Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I Trial of BAY 50-4798, an Interleukin-2–Specific Agonist in Advanced Melanoma and Renal Cancer

Purpose: BAY 50-4798 is an analogue of interleukin-2 that selectively activates T cells over natural killer cells. This phase I study was designed to determine the maximum tolerated dose (MTD) and safety of BAY 50-4798, screen for tumor response, and assess pharmacokinetics. Experimental Design: Forty-five patients with metastatic melanoma or renal cancer were enrolled, 31 on escalating doses to determine the MTD, with 20 renal cell carcinoma patients treated at MTD to detect antitumor activity. BAY 50-4798 was delivered i.v. every 8 h, days 1 to 5 and 15 to 19, and could be repeated after 9 weeks if tumor was stable or responding. Results: The MTD was defined by and reported in terms of doses received. The doses tested ranged from 1.3 to 26.1 μg/kg, and the MTD was defined as 10.4 μg/kg based on toxicities similar to those of aldesleukin. Two patients achieved partial responses, one with melanoma and one with renal cell carcinoma. Among all 45 patients, 53% and 9% experienced a grade 3 and 4 toxicity, respectively. Among the patients treated at the MTD of 10.4 μg/kg, 71% and 10% experienced a grade 3 and 4 toxicity, respectively. Pharmacokinetics showed dose-dependent peak concentrations (Cmax) and area under the curve with a half-life of ∼2 h and no evidence of accumulation. Lymphocyte subset analysis confirmed the preferential expansion of T-cell subsets over natural killer cells. Conclusions: The antitumor activity of BAY 50-4798 in malignancies that respond to high-dose interleukin-2 was low. BAY 50-4798 might provide advantages over aldesleukin in antigen-specific immunotherapies.
A Comparison of the Effects of Hypothermia, Pentobarbital, and Isoflurane on Cerebral Energy Stores at the Time of Ischemic Depolarization

Background In an accompanying article, we report that hypothermia (27–28 degrees Celsius) delayed postischemic cortical depolarization longer than did large‐dose pentobarbital or isoflurane anesthesia, even though preischemic cerebral metabolic rates for glucose were similar in the three groups. To examine the mechanism that may underlie these differences, we measured the cerebral concentrations of high‐energy phosphates (including adenosine triphosphate [ATP] and adenosine diphosphate) in normal conditions and at the moment of depolarization. Methods Rats were anesthetized with 0.8% halothane/50% N2 O and prepared for measurement of the cortical direct‐current potential by glass microelectrodes. Animals were assigned to one of four groups: (1) halothane/nitrous oxide anesthesia, pericranial temperature approximately 38 degrees Celsius; (2) halothane/nitrous oxide, approximately 28 degrees Celsius; (3) halothane/nitrous oxide anesthesia with pentobarbital added to achieve electroencephalographic isoelectricity, approximately 38 degrees Celsius; or (4) 2.4% isoflurane/50% N2 O anesthesia (with electroencephalographic isoelectricity), approximately 38 degrees Celsius. The latter three groups were chosen on the basis of earlier work showing similar cerebral metabolic rates for glucose. In a subgroup of each, circulatory arrest was induced with KCl and the brain was frozen in situ (with liquid nitrogen) at the moment of cortical depolarization. In remaining animals, the brain was frozen without any ischemia. Tissue ATP, adenosine diphosphate, adenosine monophosphate, and phosphocreatine concentrations were measured by high‐performance liquid chromatography. Results High‐energy phosphate concentrations in nonischemic brain tissue were similar in all groups (e.g., ATP concentration 2.47–2.79 micro mol/g brain). With ischemia, depolarization occurred when ATP concentrations had decreased to 13–18% of normal. There were no significant differences in the concentration of any compound or in the energy charge among the groups, even though the time until depolarization was much longer in hypothermic animals (242 s) than in animals receiving large doses of anesthesia (119 and 132 s) or in normmothermic halothane/nitrous oxide animals (73 s). Conclusions The ATP/energy charge threshold for cortical depolarization was similar in all groups despite differing temperature or anesthetic conditions. Because hypothermia increased the time until depolarization, the rate of decrease in ATP concentration must have been slower in these animals than in the two groups receiving large‐dose anesthetics, despite similar preischemic cerebral metabolic rates for glucose. This finding is similar to that of earlier studies and indicates that factors other than preischemic metabolic rate are responsible for controlling energy utilization after ischemia.
A Unified Proteochemometric Model for Prediction of Inhibition of Cytochrome P450 Isoforms

