Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetics of Pegylated Liposomal CKD‐602 (S‐CKD602) in Patients With Advanced Malignancies

S‐CKD602 is a pegylated long‐circulating liposomal formulation of CKD‐602, a potent topoisomerase I inhibitor. A population pharmacokinetic (PK) model for encapsulated and released CKD‐602 following administration of S‐CKD602 was developed to assess factors that may influence S‐CKD602 PK. Plasma samples from 45 patients with solid tumors were collected in a phase 1 study. S‐CKD602 was administered as a 1‐hour intravenous infusion with doses ranging from 0.1 to 2.5 mg/m2. Plasma concentrations of encapsulated and released CKD‐602 were used to develop a population PK model using NONMEM. PK of encapsulated CKD‐602 was described by a 1‐compartment model with nonlinear clearance, and PK of released CKD‐602 was described by a 2‐compartment model with linear clearance for all patients. Covariate analysis revealed that tumor in the liver was a significant covariate for clearance of encapsulated CKD‐602 and that age significantly influenced the release rate of CKD‐602 from S‐CKD602. Maximum elimination rate in patients with liver tumor is 1.5‐fold higher compared with patients without liver tumor. Release rate of CKD‐602 from S‐CKD602 in patients less than 60 years old was 2.7‐fold higher compared with patients 60 years old or older. These observations have potential implications in the optimal dosing of liposomal agents.
Validating and Verifying Memory Safety for Concurrent Operating System Code

The current practice of finding programming errors in operating system development is by testing and debugging. However, testing techniques are expensive because of their requirement of manual labour. Furthermore, they are susceptible to missing severe errors. This problem can be solved by applying automated verification techniques such as software model checking. Most of these techniques suffer from limitations in analysing pointer programs and dealing with concurrency. Because of this, verification methods available today are not sufficient to cover the class of software defects related to memory safety in concurrent reactive software systems. In this dissertation we give a review on current practice and state-ofthe-art techniques and tools for detecting memory safety errors in computer programs. Furthermore we outline a new approach in validating and verifying memory safety properties for concurrent reactive software systems such as device drivers. Our approach is based on both, program simulation and software model checking. In contrast to previous work on memory safety problems, we intend to provide a fully automatic analysis and verification framework covering a broad range of memory safety related problems.
The effect of thematic structure on the variability of annual report readability

The readability of annual reports has been the focus of extensive prior research. However, the extent of readability variability has only recently received specific attention. In response to a perceived need for further research into this area, an analysis of 60 UK chairman’s statements was conducted in order to test for possible determinants of readability variability. Results show the introduction to the chairman’s statement is systematically easier to read than other parts of the chairman’s statement. No evidence was found to support prior research that, rather than present accounting narratives objectively, managers use readability variability to emphasise good news and obfuscate bad news. The thematic structures within the chairman’s statement were investigated to explore whether they were responsible for systematic patterns in the variability of annual report readability. Findings indicate that thematic structure of the chairman’s statement is indeed a key driver of the variability of annual report readability.
PERK Is Required in the Adult Pancreas and Is Essential for Maintenance of Glucose Homeostasis

ABSTRACT Germ line PERK mutations are associated with diabetes mellitus and growth retardation in both rodents and humans. In contrast, late embryonic excision of PERK permits islet development and was found to prevent onset of diabetes, suggesting that PERK may be dispensable in the adult pancreas. To definitively establish the functional role of PERK in adult pancreata, we generated mice harboring a conditional PERK allele in which excision is regulated by tamoxifen administration. Deletion of PERK in either young adult or mature adult mice resulted in hyperglycemia associated with loss of islet and β cell architecture. PERK excision triggered intracellular accumulation of proinsulin and Glut2, massive endoplasmic reticulum (ER) expansion, and compensatory activation of the remaining unfolded-protein response (UPR) signaling pathways specifically in pancreatic tissue. Although PERK excision increased β cell death, this was not a result of decreased proliferation as previously reported. In contrast, a significant and specific increase in β cell proliferation was observed, a result reflecting increased cyclin D1 accumulation. This work demonstrates that contrary to expectations, PERK is required for secretory homeostasis and β cell survival in adult mice.
STABILITY ANALYSIS FOR A CLASS OF NONLINEARSWITCHED

