Miracle-dz/UniFAR-FTUs huggingface dataset:
A self-repairing prefetcher in an event-driven dynamic optimization framework

Software prefetching has been demonstrated as a powerful technique to tolerate long load latencies. However, to be effective, prefetching must target the most critical (frequently missing) loads, and prefetch them sufficiently far in advance. This is difficult to do correctly with a static optimizer, because locality characteristics and cache latencies vary across data inputs and across different machines. This paper presents a mechanism that dynamically inserts prefetch instructions into frequently executed hot traces. Hot traces are dynamically analyzed to identify delinquent loads and the appropriate prefetch distance for those loads. Those prefetches are then inserted into the hot trace. The low overhead of the event-driven dynamic optimization system allows the optimizer to continuously monitor the performance of the software prefetches. This is done to find an accurate and stable prefetch distance and to adapt to changes in program behavior using what we call self-repairing prefetching. Relative to the baseline hardware stride prefetching, we find a total 23% improvement when we use the self-repairing mechanism to adoptively discover the best prefetch distance for each load, which is 12% better performance than dynamic prefetching techniques without adaptive repairing.
Material properties of Thera-Band Tubing.

BACKGROUND AND PURPOSE Thera-Band Tubing has been used in rehabilitation to provide resistance for exercise and splinting. However, the forces required to stretch the tubing have not been thoroughly quantified. Therefore, the therapist cannot assess, with certainty, how much force is applied when using a given length and type of Thera-Band Tubing. The purpose of this study was to quantify the material properties of Thera-Band Tubing. METHODS Force versus percentage of strain for all types of Thera-Band Tubing was measured during elongation in a mechanical testing machine. RESULTS The material is very compliant and displays nonlinear behavior in the initial stretching phase and linear behavior after 50% elongation. DISCUSSION AND CONCLUSION From the data obtained in this project, plots that can provide the therapist with information about the forces needed for exercises with Thera-Band Tubing were generated. These data should allow therapists to make better choices about which size of tubing to use for each patient.
More than 500,000 years of right-handedness in Europe

Considerable research supports the high frequency of right-handedness in living Homo sapiens, with worldwide rates of approximately nine right- for every one left-hander. Right-handedness appears to be a uniquely human trait, as no other primate species, no matter how proficient in tool use, shows frequencies even close to the strong right bias typical of humans (Cashmore, Uomini, & Chapelain, 2008; McGrew & Marchant 1997; Steele & Uomini, 2009). Here we review our research on human fossils from Sima de los Huesos (Atapuerca, Spain) and their likely descendants, the European Neandertals. We document hand preference in fossils by scratch patterns that occur on the labial (lip) face of incisors and canines, and contend that these patterns provide a reliable means for identifying predominant hand use in these samples. Manipulatory marks on the anterior teeth show a persistent pattern of right-handed actions, implying that the modern human pattern of dominant right-handedness extends deep into the European past.
Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment

Targeting of MHC class II molecules to the endocytic compartment where they encounter processed antigen is determined by the invariant chain (Ii). By analysis of Ii-transferrin receptor (TR) chimera trafficking, we have identified sorting signals in the Ii cytoplasmic tail and transmembrane region that mediate this process. Two non-tyrosine-based sorting signals in the Ii cytoplasmic tail were identified that mediate localization to plasma membrane clathrin-coated pits and promote rapid endocytosis. Leu7 and Ile8 were required for the activity of the signal most distal to the cell membrane whereas Pro15 Met16 Leu17 were important for the membrane-proximal signal. The same or overlapping non- tyrosine-based sorting signals are essential for delivery of Ii-TR chimeras, either by an intracellular route or via the plasma membrane, to an endocytic compartment where they are rapidly degraded. The Ii transmembrane region is also required for efficient delivery to this endocytic processing compartment and contains a signal distinct from the Ii cytoplasmic tail. More than 80% of the Ii-TR chimera containing the Ii cytoplasmic tail and transmembrane region is delivered directly to the endocytic pathway by an intracellular route, implying that the Ii sorting signals are efficiently recognized by sorting machinery located in the trans-Golgi.
Selection of hprt mutant T cells as surrogates for dividing cells reveals a restricted T cell receptor BV repertoire in insulin-dependent diabetes mellitus.

