Miracle-dz/UniFAR-FTUs huggingface dataset:
Impulsive synchronization of networked Lagrange systems

This present paper is concerned with the synchronization problem of networked Lagrange systems with fixed and switching topologies. A preliminary feedback control strategy incorporated with impulsive constraints is proposed to achieve output global synchronization in networked Lagrange mechanical systems. Some generic criteria on global synchronization of the system output with respect to generalized coordinates and its velocities over, respectively, undirected fixed and switching network topologies, are derived analytically. It is shows that impulsive synchronization motion of networked Lagrange systems can achieve by impulsive constraints strategies. Two example and simulations show the effectiveness of the theoretical results.
Eight novel ABCD1 gene mutations and three polymorphisms in patients with X‐linked adrenoleukodystrophy: The first polymorphism causing an amino acid exchange

X‐ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long‐chain fatty acid β‐oxidation. We examined the ABCD1 gene in probands from 11 unrelated X‐ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single‐base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective β‐oxidation in X‐ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchange in the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X‐ALD patients who have been sequenced so far world‐wide, it seems to be very rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c. –59 C/T in the 5′untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively. Hum Mutat 18:52–60, 2001. © 2001 Wiley‐Liss, Inc.
High capacity audio watermarking using FFT amplitude interpolation

An audio watermarking technique in the frequency domain which takes advantage of interpolation is proposed. Interpolated FFT samples are used to generate imperceptible marks. The experimental results show that the suggested method has very high capacity (about 3kbps), without significant perceptual distortion (ODG about -0.5) and provides robustness against common audio signal processing such as echo, add noise, filtering, resampling and MPEG compression (MP3). Depending on the specific application, the tuning parameters could be selected adaptively to achieve even more capacity and better transparency.
Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese Coronary Artery Disease (JCAD) study.

BACKGROUND Nicorandil has cardioprotective effects in the ischemic myocardium, mimicking ischemic preconditioning, and is thus expected to improve the prognosis of ischemic heart disease (IHD). As part of the Japanese Coronary Artery Disease (JCAD) Study, a multicenter collaborative prospective observational study of a large cohort of coronary artery disease patients, the effect of nicorandil on outcome was examined. METHODS AND RESULTS In total, 2,558 patients with nicorandil treatment and controls subjected to propensity score matching were eligible among 13,812 patients registered in the JCAD study. The mean follow-up interval was 2.7 years. The primary endpoint, death from all causes, was significantly lower, by 35% (hazard ratio 0.65, P=0.0008), in the nicorandil group than in the control group. There were also significant reductions in secondary endpoints, including cardiac death (56%), fatal myocardial infarction (56%), cerebral or vascular death (71%), and congestive heart failure (33%) in the nicorandil group, with no excess of deaths from other non-cardiovascular causes. Treatment with nicorandil reduced the number of deaths from all causes to a similar extent with or without treatment with sulfonylureas. CONCLUSIONS The reduction in cardiovascular death with nicorandil was large in patients with IHD, which has important implications for treatment.
On the Parametric Rolling of Container Vessels

The main objective of this article is to outline a simple method to identify whether a ship is susceptible to extreme rolling, in order to avoid or to reduce the effects of that phenomenon. A short review of the current classifi cation societies’ recommendations is given, as well as a brief description of the physical phenomenon of parametric roll resonance. Analysis criteria to determine the vulnerability of a particular vessel to parametric roll (susceptibility criteria) are applied following the American Bureau of Shipping operational guidelines for the assessment of parametric roll resonance in the estimation of container carriers attainable ship speed and heading. The calculations and checks for particular vessels are done for the design wave and forward speed which will most likely lead to the development of parametric roll. Using a time-domain, non-linear numerical model of ship’s motions in 6 degrees-of-freedom analysis for regular head waves is conducted for a C11 class containership (severity criteria).
Melanoma‐derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature

