Miracle-dz/UniFAR-FTUs huggingface dataset:
BacMam System for FRET-Based cAMP Sensor Expression in Studies of Melanocortin MC1 Receptor Activation

Cyclic adenosine monophosphate (cAMP) is a second messenger of many G-protein-coupled receptors (GPCRs) and a useful readout molecule to estimate the biological activity of various GPCR-specific agents. Here we report the development and use of a Förster resonance energy transfer (FRET) biosensor for cAMP (Epac2-camps) combined with a baculovirus-based BacMam transduction system. The constructed BacMam-Epac2-camps viral transduction system is a simple and robust tool for ligand screening at the second-messenger level in a variety of mammalian cell lines. The level of biosensor protein expression can easily be adjusted in a dose-dependent manner depending on the multiplicity of viral infection. For setting up the assay, we used a B16F10 murine melanoma cell line with endogenous expression of melanocortin-1 receptor (MC1R). The receptor activation was characterized by a set of MC1R full and partial agonists. Bivalent ions Ca2+ as well as Mg2+ modulated ligand potencies, whereas the effect was ligand and ion specific. Results obtained for MC1R indicate that the BacMam-Epac2-camps system may also be applicable for studying the activation of other GPCRs and may be implemented in routine analysis as well as in high-throughput screening.
GENETIC DIFFERENTIATION IN TWO MEMBERS OF THE DROSOPHILA ATHABASCA COMPLEX

One central question of much interest to students of evolution is the amount of genetic change required for speciation. Situations which should provide information of particular interest are those where: (1) the level of phylogenetic relationship between the groups of organisms is unambiguously specified and (2) the process of speciation is not complete or is known to have been recently completed. For this question the concern with partial or recent speciation arises because the divergence of species involves two sources of differentiation: (1) the genetic variation responsible for reproductive isolation may be accompanied by or follow genetic differentiation in ecological preferences or niches of the two incipient species and (2) genetic variation may arise within each species after speciation is complete. Measurement of variation in species which have long been isolated from one another cannot discriminate between the two sources of variation. The application of electrophoresis to the detection of allozyme variability has made further study of speciation possible (see Ayala, 1975, and references therein). However, relatively few studies have been done using subspecific groups or incipient species. These include studies of subspe-. cies of mice (Selander et al., 1969; Hunt and Selander, 1973), studies of subspecies and semispecies in Drosophila (Zouros, 1973; Richmond, 1972; Ayalaetal. , 1974; Prakash, 1972; Ayala and Dobzhansky,
Susceptibility to daptomycin, quinupristin-dalfopristin and linezolid and some other antibiotics in clinical isolates of methicillin resistant and methicillin sensitive S.aureus from the Oslo area

Our study compared the susceptibility of 136 clinical isolates of Staphylococcus aureus and 119 multidrug-resistant Staphylococcus aureus (MRSA) isolates from Oslo to a range of antibiotics, including the novel antibiotics quinopristin-dalfopristin, linezolid and daptomycin. All isolates were susceptible to daptomycin, linezolid and quinupristin-dalfopristin, although a subgroup was less susceptible to the latter. There was no linkage between reduced susceptibility to daptomycin, linezolid or quinupristin-dalfopristin and resistance to other classes of antimicrobials. In addition, MRSA strains from 2004 have become more sensitive to fucidin and rifampicin.The results can be used to evaluate the appropriateness of breakpoints and to define a baseline for monitoring possible future emergence of resistance to daptomycin, quinupristin-dalfopristin and linezolid in Staphylococcus aureus in Norway.
Inhibition of calcineurin‐NFAT signaling by the pyrazolopyrimidine compound NCI3

