Miracle-dz/UniFAR-FTUs huggingface dataset:
Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.

BACKGROUND The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.
Intelligent Custom Block Generation

The current density of integration circuits, yields extremely complex Systems-on-a-Chip (SoCs) that take a long time to design and develop and thus, many times, they miss the market window for these products. This has motivated intensive research on High-level Synthesis (HLS) methodologies, so that such complex and custom systems are rapidly designed and prototyped. The contribution of this work is a formal and intelligent HLS synthesis and rapid verification methodology with custom options, which re-uses and incorporates the generation of predesigned custom hardware functional units, from abstract behavioural ADA code. The usability of the proposed methodology is confirmed with a number of HLS benchmarks including a hierarchical RSA crypto-processor design and a line-drawing algorithm from computer graphics.
A Study of Virtual Machine Placement Optimization in Data Centers

In recent years, cloud computing has shown a valuable way for accommodating and providing services over the Internet such that data centers rely increasingly on this platform to host a large amount of applications (web hosting, e-commerce, social networking, etc.). Thus, the utilization of servers in most data centers can be improved by adding virtualization and selecting the most suitable host for each Virtual Machine (VM). The problem of VM placement is an optimization problem aiming for multiple goals. It can be covered through various approaches. Each approach aims to simultaneously reduce power consumption, maximize resource utilization and avoid traffic congestion. The main goal of this literature survey is to provide a better understanding of existing approaches and algorithms that ensure better VM placement in the context of cloud computing and to identify future directions.
Cell type and function of neurons in the ascidian nervous system

Ascidians, or sea squirts, are primitive chordates, and their tadpole larvae share a basic body plan with vertebrates, including a notochord and a dorsal tubular central nervous system (CNS). The CNS of the ascidian larva is formed through a process similar to vertebrate neurulation, while the ascidian CNS is remarkably simple, consisting of about 100 neurons. Recent identification of genes that are specifically expressed in a particular subtype of neurons has enabled us to reveal neuronal networks at single‐cell resolution. Based on the information on neuron subtype‐specific genes, different populations of neurons have been visualized by whole‐mount in situ hybridization, immunohistochemical staining using specific antibodies, and fluorescence labeling of cell bodies and neurites by a fluorescence protein reporter driven by neuron‐specific promoters. Neuronal populations that have been successfully visualized include glutamatergic, cholinergic, γ‐aminobutyric acid/glycinergic, and dopaminergic neurons, which have allowed us to propose functional regionalization of the CNS and a neural circuit for locomotion. Thus, the simple nervous system of the ascidian larva can serve as an attractive model system for studying the development, function, and evolution of the chordate nervous system.
Drawing Conclusions about Short-Term Variability in Liver Function Test Results

TO THE EDITOR: We read with great interest the recent study by Lazo and colleagues (1) on the short-term variability of various biochemical liver tests and want to share some concerns. First, this study is based on a nonrandom, convenience sample that represents only 9.5% (1864 out of 19618) of the original NHANES (National Health and Nutrition Examination Survey) study population, raising questions about the generalizability of the findings, given the strong likelihood for selection bias. Second, the very small percentage of persons from racial or ethnic groups other than white, black, and Hispanic restricts the applicability of the results, particularly for Asians. The cutoff values of normal levels of serum alanine aminotransferase (ALT) that were used in this study40 IU/L for men and 31 IU/L for womenare probably overestimates, as has been shown in 2 large studies from Italy and Korea (2, 3). These studies recommend using cutoff values of 30 IU/L for men and 19 IU/L for women. On the basis of these recommended cutoff values, a substantial percentage of patients in Lazo and colleagues' study classified as having elevated ALT levels at examination 1 (median, 43 IU/L) who returned to normal in examination 2 (median, 27 IU/L) would probably still have abnormal levels of ALT. These distinctions are not trivial, as evidenced by the increased risk for death in individuals with ALT levels greater than 20 IU/L compared with those with ALT levels less than 20 IU/L (relative risk for patients with ALT levels of 20 to 29 IU/L, 2.9; relative risk for patients with ALT levels of 30 to 39 IU/L, 9.5) (3). The American Association for the Study of Liver Diseases has also called for recalibration of the normal range for ALT level (4). Finally, the Gilbert syndrome, a genetic disease with a prevalent homozygosity of 9% in the Western population, can result in values outside the normal range of total bilirubin level, varying with fasting status or stress. This may affect the determination of normal versus abnormal values in Lazo and colleagues' study.
Human Anulus Fibrosis and Nucleus Pulposus Cells of the Intervertebral Disc: Effect of Degeneration and Culture System on Cell Phenotype

