Miracle-dz/UniFAR-FTUs huggingface dataset:
Microenvironmental stromal cells abrogate NF-κB inhibitor-induced apoptosis in chronic lymphocytic leukemia

Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) is known to play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). Several NF-κB inhibitors were shown to successfully induce apoptosis of CLL cells in vitro. Since the microenvironment is known to be crucial for the survival of CLL cells, herein, we tested whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ). Microenvironmental support was mimicked by co-culturing CLL cells with bone marrow-derived stromal cell lines (HS-5 and M2-10B4). NF-κB inhibition by DHMEQ in CLL cells could be confirmed in both the monoculture and co-culture setting. In line with previous reports, NF-κB inhibition induced apoptosis in the monoculture setting by activating the intrinsic apoptotic pathway resulting in poly (ADP-ribose) polymerase (PARP)-cleavage; however, it was unable to induce apoptosis in leukemic cells co-cultured with stromal cells. Similarly, small interfering ribonucleic acid (siRNA)-mediated RELA downregulation induced apoptosis of CLL cells cultured alone, but not in the presence of supportive stromal cells. B-cell activating factor (BAFF) was identified as a microenvironmental messenger potentially protecting the leukemic cells from NF-κB inhibition-induced apoptosis. Finally, we show improved sensitivity of stroma-supported CLL cells to NF-κB inhibition when combining the NF-κB inhibitor with the SYK inhibitor R406 or the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, agents known to inhibit the stroma-leukemia crosstalk. We conclude that NF-κB inhibitors are not promising as monotherapies in CLL, but may represent attractive therapeutic partners for ibrutinib and R406.
Secure Coding: Building Security into the Software Development Life Cycle

Abstract Many of the security properties that are outlined repeatedly in the newer regulations and standards can easily be side-stepped. Too often the culprits are unsophisticated software development techniques, a lack of security- focused quality assurance, and scarce security training for software developers, software architects, and project managers. To meet future needs, opportunities, and threats associated with information security, security needs to be “baked in” to the overall systems development life-cycle process.
Columnar versus smectic order in binary mixtures of hard parallel spherocylinders.

We present Monte Carlo simulations of binary mixtures of hard parallel spherocylinders with length-to-width ratios L 1 /D=1.0 and L 2 /D ranging from 1.3 to 2.1. The composition is such that the partial volume fractions are equal. For L 2 /D>1.6, we observe a thermodynamically stable columnar phase which is not formed by the monodisperse components separately
Evaluation Metrics Trade-off for Recommendation Systems

Following the famous Netflix Prize competition, accuracy metrics (such as RMSE) became a de facto standard in the community to evaluate and compare performance of recommendation algorithms. However, it has been shown, that accuracy is not the best way to quantify the quality of recommendations, especially in the context of predicting online performance from offline evaluations [1]. Thus, it makes sense to look at other metrics, such as novelty, coverage, or serendipity, and in particular, trade-off between these metrics [2]. In this project, a student will work with large news recommendation datasets, collected online on swissinfo.ch and lepoint.fr. The goal would be to implement a number of recommender algorithms with tunable hyperparameters, and generate trade-offs between different evaluation metrics by varying these hyperparametrs. A student will then analyse these trade-offs by plotting trade-off curves, comparing them for various algorithms, examining the area under the curves, and possibly looking at their impact on CTR and online success rate.
Replication of Putative Susceptibility Loci from Genome-Wide Association Studies Associated with Coronary Atherosclerosis in Chinese Han Population

Background Coronary atherosclerosis, the main cause of cardiovascular disease, is a progressive disease. Recent Genome Wide Association Studies (GWASs) discovered several novel loci associated with coronary artery disease (CAD) or its main complication myocardial infarction (MI). In this study, we investigated the associations between previously reported CAD- and MI-associated variants and coronary atherosclerosis in Chinese Han population. Methodology/Principal Findings We performed a case-control association study with 2,335 coronary atherosclerosis patients and 1,078 controls undergoing coronary angiography of Chinese Han from China. Fourteen single nucleotide polymorphisms (SNPs), located at 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21.3, 10q11.21 and 15q22.33, were genotyped in our sample collection. Six SNPs at 9p21 were associated with coronary atherosclerosis susceptibility (Ptrend<0.05) and rs10757274 showed the most significant association (P = 2.38×10−08, OR = 1.34). These associations remained significant after adjustment for multiple comparisons. Rs17465637 at 1q41 (Ptrend = 6.83×10−03, OR = 0.86) also showed significant association with coronary atherosclerosis, but the association was not significant after multiple comparisons. Additionally, rs501120 (P = 8.36×10−03, OR = 0.80) at 10q11.21 was associated with coronary atherosclerosis in females, but did not show association in males and all participants. Variants at 1p13.3, 2q36.3, 6q25.1 and 15q22.33 showed no associations with coronary atherosclerosis and main cardiovascular risk factors in our data. Conclusions/Significance Our findings indicated variants at 9p21 were significantly associated with coronary atherosclerosis in Han Chinese. Variants at 1q41 showed suggestive evidence of association and variants at 10q11.21 showed suggestive evidence of association in females, which warrant further study in a larger sample.
Reconfigurable Computing for Computational Science: A New Focus in High Performance Computing

