Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling long-term longitudinal HIV dynamics with application to an AIDS clinical study

A virologic marker, the number of HIV RNA copies or viral load, is currently used to evaluate antiretroviral (ARV) therapies in AIDS clinical trials. This marker can be used to assess the ARV potency of therapies, but is easily affected by drug exposures, drug resistance and other factors during the long-term treatment evaluation process. HIV dynamic studies have significantly contributed to the understanding of HIV pathogenesis and ARV treatment strategies. However, the models of these studies are used to quantify short-term HIV dynamics (< I month), and are not applicable to describe long-term virological response to ARV treatment due to the difficulty of establishing a relationship of antiviral response with multiple treatment factors such as drug exposure and drug susceptibility during long-term treatment. Long-term therapy with ARV agents in HIV-infected patients often results in failure to suppress the viral load. Pharmacokinetics (PK), drug resistance and imperfect adherence to prescribed antiviral drugs are important factors explaining the resurgence of virus. To better understand the factors responsible for the virological failure, this paper develops the mechanism-based nonlinear differential equation models for characterizing long-term viral dynamics with ARV therapy. The models directly incorporate drug concentration, adherence and drug susceptibility into a function of treatment efficacy and, hence, fully integrate virologic, PK, drug adherence and resistance from an AIDS clinical trial into the analysis. A Bayesian nonlinear mixed-effects modeling approach in conjunction with the rescaled version of dynamic differential equations is investigated to estimate dynamic parameters and make inference. In addition, the correlations of baseline factors with estimated dynamic parameters are explored and some biologically meaningful correlation results are presented. Further, the estimated dynamic parameters in patients with virologic success were compared to those in patients with virologic failure and significantly important findings were summarized. These results suggest that viral dynamic parameters may play an important role in understanding HIV pathogenesis, designing new treatment strategies for long-term care of AIDS patients.
Fictitious reference iterative tuning for a system with a time-delay and/or unstable zeros in the internal model control architecture

As one of the interesting and meaningful applications of a controller parameter tuning, this paper proposes a simultaneous attainment of both of a desired controller and a mathematical model of a plant in the internal model control (IMC) architecture. Particularly, we focus on systems with a time-delay and/or unstable zeros which cannot be neglected in many applications. For the purpose of the simultaneous attainment of a controller and a model of the plant, we introduce a specific structure of the feedback controller with a tunable parameter in IMC. And then, we utilize the fictitious reference iterative tuning (FRIT), which is a useful controller parameter tuning with only one-shot experimental data, for the tuning of the parametrized feedback controller and the parameterized internal model. In addition, we explain how the utilization of FRIT and the proposed structure on the feedback controller are effective for obtaining not only the desired control parameter but also an appropriate mathematical model of the plant. Finally, in order to show the validity of the proposed method, we give an illustrative example.
Designing High Performance Cmos Microprocessors Using Full Custom Techniques

In this paper, we describe a full customCMOS design methodology and supporting CADtechnologies used to develop ALPHA and StrongARMmicroprocessors at Digital Semiconductor. The paper issubdivided into four parts, starting with a description ofthe design methodology and general CAD flows.Additional sections focus on two particular areas ofinterest: high performance low-power and full customdesign benefits and verification issues.
Developmental dyslexia: A motor‐articulatory feedback hypothesis

Reading is mediated by parallel and widely distributed modular systems. There are, therefore, multiple loci in these systems where dysfunction may lead to developmental dyslexia. However, most normal children learn to read using the alphabetic system. Learning to use this system requires awareness that words are comprised of a series of speech sounds (phonological awareness) and the knowledge of how to conyert letters (graphemes) into these speech sounds (phonemes). Most dyslexic children have deficient phonological awareness and have difficulty converting graphemes into phonemes. Studies of patients with acquired lesions who are unable to convert graphemes into phonemes, as well as positron emission tomographic studies of normal subjects, suggest that the left inferior frontal lobe is important in phonologic reading. Phonetic gestures are represented in the brain as invariant motor commands that program the articulators. Phono‐ logic reading may activate the left inferior frontal lobe because grapheme‐to‐phoneme conversion requires activation of these motor‐articulatory gestures. Dyslexic children are unaware of the position of their articulators during speech. The inability to associate the position of their articulators with speech sounds may impair the development of phonological awareness and the ability to convert graphemes to phonemes. Unawareness of their articulators may be related to programming or feedback deficits.
sub-SAT: a formulation for relaxed boolean satisfiability with applications in routing

Advances in methods for solving Boolean satisfiability (SAT) for large problems have motivated recent attempts to recast physical de¿sign problems as Boolean SAT problems. One persistent criticism of these approaches is their inability to supply partial solutions, i.e, to satisfy most but not all of the constraints cast in the SAT style. In this paper we present a formulation for "subset satisfiable" Boolean SAT: we transform a "strict" SAT problem with N constraints into a new, "relaxed" SAT problem which is satisfiable just if not more than k < < N of these constraints cannot be satisfied in the original problem. We describe a transformation based on explicit thresholding and counting for the necessary SAT relaxation. Examples from FPGA routing show how we can determine efficiently when we can satisfy "almost all" of our geometric constraints.
Nevus lipomatosus cutaneus superficialis associated with nevus sebaceous of Jadassohn.

