Miracle-dz/UniFAR-FTUs huggingface dataset:
Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.

BACKGROUND The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan. METHODS We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment. RESULTS The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combination-therapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone. CONCLUSIONS Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.
Human co-transcriptional splicing kinetics and coordination revealed by direct nascent RNA sequencing

Human genes have numerous exons that are differentially spliced within pre-mRNA. Understanding how multiple splicing events are coordinated across nascent transcripts requires quantitative analyses of transient RNA processing events in living cells. We developed nanopore analysis of CO-transcriptional Processing (nano-COP), in which nascent RNAs are directly sequenced through nanopores, exposing the dynamics and patterns of RNA splicing without biases introduced by amplification. nano-COP showed that in both human and Drosophila cells, co-transcriptional splicing occurs after RNA polymerase II transcribes several kilobases of pre-mRNA, suggesting that metazoan splicing transpires distally from the transcription machinery. Inhibition of the branch-site recognition complex SF3B globally abolished co-transcriptional splicing in both species. Our findings revealed that splicing order does not strictly follow the order of transcription and is influenced by cis-regulatory elements. In human cells, introns with delayed splicing frequently neighbor alternative exons and are associated with RNA-binding factors. Moreover, neighboring introns in human cells tend to be spliced concurrently, implying that splicing occurs cooperatively. Thus, nano-COP unveils the organizational complexity of metazoan RNA processing.
Vibrio Species in Fish and Shell Fish

A grand total of 100 random samples of fresh water fish with average weight 100-250g(Oreochromis niloticus), marine water fish (Mugil cephalus), and shell fish (shrimp and crab) withaverage weight 10-50g were collected from different markets in Gharbia governorate for detectionof Vibrio spp. The obtained results revealed that the incidence of Vibrio spp. in fresh water fish(Oreochromis niloticus) were 8 (32%), with frequency of 2 (8%), 2 (8%), 2 (8%), 1 (4%) and 1 (4%)for V. parahaemolyticus, V. mimicus, V. vulnificus, V. alginolyticus and V. fluvialis, respectively. Inmarine fish (Mugil cephalus),Vibrio spp. were 10 (40%), the overall incidence in the samples wasfor V. parahaemolyticus 3(12%), V. mimicus 2(8%), V. alginolyticus 2 (8%), V. vulnificus 1 (4%)and V. fluvialis 2 (8%). In shell fish (shrimp), Vibrio spp. were 13 (52%) while the overall incidencein the samples was V. parahaemolyticus 4 (16%), mimicus 3 (12%), V. alginolyticus 2 (8%), V.vulnificus 1 (4%), V. fluvialis 2 (8%) and V. cholera 1 (4%). Regarding crab, Vibrio spp. were 11(44%) while the overall incidence in the samples was V. parahaemolyticus 3 (12%), mimicus 2 (8%),V. alginolyticus 2 (8%), V. vulnificus 1 (4%), V. fluvialis 2 (8%) and V. cholera 1 (4%).
A calcium-binding, asparagine-linked oligosaccharide is involved in skeleton formation in the sea urchin embryo

We have previously identified a 130-kD cell surface protein that is involved in calcium uptake and skeleton formation by gastrula stage embryos of the sea urchin Strongylocentrotus purpuratus (Carson et al., 1985. Cell. 41:639-648). A monoclonal antibody designated mAb 1223 specifically recognizes the 130-kD protein and inhibits Ca+2 uptake and growth of the CaCO3 spicules produced by embryonic primary mesenchyme cells cultured in vitro. In this report, we demonstrate that the epitope recognized by mAb 1223 is located on an anionic, asparagine- linked oligosaccharide chain on the 130-kD protein. Combined enzymatic and chemical treatments indicate that the 1223 oligosaccharide contains fucose and sialic acid that is likely to be O-acetylated. Moreover, we show that the oligosaccharide chain containing the 1223 epitope specifically binds divalent cations, including Ca+2. We propose that one function of this negatively charged oligosaccharide moiety on the surfaces of primary mesenchyme cells is to facilitate binding and sequestration of Ca+2 ions from the blastocoelic fluid before internalization and subsequent deposition into the growing CaCO3 skeleton.
Towards systematic grammar profiling.Test suite technology 10 years after

