Miracle-dz/UniFAR-FTUs huggingface dataset:
A New Focal Adhesion Protein That Interacts with Integrin-Linked Kinase and Regulates Cell Adhesion and Spreading

Integrin-linked kinase (ILK) is a multidomain focal adhesion (FA) protein that functions as an important regulator of integrin-mediated processes. We report here the identification and characterization of a new calponin homology (CH) domain-containing ILK-binding protein (CH-ILKBP). CH-ILKBP is widely expressed and highly conserved among different organisms from nematodes to human. CH-ILKBP interacts with ILK in vitro and in vivo, and the ILK COOH-terminal domain and the CH-ILKBP CH2 domain mediate the interaction. CH-ILKBP, ILK, and PINCH, a FA protein that binds the NH2-terminal domain of ILK, form a complex in cells. Using multiple approaches (epitope-tagged CH-ILKBP, monoclonal anti–CH-ILKBP antibodies, and green fluorescent protein–CH-ILKBP), we demonstrate that CH-ILKBP localizes to FAs and associates with the cytoskeleton. Deletion of the ILK-binding CH2 domain abolished the ability of CH-ILKBP to localize to FAs. Furthermore, the CH2 domain alone is sufficient for FA targeting, and a point mutation that inhibits the ILK-binding impaired the FA localization of CH-ILKBP. Thus, the CH2 domain, through its interaction with ILK, mediates the FA localization of CH-ILKBP. Finally, we show that overexpression of the ILK-binding CH2 fragment or the ILK-binding defective point mutant inhibited cell adhesion and spreading. These findings reveal a novel CH-ILKBP–ILK–PINCH complex and provide important evidence for a crucial role of this complex in the regulation of cell adhesion and cytoskeleton organization.
The Strategy Approval Decision: A Sharpe Ratio Indifference Curve Approach

The problem of capital allocation to a set of strategies could be partially avoided or at least greatly simplified with an appropriate strategy approval decision process. This paper proposes such a procedure. We begin by splitting the capital allocation problem into two sequential stages: strategy approval and portfolio optimization. Then we argue that the goal of the second stage is to beat a naive benchmark, and the goal of the first stage is to identify which strategies improve the performance of such a naive benchmark. We believe that this is a sensible approach, as it does not leave all the work to the optimizer, thus adding robustness to the final outcome. We introduce the concept of the Sharpe ratio indifference curve, which represents the space of pairs (candidate strategy's Sharpe ratio, candidate strategy's correlation to the approved set) for which the Sharpe ratio of the expanded approved set remains constant. We show that selecting strategies (or portfolio managers) solely based on past Sharpe ratio will lead to suboptimal outcomes, particularly when we ignore the impact that these decisions will have on the average correlation of the portfolio. Our strategy approval theorem proves that, under certain circumstances, it is entirely possible for firms to improve their overall Sharpe ratio by hiring portfolio managers with negative expected performance. Finally, we show that these results have important practical business implications with respect to the way investment firms hire, layoff and structure payouts.
Locating Pleistocene Refugia: Comparing Phylogeographic and Ecological Niche Model Predictions

Ecological niche models (ENMs) provide a means of characterizing the spatial distribution of suitable conditions for species, and have recently been applied to the challenge of locating potential distributional areas at the Last Glacial Maximum (LGM) when unfavorable climate conditions led to range contractions and fragmentation. Here, we compare and contrast ENM-based reconstructions of LGM refugial locations with those resulting from the more traditional molecular genetic and phylogeographic predictions. We examined 20 North American terrestrial vertebrate species from different regions and with different range sizes for which refugia have been identified based on phylogeographic analyses, using ENM tools to make parallel predictions. We then assessed the correspondence between the two approaches based on spatial overlap and areal extent of the predicted refugia. In 14 of the 20 species, the predictions from ENM and predictions based on phylogeographic studies were significantly spatially correlated, suggesting that the two approaches to development of refugial maps are converging on a similar result. Our results confirm that ENM scenario exploration can provide a useful complement to molecular studies, offering a less subjective, spatially explicit hypothesis of past geographic patterns of distribution.
Towards general purpose computations on low-end mobile GPUs

GPUs traditionally offer high computational capabilities, frequently higher than their CPU counterparts. While high-end mobile GPUs vendors introduced recently general purpose APIs, such as OpenCL, to leverage their computational power, the vast majority of the mobile devices lack such support. Despite that their graphics APIs have similarities with desktop graphics APIs, they have significant differences, which prevent the use of well-known techniques that offer general-purpose computations over such interfaces. In this paper we show how these obstacles can be overcome, in order to achieve general purpose programmability of these devices. As a proof of concept we implemented our proposal on a real embedded platform (Raspberry Pi) based on Broadcom's VideoCore IV GPU, obtaining a speedup of 7.2× over the CPU.
To qualify as a social partner, humans hide severe punishment, although their observed cooperativeness is decisive

