cssi/SciSciGPT-SciSciNet huggingface dataset:
Multiple interactions between BRG1 and MHC class II promoter binding proteins.

Abstract The class II transactivator (CIITA) interacts with the chromatin remodeling factor brahma related gene 1 (BRG1) as a necessary component of the transcriptional activation of human major histocompatibility complex (MHC) class II genes. We report here that RFXAP, a subunit of the DNA-binding RFX complex, also binds BRG1 and therefore provides a mechanism by which MHC class II gene chromatin can be remodeled in the absence of CIITA. RFXAP and CIITA bind to different regions of BRG1. The region of the RFXAP protein that binds BRG1 coincides with the minimally required fragment of RFXAP previously reported to be necessary to mediate MHC class II gene transcription. For CIITA, we found that BRG1 interacts with both the N-terminal acidic amino acid rich transactivation domain and a central region of CIITA that contains GTP-binding motifs. Analysis of chromatin structure of MHC class II genes in cell lines lacking CIITA or RFXAP, suggests that the RFXAP–BRG1 interaction may, in some cell types, produce chromatin remodeling.
Underwater hearing in California sea lions (Zalophus californianus): Expansion and interpretation of existing data

Measurements of underwater hearing sensitivity of pinnipeds have been made for 9 of 33 species, with most studies involving just one or two trained individuals. There is a need to refine and expand this limited knowledge base to improve understanding of hearing and possible anthropogenic noise effects, especially in cases where data may be extrapolated to other species (see National Research Council 2000, Southall et al. 2007). Schusterman et al. (1972) published what is still the only complete underwater audiogram for a California sea lion (Zalophus californianus). The purpose of this brief communication is to present hearing data from another trained California sea lion for comparison with the classic audiogram. Schusterman et al. (1972) originally tested the underwater hearing ability of an adult male sea lion—identified as “Sam”—using an operant conditioning method of vocal response. Sam was trained to either vocalize upon detecting a 500 ms pure tone signal or to remain silent when no signal was detected. The signals were varied in level in an adaptive, up-down fashion to obtain hearing thresholds at frequencies from 0.25 to 64 kHz. Thresholds were defined as the stimulus sound pressure level (SPL) in dB re: 1 bar corresponding to the 75% correct detection probability at each test frequency. The underwater hearing sensitivity of another captive California sea lion—an adult female identified as “Rio”—was later evaluated at relatively low frequencies (0.1–6.4 kHz) during similar auditory detection tasks conducted by Kastak and Schusterman (1998) and then again by Southall et al. (2005). The absolute threshold measurements obtained in these studies were subsequently extended to cover the full functional hearing range. The higher frequency data for Rio
The wind-driven circulation of the South Atlantic-Indian ocean — II. Experiments using a multi-layer numerical model

Abstract A numerical modeling study of the circulation of the South Atlantic-Indian Ocean in a geometrically simplified domain is extended to include baroclinicity using the quasi-isopycnic coordinate model of Bleck and Boudra (1981, Journal of Physical Oceanography , 11 , 755–770). Within this framework a number of model parameters are varied in an attempt to understand processes related to exchange of fluid between the two ocean basins. The importance of nonlinearity of the boundary currents is determined by varying mean upper layer depth among three experiments. Sensitivities of the model Agulhas retroflection to upper ocean stratification, lateral friction, presence of eastward drift and bottom drag are examined. The role of friction in the Indian Ocean western boundary layer is investigated and found to be important in separation from the boundary. Finally, horizontal resolution is doubled to resolve better the boundary layer and release of baroclinic instability. In advancing from the barotropic ( de Ruijter and Boudra , 1985, Dee-Sea Research , 32 , 557–574), to the baroclinic model, an important new feature is development of an intense recirculation eddy just beyond the point where the Agulhas Current overshoots the tip of South Africa. The center of this recirculation becomes the pivoting axis of the model retroflection, and its intensity increases with increasing Rossby number. At the same time, less top layer water is exchanged between the basins. The retroflection region acts as a source-sink of available potential and kinetic energy for the Atlantic-Indian Ocean in the low Rossby number case. This source-sink is essentially shut off in the high Rossby number case. Energy is pumped into the bottom layer underneath the recirculation, however, and radiates westward in weak anticyclonic eddies. Similar to the one-layer case, the mechanism of the modeled retroflection is adjustment to a change in the vorticity balance as the Agulhas leaves the coast of Africa. Along that coast, the β-induced gain of relative vorticity is balanced by diffusion into the no-slip boundary. After separation, potential vorticity is essentially conserved and the gain of relative vorticity is manifested in an eastward turn. Agulhas ring formation in the model occurs only for certain parameter ranges, and is due to a closing of the retroflecting current onto itself. In the highly nonlinear case, interaction with the cold, low potential vorticity, eastward drift south of the retroflection area is also required for ring formation.
Location of nerve cells producing the synaptic vesicles situated in the substantia gelatinosa of the spinal cord (1)