The presence of tumor‐associated macrophages (TAMs) in melanomas is correlated with a poor clinical prognosis. However, there is limited information on the characteristics and biological activities of human TAMs in melanomas. In this study, we developed an in vitro method to differentiate human monocytes to macrophages using modified melanoma‐conditioned medium (MCM). We demonstrate that factors from MCM‐induced macrophages (MCMI‐Mφ) express both M1‐Mφ and M2‐Mφ markers and inhibit melanoma‐specific T‐cell proliferation. Furthermore, microarray analyses reveal that the majority of genes up‐regulated in MCMI‐Mφ are associated with tumor invasion. The most strikingly up‐regulated genes are CCL2 and MMP‐9. Consistent with this, blockade of both CCL‐2 and MMPs diminish MCMI‐Mφ‐induced melanoma invasion. Finally, we demonstrated that both MCMI‐Mφ and in vivo TAMs express the pro‐invasive, melanoma‐associated gene, glycoprotein non‐metastatic melanoma protein B. Our study provides a framework for understanding the mechanisms of cross‐talk between TAMs and melanoma cells within the tumor microenvironment.
Are we free to break the laws

SOFT DETERMINISM seems to have an incredible consequence. It seems to imply, given certain acceptable further premises, that sometimes we are able to act in such a way that the laws of nature are broken. But if we distinguish a strong and a weak version of this incredible consequence, I think we shall find that it is the strong version that is incredible and the weak version that is the consequence. Soft determinism is the doctrine that sometimes one freely does what one is predetermined to do; and that in such a case one is able to act otherwise though past history and the laws of nature determine that one will not act otherwise. Compatibilism is the doctrine that soft determinism may be true. A compatibilist might well doubt soft determinism because he doubts on physical grounds that we are ever predetermined to act as we do, or perhaps because he doubts on psychoanalytic grounds that we ever act freely. I myself am a compatibilist but no determinist, hence I am obliged to rebut some objections against soft determinism but not others. But for the sake of the argument, let me feign to uphold soft determinism, and indeed a particular instance thereof. I have just put my hand down on my desk. That, let me claim, was a free but predetermined act. I was able to act otherwise, for instance to raise my hand. But there is a true historical proposition H about the intrinsic state of the world long ago, and there is a true proposition L specifying the laws of nature that govern our world, such that H and L jointly determine what I did. They jointly imply the proposition that I put my hand down. They jointly contradict the proposition that I raised my hand. Yet I was free; I was able to raise my hand. The way in which I was determined not to was not the sort of way that counts as inability.
Heparin Stimulates Staphylococcus aureus Biofilm Formation

ABSTRACT Heparin, known for its anticoagulant activity, is commonly used in catheter locks. Staphylococcus aureus, a versatile human and animal pathogen, is commonly associated with catheter-related bloodstream infections and has evolved a number of mechanisms through which it adheres to biotic and abiotic surfaces. We demonstrate that heparin increased biofilm formation by several S. aureus strains. Surface coverage and the kinetics of biofilm formation were stimulated, but primary attachment to the surface was not affected. Heparin increased S. aureus cell-cell interactions in a protein synthesis-dependent manner. The addition of heparin rescued biofilm formation of hla, ica, and sarA mutants. Our data further suggest that heparin stimulation of biofilm formation occurs neither through an increase in sigB activity nor through an increase in polysaccharide intracellular adhesin levels. These finding suggests that heparin stimulates S. aureus biofilm formation via a novel pathway.
Validation of a P2Y12-receptor specific whole blood platelet aggregation assay

Abstract Testing of P2Y12-receptor antagonist effects can support clinical decision-making. However, most platelet function assays use only ADP as agonist which is not P2Y12-receptor specific. For this reason P2Y12-receptor specific assays have been developed by adding prostaglandin E1 (PGE1) to reduce ADP-induced platelet activation via the P2Y1-receptor. The present study sought to evaluate a P2Y12-receptor specific assay for determination of pharmacodynamic and clinical outcomes. This study enrolled 400 patients undergoing coronary stenting after loading with clopidogrel or prasugrel. ADP-induced platelet reactivity was assessed by whole blood aggregometry at multiple time points with a standard ADP assay (ADPtest) and a P2Y12-receptor specific assay (ADPtest HS, both run on Multiplate Analyzer, Roche Diagnostics). Patients were clinically followed for 1 month and all events adjudicated by an independent committee. In total, 2084 pairs of test results of ADPtest and ADPtest HS were available showing a strong correlation between results of both assays (r = 0.96, p < 0.001). These findings prevailed in multiple prespecified subgroups (e.g., age; body mass index; diabetes). Calculated cutoffs for ADPtest HS and the established cutoffs of ADPtest showed a substantial agreement for prediction of ischemic and hemorrhagic events with a Cohen’s κ of 0.66 and 0.66, respectively. The P2Y12-receptor specific ADPtest HS assay appears similarly predictive for pharmacodynamic and clinical outcomes as compared to the established ADPtest assay indicating its applicability for clinical use. Further evaluation in large cohorts is needed to determine if P2Y12-receptor specific testing offers any advantage for prediction of clinical outcome.
A Kinesin Switch I Arginine to Lysine Mutation Rescues Microtubule Function*