Conflicts of interest between the community and its members are at the core of human social dilemmas. If observed selfishness has future costs, individuals may hide selfish acts but display altruistic ones, and peers aim at identifying the most selfish persons to avoid them as future social partners. An interaction involving hiding and seeking information may be inevitable. We staged an experimental social-dilemma game in which actors could pay to conceal information about their contribution, giving, and punishing decisions from an observer who selects her future social partners from the actors. The observer could pay to conceal her observation of the actors. We found sophisticated dynamic strategies on either side. Actors hide their severe punishment and low contributions but display high contributions. Observers select high contributors as social partners; remarkably, punishment behavior seems irrelevant for qualifying as a social partner. That actors nonetheless pay to conceal their severe punishment adds a further puzzle to the role of punishment in human social behavior. Competition between hiding and seeking information about social behavior may be even more relevant and elaborate in the real world but usually is hidden from our eyes.
Characterizing SMP Virtual Machine Scheduling in Virtualization Environment

Virtualization allows multiple virtual machines to run concurrently on a server. The key to making it possible is to schedule virtual CPUs according to their proportional shares and needs. This paper explores SMP VM scheduling in virtualization environment and seeks to understand its implication to application performance and administration. We designed a monitoring tool in Xen hyper visor to online capture VCPU scheduling events and derive the characteristics. A variety of workloads are measured to analyze the Credit scheduler in three categories: basic scheduling, I/O performance, and co-scheduling. We also discussed how to use our characterizing tool to tune performance for ad hoc applications.
[Destabilase: an enzyme of medicinal leech salivary gland secretion hydrolyzes the isopeptide bonds in stabilized fibrin].

The salivary gland secretion of the leech Hirudo medicinalis contains an enzyme termed by us as destabilase, which hydrolyzes the epsilon-(gamma-glutamyl)-lysine bonds as a result of fibrin stabilization by factor XIIIa in the presence of Ca2+. This hydrolysis, apart from the original lysine and glutamine, is characterized by an appearance of lysine and glutamic acid residues. The accumulation of glutamic acid residues leads to spontaneous depolymerization of the destabilized fibrin. As a result, fluid "spots" of destabilized fibrin depolymerization (DFD) begin to appear at the sites of leech secretion application on the surface of stabilized fibrin plates. The DFD activity of the leech salivary gland secretion manifests itself only in case of stabilized fibrin and increases with an increase in the stabilization degree. Treatment of leech secretion with diisopropylfluorophosphate does not affect the enzyme activity, which is completely blocked by monoiodoacetate. The mechanism of action of leech salivary gland secretion and the enzyme isolated from it, i. e. , destabilase, was studied, using a synthetic chromogenic substrate - p-nitroanilide-gamma-glutamic acid. The amidolytic activity of leech salivary gland secretion is 2.2 +/- 0.18 nkat/ml, Km(app) for destabilase is 0.6 X 10(-5) M, V = 5.4 X 10(-3) mol/min.
IP-10 in chronic hepatitis C patients treated with high-dose interferon.

INTRODUCTION Interferon-g-inducible protein-10 (IP-10) serum levels are associated with IL28B genotype and may predict response to interferon÷ribavirin-based therapy in chronic hepatitis C patients. Our aim was to relate IP-10 levels before and during treatment to treatment outcome, viral HCV-RNA kinetics and IL28B genotype. PATIENTS AND METHODS A cohort of chronic hepatitis C patients was treated with high-dose interferon for six weeks, followed by standard peginterferon÷ ribavirin for 24 or 48 weeks. IP-10 and HCV-RNA levels were frequently determined before, during and after treatment. RESULTS IP-10 levels increased from log2.56 pg÷ml at baseline to log3.48 pg÷ml at Day 1 and gradually diminished thereafter. IP-10 levels at any time point were not statistically different between patients with or without sustained viral response (SVR). Patients with IL28B CC genotype had significantly lower baseline IP-10 levels (p = 0.019) and a higher increase of IP-10 levels from baseline to Day 1 than patients with IL28B non-CC genotypes (p = 0.015). Patients with HCV-RNA decline ≥ 2.28log10 at Day 1 had significantly lower baseline IP-10 levels (p = 0.016) and a higher increase of IP-10 levels from baseline to Day1 (p = 0.047) than patients with HCV-RNA decline of < 2.28log10 at Day 1. CONCLUSIONS In patients treated with high induction dose interferon, IP-10 levels at any time point were not predictive for SVR. Low baseline IP-10 levels and a higher increase of IP-10 levels from baseline to Day 1 were associated with IL28B CC genotype and HCV-RNA decline ≥ 2.28log10 at Day 1. This suggests that, in our cohort, for prediction of SVR the added value of IP-10 to IL28B genotype and early viral kinetics is limited.
Rationality criteria for motivic zeta functions