T cells with somatically acquired mutations in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene were isolated from patients with insulin-dependent diabetes mellitus (IDDM) as representatives of populations potentially enriched for in vivo activated T cells. TCRB gene V region usage among mutant isolates from individual IDDM patients, but not from normal controls, showed a pronounced preference for BV14 and, to a lesser extent, BV6. Wild-type (nonmutant) isolates did not show such preferences. Extensive in vivo clonal expansions of the BV14 expressing mutant T cells from IDDM patients were revealed by sequence identity of TCRB chain junctional regions. These data support restricted TCRB gene usage in T cell populations enriched for in vivo activated clones in patients with IDDM.
BIOINFORMATICS ORIGINAL PAPER

Motivation: It is well known that patterns of differential gene expression across biological conditions are often shared by many genes, particularly those within functional groups. Taking advantage of these patterns can lead to increased statistical power and biological clarity when testing for differential expression in a microarray experiment. The optimal discovery procedure (ODP), which maximizes the expected number of true positives for each ﬁxed number of expected false positives, is a framework aimed at this goal. Storey et al. introduced an estimator of the ODP for identifying differentially expressed genes. However, their ODP estimator grows quadratically in computational time with respect to the number of genes. Reducing this computational burden is a key step in making the ODP practical for usage in a variety of high-throughput problems. Results: Here, we propose a new estimate of the ODP called the modular ODP (mODP). The existing ‘full ODP’ requires that the likelihood function for each gene be evaluated according to the parameter estimates for all genes. The mODP assigns genes to modules according to a Kullback–Leibler distance, and then evaluates the statistic only at the module-averaged parameter estimates. We show that the mODP is relatively insensitive to the choice of the number of modules, but dramatically reduces the computational complexity from quadratic to linear in the number of genes. We compare the full ODP algorithm and mODP on simulated data and gene expression data from a recent study of Morrocan Amazighs. The mODP and full ODP algorithm perform very similarly across a range of comparisons. Availability: The mODP methodology has been implemented into EDGE , a comprehensive gene expression analysis software package in R, available at http:
DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals

Death-associated protein kinase (DAP-kinase) is a calcium/calmodulin-dependent serine/threonine kinase, and participates in various apoptosis systems. However, its apoptosis-promoting mechanism is poorly understood. Here, we demonstrate that DAP-kinase suppresses integrin-mediated cell adhesion and signal transduction, whereas dominant-negative interference of this kinase promotes adhesion. This effect of DAP-kinase is neither a consequence of apoptosis nor a result of decreased expression of integrins. Rather, DAP-kinase downregulates integrin activity through an inside-out mechanism. We present evidence indicating that this adhesion-inhibitory effect accounts for a major mechanism of the apoptosis induced by DAP-kinase. First, in growth-arrested fibroblasts, DAP-kinase triggers apoptosis in cells plated on fibronectin, but does not affect the death of cells on poly-l-lysine. Second, in epithelial cells, DAP-kinase induces apoptosis in the anoikis-sensitive MCF10A cells, but not in the anoikis-resistant BT474 cells. Most importantly, the apoptosis-promoting effect of DAP-kinase is completely abolished by enforced activation of integrin-mediated signaling pathways from either integrin itself or its downstream effector, FAK. Finally, we show that integrin or FAK activation blocks the ability of DAP-kinase to upregulate p53. Our results indicate that DAP-kinase exerts apoptotic effects by suppressing integrin functions and integrin-mediated survival signals, thereby activating a p53-dependent apoptotic pathway.
Shared metamorphic histories of various Palaeoproterozoic granulites from Datong–Huai’an area, North China Craton (NCC): constraints from zircon U–Pb ages and petrology

ABSTRACT Different tectonic interpretations have been proposed for the various spatially associated Palaeoproterozoic granulite-facies lithologies (metasedimentary rocks, metabasites, and felsic granulites) from north-central part of the North China Craton, which hinges primarily on controversies about metamorphic histories of these granulites, especially on the timing of peak metamorphism. Published data exhibit two controversial peak metamorphic ages of 1950–1900 Ma and 1850–1800 Ma. We report here LA-ICPMS U–Pb zircon ages of seven representative granulite-facies samples of different lithologies to constrain the timing of metamorphism, and then discuss their geological significance. Most zircon grains from these rocks display weak core-and-rim structures and yield two comparable group metamorphic ages of 1970–1900 Ma and 1880–1790 Ma, although their formation ages vary from Neoarchaean to Palaeoproterozoic. The older population metamorphic ages are interpreted to approximate timing of high-pressure granulite-facies metamorphism, and the younger population ages as the approximate timing of intermediate- to low-pressure granulite-facies metamorphism. Combined with recent petrological studies, we propose these granulites have shared metamorphic histories at least since ~1970–1900 Ma, and they are probably formed in one single metamorphic cycle in response to crustal-scale subduction–collision–exhumation processes involved in Palaeoproterozoic mobile belt. GRAPHICAL ABSTRACT
Effect of brain tumour laterality on patients' perceived quality of life

