Miracle-dz/UniFAR-FTUs huggingface dataset:
Scholarship at UWindsor Scholarship at UWindsor

This study investigates Pareto-improving congestion pricing and revenue refunding schemes in general transportation networks, which make every road user better off as compared with the situation without congestion pricing. We consider user heterogeneity in value of time (VOT) by adopting a multiclass user model with fixed origin-destination (OD) demands. We first prove that an OD and class-based Pareto-improving refunding scheme exists if and only if the total system monetary travel disutility is reduced. In view of the practical difficulty in identifying individual user’s VOT, we further investigate class-anonymous refunding schemes that give the same amount of refund to all user classes traveling between the same OD pair regardless of their VOTs. We establish a sufficient condition for the existence of such OD-specific but class-anonymous Pareto-improving refunding schemes, which needs information only on the average toll paid and average travel time for trips between each OD pair.
The crystal structure of human deoxyhaemoglobin at 1.74 A resolution

The structure of human deoxyhaemoglobin was refined at 1.74 A resolution using data collected on film at room temperature from a synchrotron X-ray source. The crystallographic R-factor is 16.0%. The estimated error in atomic positions is 0.1 A overall, 0.14 A for main-chain atoms of internal segments, and 0.05 A for the iron atoms. The effects of intermolecular contacts on the structure were investigated; such contacts cause only highly localized distortions, as judged from the degree of molecular asymmetry that they induce. The geometry of the iron-nitrogen complex closely resembles that of the deoxymyoglobin structure of Takano (1977) and of the 5-co-ordinated model compounds of Hoard (1975) and Jameson et al. (1980). The distance of the iron from the mean plane of N(porphyrin) is 0.40(5) A and 0.36(5) A, respectively, at the alpha and beta haems, in contrast to the corresponding distance of +0.12(8) A and -0.11(8) A in oxyhaemoglobin ( Shaanan , 1983); the Fe-N epsilon (F8) bond length is 2.12(4) A and the Fe-N(porphyrin) bond length is 2.06(2) A; the last is also in good agreement with extended X-ray fluorescence spectroscopy measurements on deoxyhaemoglobin ( Eisenberger et al., 1978; Perutz et al., 1982). The haems are domed toward the proximal side; the separation between the mean planes of N(porphyrin) and C(porphyrin) being 0.16(6) A and 0.10(6) A, respectively at the alpha and beta haems. At the alpha haems, the normals to the mean pyrrole planes are tilted uniformly toward the haem centre, by about three degrees relative to the haem normal, and there is a folding of about four degrees of the haem about an axis running between the methene carbons that are between the pyrrole rings bearing like-type side-chains. At the beta haems, there is no such folding, and only pyrroles II and IV (those eclipsed by His F8) are appreciably tilted, by about eight degrees. The independence of these parameters from restraints imposed on the model was verified by unrestrained refinement of the entire molecule starting from a structure with modified haem geometry.
DNA sequence encoding the amino-terminal region of the human c-src protein: implications of sequence divergence among src-type kinase oncogenes

We sequenced the 5'-coding region of the human c-src gene, exons 2 through 5, corresponding to one-third of the human c-src protein consisting of 536 amino acids. Sequence analysis of the src type of protein kinases revealed that the amino-terminal region encoded by exon 2 contains sequences specific for the src proteins and raised the possibility that this region is involved in the recognition of a src-specific substrate(s) or receptor(s).
Plasma Spectroscopy Diagnostics in Pulsed-Power X-Ray Radiography Diode Research

