Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Potential of Spleen Tyrosine Kinase Inhibition for Treating High-Risk Precursor B Cell Acute Lymphoblastic Leukemia

Pre-BCR–independent activation of spleen tyrosine kinase plays a pathogenic role in high-risk B cell acute lymphoblastic leukemia. Targeting the “SYK-ness” in B-ALL Intensive chemotherapy in B cell acute lymphoblastic leukemia (B-ALL) provides improved outcomes for children and achieves remission in adults, but patients in both groups relapse, resulting in low survival rates. The discovery of aberrant signaling pathways in cancers has spurred development of targeted kinase inhibitors. In a mouse model of spontaneous B-ALL, Perova et al. demonstrate that aberrant activation of the spleen tyrosine kinase (SYK) was required for leukemic cell growth. SYK pathway activity and B-ALL cell survival were sensitive to two inhibitors of SYK signaling. Like the mouse model, the authors show that primary pediatric and adult human B-ALL samples exhibited basal SYK activation. Phosphorylation of SYK and its targets and leukemic cell proliferation were attenuated by in vitro treatment of the human leukemic cells with SYK inhibitors. Xenotransplantation of poor-prognosis primary human B-ALL samples into immunodeficient mice resulted in extensive bone marrow engraftment and dissemination to spleen, liver, and central nervous system. In vivo treatment of the transplanted animals with SYK inhibitors reduced human leukemia burden in these tissues. Thus, SYK activation regulates key signal transduction pathways of abnormal growth in multiple subtypes of B-ALL, suggesting that small-molecule SYK inhibitors may be promising agents for treating poor-prognosis and relapsed B-ALL. Intensified and central nervous system (CNS)–directed chemotherapy has improved outcomes for pediatric B cell acute lymphoblastic leukemia (B-ALL) but confers treatment-related morbidities. Moreover, many patients suffer relapses, underscoring the need to develop new molecular targeted B-ALL therapies. Using a mouse model, we show that leukemic B cells require pre–B cell receptor (pre-BCR)–independent spleen tyrosine kinase (SYK) signaling in vivo for survival and proliferation. In diagnostic samples from human pediatric and adult B-ALL patients, SYK and downstream targets were phosphorylated regardless of pre-BCR expression or genetic subtype. Two small-molecule SYK inhibitors, fostamatinib and BAY61-3606, attenuated the growth of 69 B-ALL samples in vitro, including high-risk (HR) subtypes. Orally administered fostamatinib reduced heavy disease burden after xenotransplantation of HR B-ALL samples into immunodeficient mice and decreased leukemia dissemination into spleen, liver, kidneys, and the CNS of recipient mice. Thus, SYK activation sustains the growth of multiple HR B-ALL subtypes, suggesting that SYK inhibitors may improve outcomes for HR and relapsed B-ALL.
Bone response of Mg ion-implanted clinical implants with the plasma source ion implantation method.

OBJECTIVES This study examined the bone response of magnesium (Mg) ion-implanted implants produced using a plasma source ion implantation method. MATERIALS AND METHODS The surface characteristics were evaluated by scanning electron microscopy, Auger electron spectroscopy, X-ray photoelectron spectroscopy, and Rutherford backscattering spectroscopy. The screw-type titanium implants were treated with resorbable blasting media (RBM) and divided into one control group (RBM implants) and three test groups (Mg ion-implanted implants with different retained Mg doses). Twenty-four implants from each group were placed into the tibiae of 24 New Zealand white rabbits. After allowing 6 weeks for healing, the removal torque (RTQ) was measured and the implants were subjected to histomorphometric analysis. RESULTS The surface roughness and surface morphology of the test groups were similar. The Mg ion-implanted implants with a 2.3 x 10(15) ions/cm(2) retained dose showed a significantly higher RTQ than the other implants. Histomorphometric analysis indicated that the bone contact of this group was superior to the other groups. CONCLUSION The bone response of Mg ion-implanted implant showed results superior or similar to an RBM-treated implant. The optimal Mg ion concentration that induced the strongest osseointegration was approximately 9%.
Plant survival in relation to seed size along environmental gradients: a long‐term study from semi‐arid and Mediterranean annual plant communities