A unified proteochemometric (PCM) model for the prediction of the ability of drug-like chemicals to inhibit five major drug metabolizing CYP isoforms (i.e. CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) was created and made publicly available under the Bioclipse Decision Support open source system at www.cyp450model. org. In regards to the proteochemometric modeling we represented the chemical compounds by molecular signature descriptors and the CYP-isoforms by alignment-independent description of composition and transition of amino acid properties of their protein primary sequences. The entire training dataset contained 63 391 interactions and the best PCM model was obtained using signature descriptors of height 1, 2 and 3 and inducing the model with a support vector machine. The model showed excellent predictive ability with internal AUC = 0.923 and an external AUC = 0.940, as evaluated on a large external dataset. The advantage of PCM models is their extensibility making it possible to extend our model for new CYP isoforms and polymorphic CYP forms. A key benefit of PCM is that all proteins are confined in one single model, which makes it generally more stable and predictive as compared with single target models. The inclusion of the model in Bioclipse Decision Support makes it possible to make virtual instantaneous predictions (∼100 ms per prediction) while interactively drawing or modifying chemical structures in the Bioclipse chemical structure editor.
Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older : the tPA stroke survey experience.

BACKGROUND AND PURPOSE Intravenous tissue plasminogen activator (tPA) administered within 3 hours of symptom onset is the first available effective therapy for acute ischemic stroke (AIS). Few data exist, however, on its use in very elderly patients. We examined the characteristics, complications, and short-term outcome of AIS patients aged >/=80 years treated with tPA. METHODS Patients aged >/=80 years (n=30) were compared with counterparts aged <80 years (n=159) included in the tPA Stroke Survey, a US retrospective survey of 189 consecutive AIS patients treated with intravenous tPA at 13 hospitals. RESULTS Risk of intracerebral hemorrhage (fatal, symptomatic, and total) was 3%, 3%, and 7% in the elderly age group and 2%, 6%, and 9%, respectively, in their younger counterparts (P=NS for all comparisons). Likelihood of favorable outcome, defined as modified Rankin score 0 to 1, National Institutes of Health Stroke Scale score </=5, or marked improvement by hospital discharge, was comparable between groups (37%, 54%, and 43% versus 30%, 54%, and 43%, respectively; P=NS for all comparisons). Elderly patients were more likely to be treated by stroke specialists (87% versus 60%; P=0.005) and less likely to have an identified protocol deviation (13% versus 33%; P=0.03). Elderly patients were discharged more often to nursing care facilities (17% versus 5%; P=0.003). In logistic regression models there were no differences in odds ratio for favorable or poor outcome, other than tendency for higher in-hospital mortality in elderly patients (odds ratio, 2.8; 95% CI, 0.81 to 9.62; P=0.10). CONCLUSIONS Among AIS patients treated with intravenous tPA, age-related differences in characteristics and disposition were identified. No evidence for withholding tPA treatment for AIS in appropriately selected patients aged >/=80 years was identified.
Identifying Different Meanings of a Chinese Morpheme through Semantic Pattern Matching in Augmented Minimum Spanning Trees