Spectroscopic investigations in the visible and near UV are underway to study plasmas present in X-ray radiography diodes during the time of the electron beam propagation. These studies are being performed on the RITS-3 accelerator (5.25 MV and 120 kA) at Sandia National Laboratories using several diode configurations. The proper characterization of the plasmas occurring during the time of the X-ray pulse can lead to a greater understanding of diode behavior and X-ray spot size evolution. By studying these plasmas along with the use of selective dopants, insights into such phenomena as impedance collapse, thermal and non-thermal species behavior, charge and current neutralization, anode and cathode plasma formation and propagation, and beam/foil interactions, can be obtained. Information from line and continuum emission and absorption can give key plasma parameters such as temperatures, densities, charge states, and expansion velocities. This information is important for proper modeling and future predictive capabilities for the design and improvement of flash X-ray radiography diodes. Diagnostics include a gated, intensified multichannel plate camera combined with a 1 meter Czerny-Turner monochromator with a multi-fiber spectral input, allowing for both temporal and spatial resolution. Recent results are presented.
Difference of Critical Shoulder Angle (CSA) According to Minimal Rotation: Can Minimal Rotation of the Scapula Be Allowed in the Evaluation of CSA?

Background Minimal rotation of the scapula may affect the measurement of critical shoulder angle (CSA). We investigated the difference in the CSA measured in minimal rotation between the patients with rotator cuff tear and those without non-rotator cuff tear and the CSA measurement error by comparing with computed tomography (CT). Methods We retrospectively reviewed patients with full-thickness rotator cuff tear and whose X-ray views correspond to Suter-Henninger classification type A1 and C1. The CSA values between the normal control group (without rotator cuff tear) and the rotator cuff tear group were compared according to A1 type and C1 type. In the rotator cuff tear group, we compared the CSA values measured by using X-ray and CT. Results A total of 238 patients (rotator cuff tear group, 139 patients; normal cuff group, 99 patients) were included in this study. The mean CSA of the rotator cuff tear group was 33.4° ± 3.5°, and that of the normal cuff group was 32.6° ± 3.9° (p = 0.085). On comparison of the CSA according to the Suter-Henninger classification type, the CSA values on the A1 type view and C1 type view were 32.7° ± 3.5° and 33.7° ± 3.5°, respectively, in the rotator cuff tear group and 30.5° ± 3.1° and 33.1 ± 3.9°, respectively, in the normal cuff group (p = 0.024 and p = 0.216, respectively). The mean CSA was 32.5° ± 3.1° in CT and 33.3° ± 3.2° in X-ray (p = 0.184). On comparison of the CSA according to the Suter-Henninger classification type, the CSA values on the A1 type view and C1 type view were 32.6° ± 3.6° and 32.5° ± 2.4°, respectively, in CT and 32.5° ± 3.5° and 34.2° ± 2.6°, respectively, in X-ray (p = 0.905 and p = 0.017, respectively). Conclusions The X-ray view corresponding to Suter-Henninger classification type A1 or CT-reconstructed image can be used to reduce the measurement error and obtain reliable CSA values. The CSA measured on the X-ray view corresponding to Suter-Henninger classification type A1 may be related with rotator cuff tear.
P311 accelerates nerve regeneration of the axotomized facial nerve

In axotomized adult neurons, a process of axonal regrowth and re‐establishment of the neuronal function has to be activated. Developmentally regulated factors may be reactivated during neuronal regeneration. Here we identify a gene, previously designated P311, that is up‐regulated in the axotomized facial motoneurons. Ectopically expressed P311 localizes in the cytoplasm and the nucleus. Over‐expression of P311 induces p21WAF1/Cip1 expression, leading PC12 cells to differentiate and to have neuron‐like morphologies. Adenovirus‐mediated P311 gene transfer promotes neurite outgrowth of postnatal dorsal root ganglion neurons and embryonic hippocampal neurons in vitro. This effect is abolished by the activation of Rho kinase. P311 also facilitates nerve regeneration following facial nerve injury in vivo. Our data provide evidence that genes involved in the differentiation process contribute to the regeneration of injured mature neurons, and may provide a practical molecular target.
Analysis of Non-Cooperative and Cooperative Type II Hybrid ARQ Protocols with AMC over Correlated Fading Channels