A search for the cells of origin of synaptic vesicles with electron-opaque cores and located in the substantia gelatinosa was attempted by subjecting cats to transection of dorsal roots and double hemisection in the upper lumbar region. The hemisections were accompanied by interruption of the dorsal rootlets to the affected segment. The cats were perfused with buffered aldehydes and processed for electron microscopy 55–71 days after the operations. Comparison of intact and operated sides of the rhizotomized cats revealed no discernible differences in numbers and location of the granulated vesicles associated with the substantia gelatinosa. In cats with double hemi-section plus rhizotomy the distribution of the granules was the same on the normal and operated sides but the numbers appeared to be reduced especially close to the surgical incisions. Dark-core vesicles were situated in association with the Golgi apparatus of substantia gelatinosa neurons, in dendrites, in small axons and in synaptic sacs in all material studied. It was concluded that most of the granulated vesicles located in the substantia gelatinosa are produced by small neurons in the immediate vicinity of their axon terminals.
Incorporation of Transition Metal Ions into MeAPO/MeAPSO Molecular Sieves

The synthetic incorporation of transition metal ions into aluminophosphate and silicoaluminophosphate molecular sieve frameworks is studied by electron spin−echo modulation (ESEM) spectroscopy. Based mainly on bulk chemical composition of the product, it has been suggested that divalent and trivalent metal ions such as Mn(II), Co(II), Cr(III), and Fe(III) substitute for framework aluminum sites. On the basis of 31P ESEM results, we originally suggested a framework phosphorus site for the incorporation of metal ions such as Ni(II) and Cr(III) in NiAPSO-5 and CrAPSO-5 molecular sieves. This site was later supported for other metal ions such as Ti(IV), V(IV), and Cu(II). In this work, we have extended such studies to Mn(II) and Fe(III) to better understand the metal substitution sites in AlPO4 frameworks. Irrespective of the particular metal ion, the 31P ESEM spectra of MeAPO/MeAPSO molecular sieves can be interpreted best on the basis of metal incorporation at a framework phosphorus site. Strong 27Al modula...
Too Many Sensitivity Data

Excerpt To the editor: In the October issue, Peacock and associates (1) presented results of qualitative and quantitative antibiotic sensitivity testing on 34 isolates of methicillin-resistantStaph...
Simulating VLSI wafer topography

As dimensions of the classical "planar" process are reduced the device features in the third dimension pose major fabrication and performance problems. Establishing techniques to characterize and optimize these non-planar device features is a primary goal of research on modeling and simulation. Lithography, etching and deposition models have been established which agree well with experiment. In many cases the dominant physical mechanism is a surface reaction process which can be simulated by a surface advancing algorithm such as the cell, ray or string approach. Prime examples of the usefulness of simulation are in understanding projection printing, step coverage in deposition, wafer planarization and linewidth bias and control for composite process sequences. Simulations for individual IC fabrication processes are being combined in a user oriented program for Simulation And Modeling of Profiles in Lithography and Etching (SAMPLE).
Development of a Work Sampling Methodology for Behavioral Observations: Application to Teamwork

Engineering programs must assess students’ abilities to master “crite-ria 3 a-k.” Skills such as teamwork, problem solving, design, and ethi-cal understanding entail learning various processes; hence, assessingthese outcomes is better accomplished by focusing on the processrather than the result. Methods for observing students’ performance,such as 100 percent behavioral observation, are ideal but expensive.We extend work sampling, an economic industry-based alter-native, to observe cognitive and behavioral processes. Specifically,we describe a work sampling methodology to assess studentsengaged in teamwork. We then determine attributes of team-work, establish target time proportions using 100 percent obser-vation, and statistically compare the targets to proportionsobtained from work sampling intervals to determine the effectiveinterval. The robustness of work sampling is tested in four learn-ing environments. Results indicate that sampling provides a sta-tistically valid alternative for assessing teamwork. However, whenobserving design and ethical understanding processes, additionalresearch is needed to make work sampling viable.Keywords: behavioral observation, teamwork, work sampling
Cardiac segmentation in MR cine data using inverse consistent deformable registration