Dephosphorylation of NFAT by the Ca2+‐calmodulin‐dependent Ser/Thr protein phosphatase calcineurin is a bottleneck of T cell receptor‐dependent activation of T cells. In dimeric complexes with immunophilins, the immunosuppressants cyclosporine A (CsA) and tacrolimus (FK506) block this process by inhibition of the enzymatic activity of calcineurin. We have identified the pyrazolopyrimidine compound NCI3 as a novel inhibitor of calcineurin‐NFAT signaling. Similar to CsA and FK506, NCI3 inhibits dephosphorylation and nuclear translocation of NFAT, IL‐2 production and proliferation of stimulated human primary T cells with IC50 values from 2 to 4.5 µM. However, contrary to CsA and FK506, NCI3 neither blocks calcineurin`s phosphatase activity nor requires immunophilins for inhibiting NFAT activation. Our data suggest that NCI3 binds to calcineurin and causes an allosteric change interfering with NFAT dephosphorylation in vivo but not in vitro. NCI3 acts not only on the endogenous calcineurin but also on a C‐terminally truncated, constitutively active version of calcineurin. The novel inhibitor described herein will be useful in better defining the cellular regulation of calcineurin activation and may serve as a lead for the development of a new type of immunosuppressants acting not by direct inhibition of the calcineurin phosphatase activity.
Effectiveness of electrical stimulation on rehabilitation after ligament and meniscal injuries: a systematic review

ABSTRACT CONTEXT AND OBJECTIVE: Electrical stimulation (ES) is widely used to strengthen muscles following ligament and meniscal injuries. The aim of this study was to evaluate the effectiveness of ES for rehabilitation after soft tissue injuries of the knee treated surgically or conservatively. DESIGN AND SETTING: Systematic review at the Brazilian Cochrane Center. METHODS: We searched the Cochrane Central Register of Controlled Trials (2010, Issue 12), Medline (Medical Analysis and Retrieval System Online) via PubMed (1966 to December 2010), Embase (Excerpta Medica database, 1980 to December 2010), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde, 1982 to December 2010), and PEDro (Physiotherapy Evidence Database, 1929 to December 2010). The studies included were randomized controlled trials using ES to increase muscle strength for rehabilitation of patients with soft tissue injuries of the knee. Two authors independently evaluated studies for inclusion and performed data extraction and methodological quality assessment. RESULTS: Seventeen studies evaluating ES after anterior cruciate ligament reconstruction and two studies evaluating ES after meniscectomy were included. There was a statistically significant improvement in quadriceps strength through ES (mean difference, MD: −32.7; 95% confidence interval, CI: −39.92 to −25.48; n = 56) and in functional outcomes (MD −7; −12.78 to −1.22; n = 43) six to eight weeks after surgical reconstruction of the anterior cruciate ligament. CONCLUSION: There is evidence that ES coupled with conventional rehabilitation exercises may be effective in improving muscle strength and function two months after surgery.
Load‐displacement properties of the human triceps surae aponeurosis in vivo

1 The present investigation measured the load‐displacement and stress‐strain characteristics of the proximal and distal human triceps surae aponeurosis and tendon in vivo during graded voluntary 10 s isometric plantarflexion efforts in five subjects. 2 During the contractions synchronous real‐time ultrasonography of aponeurosis displacement, electromyography of the gastrocnemius, soleus and dorsiflexor muscles, and joint angular rotation were obtained. Tendon cross‐sectional area and moment arm were obtained from magnetic resonance (MR) images. Force and electromyography data from dorsiflexion efforts were used to examine the effect of coactivation. 3 Tendon force was calculated from the joint moments and tendon moment arm, and stress was obtained by dividing force by cross‐sectional area. Aponeurosis and tendon strain were obtained from the displacements normalised to tendon length. 4 Tendon force was 3171 ± 201 N, which corresponded to 2.6 % less than the estimated force when coactivation was accounted for (3255 ± 206 N). Aponeurosis displacement (13.9‐ 12.9 mm) decreased 30 % (9.6‐10.7 mm) when accounting for joint angular rotation (3.6 deg). Coactivation and angular rotation‐corrected stiffness yielded a quadratic relationship, R2= 0.98± 0.01, which was similar for the proximal (467 N mm−1) and distal (494 N mm−1) aponeurosis and tendon. Maximal strain and stress were 4.4‐5.6 % and 41.6 ± 3.9 MPa, respectively, which resulted in a Young's modulus of 1048‐1474 MPa. 5 The mechanical properties of the human triceps surae aponeurosis and tendon in vivo were for the first time examined. The stiffness and Young's modulus exceeded those previously reported for the tibialis anterior tendon in vivo, but were similar to those obtained for various isolated mammalian and human tendons.
Capillary separations enabling tissue proteomics‐based biomarker discovery

