which are altered in the presence of arginine depletion. Therefore, BCT‐100 provides a new clinically relevant therapeutic approach to target arginine metabolism in ALL.
Harnessing mesenchymal stem cell homing as an anticancer therapy

ABSTRACT Introduction: Mesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that have been exploited as vehicles for cell-based cancer therapy. The general approach is based on the innate potential of adoptively applied MSC to undergo facilitated recruitment to malignant tissue. MSC from different tissue sources have been engineered using a variety of therapy genes that have shown efficacy in solid tumor models. Areas covered: In this review we will focus on the current developments of MSC-based gene therapy, in particular the diverse approaches that have been used for MSCs-targeted tumor therapy. We also discuss some outstanding issues and general prospects for their clinical application. Expert opinion: The use of modified mesenchymal stem cells as therapy vehicles for the treatment of solid tumors has progressed to the first generation of clinical trials, but the general field is still in its infancy. There are many questions that need to be addressed if this very complex therapy approach is widely applied in clinical settings. More must be understood about the mechanisms underlying tumor tropism and we need to identify the optimal source of the cells used. Outstanding issues also include the therapy transgenes used, and which tumor types represent viable targets for this therapy.
Enabling the generation of web applications from mockups

Mockups are widely used to elicit and validate user requirements in web applications, and several intuitive tools have been developed in recent years, actively involving the end user in the requirements solicitation process. However, most current web development approaches and tools discard mockups after the information‐gathering process, abandoning the opportunity to exploit underlying information in them for autogenerating functional web applications. To overcome this limitation, we have devised a method for deriving the database schema and the logic of the web application from the information contained within mockups. In particular, the method gathers clues on how to organize the data and the control flow of the web application by analyzing the structure and relationships of the widgets in the mockup. Based on the proposed method, we have implemented a tool supporting the generation of web applications abiding by the model‐view‐controller architectural pattern. The tool has been evaluated by involving several end users in the development of web applications for different domains.
Effect of oral calcium bolus administration on milk production, concentrations of minerals and metabolites in serum, early-lactation health status, and reproductive performance of Holstein dairy cows

AIMS: To determine the effects of oral Ca bolus administration in the early postpartum period of cows on milk yield and composition, blood metabolites, early-lactation health status, and reproductive performance. METHODS: Multiparous Holstein dry cows (n=66) with a mean parity of 3.1 (SD 0.35) were fed a diet with a positive dietary cation–anion difference (DCAD) prior to calving. They were randomly assigned to receive no treatment (Control; n=33) or two oral Ca boluses (n=33, 45 g of Ca per bolus); one was administered immediately after calving (Day 0) and the second 24 hours (±30 minutes) later. Blood samples were collected at calving, and on Days 2 and 7 to determine concentrations in serum of Ca, P, Mg, glucose, non-esterified fatty acids (NEFA), and β-hydroxybutyric acid (BHBA). Milk yield was recorded daily and milk composition was determined weekly from calving until 28 day postpartum. Health and outcomes were determined during the first 30 days postpartum and reproductive outcomes to 180 days postpartum. RESULTS: Mean milk yields and composition over the first month of lactation were similar between cows in the two treatment groups (p>0.1). Mean concentrations of Ca in serum were not different between treatment groups on Day 0, but were higher on Day 2 for cows that received oral Ca boluses (1.77 (SE 0.07)) compared with Control cows (1.54 (SE 0.08)) (p=0.04). Concentrations in serum of P, Mg, glucose, NEFA and ΒHBA did not differ between treatment groups on any day of measurement. Fewer cows that received oral Ca were diagnosed with hypocalcaemia (total concentrations of Ca in serum <1.5 mmol/L) by Day 2 (2/33; 6%) compared with Control cows (12/33; 36%) (p=0.01). There was no difference in the prevalence of other health outcomes between treatment groups. The proportion of cows conceiving to first insemination was greater in cows that received an oral Ca bolus (19/29; 65%) than Control cows (12/29; 41%) (p=0.01). CONCLUSIONS: Oral Ca bolus administration increased concentrations of Ca in serum on Day 2 postpartum, and increased first service conception rates, in cows fed a diet with a positive DCAD prior to calving compared to cows that received no oral Ca bolus supplementation. Because of the small number of cows used in this study, further studies in large-scale dairy farms should be carried out to confirm these findings.
Transparent User-Level Checkpointing for the Native Posix Thread Library for Linux

Checkpointing of single-threaded applications has been long studied [3], [6], [8], [12], [15]. Much less research has been done for user-level checkpointing of multithreaded applications. Dieter and Lumpp studied the issue for LinuxThreads in Linux 2.2. However, that solution does not work on later versions of Linux. We present an updated solution for Linux 2.6, which uses the more recent NPTL (Native POSIX Thread Library). Unlike the earlier solution, we do not need to patch glibc. Additionally, the new implementation can take advantage of the ELF architecture to eliminate the earlier requirement to patch the user’s main routine. This fills in the missing link for full transparency. As one demonstration of the robustness, we checkpoint the Kaffe Java Virtual Machine including any of several multithreaded Java programs running on top of it.
Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma

Ependymomas in children can arise throughout all compartments of the central nervous system (CNS). Highly malignant paediatric ependymoma subtypes are Group A tumours of the posterior fossa (PF-EPN-A) and RELA-fusion positive (ST-EPN-RELA) tumours in the supratentorial compartment. It was repeatedly reported in smaller series that accumulation of p53 is frequently observed in ependymomas and that immunohistochemical staining correlates with poor clinical outcome, while TP53 mutations are rare. Our TP53 mutation analysis of 130 primary ependymomas identified a mutation rate of only 3%. Immunohistochemical analysis of 398 ependymomas confirmed previous results correlating the accumulation of p53 with inferior outcome. Among the p53-positive ependymomas, the vast majority exhibited a RELA fusion leading to the hypothesis that p53 inactivation might be linked to RELA positivity. In order to assess the potential of p53 reactivation through MDM2 inhibition in ependymoma, we evaluated the effects of Actinomycin-D and Nutlin-3 treatment in two preclinical ependymoma models representing the high-risk subtypes PF-EPN-A and ST-EPN-RELA. The IC-50 of the agent as determined by metabolic activity assays was in the lower nano-molar range (0.2–0.7 nM). Transcriptome analyses of high-dose (100 nM), low-dose (5 nM) and non-treated cells revealed re-expression of p53 dependent genes including p53 upregulated modulator of apoptosis (PUMA) after low-dose treatment. At the protein level, we validated the Actinomycin-D induced upregulation of PUMA, and of p53 interaction partners MDM2 and p21. Proapoptotic effects of low-dose application of the agent were confirmed by flow cytometry. Thus, Actinomycin-D could constitute a promising therapeutic option for ST-EPN-RELA ependymoma patients, whose tumours frequently exhibit p53 inactivation.