The search for the IFN-gamma receptor in fish: Functional and expression analysis of putative binding and signalling chains in rainbow trout Oncorhynchus mykiss

Interferons (IFNs), consisting of three major subfamilies, type I, type II (gamma) and type III (lambda) IFN, activate vertebrate antiviral defences once bound to their receptors. The three IFN subfamilies bind to different receptors, IFNAR1 and IFNAR2 for type I IFNs, IFN gamma R1 and IFN gamma R2 for type II IFN, and IL-28R1 and IL-10R2 for type III IFNs. In fish, although many types I and II IFN genes have been cloned, little is known about their receptors. In this report, two putative IFN-gamma receptor chains were identified and sequenced in rainbow trout (Oncorhynchus mykiss), and found to have many common characteristics with mammalian type II IFN receptor family members. The presented gene synteny analysis, phylogenetic tree analysis and ligand binding analysis all suggest that these molecules are the authentic IFN gamma Rs in fish. They are widely expressed in tissues, with IFN gamma R1 typically more highly expressed than IFN gamma R2. Using the trout RTG-2 cell line it was possible to show that the individual chains could be differentially modulated, with rIFN-gamma and rIL-1 beta down regulating IFN gamma R1 expression but up regulating IFN gamma R2 expression. Overexpression of the two receptor chains in RTG-2 cells revealed that the level of IFN gamma R2 transcript was crucial for responsiveness to rIFN-gamma, in terms of inducing gamma IP expression. Transfection experiments showed that the two putative receptors specifically bound to rIFN-gamma. These findings are discussed in the context of how the IFN gamma R may bind IFN-gamma in fish and the importance of the individual receptor chains to signal transduction. (c) 2009 Elsevier Ltd. All rights reserved.

Density Gradient Ultracentrifugation of Nanotubes: Interplay of Bundling and Surfactants Encapsulation

Density gradient ultracentrifugation (DGU) has emerged as a promising tool to prepare chirality enriched nanotube samples. Here, we assess the performance of different surfactants for DGU. Bile salts (e.g., sodium cholate (SC), sodium deoxycholate (SDC), and sodium taurodeoxycholate (TDC)) are more effective in individualizing Single Wall Carbon Nanotubes (SWNTs) compared to linear chain surfactants (e.g., sodium dodecylbenzene sulfonate (SDBS) and sodium dodecylsulfate (SDS)) and better suited for DGU. Using SC, a narrower diameter distribution (0.69-0.81 nm) is achieved through a single DGU step on CoMoCAT tubes, when compared to SDC and TDC (0.69-0.89 nm). No selectivity is obtained using SDBS. due to its ineffectiveness in debundling. We assign the reduce selectivity of dihydroxy bile salts (S DC and TDC) in comparison with trihydroxy SC to the formation of secondary micelles. This is determined by the number and position of hydroxyl ( OH) groups on the a-side of the steroid backbone. We also enrich CoMoCAT SWNT in the 0.84-0.92 nm range using the Pluronic F98 triblock copolymer. Mixtures of bile salts (SC) and linear chain surfactants (SOS) are used to enrich metallic and semiconducting laser-ablation grown SWNTs. We demonstrate enrichment of a single chirality, (6,5), combining diameter and metallic versus semiconductillg separation on CoMoCAT samples.

Pion Production in Heavy-Ion Collisions in the 1 A GeV Region

Within the framework of the improved isospin dependent quantum molecular dynamics (ImIQMD) model, pion emission in heavy-ion collisions in the region 1 A GeV is investigated systematically, in which the pion is considered to be mainly produced by the decay of resonances Delta(1232) and N*(1440). The in-medium dependence and Coulomb effects of pion production are included in the calculation. Total pion multiplicity and pi(-)/pi(+) yields are calculated for the reaction Au-197+(197) Au in central collisions for selected Skyrme parameters SkP, SLy6, Ska, SIII and compared with the measured data of the FOPI collaboration.

Learning object segmentation from video data

This memo describes the initial results of a project to create a self-supervised algorithm for learning object segmentation from video data. Developmental psychology and computational experience have demonstrated that the motion segmentation of objects is a simpler, more primitive process than the detection of object boundaries by static image cues. Therefore, motion information provides a plausible supervision signal for learning the static boundary detection task and for evaluating performance on a test set. A video camera and previously developed background subtraction algorithms can automatically produce a large database of motion-segmented images for minimal cost. The purpose of this work is to use the information in such a database to learn how to detect the object boundaries in novel images using static information, such as color, texture, and shape. This work was funded in part by the Office of Naval Research contract #N00014-00-1-0298, in part by the Singapore-MIT Alliance agreement of 11/6/98, and in part by a National Science Foundation Graduate Student Fellowship.