This paper presents performance analysis and cross-layer design approaches for hybrid ARQ (HARQ) protocols in wireless networks, which employ adaptive modulation and coding (AMC) in conjunction with adaptive cooperative diversity and are subject to time-correlated fading channels. We first consider a point-to-point scenario, i.e., non-cooperative HARQ with AMC. Utilizing a Markov channel model which accounts for the temporal correlation in the successive transmission of incremental redundancy by the HARQ protocol, we derive the system throughput and the packet loss probability based on a rate compatible punctured convolutional code family. Next, we consider a cooperative HARQ (CHARQ) scheme in which a relay node, also equipped with AMC, retransmits redundancy packets when it is able to decode the source information packet correctly. For this scenario, we also derive the throughput and packet loss performance. Finally, we present a cross-layer AMC design approach which takes into account the hybrid ARQ protocol at the link layer. The results illustrate that including AMC in the HARQ protocols leads to a substantial throughput gain. While the performance of the AMC with HARQ protocol is strongly affected by the channel correlation, the CHARQ protocol provides noticeable performance gains over correlated fading channels as well.
The "New" Science Specialists: Promoting and Improving the Teaching of Science in Primary Schools.

A Victorian government initiative called The Primary Science Specialists Professional Learning Program is designed to tackle students' falling interest in science by investing in the building of teacher capacity. The aims of the initiative are: to improve the science knowledge base of all teachers and therefore increase teachers' capacity to engage students in their learning of science; to increase student interest, aspirations and participation in science and to raise the level of science achievement. The role of the "new" science specialist is not necessarily to teach science to all students, rather to promote science, organise the teaching programs and resources for teaching science and support other teachers in teaching science in their school. The results, to date, show that by creating the role of science specialists in primary schools, and investing in science as a specialised knowledge area, science can be promoted, science teaching resources better managed, and teachers who are not confident in science, mentored. In this way, the impact of promoting and improving the teaching of science can extend from the science specialists to other teachers, to students, the school and the wider community.
Human dopamine transporter: the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities

Parkinson’s disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra and corpus striatum. Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required. By means of homology modeling, molecular docking, and molecular dynamics simulations, we have generated 3D structure models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding affinity of these compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico approach allowed the identification of promising substrate compounds that were subsequently analyzed for their efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken together, our work presents the first implementation of a combined in silico/in vitro approach enabling the selection of promising dopaminergic neuron-specific substrates.
Altered angiogenesis and survival in human tumor‐derived endothelial cells

Knowledge on the functional properties of tumor‐derived endothelial cells (TEC) can be relevant for the development of antiangiogenic therapeutic strategies. In the present study, we obtained and characterized endothelial cell lines from human renal carcinomas. TEC did not undergo senescence and showed constant expression of markers of endothelial activation and angiogenesis. In vitro, TEC, in contrast to normal endothelial cells, were resistant to apoptosis, proadhesive for renal carcinoma cells, and able to grow and organize in the absence of serum in persistent capillary‐like structures. In vivo, TEC were able to grow in immunodeficient mice and to form vascular structures connected with the circulation. At a molecular level, gene array analysis showed an increased expression of genes involved in survival and cell adhesion compared with expression in normal microvascular endothelial cells. Moreover, expression of angiopoietin‐1 and vascular endothelial growth factor (VEGF)‐D and the Akt survival pathway were up‐regulated. Inhibition of interaction of VEGFR‐2 or VEGFR‐3 with VEGF‐D but not of Tie‐2‐angiopoietin‐1 interaction with soluble receptors abrogated Akt activation and survival of TEC. These results indicate that at least some of the TEC within a tumor display abnormal characteristics in terms of survival and angiogenic properties and also indicate the presence of a functional autocrine pathway related to VEGF‐D.
Comparison of 3 Clinical Models for Predicting the Probability of Pulmonary Embolism

