Miracle-dz/UniFAR-FTUs huggingface dataset:
The Orphan Drug Act: Restoring the Mission to Rare Diseases

The Orphan Drug Act has fostered drug development for patients with rare cancers and other diseases; however, current data suggest that companies are gaming the system to use the law for mainstream drugs. We identify a pattern of pharmaceutical companies submitting drugs to the Food and Drug Administration (FDA) as orphan drugs but once approved, the drugs are used broadly off-label with the lucrative orphan drug protections and exclusivity benefits. Since the law was passed, the proportion of new FDA-approved drugs that were submitted as orphan drugs has increased with a peak last year of 41% of all FDA-approved drugs approved as orphan drugs. On the basis of the current data, we suggest that patients with rare cancers and other diseases may suffer due to dilution of the incentives and benefits. We propose reform to increase submission scrutiny, decrease benefits based on off-label use, and increase price transparency.
A Flexible Failure-Recovery Model for Workflow Management Systems

In this paper, we propose a new failure-recovery model for workflow management systems (WfMSs). This model is supported with a new language, called the workflow failure-handling (WfFH) language, which allows the workflow designer to write programs so that he can use data-flow analysis technology to guide the failure recovery in workflow execution. With the WfFH language, the computation of the end compensation point and the compensation set for failure recovery can proceed during the workflow process run-time according to the execution results and status of workflow activities. Also, the failure-recovery definitions programmed with the WfFH language can be independent, thereby dramatically reducing the maintenance overhead of workflow processes. A prototype is built in a Java-based object-oriented workflow management system, called JOO-WfMS. We also report our experiences in constructing this prototype.
Partitioning and Bioavailability of Polynuclear Aromatic Hydrocarbons in an Intertidal Marsh

Polycyclic aromatic hydrocarbons (PAHs) are trace organic pollutants now so ubiquitous in aquatic ecosystems that the major organic signature in urban storm runoff is that of weathered PAHs. PAHs are formed by combustion of organic matter including petroleum and wood but anthopogenically produced PAHs have increased greatly over the last century. PAHs are a problem in the environment since some are potent carcinogens to humans and wildlife alike. PAHs include the most toxic fraction of tobacco smoke, benzo(a)pyrene, naphalene, and phenanthrene and are often found in association with other organic pollutants such as chlorinated biphenyls (PCBs), and organochlorine compounds such as DDT. The persistence of PAHs in the environment and their concentration in the fat of living organisms increases the toxicity of PAHs and current regulatory standards are based on the bulk concentration of PAHs in the sediments and the amount of organic carbon in the sediments. Our research was intended to improve the understanding of PAHs in sediments, particularly the spatial and temporal variations in the bioavailabilty and bioaccumulation in shellfish and polychaete worms in the sediments of the San Francisco Bay Estuary. We concentrated on 18 individual PAH compounds and measured their seasonal and spatial variations in the intertidal sediments and biota. We found that the sediment pore water concentration of PAHs may be more important in determining the bioconcentration of PAHs in living tissue than the simple bulk concentrations in the sediments. Similarly, we found that the kind of organic carbon present is more important in determining the bioconcentration of PAHs in shellfish and polychaete worms than the simple total amount of carbon present. The explanation is probably that silt and small organic fragments, especially soot, may be mostly composed of PAHs while other organic carbon such a decaying leaves is not. Soot contains a lot of PAHs but they are strongly bound to the carbon matrix and are paradoxically less bioavailable than lower amounts of PAH bound to naturally-occurring carbon. Winter storms carrying accumulated sooty fallout and auto crankcase drippings from the watershed and depositing them preferentially in the upper intertidal of the estuary explains the observed PAH speciation and distribution as well as the observed bioconcentration patterns in the sediment-dwelling biota. We recommend that attention be paid to the kind of organic carbon and its site in the porewaters in the setting of future regulatory standards.
De gereformeerde zending in Midden Java, 1859-1931: Een bronnenpublicatie