This paper proposes a registration-based segmentation technique to fully automatically segment the left ventricle in cardiac cine magnetic resonance studies. We propose an inverse consistent deformable registration algorithm to recover one set of forward and backward deformation fields that allow us to access the deformation from any frame to any other frame in the cardiac sequence. Cardiac phases are segmented using a shortest path algorithm and time consistency is enforced through the deformation fields. We demonstrate on 52 datasets with expert outlined ground truth that the algorithm produces accurate (1.39 pixels median error, 2.10 pixels RMS error, 0.88 Dice coefficient) and fast (0.3 s/image) results.
Fostering Critical Literacy: The Art of Assignment Design

Applying reading and writing theory to cases in composition, this chapter troubleshoots assignments that produced disappointing results and illustrates how the model of the “ill-structured problem” can help writing instructors craft assignments that foster the cognitive and affective maturation essential to college-level literacy.
Time-Varying Autoregressions in Speech: Detection Theory and Applications

This paper develops a general detection theory for speech analysis based on time-varying autoregressive models, which themselves generalize the classical linear predictive speech analysis framework. This theory leads to a computationally efficient decision-theoretic procedure that may be applied to detect the presence of vocal tract variation in speech waveform data. A corresponding generalized likelihood ratio test is derived and studied both empirically for short data records, using formant-like synthetic examples, and asymptotically, leading to constant false alarm rate hypothesis tests for changes in vocal tract configuration. Two in-depth case studies then serve to illustrate the practical efficacy of this procedure across different time scales of speech dynamics: first, the detection of formant changes on the scale of tens of milliseconds of data, and second, the identification of glottal opening and closing instants on time scales below ten milliseconds.
On the limits of black-box reductions in mechanism design

We consider the problem of converting an arbitrary approximation algorithm for a single-parameter optimization problem into a computationally efficient truthful mechanism. We ask for reductions that are black-box, meaning that they require only oracle access to the given algorithm and in particular do not require explicit knowledge of the problem constraints. Such a reduction is known to be possible, for example, for the social welfare objective when the goal is to achieve Bayesian truthfulness and preserve social welfare in expectation. We show that a black-box reduction for the social welfare objective is not possible if the resulting mechanism is required to be truthful in expectation and to preserve the worst-case approximation ratio of the algorithm to within a subpolynomial factor. Further, we prove that for other objectives such as makespan, no black-box reduction is possible even if we only require Bayesian truthfulness and an average-case performance guarantee.
Extending Naturalistic Decision Making to Complex Organizations: A Dynamic Model of Situated Cognition

Naturalistic decision making (NDM) has become established as a methodological and theoretical perspective. It describes how practitioners actually make decisions in complex domains. However, NDM theories tend to focus on the human agents in the system. We extend the NDM perspective to include the technological agents in complex systems and introduce the dynamic model of situated cognition. We describe the general characteristics of NDM and the field of situated cognition, and provide a detailed description of our model. We then apply the model to a recent accident in which a US Navy submarine (USS Greeneville) collided with a Japanese fishing vessel (Ehime Maru). The discussion of the accident illustrates how decisions made are often a result of the interaction between a variety of technological and human agents and how errors introduced into the complex system can propagate through it in unintended ways. We argue that the dynamic model of situated cognition can be used to describe activities in virtually any complex domain.
Exclusion of lipid rafts and decreased mobility of CD94/NKG2A receptors at the inhibitory NK cell synapse.

CD94/NKG2A is an inhibitory receptor expressed by most human natural killer (NK) cells and a subset of T cells that recognizes human leukocyte antigen E (HLA-E) on potential target cells. To elucidate the cell surface dynamics of CD94/NKG2A receptors, we have expressed CD94/NKG2A-EGFP receptors in the rat basophilic leukemia (RBL) cell line. Photobleaching experiments revealed that CD94/NKG2A-EGFP receptors move freely within the plasma membrane and accumulate at the site of contact with ligand. The enriched CD94/NKG2A-EGFP is markedly less mobile than the nonligated receptor. We observed that not only are lipid rafts not required for receptor polarization, they are excluded from the site of receptor contact with the ligand. Furthermore, the lipid raft patches normally observed at the sites where FceR1 activation receptors are cross-linked were not observed when CD94/NKG2A was coengaged along with the activation receptor. These results suggest that immobilization of the CD94/NKG2A receptors at ligation sites not only promote sustenance of the inhibitory signal, but by lipid rafts exclusion prevent formation of activation signaling complexes.
Disturbance-Generated Bifurcation in an Adaptive System with e 1 -Modification Law

The so-called e 1 -modification law proposed by Narendra and Annaswamy (1987) has been studied through a prototype adaptve control system, with a single unknown pole and an unknown constant disturbance at its input. This paper reveals that using this law in the case of regulation the system possesses multiple equilibria and undergoes various bifurcations.
An observed tropical oceanic radiative-convective cloud feedback.

