Miracle-dz/UniFAR-FTUs huggingface dataset:
Broadening the clinical use of platinum drug–based chemotherapy with new analogues

The three platinum-containing drugs that have been thus far approved by the FDA – cisplatin, carboplatin and oxaliplatin – have had a significant effect in the treatment of patients with some malignancies such as testicular, ovarian and colorectal cancer. However, much more remains to be achieved to widen the therapeutic use of this important class of drug, either via further analogue development or by judicious use of combining the existing drugs with new molecularly targeted agents. Two analogues arising from an academic (Institute of Cancer Research)/pharmaceutical (Johnson Matthey/AnorMed) collaboration – satraplatin (JM-216) and picoplatin (JM-/AMD-473) – have recently shown promising clinical activity; satraplatin (an orally available drug) in hormone-refractory prostate cancer and picoplatin in small-cell lung cancer. There have also been advances in delivery vehicles for platinum drugs (e.g., the diaminocyclohexane [DACH]-based AP-5346 and aroplatin/liposomal cis-bis-neodecanoato-trans-(R,R)-1,2-diaminocyclohexane platinum (II) [L-NDDP] are in early clinical development). Platinum-based drugs have also been successfully combined with molecularly targeted drugs (e.g., the recent approval of the vascular endothelial growth factor monoclonal antibody bevacizumab with carboplatin and paclitaxel in patients with NSCLC).
Training as a factor of business excellence

Purpose: Adopting a specific strategy is sometimes the key to the survival of companies. Given the increasing interest on the part of the companies to have the best strategy that allows them to differentiate themselves from their competitors, the aim of this empirical work is to study the relationship that exists between training and business results. Design/methodology/approach: The empirical set of this paper is comprised by a survey applied to 381 large organizations in Catalonia region during the time frame of 2066-2007. At one hand, the survey allowed identifying the independent (training) variables, and at other, the dependent variables (economical) were obtained from Sabi Data Base and from the “Fomento de la Produccion” Magazine. Findings: According to data obtained, it is possible to consider training as an additional strategic tool that should be used by companies to improve their performance outcomes. Originality/value: Taking into account that the literature review only demonstrates studies linking training and results such as total shareholder return, productivity, higher quality of customer services, reduced staff turnover, organizational performance, growth on the staff wages, etc., therefore, the key value of the paper rely at one hand on providing an analysis of the impact of training on billing and at other, on the use of the Model of Industrial Economy as part of the theoretical framework for the causal model development.
A new way of decomposition of tangential and orbital noise into phase noise and amplitude noise shown with a simple 2-D oscillator

Low oscillator phase noise is crucial for the performance of nearly all communication systems. There are very good, mathematically rigorous theories describing the noise processes in oscillating circuits and the resulting output signal corrupted by phase noise and orbital noise. Although these theories describe the oscillator circuit in a correct manner, the results were not yet applied to a common receiver. In this paper, a simple mathematical oscillator is used to show that the theory describing noise in oscillators has to be adapted for the sake of describing the phase noise correctly which finally corrupts the demodulation results of the receiver.
A Thermal-Diffusivity-Based Frequency Reference in Standard CMOS With an Absolute Inaccuracy of ±0.1% From - 55°C to 125°C

An on-chip frequency reference exploiting the well-defined thermal-diffusivity (TD) of IC-grade silicon has been realized in a standard 0.7 μm CMOS process. A frequency-locked loop (FLL) locks the frequency of a digitally controlled oscillator (DCO) to the process-insensitive phase shift of an electrothermal filter (ETF). The ETF's phase shift is determined by its geometry and by the thermal diffusivity of bulk silicon (D). The temperature dependence of is compensated for with the help of die-temperature information obtained by an on-chip band-gap temperature sensor. The resulting TD frequency reference has a nominal output frequency of 1.6 MHz and dissipates 7.8 mW from a 5 V supply. Measurements on 16 devices show that it has an absolute inaccuracy of ±0.1% (σ = ±0.05%) over the military temperature range (-55°C to 125°C ), with a worst case temperature coefficient of ± 11.2 ppm/°C.
The antioxidative function, preventive action on disease and utilization of proanthocyanidins