Colliding and Moving Bose-Einstein Condensates: Studies of superfluidity and optical tweezers for condensate transport

In this thesis, two different sets of experiments are described. The first is an exploration of the microscopic superfluidity of dilute gaseous Bose- Einstein condensates. The second set of experiments were performed using transported condensates in a new BEC apparatus. Superfluidity was probed by moving impurities through a trapped condensate. The impurities were created using an optical Raman transition, which transferred a small fraction of the atoms into an untrapped hyperfine state. A dramatic reduction in the collisions between the moving impurities and the condensate was observed when the velocity of the impurities was close to the speed of sound of the condensate. This reduction was attributed to the superfluid properties of a BEC. In addition, we observed an increase in the collisional density as the number of impurity atoms increased. This enhancement is an indication of bosonic stimulation by the occupied final states. This stimulation was observed both at small and large velocities relative to the speed of sound. A theoretical calculation of the effect of finite temperature indicated that collision rate should be enhanced at small velocities due to thermal excitations. However, in the current experiments we were insensitive to this effect. Finally, the factor of two between the collisional rate between indistinguishable and distinguishable atoms was confirmed. A new BEC apparatus that can transport condensates using optical tweezers was constructed. Condensates containing 10-15 million sodium atoms were produced in 20 s using conventional BEC production techniques. These condensates were then transferred into an optical trap that was translated from the ‘production chamber’ into a separate vacuum chamber: the ‘science chamber’. Typically, we transferred 2-3 million condensed atoms in less than 2 s. This transport technique avoids optical and mechanical constrainsts of conventional condensate experiments and allows for the possibility of novel experiments. In the first experiments using transported BEC, we loaded condensed atoms from the optical tweezers into both macroscopic and miniaturized magnetic traps. Using microfabricated wires on a silicon chip, we observed excitation-less propagation of a BEC in a magnetic waveguide. The condensates fragmented when brought very close to the wire surface indicating that imperfections in the fabrication process might limit future experiments. Finally, we generated a continuous BEC source by periodically replenishing a condensate held in an optical reservoir trap using fresh condensates delivered using optical tweezers. More than a million condensed atoms were always present in the continuous source, raising the possibility of realizing a truly continuous atom lase.

Metallic foam processing from the liquid state

Cox, S.J., Bradley, G. and Weaire, D. (2001) Metallic foam processing from the liquid state: the competition between solidification and drainage. Eur. Phys. J. AP 14:87-97. Sponsorship: This research was supported by the Prodex programme of ESA, and is a contribution to ESA contract C14308/AO-075-99. SJC was supported by Enterprise Ireland and a Marie Curie fellowship. GB was supported by the HPC Programme of TCD.

What children learn from adults’ utterances: an ephemeral lexical boost and persistent syntactic priming in adult–child dialogue

We show that children’s syntactic production is immediately affected by individual experiences of structures and verb–structure pairings within a dialogue, but that these effects have different timecourses. In a picture-matching game, three- to four-year-olds were more likely to describe a transitive action using a passive immediately after hearing the experimenter produce a passive than an active (abstract priming), and this tendency was stronger when the verb was repeated (lexical boost). The lexical boost disappeared after two intervening utterances, but the abstract priming effect persisted. This pattern did not differ significantly from control adults. Children also showed a cumulative priming effect. Our results suggest that whereas the same mechanism may underlie children’s immediate syntactic priming and long-term syntactic learning, different mechanisms underlie the lexical boost versus long-term learning of verb–structure links. They also suggest broad continuity of syntactic processing in production between this age group and adults.