In the present paper, we study several qualitative properties of a class of nonlinear switched systems under certain switching laws. First, we show that if all the subsystems are linear time-invariant and the system matrices are commutative componentwise and stable , then the entire switched system is globally exponentially stable under arbitrary switching laws. Next, we study the above linear switched systems with certain nonlinear perturbations, which can be either vanishing or non-vanishing. Under reasonable assumptions, global exponential stability is established for these systems. We further study the stability and instability properties, under certain switching laws, for switched systems with commutative subsystem matrices that may be unstable. Results for both continuous-time and discrete-time cases are presented.
The Concept of 'Region': Theoretical and Methodological Notes on its Reconstruction

The vast array of entities commonly labelled 'regions' actually encompasses a wide range of quite different phenomena. We tend to call the Baltic Sea a region as we do the Near East, Lombardy, North Rhine-Westphalia, the Baranya and the Öresund. We further refer on frequent occasions to administrative regions, economic regions, labour regions and statistical regions. This proliferation of uses begs a central question: Do common parameters and methods exist for analysing these different phenomena? This article tackles the challenge of (re)constructing a definition of region, which is a prerequisite for subsequent empirical research and practical application. Failing to find in extant academic approaches an acceptable transdisciplinary definition of region, the article offers a spatial definition of region and derives from it the core elements of a regional system. Based on these elements a typology of the regional phenomenon (subnational, transnational and international) is developed, which can be useful for policy research, especially the regional dimension within the process of European integration.
Helping a woman meet her stillborn baby while it is soft and warm

For the first 30 minutes, a stillborn baby feels soft and warm, just like a live baby. The time immediately after birth can be seen as an “acute” situation – a time that can never be relived. After just 30 minutes, the baby will grow cold, and its colour will change. Following stillbirth, parents are in a state of shock, and asking whether they want to see and hold their baby may suggest that it is not obvious that they would want to do so. This creates doubt, and for many the spontaneous reaction may be to reply with a refusal they later regret. Not seeing the baby immediately after delivery also means not holding the baby immediately afterwards. Parents who have both seen and held the baby during the first 30 minutes describes this as the most valuable time they had with their baby.
Effect of components relative tolerance in the magnitude response of a Gm-C biquad

We analyze the effects of relative mismatches in transconductances and in capacitances onto the magnitude of the Gm-C biquad filter section. It is confirmed that deviation from the ideal magnitude increases with Q and with mismatches, being those associated with transcondunctances the relevant ones. The obtained data can be used at an early design stage to limit the magnitude error of a cascaded filter to a specified value by limiting the Q factor of each biquad.
CTL quality and the control of human retroviral infections

The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T‐cell phenotype and function indicate that individual differences in the efficiency of the virus‐specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV‐1 and HIV‐1. It is now believed that differences in anti‐viral CTL efficiency or “quality” at the single‐cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects – or both – of the variation in the efficiency of virus control.
Development of Receptive Field Structure of Simple Cell using Spike Timing Dependent Plasticity (STDP)

Simple cells found in primary visual cortex are orientation selective. It has been experimentally found that they acquire this property with time i.e. learning of orientation selectivity takes place. Many computational models have been proposed for the development of orientation selectivity. Most of the models proposed so far are either abstract in nature or are very simplified version of actual learning mechanism. In this work we propose a model for development of orientation selectivity based on spike timing dependent plasticity (STDP), which till now is considered to be the actual learning mechanism adopted by neural circuits. We could obtain elongated segregated receptive field structure thus giving simple cells the property of orientation selectivity. We also observe that input activity plays a major role in the development of orientation selectivity, too much or too less a correlation between the inputs activities do not result in the formation of segregated ON and OFF regions in the RF structure [1]. There is also a need of normalization for the development of orientation selectivity.
DESIGNING ANMPI-BASED PARALLEL AND DISTRIBUTED MACHINE LEARNING PLATFORM ON LARGE-SCALE HPC CLUSTERS

This paper presents the design of an MPI-based parallel and distributed machine learning platform on large-scale HPC clusters. Researchers and practitioners can implement easily a class of parallelizable machine learning algorithms on the platform, or port quickly an existing non-parallel implementation of a parallelizable algorithm to the platform with only minor modifications. Complicated functions in parallel programming such as scheduling, caching and load balancing are handled automatically by the platform. The platform performance was evaluated in a series of stress tests by using a k-means clustering task on 7,500 hours of speech data (about 2.7 billion 52dimensional feature vectors). Good scalability is demonstrated on an HPC cluster with thousands of CPU cores.
Working Conditions In Charter Schools