Abstract Anomalies of precipitation, cloud, thermodynamic, and radiation variables are analyzed on the large spatial scale defined by the tropical oceans. In particular, relationships between the mean tropical oceanic precipitation anomaly and radiative anomalies are examined. It is found that tropical mean precipitation is well correlated with cloud properties and radiative fields. In particular, the tropical mean precipitation anomaly is positively correlated with the top of the atmosphere reflected shortwave anomaly and negatively correlated with the emitted longwave anomaly. The tropical mean relationships are found to primarily result from a coherent oscillation of precipitation and the area of high-level cloudiness. The correlations manifest themselves radiatively as a modest decrease in net downwelling radiation at the top of the atmosphere, and a redistribution of energy from the surface to the atmosphere through reduced solar radiation to the surface and decreased longwave emission to space. Inte...
In-line performance monitoring for RZ-DPSK signals using asynchronous amplitude histogram evaluation

The asynchronous amplitude histogram evaluation technique has been applied to in-line performance monitoring for return-to-zero differential phase-shift keying (RZ-DPSK) signals. The principle of operation was studied by simulation and experiment. It has been demonstrated that residual dispersion and signal optical signal-to-noise ratio can be obtained by Gaussian curve fitting of only one peak in the amplitude histogram of the RZ-DPSK signal
A socialist model of economic development: The Polish and Bulgarian experiences

Abstract A socialist economy provides a significant opportunity for simulataneously solving the problems of capital accumulation, aggregate demand, and income distribution. In deciding, on the growth acceleration manoeuvre the planner has to take into account the consumers' frustration barrier and a number of other physical and organizationl constraints. The past experiences of Poland and Bulgaria indicate that more sustained growth rates could have been achieved, at a lower material and non-material cost to the population, had the planners been more realistic in plan construction and flexible in devising effective means of implementation. Even the initially successful import-led and externally-financed Polish industrialization of the first half of the 1970s — a clear break with the traditional growth strategy — backfired in mounting and unsustainable costs in the latter part of the decade, largely due to overoptimism, casting a gloomy shadow over the 1980s.
Inductor design for VHF tapped-inductor dc-dc power converters

The design and fabrication of coupled inductors with low profile, low cost, and high power density for tapped-inductor high-step-down dc-dc power converters in the very high frequency (30–300 MHz) range are presented. The inductor consists of a multi-layer thin-polyimide printed circuit board (PCB) and nano-granular thin-film magnetic material deposited on both sides and on beveled cuts to form a fully linked closed core. The magnetic material Co-Zr-O has good soft magnetic properties, high resistivity and high flux density capability. Multi-layer Co-Zr-O/ZrO 2 thin films are used to improve the performance of the magnetic core. A winding loss model of this coupled inductor is presented. Coupled inductors with turns ratios 2 and 10 for several different converter applications have been fabricated.
FPGA implementation of respiration signal classification using a soft-core processor

This paper proposes an implementation of automatic classification of respiratory signals using a field programmable gate array (FPGA). It has been shown for this type of respiratory signal that second order autoregressive modeling (AR) combined with a modified zero-crossing algorithm results in close to 100% consistency between manual and automatic classification methods. This algorithm was improved by adding calibration procedures and adjusted to run on an FPGA. Altera's development tools and intellectual property (IP) mega-core functions were utilized to implement a "soft-core" processor capable of running compiled C algorithms inside the Stratii FPGA chip. In addition, the high density and flexibility of the FPGA allowed for coupling of the soft-core processor with other hardware modules to form a fast interface between off-chip devices. The external SRAM, flash memory, and an LCD were interfaced with the NIOS II soft-core processor through a system on a programmable chip (SOPC) design.
A Common Interest Share Model for On-line Peer Communities

On-line communities on the Internet are highly self- organizing, dynamic and ubiquitous. The prime interest of peers in this community is often sharing common interest, even when compromising privacy. This paper presents a peer coordination strategy and a data sharing process for peers on the Internet which allows them to discover their common interest in terms of sets of frequently visited URLs. To this end, sample data was collected by randomly following links on popular Websites to simulate the algorithm in operation. Experiments were then performed to compare the number of discovered frequently visited URL sets and association rules with the overhead induced by our network.
Physical Disability Trajectories in Older Americans With and Without Diabetes: The Role of Age, Gender, Race or ethnicity, and Education