Abstract An experiment with recent test suite and grammar (engineering) resources is outlined: a criticial assessment of the EU-funded tsnlp (Test Suites for Natural Language Processing) package as a diagnostic and benchmarking facility for a distributed (multi-site) large-scale hpsg grammar engineering effort. This paper argues for a generalized, systematic, and fully automated testing and diagnosis facility as an integral part of the linguistic engineering cycle and gives a practical assessment of existing resources; both a flexible methodology and tools for competence and performance profiling are presented. By comparison to earlier evaluation work as reflected in the Hewlett-Packard test suite data, released exactly 10 years before tsnlp , it is judged where test-suite-based evaluation has improved (and where not) over time.
Prioritization of Software Process Improvements - A COQUALMO-based Case Study and Derived Decision Support Scheme

Quality assurance has always been a major concern for software engineers. While a lot of work has been devoted to technical quality assurance aspects, its economics have rarely been addressed. This is remarkable in the light of the current endeavor of the software industry to learn from more mature industries and to adapt their ‘lean’ and process improvement philosophies. We advance this debate by proposing a decision support scheme. It facilitates the selection and prioritization of quality assurance activities for improvement initiatives. The prioritizing order is based on the expected quality gains in terms of reduced number of defects in the software product. Our scheme supports managers in their decision process, as shown in three industrial case studies. It can be instantiated with low data-collection effort because it makes use of calibration data and model characteristics of COQUALMO.
The relationships between testosterone, body composition, and insulin resistance: a lesson from a case of extreme hyperandrogenism.

Association between hyperandrogenism and insulin resistance is well recognized in women with polycystic ovary syndrome (PCOS) (1). However, earlier evidence (2) suggesting an insulin-antagonizing effect of androgens has been overshadowed by more recent studies demonstrating that antiandrogen treatment with flutamide (3) or GnRH agonists (4,5) does not alter insulin resistance in PCOS. Conflicting results have been reported in non-PCOS women, with some studies (1,6–9) suggesting that testosterone may be related to insulin resistance and others (10,11) showing no correlation. Recent data suggest that some of these discrepancies may be explained by racial disparities, since only obese African-American women exhibited a positive relationship between insulin resistance and gonadal androgens (6). Inconclusive data have also been reported in men given testosterone in replacement or supraphysiologic doses, with some studies (12) suggesting a sensitizing effect of testosterone on glucose metabolism and others (13–16) showing no effect. Nonetheless, androgens can influence body composition, which is associated with insulin sensitivity. Thus, it is conceivable that testosterone might indirectly influence insulin sensitivity via its effects on body composition. We report the results of hormonal, metabolic, and body composition studies before and 1 month and 9 months after a Leydig cell tumor removal in a postmenopausal woman. A 64-year-old gravida 7, para 7, Hispanic woman was referred for evaluation of virilization starting ∼10 years earlier and progressing over the past 3 years. Menses were regular before menopause (age 50). Diabetes was diagnosed 2 months before presentation and was well controlled by 1.5 mg glyburide daily (HbA1c 4.8%). She had a 22-year history of hypertension, treated with benazepril and amlodipine. A physical examination revealed male pattern alopecia, masculine habitus, abdominal obesity, clitoromegaly, and breast atrophy …
Differential recovery of protein kinase C-alpha and -epsilon isozymes after long-term phorbol ester treatment in rat renal mesangial cells.