Sir,Nevus lipomatosus cutaneous superficialis is an uncommon disease of unknown etiology characterized by lipocyte collections situated ectopically within the dermis. Hoffman and Zurhelle first described nevus lipomatosus cutaneous superficialis, (which is also termed pedunculated lipofibroma), in 1921. The typical presentation is as clustered, multiple skin-coloured or yellowish papules or nodules present on the lower trunk, especially on the buttocks. Two types of nevus lipomatosus cutaneous superficialis are defined: the multiple or classic type consists of zonal or segmentally distributed multiple lesions while the solitary type presents as a solitary papule or nodule. [1]A 21-year-old man presented to our clinic with many asymptomatic nodular lesions distributed in a segmental pattern on the left buttock and left lumbar area. The lesion began 10 years ago and was gradually increasing in size. On dermatologic examination, multiple, skin-colored, soft coalescent papules and nodular lesions were observed in an approximately 15 × 25 cm area in the left sacral and left lumbar region. The lesions were unilateral and did not cross the midline. A 5 × 11 cm diameter flesh-colored, soft to firm, lobulated and smooth surfaced, non-tender, rubbery, sessile cerebriform
Is it time to revisit the role of psychedelic drugs in enhancing human creativity?

Human creativity is difficult to define and measure, but it is undoubtedly an important cognitive process. This makes it an interesting challenge for modern neuroscientific exploration — especially given the current interest in developing cognitive enhancers for commercial and clinical uses. There are similarities between the typical traits of creative people and the subjective psychological characteristics of the psychedelic (hallucinogenic) drug experience. This phenomenon was studied in a number of small trials and case studies in the 1960s. Results were inconclusive, and the quality of these studies — by modern research standards — was merely anecdotal. Nevertheless, with today's current renaissance in psychedelic drug research and the growing interest in cognitive enhancing drugs, now may be the time to re-visit these studies with contemporary research methods.
Genetic conflicts, multiple paternity and the evolution of genomic imprinting.

We present nine diallelic models of genetic conflict in which one allele is imprintable and the other is not to examine how genomic imprinting may have evolved. Imprinting is presumed to be either maternal (i.e., the maternally derived gene is inactivated) or paternal. Females are assumed to be either completely monogamous or always bigamous, so that we may see any effect of multiple paternity. In contrast to previous verbal and quantitative genetic models, we find that genetic conflicts need not lead to paternal imprinting of growth inhibitors and maternal imprinting of growth enhancers. Indeed, in some of our models--those with strict monogamy--the dynamics of maternal and paternal imprinting are identical. Multiple paternity is not necessary for the evolution of imprinting, and in our models of maternal imprinting, multiple paternity has no effect at all. Nevertheless, multiple paternity favors the evolution of paternal imprinting of growth inhibitors and hinders that of growth enhancers. Hence, any degree of multiple paternity means that growth inhibitors are more likely to be paternally imprinted, and growth enhancers maternally so. In all of our models, stable polymorphism of imprinting status is possible and mean fitness can decrease over time. Neither of these behaviors have been predicted by previous models.
Polymorphism in the &bgr;1-Adrenergic Receptor Gene and Hypertension

Background—The Arg389 variant of the &bgr;1-adrenergic receptor gene mediates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly polymorphism is associated with hypertension in Scandinavians. Methods and Results—A total of 292 unrelated, nondiabetic, hypertensive patients and 265 unrelated healthy control subjects were included in a case-control association study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive medication who were discordant for the Arg389Gly polymorphism were selected for a sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly polymorphisms were compared between hypertensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes. In the case-control study, the age- and body mass index-adjusted odds ratio for hypertension in subjects homozygous for the Arg389 allele was 1.9 (95% confidence interval, 1.3 to 2.7;P =0.0005) when compared with carriers of 1 or 2 copies of the Gly389 allele. The genotype-discordant sibling pair analysis revealed that siblings homozygous for the Arg389 allele had significantly higher diastolic blood pressures (79.4±9.9 versus 76.0±10.1 mm Hg;P =0.003) and higher heart rates (68.3±11.0 versus 65.1±9.4 bpm;P =0.02) than siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly polymorphism was not associated with hypertension. Conclusion—Our data suggest that individuals homozygous for the Arg389 allele of the &bgr;1-adrenergic receptor gene are at increased risk to develop hypertension.
Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive tumor and a leading cause of cancer-related deaths globally. The mortality rate remains high despite many advances in treatment. HCC is frequently diagnosed late in its course due to lack of classical symptoms at earlier stages. Endoscopic ultrasound (EUS) has emerged as an important diagnostic tool for the diagnostic evaluation, staging, and treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration has been a valuable addition to EUS by being able to obtain tissue under direct visualization. Here, we review the potential role of EUS in the diagnosis and management of HCC. EUS seems to be a safe and reliable alternative method for obtaining tissue for diagnosis of liver cancer, especially for lesions that are inaccessible by traditional methods. EUS could play an important role in the diagnosis and management of HCC.
Object-based attentional selection modulates anticipatory alpha oscillations

