Miracle-dz/UniFAR-FTUs huggingface dataset:
Perspectives on molecular targeted therapies and clinical trials for neurodegenerative diseases

Recent advancements in neurobiology have provided increasing insights into the pathophysiology of neurodegenerative diseases, and opened doors to the development of molecular targeted therapies. Although many compounds showed positive results in animal studies, there is almost no drug for which the efficacy has been confirmed in clinical trials. This failure reflects a number of unsolved problems: limited knowledge of the exact pathways of neuron loss; safety and delivery issues of compounds; lack of established animal models that faithfully recapitulate human pathology; lack of validated, sensitive outcome measures; and limited tools to diagnose pre-symptomatic patients. To investigate the efficacy of potential disease modifying agents with limited financial and patient resources, the efficiency of both basic and clinical studies should be improved by integrated approaches. The reproduction of positive results from animal experiments that analyse the efficacy of compounds at symptomatic stages is needed to improve the credibility of preclinical studies. To effectuate proof of concept processes, novel designs of phase 2 clinical trials, such as the futility study, are being developed. Given the modest effects of molecular targeted therapies in human, it is necessary to explore clinical outcome measures that are resistant to variability, subjectivity and placebo. Furthermore, there is an increasing need for testing interventions before the onset of symptoms. Analyses of natural histories of biological and neurophysiological markers may provide indispensable information for designing such preventive trials. As it is now clear that conventional approaches are not necessarily appropriate for the development of molecular targeted therapies, both basic and clinical studies require conceptual innovation.
Together They Stand: Interpreting Not-At-Issue Content

Potts unified the account of appositives, parentheticals, expressives, and honorifics as 'Not- At-Issue’ (NAI) content, treating them as a natural class semantically in behaving like root (unembedded) structures, typically expressing speaker commitments, and being interpreted independently of At-Issue content. We propose that NAI content expresses a complete speech act distinct from the speech act of the containing utterance. The speech act hypothesis leads us to expect the semantic properties Potts established. We present experimental confirmation of two intuitive observations made by Potts: first that speech act adverbs should be acceptable as NAI content, supporting the speech act hypothesis; and second, that when two speech acts are expressed as successive sentences, the comprehender assumes they are related by some discourse coherence relation, whereas an NAI speech act need not bear a restrictive discourse coherence relation to its containing utterance, though overall sentences containing relevant content are rated more acceptable than those that do not. The speech act hypothesis accounts for these effects, and further accounts for why judgments of syntactic complexity or evaluations of whether or not a statement is true interact with the at-issue status of the material being judged or evaluated.
A novel technique of dual-arm robot manipulators: Path-contouring control problem

The problem of Path-contouring Control of dual arm robot manipulators is defined by the equivalent contour errors determining the desired path. Equivalent errors approach utilizes the n − 1 equivalent contour error in terms of algebraic equation and one tangential error to obtain the new nonlinear coordinate system. It becomes the problem of stabilization of Path-contouring Control. As a result, the existing control techniques can be considered to deal with such the problem of stabilization. The results of experiment demonstrate the excellent performance of the proposed technique.
Studies on immunological paralysis IV. The relative contributions of continuous antibody neutralization and central inhibition to paralysis with type III pneumococcal polysaccharide

