OSIA: Out-of-order scheduling for in-order arriving in concurrent multi-path transfer.

One major problem of concurrent multi-path transfer (CMT) scheme in multi-homed mobile networks is that the utilization of different paths with diverse delays may cause packet reordering among packets of the same ?ow. In the case of TCP-like, the reordering exacerbates the problem by bringing more timeouts and unnecessary retransmissions, which eventually degrades the throughput of connections considerably. To address this issue, we ?rst propose an Out-of-order Scheduling for In-order Arriving (OSIA), which exploits the sending time discrepancy to preserve the in-order packet arrival. Then, we formulate the optimal traf?c scheduling as a constrained optimization problem and derive its closedform solution by our proposed progressive water-?lling solution. We also present an implementation to enforce the optimal scheduling scheme using cascaded leaky buckets with multiple faucets, which provides simple guidelines on maximizing the utilization of aggregate bandwidth while decreasing the probability of triggering 3 dupACKs. Compared with previous work, the proposed scheme has lower computation complexity and can also provide the possibility for dynamic network adaptability and ?ner-grain load balancing. Simulation results show that our scheme signi?cantly alleviates reordering and enhances transmission performance.

The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand

The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury or stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1 antigen (Mac-1). However, ICAM-1 is also used as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry. The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2-Å resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus–ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino-terminal Ig-like domain (D1) at the end distal to the cellular membrane. The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1, which do not bind rhinoviruses. There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the insertion (I)-domain on the α chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs. Domain D1 has been docked with the known structure of the I-domain. The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules.

Kinesin’s processivity results from mechanical and chemical coordination between the ATP hydrolysis cycles of the two motor domains

Kinesin is a processive motor protein: A single molecule can walk continuously along a microtubule for several micrometers, taking hundreds of 8-nm steps without dissociating. To elucidate the biochemical and structural basis for processivity, we have engineered a heterodimeric one-headed kinesin and compared its biochemical properties to those of the wild-type two-headed molecule. Our construct retains the functionally important neck and tail domains and supports motility in high-density microtubule gliding assays, though it fails to move at the single-molecule level. We find that the ATPase rate of one-headed kinesin is 3–6 s−1 and that detachment from the microtubule occurs at a similar rate (3 s−1). This establishes that one-headed kinesin usually detaches once per ATP hydrolysis cycle. Furthermore, we identify the rate-limiting step in the one-headed hydrolysis cycle as detachment from the microtubule in the ADP⋅Pi state. Because the ATPase and detachment rates are roughly an order of magnitude lower than the corresponding rates for two-headed kinesin, the detachment of one head in the homodimer (in the ADP⋅Pi state) must be accelerated by the other head. We hypothesize that this results from internal strain generated when the second head binds. This idea accords with a hand-over-hand model for processivity in which the release of the trailing head is contingent on the binding of the forward head. These new results, together with previously published ones, allow us to propose a pathway that defines the chemical and mechanical cycle for two-headed kinesin.

Altered ratios of alternatively spliced long and short γ2 subunit mRNAs of the γ-amino butyrate type A receptor in prefrontal cortex of schizophrenics

The relative abundance of alternatively spliced long (γ2L) and short (γ2S) mRNAs of the γ2 subunit of the γ-amino butyrate type A (GABAA) receptor was examined in dorsolateral prefrontal cortex of schizophrenics and matched controls by using in situ hybridization histochemistry and semiquantitative reverse transcription–PCR (RT-PCR) amplification. A cRNA probe identifying both mRNAs showed that the transcripts are normally expressed at moderately high levels in the prefrontal cortex. Consistent with previous studies, overall levels of γ2 transcripts in prefrontal cortex of brains from schizophrenics were reduced by 28.0%, although this reduction did not reach statistical significance. RT-PCR, performed under nonsaturating conditions on total RNA from the same blocks of tissue used for in situ hybridization histochemistry, revealed a marked reduction in the relative proportion of γ2S transcripts in schizophrenic brains compared with controls. In schizophrenics, γ2S transcripts had fallen to 51.7% (±7.9% SE; P < 0.0001) relative to control levels. Levels of γ2L transcripts showed only a small and nonsignificant reduction of 16.9% (±12.0% SE, P > 0.05). These findings indicate differential transcriptional regulation of two functionally distinct isoforms of one of the major GABAA receptor subunits in the prefrontal cortex of schizophrenics. The specific reduction in relative abundance of γ2S mRNAs and the associated relative increase in γ2L mRNAs should result in functionally less active GABAA receptors and have severe consequences for cortical integrative function.

Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex

Cortical blood flow at the level of individual capillaries and the coupling of neuronal activity to flow in capillaries are fundamental aspects of homeostasis in the normal and the diseased brain. To probe the dynamics of blood flow at this level, we used two-photon laser scanning microscopy to image the motion of red blood cells (RBCs) in individual capillaries that lie as far as 600 μm below the pia mater of primary somatosensory cortex in rat; this depth encompassed the cortical layers with the highest density of neurons and capillaries. We observed that the flow was quite variable and exhibited temporal fluctuations around 0.1 Hz, as well as prolonged stalls and occasional reversals of direction. On average, the speed and flux (cells per unit time) of RBCs covaried linearly at low values of flux, with a linear density of ≈70 cells per mm, followed by a tendency for the speed to plateau at high values of flux. Thus, both the average velocity and density of RBCs are greater at high values of flux than at low values. Time-locked changes in flow, localized to the appropriate anatomical region of somatosensory cortex, were observed in response to stimulation of either multiple vibrissae or the hindlimb. Although we were able to detect stimulus-induced changes in the flux and speed of RBCs in some single trials, the amplitude of the stimulus-evoked changes in flow were largely masked by basal fluctuations. On average, the flux and the speed of RBCs increased transiently on stimulation, although the linear density of RBCs decreased slightly. These findings are consistent with a stimulus-induced decrease in capillary resistance to flow.

Emergence of order in visual system development.

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns.

The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction.

Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2], also called DT diaphorase, is a homodimeric FAD-containing enzyme that catalyzes obligatory NAD(P)H-dependent two-electron reductions of quinones and protects cells against the toxic and neoplastic effects of free radicals and reactive oxygen species arising from one-electron reductions. These two-electron reductions participate in the reductive bioactivation of cancer chemotherapeutic agents such as mitomycin C in tumor cells. Thus, surprisingly, the same enzymatic reaction that protects normal cells activates cytotoxic drugs used in cancer chemotherapy. The 2.1-A crystal structure of rat liver quinone reductase reveals that the folding of a portion of each monomer is similar to that of flavodoxin, a bacterial FMN-containing protein. Two additional portions of the polypeptide chains are involved in dimerization and in formation of the two identical catalytic sites to which both monomers contribute. The crystallographic structures of two FAD-containing enzyme complexes (one containing NADP+, the other containing duroquinone) suggest that direct hydride transfers from NAD(P)H to FAD and from FADH2 to the quinone [which occupies the site vacated by NAD(P)H] provide a simple rationale for the obligatory two-electron reductions involving a ping-pong mechanism.

Separation and fractionation of order and disorder in highly polydisperse systems

We study a polydisperse soft-spheres model for colloids by means of microcanonical Monte Carlo simulations. We consider a polydispersity as high as 24%. Although solidification occurs, neither a crystal nor an amorphous state are thermodynamically stable. A finite size scaling analysis reveals that in the thermodynamic limit: a the fluid-solid transition is rather a crystal-amorphous phase-separation, b such phase-separation is preceded by the dynamic glass transition, and c small and big particles arrange themselves in the two phases according to a complex pattern not predicted by any fractionation scenario.