Proanthocyanidins, which belong to a class of polyphenols, are widely distributed throughout the plant kingdom. Most people ingest trace amounts of proanthocyanidins through foods such as red wine and cranberry juice. However, the functional properties of proanthocyanidins have been little understood. Since 1983, we have studied the antioxidative functions, preventive actions on diseases and utilization of proanthocyanidins. The antioxidative activities of proanthocyanidins were found to be much stronger than vitamin C or vitamin E in aqueous systems. The mechanisms for their antioxidative actions were shown to involve radical scavenging, quenching, and enzyme‐inhibiting actions. The preventive actions of proanthcyanidins on diseases relating to reactive oxygen species was examined using animal tests. Proanthocyanidin‐rich grape seed extract was showed to have preventive actions on diseases such as atherosclerosis, gastric ulcer, large bowel cancer, cataracts and diabetes. In human intervention trials, grape seed extract was shown to have preventive effects on the increase in lipid peroxides in human plasma after exercise and on muscle fatigue after training. The uses and manufacturing techniques of proanthocyanidin products were subsequently developed. The products were launched as antioxidants in food additives, ingredients in nutritional supplements, and cosmetics.
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Cardiovascular Disease in Chronic Renal Failure: Pathophysiologic Aspects

Cardiovascular complications are the leading cause of mortality in patients with end‐stage renal disease (ESRD). The excess cardiovascular risk and mortality is already demonstrable in early renal disease and in patients with chronic renal failure (CRF), with the highest relative risk of mortality in the youngest patients. The high risk for cardiovascular disease (CVD) results from the additive effect of multiple factors, including hemodynamic overload and several metabolic and endocrine abnormalities more or less specific to uremia. CVD includes disorders of the heart (left ventricular hypertrophy [LVH], cardiomyopathy) and disorders of the vascular system (atherosclerosis, arteriosclerosis), these two disorders being usually associated and interrelated. LVH is the most frequent cardiac alteration in ESRD, resulting from a combined pressure and volume overload. LVH in general is an ominous prognostic sign and an independent risk factor for arrhythmias, sudden death, heart failure, and myocardial ischemia. Regression of LVH needs a combined intervention to reduce hemodynamic overload and is associated with improved prognosis and survival. Clinical studies have shown that damage of large conduit arteries is a major contributing factor for the high incidence of congestive heart failure (CHF), LVH, ischemic heart disease (IHD), sudden death, cerebrovascular accidents, and peripheral artery diseases. Damage to large conduit arteries is principally related to highly calcified occlusive atherosclerotic lesions and to stiffening of large capacitive arteries. These two complications are independent risk factors for survival, and improvement of arterial stiffness is associated with better prognosis and survival. The present review summarizes the most recent works dealing with the pathophysiology of CVD and some aspects of the therapeutic approach.
A method to measure muscular fatigue in VDT tasks

This study was designed to evaluate localized muscular fatigue induced during VDT tasks, using an experimental paradigm where EMG signals were not recorded during the VDT task but during isometric contractions in which the load imposed on the shoulder muscle was kept constant. The change in MPF and the root mean square (RMS) values of EMG signals with time was explored. The correspondence between these measures and the psychological rating of localized muscular fatigue was also examined. On the basis of the results, the effectiveness of the experimental paradigm and of the measures used for evaluation of localized muscular fatigue was discussed. As a result, MPF measured during isometric contraction was found to be a sensitive measure of localized muscular fatigue.
Classification of cancer types by measuring variants of host response proteins using SELDI serum assays

Protein expression profiling has been increasingly used to discover and characterize biomarkers that can be used for diagnostic, prognostic or therapeutic purposes. Most proteomic studies published to date have identified relatively abundant host response proteins as candidate biomarkers, which are often dismissed because of an apparent lack of specificity. We demonstrate that 2 host response proteins previously identified as candidate markers for early stage ovarian cancer, transthyretin and inter‐alpha trypsin inhibitor heavy chain 4 (ITIH4), are posttranslationally modified. These modifications include proteolytic truncation, cysteinylation and glutathionylation. Assays using Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI‐TOF‐MS) may provide a means to confer specificity to these proteins because of their ability to detect and quantitate multiple posttranslationally modified forms of these proteins in a single assay. Quantitative measurements of these modifications using chromatographic and antibody‐based ProteinChip® array assays reveal that these posttranslational modifications occur to different extents in different cancers and that multivariate analysis permits the derivation of algorithms to improve the classification of these cancers. We have termed this process host response protein amplification cascade (HRPAC), since the process of synthesis, posttranslational modification and metabolism of host response proteins amplifies the signal of potentially low‐abundant biologically active disease markers such as enzymes. © 2005 Wiley‐Liss, Inc.
Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis

Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with 31P and 13C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements.
Congenital tracheal malformation in cystic fibrosis transmembrane conductance regulator‐deficient mice

In cystic fibrosis (CF) patients, the major alteration in pulmonary function is due to peripheral airway obstruction. In the present study, we investigated the possibility that alterations in the extrathoracic airways, particularly in the trachea that expresses high levels of CFTR (CF transmembrane conductance regulator), may contribute to respiratory dysfunction. We performed morphological analyses of the trachea and airway functional studies in adult Cftr knockout (Cftr−/−) and F508del‐CFTR mice and their controls. Macroscopic and histological examination of the trachea showed the presence of one to seven disrupted or incomplete cartilage rings in Cftr−/− mice (23/25) while only a few Cftr+/+ mice (6/25) had one abnormal ring. Tracheal defects were mainly localized in the proximal trachea. In 14 Cftr−/− mice, frontal disruption of the first three to six rings below the cricoid cartilage were associated with upper tracheal constriction. Similar tracheal abnormalities were detected in adult F508del‐CFTR and in newborn Cftr−/− and F508del‐CFTR mice. Tracheal and ventilatory function analyses showed in Cftr−/− mice a decreased contractile response of the proximal trachea and a reduced breathing rate due to an increase in the inspiratory and expiratory times. In F508del‐CFTR mice, the expiratory time was longer than in controls. Therefore, these structural and functional abnormalities detected in adult and newborn CF mouse models may represent congenital malformations related to CFTR dysfunction. These results raise important questions concerning the mechanisms governing tracheal development within the context of CFTR protein dysfunction and the implication of such abnormalities in the pathogenesis of airway disease in CF.
Atopy patch test reactions are associated with T lymphocyte‐mediated allergen‐specific immune responses in atopic dermatitis

Positive test reactions to epicutaneous application of aeroallergens served as a model of ‘early’ eczema in atopic dermatitis (AD) in a number of dermato‐immunological studies. However, no quantitative evaluation has been performed so far comparing specific T‐cell activation parameters in the peripheral blood of AD patients with positive or negative atopy patch tests (APT).
Nouns and verbs in the vocabulary acquisition of Italian children*

ABSTRACT The vocabulary development of 24 Italian children aged between 1 ; 4 and 1 ; 6 at the beginning of the study was longitudinally monitored on a monthly basis using the Italian version of the MacArthur Communicative Development Inventory drawn up by their mothers. This study analyzes data from children for whom two sampling stages were available; the first corresponding to a vocabulary size as close as possible to 200 words (mean 217, range 167–281), the second to a vocabulary size ranging from 400 to 650 words (mean 518, range 416–648). The children's vocabulary composition was analyzed by calculating, for each sampling stage, the percentage of common nouns, verbs and closed-class words. The increase in percentage points of the various lexical items between the first and second sampling stages was also analyzed. Data confirmed the predominance of nouns over verbs and closed-class words at both sampling stages, while verbs and closed-class words showed a higher percentage increase than nouns. The results provide evidence that children who reached the first sampling point at an earlier age had a higher percentage of nouns than children who reached the same stage at an older age. However, in the passage from the first to the second sampling point no relationship emerged between a style of acquisition based on the acquisition of nouns and an increase in the rate of vocabulary growth.
Surface antigen detected by a Schistosoma mansoni monoclonal antibody in worm extracts and kidney deposits of infected mice and hamsters

Four monoclonal antibodies (MAbs) derived from a Schistosoma mansoni-infected mouse reacted against the tegument or the cell layer of the digestive tract of the adult worm. They also showed similar patterns of immunofluorescence staining when schistosomula were used as antigens. Two of the MAbs (4A10 and 4D3) recognized immune complexes deposited in the kidneys of infected mice and hamsters as detected by indirect and direct immunofluorescence reactions. When adsorbed to polystyrene beads, both MAbs allowed the quantitative detection of antigen by an enzyme immunoassay. 125I-labeled 4A10 binding to live schistosomula and corresponding inhibition assay ruled out the possibility that this binding could be through its Fc fragment. The same MAb detected an antigen migrating as an 80-kilodalton protein by Western blot analysis of soluble worm antigen preparation after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Use of MAb 4A10 may help to elucidate mechanisms of renal pathology and also be of value in the development of immunodiagnostic assays.
Midface: Clinical Anatomy and Regional Approaches with Injectable Fillers