This article synthesizes past research findings on the work of charter school teachers and juxtaposes this research with case studies of forty charter school teachers in six urban charter elementary schools. Charter schools, with increased autonomy over personnel and budget, are given the freedom to make many decisions related to hiring, salary, and working conditions. In general, charter school teachers work longer hours and receive less job security than colleagues in traditional public schools. In some states, charter school teachers earn significantly less than other public school colleagues. The evidence also suggests, however, that teachers generally enjoy their professional lives in charter schools—their colleagues and the school’s education program. The authors argue that in order to continue to attract and retain teachers, charter schools may need to extend their use of autonomy to improve the working conditions of teachers and ultimately, to extend the life of the school.
A comparison on timing analysis using probabilistic approaches

This paper presents a comparison on various timing analysis methods. Timing analysis is a critical step in any digital integrated circuits. Static timing analysis is a method to validate the timing performance of a digital circuit without requiring simulation. Technology and the process scaling to nanometer regime have lead to significant increase in process variations. These variations are needed to incorporate in static timing analysis. In the proposed method the delays of the gates and the arrival time are modeled by probabilistic distributions. The gate delays and the arrival time are modeled by using the operations statistical convolution integration and the statistical maximum. The delay values used is extracted from the standard delay format file for each gate. The method is tested by using various ISCAS benchmark circuits. Further statistical static timing analysis with arrival time at 3σ points away from the mean is calculated. The statistical static timing analysis results are found to be more accurate as it considers process variations.
Endothelial dysfunction in patients with chronic kidney disease results from advanced glycation end products (AGE)-mediated inhibition of endothelial nitric oxide synthase through RAGE activation.

BACKGROUND AND OBJECTIVES Advanced glycation end products, known pro-inflammatory and pro-oxidative compounds that accumulate in patients with chronic kidney disease, may play a major role in their high prevalence of endothelial dysfunction and subsequent cardiovascular disease. This study examined the association of advanced glycation end product accumulation with cellular receptor for advanced glycation end product expression and endothelial dysfunction as well as the mechanisms of this association in chronic kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cross-sectional study was conducted of ambulatory patients without diabetes and with different stages of chronic kidney disease (n = 51), compared with gender- and age-matched healthy subjects. Fasting blood was obtained for measurement of advanced glycation end products and mRNA receptor for advanced glycation end product expression in peripheral blood mononuclear cells. Endothelial reactivity was assessed by the microcirculatory response to local ischemia (postocclusive reactive hyperemia) and local hyperthermia (thermal hyperemia). Sera were pooled and passed through affinity columns to separate advanced glycation end product-rich fractions, which were incubated with human aortic endothelial cells, with or without blockade of receptor for advanced glycation end product, to measure their effect on endothelial nitric oxide synthase. RESULTS Glomerular filtration rate correlated with serum advanced glycation end product, mRNA receptor for advanced glycation end product levels, postocclusive reactive hyperemia, and thermal hyperemia. Serum advanced glycation end product correlated with receptor for advanced glycation end product and inversely with postocclusive reactive hyperemia. Advanced glycation end product-rich fractions from chronic kidney disease sera suppressed endothelial nitric oxide synthase expression of human aortic endothelial cells compared with sera from healthy subjects, an effect abrogated by receptor for advanced glycation end product blockade. CONCLUSIONS This study demonstrates for the first time an association of excess advanced glycation end product burden with increased peripheral blood mononuclear cell mRNA receptor for advanced glycation end product and in vivo endothelial dysfunction in patients with chronic kidney disease. Endothelial dysfunction in chronic kidney disease may be partly mediated by advanced glycation end product-induced inhibition of endothelial nitric oxide synthase through receptor for advanced glycation end product activation.
ON ELEMENTARY FLUX MODES IN BIOCHEMICAL REACTION SYSTEMS AT STEADY STATE

A mathematical definition of the concept of elementary mode is given so as to apply to biochemical reaction systems subsisting at steady state. This definition relates to existing concepts of null-space vectors and includes a condition of simplicity. It is shown that for systems in which all flux- have fixed signs, all elementary modes are given by the generating vectors of a convex cone and can, thus, be computed by an existing algorithm. The present analysis allows for the more general case that some reactions can proceed in either direction. Basic ideas on how to compute the complete set of elementary modes in this situation are outlined and verified by way of several examples, with one of them repraenting glycolysis and gluconeogenesis. These examples show that the elementary modes can be interpreted in terms of the particular biochemical functions of the network. The relationships to (futile) substrate cycles are elucidated.
Systems of Ultimate Phonological Units