Switch I and II are key active site structural elements of kinesins, myosins, and G-proteins. Our analysis of a switch I mutant (R210A) in Drosophila melanogaster kinesin showed a reduction in microtubule affinity, a loss in cooperativity between the motor domains, and an ATP hydrolysis defect leading to aberrant detachment from the microtubule. To investigate the conserved arginine in switch I further, a lysine substitution mutant was generated. The R210K dimeric motor has lost the ability to hydrolyze ATP; however, it has rescued microtubule function. Our results show that R210K has restored microtubule association kinetics, microtubule affinity, ADP release kinetics, and motor domain cooperativity. Moreover, the active site at head 1 is able to distinguish ATP, ADP, and AMP-PNP to signal head 2 to bind the microtubule and release mantADP with kinetics comparable with wild-type. Therefore, the structural pathway of communication from head 1 to head 2 is restored, and head 2 can respond to this signal by binding the microtubule and releasing mantADP. Structural modeling revealed that lysine could retain some of the hydrogen bonds made by arginine but not all, suggesting a structural hypothesis for the ability of lysine to rescue microtubule function in the Arg210 mutant.
Profiling B cell chronic lymphocytic leukemia by reverse phase protein array: Focus on apoptotic proteins

B cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B lymphocytes from proliferative activity and apoptosis resistance. The increased awareness of the importance of B cell receptor signaling in CLL has raised new opportunities for targeted intervention. Herein, we describe a study performed with the high‐throughput RPPA (reverse phase protein array) technique, which allowed us to simultaneously study different molecules in a large series of patients. We analyzed B lymphocytes from 57 patients with CLL and 11 healthy subjects. Different pathways were assessed for activation/expression of key signaling proteins. Data obtained were validated by Western blotting and confocal microscopy. The RPPA investigation and its validation, identified 3 series of proteins: 1) molecules whose expression levels reached statistically significant differences in CLL vs. healthy controls (HSP70, Smac/DIABLO, cleaved PARP, and cleaved caspase‐6); 2) proteins with a positive trend of difference in CLL vs. healthy controls (HS1, γ‐tubulin, PKC α/β‐II Thr‐638/641, p38 MAPK Thr‐180/Tyr‐182, NF‐κB Ser‐536, Bcl2 Ser‐70 and Src Tyr‐527); and 3) molecules differentially expressed in patients with IGHV mutations vs. those without mutations (ZAP70, PKC‐ζλ, Thr‐410/403, and CD45). This study identified some molecules, particularly those involved in apoptosis control, which could be considered for further studies to design new therapeutic strategies in CLL.
PROutine: a feasibility study assessing surveillance of electronic patient reported outcomes and adherence via smartphone app in advanced cancer.