Purpose: This research combined cross-sectional and longitudinal data to characterize age-related tra jectories in physical disability for adults with and without diabetes in the United States and to investigate if those patterns differ by age, gender, race or ethnicity, and education. Design and Methods: Data were examined on 20,433 adults aged 51 and older from the 1998 to 2006 Health and Retirement Study. Multilevel models and a cohort-sequential design were applied to quantitatively depict the age norm of physical disability after age 50. Results: Adults with diabetes not only experience greater levels of physical disability but also faster rates of deterioration over time. This pattern is net of attrition, timeinvariant sociodemographic factors, and time-varying chronic disease conditions. Differences in physical disability between adults with and without diabetes were more pronounced in women, non-White, and those of lower education. The moderating effects of gender and education remained robust even after controlling for selected covariates in the model. Implications: This study highlighted the consistently greater development of disability over time in adults with diabetes and particularly in those who are women, non-White, or adults of lower education. Future studies are recommended to examine the mechanisms underlying the differential effects of diabetes on physical disability by gender and education.
Alveolar macrophages lack CCR2 expression and do not migrate to CCL2.

Background The recruitment of mononuclear cells has important implications for tissue inflammation. Previous studies demonstrated enhanced CCR1 and CCR5 expression and decreased CCR2 expression during in vitro monocyte to macrophage differentiation. To date, no study examined the in vivo differences in chemokine receptor expression between human peripheral blood monocytes and alveolar macrophages.
On the irreducible components of an ideal

Let I be an M -primary ideal in a local ring (R, M) and let irr(I) denote the set of irreducible components of I, where an ideal q is an irreducible component of I if q occurs as a factor in some decomposition of I as an irredundant intersection of irreducible ideals. We give several characterizations of the ideals in irr(I) and show that if J is an ideal between I and an irreducible component of I, then J is the intersection of ideals in irr(I). We also exhibit examples showing that there may exist irreducible ideals containing I that contain no ideal in irr(I). Also, we determine necessary and sufficient conditions that the pricipal ideal uR[u, tI] of the Rees ring R[u, tI] have a unique cover, and apply this to the study of the form ring of R with respect to I.
Network Traffic Modeling

From the viewpoint of a service provider, demands on the network are not entirely predictable. Traffic modeling is the problem of representing our understanding of dynamic demands by stochastic processes. Accurate traffic models are necessary for service providers to properly maintain quality of service. Many traffic models have been developed based on traffic measurement data. This chapter gives an overview of a number of common continuous-time and discrete-time traffic models. Sources are sometimes policed or regulated at the network access, usually by a leaky-bucket algorithm. Access policing can change the shape of source traffic by limiting the peak rate or burstiness. Source traffic may also be regulated by protocol mechanisms such as sliding windows or congestion windows (as in TCP), leading to other traffic models. INTRODUCTION Teletraffic theory is the application of mathematics to the measurement, modeling, and control of traffic in telecommunications networks (Willinger and Paxson, 1998). The aim of traffic modeling is to find stochastic processes to represent the behavior of traffic. Working at the Copenhagen Telephone Company in the 1910s, A. K. Erlang famously characterized telephone traffic at the call level by certain probability distributions for arrivals of new calls and their holding times. Erlang applied the traffic models to estimate the telephone switch capacity needed
Pseudorenin: A NEW ANGIOTENSIN-FORMING ENZYME

A new enzyme, pseudorenin, has been discovered which resembles renin in its ability to form angiotensin I from the synthetic tetradecapeptide renin substrate and from purified hog renin substrate A. Its maximal activity occurs at a much lower pH value than does that of renin. The two enzymes may be easily separated by DEAE-cellulose chromatography. Unlike renin, pseudorenin does not attack substrate A in the presence of serum, nor does it produce angiotensin I from renin substrate as it exists in serum. In contrast to renin, which occurs primarily in the kidney, pseudorenin has been found in every one of the 13 different tissues which have been tested, and also in the plasma. The natural substrate for the new enzyme as well as its physiological function are not known.
Reform and Renewal: Thomas Cromwell and the Common Weal

Preface Abbreviations 1. Introduction 2. Thomas Cromwell 3. Cromwell and his men 4. The instrument 5. Agriculture, trade and industry 6. Law reform 7. The achievement Index of Statutes cited Index of failed Bills General index.
Silicon compilation from register-transfer schematics

A silicon compiler system for layout generation from generalized register-transfer schematics is described. This system uses the SLAM floorplan compiler and the ICDB component server with parameterizable bit-sliced and glue-logic generators. The SLAM compiler partitions the netlist into component sets best suited for different layout styles, such as bit-sliced or strip-oriented logic. Based on a stripped and sliced layout architecture, each component set is partitioned further into clusters to achieve better floorplanning. The ICDB component server is capable of optimizing logic and producing layouts for the component sets according to performance constraints. The component server provides layouts with different aspect ratios and I/O pin location for better floorplanning. Several experiments demonstrate that highly dense layouts can be achieved using this system. >
Transmission Rate Allocation in Multisensor Target Tracking Over a Shared Network