The zeta function of a complex variety is a power series whose nth coefficient is the nth symmetric power of the variety, viewed as an element in the Grothendieck ring of complex varieties. We prove that the zeta function of a surface is rational if and only if the Kodaira dimension of the surface is negative.
Pedestrian dead reckoning for mobile phones through walking and running mode recognition

In this paper, we propose a novel model of stride length estimation for pedestrian dead reckoning (PDR) that allows a PDR system to switch its estimation method according to whether the pedestrian is walking or running. Then, we study the application of the mode switching to a PDR/GPS/map-matching integrated positioning system for mobile phones. The experimental results show that this mode switching makes stride length estimation more adaptive, and improves the total accuracy of positioning.
(De)constructions of Radical Humanist Discourses in South Africa's Education White Paper 6.

In this article we (de)construct radical humanist discourses in South Africa's recently published White Paper on Special Needs Education. In particular, we (de)construct objects, agents, actions and binaries constituted by democracy, human rights and social justice discourses as well as the voices these discourses marginalise. We discuss the implications that democracy, human rights and social justice discourses have for inclusion / exclusion, as we deconstruct them in White Paper 6: Special Needs Education (hereafter White Paper 6).
Comparative functional evaluation of immunocompetent mouse breast cancer models established from PyMT-tumors using small animal PET with [(18)F]FDG and [(18)F]FLT.

Positron emission tomography (PET) allows detection of functional changes in malignant tissue. Establishment of an immortalized immunocompetent breast cancer mouse model would provide a useful platform for the analysis of novel cancer treatment strategies. This study describes a comparative functional evaluation of murine breast cancer models established from polyoma virus middle T antigen (PyMT)-derived tumors using small animal PET imaging with [(18)F]FDG and [(18)F]FLT. Primary PyMT tumor-derived cells and a cell line derived from these tumors (MTHJ) were injected subcutaneously into immunocompetent FVB mice to generate breast cancer xenografts. Tumor growth rates were comparable in both models and tumors were analyzed after 4-5 weeks post-injection. [(18)F]FDG uptake in vitro followed a comparable trend in both models but reached higher uptake levels in primary PyMT cells vs. MTHJ cells after 120 min. At all time points, [(18)F]FLT uptake was significantly higher in MTHJ compared to primary PyMT cells. Dynamic small animal PET imaging with [(18)F]FDG revealed standardized uptake values (SUVs) of 2.5±0.1 (n=8) in tumors from primary cells and 2.8±0.4 (n=6) in MTHJ tumors after 60 min p.i. The corresponding tumor-muscle-ratios were 9.3±1.5 and 10.4±0.9, respectively. Uptake of [(18)F]FLT resulted in slightly higher SUV(60min) in MTHJ tumors (1.1±0.1, n=6) compared to tumors from primary cells (SUV(60min)=0.9±0.05, n=8, p=0.07). The tumor-muscle-ratio was comparable in both tumors (2.1±0.2 and 1.8±0.1, respectively). The PET imaging data demonstrates that the functional profile of immunocompetent murine breast tumor model MTHJ remains the same as in primary-derived PyMT tumors in vivo. Metabolic and proliferative rates as assessed with [(18)F]FDG and [(18)F]FLT are comparable in both tumor models. The observed high SUV(60min) of 2.8±0.4 with [(18)F]FDG in MTHJ tumors allows one to monitor efficacy of therapeutic interventions connected with changes in metabolic response of the tumor by means of small animal PET.
A path-specific approach to SEIR modeling

