Miracle-dz/UniFAR-FTUs huggingface dataset:
A family of multifunctional thiamine‐repressible expression vectors for fission yeast

A series of thiamine‐repressible shuttle vectors has been constructed to allow a more efficient DNA manipulation in Schizosaccharomyces pombe. These high‐copy‐number vectors with regulatable expression (pJR) are based on the backbone of the pREP‐3X, pREP‐41X and pREP‐81X plasmids. The pJR vectors are all uniform in structure, containing: (a) sequences for replication (ori) and selection (AmpR) in Escherichia coli; (b) the f1 ori sequence of the phage f1 for packaging of ssDNA, making them suitable for site‐directed mutagenesis; and (c) the ars1 sequence for replication in S. pombe. The pJR vectors differ among them in: (a) the selectable marker (Saccharomyces cerevisiae LEU 2 gene, which complements S. pombe leu1− gene and S. pombe ura4+ and his3+ genes); (b) the thiamine‐repressible nmt1 promoter (3X, 41X and 81X with extremely high, moderate or low transcription efficiency, respectively); and (c) the multiple cloning site (two multiple cloning sites, with 12 restriction sites each). The expression level of the pJR vectors has been analysed using the β‐galactosidase gene as reporter. Three levels of expression for each nmt1 promoter version, with any selectable marker and for either repressed or induced conditions, have been found. The expression is dependent on the distance to the initiation codon, varying from 0.001 to 15 times the activity characterized for the pREP plasmids. Also, the gene expression has been found to be extremely sensitive to the nucleotide sequence prior to the initiation codon, being up to 50‐fold higher with an A/T sequence than with a G/C sequence. Finally, the β‐galactosidase mRNA levels were found to be similar in each nmt1 series, suggesting a translational effect on gene expression. As a result, any of these 18 new vectors allow performing gene expression in fission yeast, as well as a more versatile cloning, sequencing and mutagenesis, directly in the plasmid without the need for subcloning into intermediary vectors. Copyright © 2000 John Wiley & Sons, Ltd.
Multiple Double Cross-Section Transmission Electron Microscope Sample Preparation of Specific Sub-10 nm Diameter Si Nanowire Devices

Abstract The ability to prepare multiple cross-section transmission electron microscope (XTEM) samples from one XTEM sample of specific sub-10 nm features was demonstrated. Sub-10 nm diameter Si nanowire (NW) devices were initially cross-sectioned using a dual-beam focused ion beam system in a direction running parallel to the device channel. From this XTEM sample, both low- and high-resolution transmission electron microscope (TEM) images were obtained from six separate, specific site Si NW devices. The XTEM sample was then re-sectioned in four separate locations in a direction perpendicular to the device channel: 90° from the original XTEM sample direction. Three of the four XTEM samples were successfully sectioned in the gate region of the device. From these three samples, low- and high-resolution TEM images of the Si NW were taken and measurements of the NW diameters were obtained. This technique demonstrated the ability to obtain high-resolution TEM images in directions 90° from one another of multiple, specific sub-10 nm features that were spaced 1.1 μm apart.
Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6

Significance 2-Arachidonoylglycerol (2-AG) is an endogenous bioactive lipid implicated in numerous (patho)physiological processes. 2-AG classically activates the cannabinoid receptors, and its activity is terminated by enzymatic hydrolysis. The main enzyme studied in this context is monoacylglycerol lipase (MAGL). Although its inhibition, to increase 2-AG levels, has proven beneficial, it is hindered by psychotropic side effects due to drastically elevated brain 2-AG. Here we show the anti-inflammatory effects of inhibition of another 2-AG hydrolase, α/β-hydrolase domain 6, without the side effects associated with MAGL inhibition. We also show that 2-AG decreases macrophage activation and this effect is not mediated by its classical receptors. Furthermore, we demonstrate that a cyclooxygenase-2–derived metabolite of 2-AG, prostaglandin D2-glycerol ester, is responsible for the documented effects. Proinflammatory macrophages are key mediators in several pathologies; thus, controlling their activation is necessary. The endocannabinoid system is implicated in various inflammatory processes. Here we show that in macrophages, the newly characterized enzyme α/β-hydrolase domain 6 (ABHD6) controls 2-arachidonoylglycerol (2-AG) levels and thus its pharmacological effects. Furthermore, we characterize a unique pathway mediating the effects of 2-AG through its oxygenation by cyclooxygenase-2 to give rise to the anti-inflammatory prostaglandin D2-glycerol ester (PGD2-G). Pharmacological blockade of cyclooxygenase-2 or of prostaglandin D synthase prevented the effects of increasing 2-AG levels by ABHD6 inhibition in vitro, as well as the 2-AG–induced increase in PGD2-G levels. Together, our data demonstrate the physiological relevance of the interaction between the endocannabinoid and prostanoid systems. Moreover, we show that ABHD6 inhibition in vivo allows for fine-tuning of 2-AG levels in mice, therefore reducing lipopolysaccharide-induced inflammation, without the characteristic central side effects of strong increases in 2-AG levels obtained following monoacylglycerol lipase inhibition. In addition, administration of PGD2-G reduces lipopolysaccharide-induced inflammation in mice, thus confirming the biological relevance of this 2-AG metabolite. This points to ABHD6 as an interesting therapeutic target that should be relevant in treating inflammation-related conditions, and proposes PGD2-G as a bioactive lipid with potential anti-inflammatory properties in vivo.
Psychosocial Therapies for Patients With Cancer