Visual cortical alpha oscillations are involved in attentional gating of incoming visual information. It has been shown that spatial and feature-based attentional selection result in increased alpha oscillations over the cortical regions representing sensory input originating from the unattended visual field and task-irrelevant visual features, respectively. However, whether attentional gating in the case of object based selection is also associated with alpha oscillations has not been investigated before. Here we measured anticipatory electroencephalography (EEG) alpha oscillations while participants were cued to attend to foveal face or word stimuli, the processing of which is known to have right and left hemispheric lateralization, respectively. The results revealed that in the case of simultaneously displayed, overlapping face and word stimuli, attending to the words led to increased power of parieto-occipital alpha oscillations over the right hemisphere as compared to when faces were attended. This object category-specific modulation of the hemispheric lateralization of anticipatory alpha oscillations was maintained during sustained attentional selection of sequentially presented face and word stimuli. These results imply that in the case of object-based attentional selection—similarly to spatial and feature-based attention—gating of visual information processing might involve visual cortical alpha oscillations.
A Comparison of Portable Dynamic Web Content Technologies for the Apache Server

Apache is considered to be the most extensible, secure and widely used server on the Internet. On our talk we focus on its first characteristic, extensibility, analyzing many techniques used to provide dynamic content. Available solutions are based either on extensions to the web server itself or on the execution of userspace programs. These solutions include, among others, CGI scripts, PHP, mod perl, mod python and Java Servlets. For each technology we present its basic design goals and the development facilities it offers. We compare the efficiency of these technologies by means of custom-made benchmarks we run to measure each solution’s throughput. Finally, we present each technique’s drawbacks, with references to lessons learned during the complete deploy-and-test process.
The hyper-cube framework for ant colony optimization

Ant colony optimization is a metaheuristic approach belonging to the class of model-based search algorithms. In this paper, we propose a new framework for implementing ant colony optimization algorithms called the hyper-cube framework for ant colony optimization. In contrast to the usual way of implementing ant colony optimization algorithms, this framework limits the pheromone values to the interval [0,1]. This is obtained by introducing changes in the pheromone value update rule. These changes can in general be applied to any pheromone value update rule used in ant colony optimization. We discuss the benefits coming with this new framework. The benefits are twofold. On the theoretical side, the new framework allows us to prove that in the ant system, the ancestor of all ant colony optimization algorithms, the average quality of the solutions produced increases in expectation over time when applied to unconstrained problems. On the practical side, the new framework automatically handles the scaling of the objective function values. We experimentally show that this leads on average to a more robust behavior of ant colony optimization algorithms.
Physiological cross‐sectional area of human leg muscles based on magnetic resonance imaging

Magnetic resonance imaging techniques were used to determine the physiological cross‐sectional areas (PCSAs) of the major muscles or muscle groups of the lower leg. For 12 healthy subjects, the boundaries of each muscle or muscle group were digitized from images taken at 1‐cm intervals along the length of the leg. Muscle volumes were calculated from the summation of each anatomical CSA (ACSA) and the distance between each section. Muscle length was determined as the distance between the most proximal and distal images in which the muscle was visible. The PCSA of each muscle was calculated as muscle volume times the cosine of the angle of fiber pinnation divided by fiber length, where published fiber length:muscle length ratios were used to estimate fiber lengths. The mean volumes of the major plantarflexors were 489, 245, and 140 cm3 for the soleus and medial (MG) and lateral (LG) heads of the gastrocnemius. The mean PCSA of the soleus was 230 cm2, about three and eight times larger than the MG (68 cm2) and LG (28 cm2), respectively. These PCSA values were eight (soleus), four (MG), and three (LG) times larger than their respective maximum ACSA. The major dorsiflexor, the tibialis anterior (TA), had a muscle volume of 143 cm2, a PCSA of 19 cm2, and an ACSA of 9 cm2. With the exception of the soleus, the mean fiber length of all subjects was closely related to muscle volume across muscles. The soleus fibers were unusually short relative to the muscle volume, thus potentiating its force potential. Using the relationship between PCSA and fiber length to represent the maximum force‐velocity potential of a muscle and assuming a similar moment arm, the soleus, MG, and LG would be expected to produce ±71, 22, and 7% of the force and 54, 30, and 16% of the power of the major plantarflexors. These data illustrate some of the major limitations in the use of ACSA measurements to predict the functional properties of a muscle.
An investigation into the notion of non-functional requirements