Dit boek verschijnt in de reeks publicaties uit Nederlandse zendingsarchieven betreffende de zending in Indonesie. Deze publicaties geven een globaal beeld van de structuur en werkwijze van zendingsorganisaties en vormen een belangrijk hulpmiddel voor de bestudering van hun geschiedenis. Aan de orde kwamen reeds de zending in Tanah Toraja, Sumba, Zuid-Sulawesi, West-Java en Midden-Java (1931-1975). Deze uitgave is de tweede publicatie over Midden-Java.
A Class of Multi-Carrier CDMA Access Methods for Wide-Bandwidth Wireless Channels

In this article we describe and evaluate a general class of synchronous multi-carrier CDMA methods. In the proposed methods each accessing user is encoded by a Hadamard sequence and a multi-carrier (MC) encoder. The MC-encoder may provide one or many sub-carriers for each access channel while each accessing user may distribute its transmit power over all sub-carriers of its own access channel or over all subcarriers of all access channels. Each sub-carrier then carries the transmitted symbols of all users which are distinguished by their Hadamard sequences. In the performance evaluation presented herein we have examined their tolerance to synchronization jitter
Seven-year follow-up of vaccine response in extremely premature infants.

OBJECTIVE To assess the immune response of 7-year-old former extremely preterm (PT) infants to routine childhood immunizations. METHODS Sixteen PT (<29 weeks and <1000 g) infants, followed since their primary immunizations at the recommended chronological ages, and 16 age-matched full-term (FT) control subjects were evaluated at 7 years of age. Antibodies to Haemophilus influenzae type b polyribosylribitol phosphate (Hib-PRP), tetanus, pertussis, diphtheria, polio, and hepatitis B (HBsAb) were measured. RESULTS The FT group had higher antidiphtheria geometric mean titers (GMT) than the PT group (1.07 vs 0.36 IU/mL). All FT and 13 of 16 PT had protective diphtheria antibody titers (>0.1 IU/mL). The tetanus GMT were 4.22 IU/mL (FT) and 1.99 IU/mL (PT). All children had protective tetanus titers (>0.01 IU/mL). Pertussis titers did not differ between FT and PT. Hib-PRP GMT were higher in FT than in PT (3.21 vs 1.41 microg/mL). All children had anti-PRP > or = 0.15 microg/mL; 12 of 16 FT and 10 of 16 PT had levels > or = 1.0 microg/mL. Polio serotype 1 and 2 GMT were similar between groups, and all children had protective titers (> or = 8). Polio serotype 3 GMT were 59 (FT) and 24 (PT) Karber units; all FT and 12 of 16 PT had protective titers. Among children who had received hepatitis B vaccine, GMT were similar in FT and PT children (120 vs 186 mIU/mL, and similar proportions of children (11 of 16 FT and 12 of 14 PT) had protective HBsAb titers (>10 mIU/mL). CONCLUSIONS At 7 years of age, PT children had lower antibody titers to many vaccine antigens than FT children. However, most PT children maintained antibody titers in the protective range.
Small Delay Fault Model for Intra-Gate Resistive Open Defects

We propose the fault model considering weak resistive opens inside the gate which might cause pattern-sequence-dependent and timing-dependent malfunction of the circuit. We assume the fixed observation interval for the signal transition, and derive the minimum resistance of intra-gate resistive opens to be detected as a fault by SPICE simulation. Based on the simulation results, we establish three fault models, that is, the one considering the location of the resistance, the one considering both the location and the resistance distribution, and the simplified one where str and stf faults considering the signal transition of the input ports are assumed. The coverage calculation for the primitive gates and small benchmark circuit reveals that the proposed models have more accuracy on the detection of weak open defects.
Using the baseline CT scan to select acute stroke patients for IV-IA therapy.