Background. As part of a new standard of quality cancer care, the Institute of Medicine has recommended inclusion of therapies that address psychosocial needs of cancer patients. A range of psychosocial therapies for managing acute and chronic stress have been developed for patients with cancer, based on the scientific framework of psychoneuroimmunology (PNI). The current review aimed to identify studies of new and emerging PNI-based psychosocial therapies in patients with cancer that have used neuroendocrine–immune biomarkers as outcomes. Specifically, this review aimed to evaluate studies based on the cancer populations involved, types of psychosocial therapies, and PNI measures employed. Methods. Methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed, EMBASE, PsychINFO, CINAHL, and Google Scholar online databases were searched using combinations of keywords obtained from previous reviews of psychosocial interventions. Studies from 2001 to 2012 were included if they (a) were published in English, (b) used experimental or quasi-experimental designs, (c) evaluated psychosocial therapies, (d) involved cancer patients, and (e) reported results on at least one neuroendocrine or immune outcome measure. The search strategy identified 403 records and 2 stages of screening were used to eliminate irrelevant studies. Results. A total of 24 cancer-specific studies of psychosocial therapies that used PNI-based outcome measures were included in this review. Most studies included early-stage breast cancer patients, and 2 major types of therapies emerged, cognitive–behavioral therapies and complementary medical therapies. Durations of interventions ranged widely, from 1.3 hours over a single week to 27 hours over 18 weeks. Considerable diversity in PNI outcomes made statistical comparisons problematic. Studies of cognitive–behavioral therapies were found to have reported the most success in impacting PNI-based measures, which were typically functional measures of the immune system, for example, cytokines. Conclusions. Several issues related to research methodology are discussed. Most important, studies examining dose–response associations and resource allocation are needed to guide future research. A standardized panel of psychosocial instruments and biomarkers for PNI-based studies would enhance comparability of findings across studies when evaluating this body of research and assist with integrating psychosocial therapies into the standard of cancer care.
Nonlinear Response in a Field Portable Spectroradiometer: Characterization and Effects on Output Reflectance

We report the characterization and correction of nonlinear responses of a commercial field portable spectroradiometer intended to be used to monitor vegetation physiology. Calibration of photoresponse allowed the successful correction of spectral data and the modeling of biases in reflectance at different levels of the dynamic range. Finally, the impact of nonlinearities on a spectral estimator of photosynthetic status, the photochemical reflectance index (PRI) is discussed. Significance of the biases proved that, although nonlinearity can potentially affect reflectance along most of the dynamic range of the instrument, experimental uncertainties can limit its impact. Nonlinearity biased PRI by affecting the reference band of the index and suggested unreal changes on plant physiology. Results show that nonlinearity could be a significant problem in field spectroscopy, especially in the case of spectroradiometers integrated in unattended systems to monitor vegetation responses to radiation. An automatic adjustment of integration time to reach only a certain level of the dynamic range may reduce nonlinearity effects, though may not always avoid them. We conclude that linearity characterization is necessary to understand impacts and correct potential biases.
Pairwise RNA secondary structure alignment with conserved stem pattern

MOTIVATION The regulatory functions performed by non-coding RNAs are related to their 3D structures, which are, in turn, determined by their secondary structures. Pairwise secondary structure alignment gives insight into the functional similarity between a pair of RNA sequences. Numerous exact or heuristic approaches have been proposed for computational alignment. However, the alignment becomes intractable when arbitrary pseudoknots are allowed. Also, since non-coding RNAs are, in general, more conserved in structures than sequences, it is more effective to perform alignment based on the common structural motifs discovered. RESULTS We devised a method to approximate the true conserved stem pattern for a secondary structure pair, and constructed the alignment from it. Experimental results suggest that our method identified similar RNA secondary structures better than the existing tools, especially for large structures. It also successfully indicated the conservation of some pseudoknot features with biological significance. More importantly, even for large structures with arbitrary pseudoknots, the alignment can usually be obtained efficiently. AVAILABILITY AND IMPLEMENTATION Our algorithm has been implemented in a tool called PSMAlign. The source code of PSMAlign is freely available at http://homepage.cs. latrobe.edu. au/ypchen/psmalign/.
Targeting the urokinase plasminogen activator receptor with a monoclonal antibody impairs the growth of human colorectal cancer in the liver