Development of the capability to enable large‐scale proteome studies, analogous to comprehensive gene expression analysis, will clearly have far‐reaching impacts on protein biomarker investigations of human diseases such as cancer through interrogation of the archived fresh frozen and formalin‐fixed and paraffin‐embedded tissue collections. This review therefore focuses on the most recent advances in microdissection techniques and proteome platforms for procuring homogeneous subpopulations of tumor cells or structures and performing comprehensive analysis of protein profiles within tissue specimens, respectively. Developments in capillary separations capable of providing extremely high resolving power and selective analyte enrichment are particularly highlighted for their roles within the broader context of a state‐of‐the‐art integrated tissue proteome effort. The capabilities of CIEF‐based multidimensional separations for performing proteome analysis from minute samples create new opportunities in the pursuit of biomarker discovery using enriched and selected cell populations procured from tissue specimens. These proteome technological advances combined with recently developed tissue microdissection techniques provide powerful tools for those seeking to gain a greater understanding at the global level of the cellular machinery associated with human diseases such as cancer.
Partitioning Graph Databases - A Quantitative Evaluation

Electronic data is growing at increasing rates, in both size and connectivity: the increasing presence of, and interest in, relationships between data. An example is the Twitter social network graph. Due to this growth demand is increasing for technologies that can process such data. Currently relational databases are the predominant technology, but they are poorly suited to processing connected data as they are optimized for index-intensive operations. Conversely, graph databases are optimized for graph computation. They link records by direct references, avoiding index lookups, and enabling retrieval of adjacent elements in constant time, regardless of graph size. However, as data volume increases these databases outgrow the resources of one computer and data partitioning becomes necessary. We evaluate the viability of using graph partitioning algorithms to partition graph databases. A prototype partitioned database was developed. Three partitioning algorithms explored and one implemented. Three graph datasets were used: two real and one synthetically generated. These were partitioned in various ways and the impact on database performance measured. We defined one synthetic access pattern per dataset and executed each on the partitioned datasets. Evaluation took place in a simulation environment, ensuring repeatability and allowing measurement of metrics like network traffic and load balance. Results show that compared to random partitioning the partitioning algorithm reduced traffic by 40-90%. Executing the algorithm intermittently during usage maintained partition quality, while requiring only 1% the computation of initial partitioning. Strong correlations were found between theoretic quality metrics and generated network traffic under non-uniform access patterns.
Detection and significance of occult axillary node metastases in patients with invasive breast cancer

Blocks of axillary lymph nodes from 78 patients with invasive breast cancer, which after “routine”pathological examination were regarded as negative for metastases, were step‐sectioned at 20 u intervals. Occult metastases were detected in 24% of the cases. A significant association between such metastases and a lack of or slight degree of an intraductal carcinomatous component of the dominant cancer was noted. There was no relationship between occult metastases and 15 other histopathological and 3 clinical features investigated, including an average 5 year survival rate. Similarly there was no correlation between any of the possible discriminants investigated in the 24% of patients who have died of their diseases or are living with recurrence regardless of the presence of occult metastases. Factors accounting for the lack of universal survival in patients with Stage I (and those with occult metastases that might be designated as Stage 1 1/2) remain enigmatic. It is concluded that attempts to detect occult metastases by extending histopathological methods may be more academic than practical or therapeutically significant. Cancer 42:2025–2031, 1978.
Generalists and Oncologists Show Similar Care Practices and Outcomes for Hospitalized Late-Stage Cancer Patients