Abstract: Two clinical models have been described to predict the probability of pulmonary embolism: the Canadian (or Wells) model, and the Geneva model. A third model has been developed recently at our institution (the Pisa model). We compared the performance of the 3 models in 215 consecutive patients with suspected pulmonary embolism. The clinical probability predicted by the models was categorized as low, intermediate, or high. In all patients, pulmonary angiography was used as the reference diagnostic standard. In patients with pulmonary embolism, the extent of pulmonary embolization was assessed on the lung scan as an index of disease severity. The prevalence of pulmonary embolism was 43.3%, and the median extent of pulmonary embolization at diagnosis was 39.8% (range, 4.5%-75.3%). The proportions of patients categorized as having low, intermediate, or high probability were, respectively: 12%, 60%, and 28%, for the Geneva model; 30%, 55%, and 15%, for the Wells model; 37%, 37%, and 26% for the Pisa model. The frequencies of pulmonary embolism in the low, intermediate, and high probability categories were, respectively: 50%, 39%, and 49% for the Geneva model; 12%, 54%, and 64% for the Wells model; 5%, 42%, and 98% for the Pisa model. Among patients with pulmonary embolism, there was a strong, positive relation between clinical probability predicted by the Pisa model and the extent of pulmonary embolization. The Pisa model proved more accurate than the 2 other models. It may be useful to physicians in defining precisely the pretest probability of pulmonary embolism.
Energy-efficient waveform shapes for neural stimulation revealed with a genetic algorithm

The energy efficiency of stimulation is an important consideration for battery-powered implantable stimulators. We used a genetic algorithm (GA) to determine the energy-optimal waveform shape for neural stimulation. The GA was coupled to a computational model of extracellular stimulation of a mammalian myelinated axon. As the GA progressed, waveforms became increasingly energy efficient and converged upon an energy-optimal shape. The results of the GA were consistent across several trials, and resulting waveforms resembled truncated Gaussian curves. When constrained to monophasic cathodic waveforms, the GA produced waveforms that were symmetric about the peak, which occurred approximately during the middle of the pulse. However, when the cathodic waveforms were coupled to rectangular charge-balancing anodic pulses, the location and sharpness of the peak varied with the duration and timing (i.e., before or after the cathodic phase) of the anodic phase. In a model of a population of mammalian axons and in vivo experiments on a cat sciatic nerve, the GA-optimized waveforms were more energy efficient and charge efficient than several conventional waveform shapes used in neural stimulation. If used in implantable neural stimulators, GA-optimized waveforms could prolong battery life, thereby reducing the frequency of recharge intervals, the volume of implanted pulse generators, and the costs and risks of battery-replacement surgeries.
High power-supply rejection low drop-out regulator

An off-chip load driving low drop-out regulator with high power-supply rejection is proposed in this paper. The 1.2-V regulator uses adaptive frequency compensation and is stable at all load currents. A power-supply rejection of 70dB with load and line regulation figures of under 2mV and 10mV for 1–350mA and 2.1–3.6V load current and power supply variations were measured on a 65-nm CMOS prototype consuming under 0.05mm2 core area and 40µA quiescent current.
Open research issues on Computational Techniques for Financial Applications

We present in the following the state of the art for computational techniques for financial applications both from the methodological and applicative points of view. The techniques are applied to a variety of applicative domains (economic growth, financial assets, agriculture output, inventory in supply chains) to illustrate the extension of the research area.
Aberrant splicing in the ocular albinism type 1 gene (OA1/GPR143) is corrected in vitro by morpholino antisense oligonucleotides