Identifying Different Meanings of a Chinese Morpheme through Semantic Pattern Matching in Augmented Minimum Spanning Trees Galmar and Chen (2010) introduced the first corpus-based computational approach to the problem of identifying the different meanings of a polysemous Chinese morpheme embedded in polymorphemic words. The approach is based on the successive application of a dimensionality reduction method - Latent Semantic Analysis, a graph-theory algorithm - Prim's algorithm and a semantic pattern recognition search used for meaning inference. Our present work adds major changes and contributions to Galmar and Chen (2010). Firstly, we theoretically defined and detailed what are the Chinese semantic patterns to be searched in the augmented minimum spanning trees. Then, we modified the computational approach to include the use of Nearest Neighbors lists. This change allows for a major contribution: a proof is given that all the possible outputs of Prim's algorithm in our experiment - the minimum spanning trees - contain all the same amount of semantic information to be used for meaning inference. Thus, our final meaning inference results are optimal. Practically, this work could serve as a first step to add a new feature to current Chinese Wordnets: the listing of all the Chinese words embedding a certain polysemous morpheme with a fixed identified meaning. Finally, future directions are sketched.
RNAi, DRD1, and Histone Methylation Actively Target Developmentally Important Non-CG DNA Methylation in Arabidopsis

Cytosine DNA methylation protects eukaryotic genomes by silencing transposons and harmful DNAs, but also regulates gene expression during normal development. Loss of CG methylation in the Arabidopsis thaliana met1 and ddm1 mutants causes varied and stochastic developmental defects that are often inherited independently of the original met1 or ddm1 mutation. Loss of non-CG methylation in plants with combined mutations in the DRM and CMT3 genes also causes a suite of developmental defects. We show here that the pleiotropic developmental defects of drm1 drm2 cmt3 triple mutant plants are fully recessive, and unlike phenotypes caused by met1 and ddm1, are not inherited independently of the drm and cmt3 mutations. Developmental phenotypes are also reversed when drm1 drm2 cmt3 plants are transformed with DRM2 or CMT3, implying that non-CG DNA methylation is efficiently re-established by sequence-specific signals. We provide evidence that these signals include RNA silencing though the 24-nucleotide short interfering RNA (siRNA) pathway as well as histone H3K9 methylation, both of which converge on the putative chromatin-remodeling protein DRD1. These signals act in at least three partially intersecting pathways that control the locus-specific patterning of non-CG methylation by the DRM2 and CMT3 methyltransferases. Our results suggest that non-CG DNA methylation that is inherited via a network of persistent targeting signals has been co-opted to regulate developmentally important genes.
The dynamic speckle-based wavemeter

Based on a previously devised speckle-based set-up for probing minute wavelength changes for a coherent field [1], [2] we will here present the first experiments where these changes are resolved on a millisecond time scale. The setup is based on probing the lateral shift of a speckle pattern arising from a slanted rough object, the speckle displacement being linearly proportional to the wavenumber change. Thus, by shearing the speckle pattern across a grating-like structure [3],[4] and [5], a frequency proportional to the frequency of the wavelength change can be derived as will the irradiance. Thus, a cordial display of the complex field amplitude may be obtained with a high temporal resolution and a reasonable spectral resolution. The spatial filter is here preliminarily implemented by recording the speckle pattern with a CMOS array with subsequent digital image processing mimicking the use of a spatial filter.
Accurate frequency estimation for real harmonic sinusoids

A linear prediction based method is proposed for real harmonic sinusoidal frequency estimation. The estimator basically involves two steps. An initial fundamental frequency estimate is first obtained by solving a standard least-squares equation with exploitation of the harmonic structure of the sinusoidal signal or by using the MUSIC approach. Based on the initial estimate, an optimally weighted least squares cost function is then constructed from which the final estimate is acquired. Computer simulations show that the performance of the estimator approaches Crame/spl acute/r-Rao lower bound for sufficiently high signal-to-noise ratios and/or data lengths.
Sentence Completion for Understanding Users and Evaluating User Experience

