cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of a Region of Troponin I Important in Signaling Cross-bridge-dependent Activation of Cardiac Myofilaments

Force generating strong cross-bridges are required to fully activate cardiac thin filaments, but the molecular signaling mechanism remains unclear. Evidence demonstrating differential extents of cross-bridge-dependent activation of force, especially at acidic pH, in myofilaments in which slow skeletal troponin I (ssTnI) replaced cardiac TnI (cTnI) indicates the significance of a His in ssTnI that is an homologous Ala in cTnI. We compared cross-bridge-dependent activation in myofilaments regulated by cTnI, ssTnI, cTnI(A66H), or ssTnI(H34A). A drop from pH 7.0 to 6.5 induced enhanced cross-bridge-dependent activation in cTnI myofilaments, but depressed activation in cTnI(A66H) myofilaments. This same drop in pH depressed cross-bridge-dependent activation in both ssTnI myofilaments and ssTnI(H34A) myofilaments. Compared with controls, cTnI(A66H) myofilaments were desensitized to Ca2+, whereas there was no difference in the Ca2+-force relationship between ssTnI and ssTnI(H34A) myofilaments. The mutations in cTnI and ssTnI did not affect Ca2+ dissociation rates from cTnC at pH 7.0 or 6.5. However, at pH 6.5, cTnI(A66H) had lower affinity for cTnT than cTnI. We also probed cross-bridge-dependent activation in myofilaments regulated by cTnI(Q56A). Myofilaments containing cTnI(Q56A) demonstrated cross-bridge-dependent activation that was similar to controls containing cTnI at pH 7.0 and an enhanced cross-bridge-dependent activation at pH 6.5. We conclude that a localized N-terminal region of TnI comprised of amino acids 33–80, which interacts with C-terminal regions of cTnC and cTnT, is of particular significance in transducing signaling of thin filament activation by strong cross-bridges.
Role of Cholesterol in House Fly Reproduction

IT is well established that immature insects, including the larvae of Musca vicina Macq., require a dietary source of sterols for growth and development1,2. Chauvin3 reported that sterols are necessary for reproduction in the German cockroach but did not present supporting evidence or describe the effect of sterol deficiency on the reproductive processses. The house fly, which has been found to lack the mechanism for sterol biosynthesis from 14C-sodium acetate4, utilizes a high percentage of administered 14C-cholesterol in egg production5. The following study was undertaken to determine the effect of dietary cholesterol on reproduction of the house fly.
Impact of a short intervention on novices' categorization criteria

Research on physics problem categorization has established that proficient problem solvers are able to group together physics problems that would be solved by similar principles and use conceptual approaches when solving problems, whereas weak solvers rely more heavily upon surface features (objects, contexts, and quantities provided) to identify specific equations that match to the problem situation. This study explores the degree to which novices are able to shift their categorization strategies toward one that is more principle based as a result of a brief, computer-based intervention designed to highlight the role of principles as categorization criteria. Students finishing an introductory algebra-based mechanics course were presented with a sequence of problem pairs, asked to judge whether each pair would be solved similarly, and provided with feedback. Students in one condition received feedback that was very sparse and only indicated correctness, whereas students in a second condition viewed elaborate feedback that linked problem features to the appropriate concepts and principles to solve each problem. We found an increased use of physics principles in the reasoning provided by students who received the elaborate feedback whereas students who did not view this elaboration primarily cited quantities in the problem statement. Although these results suggest it is possible to increase students' attention to principles when approaching problems, poor performance on the items indicates that considering the appropriateness of principles remains a difficult task for beginning physics students.
Atorvastatin affects interleukin-2 signaling by altering the lipid raft enrichment of the interleukin-2 receptor β chain

Although the immunomodulatory properties of statins are in part independent of their lipid-lowering effects, cholesterol is a major component of lipid rafts. We therefore studied the effects of atorvastatin (AS) on the raft enrichment of the interleukin-2 receptor (IL-2R) beta chain previously described by us and on early IL-2R signaling events in activated human T cells. We found that concomitant AS exposure during a 3-day stimulation with phytohemagglutinin (PHA) attenuates activation-associated events, such as the enhanced surface expression of the raft marker GM-1 and the induced expression of the activation marker CD25 (the IL-2R alpha chain). In contrast, brief AS treatment after PHA stimulation increased GM-1 surface expression and virtually abolished the selective raft enrichment of the IL-2R beta chain. Although this AS-associated increase in GM-1 expression resembled that seen in the presence of the raft-disrupting cholesterol chelator methyl-beta-cyclodextrin (MBCD), the two agents had contrasting effects on the tyrosine phosphorylation of the IL-2R beta chain by exogenous IL-2: MBCD essentially abolished this event, whereas AS tended to enhance it and shifted its occurrence out of rafts. We conclude that AS affects IL-2R signaling by altering the raft enrichment of the IL-2R beta chain and propose that this effect is one mechanism underlying the immunomodulatory properties of statins.
Blood pressure-lowering effects of statins: who benefits?