Study Design. Human intervertebral disc cells were harvested from patients with adolescent idiopathic scoliosis (AIS) and from donors with degenerative disc disease. Anulus fibrosis (AF) was separated from nucleus pulposus (NP), and cells were cultured separately in two different cell culture models. Objectives. To investigate changes in gene expression of human disc cells during in vitro expansion and to determine whether cells from adolescent idiopathic scoliosis donors show different gene expression profiles compared with cells from patients operated for degenerative disc disease. Summary of Background Data. During in vitro expansion, cells undergo a dedifferentiation process, which is characterized by a switch in gene expression. Markers for the differentiation and dedifferentiation status of human disc cells are not yet known. Moreover, it is not known whether changes in the gene expression pattern occur during the degeneration process. Methods. Cells from AF and NP tissues were expanded in monolayer and alginate cultures under controlled and defined conditions. Cells were then harvested, and analysis of phenotype was performed using quantitative real-time polymerase chain reaction (PCR). The mRNA expression of Type I, II, and X collagen, aggrecan, and interleukin-1β in scoliosis and degenerative human intervertebral disc cells was analyzed. Results. The gene expression of Type II and X collagen and of aggrecan significantly decreased for both cell types during monolayer expansion. Reexpression of all genes was observed when cells were cultured in alginate. Additionally, NP cells from degenerative tissues displayed significant lower levels of Type II collagen compared with NP cells from scoliosis donors. Conclusions. These results provide a better understanding of how the phenotype of human healthy anddegenerative disc cells is influenced by in vitro expansion. This may be useful for future tissue engineering purposes.
A new type of master robot for teleoperation using a radial wire drive system

A new type of master robot for teleoperation is proposed. In the proposed master robot, several wires are stretched from a handle which is moved by a human operator. In this paper, the authors explain how many wires are necessary to control a handle with six degrees of freedom in a three dimensional space. Moreover, to feed forces from a slave robot to the handle, an algorithm to determine each wire tension is proposed. Finally, they show experimental results in which a handle is moved by seven wires in a three dimensional space.
ANTERIOR CHAMBER ASSOCIATED IMMUNE DEVIATION (ACAID): REGULATION, BIOLOGICAL RELEVANCE, AND IMPLICATIONS FOR THERAPY

Immune privilege was first explored in the late 1800s by van Dooremaal, and was then extended by Medawar in the mid 1900s to fit in with emerging concepts of transplantation immunology. Modern concepts and understanding of immune privilege come from subsequent studies produced by Medawar, Billingham, and Streilein. The exploitation of the model of anterior chamber immune deviation (ACAID) in mice has allowed us to look at both cellular and molecular mechanisms involved in the prevention of potentially damaging immune responses in such privileged sites. This review gives a historical perspective of the immune privilege research and provides up-to-date information of molecules, cells, and concepts newly recognized as contributing to tolerance induction induced in such specialized areas of the body. Evidence is given to support the idea that application of such information may lead to potential for therapeutic applications of ACAID mechanisms in prevention of progression of immune-inflammatory diseases in humans.
Muscle and Plasma Amino Acids after Injury: Hypocaloric Glucose vs. Amino Acid Infusion