In a multisensor target tracking application running on a shared network, at what bit rates should the sensors send their measurements to the tracking fusion center? Clearly, the sensors cannot use arbitrary rates in a shared network, and a standard network rate control algorithm may not provide rates amenable to effective target tracking. For Kalman filter-based multisensor target tracking, we derive a utility function that captures the tracking quality of service as a function of the sensor bit rates. We incorporate this utility function into a network rate resource allocation framework, deriving a distributed rate control algorithm for a shared network that is suitable for current best effort packet networks, such as the Internet. In simulation studies, the new rate control algorithm engenders significantly better tracking performance than a standard rate control method, while the ordinary data transfer flows continue to effectively operate while using their standard rate control methods.
New Early Permian Colonial Rugose Corals from the Central Cordilleran Miogeocline, U.S.A

Abstract Five new species of Early Permian (late Sakmarian to Kungurian) colonial corals from eastern Nevada and southeastern California, one assigned to a new genus, are described and illustrated. These include Heintzella playfordi n. sp. from the Arcturus Formation in Nevada and the Darwin Canyon Formation in California, Paraheritschioides fergusonensis n. sp. from the Ferguson Mountain and Bird Spring formations in Nevada, and Wendoverella arca n. gen. and n. sp., Permastraea nevadensis n. sp., and Pararachnastraea moormanensis n. sp. from the Pequop Formation in eastern Nevada. These new taxa are distinct from all previously described species, but most are related to other species in the North American miogeocline. Wendoverella arca n. sp., however, is unlike any other species described from North America but is quite similar to a Russian species, indicating faunal communication between the Ural Mountains and the Cordilleran miogeocline at least into Artinskian time.
Land Reform and Economic Development

DURING recent years the terms "land reform" and "economic development" have come into common usage in the day-to-day vocabularies of millions of people. For most people, the concepts suggested by these terms are probably distinct and separate. Economists, political scientists, and other students of world affairs, however, frequently use these terms in close association with each other. In this process of association, land reform often is treated as a necessary or highly desirable condition of economic development, although it might also be viewed as a partial consequence of the development process. The importance of the interrelationship between these two concepts warrants further scrutiny. With this purpose in mind, an effort will be made in this paper to (1) examine the general nature and importance of land reform, (2) classify the principal types of land reform that are current in the world today, and (3) analyze the general effect that these reform programs may have upon economic development.
STATISTICAL ANALYSIS OF GENE EXPRESSION MICROARRAYS

This manuscript is composed of two major sections. In the rst section of the manuscript we introduce some of the biological principles that form the bases of cDNA microarrays and explain how the dierent analytical steps introduce variability and potential biases in gene expression measurements that can sometimes be dicult to properly address. We address statistical issues associated to the measurement of gene expression (e.g., image segmentation, spot identication), to the correction for background uorescence and to the normalization and re-scaling of data to remove eects of dye, print-tip and others on expression. In this section of the manuscript we also describe the standard statistical approaches for estimating treatment eect on gene expression, and briey address the multiple comparisons problem, often referred to as the big p small n paradox. In the second major section of the manuscript, we discuss the use of multiple scans as a means to reduce the variability of gene expression estimates. While the use of multiple scans under the same laser and sensor settings has already been proposed (Romualdi et al. 2003), we describe a general hierarchical modeling approach proposed by Love and Carriquiry (2005) that enables use of all the readings obtained under varied laser and sensor settings for each slide in the analyses, even if the number of readings per slide vary across slides. This technique also uses the varied settings to correct for some amount of the censoring discussed in the rst section. It is to be expected that when combining scans and correcting for censoring, the estimate of gene expression will have smaller variance than it would have if based on a single spot measurement. In turn, expression estimates with smaller variance are expected to increase the power of statistical tests performed on them.
KIN-RECOGNITION AND THE SPATIAL DISTRIBUTION OF LARVAE OF THE BRYOZOAN BUGULA NERITINA (L.)