Glomerular mesangial cells have been shown to express two protein kinase C (PKC) isozymes, PKC-alpha and PKC-epsilon. Upon long-term treatment with phorbol ester PKC-alpha is depleted faster than PKC-epsilon. Here we demonstrate that removal of phorbol ester results in a differential recovery of PKC-alpha and -epsilon isozymes. Whereas PKC-epsilon starts to recover within 1h, PKC-alpha does not begin to recover before 4 h after removal of phorbol ester. These data suggest a differential rate of protein synthesis of PKC-alpha and -epsilon. In parallel to the recovery of PKC isozymes mesangial cells also regained their functional responsiveness, i.e., stimulation of prostaglandin synthesis and feedback inhibition of angiotensin II-stimulated InsP3 formation.
Using Machine Learning Techniques to Evaluate Multicore Soft Error Reliability

Virtual platform frameworks have been extended to allow earlier soft error analysis of more realistic multicore systems (i.e., real software stacks and state-of-the-art ISAs). The high observability and simulation performance of underlying frameworks enable to generate and collect more error/failure-related data, considering complex software stack configurations, in a reasonable time. When dealing with sizeable failure-related data sets obtained from multiple fault campaigns, it is essential to filter out parameters (i.e., features) without a direct relationship with the system soft error analysis. In this regard, this paper proposes the use of supervised and unsupervised machine learning techniques, aiming to eliminate non-relevant information as well as identify the correlation between fault injection results and application and platform characteristics. This novel approach provides engineers with appropriate means to investigate new and more efficient fault mitigation techniques. The underlying approach is validated with an extensive data set gathered from more than 1.2 million fault injections, comprising several benchmarks, a Linux OS and parallelization libraries (e.g., MPI and OpenMP), as well as through a realistic automotive case study.
CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.

CONTEXT Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
Speciation genetics: current status and evolving approaches

The view of species as entities subjected to natural selection and amenable to change put forth by Charles Darwin and Alfred Wallace laid the conceptual foundation for understanding speciation. Initially marred by a rudimental understanding of hereditary principles, evolutionists gained appreciation of the mechanistic underpinnings of speciation following the merger of Mendelian genetic principles with Darwinian evolution. Only recently have we entered an era where deciphering the molecular basis of speciation is within reach. Much focus has been devoted to the genetic basis of intrinsic postzygotic isolation in model organisms and several hybrid incompatibility genes have been successfully identified. However, concomitant with the recent technological advancements in genome analysis and a newfound interest in the role of ecology in the differentiation process, speciation genetic research is becoming increasingly open to non-model organisms. This development will expand speciation research beyond the traditional boundaries and unveil the genetic basis of speciation from manifold perspectives and at various stages of the splitting process. This review aims at providing an extensive overview of speciation genetics. Starting from key historical developments and core concepts of speciation genetics, we focus much of our attention on evolving approaches and introduce promising methodological approaches for future research venues.
Update on Mechanisms of Plant Cell Wall Biosynthesis: How Plants Make Cellulose and Other (1→4)-β-d-Glycans1

The discovery of a gene that encodes a cotton ( Gossypium hirsutum ) cellulose synthase ([Pear et al., 1996][1]) revolutionized and invigorated the plant cell wall community to find the genes that encode the machinery of cell wall polysaccharide synthesis. The landscape was framed by the completion
β‐Adrenergic Binding Sites in Fetal Rat Brain

Abstract: The ontogeny of β‐adrenergic binding sites was studied in forebrain homogenates from male and female rats. Specific [3H]dihydroalprenolol binding was defined by the difference between binding in the presence and in the absence of 330 nM (+)oxprenolol. Significant binding was detected at prenatal stages. The dissociation constants (KD of [3H]dihydroalprenolol binding were similar at gestational day (GD) 193/4 and postnatal day (PN) 31. Binding was first detected in forebrain at GD 153/4. The amount of binding sites increased until PN 31, when adult values were reached. No sex differences could be detected at any of the stages tested (GD 193/4‐PN 31).
Titling and Chronic Diseases: Evidence from A Natural Experiment in Uruguay

In this paper the author exploits a natural experiment to study the effects of granting formal property rights on health for households in Uruguay. Titling could improve health outcomes through various channels: housing investment, income or family cohesion. The author found that titling diminishes the probability of suffering several chronic diseases (hypertension, diabetes, sinusitis and rheumatism) but could not find supporting evidence for the housing channel.
The organization of the inner nuclear layer of the rabbit retina

