An Intelligent Advisor for City Traffic Policies

Nowadays, city streets are populated not only by private vehicles but also by public transport, fleets of workers, and deliveries. Since each vehicle class has a maximum cargo capacity, we study in this article how authorities could improve the road traffic by endorsing long term policies to change the different vehicle proportions: sedans, minivans, full size vans, trucks, and motorbikes, without losing the ability of moving cargo throughout the city. We have performed our study in a realistic scenario (map, road traffic characteristics, and number of vehicles) of the city of Malaga and captured the many details into the SUMO microsimulator. After analyzing the relationship between travel times, emissions, and fuel consumption, we have defined a multiobjective optimization problem to be solved, so as to minimize these city metrics. Our results provide a scientific evidence that we can improve the delivery of goods in the city by reducing the number of heavy duty vehicles and fostering the use of vans instead.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This research has been partially funded by the Spanish MINECO and FEDER projects TIN2014-57341-R, TIN2016-81766-REDT, and TIN2017-88213-R. University of Malaga, Andalucia TECH. Daniel H. Stolfi is supported by a FPU grant (FPU13/00954) from the Spanish MECD. Christian Cintrano is supported by a FPI grant (BES-2015-074805) from Spanish MINECO

The Berkeley Contact Lens Extended Wear Study. Part I : Study design and conduct.

ObjectiveThe primary aim of the Berkeley Contact Lens Extended Wear Study (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence of contact lens-associated keratopathy (CLAK) and increases the survival rate in RGP extended wear (EW). In this article we describe the clinical trial design in detail, present the results of subject recruitment and retention, and provide the baseline demographic and ocular characteristics of the CLEWS subjects, whose data will be analyzed to address the study aims in a companion article.DesignA randomized, concurrently controlled clinical trial.InterventionSubjects were fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses for 12 months of 6-nights/week EW.Main outcome measuresSlit-lamp assessment and grading of 17 possible keratopathies, measurement of refractive error and corneal curvature, and symptoms. Follow-up data were collected every 3 months.ResultsFrom 545 subjects entering the DW adaptation phase, 201 adapted to EW and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The baseline characteristics of the two study groups were similar and did not differ from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen transmissibility for the two study groups were disjoint, indicating that each group received distinctly different levels of hypoxia.ConclusionsWe show that CLEWS was appropriately designed to address the study hypotheses, was conducted with regard for the safety of the subjects, and adhered to rigorous protocols designed to control for bias and ensure the integrity of study data. We establish the internal validity of between-group statistical comparisons and characterize our study population to permit informed evaluation of the applicability of our results to the contact lens-wearing population in general

The Berkeley Contact Lens Extended Wear Study. Part II : Clinical results.

ObjectiveTo describe the principal clinical outcomes associated with 12 months use of rigid gas-permeable (RGP) extended wear contact lenses and address two primary study questions: (1) does extended wear (EW) of high oxygen transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications, and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to maintain 6-night RGPEW over 12 months?DesignA randomized, concurrently controlled clinical trial.InterventionSubjects who adapted to EW with high Dk (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk RGP lenses for 12 months of 6-night EW.Main outcome measuresContact lens-associated keratopathies (CLAK), changes in refractive error and corneal curvature, and survival in EW.ResultsTwo hundred one subjects were randomized to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the subjects in each group completed 12 months of EW; however, the probability of failure was significantly greater for the medium-Dk group. Although the risk of complications was similar for the two groups, the number of CLAK events that led to termination were 16 versus 5 for the medium-Dk and high-Dk groups, respectively. This suggests that the type of adverse response or the inability to reverse an adverse event was different for the group being exposed to the lower oxygen dose.ConclusionsThe level of oxygen available to the cornea has a significant impact on maintaining successful RGP extended contact lens wear, but not on the initial onset of CLAK. The number of clinical events leading to termination was substantially higher for the medium Dk group, which suggests that corneal hypoxia is an important factor in the development of CLAK. Although overnight contact lens wear should be recommended with caution and carefully monitored for early detection of ocular complications, it appears that high-Dk RGP lenses can be a safe and effective treatment for correction of refractive error for most individuals who can adapt to EW

Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.

The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts

3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell

The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

Hospitalization for pertussis: profiles and case costs by age

BACKGROUND: Pertussis, a highly contagious respiratory illness, affects people of all ages and can have serious clinical consequences. It has been reported that from 1997–2000, 20% of all pertussis cases required hospitalization in the US. This analysis examined demographics, case fatality rate, resource use and costs of hospital care related to pertussis by age. METHODS: ICD-9 codes (033.0, 033.9) were used to identify cases of pertussis in hospital discharge databases from roughly 1,000 US hospitals in 4 states (California, Florida, Maryland, Massachusetts). Data from 1996–1999 were examined by age group. Separate analyses were done for infants (<1 year) and children (1–11 years); however, adolescent and adult cases were combined into one group (12+ years), due to the small number of cases. Databases were used to determine demographics, health service utilization and care costs. Cost estimates include accommodations, ancillary and physician services, reported in 2002 US$. RESULTS: Of the 2,518 cases identified, 90$9,586 per stay. Children (n = 191) had a mean LOS of 3.7 and cost of $4,729; adolescents/adults (n = 61, mean age 40 years) stayed on average 3.4 days with a cost of$5,683 per hospitalization. CONCLUSION: Infants are responsible for the bulk of hospitalizations and generate higher inpatient costs. Costly hospital care occurs, however, in patients with pertussis at all ages