The distribution of many sessile marine invertebrates is heterogeneous on very small spatial scales and, in many cases, the distributional pattern is produced when larvae settle from the plankton (e.g., Connell, 1961; Caffey, 1982; Keough and Downes, 1982). Thus, some larvae settle near conspecific individuals, while others settle in relative isolation. It is of interest to identify the factors responsible for such variation in settlement, since they may result in spatial variation in a number of agents that may influence an organism's fitness such as the intensity of intraor interspecific competition and the risks of predation. These settlement patterns may result from heterogeneity in the distribution of larvae in the plankton or from variation in the intensity of settlement cues, with larvae settling in proportion to the strength of such cues. Alternatively, larval behavior may vary, and such variation and its sources are the foci of this study. Larvae of a colonial invertebrate, the bryozoan Bugula neritina (L.), were hypothesized to settle preferentially near conspecific larvae or newly attached individuals (hypothesis 1) or conspecific adults (hypothesis 2). This behavior was hypothesized to vary in strength either between (hypothesis 3) or within (hypothesis 4) maternal groups of larvae. Variation in settlement may also be derived from changes in the behavior of individual larvae with time or age (hypothesis 5), since some larvae become less selective with increasing time spent searching unsuccessfully for settlement cues (Knight-Jones, 1953). At the study site in southern California, Bugula neritina colonies live attached to a variety of substrata at depths of 0-20 m and are usually found in clumps of two to eight colonies, with well-established lone colonies being rare. The mode of fertilization is poorly known for this genus, but evidence from a number of species suggests that colonies are composed of protandrously hermaphroditic zooids, with cross-fertilization occurring between colonies (Silen, 1972; Schopf, 1977). Embryos are brooded, and a single colony may release up to 100 large (diameter 300-400 ,um), coronate larvae daily. It is possible that release of both sperm and larvae may be synchronized chemically between neighboring colonies (Str6m, 1969; Silen, 1972). The larvae are initially photopositive, but soon become photonegative/geopositive, and usually settle within a few hours of release (Lynch, 1947).
Slipstream Measurements of Small-Scale Propellers at Low Reynolds Numbers

The continuing growth in the use of small UAVs has required the need to more fully understand the propellers that power them. Part of this understanding is the behavior of the propeller slipstream. Using a 7-hole probe, the slipstreams of several small-scale propellers (diameters of 4.2, 5, and 9 in) were measured in both static (V∞ =0 )a nd advancing-flow (V∞ > 0) conditions at several locations downstream. For static conditions, as the slipstream expanded downstream, the maximum values of the axial and swirl velocities decreased. The general shape of the static slipstream was also found to be nearly the same for the propellers even though their planforms were different. During advancing-flow conditions, a contraction in the slipstream occurred by 0.5 diameters behind the propeller. Beyond that location, the size of the slipstream was relatively constant up to 3 diameters downstream (furthest distance measured). For advancing-flow slipstreams, the shape of the axial velocity distribution was observed to be dependent on the planform shape of the propeller. The static slipstream of a propeller-wing configuration showed that the slipstream portions above and below the wing moved away from each other towards opposite wing tips. However, the maximum axial and swirl velocities in the propeller-wing slipstream did not diminish compared with the isolated propeller slipstream.
Scaffold diversification enhances effectiveness of a superlibrary of hyperthermophilic proteins.

The use of binding proteins from non-immunoglobulin scaffolds has become increasingly common in biotechnology and medicine. Typically, binders are isolated from a combinatorial library generated by mutating a single scaffold protein. In contrast, here we generated a “superlibrary” or “library-of-libraries” of 4 × 108 protein variants by mutagenesis of seven different hyperthermophilic proteins; six of the seven proteins have not been used as scaffolds prior to this study. Binding proteins for five different model targets were successfully isolated from this library. Binders obtained were derived from five out of the seven scaffolds. Strikingly, binders from this modestly sized superlibrary have affinities comparable or higher than those obtained from a library with 1000-fold higher sequence diversity but derived from a single stable scaffold. Thus scaffold diversification, i.e., randomization of multiple different scaffolds, is a powerful alternate strategy for combinatorial library construction.
Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus – Mechanisms, Management, and Clinical Considerations

Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting.
Urban Transit System Microbial Communities Differ by Surface Type and Interaction with Humans and the Environment