BACKGROUND Intra-arterial therapies for acute ischemic stroke are increasingly available. Intravenous therapy (IV) followed immediately by intra-arterial therapy (IA) has been shown to be safe, but such therapy is resource intensive. Selecting the best patients for this therapy may be accomplished with the use of baseline neuroimaging. METHODS We used data from the IMS-1 and National Institute for Neurological Disorders and Stroke tissue plasminogen activator (tPA) stroke studies to compare outcomes among IV-IA tPA, IV-tPA, and placebo treatment stratified by the baseline CT scan appearance. The CT scans were scored using the Alberta Stroke Program Early CT (ASPECT) score and dichotomized into ASPECT score > 7 (favorable scan) and ASPECT score < or = 7 (unfavorable scan). Logistic regression was used to assess for an ASPECT score by treatment interaction. RESULTS A total of 460 patients was included. Age and sex were similar among the 3 groups. The IV-IA tPA cohort had a higher median National Institutes of Health stroke scale (NIHSS) score (18 versus 17) compared with the IV tPA cohort. The proportion of patients with favorable CT scans (ASPECT score > 7) was lowest in the IV-IA tPA group. A multiplicative interaction effect was shown indicating that patients with an ASPECT score > 7 in the IV-IA cohort were more likely to have a good outcome compared with IV tPA and with placebo. Harm may accrue to patients treated with IV-IA therapy who have an unfavorable baseline CT scan appearance. CONCLUSIONS Patients with a favorable baseline CT scan appearance are the most likely to benefit from IV-IA therapy. This hypothesis will be tested in the IMS-3 study.
Modeling the Performance of Geometric Multigrid Stencils on Multicore Computer Architectures

The basic building blocks of the classic geometric multigrid algorithm all have a low ratio of executed floating point operations per byte fetched from memory. On modern computer architectures, such computational kernels are typically bound by memory traffic and achieve only a small percentage of the theoretical peak floating point performance of the underlying hardware. We suggest the use of state-of-the-art (stencil) compiler techniques to improve the flop per byte ratio, also called the arithmetic intensity, of the steps in the algorithm. Our focus will be on the smoother which is a repeated stencil application. With a tiling approach based on the polyhedral loop optimization framework, data reuse in the smoother can be improved, leading to a higher effective arithmetic intensity. For an academic constant coefficient Poisson problem, we present a performance model for the multigrid $V$-cycle solver based on the tiled smoother. For increasing numbers of smoothing steps, there is a trade-off between the .
Modélisation bioénergétique de la croissance, du développement et de la reproduction d'un petit pélagique : l'anchois du golfe de Gascogne

Comprendre la variabilite du recrutement est une problematique majeure en halieutique. Dans ce travail, nous explorons une nouvelle approche pour etudier les facteurs qui determinent le recrutement, dans le cadre de la modelisation biophysique. Le schema de ponte des adultes peut influencer la survie des larves car il determine les conditions environnementales qu'elles rencontrent pendant cette periode critique. Notre cas d'etude est l'anchois du golfe de Gascogne Engraulis encrasicolus, qui est une espece a pontes multiples. L'objectif de la these est de comprendre l'effet de l'environnement vecu par un individu i) sur l'energie disponible pour la reproduction et ii) sur l'etalement des pontes et ses consequences sur la croissance, le developpement et la survie des larves. Pour apprehender les processus metaboliques en jeu, la theorie Dynamic Energy Budget est un outil particulierement adapte. Cette theorie permet d'identifier les processus communs et les specificites de chaque stade. Nous apportons tout d'abord une revision de la courbe de croissance de l'anchois du golfe de Gascogne. Nous reproduisons la croissance des juveniles en tenant compte du fait qu'ils experimentent en moyenne une temperature plus elevee durant cette phase que celle vecue ensuite par les adultes. La croissance larvaire differe de la croissance des juveniles et des adultes. Nous proposons de considerer la relation entre prise de nourriture et longueur de l'individu pour expliquer cette croissance. Ce travail nous permet ensuite de mieux comprendre et de quantifier l'effet des conditions environnementales vecues par un individu sur la duree de sa saison de reproduction. Ces conditions determinent d'une part la taille de l'individu donc son potentiel reproducteur et d'autre part la quantite d'energie qu'il peut effectivement mettre en reserve pour la reproduction. En conditions limitantes de nourriture, cette energie peut en effet etre mobilisee pour sa survie.
An optimal method of DNA silver staining in polyacrylamide gels