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Meanings of the Sabbath for Worship in the Seventh-Day Adventist Church

This study investigates the meanings and significance of the seventh-day Sabbath for worship in the Seventh-day Adventist Church. In recent years, both the day and concept of Sabbath have attracted ecumenical attention, but the focus of scholarship has been placed on Sunday as the Lord's Day or Sabbath with little consideration given to the seventh-day Sabbath. In contrast, this project examines the seventh-day Sabbath and worship on that day from theological, liturgical, biblical and historical perspectives. Although not intended as an apology for Seventh-day Adventist practices, the work does strive to promote a critical and creative conversation with other theological and liturgical traditions in order to promote mutual, ecumenical understanding. Historical research into the origins and nature of the principal day for weekly Christian worship provides a starting point for discussion on Sabbath. Reconsideration of the relationship between Judaism and early Christianity in recent studies suggests that the influence of Judaism lasted longer than previously supposed, thereby prolonging the developmental process of Sabbath (seventh day) to Sunday. A possible coexistence of Sabbath and Sunday in early Christianity offers an alternative to perspectives that dichotomize Sabbath and Sunday from Christian antiquity onward, and thus for the Seventh-day Adventist Church, suggests biblical and historical validity for their Sabbath worship practice. Recent theological perspectives on Sabbath and Sunday are examined, particularly those of Karl Barth, Jürgen Moltmann and Pope John Paul II. While all three of these theologians stress the continuity of Sabbath and Sunday and speak mainly to a theology of Sunday, they do highlight the significance of Sabbath—which is relevant to an interpretation of seventh-day Sabbath worship. The study concludes that the seventh-day Sabbath is significant for worship in the Seventh-day Adventist Church because it symbolizes the relationship between God and human beings, reminds humanity of the creating and redeeming God who acts in history, and invites persons to rest and fellowship with God on a day sanctified by God.

INVESTIGATION OF OCEAN ACOUSTICS USING AUTONOMOUS INSTRUMENTATION TO QUANTIFY THE WATER-SEDIMENT BOUNDARY PROPERTIES

Sound propagation in shallow water is characterized by interaction with the oceans surface, volume, and bottom. In many coastal margin regions, including the Eastern U.S. continental shelf and the coastal seas of China, the bottom is composed of a depositional sandy-silty top layer. Previous measurements of narrow and broadband sound transmission at frequencies from 100 Hz to 1 kHz in these regions are consistent with waveguide calculations based on depth and frequency dependent sound speed, attenuation and density profiles. Theoretical predictions for the frequency dependence of attenuation vary from quadratic for the porous media model of M.A. Biot to linear for various competing models. Results from experiments performed under known conditions with sandy bottoms, however, have agreed with attenuation proportional to f1.84, which is slightly less than the theoretical value of f2 [Zhou and Zhang, J. Acoust. Soc. Am. 117, 2494]. This dissertation presents a reexamination of the fundamental considerations in the Biot derivation and leads to a simplification of the theory that can be coupled with site-specific, depth dependent attenuation and sound speed profiles to explain the observed frequency dependence. Long-range sound transmission measurements in a known waveguide can be used to estimate the site-specific sediment attenuation properties, but the costs and time associated with such at-sea experiments using traditional measurement techniques can be prohibitive. Here a new measurement tool consisting of an autonomous underwater vehicle and a small, low noise, towed hydrophone array was developed and used to obtain accurate long-range sound transmission measurements efficiently and cost effectively. To demonstrate this capability and to determine the modal and intrinsic attenuation characteristics, experiments were conducted in a carefully surveyed area in Nantucket Sound. A best-fit comparison between measured results and calculated results, while varying attenuation parameters, revealed the estimated power law exponent to be 1.87 between 220.5 and 1228 Hz. These results demonstrate the utility of this new cost effective and accurate measurement system. The sound transmission results, when compared with calculations based on the modified Biot theory, are shown to explain the observed frequency dependence.

On Learning Counting Functions With Queries

We investigate the problem of learning disjunctions of counting functions, which are general cases of parity and modulo functions, with equivalence and membership queries. We prove that, for any prime number p, the class of disjunctions of integer-weighted counting functions with modulus p over the domain Znq (or Zn) for any given integer q ≥ 2 is polynomial time learnable using at most n + 1 equivalence queries, where the hypotheses issued by the learner are disjunctions of at most n counting functions with weights from Zp. The result is obtained through learning linear systems over an arbitrary field. In general a counting function may have a composite modulus. We prove that, for any given integer q ≥ 2, over the domain Zn2, the class of read-once disjunctions of Boolean-weighted counting functions with modulus q is polynomial time learnable with only one equivalence query, and the class of disjunctions of log log n Boolean-weighted counting functions with modulus q is polynomial time learnable. Finally, we present an algorithm for learning graph-based counting functions.