1. A positive relationship between seed size and subsequent offspring survival is a key assumption in ecological theory concerning life‐history strategies. Yet, this relationship is uncertain in respect to lifetime survival because sound evidence only exists for early seedling stages. Furthermore, the effect of environmental variation in space and time, and of contrasting plant functional groups, on this relationship has been scarcely examined.
The importance of Raf dimerization in cell signaling

The Raf family of protein kinases are key signaling intermediates, acting as a central link between the membrane-bound Ras GTPases and the downstream kinases MEK and ERK. Raf kinase regulation is well-known for its complexity but only recently has it been realized that many of the mechanisms involved in Raf regulation also modulate Raf dimerization, now acknowledged to be a required step for Raf signaling in multiple cellular contexts. Recent studies have shown that Raf dimerization is necessary for normal Ras-dependent Raf kinase activation and contributes to the pathogenic function of disease-associated mutant Raf proteins with all but high intrinsic kinase activity. Raf dimerization has also been found to alter therapeutic responses and disease progression in patients treated with ATP-competitive Raf inhibitors as well as certain other kinase-targeted drugs. This demonstration of clinical significance has stimulated the recent development of biosensor assays that can monitor inhibitor-induced Raf dimerization as well as studies demonstrating the therapeutic potential of blocking Raf dimerization.
Spicer Off-Highway Products Division-Brugge Improves its Lead-Time and Scheduling Performance

Spicer Off-Highway Products Division (a division of Dana Corporation) asked us to develop OR tools to improve the due date performance and to shorten the manufacturing lead time of its powershift transmission plant in Brugge, Belgium. We modeled the manufacturing system as a queueing model and used the model to analyze and evaluate improvement schemes (layout changes, product-mix decisions, lot-sizing decisions, and lead-time estimations). Next, we developed a finite scheduler to improve the detailed scheduling of the shop. Our modeling effort contributed to the successful combination of analysis, planning, and detailed scheduling. The plant increased productivity by 27.3 percentage points, decreased manufacturing lead times by a factor of two to three, increased its workforce by 41 percent, and decreased its operating costs. The division is now profitable.
Learning the dynamics of doors for robotic manipulation

Opening doors is a fundamental skill for mobile robots operating in human environments. In this paper we present an approach to learn a dynamic model of a door from sensor observations and utilize it for effectively swinging the door open to a desired angle. The learned model enables the realization of dynamic door-opening strategies and reduces the complexity of the door opening task. For example, the robot does not need to maintain a grasp of the handle, which would form a closed kinematic chain. Accordingly, it reduces the degrees of freedom required of the manipulator and facilitates motion planning. Additionally, execution is faster, because the robot merely needs to push the door long enough to achieve the right combination of position and speed such that the door stops at the desired state. Our approach applies Gaussian process regression to learn the deceleration of the door with respect to position and velocity of the door. This model of the dynamics can be easily learned from observing a human teacher or by interactive experimentation.
Malware categorization and recognition problem

Nowadays, in this modern technology based society, information is the most valuable commodity on the market. Because of its prize, ways of stealing and misusing of the information are still being developed. This developing process is done each time by more and more sophisticated ways. To be able to react on this kind of thread, to protect sensitive data and to be able to choose appropriate solution for protecting them and for preventing them from damage, man should be familiar with processes behind and should be able to exactly define the whole menace and every possible dangerous scenario behind it.
Using the Software CMM in Small Organizations