Abstract : Computational science applications and advanced scientific computing have made tremendous gains in the past decade. Researchers are regularly employing the power of large computing systems and parallel processing to tackle larger and more complex problems in all of the physical sciences. For the past decade or so, most of this growth in computing power has been "free" with increased efficiency more-or-less governed by Moore's Law. However, increases in performance are becoming harder to achieve due to the complexity of the parallel computing platforms and the software required for these systems. Reconfigurable computing, or heterogeneous computing, is offering some hope to the scientific computing community as a means to continued growth in computing capability. This paper offers a glimpse of the hardware and software associated with this new technology and discusses how the new paradigm functions for computational science.
Don't Fence Me in: Fragmented Markets for Technology and the Patent Acquisition Strategies of Firms

How do firms avoid being "fenced in" by owners of patented technologies used, perhaps unknowingly, in the design or manufacture of their products? This paper examines the conditions under which firms expand their own portfolios of patents in response to potential hold-up problems in markets for technology. Combining insights from transactions cost theory with recent scholarship on intellectual property and its exchange, I predict firms will patent more aggressively than otherwise expected when markets for technology are highly fragmented (i.e., ownership rights to external technologies are widely distributed); this effect should be more pronounced for firms with large investments in technology-specific assets and under a strong legal appropriability regime. Although these characteristics of firms and their external environments have been highlighted in the theoretical literature, prior research has not explored the extent to which such factorsinteract to shape the patenting behavior of firms. To empirically test these hypotheses, I develop a citations-based "fragmentation index" and estimate the determinants of patenting for 67 U.S. semiconductor firms between 1980 and 1994. Accumulating exclusionary rights of their own may enable firms to safeguard their investments in new technologies while foregoing some of the costs and delays associated with ex ante contracting.
Semiglobal finite-time stabilization via output-feedback for a class of uncertain high-order planar nonlinear systems

This paper is devoted to the semiglobal finite-time stabilization via output-feedback for a class of uncertain highorder planar nonlinear systems. The systems under investigation contain unknown control coefficients and possess more serious nonlinearities. In this paper, with the assumption that all the system states are available for feedback, a state-feedback controller is first constructed by adding a power integrator, which ensures that the closed-loop system is globally finite-time stable. Then, by certainty equivalence principle and saturation technique, an output-feedback controller is successfully constructed, which makes the closed-loop system semiglobal attractive and local finite-time stable. A simulation example is presented to illustrate the effectiveness of the proposed method.
Curbing activation: proprotein convertases in homeostasis and pathology

The proprotein convertases (PCs) are a seven‐member family of endoproteases that activate proproteins by cleavage at basic motifs. Expression patterns for individual PCs vary widely, and all cells express several members. The list of substrates activated by PCs has grown to include neuropeptides, peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules, blood coagulation factors, plasma proteins, viral coat proteins, and bacterial toxins. It has become clear that the PC family plays a crucial role in a variety of physiological processes and is involved in the pathology of diseases such as cancer, viral infection, and Alzheimer's disease. Recent studies using PC inhibitors have demonstrated their potential as therapeutic targets. Despite the avalanche of in vitro data, the physiological role of individual PCs has remained largely elusive. Recently, however, knockout mouse models have been developed for furin, PC1, PC2, PC4, PC6B, LPC, and PACE4, and human patients with PC1 deficiency have been identified. The phenotypes range from undetectable to early embryonic lethality. The major lesson learned from these studies is that specific PC‐substrate pairs do exist, but that there is substantial redundancy for the majority of substrates. To some extent, redundancy may be cell type and even species dependent.
Radiographic prevalence of femoroacetabular impingement in collegiate football players: AAOS Exhibit Selection.