The initial goal of this study was to establish an accounting of the major classes of cells present in the inner nuclear layer (INL) of the rabbit's retina. Series of 80–100 radial sections 1 micron thick were cut from retinal blocks dissected at intervals along the vertical meridian. They were photographed at high magnification in the light microscope. By visualizing the initial segments of processes leaving the somata, we could identify each cell as a bipolar, amacrine, horizontal, or Muller cell. The identifications made by light microscopy were confirmed by electron microscopy of alternating ultrathin sections. On average, bipolar cells made up 41% of the total INL cells, amacrine cells 32%, horizontal cells 1.5%, and Muller cells 24%. These fractions varied relatively little across the retina or among different animals. We next immunolabeled the rod bipolar cells of whole-mounted retinas with antibodies against protein kinase C, using FITC as the visualizing agent. The same retinas were counterstained with a DNA-binding probe that fluoresces at longer wavelengths. Serial optical horizontal sections of the double-labeled wholemounts were made by confocal microscopy. On average, rod bipolars accounted for 10% of the total INL cells. By subtraction, the cone bipolars made up 31% of the total cells. We conclude that cone bipolars substantially outnumber rod bipolars, even in a retina in which rods outnumber cones by more than 20:1. Using the base of reference created here, a similar analysis can be carried out for other subclasses of retinal neuron. Because the analysis does not depend on absolute cell densities or corrections for shrinkage, data acquired by different histochemical techniques may be combined.
Road Proximity Increases Risk of Skeletal Abnormalities in Wood Frogs from National Wildlife Refuges in Alaska

Background Skeletal and eye abnormalities in amphibians are not well understood, and they appear to be increasing while global populations decline. Here, we present the first study of amphibian abnormalities in Alaska. Objective In this study we investigated the relationship between anthropogenic influences and the probability of skeletal and eye abnormalities in Alaskan wood frogs (Rana sylvatica). Methods From 2000 to 2006, we examined 9,269 metamorphic wood frogs from 86 breeding sites on five National Wildlife Refuges: Arctic, Innoko, Kenai, Tetlin, and Yukon Delta. Using road proximity as a proxy for human development, we tested relationships between skeletal and eye abnormalities and anthropogenic effects. We also examined a subsample of 458 frogs for the trematode parasite Ribeiroia ondatrae, a known cause of amphibian limb abnormalities. Results Prevalence of skeletal and eye abnormalities at Alaskan refuges ranged from 1.5% to 7.9% and were as high as 20% at individual breeding sites. Proximity to roads increased the risk of skeletal abnormalities (p = 0.004) but not eye abnormalities. The only significant predictor of eye abnormalities was year sampled (p = 0.006). R. ondatrae was not detected in any Alaskan wood frogs. Conclusions Abnormality prevalence at road-accessible sites in the Kenai and Tetlin refuges is among the highest reported in the published literature. Proximity to roads is positively correlated with risk of skeletal abnormalities in Alaskan wood frogs.
The heterogeneous Colonel Blotto game

The Colonel Blotto game, proposed by Borel in 1921, is a fundamental model of strategic resource allocation. Two players allocate an exogenously given amount of resources to a fixed number of battlefields with given values. Each battlefield is then won by the player who allocated more resources to it, and each player maximizes the aggregate value of battlefields he wins. This game allows modeling many practical problems of resource allocation in various strategic settings ranging from international war to competition for attention in social networks; it is particularly useful in security to model the allocation of defense resources on different potential targets. The scope of applications, however, has been limited by the lack of solutions of the game in realistic scenarios. Indeed, despite its apparent simplicity, the Colonel Blotto game is very intricate and it remains unsolved in the case with asymmetric players (i.e., with different resources) and with an arbitrary number of battlefields that can have different values. In this paper, we propose a solution of the heterogeneous Colonel Blotto game with asymmetric players and heterogeneous battlefield values, under the assumption that there is a sufficient number of battlefields of each possible value relative to the players' resources asymmetry. In particular, our assumption implies that there must be at least three battlefields of each possible value. Then, we characterize the unique equilibrium payoffs and univariate marginal distributions, along with the proof that there exist n-variate joint distributions with such marginals. Our results expand the scope of potential applications of the Colonel Blotto game, and mark a new step towards a complete solution of the game.