Urokinase plasminogen activator receptor (uPAR) expression has been shown to correlate with poor prognosis in colorectal cancer (CRC). The authors hypothesized that targeting uPAR, a receptor involved in cell proliferation, migration, invasion, adhesion, and angiogenesis, would impair the growth of CRC in the liver, the most common site of metastasis.
Multi-goal Path Planning Autonomous System for Picking up and Delivery Tasks in Mobile Robotics

Intelligent service robots are needed in office-like environments to perform common tasks of picking up, and delivering things such as mail, goods, trash recycled paper, etc. These tasks are challenging since robots must avoid static and dynamic obstacles, and mainly robots have to perform path planning considering multiple goals as saving energy. This work proposes an autonomous multi-goal path planning system for picking up or delivering tasks in mobile robotics. The multi-goal path planning method is based on the Lin-Kernighan Heuristics (LKH) algorithm [1], which was modified in order to implement an autonomous system for picking up/delivering tasks using non-Euclidean distances, Hamiltonian paths, and a Pioneer 3DX mobile robot. This work proposes a client ‑ robot system ARMM [2] where many clients request pickup / delivery services, then the robot continuously plan a Hamiltonian path to visit each one of the requested pickup / delivery goals, and return to its base station. To validate the results of this work two well-known metrics were performed [3]: distance traveled and time elapsed. A comparison between the nearest goal, random selection, the LKH with Euclidean distances, and the LKH with non-Euclidean distances algorithms were performed.
Monte Carlo tests for associations between disease and alleles at highly polymorphic loci

In an association analysis comparing cases and controls with respect to allele frequencies at a highly polymorphic locus, a potential problem is that the conventional chi‐squared test may not be valid for a large, sparse contingency table. However, reliance on statistics with known asymptotic distribution is now unnecessary, as Monte Carlo simulations can be performed to estimate the significance level of any test statistic. We have implemented a Monte Carlo method for four ‘chi‐squared’ test statistics, three of which involved combination of alleles, and evaluated their performance on a real data set. Combining rare alleles to avoid small expected cell counts, and considering each allele in turn against the rest, reduced the power to detect a genuine association when the number of alleles was very large. We should either not combine alleles at all, or combine them in such a way that preserves the evidence for an association.
Insulin Resistance in Latent Autoimmune Diabetes of Adulthood

Abstract: Insulin resistance in patients with latent autoimmune diabetes of adulthood (LADA) was determined by homeostasis model assessment (HOMA). LADA was identified by a clinical phenotype of type 2 diabetes with antibodies to GAD65 and/or IA‐2/ICA512. All patients were managed with insulin therapy. Insulin resistance in LADA was lower than in antibody‐negative type 2 diabetes, higher than in normal humans and in recent‐onset type 1 diabetes, and similar to that in long‐term type 1 diabetes. Mean values for HOMA varied linearly with mean values for BMI, which accounted for much of the insulin resistance in these forms of diabetes. LADA resembles long‐term type 1 diabetes with respect to insulin resistance and BMI, but occurs at an older age.
A COLLABORATIVE VIRTUAL REALITY ENVIRONMENT FOR NEUROSURGICAL PLANNING AND TRAINING

OBJECTIVE We have developed a highly interactive virtual environment that enables collaborative examination of stereoscopic three-dimensional (3-D) medical imaging data for planning, discussing, or teaching neurosurgical approaches and strategies. MATERIALS AND METHODS The system consists of an interactive console with which the user manipulates 3-D data using hand-held and tracked devices within a 3-D virtual workspace and a stereoscopic projection system. The projection system displays the 3-D data on a large screen while the user is working with it. This setup allows users to interact intuitively with complex 3-D data while sharing this information with a larger audience. RESULTS We have been using this system on a routine clinical basis and during neurosurgical training courses to collaboratively plan and discuss neurosurgical procedures with 3-D reconstructions of patient-specific magnetic resonance and computed tomographic imaging data or with a virtual model of the temporal bone. Working collaboratively with the 3-D information of a large, interactive, stereoscopic projection provides an unambiguous way to analyze and understand the anatomic spatial relationships of different surgical corridors. In our experience, the system creates a unique forum for open and precise discussion of neurosurgical approaches. CONCLUSION We believe the system provides a highly effective way to work with 3-D data in a group, and it significantly enhances teaching of neurosurgical anatomy and operative strategies.
The Thoughts Questionnaire (TQ) for family caregivers of people with dementia