BACKGROUND The prevalence of femoroacetabular impingement may be greater in athletes than in the general population because of increased loading of the hip during sports. This study evaluated the radiographs of collegiate football players in order to quantify the prevalence of femoroacetabular impingement in asymptomatic athletes. METHODS Sixty-seven male collegiate football players (age, 21 ± 1.9 years) participated in this prospective study. Both hips (n = 134) were evaluated independently by two orthopaedic surgeons for radiographic signs of femoroacetabular impingement. The alpha angle and femoral head-neck offset were measured on frog-leg lateral radiographs. The lateral center-edge angle, acetabular index, crossover sign, and alpha angle were measured on anteroposterior radiographs. Data for continuous variables were averaged between observers prior to assessing prevalence. Cam femoroacetabular impingement was considered to be present if the femoral head-neck offset was <8 mm and/or the alpha angle was >50° on either radiograph. Pincer femoroacetabular impingement was considered to be present if the lateral center-edge angle was >40°, the acetabular index was <0°, and/or a positive crossover sign was detected by both observers. RESULTS Ninety-five percent of the 134 hips had at least one sign of cam or pincer impingement, and 77% had more than one sign. Twenty-one percent had only one sign of cam femoroacetabular impingement and 57% had both signs. Fifty-two percent had only one sign of pincer femoroacetabular impingement, 10% had two, and 4% had all three signs. Specifically, 72% had an abnormal alpha angle, 64% had a decreased femoral head-neck offset, 61% had a positive crossover sign, 16% had a decreased acetabular index, and 7% had an increased lateral center-edge angle. Fifty percent of all hips had at least one sign of pincer femoroacetabular impingement and at least one sign of cam impingement. Interobserver and intraobserver repeatability was moderate or better for each measure (range, 0.59 to 0.85). CONCLUSIONS Morphologic abnormalities associated with cam and pincer femoroacetabular impingement were common in these collegiate football players. The prevalence of cam and pincer femoroacetabular impingement was substantially higher than the previously reported prevalence in the general population.
Acquired hypercoagulable state in renal transplant recipients

Summary Stable renal transplant recipients manifest a chronic hypercoagulable state with an increased risk of thromboembolic complications, which appears to be multifactorial. While this group of patients could present the known risk factors for thromboembolism in the general population (e.g. diabetes, cancer, pregnancy), they may also suffer from other situations which are mostly related to transplantation and are consequently specific to them. Here, we review briefly the clinical aspects and controversies of the most important of these factors including immunosuppressive agents, antiphospholipid antibodies, hyperhomocysteinemia, pre-transplant dialysis modality, and posttransplant erythrocytosis. In addition, other more recent topics including hypercysteinemia, recurrent proteinuria, and acute CMV infection are discussed.
Coronary Pressure Measurement to Assess the Hemodynamic Significance of Serial Stenoses Within One Coronary Artery: Validation in Humans

BackgroundWhen several stenoses are present within 1 coronary artery, the hemodynamic significance of each stenosis is influenced by the presence of the other(s), and the calculation of coronary and fractional flow reserve (CFR and FFR) for each individual stenosis is confounded. Recently, we developed and experimentally validated a method to determine the true FFR of each stenosis as it would be after the removal of the other stenosis; the true FFR can be reliably predicted by coronary pressures measured before treatment at specific locations within the coronary artery using equations accounting for stenosis interaction. The aim of the present study was to test the validity of these equations in humans. Methods and ResultsIn this study of 32 patients with 2 serial stenoses in 1 coronary artery, relevant pressures were measured before the intervention, after the treatment of 1 stenosis, and after the treatment of both stenoses. The true FFR of each stenosis (FFRtrue) was directly measured after the elimination of the other stenosis and compared with the value predicted (FFRpred) from the initial pressure measurements before treatment. Although the hyperemic gradient across 1 stenosis increased significantly (from 10±7 to 19±11 mm Hg after treatment of the other stenosis), FFRpred was close to FFRtrue in all patients (0.78±0.12 versus 0.78±0.11 mm Hg;r =0.92; &Dgr;%=4±0%). Without accounting for stenosis interaction, the value of FFR for each stenosis would have been significantly overestimated (0.85±0.08;P <0.01). ConclusionsCoronary pressure measurements made by a pressure wire at maximum hyperemia provide a simple, practical method for assessing the individual hemodynamic significance of multiple stenoses within the same artery.
An Efficiency-Enhanced Hybrid Supply Modulator With Single-Capacitor Current-Integration Control

This paper presents a high-efficiency wideband hybrid supply modulator (HSM). We show that proper control of the average current from the class-AB linear amplifier (LA) and proper selection of the inductor value are essential to efficiency optimization. In line with the above criteria, a single-capacitor current-integration (SCCI) control method is proposed. Current integration is achieved by using a single capacitor, circumventing the need of the high-speed full-range current sensor required for conventional HSMs and reducing the design complexity greatly. The ripple current of the LA is controlled indirectly, and enhanced efficiency is achieved by enforcing the average output current from the LA to be around zero. A wideband LA is proposed to suppress the output voltage ripple. A proof-of-concept design using an inductor with an optimized value of 100 nH is fabricated in 130 nm CMOS technology. It switches at a peak frequency of 50 MHz, achieves up to 8% efficiency improvement when compared to recent works, and is able to track a 0.8 Vpp sinusoidal signal with high fidelity up to 10 MHz. The measured output voltage ripple is reduced to below 8 mV. The peak conversion efficiency is 88.3% at the maximum output power of 23 dBm.
Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3