BACKGROUND In advanced cancer, quality of life (QoL) is a major treatment goal. In order to achieve this, the identification of suffering by screening for patient-reported-outcomes (PROs, i.e., symptoms) is of utmost importance. The use of paper-pencil questionnaires is associated with significant shortcomings due to missing data, recall bias and transcription errors. Other than that, the electronic recording of PROs by mobile Health (mHealth) offers a number of advantages. The aim of this study was to test whether the routine assessment of PROs via a newly developed smartphone application (MeQoL®) is feasible. METHODS A prospective, uncontrolled, multi-center, feasibility trial was performed in adult outpatients with advanced, solid cancer. Patients under anti-cancer therapy and with regular outpatient visits were eligible. Patients daily recorded the degree of perceived distress (NCCN Distress Thermometer®), pain intensity {average and worst [numerical rating scale (NRS), 0-10]}, the number of breakthrough pain episodes (BPE) and ten questions from a modified version of the Edmonton Symptom Assessment Scale (ESAS). Weekly, five questions concerning different domains of QoL from the short-form 8 (SF-8) questionnaire were obtained. Also, patients recorded the intake of their opioid rescue medication. According to the main scope of the trial (feasibility), no primary endpoint was defined. Rather, the following main feasibility criteria were assessed: missing data, drop-out- and acceptance-rate, patient satisfaction, patients' judgement of practicability, patients' and physicians' suggestions for improvement and basic clinical and demographic data of the participating patients. The study was registered in the German Clinical Trials Register (ID: DRKS00008761). RESULTS In three German cancer centers, 40 patients {female: 28 (70%); average age, 57 years [range, 27-73 years; standard deviation (SD), 12]} were included. As three devices were lost on transport, 37 devices could be evaluated. The median investigation period per device was 99.5 days (SD, 31). Patient adherence in using the smartphone app to document their distress and symptoms was high and missing data were low: In median daily reviews were performed on 70 (SD, 29) of these days (70%) and median weekly recordings were 13 weeks (87%). Most often, patients recorded symptom intensity (89%, MIDOS) and distress (85%, NCCN thermometer). On feedback forms, patients reported a good to very good user friendliness of MeQoL® and a high motivation to use this tool again. CONCLUSIONS Even though participants were asked to record PROs rather frequently (daily), missing data were low and patient satisfaction was high. Having in mind the findings of other working groups, such routine implementation of mHealth solutions may substantially improve outcomes of cancer therapy and increase the value of trials' findings. For the individual patient, MeQoL® allows for monitoring adherence to pharmacotherapy and can facilitate patient guidance.
A NEUROPHYSIOLOGICAL STUDY OF CHILDREN WITH READING, WRITING AND SPELLING DIFFICULTIES

Recordings of early and late auditory evoked potentials and spectral analysis of scalp EEGs of 14 eight‐ and nine‐year‐old boys with difficulties in reading, writing and spelling were compared with those of 18 matched controls. The recordings of the poor readers lacked the normal asymmetry of central conduction time and wave amplitude in the early (brainstem) auditory evoked potentials, and late (cortical) evoked potential components were reduced in amplitude. Spontaneous EEG activity was significantly increased in power in all spectral bands, and this activity was less responsive to changes in sensory stimulation. These observations provide evidence for disturbed early and late auditory processing and altered cortical function. Correlations with behavioural measures considered to be indices of reading, writing and spelling ability support the view that the electrophysiological differences in the group of poor readers reflect a disturbance in the mechanisms subserving the acquisition of written language. These differences are consistent with a primary disturbance of selective attention, which may contribute to a less efficient cognitive strategy for the acquisition of reading skills.
Anthropometric Measurements and Nutrient Intake of Adolescent Girls

Abstract Recognizing the importance of anthropometric measurements among adolescent girls, this study was undertaken to view the anthropometric measurements and to explore the nutrient intake of the selected adolescent girls. A cross - sectional study was carried out targeting 208 school going post- pubescent girls. Using the body mass index as an index of adiposity, 33.7 and 15.9% of government and matriculation school girls respectively were found to be severely undernourished. Further, 17.4 and 25% were found to be normal and 20 and 37 % of them were obese. Anthropometric measurements of the selected girls were lower when compared with National Centre for Health Statistics as a reference population. A significant difference was observed between selected girls and Indian adolescent girls with respect to weight, except girls in the age group between 15 and 16 years from matriculation school. Mean nutrient intake of the selected government school girls was significantly lower when compared with Recommended Dietary Allowance of Indians. Nutritional inadequacy is one of the main causes of prevalence of malnutrition that can lead to higher incidence of diseases among adolescents.
Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profiles of three pluripotency-associated genes, OCT4, NANOG and SOX2, G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand CXCL2, and alpha-fetoprotein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the six target genes using the Livak method. In silico network analysis was also executed to explore the pluripotency and tumorigenetic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly upregulated in late clinical stage HCC patients. In contrast, SOX2 and CXCL2 were markedly overexpressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of the SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high expression with late HCC could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have potential application in HCC prognosis and treatment.