Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on imatinib for gastrointestinal stromal tumors: duration of treatment

Gastrointestinal stromal tumors (GISTs) are the most common sarcoma of the gastrointestinal tract, with transformation typically driven by activating mutations of c-KIT and less commonly platelet-derived growth factor receptor alpha (PDGFRA). Successful targeting of c-KIT and PDGFRA with imatinib, a tyrosine kinase inhibitor (TKI), has had a major impact in advanced GIST and as an adjuvant and neoadjuvant treatment. If treatment with imatinib fails, further lines of TKI therapy have a role, but disease response is usually only measured in months, so strategies to maximize the benefit from imatinib are paramount. Here, we provide an overview of the structure and signaling of c-KIT coupled with a review of the clinical trials of imatinib in GIST. In doing so, we make recommendations about the duration of imatinib therapy and suggest how best to utilize imatinib in order to improve patient outcomes in the future.
Comparison of single-mother and two-parent families on metabolic control of children with diabetes.

OBJECTIVE To understand the impact of family structure on the metabolic control of children with diabetes, we posed two research questions: 1) what are the differences in sociodemographic, family, and community factors between single-mother and two-parent families of diabetic children? and 2) to what extent do these psychosocial factors predict metabolic control among diabetic children from single-mother and two-parent families? RESEARCH DESIGN AND METHODS This cross-sectional study included 155 diabetic children and their mothers or other female caregivers. The children were recruited if they had been diagnosed with diabetes for at least 1 year, had no other comorbid chronic illnesses, and were younger than 18 years of age. Interviews and self-report questionnaires were used to assess individual, family, and community variables. RESULTS The findings indicate that diabetic children from single-mother families have poorer metabolic control than do children from two-parent families. Regression models of children's metabolic control from single-mother families indicate that age and missed clinic appointments predicted HbA1c levels; however, among two-parent families, children's ethnicity and adherence to their medication regimen significantly predicted metabolic control. CONCLUSIONS This study suggests that children from single-mother families are at risk of poorer metabolic control and that these families have more challenges to face when raising a child with a chronic illness. Implications point to a need for developing strategies sensitive to the challenges of single mothers.
A Novel Signal Transduction Cascade Involving Direct Physical Interaction of the Renin/Prorenin Receptor With the Transcription Factor Promyelocytic Zinc Finger Protein

A human renin/prorenin receptor (RER) has recently been cloned. To gain insight into the molecular function of the RER, we studied its signal transduction mechanisms. Initially, we found a ubiquitous and intracellular expression pattern of the human RER. Consistently, we observed several transcriptional start sites and a high promoter activity of the human RER. We could identify the transcription factor promyelocytic zinc finger (PLZF) protein as a direct protein interaction partner of the C-terminal domain of the RER by yeast 2-hybrid screening and coimmunoprecipitation. Coimmunoprecipitation experiments also indicated homodimerization of the RER. On activation of the RER by renin, PLZF is translocated into the nucleus and represses transcription of the RER itself, thereby creating a very short negative feedback loop, but activates transcription of the p85α subunit of the phosphatidylinositol-3 kinase (PI3K-p85α). Small interfering RNA against the RER abolished these effects. A PLZF cis-element in the RER promoter was identified by site-directed mutagenesis and electrophoretic mobility-shift assay. Renin stimulation caused a 6-fold recruitment of PLZF to this promoter region as shown by chromatin immunoprecipitation. Moreover, renin stimulation of rat H9c2 cardiomyoblasts induced an increase of cell number and a decrease of apoptosis. These effects were partly abolished by PI3K inhibition and completely abrogated by small interfering RNA against PLZF. Finally, experiments in PLZF knockout mice confirmed the role of PLZF as an upstream regulator of RER and PI3K-p85α. Our data demonstrate the existence of a novel signal transduction pathway involving the ligand renin, RER, and the transcription factor PLZF, which is of physiological and putative pathophysiological relevance.
Deuterostome neuroanatomy and the body plan paradox

SUMMARY The paradox of deuterostome body plans is that genome analyses indicate deuterostomes are a group with strong kinship, yet they are an assemblage with what appear to be distinctly different body plans. The two major deuterostome groups, chordates and ambulacraria, are allied by features of their anatomy that do not include the nervous systems. Here I review data emerging from neuroanatomical studies that indicate echinoderms and hemichordates have two distinct parts to their nervous systems. In this brief perspective, I propose the hypothesis that in the ambulacraria the two parts are separated spatially and temporally over life history stages, whereas in chordates the two parts are united in a single central nervous systems. This view provides a means of including neuroanatomy in a common deuterostome body plan.
Numerical Methods for p-Harmonic Flows and Applications to Image Processing