Summary: The clinical approach towards the midface is one of the most important interventions for practitioners when treating age-related changes of the face. Currently a plethora of procedures are used and presented. However, few of these approaches have been validated or passed review board assigned evaluations. Therefore, it is the aim of this work to establish a guideline manual for practitioners for a safe and effective mid-face treatment based on the most current concepts of facial anatomy. The latter is based on the 5-layered structural arrangement and its understanding is the key towards the favoured outcome and for minimizing complications.
Crystal structures of the PLP‐ and PMP‐bound forms of BtrR, a dual functional aminotransferase involved in butirosin biosynthesis

The aminotransferase (BtrR), which is involved in the biosynthesis of butirosin, a 2‐deoxystreptamine (2‐DOS)‐containing aminoglycoside antibiotic produced by Bacillus circulans, catalyses the pyridoxal phosphate (PLP)‐dependent transamination reaction both of 2‐deoxy‐scyllo‐inosose to 2‐deoxy‐scyllo‐inosamine and of amino‐dideoxy‐scyllo‐inosose to 2‐DOS. The high‐resolution crystal structures of the PLP‐ and PMP‐bound forms of BtrR aminotransferase from B. circulans were solved at resolutions of 2.1 Å and 1.7 Å with Rfactor/Rfree values of 17.4/20.6 and 19.9/21.9, respectively. BtrR has a fold characteristic of the aspartate aminotransferase family, and sequence and structure analysis categorises it as a member of SMAT (secondary metabolite aminotransferases) subfamily. It exists as a homodimer with two active sites per dimer. The active site of the BtrR protomer is located in a cleft between an α helical N‐terminus, a central αβα sandwich domain and an αβ C‐terminal domain. The structures of the PLP‐ and PMP‐bound enzymes are very similar; however BtrR‐PMP lacks the covalent bond to Lys192. Furthermore, the two forms differ in the side‐chain conformations of Trp92, Asp163, and Tyr342 that are likely to be important in substrate selectivity and substrate binding. This is the first three‐dimensional structure of an enzyme from the butirosin biosynthesis gene cluster. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Performance measures for locomotion robots

We design two performance measures for a planar locomotion robot, modeled closely after the Platonic Beast. The first measure is proportional to the total motion of all joints during locomotion of the robot. This is a rough approximation to the energy consumption of the robot. The second measure determines the maximal speed of locomotion, for given limits on the joint speeds. We compute optimal modes of locomotion on different slopes for various designs. The results indicate that a variable link length can greatly improve the ability of the robot to walk on steep slopes.  1997 John Wiley & Sons, Inc.
On-line metrics for assessment of fused tracking performance

We study the possibility of improved tracking of underwater targets based on sensor data from a network of underwater sensors. The improvement by fusion implicitly assumes that the tracking can be assessed in a reliable and objective way. How tracking performance can be assessed is the main issue in this paper. We introduce two categories of performance metrics. The first set, the On-line metrics, have been defined to be independent of a priori knowledge of the target positions. The On-line metrics are intended to be usable in real-time. The second set, the Off-line metrics, is based on comparisons between the estimated tracks and the a, priori known positions (e.g. GPS-positions) of the target. The Off-line metrics are intended for evaluation purposes of the On-line metrics only. The key question is whether the On-line metrics correlate well with the Off-line metrics. In this paper we use experimental data from underwater sensors to assess the tracking performance of underwater targets. Data from acoustic and electric sensor arrays are used either standalone or fused using a Kalman filter. The evaluation is done based on sea-trial data from both sensor-types. The results from applying the On-line and Off-line metrics are discussed. We demonstrate a high correlation between the On-line and Offline metrics estimated from real data. Our conclusion is that the suggested On-line metrics are possible to use as tools for evaluation of tracking performance in real time.