Objective.The objective of this work was to identify similarities and differences in primary attending physicians’ (generalists’ versus oncologists’) care practices and outcomes for seriously ill hospitalized patients with malignancy. Design.This was a prospective cohort study (SUPPORT project). Setting.Subjects were recruited from 5 US teaching hospitals; data were gathered from 1989 to 1994. Subjects.Included in the study was a matched sample of 642 hospitalized patients receiving care for non–small-cell lung cancer, colon cancer metastasized to the liver, or multiorgan system failure associated with malignancy with either a generalist or an oncologist as the primary attending physician. Measurements.Care practices and patient outcomes were determined from hospital records. Length of survival was identified with the National Death Index. Physicians’ perceptions of patient’s prognosis, preference for cardiopulmonary resuscitation (CPR), and length of relationship were assessed by interview. A propensity score for receiving care from an oncologist was constructed. After propensity-based matching of patients, practices and outcomes of oncologists’ and generalists’ patients were assessed through group comparison techniques. Results.Generalist and oncologist attendings showed comparable care practices, including the number of therapeutic interventions, eg, “rescue care” and chemotherapy, and the number of care topics discussed with patients/families. Length of stay, discharge to supportive care, readmission, total hospital costs, and survival rates were similar. For both physician groups, perception of patients’ wish for CPR was associated with rescue care (P <0.03), and such care was related to higher hospital costs (P <0.000). Poorer prognostic estimates predicted aggressiveness-of-care discussions by both types of physicians. Length of the patient-doctor relationship was associated with oncologists’ care practices. More documented discussion about aggressiveness of care was related to higher hospital costs and shorter survival for patients in both physician groups (P <0.001). Conclusions.Generalists and oncologists showed similar care practices and outcomes for comparable hospitalized late-stage cancer patients. Physicians’ perceptions about patients’ preferences for CPR and prognosis influenced decision making and outcomes for patients in both physician groups. Length of relationship with patients was associated only with oncologists’ care practices. Rescue care increased hospital costs but had no effect on patient survival. Future studies should compare physicians’ palliative care as well as acute-care practices in both inpatient and ambulatory care settings. Patients’ end-of-life quality and interchange between physician groups should also be documented and compared.
Data consistency-driven scatter kernel optimization for x-ray cone-beam CT

Accurate and efficient scatter correction is essential for acquisition of high-quality x-ray cone-beam CT (CBCT) images for various applications. This study was conducted to demonstrate the feasibility of using the data consistency condition (DCC) as a criterion for scatter kernel optimization in scatter deconvolution methods in CBCT. As in CBCT, data consistency in the mid-plane is primarily challenged by scatter, we utilized data consistency to confirm the degree of scatter correction and to steer the update in iterative kernel optimization. By means of the parallel-beam DCC via fan-parallel rebinning, we iteratively optimized the scatter kernel parameters, using a particle swarm optimization algorithm for its computational efficiency and excellent convergence. The proposed method was validated by a simulation study using the XCAT numerical phantom and also by experimental studies using the ACS head phantom and the pelvic part of the Rando phantom. The results showed that the proposed method can effectively improve the accuracy of deconvolution-based scatter correction. Quantitative assessments of image quality parameters such as contrast and structure similarity (SSIM) revealed that the optimally selected scatter kernel improves the contrast of scatter-free images by up to 99.5%, 94.4%, and 84.4%, and of the SSIM in an XCAT study, an ACS head phantom study, and a pelvis phantom study by up to 96.7%, 90.5%, and 87.8%, respectively. The proposed method can achieve accurate and efficient scatter correction from a single cone-beam scan without need of any auxiliary hardware or additional experimentation.
Excitability and Synaptic Communication within the Oligodendrocyte Lineage