We propose in this paper an alternative approach for computing p-harmonic maps and flows: instead of solving a constrained minimization problem on SN-1, we solve an unconstrained minimization problem on the entire space of functions. This is possible, using the projection on the sphere of any arbitrary function. Then we show how this formulation can be used in practice, for problems with both isotropic and anisotropic diffusion, with applications to image processing, using a new finite difference scheme.
Uncoupling of Natural IgE Production and CD23 Surface Expression Levels

CD23, the low affinity receptor for immunoglobulin E (IgE), has been proposed to play a critical role in the regulation of IgE production, based on altered IgE levels in CD23-deficient mice and transgenic mouse models, as well as in mouse strains with mutations in the CD23 gene, e.g. 129 substrains. Here, we have investigated a mouse line termed LxT1 that expresses reduced CD23 surface levels on B cells, and its influence on natural IgE production. Extensive phenotypic analysis showed that CD23 surface expression was reduced in LxT1 compared to the control, without affecting B cell development in general. This CD23low surface level in LxT1 mice is not as a result of reduced CD23 mRNA expression levels or intracellular accumulation, but linked to a recessive locus, a 129-derived region spanning 28 Mb on chromosome 8, which includes the CD23 gene. Sequence analysis confirmed five mutations within the CD23 coding region in LxT1 mice, the same as those present in New Zealand Black (NZB) and 129 mice. However, this CD23low phenotype was not observed in all 129 substrains despite carrying these same CD23 mutations in the coding region. Moreover, serum IgE levels in LxT1 mice are as low as those in the C57BL/6 (B6) strain, and much lower than those in 129 substrains. These data indicate that the CD23 surface level and serum IgE level are uncoupled and that neither is directly regulated by the mutations within the CD23 coding region. This study suggests that caution should be taken when interpreting the immunological data derived from mice with different genetic background, especially if the gene of interest is thought to influence CD23 surface expression or serum IgE level.
Calcium-Dependent Inhibition of L, N, and P/Q Ca2+Channels in Chromaffin Cells: Role of Mitochondria

The hypothesis that the buffering of Ca2+ by mitochondria could affect the Ca2+-dependent inhibition of voltage-activated Ca2+ channels, (ICa), was tested in voltage-clamped bovine adrenal chromaffin cells. The protonophore carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), the blocker of the Ca2+ uniporter ruthenium red (RR), and a combination of oligomycin plus rotenone were used to interfere with mitochondrial Ca2+ buffering. In cells dialyzed with an EGTA-free solution, peak ICa generated by 20 msec pulses to 0 or +10 mV, applied at 15 sec intervals, from a holding potential of −80 mV, decayed rapidly after superfusion of cells with 2 μm CCCP (τ = 16.7 ± 3 sec;n = 8). In cells dialyzed with 14 mm EGTA, CCCP did not provoke ICa loss. Cell dialysis with 4 μm ruthenium red or cell superfusion with oligomycin (3 μm) plus rotenone (4 μm) also accelerated the decay of ICa. After treatment with CCCP, decay of N- and P/Q-type Ca2+ channel currents occurred faster than that of L-type Ca2+channel currents. These data are compatible with the idea that the elevation of the bulk cytosolic Ca2+ concentration, [Ca2+]c, causes the inhibition of L- and N- as well as P/Q-type Ca2+ channels expressed by bovine chromaffin cells. This [Ca2+]c signal appears to be tightly regulated by rapid Ca2+ uptake into mitochondria. Thus, it is plausible that mitochondria might efficiently regulate the activity of L, N, and P/Q Ca2+ channels under physiological stimulation conditions of the cell.
A FIRST LOOK AT BUILD-ORDER OPTIMIZATION IN REAL-TIME STRATEGY GAMES

Planning is an important cognitive process. We are constantly involved in planning even when executing seemingly simple tasks such as driving to school. The ability to plan becomes essential in unfamiliar environments where we cannot rely on previously learned action sequences, but instead have to generate novel solutions by considering consequences of action choices on the fly. Planning in real-world domains poses a big challenge to current AI systems because of inadequate abstraction and search mechanisms. Human planning ability is therefore still considered superior. A good example is modern video games in which it is apparent that computer characters lack human planning, learning, and reasoning abilities. In this paper we approach the real-time planning problem by considering build-order optimization in real-time strategy games. This problem class can be formulated as a resource accumulation and allocation problem where an agent has to decide what objects to produce at what time in order to meet one of two goals: either maximizing the number of produced objects in a given time period or producing a certain number of objects as fast as possible. We identify challenges related to this planning problem, namely creating and destroying objects, concurrent action generation and execution, and present ideas how to address them.
A Universe without Weak Interactions