DNA silver staining has widely been used to detect DNA fragments in polyacrylamide gels with high sensitivity. We developed an optimal method for DNA silver staining on polyacrylamide gels. The novel procedure can be completed within 10 min instead of over 20 min with the conventional methods. The sensitivity is significantly improved by the silver‐ion sensitizer (Eriochrome black T (EBT)) and the minimum of 0.11 and 1.75 ng of DNA amount can be detected in denaturing and nondenaturing polyacrylamide gel, respectively. Compared with the conventional silver staining methods, the improved optimal method can save time and display high sensitivity, color uniformity, and long storage time of the staining gels.
A new resonant gate driver for switching loss reduction of high side switch in buck converter

In this paper, a new resonant gate driver circuits is proposed to reduce the switching loss of high side switch in buck converter. Hard switching causes major parts of the power loss in high side switch and limits high switching frequency application of DC-DC converter. The proposed resonant gate driver behaves more like the ideal current source driver which can fast turn-on/turn-off power switch to reduce switching loss. In addition, with proposed resonant gate driver, impact of parasitic gate resistance on switching speed of power switch can be greatly reduced. Test results show that, for buck converter with 12V input voltage, 1.3V output voltage, 10A load current and 5. 5Ω gate resistance, comparing to conventional driver, with the proposed resonant gate driver for high side switch, total efficiency of buck converter can be improved by more than 3.5%.
Shared Mechanisms of Perceptual Learning and Decision Making

Perceptual decisions require the brain to weigh noisy evidence from sensory neurons to form categorical judgments that guide behavior. Here we review behavioral and neurophysiological findings suggesting that at least some forms of perceptual learning do not appear to affect the response properties of neurons that represent the sensory evidence. Instead, improved perceptual performance results from changes in how the sensory evidence is selected and weighed to form the decision. We discuss the implications of this idea for possible sites and mechanisms of training-induced improvements in perceptual processing in the brain.
Linkage between X‐chromosome markers and manic‐depressive illness

ABSTRACT– Pedigrees of manic‐depressive patients in treatment at the Lithium Clinic of the Institute of Clinical Pharmacology, University of Cagliari, were evaluated for linkage between major affective illness and the protan‐deulan‐glucose‐6‐phosphatc‐dehydrogenase region of the X‐chromosome. Two informative pedigrees were found, investigated and analyzed for linkage using a multigenerational model and considering age‐dependent penetrance. The results are consistent with the hypothesis of X‐linkage in major affective illness.
Relocating the active-site lysine in rhodopsin and implications for evolution of retinylidene proteins

Type I and type II rhodopsins share several structural features including a G protein-coupled receptor fold and a highly conserved active-site Lys residue in the seventh transmembrane segment of the protein. However, the two families lack significant sequence similarity that would indicate common ancestry. Consequently, the rhodopsin fold and conserved Lys are widely thought to have arisen from functional constraints during convergent evolution. To test for the existence of such a constraint, we asked whether it were possible to relocate the highly conserved Lys296 in the visual pigment bovine rhodopsin. We show here that the Lys can be moved to three other locations in the protein while maintaining the ability to form a pigment with 11-cis-retinal and activate the G protein transducin in a light-dependent manner. These results contradict the convergent hypothesis and support the homology of type I and type II rhodopsins by divergent evolution from a common ancestral protein.
Thermoluminescence and P700 redox kinetics as complementary tools to investigate the cyclic/chlororespiratory electron pathways in stress conditions in barley leaves.