Objectives: There is little reliable quantitative information on preoperative quality of life of patients with brain tumours. The aim of this study was to clarify the effect of the volume, location, and histological grade of brain tumours on the preoperative quality of life of patients. Methods: The study population consisted of 101 successive patients with brain tumour at Oulu Clinic for Neurosurgery studied with CT or MRI for preoperative determination of tumour location and size. The Nottingham health profile (NHP) and Sintonen's 15D scale were used at that time to measure quality of life. Results: Tumour size did not correlate linearly with impairment of quality of life. Large tumours (>25 ml) were associated with poorer quality of life than small tumours (≤25 ml). The patients with a tumour located on the right side or in the anterior region reported a poorer quality of life than those with a tumour on the left side or posteriorly. Quality of life assessments made by doctors using the Karnofsky performance scale showed no differences between the two hemispheres. Patients with the most malignant gliomas (grades III-IV) displayed the poorest quality of life. Conclusions: Large tumours apparently damage several parts of the brain and/or raise intracranial pressure to a level that exceeds the brain's compensatory capacity. Contrary to earlier understanding, tumours in the right hemisphere seemed to be related to poorer quality of life. This effect was especially clear in the patients' subjective evaluation of their quality of life. As the location of the brain tumour thus affects perceived quality of life, any measurements of the quality of life of patients with brain tumours should take into account the location and laterality of the tumour.
Analysis of Electric Fields inside Microchannels and Single Cell Electrical Lysis with a Microfluidic Device

Analysis of electric fields generated inside the microchannels of a microfluidic device for electrical lysis of biological cells along with experimental verification are presented. Electrical lysis is the complete disintegration of cell membranes, due to a critical level of electric fields applied for a critical duration on a biological cell. Generating an electric field inside a microchannel of a microfluidic device has many advantages, including the efficient utilization of energy and low-current requirement. An ideal microchannel model was compared with a practical microchannel model using a finite element analysis tool that suggests that the overestimation error can be over 10%, from 2.5 mm or smaller, in the length of a microchannel. Two analytical forms are proposed to reduce this overestimation error. Experimental results showed that the high electric field is confined only inside the microchannel that is in agreement with the simulation results. Single cell electrical lysis was conducted with a fabricated microfluidic device. An average of 800 V for seven seconds across an 8 mm-long microchannel with the dimension of 100 μm × 20 μm was required for lysis, with electric fields exceeding 100 kV/m and consuming 300 mW.
Objective concurrent measures of open-loop accommodation and vergence under photopic conditions.

PURPOSE To investigate the relationship between photopic open-loop accommodation and vergence and the effect of mental effort on these positions. METHODS Twenty subjects (11 men and 9 women) viewed monocularly a photopic (25 cdm-2), high-contrast (90%) Maltese cross-target for 3 minutes, through a 0.5-mm pinhole drilled into an infrared filter. Accommodation was measured objectively at 1-second intervals using a Canon Autoref R-1 infrared optometer, and vergence was recorded continuously and objectively using a differential infrared eye tracking system. RESULTS Under passive viewing conditions there was a significant correlation between photopic open-loop accommodation and vergence (R = 0.671, P = 0.0012); for the majority of subjects the imposition of mental effort shifted the passive levels of both open-loop accommodation and vergence, but these shifts were unsystematic and uncorrelated (R = 0.259, P = 0.270). The active open-loop positions of accommodation and vergence were also found to be correlated (R = 0.692, P = 0.0007). CONCLUSIONS The influence of proximal stimuli can explain the correlations identified between photopic open-loop positions of accommodation and vergence. The uncorrelated responses of the accommodation and vergence systems to mental effort are likely to reflect interactions between various spatiotopic stimuli including mental effort and perceived proximity.
Multimodality Treatment May Improve the Survival Rate of Patients with Metastatic Nasopharyngeal Carcinoma with Good Performance Status

The aim of the present study was to evaluate the benefit of chemotherapy, combined with palliative radiotherapy (PRT) and other local treatments to the metastatic sites, for patients with metastatic nasopharyngeal carcinoma (NPC) who had a performance status 0–2. We conducted a retrospective review of available data from 197 biopsy-proven NPC patients who developed metastasis after their initial definitive treatment. These patients were grouped into three categories according to the different treatment paths that were followed: the best supportive care (64 patients), chemotherapy alone (55 patients), and multimodality treatment with chemotherapy combined with PRT and other local treatments to metastatic sites (78 patients). The 2-year metastatic survival rate of patients in the multimodality treatment group was 57.7%, which was significantly better than that of the patients in both the chemotherapy alone group and the best supportive care group (32.7% and 1.6%, respectively). The independent significant factors affecting survival were the disease-free interval prior to the detection of metastatic disease, the number of metastases, the number of chemotherapy cycles and the biological effective dose of PRT. In conclusion, multimodality treatment may improve survival of select patients with recurrent NPC with distant metastases.
RNA interference--2001.