SLAC-PUB-11795, hep-ph/0604027 A Universe Without Weak Interactions arXiv:hep-ph/0604027v1 4 Apr 2006 Roni Harnik 1 , Graham D. Kribs 2 , and Gilad Perez 3 1 Stanford Linear Accelerator Center, Stanford University, Stanford, CA 94309 and Physics Department, Stanford University, Stanford, CA 94305 2 Department of Physics and Institute of Theoretical Science University of Oregon, Eugene, OR 97403 3 Theoretical Physics Group, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 roni@slac.stanford. edu, kribs@uoregon.edu, gperez@lbl.gov Abstract A universe without weak interactions is constructed that undergoes big-bang nucleosynthesis, matter domination, structure formation, and star formation. The stars in this universe are able to burn for billions of years, synthesize elements up to iron, and undergo supernova explosions, dispersing heavy elements into the interstellar medium. These deﬁnitive claims are supported by a detailed analysis where this hypothetical “Weakless Universe” is matched to our Universe by simultaneously adjusting Standard Model and cosmological parameters. For instance, chemistry and nuclear physics are essentially unchanged. The apparent habitability of the Weakless Universe suggests that the anthropic principle does not determine the scale of electroweak breaking, or even require that it be smaller than the Planck scale, so long as technically natural parameters may be suitably adjusted. Whether the multi-parameter adjustment is realized or probable is dependent on the ultraviolet completion, such as the string landscape. Considering a similar analysis for the cosmological constant, however, we argue that no adjustments of other parameters are able to allow the cosmological constant to raise up even remotely close to the Planck scale while obtaining macroscopic structure. The ﬁne-tuning problems associated with the electroweak breaking scale and the cosmological constant therefore appear to be qualitatively diﬀerent from the perspective of obtaining a habitable universe.
Topological subsystem codes

We introduce a family of two-dimensional (2D) topological subsystem quantum error-correcting codes. The gauge group is generated by two-local Pauli operators, so that two-local measurements are enough to recover the error syndrome. We study the computational power of code deformation in these codes and show that boundaries cannot be introduced in the usual way. In addition, we give a general mapping connecting suitable classical statistical mechanical models to optimal error correction in subsystem stabilizer codes that suffer from depolarizing noise.
Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone

Type I diabetes mellitus is caused by autoimmune destruction of pancreatic β cells, and effective treatment of the disease might require rescuing β cell function in a context of reinstalled immune tolerance. Sertoli cells (SCs) are found in the testes, where their main task is to provide local immunological protection and nourishment to developing germ cells. SCs engraft, self-protect, and coprotect allogeneic and xenogeneic grafts from immune destruction in different experimental settings. SCs have also been successfully implanted into the central nervous system to create a regulatory environment to the surrounding tissue which is trophic and counter-inflammatory. We report that isolated neonatal porcine SC, administered alone in highly biocompatible microcapsules, led to diabetes prevention and reversion in the respective 88 and 81% of overtly diabetic (nonobese diabetic [NOD]) mice, with no need for additional β cell or insulin therapy. The effect was associated with restoration of systemic immune tolerance and detection of functional pancreatic islets that consisted of glucose-responsive and insulin-secreting cells. Curative effects by SC were strictly dependent on efficient tryptophan metabolism in the xenografts, leading to TGF-β–dependent emergence of autoantigen-specific regulatory T cells and recovery of β cell function in the diabetic recipients.
An Optimistic Protocol for Distributed Fair Exchange

This paper presents an optimistic protocol based on the scheme of public verifiable secret share for distributed fair exchange. A distributed third party is designed to guarantee the fairness of exchange. Comparing to traditional trusted third party, this distributed third party is not fixed but dynamically selected by the players of exchange. This solution can effectively remove the risk of single point of failure and defend compromising attacks. The results of protocol analysis show that the protocol guarantees strong fairness and effectiveness of up to one-half malicious participants in distributed third party.
Design of a Restartable Crystal Controlled Clock for Use in a Globally Asynchronous, Locally Synchronous Design Methodology

This paper presents the design of a restartable crystal controlled clock. The clock generator is a critical component in a newly proposed blended design methodology which combines clockless and clocked subsystems and is a special case of a Globally Asynchronous Locally Synchronous (GALS) design strategy. The clock generator has been successfully implemented in the TSMC 0. 25μm NWELL process, occupies an area of 0.016mm (700 NAND gate equivalents), dissipates 20 mW of power, and operates at frequencies up to 200 MHz. The delay in starting the clock is 6 nsec +/45 ps.
Identifying risk factors for postpartum depressive symptoms: the importance of social support, self-efficacy, and emotion regulation