Cyclic electron flow around photosystem I drives additional proton pumping into the thylakoid lumen, which enhances the protective non-photochemical quenching and increases ATP synthesis. It involves several pathways activated independently. In whole barley leaves, P700 oxidation under far-red illumination and subsequent P700(+) dark reduction kinetics provide a major probe of the activation of cyclic pathways. Two 'intermediate' and 'slow' exponential reduction phases are always observed and they become faster after high light illumination, but dark inactivation of the Benson-Calvin cycle causes the emergence of both a transient in the P700 oxidation and a 'fast' phase in the P700(+) reduction. We investigate here the afterglow (AG) thermoluminescence emission as another tool to detect the activation of cyclic electron pathways from stroma reductants to the acceptor side of photosystem II. This transfer is activated by warming, yielding an AG band at about 45°C. However, treatments that accelerate the 'intermediate' and 'slow' P700(+) reduction phases (brief anoxia, hexose infiltration, fast dehydration of excised leaves) also produced a downshift of this AG band. This pathway ascribable to NADPH dehydrogenase (NDH) would be triggered by a deficit in ATP, while the 'fast' reduction phase corresponding to the ferredoxin plastoquinone reductase pathway is triggered by an overreduction of the photosystem I acceptor pool and is undetected in thermoluminescence. Contrastingly, slow dehydration of unwatered plants did not cause faster reduction of P700(+) nor temperature downshift of the AG band, that is no induction of the NDH pathway, whereas an increased intensity of the AG band indicated a strong NADPH + ATP assimilatory potential.
Pareto Fronts of Many-Objective Degenerate Test Problems

In general, an M-objective continuous optimization problem has an (M - 1)-dimensional Pareto front in the objective space. If its dimension is smaller than (M - 1), it is called a degenerate Pareto front. Deb-Thiele-Laumanns-Zitzler (DTLZ)5 and Walking Fish Group (WFG)3 have often been used as many-objective continuous test problems with degenerate Pareto fronts. However, it was noted that DTLZ5 has a nondegenerate part of the Pareto front. Constraints have been proposed to remove the nondegenerate part. In this letter, first we show that WFG3 also has a nondegenerate part. Then, we derive constraints to remove the nondegenerate part. Finally, we show that the existence of the nondegenerate part makes WFG3 an interesting test problem through computational experiments.
Computing Ritz approximations of primary images

Ritz vectors approximate eigenvectors that are a common choice for primary images in content based indexing. They can be computed efficiently even when the images are accessed through slow communication such as the Internet. We develop an algorithm that computes Ritz vectors in one pass through the images. When iterated, the algorithm can recover the exact eigenvectors. In applications to image indexing and learning it may be necessary to compute primary images for indexing many sub-categories of the image set. The proposed algorithm can compute these age data. Similar computation by other algorithms is much more costly even when access to the images is inexpensive.
Capacité de deux accéléromètres (SenseWear Armband et l’Actical) à estimer la dépense énergétique totale chez les adultes sains

L’augmentation de la depense energetique (DE) par une augmentation de l'activite physique (AP) participe au maintien et a l’amelioration de la sante. La mesure a grande echelle de la DE totale (DET) en general et AP en particulier se heurte a des difficultes pratiques de recueil de donnees, de validite et aux couts. Bien que dans la litterature de nombreux accelerometres permettent d’estimer la DET, il y a encore des limites quant a la mesure de l’intensite de l’AP, element qui influence l’etat de la balance energetique et le benefice pour la sante de l’AP. De plus, peu de comparaisons entre les differents accelerometres sont disponibles. La presente etude avait pour but d’evaluer la capacite de deux accelerometres (Actical et Sensewear Armband) pour estimer la DET en comparaison avec la technique de l’eau doublement marquee (EDM) ; d’evaluer la concordance entre les accelerometres dans la mesure de la DE au repos (DER) en comparaison avec la technique de la calorimetrie indirecte (CI) et d’evaluer la DE liee a l’AP en comparaison avec la technique de la CI. Les resultats montrent qu’il y a une tres bonne correlation entre la CI et les accelerometres dans la mesure de la DER(r > 0.80, p 0.75, p<0.001). Pour la mesure de l’intensite de l’AP, l’ACT est plus precis (r=0.80, p<0.001)) que le SWA a la marche, le SWA est meilleur(r=0.80, p<0.001) au velo. Cette etude permet d’affirmer que le SWA et l’ACT sont des alternatives valables pour mesurer la DE.