Significance The homeostasis of FoxP3+ Treg cells, essential controllers of immune and autoimmune responses, integrates inputs from the antigen-specific T-cell receptor (TCR) and from trophic cytokines or chemotactic cues. Expanding upon previous indications that Treg cells might be hyporesponsive, we find that TCR triggering induces dampened responses along all tested pathways in Treg compared with conventional CD4+ T cells, whereas their responses to IFN-I, IL6, or IL2 were equal or stronger. This imbalance indicates that Treg cells are less sensitive to direct recognition of novel antigens, for instance of an infectious nature, and more to cytokine-based cues or intercellular communication. FoxP3+ T regulatory (Treg) cells have a fundamental role in immunological tolerance, with transcriptional and functional phenotypes that demarcate them from conventional CD4+ T cells (Tconv). Differences between these two lineages in the signaling downstream of T-cell receptor-triggered activation have been reported, and there are different requirements for some signaling factors. Seeking a comprehensive view, we found that Treg cells have a broadly dampened activation of several pathways and signaling nodes upon TCR-mediated activation, with low phosphorylation of CD3ζ, SLP76, Erk1/2, AKT, or S6 and lower calcium flux. In contrast, STAT phosphorylation triggered by interferons, IL2 or IL6, showed variations between Treg and Tconv in magnitude or choice of preferential STAT activation but no general Treg signaling defect. Much, but not all, of the Treg/Tconv difference in TCR-triggered responses could be attributed to lower responsiveness of antigen-experienced cells with CD44hi or CD62Llo phenotypes, which form a greater proportion of the Treg pool. Candidate regulators were tested, but the Treg/Tconv differential could not be explained by overexpression in Treg cells of the signaling modulator CD5, the coinhibitors PD-1 and CTLA4, or the regulatory phosphatase DUSP4. However, transcriptome profiling in Dusp4-deficient mice showed that DUSP4 enhances the expression of a segment of the canonical Treg transcriptional signature, which partially overlaps with the TCR-dependent Treg gene set. Thus, Treg cells, likely because of their intrinsically higher reactivity to self, tune down TCR signals but seem comparatively more attuned to cytokines or other intercellular signals.
Origin and Attenuation of Mesoscale Structure in Circumpolar Deep Water Intrusions to an Antarctic Shelf

Cross-isobath transport of Upper Circumpolar Deep Water (UCDW) provides a major source of heat to the Antarctic continental shelves. Adaptive sampling with a Slocum glider revealed that the UCDW regularly intrudes onto the western Antarctic Peninsula shelf within mesoscale eddies, and a linear stability analysis of the shelf-break current upstream confirmed eddy length scales and vertical structure are consistent with the baroclinic instability of the current. The properties of the most unstable mode are insensitive to current orientation but sensitive to bottom slope in accordance with modified Eady theory. Once on the shelf, the eddies’ core properties mix with ambient shelf water to form modified CDW (mCDW). Concurrent shipboard CTD and ADCP data are used to diagnose the responsible mixing processes and highlight the importance of thermohaline intrusions. The genesis mechanism of the interleaving layers cannot be confirmed, however a simple analytic model suggests the upper limit contribution of advection by internal waves cannot account for the observed temperature variance unless the cross-eddy temperature gradient is large. Data-adaptive sampling of an eddy with the glider revealed it lost heat across two isopycnals and a fixed radius at a rate of 7 × 109 J s−1 over 3.9 days. This rate is corroborated by a diffusion model initialized with the eddy’s initial hydrographic properties and informed by the heat fluxes parameterized from the shipboard data. The results suggest eddies predominately lose heat laterally and downward, which preserves subsurface heat for melting of marine-terminating glaciers.
Symbol Generation and Grounding for Reinforcement Learning Agents Using Affordances and Dictionary Compression

One of the challenges for artificial agents is managing the complexity of their environment as they learn tasks especially if they are grounded in the physical world. A scalable solution to address the state explosion problem is thus a prerequisite of physically grounded, agentbased systems. This paper presents a framework for developing grounded, symbolic representations aimed at scaling subsequent learning as well as forming a basis for symbolic reasoning. These symbols partition the environment so the agent need only consider an abstract view of the original space when learning new tasks and allows it to apply acquired symbols to novel situations.