ABSTRACT Public transit systems are ideal for studying the urban microbiome and interindividual community transfer. In this study, we used 16S amplicon and shotgun metagenomic sequencing to profile microbial communities on multiple transit surfaces across train lines and stations in the Boston metropolitan transit system. The greatest determinant of microbial community structure was the transit surface type. In contrast, little variation was observed between geographically distinct train lines and stations serving different demographics. All surfaces were dominated by human skin and oral commensals such as Propionibacterium , Corynebacterium , Staphylococcus , and Streptococcus . The detected taxa not associated with humans included generalists from alphaproteobacteria, which were especially abundant on outdoor touchscreens. Shotgun metagenomics further identified viral and eukaryotic microbes, including Propionibacterium phage and Malassezia globosa . Functional profiling showed that Propionibacterium acnes pathways such as propionate production and porphyrin synthesis were enriched on train holding surfaces (holds), while electron transport chain components for aerobic respiration were enriched on touchscreens and seats. Lastly, the transit environment was not found to be a reservoir of antimicrobial resistance and virulence genes. Our results suggest that microbial communities on transit surfaces are maintained from a metapopulation of human skin commensals and environmental generalists, with enrichments corresponding to local interactions with the human body and environmental exposures. IMPORTANCE Mass transit environments, specifically, urban subways, are distinct microbial environments with high occupant densities, diversities, and turnovers, and they are thus especially relevant to public health. Despite this, only three culture-independent subway studies have been performed, all since 2013 and all with widely differing designs and conclusions. In this study, we profiled the Boston subway system, which provides 238 million trips per year overseen by the Massachusetts Bay Transportation Authority (MBTA). This yielded the first high-precision microbial survey of a variety of surfaces, ridership environments, and microbiological functions (including tests for potential pathogenicity) in a mass transit environment. Characterizing microbial profiles for multiple transit systems will become increasingly important for biosurveillance of antibiotic resistance genes or pathogens, which can be early indicators for outbreak or sanitation events. Understanding how human contact, materials, and the environment affect microbial profiles may eventually allow us to rationally design public spaces to sustain our health in the presence of microbial reservoirs. Author Video : An author video summary of this article is available.
Violet 405-nm light: a novel therapeutic agent against common pathogenic bacteria.

Abstract Background The increasing incidence of healthcare-associated infections (HAIs) and multidrug-resistant organisms demonstrate the need for innovative technological solutions. Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, and Pseudomonas aeruginosa in particular are common pathogens responsible for a large percentage of indwelling medical device-associated clinical infections. The bactericidal effects of visible light sterilization (VLS) using 405-nm is one potential therapeutic under investigation. Materials and methods Light-emitting diodes of 405-nm were used to treat varying concentrations of S aureus, S pneumonia, E coli, and P aeruginosa. Irradiance levels between 2.71 ± 0.20 to 9.27 ± 0.36 mW/cm2 and radiant exposure levels up to 132.98 ± 6.68 J/cm2 were assessed. Results Dose-dependent effects were observed in all species. Statistically significant reductions were seen in both Gram-positive and Gram-negative bacteria. At the highest radiant exposure levels, bacterial log10 reductions were E coli—6.27 ± 0.54, S aureus—6.10 ± 0.60, P aeruginosa—5.20 ± 0.84, and S pneumoniae—6.01 ± 0.59. Statistically significant results ( Conclusions We have successfully demonstrated high-efficacy bacterial reduction using 405-nm light sterilization. The VLS showed statistical significance against both Gram-positive and Gram-negative species with the given treatment times. The β-lactam antibiotic-resistant E coli was the most sensitive to VLS, suggesting light therapy could a suitable option for sterilization in drug-resistant bacterial species. This research illustrates the potential of using VLS in treating clinically relevant bacterial infections.
A nonlocal approach to the cosmological constant problem

We construct a model in which the cosmological constant is canceled from the gravitational equations of motion. Our model relies on two key ingredients: a nonlocal constraint on the action, which forces the spacetime average of the Lagrangian density to vanish, and a dynamical way for this condition to be satisfied classically with arbitrary matter content. We implement the former condition with a spatially constant Lagrange multiplier associated with the volume form and the latter by including a free four-form gauge field strength in the action. These two features are enough to remove the cosmological constant from the Einstein equation. The model is consistent with all cosmological and experimental bounds on modification of gravity and allows for both cosmic inflation and the present epoch of acceleration.
IL-10 expression in pyramidal neurons after neuropathogenic coronaviral infection

The apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus is induced after infection with Mu-3 virus (Mu-3), a neuropathogenic strain of the JHM virus (JHMV), at 4–5 days post-inoculation (dpi). The viral antigens in the hippocampus are mainly found in the CD11b-positive cells distributed in the stratum oriens located outside the pyramidal layer, and only a few pyramidal neurons are infected. Furthermore, the apoptotic cells, indicated as showing caspase 3 (Cas3) activation, consist of a high number of uninfected cells. Therefore, it is considered that the apoptotic lesions occur through the indirect effects of infection, and not as a result of direct infection with Mu-3, similar to the reported neuronal apoptosis in the hippocampus after other types of infection. The apoptosis in the pyramidal neurons is accompanied by various types of proinflammatory cytokines depending on the causative agents. Thus, the local expression of proinflammatory cytokines was studied, revealing no correlation in the distribution of cytokine expression with the subregions showing apoptosis. However, the anti-inflammatory cytokine IL-10 was produced by pyramidal neurons of CA2 and CA3 at 3 dpi when there is no destructive change or viral invasion in the hippocampus.