Despite being developed in the late 1920s, compartmental epidemic modeling is still a rich and fruitful area of research. The original compartmental epidemic models were SIR (Susceptible, Infectious, Removed) models, which assume permanent immunity after recovery. SIR models, along with the more recent SEIR (Susceptible, Exposed, Infectious, Removed) models are still the gold standard in modeling pathogens that confer permanent immunity. This dissertation expands the SEIR structure to include a new class of spatial SEIR models. The exponential assumption of these models states that the latent and infectious times of the pathogen are exponentially distributed. Work that relaxes this assumption and still allows for mixing to occur at the population level is limited, thereby making strong assumptions about these times. We relax this assumption in a flexible way, by considering a hybrid approach that contains characteristics of both population level and individual level approaches. Next, we expand the Conditional Autoregressive (CAR) class of spatial models. This is to account for the Mumps data set we have procured, which contains mismatched lattice structures that cannot be handled by traditional CAR models. The use of CAR models is desirable here, as these models are known to produce spatial smoothing on lattices, and are a natural way to draw strength spatially in estimating spatial effects. Finally, we develop a pair of spatial SEIR models utilizing our CAR structure. The first utilizes the exponential assumption, which is very robust. The second develops a highly flexible spatial SEIR model by embedding the CAR structure into the SEIR structure. This allows for a realistic analysis of epidemic data occurring on a lattice.
Bioinformatics-Aided Venomics

Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future.
The Chemopreventive Polyphenol Curcumin Prevents Hematogenous Breast Cancer Metastases in Immunodeficient Mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitroand in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA-MB-231 cells in correlation with reduced activation of the survival pathway NFĸB, as a consequence of diminished ΙĸB and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NFĸ B activity and transcriptional downregulation of AP-1. NFĸ B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NFĸ B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NFĸ B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible.
Model reduction and control for networked systems with high energy throughput

The present paper analyzes the energy dynamics of networked process units. In such systems, the material recycle streams interconnecting the units take on the additional role of energy carriers. In the presence of large energy input and output flows, the process networks considered are shown to exhibit a dynamic behavior with multiple time scales, with the variables in the energy balance evolving over a short time horizon, and the variables in the material balance exhibiting both fast and slow transients. A singular perturbation analysis is employed for the derivation of reduced order models for the fast and slow dynamics, and a controller design framework that rationally accounts for this time scale separation is subsequently proposed. Finally, an illustrative example and numerical simulation results are presented
Regulation of the Intermediate Filament Protein Nestin at Rodent Neuromuscular Junctions by Innervation and Activity

The intermediate filament nestin is localized postsynaptically at rodent neuromuscular junctions. The protein forms a filamentous network beneath and between the synaptic gutters, surrounds myofiber nuclei, and is associated with Z-discs adjacent to the junction. In situ hybridization shows that nestin mRNA is synthesized selectively by synaptic myonuclei. Although weak immunoreactivity is present in myelinating Schwann cells that wrap the preterminal axon, nestin is not detected in the terminal Schwann cells (tSCs) that cover the nerve terminal branches. However, after denervation of muscle, nestin is upregulated in tSCs and in SCs within the nerve distal to the lesion site. In contrast, immunoreactivity is strongly downregulated in the muscle fiber. Transgenic mice in which the nestin neural enhancer drives expression of a green fluorescent protein (GFP) reporter show that the regulation in SCs is transcriptional. However, the postsynaptic expression occurs through enhancer elements distinct from those responsible for regulation in SCs. Application of botulinum toxin shows that the upregulation in tSCs and the loss of immunoreactivity in muscle fibers occurs with blockade of transmitter release. Extrinsic stimulation of denervated muscle maintains the postsynaptic expression of nestin but does not affect the upregulation in SCs. Thus, a nestin-containing cytoskeleton is promoted in the postsynaptic muscle fiber by nerve-evoked muscle activity but suppressed in tSCs by transmitter release. Nestin antibodies and GFP driven by nestin promoter elements serve as excellent markers for the reactive state of SCs. Vital imaging of GFP shows that SCs grow a dynamic set of processes after denervation.
Transition Experiences of Stroke Survivors Following Discharge Home

Abstract Background: Little is known about the transition experiences of stroke survivors after discharge home. Purpose: The purpose of this article is to describe three domains of psychosocial experiences of stroke survivors during the first month following discharge for acute stroke. Method: Data were collected from 125 stroke survivors interviewed at 1 month following discharge home. Results: Findings indicate that changes in sense of self, connectedness with others, and community integration presented the major challenges.
Case Studies of Exceptional People: What Can They Teach Us?.

AbstractThis article describes the use of the case study method for the investigation of exceptional moral commitment. William Damon and I used the case study method in this research because we were interested in sustained, long-term moral commitment and in the transformation of moral goals over time within the context of life histories, social relationships, and other influences. The study yielded in-depth life history interviews with 23 people who were selected for having worked for many years to address such issues as civil rights, poverty, and peace. Case material was used to illustrate and flesh out a theoretical account of a developmental process called the transformation of goals through social influence. The use of 23 diverse cases also allowed us to identify common characteristics that cut across the interviews. The three main themes that emerged from the case material were certainty, positivity, and unity of self and moral goals. (Psychology; Human Development; Case Study)