Abstract The paper upholds the existence of a phonological unit smaller than the phoneme, serving as the component of the latter. This is the linguistic correlate of articulatory movements together with their auditory reflexes, i.e. Baudouin de Courtenay’ kinakeme. The acceptance of the kinakeme as the ultimate phonological unit makes the notion of distinctive phonemic features redundant in linguistic theory. The kinakemes of any given language form a paradigmatic system and combine syntagmatically in phonemes.
Post‐Fordism and the Theorisation of Educational Change: what's in a name?

Abstract Post‐Fordist approaches offer a stimulating account of recent educational restructuring. There is, however, a problem with the term itself and the way it has framed and defined the debate. Mot only does it combine a number of diverse frameworks, applications and conclusions, but it also composites different levels of definitional coherence. In this way post‐Fordist education tries to operate as a generalised metaphor whilst also incorporating more tightly‐defined conceptual narratives. The result is that these different meanings become collapsed and the term itself swamped by overuse. A consequence is that the model is less able to offer an incisive or distinctive perspective on educational change. When specific post‐Fordist narratives are used to interrogate educational restructuring it is clear that they are unable to capture the range of levels in which change is both generated and manifest. This raises a broader issue for educational theorisation—identifying the structures that mediate and li.
The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding

Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfolding and this unfolding is prevented by GPIHBP1 (Mysling et al., 2016). We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain; (2) that binding to GPIHBP1 renders LPL largely refractory to this inhibition; and (3) that both the LU domain and the intrinsically disordered acidic domain of GPIHBP1 are required for this protective effect. Genetic studies have found that a common polymorphic variant in ANGPTL4 results in lower plasma triglyceride levels. We now report: (1) that this ANGPTL4 variant is less efficient in catalyzing the unfolding of LPL; and (2) that its Glu-to-Lys substitution destabilizes its N-terminal α-helix. Our work elucidates the molecular basis for regulation of LPL activity by ANGPTL4, highlights the physiological relevance of the inherent instability of LPL, and sheds light on the molecular defects in a clinically relevant variant of ANGPTL4. DOI: http://dx.doi. org/10.7554/eLife.20958. 001
Partner violence screening in rural health care clinics.

OBJECTIVES We sought to determine the frequency of intimate partner violence by type in a large, clinic-based, nurse-administered screening and services intervention project. METHODS A brief intimate partner violence screen, which included items to measure sexual and physical assaults and psychological battering (using the Women's Experience With Battering scale) was administered to consenting women receiving care at 1 of 8 rural clinics in South Carolina. RESULTS Between April 2002 and August 2005, 4945 eligible women were offered intimate partner violence screening, to which 3664 (74.1%) consented. Prevalence of intimate partner violence in a current (ongoing) relationship was 13.3%, and 939 women (25.6%) had experienced intimate partner violence at some point in the past 5 years. Of those ever experiencing intimate partner violence, the majority (65.6%) experienced both assaults and psychological battering; 10.1% experienced assault only, and 24.3% experienced psychological battering only. Most women (85.5%) currently experiencing both psychological battering and assaults stated that violence was a problem in their current relationship. CONCLUSIONS The intimate partner violence screening technique we used was feasible to implement, acceptable to women seeking health care at the targeted clinics, and indicated a high proportion of women reporting intimate partner violence in the past 5 years, with a majority of those women stating that such violence was a problem in their relationships. These findings demonstrated the viability of the screening technique, which supports the growing importance of implementing intimate partner violence screenings in clinical settings in order to reduce the prevalence of violence in intimate relationships.
The performance of Reed-Solomon codes on a bursty-noise channel

The performance of a Reed-Solomon coded binary communication system on a bursty-noise channel is considered. Bursty noise is defined to be background Gaussian noise plus burst noise, where burst noise is defined to be a series of finite-duration Gaussian-noise pulses with fixed duration and Poisson occurrence times. Using the noise model, along with ideal symbol interleaving, decoded bit-error probability bounds are derived for the case where the noise bursts are long with respect to the channel symbol rate. Specific performance results are presented for the (31,15,8) Reed-Solomon Joint Tactical Distribution System (JTIDS) code with a binary phase shift keyed (BPSK) modulation scheme. Simulation results are presented and they compare well with the theoretical results. >