An intronic point mutation was identified in the ocular albinism type 1 (OA1) gene (HUGO symbol, GPR143) in a family with the X‐linked form of ocular albinism. Interestingly, the mutation creates a new acceptor splice site in intron 7 of the OA1 gene. In addition to low levels of normally spliced mRNA product of the OA1 gene, the patient samples contained also an aberrantly spliced mRNA with a 165 bp fragment of intron 7 (from position +750 to +914) inserted between exons 7 and 8. The abnormal transcript contained a premature stop codon and was unstable, as revealed by Northern blot analysis. We defined that mutation NC_000023. 8:g.25288G>A generated a consensus binding motif for the splicing factor enhancer ASF/SF2, which most likely favored transcription of the aberrant mRNA. Furthermore, it activated a cryptic donor‐splice site causing the inclusion between exons 7 and 8 of the 165 bp intronic fragment. Thus, the aberrant splicing is most likely explained by the generation of a de novo splicing enhancer motif. Finally, to rescue OA1 expression in the patient's melanocytes, we designed an antisense morpholino modified oligonucleotide complementary to the mutant sequence. The morpholino oligonucleotide (MO) was able to rescue OA1 expression and restore the OA1 protein level in the patient's melanocytes through skipping of the aberrant inclusion. The use of MO demonstrated that the lack of OA1 was caused by the generation of a new splice site. Furthermore, this technique will lead to new approaches to correct splice site mutations that cause human diseases. Hum Mutat 27(5):420–426, 2006. Published 2006 Wiley‐Liss, Inc.
Mechanisms of action of unoprostone on trabecular meshwork contractility.

PURPOSE This study was performed to clarify the possible mechanism behind the ocular hypotensive effect of unoprostone isopropyl (Rescula; Novartis Ophthalmics AG, Basel, Switzerland), a new docosanoid that has been shown to reduce intraocular pressure (IOP) in patients with ocular hypertension or primary open-angle glaucoma. To gain insight into the possible mode of action, the effects of unoprostone on ciliary muscle (CM) and trabecular meshwork (TM) contractility, intracellular calcium levels, and membrane channels were investigated. METHODS The effects of unoprostone (M1 metabolite = free acid, 10(-5) M) and endothelin (ET)-1 (10(-9) M) on bovine TM (BTM) and ciliary muscle (CM) strips were investigated, by using a custom-made force-length transducer system. The effects of unoprostone and ET-1 (5 x 10(-8) M) on intracellular Ca(2+) mobilization in cultured human TM (HTM) were measured using fura-2AM as a fluorescent probe. Patch-clamp experiments were performed on HTM and BTM cells to investigate the unoprostone-dependent modulation of membrane currents. RESULTS In isolated TM and CM strips, unoprostone almost completely inhibited ET-induced contractions (TM: 2.9% +/- 4.3% vs. 19.6% +/- 5.7%, P < 0.05, n = 6; CM: 1.4% +/- 1.6% vs. 30.1% +/- 5.3%, P < 0.01, n = 6; 100% = maximal carbachol-induced (10(-6) M) contraction). However, neither carbachol-induced contraction nor baseline tension was affected by unoprostone. Furthermore, unoprostone had no effect on baseline intracellular calcium levels (baseline: 126 +/- 45 nM versus unoprostone: 132 +/- 42 nM, n = 8) in HTM cells. The endothelin-induced increase (679 +/- 102 nM), however, was almost completely (P < 0.01) blocked by unoprostone (178 +/- 40 nM). In patch-clamp recordings, unoprostone could be shown to double the amplitude of outward current (HTM: 200% +/- 33%; n = 6; BTM: 179% +/- 20%; n = 8). This effect was blocked by the specific inhibitor of maxi-K channels, iberiotoxin. CONCLUSIONS This study presents evidence for direct interaction of unoprostone with the contractility of the TM and CM. This compound may lower IOP by affecting aqueous outflow, most probably conventional outflow pathways (i.e., TM) through inhibition of ET-dependent mechanisms. In addition, unoprostone interacts with the maxi-K channel. Although primarily Ca(2+)-sensitive signal-transduction pathways seem to be involved, effects of unoprostone on Ca(2+)-independent pathways and uveoscleral outflow cannot be excluded.