The Capability Maturity ModelSM for Software developed by the Software Engineering Institute has had a major influence on software process and quality improvement around the world. Although the CMM has been widely adopted, there remain many misunderstandings about how to use it effectively for business-driven software process improvement, particularly for small organizations and small projects. Some of the common problems with interpreting the Software CMM for the small project/organization include: § What does "small" mean? In terms of people? Time? Size of project? Criticality of product? § What are the CMM "requirements"? Are there key process areas or goals that should not be applied to small projects/organizations? Are there "invariants" of good processes? § What are the drivers and motivations that cause abuse of the CMM? This paper discusses how to use the CMM correctly and effectively in any business environment, with examples for the small organization. The conclusion is that the issues associated with interpreting the Software CMM for the small project or organization may be different in degree, but they are not different in kind, from those for any organization interested in improving its software processes. Using the Software CMM effectively and correctly requires professional judgment and an understanding of how the CMM is structured to be used for different purposes. MARK C. PAULK Software Engineering Institute Carnegie Mellon University 4500 Fifth Avenue Pittsburgh, PA 15213 Telephone: +1 (412) 268-5794 Fax: +1 (412) 268-5758 Internet: mcp@sei.cmu. edu Mark is a Senior Member of the Technical Staff at the Software Engineering Institute. He has been with the SEI since 1987, initially working with the Software Capability Evaluation project. Mark has worked with the Capability Maturity Model project since its inception and was the project leader during the development of Version 1.1 of the Software CMM. He is also actively involved with software engineering standards, including § ISO 15504 (aka SPICE -Software Process Improvement and Capability dEtermination), an emerging suite of international standards for software process assessment § ISO 12207, Software Life Cycle Processes § ISO 15288, System Life Cycle Processes Prior to joining the SEI, Mark was a Senior Systems Analyst for System Development Corporation (later Unisys Defense Systems) at the Ballistic Missile Defense Advanced Research Center in Huntsville, Alabama. Mark received his master's degree in computer science from Vanderbilt University. He received his bachelor's degree in mathematics and computer science from the University of Alabama in Huntsville. Professional society memberships and certifications § Senior Member of the Institute of Electrical and Electronics Engineers (IEEE) § Senior Member of the American Society for Quality (ASQ) § ASQ Certified Software Quality Engineer
Metabolomic Applications to Decipher Gut Microbial Metabolic Influence in Health and Disease

Dietary preferences and nutrients composition have been shown to influence human and gut microbial metabolism, which ultimately has specific effects on health and diseases’ risk. Increasingly, results from molecular biology and microbiology demonstrate the key role of the gut microbiota metabolic interface to the overall mammalian host’s health status. There is therefore raising interest in nutrition research to characterize the molecular foundations of the gut microbial–mammalian cross talk at both physiological and biochemical pathway levels. Tackling these challenges can be achieved through systems biology approaches, such as metabolomics, to underpin the highly complex metabolic exchanges between diverse biological compartments, including organs, systemic biofluids, and microbial symbionts. By the development of specific biomarkers for prediction of health and disease, metabolomics is increasingly used in clinical applications as regard to disease etiology, diagnostic stratification, and potentially mechanism of action of therapeutical and nutraceutical solutions. Surprisingly, an increasing number of metabolomics investigations in pre-clinical and clinical studies based on proton nuclear magnetic resonance (1H NMR) spectroscopy and mass spectrometry provided compelling evidence that system wide and organ-specific biochemical processes are under the influence of gut microbial metabolism. This review aims at describing recent applications of metabolomics in clinical fields where main objective is to discern the biochemical mechanisms under the influence of the gut microbiota, with insight into gastrointestinal health and diseases diagnostics and improvement of homeostasis metabolic regulation.
Power Efficient Parallel Adder Design Using CNTFET Technology

