Recovery of Disruptions in Rapid Transit Networks

This paper studies the disruption management problem of rapid transit rail networks. Besides optimizing the timetable and the rolling stock schedules, we explicitly deal with the effects of the disruption on the passenger demand. We propose a two-step approach that combines an integrated optimization model (for the timetable and rolling stock) with a model for the passengers’ behavior. We report our computational tests on realistic problem instances of the Spanish rail operator RENFE. The proposed approach is able to find solutions with a very good balance between various managerial goals within a few minutes. Se estudia la gestión de las incidencias en redes de metro y cercanías. Se optimizan los horarios y la asignación del material rodante, teniendo en cuenta el comportamiento de los pasajeros. Se reallizan pruebas en varias líneas de la red de cercanías de Madrid, con resultados satisfactorios.

Toward mass production of microtextured microdevices: linking rapid prototyping with microinjection molding

The possibility of manufacturing textured materials and devices, with surface properties controlled from the design stage, instead of being the result of machining processes or chemical attacks, is a key factor for the incorporation of advanced functionalities to a wide set of micro and nanosystems. Recently developed high-precision additive manufacturing technologies, together with the use of fractal models linked to computer-aided design tools, allow for a precise definition and control of final surface properties for a wide set of applications, although the production of larger series based on these resources is still an unsolved challenge. However, rapid prototypes, with controlled surface topography, can be used as original masters for obtaining micromold inserts for final large-scale series manufacture of replicas using microinjection molding. In this study, an original procedure is presented, aimed at connecting rapid prototyping with microinjection molding, for the mass production of two different microtextured microsystems, linked to tissue engineering tasks, using different thermoplastics as ultimate materials.

Rapid prototyping of multi-scale biomedical microdevices by combining additive manufacturing technologies

The possibility of designing and manufacturing biomedical microdevices with multiple length-scale geometries can help to promote special interactions both with their environment and with surrounding biological systems. These interactions aim to enhance biocompatibility and overall performance by using biomimetic approaches. In this paper, we present a design and manufacturing procedure for obtaining multi-scale biomedical microsystems based on the combination of two additive manufacturing processes: a conventional laser writer to manufacture the overall device structure, and a direct-laser writer based on two-photon polymerization to yield finer details. The process excels for its versatility, accuracy and manufacturing speed and allows for the manufacture of microsystems and implants with overall sizes up to several millimeters and with details down to sub-micrometric structures. As an application example we have focused on manufacturing a biomedical microsystem to analyze the impact of microtextured surfaces on cell motility. This process yielded a relevant increase in precision and manufacturing speed when compared with more conventional rapid prototyping procedures.

Railway Rapid Transit timetables with variable and elastic demand.

This paper focuses on the design of railway timetables considering a variable elastic demand profile along a whole design day. Timetabling is the third stage in the classical hierarchical railway planning process. Most of previous works on this topic consider a uniform demand behavior for short planning intervals. In this paper, we propose a MINLP model for designing non-periodic timetables on a railway corridor where demand is dependent on waiting times. In the elastic demand case, long waiting times lead to a loss of passengers, who may select an alternative transportation mode. The mode choice is modeled using two alternative methods. The first one is based on a sigmoid function and can be used in case of absence of information for competitor modes. In the second one, the mode choice probability is obtained using a Logit model that explicitly considers the existence of a main alternative mode. With the purpose of obtaining optimal departure times, in both cases, a minimization of the loss of passengers is used as objective function. Finally, as illustration, the timetabling MINLP model with both mode choice methods is applied to a real case and computational results are shown.

Rapid method for spacecraft sizing

In this paper, a rapid method for spacecraft sizing is presented. This method is useful in both the conceptual and preliminary design phases of scientific and communication satellites. The aim of this method is to provide a sizing procedure similar to the ones used in the design of aircraft; actually by determining the mass of all the spacecraft subsystems. In the Introduction, the importance of an accurate initial mass budget in the design of satellites is emphasized. Literature about this topic is not very extensive and most of the existing methods have been recapitulated. The methodology followed in the proposed procedure for spacecraft mass sizing is based on these methods. Data from 26 existing satellites have been considered to obtain correlations between each subsystem mass and the mass of the whole spacecraft.