Objectives To develop a new measure of dysfunctional thoughts for family caregivers of people living with dementia. These thoughts can contribute to negative outcomes, but they may be modifiable. Method A stepwise process was used to develop the Thoughts Questionnaire, commencing with item generation, concept mapping, and pilot testing in a sample of professional and nonprofessional caregivers of people with dementia (n = 18). Next, an independent sample of 35 family caregivers of people with dementia (30 female; Mage = 64.30, standard deviation = 10.65) completed: (a) the Thoughts Questionnaire; (b) an existing measure of dysfunctional thoughts, the Dementia Thoughts Caregivers Questionnaire; and (c) separate validated measures of depressive symptoms, caregiver stress, and coping, respectively. Results The level of agreement with dysfunctional thought statements from the Dementia Thoughts Caregivers Questionnaire and Thoughts Questionnaire was low. However, a small number of Thoughts Questionnaire statements were strongly endorsed by over 85% of the sample. Both dysfunctional thought measures had adequate reliability, but total scores were not significantly intercorrelated (r = .287, p = .095). Only the Thoughts Questionnaire was significantly, positively correlated with most caregiver stress measures. Thoughts Questionnaire items required a much lower reading level than the Dementia Thoughts Caregivers Questionnaire items. Discussion This study provides preliminary data on a tool for assessing the negative role-related thoughts that family caregivers of people with dementia may experience. Given that these thoughts are implicated in depression but they may be modified, the capacity to identify dysfunctional thoughts may prove useful in caregiver support programs.
Effect of Extracellular pH on Matrix Synthesis by Chondrocytes in 3D Agarose Gel

In cartilage tissue engineering, the determination of the most appropriate cell/tissue culture conditions to maximize extracellular matrix synthesis is of major importance. The extracellular pH plays an important role in affecting energy metabolism and matrix synthesis by chondrocytes. In this study, chondrocytes were isolated from bovine articular cartilage, embedded in agarose gel, and cultured at varied pH levels (7.3–6.6). Rate of lactate production, total glycosaminoglycan (GAG) and collagen synthesis, as well as total cell numbers and cell viability were evaluated after culturing for up to 7 days. The results showed the rate of lactic acid production over the 7‐day culture was significantly affected by extracellular pH; acidic pH markedly inhibited the production of lactate. Also, a biphasic response to extracellular pH in regard to total GAG synthesis was observed; the maximum synthesis was seen at pH 7.2. However, the collagen synthesis was not pH‐dependent within the pH range explored. In addition, within the conditions studied, total cell numbers and cell viability were not significantly affected by extracellular pH. In conclusion, even minor changes in extracellular pH could markedly affect the metabolic activities and biosynthetic ability of chondrocytes. Consequently, the control of extracellular pH condition is crucially important for successful cartilage tissue engineering and for the study of chondrocyte physiology and functions.
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. METHODS In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. RESULTS In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. CONCLUSIONS In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
N-cadherin expression during periodontal ligament cell differentiation in vitro.

BACKGROUND When confluent periodontal ligament (PDL) cells were cultured in the presence of dexamethasone (Dex), ascorbic acid (AA), and beta-glycerophosphate (GP), they underwent sequential differentiation, demonstrating distinct morphological characteristics. At 1 week, localized cell proliferation led to the formation of multilayers of cells. As cell differentiation progressed, they formed nodules by deposition of matrix in the clusters of cells at 2 weeks, and mineralized the nodules at 3 weeks. These changes implicate extensive cell-to-cell interactions. Cadherins are known to play an important role in establishing cell contacts during tissue formation. METHODS To determine whether cadherins are involved in PDL cell differentiation, and the formation and mineralization of nodules by the cells in vitro, we investigated the expression of N-cadherin using immunofluorescence labeling and Northern blot analysis. RESULTS Immunolabeling showed that N-cadherin was expressed in PDL cells in the stages of nodule formation and mineralization. Northern blot analysis demonstrated a 3-fold increase in the expression of N-cadherin mRNA in the stages. However, neither E-cadherin nor P-cadherin was expressed. CONCLUSIONS Our data suggest that N-cadherin may play an important role in PDL cell differentiation and the formation of mineralized nodules by PDL cells.