This paper presents the Power efficient Parallel Adder design using carbon nano tube field effect transist or. The ternary logic is a variable one as compared to the conventi onal binary logic design technique, because in the today’s digi tal design it is possible to analyze energy efficiency and simplicit y because the circuit has reduction in the chip area and interconections. By using the load-resistive CNTFET ternary logic has d esigned to implement ternary logic which are based on the CNTFET, and is compared with the present resistive load CNTFET log ic gate design. As, it is known to us that presented ternar y logic gate technique design is combined with conventional bina ry gate technique design which have an excellent power cons umption and speed characteristics in a circuits such as mul tiplier and full adder. By the simulation results using the SPICE te chnology the proposed ternary logic gates show the delay and low power comparing with the earlier resistive load CNTFET implementation, some of the new technologies in the CNTFET are, Fin-Field Effect Transistor, Single Electron Transistor and Silicon-On-Insulator.
Tracking a Conductor's Baton

A system to track an uninstrumented conductor’s baton by computer vision techniques is developed. An initial seek mode locates a baton in an image frame without prior knowledge; a subsequent track mode uses temporal information to cope with motion blur and noise. The seek mode utilises the characteristic form of detected edges to guide a maximal intensity trace. The track mode enhances this technique by dovetailing with optical flow to give robust tracking, even with considerable motion blur and poor quality images.
Role of hydrophobic extracellular polysaccharide of Aulacoseira granulata (Bacillariophyceae) on aggregate formation in a turbulent and hypereutrophic reservoir

The highest density of aggregates (1.4 × 103 L‐1) in the hypereutrophic Barra Bonita Reservoir (mean depth of 10.2 m) coincided with the peak population density of the diatom Aulacoseira granulata (2.3 × 106 chains L‐1), which was present in 94% of the aggregates for 22 consecutive months. To investigate why this diatom, which produces very small amounts of free extracellular polysaccharide (EPS) and transparent exopolymer particles (TEP), occurs so frequently in natural aggregates, we carried out aggregation experiments with cultures of A. granulata with and without its free EPS and TEP. Stickiness (ά) was higher in exponential than stationary growth, either with or without EPS, but the highest value was obtained in cultures without EPS (0.37). During the stationary growth phase, ά decreased, both with and without EPS. Replacement of natural polymer carbohydrates by A. granulata free EPS (>14 kiloDalton [kD] < 0.4 µm), or adding cultured diatom to reservoir water, produced aggregates larger than the natural ones. The role of EPS in these aggregation characteristics was investigated by analyzing its monosaccharide composition. The proportion of terminal monosaccharides significant in the aggregation was 74.5%, 56.1% of them consisting of hydrophobic deoxy‐sugars fucose and rhamnose which increase the stickiness. Early in the growth, only hydrophobic‐adhering films are responsible for fast aggregation by chain‐to‐chain collision. With aging cells, aggregation was mainly by the trapping effect of free EPS and TEP, both formed by released adherent films. We hypothesize that aggregates have an important role in seeding A. granulata in environments with significant advective transport, such as reservoirs.
Small Deviations from Gaussianity and the Galaxy Cluster Abundance Evolution

In this paper, we raise the hypothesis that the density fluctuation field, which originates the growth of large-scale structures, is a combination of two or more distributions, instead of assuming that the observed distribution of matter stems from a single Gaussian field produced in the very early universe, as is widely accepted. By applying the statistical analysis of finite-mixture distributions to a specific combination of Gaussian plus non-Gaussian random fields, we studied the case in which just a small departure from Gaussianity is allowed. Our results suggest that even a very small level of non-Gaussianity may introduce significant changes in the cluster abundance evolution rate.
Intellectual energy in software design

In the paper we use the sequential study approach to empirical software engineering to research a novel idea about assessing the intellectual energy built into the software products. The study showed that we can use product of Function Points and α metric to calculate both the intellectual energy reflected in the software and the intellectual energy spend during the software design.
Increment of Murine Spermatogonial Cell Number by Gonadotropin-Releasing Hormone Analogue Is Independent of Stem Cell Factor c-kit Signal1