High-zone tolerance to type III pneumococcal polysaccharide (SIll) in CBA mice is demonstrable by complete inhibition of the direct plaque-forming cell (PFC) response in the spleen. The serum antibody which protects mice against pneumococcal infection and agglutinates SIll-sensitized mouse erythrocytes is not detectable following injection of amounts of antigen one order of magnitude lower. Evidence is presented that this is attributable to continuous peripheral neutralization of antibody by recirculating, non-degradable antigen. This zone of 'pseudo-paralysis’ masks an immune response which, at the cellular level, is as intense as that induced by sheep erythrocytes. Tolerance can be lost spontaneously after many weeks and be succeeded by a strong immune response, but secreted antibody can again be neutralized by the presence of antigen in serum. Raised numbers of antigen-binding cells (rosettes) are detectable in fully tolerant (PFC-suppressed) animals. Serum anti-SIII activity can be detected in 'pseudo-paralysed’ mice by haemagglutination, or preferably by haemolysis, of heavily-sensitized sheep erythrocytes. Evidence is presented that this represents the same IgM as is synthesized in immunized, protected mice, but which is here partially neutralized by co-existence with serum antigen. Only direct PFC’s were detectable in response to purified SIll and the characteristics of their specific neutralization implied that IgM of essentially similar avidity was formed in response to all antigen doses. Partial neutralization of IgM by SIll is discussed in relation to differences in availability or affinity of combining sites on macroglobulin.
Shear mode coupling and tilted grain growth of AlN thin films in BAW resonators

Polycrystalline AlN thin films were deposited by RF reactive magnetron sputtering on Pt(111)/Ti electrode films. The substrates were tilted by an angle ranging from 40° to 70° with respect to the target normal. A low deposition temperature and a high sputter gas pressure were found ideal for tilted growth. The resulting grain tilt angle amounts to about half the substrate tilt angle. For coupling evaluation, 5 GHz solidly mounted resonator structures have been realized. The tilted grain AlN films exhibited a permittivity in the 9.5-10.5 range and loss tangent of 0.3%. Two shear modes as well as the longitudinal mode could be clearly identified. The coupling coefficient k2eff, of the fundamental thickness shear mode (TSO) was found to be about 0.5%, which is compatible with a c-axis tilt of about 6°.
Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia

Nine isolates of Escherichia coli were recovered from seven blood cultures over a period of 3 months from a 19-month-old female with aplastic anemia. Initial isolates were susceptible to extended-spectrum cephalosporins, including ceftazidime (MIC, < or = 0.25 microgram/ml), but gradually became resistant to this drug (MICs, > or = 128 micrograms/ml) and other cephalosporins and the monobactam aztreonam. Molecular typing methods, including plasmid profile analysis, pulsed-field gel electrophoresis, and arbitrarily primed PCR, indicated that the nine isolates were derived from a common ancestor. Dot blot hybridization and PCR analysis of total bacterial DNA using blaSHV- and blaTEM-specific DNA probes and primers identified the presence of a blaTEM beta-lactamase gene in all of the isolates and a blaSHV gene in the isolates with elevated ceftazidime MICs. Isoelectric focusing analysis of crude lysates showed that all nine isolates contained an enzyme with a pI of 5.4 corresponding to the TEM-1 beta-lactamase, and those isolates containing an SHV-type beta-lactamase demonstrated an additional band with a pI of 7.6. The first of the ceftazidime-resistant isolates appeared to hyperproduce the SHV enzyme compared to the other resistant isolates. DNA sequencing revealed a blaSHV-1 gene in the first ceftazidime-resistant isolate and a novel blaSHV gene, blaSHV-8, with an Asp-to-Asn substitution at amino acid position 179 in the remaining four isolates. Three of the ceftazidime-resistant isolates also showed a change in porin profile. The patient had received multiple courses of antimicrobial agents during her illness, including multiple courses of ceftazidime. This collection of blood isolates from the same patient appears to represent the in vivo evolution of resistance under selective pressure of treatment with various cephalosporins.
Numerical model of rf glow discharges.

Theoretical predictions are given of the spatiotemporal distribution of charged-particle densities and electric field in a radio-frequency glow discharge. The model is based on a numerical solution of the continuity equations for electrons, positive ions, and negative ions coupled with Poisson's equation. The influence of frequency and gas composition (electropositive versus electronegative gas) on the discharge properties is analyzed and compared (qualitatively) with experimental results. In the case of electronegative gas mixtures, and at low frequencies (of the order and less than the ion plasma frequency), the numerical model predicts the formation of double layers at the plasma-sheath boundaries, in agreement with recent experimental measurements based on spectroscopic plasma-diagnostic techniques.
Cryptic lineage diversity, body size divergence, and sympatry in a species complex of Australian lizards (Gehyra)