Background and aim: 10-15% of women experience postpartum depression. First-time mothers are particularly at risk. The present qualitative study aimed to gain insight in terms of why some women find the transition of becoming a mother to be so emotionally taxing that they feel some level of depressed mood, while others feel mostly content after
Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis

Background—Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis. Methods and Results—To assess the role of IL-6 in atherosclerosis, ApoE−/−–IL-6−/− double-knockout mice were generated, fed a normal chow diet, and housed for 53±4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE−/−–IL-6−/− mice compared with ApoE−/−, wild-type (WT), and IL-6−/− mice. Plaques of ApoE−/−–IL-6−/− mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase–polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE−/−–IL-6−/− mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced. Conclusions—Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoE−/−–IL-6−/− mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.
The effect of social network sites on adolescents’ appearance investment and desire for cosmetic surgery

Although adolescents frequently use social network sites (SNS), little is known about whether the highly visual and self-presentation-centered character of such sites affects body-related outcomes. The first aim of the current study was to investigate the causal direction of the relationship between SNS use and appearance investment among adolescents. Given evidence of a relation between appearance investment and cosmetic surgery, the second aim was to test if SNS use indirectly affects adolescents’ desire to undergo cosmetic surgery through appearance investment. The third aim of the current study was to test if these relationships were more apparent among girls. We used data from a two-wave panel study among 604 Dutch adolescents (aged 11-18). Structural equation modeling showed that, among both adolescent boys and girls, SNS use and appearance investment reinforced each other. SNS use indirectly augmented adolescents’ desire to undergo cosmetic surgery through increasing appearance investment.
Designing a Collaborative Finger Painting Application for Children

We describe the design and implementation of a collaborative, computer-based finger painting program for children using a new hardware input device called a MultiTouch Surface (MTS). The MTS uses a flat surface about the size of a keyboard to track multiple, simultaneous finger motions, which we transform into paint strokes on a screen. We describe related work and explain how our program design was guided by the suggestions of children. We discuss the hardware and software of the MTS and the challenges of designing our program. Finally, we present the Finger Painting Table, a collaborative, embedded application built using the MTS, and discuss future work.
PROFcon: novel prediction of long-range contacts

MOTIVATION Despite the continuing advance in the experimental determination of protein structures, the gap between the number of known protein sequences and structures continues to increase. Prediction methods can bridge this sequence-structure gap only partially. Better predictions of non-local contacts between residues could improve comparative modeling, fold recognition and could assist in the experimental structure determination. RESULTS Here, we introduced PROFcon, a novel contact prediction method that combines information from alignments, from predictions of secondary structure and solvent accessibility, from the region between two residues and from the average properties of the entire protein. In contrast to some other methods, PROFcon predicted short and long proteins at similar levels of accuracy. As expected, PROFcon was clearly less accurate when tested on sparse evolutionary profiles, that is, on families with few homologs. Prediction accuracy was highest for proteins belonging to the SCOP alpha/beta class. PROFcon compared favorably with state-of-the-art prediction methods at the CASP6 meeting. While the performance may still be perceived as low, our method clearly pushed the mark higher. Furthermore, predictions are already accurate enough to seed predictions of global features of protein structure.
An empirical study on parameter selection for multiobjective optimization algorithms using Differential Evolution

In this work, an empirical study on multiobjective optimization algorithms based on Differential Evolution (DE) algorithm is performed. The study focuses on getting good initial choices for evolutionary parameters for DE algorithm to tackle the multiobjective problem of PI controller tuning. This is an important issue in the field of control engineering, because the PI-PID controller remains a reliable digital solution for industrial processes. This study will bring an insight to the capabilities of a basic DE algorithm for multiobjective optimization, which can be the basis for more complex approaches using this evolutionary technique.
Kinking the double helix by bending deformation

DNA bending and torsional deformations that often occur during its functioning inside the cell can cause local disruptions of the regular helical structure. The disruptions created by negative torsional stress have been studied in detail, but those caused by bending stress have only been analyzed theoretically. By probing the structure of very small DNA circles, we determined that bending stress disrupts the regular helical structure when the radius of DNA curvature is smaller than 3.5 nm. First, we developed an efficient method to obtain covalently closed DNA minicircles. To detect structural disruptions in the minicircles we treated them by single-strand-specific endonucleases. The data showed that the regular DNA structure is disrupted by bending deformation in the 64–65-bp minicircles, but not in the 85–86-bp minicircles. Our results suggest that strong DNA bending initiates kink formation while preserving base pairing.