: Projective techniques are used in psychology and consumer research to provide information about individuals' motivations, thoughts, and feelings. This paper reviews the use of projective techniques in marketing research and user experience research and discusses their potential role in understanding users, their needs and values, and evaluating user experience in practical product development contexts. A projective technique called sentence completion is evaluated through three case studies. Sentence completion produces qualitative data about users’ views in a structured form. The results are less time-consuming to analyze than interview results. Compared to quantitative methods such as AttrakDiff, the results are more time consuming to analyze, but more information is retrieved on negative feelings. The results show that sentence completion is useful in understanding users’ perceptions and that the technique can be used to complement other methods. Sentence completion can also be used online to reach wider user groups.
Pressure loss measurement in rotor-stator gap of radial flux electrical machines

The present paper investigates the effects of rotation on flow resistance of the flow passing through the rotor-stator gap of radial flux electrical machine. Rotational pressure loss was measured and compared with the results predicted using computational fluid dynamic (CFD) methods. By using dimensional analysis, correlation for the shock loss coefficient is proposed. It provides a significant contribution to the field of thermal modelling of electrical machines, such as thermofluid modelling using Motor-CAD.
The Burden of Nail Psoriasis: An Introduction

Nail involvement is an extremely common feature of psoriasis and affects approximately 50% of patients. Despite this, it is an often overlooked feature of the disease, and treatment tends to be focused on clearing the cutaneous component of psoriasis. Clinical manifestations of nail psoriasis are pitting, discolouration, onycholysis and subungual hyperkeratosis as well as nail plate crumbling and splinter haemorrhages. Nail psoriasis is associated with discomfort in many patients and leads to significant functional impairment and psychological stress. The often distressing appearance of affected nails impacts the patient tremendously in both work and social activities. Importantly, 80% of patients with psoriatic arthritis have nail psoriasis. This review discusses the incidence of nail psoriasis and the burden on the patient and illustrates when dermatologists are strategically placed to detect the early signs of more severe disease by promptly diagnosing and managing the nail component of psoriasis.
Simulation of morphogenetical gradients using a minimal functional-structural plant model (FSPM)

Context: Architectural studies highlight recurrent morphogenetical gradients that are observed on some tree species. These morphogenetical gradients are linked to morphological trends among successive shoots throughout plant structure and ontogeny. This study aims at testing a potential origin of these gradients as the complex result of some core plant functions. It will be achieved through a minimalist mathematical modelling approach.
Searching for Copy Number Changes in Nonsyndromic X-Linked Intellectual Disability

Intellectual disability (ID) has a prevalence of 2–3% with 0.3% of the population being severely retarded. Etiology is heterogeneous, owing to numerous genetic and environmental factors. Underlying etiology remains undetermined in 75–80% of mildly disabled patients and 20–50% of those severely disabled. Twelve percent of all ID is thought to be X-linked (XLID). This study covers copy number analysis of some of the known XLID genes, using multiplex ligation-dependent probe amplification (MLPA) in 100 nonsyndromic patients. One of the patients was found to have duplication in all exons of MECP2 gene, and another had duplication in the fifth exon of TM4SF2/TSPAN7 gene. Affymetrix® 6.0 whole-genome SNP microarray confirmed the duplication in MECP2 and showed duplication of exons 2–7 in TM4SF2/TSPAN7, respectively. MECP2 duplication has recently been recognized as a syndromic cause of XLID in males, whereas duplications in TM4SF2/TSPAN7 are yet to be determined as a cause of XLID. Being an efficient, rapid, easy-to-perform, easy-to-interpret, and cost-effective method of copy number analysis of specific DNA sequences, MLPA presents wide clinical utility and may be included in diagnostic workup of ID, particularly when microarrays are unavailable as a first-line approach.
NUMA (Non-Uniform Memory Access): An Overview