Understanding the joint evolutionary and ecological underpinnings of sympatry among close relatives remains a key challenge in biology. This problem can be addressed through joint phylogenomic and phenotypic analysis of complexes of closely related lineages within, and across, species and hence representing the speciation continuum. For a complex of tropical geckos from northern Australia—Gehyra nana and close relatives—we combine mtDNA phylogeography, exon‐capture sequencing, and morphological data to resolve independently evolving lineages and infer their divergence history and patterns of morphological evolution. Gehyra nana is found to include nine divergent lineages and is paraphyletic with four other species from the Kimberley region of north‐west Australia. Across these 13 taxa, 12 of which are restricted to rocky habitats, several lineages overlap geographically, including on the diverse Kimberley islands. Morphological evolution is dominated by body size shifts, and both body size and shape have evolved gradually across the group. However, larger body size shifts are observed among overlapping taxa than among closely related parapatric lineages of G. nana, and sympatric lineages are more divergent than expected at random. Whether elevated body size differences among sympatric lineages are due to ecological sorting or character displacement remains to be determined.
Offline Signature Verification & Recognition Using Angle Based Feature Extraction & Neural Network Classifier

The concept of the signature is wide used as a means of individual verification emphasizes the need for an automatic verification system because of the individual aspect effect of being easily misused by those who would pretend the Identification of an individual. A great deal of work has been done in the area of off-line signature verification over the past few decades. Verification can be performed either Offline or Online based on the application. In this paper, we present a method for Offline Verification of signatures by calculating the angle curvature of each direction in signature samples. Here we have taken 8bins and calculated in all directions and extracted the features and stored in templates. The features that are used are Area, Centre of gravity, Eccentricity and Skewness along with angle based features. Earlier the features are extracted, pre-processed a scanned image to isolate the signature part and to remove any false noise present. The system is initially trained using a database of signatures. In our experimentation MCYT signature database is used. An accuracy of 97.61 % with Feed forward Back Propagation is observed in identifying the test signatures.
Enterprise Resource Planning ( ERP ) Systems in the Egyptian Higher Education Institutions : Benefits , Challenges and Issues

Enterprise Resource Planning (ERP) system is indeed crucial for service operations competencies in Higher Education Institutions (HEIs). Previous studies ascertain that ERP system improves an operational efficiency and enhance competitiveness. Though literature has indicated the importance of ERP system for enhancing a firm’s operational performance, there is only a small-scale of ERP adopters in HEIs; hence ERP application in HEIs are still at an embryonic level. Indeed, only few research exists and little is known about strategic resources acquired for achieving high operations competencies and issues how ERP system, innovative technology enables a better performance. This implies that ERP system has not been perceived as an emerging innovation capability that improves operational cost and service efficiency. To enhancing such crucial understanding, this study reviews the benefits of ERPs, further identifies challenges and issues in implementing ERP system in HEIs in particular Egyptian HEIs. The research contributes to the advance of concepts and dimensions for ERP system from HEIs' standpoint and grants practical verification to defend the innovation of service operations in HEIs. Keywords— Benefit; Challenges; Egypt; Egyptian Education; Enterprise Resource Planning System; Higher Education; ERP; HEIs
Maternal morbidity and perinatal outcomes among women in rural versus urban areas