The mammalian CNS contains an abundant, widely distributed population of glial cells that serve as oligodendrocyte progenitors. It has been reported that these NG2-immunoreactive cells (NG2+ cells) form synapses and generate action potentials, suggesting that neural-evoked excitation of these progenitors may regulate oligodendrogenesis. However, recent studies also suggest that NG2+ cells are comprised of functionally distinct groups that differ in their ability to respond to neuronal activity, undergo differentiation, and experience injury following ischemia. To better define the physiological properties of NG2+ cells, we used transgenic mice that allowed an unbiased sampling of this population and unambiguous identification of cells in discrete states of differentiation. Using acute brain slices prepared from developing and mature mice, we found that NG2+ cells in diverse brain regions share a core set of physiological properties, including expression of voltage-gated Na+ (NaV) channels and ionotropic glutamate receptors, and formation of synapses with glutamatergic neurons. Although small amplitude Na+ spikes could be elicited in some NG2+ cells during the first postnatal week, they were not capable of generating action potentials. Transition of these progenitors to the premyelinating stage was accompanied by the rapid removal of synaptic input, as well as downregulation of AMPA and NMDA receptors and NaV channels. Thus, prior reports of physiological heterogeneity among NG2+ cells may reflect analysis of cells in later stages of maturation. These results suggest that NG2+ cells are uniquely positioned within the oligodendrocyte lineage to monitor the firing patterns of surrounding neurons.
IMPLEMENTING WORD WALL STRATEGY IN TEACHING WRITING DESCRIPTIVE TEXT FOR JUNIOR HIGH SCHOOL STUDENTS (A DESCRIPTIVE QUALITATIVE RESEARCH OF SEVENTH GRADE STUDENTS AT ONE OF THE JUNIOR HIGH SCHOOLS IN BANDUNG)

The research was aimed at investigating the use of Word Wall Strategy in helping junior high school students learn writing descriptive texts and students’ opinions toward the implementation of Word Wall Strategy in teaching writing descriptive text. The descriptive qualitative method was employed in this study. The data were obtained through observation, questionnaire, and document as the instruments of the research. The use of Word Wall as the strategy in teaching writing a descriptive text was helpful for junior high school students by facilitating teacher and students to carry out all of the steps in implementing Word Wall Strategy proposed by expert. The result also displayed that Word Wall Strategy have important roles in helping students learn to write a descriptive text with more than 50% responses were positive regarding the students’ responses to the use of Word Wall. In the end, based on the result of the study, delivering Word Wall strategy is recommended to be implemented in junior high school’s classroom.
Does Alzheimer’s Disease Affect Hippocampal Asymmetry? Evidence from a Cross-Sectional and Longitudinal Volumetric MRI Study

Objective: To determine whether Alzheimer’s disease (AD) is associated with preferential atrophy of either the left or right hippocampus. Methods: We examined right-left asymmetry in hippocampal volume and atrophy rates in 32 subjects with probable AD and 50 age-matched controls. Hippocampi were measured on two serial volumetric MRI scans using a technique that minimizes laterality bias. Results: We found a non-significant trend for right > left (R > L) asymmetry in controls at both time points (R > L: 1.7%; CI: –0.3–3.7%; p = 0.1). AD subjects showed a similar non-significant trend for R > L asymmetry at baseline (R > L: 1.8%; CI: –1.9–5.5%; p = 0.32), but not at repeat (p = 0.739). Change in R/L ratio between visits in AD patients was significant (p = 0.02). The AD group had significantly higher variance in these ratios than the controls at baseline (p = 0.02), but not repeat (p = 0.06). AD patients had higher atrophy rates than controls (p < 0.001). Mean (CI) annualized atrophy rates for left and right hippocampi were 1.2% (0.5–1.8%) and 1.1% (0.5–1.8%) for the controls, and 4.6% (3.3–6.0%) and 6.3% (4.9–7.8%) for AD subjects. There was no significant asymmetry in atrophy rates in controls (p = 0.9), but borderline significantly higher atrophy rates in the right hippocampus of the AD group (p = 0.05) compared to the left. Presence of an APOEΕ4 allele had no significant effect on the size, asymmetry or atrophy rates in AD (p > 0.20). Conclusions: We report minor R > L asymmetry in hippocampal volumes in controls and present some evidence to suggest that there is a change in the natural R > L asymmetry during the progression of AD.