Although Non-Functional Requirements (NFRs) are recognized as very important contributors to the success of software projects, studies to date indicate that there is still no general consensus in the software engineering community regarding the notion of NFRs. This paper presents the result of an extensive and systematic analysis of the extant literature over three NFRs dimensions: (1) definition and terminology; (2) types; and (3) relevant NFRs in various types of systems and application domains. Two different perspectives to consider NFRs are described. A comprehensive catalogue of NFRs types as well as the top five NFRs that are frequently considered are presented. This paper also offers a novel classification of NFRs based on types of systems and application domains. This classification could assist software developers in identifying which NFRs are important in a particular application domain and for specific systems.
EPR studies of SmBa2Cu3O7-δ/MnFe2O4 superconducting composites

Electron paramagnetic resonance (EPR) studies are carried out on composite samples of SmBa2Cu3O7-δ/(MnFe2O4)x superconductors with 0.00 ≤ x ≤ 0.20 wt% at different temperatures 100K ≤ T ≤ 295K. An EPR signal of Cu2+ ions in the orthorhombic local symmetry is observed. Moreover, the EPR signal intensity increases as the temperature decreases from room temperature down to 100 K. The temperature dependence of g-factors indicates the pseudogap onset temperature (T*), corresponding to the peak of the observed curves between 127 K and 162 K. The number of spins (N) participating in EPR resonance are calculated as a function of both nanosized MnFe2O4 addition and temperature. In particular, it is shown that any EPR signal for SmBa2Cu3O7-δ/(MnFe2O4)x is probably due to small amount of spurious phases typically present in the samples such as BaCuO2. The presence of BaCuO2 is confirmed by magnetization-field (M-H) hysteresis measurements
Plasmids Imparting Sulfonamide Resistance in Escherichia coli: Implications for Persistence

ABSTRACT Sulfonamide resistance remains prevalent among clinical isolates of Escherichia coli in the United Kingdom, despite a dramatic (>97%) national decline in the rate of prescription of sulfonamides in the 1990s. To investigate potential mechanisms accounting for this persistence, we characterized plasmids carrying sul2, the most prevalent determinant of sulfonamide resistance. Among 33 conjugative and 5 nonconjugative plasmids carrying sul2, resistance to other antimicrobial agents was common, but the spectrum of resistance profiles was diverse: 82%, 74%, and 45% carried resistance to ampicillin, streptomycin, and trimethoprim, respectively. Resistance to mercury was carried by 33% of the plasmids, but none conferred significant resistance to silver or to any of three disinfectants tested. The potential virulence genes iutA (aerobactin system) and traT (serum survival) were carried by 21% and 36% of the plasmids, respectively. The 33 conjugative plasmids belonged to five different incompatibility groups, FIB, B/O, I1, K/B, and P (42%, 33%, 9%, 3% and 3%, respectively), with 3 plasmids being unassigned, and to 19 similarity groups on the basis of their restriction profiles. The sequences flanking sul2 were diverse and suggested more than one mechanism of genetic mobility. The five nonconjugative plasmids were all related to p9123 (pBP1), which was previously found to confer a fitness advantage on its host. We propose that the persistence of sul2, despite the reduced rate of prescription of sulfonamides, is due to a combination of coselection by antibiotics still in common use, a lack of a selective disadvantage in sul2 carriage, and the genetic mobility of sul2.
Kinase Identification with Supervised Laplacian Regularized Least Squares

Phosphorylation is catalyzed by protein kinases and is irreplaceable in regulating biological processes. Identification of phosphorylation sites with their corresponding kinases contributes to the understanding of molecular mechanisms. Mass spectrometry analysis of phosphor-proteomes generates a large number of phosphorylated sites. However, experimental methods are costly and time-consuming, and most phosphorylation sites determined by experimental methods lack kinase information. Therefore, computational methods are urgently needed to address the kinase identification problem. To this end, we propose a new kernel-based machine learning method called Supervised Laplacian Regularized Least Squares (SLapRLS), which adopts a new method to construct kernels based on the similarity matrix and minimizes both structure risk and overall inconsistency between labels and similarities. The results predicted using both Phospho.ELM and an additional independent test dataset indicate that SLapRLS can more effectively identify kinases compared to other existing algorithms.