Background: Most studies examining geographic barriers to maternity care in industrialized countries have focused solely on fetal and neonatal outcomes. We examined the association between rural residence and severe maternal morbidity, in addition to perinatal mortality and morbidity. Methods: We conducted a retrospective population-based cohort study of all women who gave birth in British Columbia, Canada, between Jan. 1, 2005, and Dec. 31, 2010. We compared maternal mortality and severe morbidity (e.g., eclampsia) and adverse perinatal outcomes (e.g., perinatal death) between women residing in areas with moderate to no metropolitan influence (rural) and those living in metropolitan areas or areas with a strong metropolitan influence (urban). We used logistic regression analysis to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: We found a significant association between death or severe maternal morbidity and rural residence (adjusted OR 1.15, 95% CI 1.03–1.28). In particular, women in rural areas had significantly higher rates of eclampsia (adjusted OR 2.70, 95% CI 1.79–4.08), obstetric embolism (adjusted OR 2.16, 95% CI 1.14–4.07) and uterine rupture or dehiscence (adjusted OR 1.96, 95% CI 1.42–2.72) than women in urban areas. Perinatal mortality did not differ significantly between the study groups. Infants in rural areas were more likely than those in urban areas to have a severe neonatal morbidity (adjusted OR 1.14, 95% CI 1.02–1.29), to be born preterm (adjusted OR 1.06, 95% CI 1.01–1.11), to have an Apgar score of less than 7 at 5 minutes (adjusted OR 1.24, 95% CI 1.13–1.31) and to be large for gestational age (adjusted OR 1.14, 95% CI 1.10–1.19). They were less likely to be small for gestational age (adjusted OR 0.90, 95% CI 0.85–0.95) and to be admitted to an neonatal intensive care unit (NICU) (adjusted OR 0.36, 95% CI 0.33–0.38) compared with infants in urban areas. Interpretation: Compared with women in urban areas, those in rural areas had higher rates of severe maternal morbidity and severe neonatal morbidity, and a lower rate of NICU admission. Maternity care providers in rural regions need to be aware of potentially life-threatening maternal and perinatal complications requiring advanced obstetric and neonatal care.
Effects of anisomycin on LTP in the hippocampal CA1: long-term analysis using optical recording

Long-term potentiation (LTP) in the hippocampal CA1 region and in the dentate gyrus consists of different stages: early LTP lasting minutes or several hours, and late LTP lasting longer than 4 h. It has been suggested that the late phase of LTP is dependent on protein synthesis. However, the experimental results of the effects of protein synthesis inhibitors are still confusing. We applied optical recording techniques to rat hippocampal slices, and re-evaluated the effects of a protein synthesis inhibitor, anisomycin, on LTP. Using a voltage-sensitive oxonol dye, NK3630 (RH482), LTP in the CA1 region could be monitored optically for a long-term period (7–8 h). In the presence of anisomycin, the potentiation of the EPSP (excitatory postsynaptic potential) lasted about 2–3 h, followed by a gradual decline in the signal amplitude. Statistically, significant effects of anisomycin were observed 6 h after LTP induction for 100 Hz tetanus and 8 h after LTP induction for 400 Hz tetanus. These results suggest that the early phase of LTP is independent of protein synthesis, while the late phase of potentiation (> 3–5 h) depends on protein synthesis.
Evolutionarily conserved stress responses as potential anticancer therapeutic targets? (Comment on DOI 10.1002/bies.201300170)

Amidst all the hope (and hype) surrounding molecularly targeted drugs, Cipponi and Thomas [1] are right to raise the spectre of drug resistance, which all-too-frequently cuts short the very real clinical benefits that these drugs may deliver [2]. Indeed, it is enlightening in this respect to consider the PFS (progression-free survival, i.e. the time during which the cancer growth is overtly suppressed) relating to EGFR tyrosine-kinase inhibitors (such as gefitinib or erlotinib) in EGFR-mutated adenocarcinoma of the lung (a poster-child for oncogene-addiction), in comparison with the PFS relating to conventional cytotoxic chemotherapy in the same disease. In the former case, with the TKI’s, resistance arises (i.e. PFS comes to an end) at a median of about 9–10 months [2, 3]; in the latter case, with cytotoxic chemotherapy, resistance to the best available agents (cisplatin/ pemetrexed) emerges around 7 months into the treatment, and if maintenance Pemetrexed (a multi-target anti-tumor drug) were to have been added, the PFS would have been a bit longer; and while perhaps not quite as long as with the molecularly targeted agents, the PFS would be not too dissimilar. The point is that, although molecularly targeted agents may be somewhat non-cross-resistant to chemotherapy, and vice-versa, the same general
Improving film characteristics of pyrene derivatized carbon nanotubes by 3-aminopropyltri-ethoxysilane and N,N′-Diisopropylcarbodiimide crosslinker