Learning Unions of Rectangles with Queries

We investigate the efficient learnability of unions of k rectangles in the discrete plane (1,...,n)[2] with equivalence and membership queries. We exhibit a learning algorithm that learns any union of k rectangles with O(k^3log n) queries, while the time complexity of this algorithm is bounded by O(k^5log n). We design our learning algorithm by finding "corners" and "edges" for rectangles contained in the target concept and then constructing the target concept from those "corners" and "edges". Our result provides a first approach to on-line learning of nontrivial subclasses of unions of intersections of halfspaces with equivalence and membership queries.

Geometric Generalizations of the Power of Two Choices

A well-known paradigm for load balancing in distributed systems is the``power of two choices,''whereby an item is stored at the less loaded of two (or more) random alternative servers. We investigate the power of two choices in natural settings for distributed computing where items and servers reside in a geometric space and each item is associated with the server that is its nearest neighbor. This is in fact the backdrop for distributed hash tables such as Chord, where the geometric space is determined by clockwise distance on a one-dimensional ring. Theoretically, we consider the following load balancing problem. Suppose that servers are initially hashed uniformly at random to points in the space. Sequentially, each item then considers d candidate insertion points also chosen uniformly at random from the space,and selects the insertion point whose associated server has the least load. For the one-dimensional ring, and for Euclidean distance on the two-dimensional torus, we demonstrate that when n data items are hashed to n servers,the maximum load at any server is log log n / log d + O(1) with high probability. While our results match the well-known bounds in the standard setting in which each server is selected equiprobably, our applications do not have this feature, since the sizes of the nearest-neighbor regions around servers are non-uniform. Therefore, the novelty in our methods lies in developing appropriate tail bounds on the distribution of nearest-neighbor region sizes and in adapting previous arguments to this more general setting. In addition, we provide simulation results demonstrating the load balance that results as the system size scales into the millions.

Systematic Verification of Safety Properties of Arbitrary Network Protocol Compositions Using CHAIN

Formal correctness of complex multi-party network protocols can be difficult to verify. While models of specific fixed compositions of agents can be checked against design constraints, protocols which lend themselves to arbitrarily many compositions of agents-such as the chaining of proxies or the peering of routers-are more difficult to verify because they represent potentially infinite state spaces and may exhibit emergent behaviors which may not materialize under particular fixed compositions. We address this challenge by developing an algebraic approach that enables us to reduce arbitrary compositions of network agents into a behaviorally-equivalent (with respect to some correctness property) compact, canonical representation, which is amenable to mechanical verification. Our approach consists of an algebra and a set of property-preserving rewrite rules for the Canonical Homomorphic Abstraction of Infinite Network protocol compositions (CHAIN). Using CHAIN, an expression over our algebra (i.e., a set of configurations of network protocol agents) can be reduced to another behaviorally-equivalent expression (i.e., a smaller set of configurations). Repeated applications of such rewrite rules produces a canonical expression which can be checked mechanically. We demonstrate our approach by characterizing deadlock-prone configurations of HTTP agents, as well as establishing useful properties of an overlay protocol for scheduling MPEG frames, and of a protocol for Web intra-cache consistency.

To Queue or Not to Queue: When Queueing is Better Than Timesharing in a Distributed System

We examine the question of whether to employ the first-come-first-served (FCFS) discipline or the processor-sharing (PS) discipline at the hosts in a distributed server system. We are interested in the case in which service times are drawn from a heavy-tailed distribution, and so have very high variability. Traditional wisdom when task sizes are highly variable would prefer the PS discipline, because it allows small tasks to avoid being delayed behind large tasks in a queue. However, we show that system performance can actually be significantly better under FCFS queueing, if each task is assigned to a host based on the task's size. By task assignment, we mean an algorithm that inspects incoming tasks and assigns them to hosts for service. The particular task assignment policy we propose is called SITA-E: Size Interval Task Assignment with Equal Load. Surprisingly, under SITA-E, FCFS queueing typically outperforms the PS discipline by a factor of about two, as measured by mean waiting time and mean slowdown (waiting time of task divided by its service time). We compare the FCFS/SITA-E policy to the processor-sharing case analytically; in addition we compare it to a number of other policies in simulation. We show that the benefits of SITA-E are present even in small-scale distributed systems (four or more hosts). Furthermore, SITA-E is a static policy that does not incorporate feedback knowledge of the state of the hosts, which allows for a simple and scalable implementation.