South America, 1825 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: General-Charte von Süd-America = Carte générale de L'Amerique Méridionale : en deux grandes feuilles. d'après les observations et les cartes spéciales, rapportées du Voyage dans l'intérieur du Brèsil, pendant les années 1817-1820..., par les Docteurs de Spix et de Martius, Chevaliers de L'Ordre civil de la Couronne de Bavière, membres de L'Académie Royale de Munich ; gestochen von Joh. Bapt. Seitz, Kupferstecher im topographischen Bureau des Kön. baier. General-Quartiermeister Stab. It was published by [M. Lindauer] in 1825. Scale [ca. 1:7,000,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Map in German and French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the South America Lambert Conformal Conic projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, roads, shoreline features, and more. Relief shown by hachures.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

South America, 1825 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: General-Charte von Süd-America = Carte générale de L'Amerique Méridionale : en deux grandes feuilles. d'après les observations et les cartes spéciales, rapportées du Voyage dans l'intérieur du Brèsil, pendant les années 1817-1820..., par les Docteurs de Spix et de Martius, Chevaliers de L'Ordre civil de la Couronne de Bavière, membres de L'Académie Royale de Munich ; gestochen von Joh. Bapt. Seitz, Kupferstecher im topographischen Bureau des Kön. baier. General-Quartiermeister Stab. It was published by [M. Lindauer] in 1825. Scale [ca. 1:7,000,000]. This layer is image 2 of 2 total images of the two sheet source map, representing the northern portion of the map. Map in German and French.The image inside the map neatline is georeferenced to the surface of the earth and fit to the South America Lambert Conformal Conic projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, roads, shoreline features, and more. Relief shown by hachures.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Coast, North Africa, Tunisia and Algeria, 1829 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Carte comparée des régences d'Alger et de Tunis, dressée par le Chev. Lapie, Géographe du Roi ; les noms anciens ont été revus par ... Hase ; les noms arabes par ... Taubert ; gravé par Flahaut ; écrit par Lallemand. It was published by Chez Ch. Picquet, Quai Conti, no. 17 in 1829. Scale [ca. 1:1,632,653], 16 km=9.8 cm. This layer is image 1 of 2 total images of the two sheet source map, representing the western portion of the map. Covers the coast of North Africa including Tunisia, Algeria, and portions of Morocco and Libya. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, roads, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Coast, North Africa, Tunisia and Algeria, 1829 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Carte comparée des régences d'Alger et de Tunis, dressée par le Chev. Lapie, Géographe du Roi ; les noms anciens ont été revus par ... Hase ; les noms arabes par ... Taubert ; gravé par Flahaut ; écrit par Lallemand. It was published by Chez Ch. Picquet, Quai Conti, no. 17 in 1829. Scale [ca. 1:1,632,653], 16 km=9.8 cm. This layer is image 2 of 2 total images of the two sheet source map, representing the eastern portion of the map. Covers the coast of North Africa including Tunisia, Algeria and portions of Morocco and Libya. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, roads, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Queensland, Australia, 1896 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Queensland and British New Guinea : prepared for educational purposes, Survey Deptartment, Brisbane. It was published by The Dept. in 1896. Scale [ca. 1:1,710,720]. This layer is image 1 of 2 total images of the two sheet source map, representing north portion of the map. Covers primarily northeast Australia and a portion of Papua New Guinea.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Geocentric Datum of Australia 1994 Map Grid of Australia Zone 54 projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, coastal features, selected places of interest, administrative boundaries, and more. Relief shown by shading and spot heights. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Queensland, Australia, 1896 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Queensland and British New Guinea : prepared for educational purposes, Survey Deptartment, Brisbane. It was published by The Dept. in 1896. Scale [ca. 1:1,710,720]. This layer is image 2 of 2 total images of the two sheet source map, representing south portion of the map. Covers primarily northeast Australia and a portion of Papua New Guinea.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Geocentric Datum of Australia 1994 Map Grid of Australia Zone 54 projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, coastal features, selected places of interest, administrative boundaries, and more. Relief shown by shading and spot heights. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.