In this work, we used different pyrenes derivatives with a carboxylic acid group to modify the surface of carbon nanotubes (CNTs). This non-covalent method of functionalization can improve the dispersion of CNTs in organic solvent without damaging the desired properties of CNTs. Thin films of CNTs functionalized with pyrene derivatives were deposited onto the glass substrate, which in prior, was treated by 3-aminopropyltri-ethoxysilane (APTES). N,N'-Diisopropylcarbodiimide (DIC), a cross-linker, facilitates the reaction of carboxylic acid group on CNTs with the amino group of APTES. We found that the introduction of DIC resulted in increased robustness of CNTs thin films on the glass substrate. Increase of interfacial adhesion can be attributed to the covalent bond formed during this process. We studied the effect of concentration of APTES and DIC on film adherence by subjecting them to waterjet. Our results show that the CNTs thin films were robust and smooth. The morphology analysis by Scanning Electron Microscopy and Atomic Force Microscopy techniques reveal that the surface functionalized CNTs thin films on glass substrates were smooth and the roughness was about 21.3 nm for the APTES-treated sample. We obtained relatively smooth CNTs thin films which possess high interfacial adhesion with the glass substrate due to covalent bond formed between amino group and carboxylic acid group.
Relative motion modeling and control for autonomus UAV carrier landing

In this paper, the relative motion model and control strategy for autonomous unmanned aerial vehicle(UAV) carrier landing are addressed. Firstly, a coupled six degrees of freedom(6-DOF) non-linear relative motion model is established from (6-DOF) UAV and carrier models. Then the (6-DOF) relative motion model is simplified to the four degree of freedom (4-DOF) model to facilitate the control design, because of the underactuated characteristic of two vehicles. Secondly, the feedback linearization control law is proposed to control the UAV towards the aircraft carrier with constant forward, vertical velocity and lateral position and yaw angle. Finally, simulation results demonstrate the effectiveness of the proposed control system.
Advanced design of Automated Border Control gates: Biometric system techniques and research trends

Last few years have witnessed an ever-increasing demand of border crossing, whose processing introduces the need to speed-up the clearance process at the Border Crossing Points (BCP). Automated Border Control (ABC) gates, or shortly e-Gates, can verify the identity of the travelers crossing the borders by exploiting their biometric traits, without the need of a constant human intervention. Biometric technologies have a relevant impact on the improvement of efficiency, effectiveness and security of the checking processes. Automated biometric recognition can increase the border processing throughput of the BCP, as well as facilitate the clearance procedures. To grant the passage of the border, the e-Gate compares the biometric samples of the traveler stored into the electronic document with live acquisitions. This paper presents the latest substantial advances in the design of e-Gates. In particular, it presents the Biometric Verification System in detail, including its hardware and software components, as well as the procedures followed during the biometric verification of the traveler's identity. We address the complex issue of measuring the performance of an ABC system, considering the real applicability of the figures of merit usually adopted in biometric system's evaluation. To complete the view of the current e-Gates, we highlight the main challenges and the research trends relating to the biometric systems currently used in e-Gates.
Continuous-time lowpass and bandpass ΔΣ-modulators for closed-loop readout circuits of capacitive MEMS gyroscopes

This paper presents the design and implementation of electro-mechanical continuous-time bandpass and lowpass ΔΣ-modulators for closed-loop readout of vibratory MEMS gyroscopes. These concepts improve the performance of the readout system in terms of susceptibility to temperature and sensor parameter variations compared to open-loop solutions. Additionally, the linearity and the dynamic range are improved while the power consumption is low. Measurement results are shown of both readout concepts, which demonstrate the competitiveness and the functionality of the readout interfaces.