CXCR4 and CD4 mediate a rapid CD95-independent cell death in CD4+ T cells

AIDS is characterized by a progressive decrease of CD4+ helper T lymphocytes. Destruction of these cells may involve programmed cell death, apoptosis. It has previously been reported that apoptosis can be induced even in noninfected cells by HIV-1 gp120 and anti-gp120 antibodies. HIV-1 gp120 binds to T cells via CD4 and the chemokine coreceptor CXCR4 (fusin/LESTR). Therefore, we investigated whether CD4 and CXCR4 mediate gp120-induced apoptosis. We used human peripheral blood lymphocytes, malignant T cells, and CD4/CXCR4 transfectants, and found cell death induced by both cell surface receptors, CD4 and CXCR4. The induced cell death was rapid, independent of known caspases, and lacking oligonucleosomal DNA fragmentation. In addition, the death signals were not propagated via p56lck and Giα. However, the cells showed chromatin condensation, morphological shrinkage, membrane inversion, and reduced mitochondrial transmembrane potential indicative of apoptosis. Significantly, apoptosis was exclusively observed in CD4+ but not in CD8+ T cells, and apoptosis triggered via CXCR4 was inhibited by stromal cell-derived factor-1, the natural CXCR4 ligand. Thus, this mechanism of apoptosis might contribute to T cell depletion in AIDS and might have major implications for therapeutic intervention.

Rapid treadmilling of brain microtubules free of microtubule-associated proteins in vitro and its suppression by tau

We have determined the treadmilling rate of brain microtubules (MTs) free of MT-associated proteins (MAPs) at polymer mass steady state in vitro by using [3H]GTP-exchange. We developed buffer conditions that suppressed dynamic instability behavior by ≈10-fold to minimize the contribution of dynamic instability to total tubulin-GTP exchange. The MTs treadmilled rapidly under the suppressed dynamic instability conditions, at a minimum rate of 0.2 μm/min. Thus, rapid treadmilling is an intrinsic property of MAP-free MTs. Further, we show that tau, an axonal stabilizing MAP involved in Alzheimer’s disease, strongly suppresses the treadmilling rate. These results indicate that tau’s function in axons might involve suppression of axonal MT treadmilling. We describe mathematically how treadmilling and dynamic instability are mechanistically distinct MT behaviors. Finally, we present a model that explains how small changes in the critical tubulin subunit concentration at MT minus ends, caused by intrinsic differences in rate constants or regulatory proteins, could produce large changes in the treadmilling rate.

Rapid and efficient fusion of phospholipid vesicles by the α-helical core of a SNARE complex in the absence of an N-terminal regulatory domain

A protease-resistant core domain of the neuronal SNARE complex consists of an α-helical bundle similar to the proposed fusogenic core of viral fusion proteins [Skehel, J. J. & Wiley, D. C. (1998) Cell 95, 871–874]. We find that the isolated core of a SNARE complex efficiently fuses artificial bilayers and does so faster than full length SNAREs. Unexpectedly, a dramatic increase in speed results from removal of the N-terminal domain of the t-SNARE syntaxin, which does not affect the rate of assembly of v-t SNARES. In the absence of this negative regulatory domain, the half-time for fusion of an entire population of lipid vesicles by isolated SNARE cores (≈10 min) is compatible with the kinetics of fusion in many cell types.

Rapid evolution of sex-related genes in Chlamydomonas

Biological speciation ultimately results in prezygotic isolation—the inability of incipient species to mate with one another–but little is understood about the selection pressures and genetic changes that generate this outcome. The genus Chlamydomonas comprises numerous species of unicellular green algae, including numerous geographic isolates of the species C. reinhardtii. This diverse collection has allowed us to analyze the evolution of two sex-related genes: the mid gene of C. reinhardtii, which determines whether a gamete is mating-type plus or minus, and the fus1 gene, which dictates a cell surface glycoprotein utilized by C. reinhardtii plus gametes to recognize minus gametes. Low stringency Southern analyses failed to detect any fus1 homologs in other Chlamydomonas species and detected only one mid homolog, documenting that both genes have diverged extensively during the evolution of the lineage. The one mid homolog was found in C. incerta, the species in culture that is most closely related to C. reinhardtii. Its mid gene carries numerous nonsynonymous and synonymous codon changes compared with the C. reinhardtii mid gene. In contrast, very high sequence conservation of both the mid and fus1 sequences is found in natural isolates of C. reinhardtii, indicating that the genes are not free to drift within a species but do diverge dramatically between species. Striking divergence of sex determination and mate recognition genes also has been encountered in a number of other eukaryotic phyla, suggesting that unique, and as yet unidentified, selection pressures act on these classes of genes during the speciation process.