This study examines the effect of three different hypocaloric diets on the patterns of muscle and plasma amino acids in patients undergoing total hip replacement. Group I (seven patients) received 90 g/day of glucose, Group II (seven patients) received 70 g/day of amino acids, Group III (eight patients) received both 90 g of glucose and 70 grams of amino acids per day. Utilizing the percutaneous biopsy technique of Berg-ström, free amino acid patterns in muscle and plasma were analyzed pre- and postoperatively (day 4). The postoperative pattern of amino acids was characterized by elevated levels in muscle and plasma of the branched chain amino acids, phenylalanine, tyrosine and methionine. There was a marked decrease in muscle glutamine and smaller decreases in the basic amino acids in both muscle and plasma. Muscle:plasma concentration ratios increased for the neutral amino acids, decreased for glutamine and the basic amino acids and were unchanged for the acidic amino acids. The patterns seen after hip replacement are almost identical to those seen after colectomy or accidental injury. There was little effect of diet on amino acid concentrations in muscle. In plasma, concentrations of leucine, isoleucine valine and proline were higher in Group II in the absence of glucose intake, than in the other groups. Lysine was lower in Group I with no amino acid intake than in the other groups. Thus, there is a unique amino acid pattern associated with operative trauma which is relatively unaffected by hypocaloric, intravenous nutrition.
Distribution of Ia‐Antigen‐like Molecules on Non‐lymphoid Tissues

Ia‐antigen‐like molecules are expressed on cells within several different non‐lymphoid tissues of the guinea‐pig. In indirect immunofluorescence analyses anti‐la‐Lintigen antibodies stained epithelial cells lining the intestinal tract, the bile ducts, the respimiory tract and the urinary tract. The rabbit antibodies against la antigens also stained the cells of the parotid and the submandibular glands. Evidence was also obtained suggesting that the reticuloepithelial cells of the thymus, like the Kupffer cells of the liver, express Ia‐antigen‐like molecules. In several cases indirect immunoprecipitation analyses and SDS‐polyacrylamide gel electrophoresis confirmed the immunoprecipitation studies inasmuch as Ia‐anligen‐like subunit with apparent molecular weights of 26,000 and 34,000 could be isolated from ihe non‐lymphoid organs.
Expression of the endogenous type II secretion pathway in Escherichia coli leads to chitinase secretion

Escherichia coli K‐12, the most widely used laboratory bacterium, does not secrete proteins into the extracellular medium under standard growth conditions, despite possessing chromosomal genes encoding a putative type II secretion machinery (secreton). We show that in wild‐type E.coli K‐12, divergent transcription of the two operons in the main chromosomal gsp locus, encoding the majority of the secreton components, is silenced by the nucleoid‐structuring protein H‐NS. In mutants lacking H‐NS, the secreton genes cloned on a moderate‐copy‐number plasmid are expressed and promote efficient secretion of the endogenous, co‐regulated endochitinase ChiA. This is the first time that secretion of an endogenous extracellular protein has been demonstrated in E.coli K‐12.
9trans,11trans Conjugated Linoleic Acid Inhibits the Development of Azoxymethane-Induced Colonic Aberrant Crypt Foci in Rats

Abstract We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 9t,11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t,11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor γ were observed in the colonic mucosa of rats fed a diet supplemented with 9t,11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.
Quark spin distribution and quark-antiquark annihilation in single-spin hadron-hadron collisions.

We show that quark-antiquark annihilation processes in single-spin inclusive production experiments can yield useful information on hadron spin structure in general, and provide crucial tests for the existence of orbiting valence quarks in particular. There are several experimental indications and theoretical arguments for the existence of such orbital motion inside polarized protons or antiprotons. Simple relations between quark-spin distributions and left-right asymmetries in such production processes can be given, and quantitative predictions can be made.
Human Papillomavirus Infection in Danish Female Sex Workers: Decreasing Prevalence With Age Despite Continuously High Sexual Activity