NUMA (non-uniform memory access) is the phenomenon that memory at various points in the address space of a processor have different performance characteristics. At current processor speeds, the signal path length from the processor to memory plays a significant role. Increased signal path length not only increases latency to memory but also quickly becomes a throughput bottleneck if the signal path is shared by multiple processors. The performance differences to memory were noticeable first on large-scale systems where data paths were spanning motherboards or chassis. These systems required modified operating-system kernels with NUMA support that explicitly understood the topological properties of the system’s memory (such as the chassis in which a region of memory was located) in order to avoid excessively long signal path lengths. (Altix and UV, SGI’s large address space systems, are examples. The designers of these products had to modify the Linux kernel to support NUMA; in these machines, processors in multiple chassis are linked via a proprietary interconnect called NUMALINK.)
Inhaled nitric oxide in the management of a premature newborn with severe respiratory distress and pulmonary hypertension.

Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome, characterized by sustained elevation of pulmonary vascular resistance (PVR) with right-to-left shunting across the ductus arteriosus and/or foramen ovale, causing severe hypoxemia. Although generally associated with diseases of term or near-term newborns, including group B streptococcal sepsis, PPHN has been described in preterm neonates as well. Recent echocardiographic studies have demonstrated increased PVR in preterm neonates with hyaline membrane disease (HMD), which correlated with disease severity and mortality. Severe HMD was associated with lower aortopulmonary pressure gradients and left pulmonary artery blood flow velocities during the first 72 hours after birth, suggesting that high PVR contributes to the mortality of respiratory distress of premature neonates.
Host–parasite kinship in a female‐philopatric bird population: evidence from relatedness trend analysis

Conspecific brood parasitism (CBP), an alternative reproductive tactic where some females lay eggs in the nests of other females of the same species, occurs in many animals with egg care. It is particularly common in waterfowl, for reasons that are debated. Many waterfowl females nest near their birthplace, making it likely that some local females are relatives. We analyse brood parasitism in a Hudson Bay population of common eiders, testing predictions from two alternative hypotheses on the role of relatedness in CBP. Some models predict host–parasite relatedness, others predict that parasites avoid close relatives as hosts. To distinguish between the alternatives, we use a novel approach, where the relatedness of host–parasite pairs is tested against the spatial population trend in pairwise relatedness. We estimate parasitism, nest take‐over and relatedness with protein fingerprinting and bandsharing analysis of egg albumen, nondestructively sampled from each new egg in the nest throughout the laying period. The results refute the hypothesis that parasites avoid laying eggs in the nests of related hosts, and corroborate the alternative of host–parasite relatedness. With an estimated r of 0.12–0.14, females laying eggs in the same nest are on average closer kin than nesting neighbour females. Absence of a population trend in female pairwise relatedness vs. distance implies that host–parasite relatedness is not only an effect of strong natal philopatry: some additional form of kin bias is also involved.
Temporal Structure in Audiovisual Sensory Selection

In natural environments, sensory information is embedded in temporally contiguous streams of events. This is typically the case when seeing and listening to a speaker or when engaged in scene analysis. In such contexts, two mechanisms are needed to single out and build a reliable representation of an event (or object): the temporal parsing of information and the selection of relevant information in the stream. It has previously been shown that rhythmic events naturally build temporal expectations that improve sensory processing at predictable points in time. Here, we asked to which extent temporal regularities can improve the detection and identification of events across sensory modalities. To do so, we used a dynamic visual conjunction search task accompanied by auditory cues synchronized or not with the color change of the target (horizontal or vertical bar). Sounds synchronized with the visual target improved search efficiency for temporal rates below 1.4 Hz but did not affect efficiency above that stimulation rate. Desynchronized auditory cues consistently impaired visual search below 3.3 Hz. Our results are interpreted in the context of the Dynamic Attending Theory: specifically, we suggest that a cognitive operation structures events in time irrespective of the sensory modality of input. Our results further support and specify recent neurophysiological findings by showing strong temporal selectivity for audiovisual integration in the auditory-driven improvement of visual search efficiency.