Buoyancy-driven, rapid exhumation of ultrahigh-pressure metamorphosed continental crust

Preservation of ultrahigh-pressure (UHP) minerals formed at depths of 90–125 km require unusual conditions. Our subduction model involves underflow of a salient (250 ± 150 km wide, 90–125 km long) of continental crust embedded in cold, largely oceanic crust-capped lithosphere; loss of leading portions of the high-density oceanic lithosphere by slab break-off, as increasing volumes of microcontinental material enter the subduction zone; buoyancy-driven return toward midcrustal levels of a thin (2–15 km thick), low-density slice; finally, uplift, backfolding, normal faulting, and exposure of the UHP terrane. Sustained over ≈20 million years, rapid (≈5 mm/year) exhumation of the thin-aspect ratio UHP sialic sheet caught between cooler hanging-wall plate and refrigerating, downgoing lithosphere allows withdrawal of heat along both its upper and lower surfaces. The intracratonal position of most UHP complexes reflects consumption of an intervening ocean basin and introduction of a sialic promontory into the subduction zone. UHP metamorphic terranes consist chiefly of transformed, yet relatively low-density continental crust compared with displaced mantle material—otherwise such complexes could not return to shallow depths. Relatively rare metabasaltic, metagabbroic, and metacherty lithologies retain traces of phases characteristic of UHP conditions because they are massive, virtually impervious to fluids, and nearly anhydrous. In contrast, H2O-rich quartzofeldspathic, gneissose/schistose, more permeable metasedimentary and metagranitic units have backreacted thoroughly, so coesite and other UHP silicates are exceedingly rare. Because of the initial presence of biogenic carbon, and its especially sluggish transformation rate, UHP paragneisses contain the most abundantly preserved crustal diamonds.

Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53

The p53 tumor suppressor gene has been shown to play an important role in determining cell fate. Overexpression of wild-type p53 in tumor cells has been shown to lead to growth arrest or apoptosis. Previous studies in fibroblasts have provided indirect evidence for a link between p53 and senescence. Here we show, using an inducible p53 expression system, that wild-type p53 overexpression in EJ bladder carcinoma cells, which have lost functional p53, triggers the rapid onset of G1 and G2/M growth arrest associated with p21 up-regulation and repression of mitotic cyclins (cyclin A and B) and cdc2. Growth arrest in response to p53 induction became irreversible within 48-72 h, with cells exhibiting morphological features as well as specific biochemical and ultrastructural markers of the senescent phenotype. These findings provide direct evidence that p53 overexpression can activate the rapid onset of senescence in tumor cells.

Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV infection

Down-regulation of the initial burst of viremia during primary HIV infection is thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and the appearance of this response is associated with major perturbations of the T cell receptor repertoire. Changes in the T cell receptor repertoire of virus-specific cytotoxic T lymphocytes were analyzed in patients with primary infection to understand the failure of the cellular immune response to control viral spread and replication. This analysis demonstrated that a significant number of HIV-specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be involved in the disappearance of these monoclonally expanded HIV-specific cytotoxic T cell clones. These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response during primary infection.

In situ investigation of rapid subsurface flow : Temporal dynamics and catchment-scale implication

Non peer reviewed

In situ investigation of rapid subsurface flow : Identification of relevant spatial structures beyond heterogeneity

Non peer reviewed

A dynamin GTPase mutation causes a rapid and reversible temperature-inducible locomotion defect in C. elegans

Drosophila shibire and its mammalian homologue dynamin regulate an early step in endocytosis. We identified a Caenorhabditis elegans dynamin gene, dyn-1, based upon hybridization to the Drosophila gene. The dyn-1 RNA transcripts are trans-spliced to the spliced leader 1 and undergo alternative splicing to code for either an 830- or 838-amino acid protein. These dyn-1 proteins are highly similar in amino acid sequence, structure, and size to the Drosophila and mammalian dynamins: they contain an N-terminal GTPase, a pleckstrin homology domain, and a C-terminal proline-rich domain. We isolated a recessive temperature-sensitive dyn-1 mutant containing an alteration within the GTPase domain that becomes uncoordinated when shifted to high temperature and that recovers when returned to lower temperatures, similar to D. shibire mutants. When maintained at higher temperatures, dyn-1 mutants become constipated, egg-laying defective, and produce progeny that die during embryogenesis. Using a dyn-1::lacZ gene fusion, a high level of dynamin expression was observed in motor neurons, intestine, and pharyngeal muscle. Our results suggest that dyn-1 function is required during development and for normal locomotion.