Background: The prevalence of the human papillomavirus (HPV) has been found to decrease with age, but whether this applies to all populations is not clear. Knowledge about the generalizability of this age dependency is important to understand the natural history of the infection, but may also have implications in relation to the use of HPV testing in cervical cancer screening. Goal: To study the prevalence and risk factors for HPV infection in a selected population of female sex workers and to compare the results with persons with different sexual habits from two other populations in the same geographic area. Study Design: A case‐control study among 188 female sex workers from Copenhagen. Data were obtained by personal interviews. Cervical material was collected by a self‐administered lavage kit, and HPV testing was done by means of GP5+/6+ primers based on HPV, polymerase chain reaction, enzyme immunoassay. Results: Among sex workers, age was the most important risk factor for HPV infection. Number of private sex partners in the last 4 months was also a significant risk factor, and a protective effect of condom use was indicated. Conclusion: The HPV prevalence is declining in sex workers with age despite continuously high sexual activity, most likely indicating that an immune response is acquired over time.
MicroRNA-610 inhibits tumor growth of melanoma by targeting LRP6

Accumulating evidence showed that aberrant miRNAs expression was involved in initiation and progression of melanoma. However, the investigation of different miRNAs in melanoma remain attractive. In this research, we demonstrated that miR-610 expression was decreased in melanoma tissues and cell lines. The clinical data showed that the reduced miR-610 expression was obviously associated with adverse prognostic characteristics. Furthermore, our results suggested that miR-610 had a function of prognostic indicator for 5-year predicted-survival of melanoma patients. The ectopic overexpression of miR-610 suppressed cell proliferation, cell cycle progression and promoted apoptosis while miR-610 knockdown reversed the effect in vitro and in vivo. Additionally, miR-610 could modulate LRP6 by directly interacting to its 3’-UTR. In clinical samples of melanoma, miR-610 inversely correlated with LRP6. The biological function of miR-610 on melanoma cells was abrogated by alternation of LRP6 expression. In summary, our research indexed that miR-610 had a function of tumor suppressor in regulating the proliferation, cell cycle and apoptosis of melanoma via targeting LRP6. Hence, it may represent a novel potential therapeutic target and prognostic marker for melanoma.
Mixed Methodology to Predict Social Meaning for Decision Support

Abstract : For analysts of social content in language, popular Internet forums provide ample material for observing usage variation patterns. A single phenomenon, scrutinized through the lens of an established theoretical construct, focuses an approach to analysis, which is computationally tractable and exploitable. The contribution to ongoing work reported on here shows how diverse and complex manifestations of a style-switching variant of the code-switching phenomenon can serve profitably as data input to machine learning. On a group membership prediction task, logistic regression results for user posts containing style features were in the high 80s. A novel representation of structures in posts without style features boosted results for this group as well. We indicate how this approach may extend to popular social media sites, such as Facebook, to inter-language code-switching and diverse computational tasks.
The Praise Paradox: When and Why Praise Backfires in Children With Low Self‐Esteem

In contemporary Western society, many adults use praise to boost children's self-esteem. Accordingly, they might praise those who seem to need it the most: children with low self-esteem. In this article, we review research showing that certain types of praise can backfire, especially in children with low self-esteem. Adults are inclined to give children with low self-esteem person praise (e.g., “You're smart! ”) and inflated praise (e.g., “That's incredibly beautiful! ”). Paradoxically, such praise can lower these children's motivation and feelings of self-worth in the face of setbacks (e.g., when they struggle or fail). Lowered feelings of self-worth, in turn, might invite more person praise and inflated praise from adults, creating a self-sustaining downward spiral. We propose a transactional model to shed light on this apparent praise paradox, and we describe the model's implications for theory and research.
Impact of the cell division cycle on gene circuits

In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle.
SCRIBE : A Hardware Infrastructure Enabling Fine-Grained Software Layer Diagnosis

Recent studies have shown that intermittent faults have gained increased prominence on being responsible for computer system failures. This category of faults is harder to diagnose in comparison with permanent faults. Full hardware diagnosis techniques incur significant power and area overheads. Software layer diagnosis techniques have zero area overhead but limited visibility into many micro-architectural structures and hence cannot diagnose faults in them. We propose SCRIBE, a simple hardware infrastructure to enable fine-grained software layer diagnosis. SCRIBE records the detailed micro-architectural resource usage of each instruction in the processor and exposes it to the software diagnosis layer. Our evaluation indicates that SCRIBE has an overhead of 12 to 23% depending on the processor type.