In the few years since the discovery of RNA interference (RNAi; Fire et al. 1998), it has become clear that this process is ancient. RNAi, the oldest and most ubiquitous antiviral system, appeared before the divergence of plants and animals. Because aspects of RNAi, known as cosuppression, also control the expression of transposable elements and repetitive sequences (Ketting et al. 1999; Tabara et al. 1999), the interplay of RNAi and transposon activities have almost certainly shaped the structure of the genome of most organisms. Surprisingly, we are only now beginning to explore the molecular processes responsible for RNAi and to appreciate the breadth of its function in biology. Practical applications of this knowledge have allowed rapid surveys of gene functions (see Fraser et al. 2000 and Gönczey et al. 2000 for RNAi analysis of genes on chromosome I and III of Caenorhabditis elegans) and will possibly result in new therapeutic interventions. Genetic studies have expanded the biology of RNAi to cosuppression, transposon silencing, and the first hints of relationships to regulation of translation and development. The possible roles of RNA-dependent RNA polymerase (RdRp) in RNAi have been expanded. Many experiments indicate that dsRNA directs gene-specific methylation of DNA and, thus, regulation at the stage of transcription in plants. Cosuppression may involve regulation by polycomb complexes at the level of transcription in C. elegans and Drosophila. This article will review these topics and primarily summarize advances in the study of RNAi over the past year.
COADMINISTRATION OF THE NEW MACROLIDE IMMUNOSUPPRESSANT RAD AND MYCOPHENOLATE MOFETIL IN EXPERIMENTAL CORNEAL TRANSPLANTATION

Introduction. The effect of RAD, a new macrolide immunosuppressant, was examined as mono- and combination therapy with mycophenolate mofetil (MMF) in prevention of acute allograft rejection in murine corneal transplantation. Methods. Both drugs were administered orally for 18 days beginning at the day of transplantation. The inbred strains Fisher and Lewis were used as donors and recipients, respectively. Five groups were involved: syngeneic control, allogeneic control, 2.5 mg/kg RAD, 40 mg/kg MMF, and double drug therapy with 1.5 mg/kg RAD and 20 mg/kg MMF. Results. The median transplant survival time in the allogeneic combination was 12 (±0.3) days. Monotherapy with 2.5 mg/kg RAD and 40 mg/kg MMF led to a statistically significant prolongation of transplant survival to 25.5 (±12.5, P =0,0001) days and 19.5 (±13.9, P =0.0053) days, respectively. Combination therapy was superior to both monotherapies (100±15.8 days, P =0.03). There was a significant reduction in the number of CD4+, CD8+, as well as CD45RA+ cells in the RAD- and double drug-treated animals when compared with the allogeneic control. This significant reduction in graft-infiltrating lymphocytes has not been found in the MMF monotherapy. Conclusions. The unique finding of this first study on the combination of RAD and MMF in murine corneal transplantation is that double drug therapy produces a highly synergistic effect in prevention of acute allograft rejection without a higher incidence of complications related to drug toxicity or overimmunosuppression.
THE MECHANISM OF ANTIGENIC STIMULATION OF PRIMARY AND SECONDARY CLONAL PRECURSOR CELLS

Cell transfers to carrier-immunized irradiated mice have permitted an analysis of the in vitro stimulation of clonal precursors of anti-2,4-dinitrophenyl (DNP) antibody-producing cells derived from both immune and nonimmune mice. The results indicate that: (a) carrier-specific enhancement is obligatory for stimulation of primary precursor cells and increases both the size and number of detectable foci derived from secondary precursors. (b) This carrier-specific enhancement is most apparent in the stimulation of precursors of high-affinity antibody producer cells. (c) The antibody produced by primary foci, like that of secondary foci, appears homogeneous. (d) The frequency of clonal precursors in normal spleens is 38% that in spleens from mice 4–8 months after immunization, and the number of such precursors in normal spleens can be reduced fivefold by specific suppression of donor mice with soluble antigen. (e) The average of association constants of primary monofocal antibodies, like that of primary serum antibody produced in carrier-primed mice, is less than 10-fold lower than that of secondary clonal or serum antibody. (f) The affinity of primary monofocal antibodies shows a slight dependence on stimulating antigen concentration; however, a minimum threshold affinity consonant with stimulation is apparent. (g) Free hapten inhibits antigenic stimulation of primary precursor cells at a much lower concentration than is required for the inhibition of secondary precursors. These results are interpreted as indicating that (a) primary stimulation, like secondary stimulation, results from the selective stimulation by antigen of a population of cells differing from one another in their potential antibody product but each having only a single such product; (b) the antigen receptors of primary cells interact with antigen as if they are monovalent while receptors of secondary cells evidence multivalence; (c) antigenic stimulation appears to require both a relatively high affinity of receptors for bound antigen and an interlinking of receptors through such antigen; stimulation is thus seen as resulting from a stabilization of receptors within antigen-receptor aggregates to the cell surface; (d) T-cells appear to serve both in cross-linking antigens and in amplifying the size of stimulated clones.