Abstract Recent studies have demonstrated that GnRH-analogues can stimulate regeneration of spermatogenesis of rats when administered after testicular damages. Although the mechanism of this phenomenon has not been elucidated yet, stem cell factor (SCF) produced by Sertoli cells was proposed to mediate the effects of GnRH-analogues on spermatogonial proliferation and/or survival. In the present study, we quantitatively evaluated the proliferation of spermatogonia and addressed whether SCF mediates the effect of GnRH-analogue on spermatogonial proliferation, using a novel approach combining spermatogonial transplantation and laser confocal microscopic observation. In the first experiment, using wild-type mice as recipients for spermatogonial transplantation, the number of donor spermatogonia per 100 Sertoli cells in each spermatogenic colony was significantly higher in the experimental group of mice treated with leuprorelin, a GnRH-agonist, than that of the control group at 4 and 5 wk after transplantation. In the second experiment, Steel/Steeldickie (Sl/Sld) mutant mice, which lack expression of membrane bound form SCF, were used as recipients. As seen in the first experiment, the number of undifferentiated spermatogonia was significantly higher in leuprorelin-treated than in the control group. Since undifferentiated spermatogonia do not express the receptor of SCF, the present study clearly demonstrates that neither membrane-bound nor secreted forms of SCF are involved in the mechanism of GnRH-analogue's effect on spermatogonial proliferation and/or survival.
Hybrid architectures for speech recognition

The state-of-the-art automatic speech recognition (ASR) systems utilize a statistical pattern recognition framework called HMM/GMM (Hidden Markov Model / Gaussian Mixture Model) with short time spectral features such as Mel Frequency Cesptral Coefficients (MFCC) or Perceptual Linear Prediction (PLP). Although this approach has been shown to be effective in capturing speech patterns, recent performance using this framework has shown that the improvement has plateaued. To improve performance, many researchers have augmented or combined this framework with other techniques to build hybrid architectures. Generally, there are three main approaches in hybrid ASR systems. The first approach focuses on feature enhancement: features such as long temporal context features or discriminative features are used to replace conventional short time spectral features to improve feature’s representation of speech units. The second approach focuses on machine learning techniques such as Artificial Neural Networks (ANNs), Support Vector Machines (SVMs), Deep Belief Networks (DBNs) to replace the GMMs in the conventional HMM/GMM system. The third approach examines the combination of systems or features to improve the system’s performance. The objective of this research is to develop hybrid architectures to improve the accuracy of ASR systems over the baseline HMM/GMM architecture. This report examines three areas of work toward the development of hybrid architecture for ASR. In the first study, DBNs are investigated for phone recognition. DBNs have been applied effectively for many classification applications. Generally, DBNs are MLPs with many hidden layers. The difference between them is in the training phase. While weights of MLPs are initialized randomly, DBNs use a greedy layer-by-layer pre-training algorithm to initialize the network weights. The pre-training process in DBNs is totally unsupervised and requires no labeled training data. In this study, the performance of
Responding to Sex Offenders

The science examining institutional and community-based responses to sexual offending has been well documented. The responses to this form of criminal behavior include penal incarceration followed by civil commitment, community notification, and sex offender registration. To date, evidence-based findings report that these correctives and/or curatives yield limited effectiveness sufficient to justify their continued maintenance as statewide or even national criminal justice and mental health policy prescription. One official systems-level way that policy receives legitimacy is through the Courts. Interestingly, the precedent-setting sex offender case law indicates that current policy prescriptions are constitutionally permissible and therefore justifiable as regulatory practices, notwithstanding the empirical evidence that challenges their soundness. This article summarizes the science regarding sex offender policy from the point of imprisonment to reentry, recounts the relevant case law that judicially sanctions such institutional and community practices, and explains how the driver for sex offender law and policy is legal moralism grounded in and advanced by utilitarian reasoning and duty-based logic. This article concludes by suggesting how judicial reliance on legal moralism could further the interests of public safety and civil liberties if insights from virtue jurisprudence informed the analysis.