Objectives To evaluate if the effect of statins on blood pressure is similar in patients grouped by use of antihypertensive medication, level of blood pressure, and high-density lipoprotein cholesterol (HDL-C). Methods Blood pressure was compared in statins users (n = 995) and nonusers (n = 9536) from the National Health and Nutrition Examination Surveys. The overall effect of statins and their interactions with antihypertensive medication, blood pressure, and HDL-C were estimated using multiple linear and quantile regression. Results Adjusted systolic blood pressure was on average 1.8 mmHg lower in statins users than in nonusers (P = 0.05). Although statins had no significant effect among nonusers, it decreased systolic blood pressure by 3.3 mmHg among users of antihypertensive medication (interaction P = 0.02). The effect of statins on systolic blood pressure was similar in individuals with HDL-C levels above and below the median (49 mg/dl). Statins also lowered diastolic blood pressure by an average of 1.9 mmHg (P Conclusion Statins lower blood pressure by cholesterol-independent mechanisms, and the reduction is larger in individuals with higher blood pressure and those with low HDL-C. Statins may be beneficial in preventing hypertension and may contribute to better blood pressure control in hypertensive patients.
Simulations of high-altitude discharges initiated by runaway breakdown

Abstract Detailed 2D hydrodynamic and quasi-electrostatic simulations of high-altitude discharges driven by runaway air breakdown are presented for four cases, corresponding to sprites initiated by positive cloud-to-ground lightning strikes in which 200 C of charge is neutralized at an altitude of 11.5 km in 10, 7, 5 and 3 ms. We find that the computed optical emissions agree well with low-light level camera images of sprites, both in terms of the overall intensity and spatial distribution of the emissions. Our results show the presence of blue emissions extending down to 40 km (blue tendrils) and red sprite tops extending from 50 to 77 km. Simulated spectra show that N 2 1st positive emissions dominate in the wavelength range from 550 to 850 nm, in good agreement with observations. Strong radio pulses with durations of ∼300 μ s and peak electric field amplitudes ranging from 20 to 75 V/m at an altitude of 80 km and an approximate distance from the discharge of 50 km were computed. The magnitude and duration of these pulses is sufficient to cause breakdown and heating of the lower ionosphere (80–95 km) and leads us to suggest that sprites may also launch the EMP responsible for the production of elves. The computed values for the γ -ray fluxes are in agreement with observations of γ -ray bursts of atmospheric origin and the peak secondary electron densities which we obtain are in good agreement with recent measurements of HF echoes at mesospheric heights and associated with lightning.
Chemical Product Engineering—The third paradigm

Abstract New chemical products have historically been created by combining a broad knowledge of existing chemical products with scientific experimentation. Since a combinatorial explosion of product options will inevitably limit all experimental techniques, it should be preferable to minimize experimentation through a systematic consideration of product formulations prior to experimentation. This is the essence of product design and engineering. While the design of a chemical product and its manufacturing process are analogous, some critical differences are so fundamental that a new paradigm and new approaches are needed to successfully solve product design problems. In addition, chemical product design requires a methodology or algorithm to apply chemical engineering fundamentals. Product design techniques should draw largely on heuristics when data are limited, followed by more detailed calculations when data become available. Significant work is still needed to establish a comprehensive generic methodology for engineering chemical products in the absence of complete data.
Estimation efficiency for Markov chain models

In this paper, we evaluate and compare four algorithms for estimating stationary Markov chain models with embedded parameters from aggregate frequency data. By means of factorially designed Monte Carlo simulation experiments, we are able to determine the effects of model characteristics on algorithm accuracy and efficiency. We then present an application, using the best-performing algorithm, for U.S. population migration.
Optical Flow-Switched Transport Layer Protocol Design and Performance Analysis

We explore transport layer protocol design for a scheduled optical flow-switched network. The design guarantees the reliable delivery of large data files (“elephant” flows) over an all-optical end-to-end flow-switched network that can be modeled as a burst-error channel. We describe a good first-order channel model for optical flow-switched networks with optical amplifier transients. First, we show that transmission control protocol (TCP) performs poorly in such networks. Specifically, flow control and fair resource allocation with windowing in TCP are unnecessary since they are done via scheduling. Instead, we propose a transport protocol that uses file segmentation and reassembly, interleaving with forward error correction, and frame retransmission to combat burst errors. We analyze the protocol performance using standard results from information theory and probability theory and optimize throughput efficiency and delay, find practical frame lengths, and optimize flow durations.
Characterizing Conformational Ensemble and Free Energy Landscape of ABC Exporters using a Novel System-Specific Sampling Approach

During their transport cycle, ATP-binding cassette (ABC) exporters undergo large-scale conformational changes between inward-facing (IF) and outward-facing (OF) states. Using a novel approach based on designing system-specific reaction coordinates and employing nonequilibrium simulations, we have recently characterized the IF-OF conformational transition pathway of MsbA, a bacterial ABC exporter whose structure has been solved in multiple functional states including an OF conformation and two IF conformations (termed IF-closed and IF-open based on the extent to which the cytoplasmic side is open). Due to low resolution of MsbA crystal structures in IF conformation, only Cα atoms have been reported; however our unique system-specific sampling strategy results in a stable all-atom model of MsbA in the IF conformation in the presence of explicit membrane and water. In order to more accurately characterize the conformational ensemble of nucleotide-free apo MsbA, we also employ a free energy calculation technique based on a combination of umbrella sampling and replica exchange methods, using a reaction coordinate defined based on the orientation of transmembrane helices. The results indicate that the IF-closed conformation is associated with a relatively deep minimum and the IF-open-like conformations are also thermally accessible. However, the deepest free energy basin is associated with an IF conformation, more open than IF-closed and less open than IF-open, resembling the crystal structures of P-glycoprotein (a MsbA homolog) which are obtained at higher resolutions. The overall picture emerging from the reconstructed free energies is that MsbA is fairly flexible in its resting state in the absence of nucleotides and substrates. The approach proposed here provides a framework to study large-scale conformational changes of membrane transporters whose computational investigation at an atomic resolution may not be currently feasible using conventional methods.
What to Do (and Not Do) with Time-Series Criss-Section Data

We examine some issues in the estimation of time-series cross-section models, calling into question the conclusions of many published studies, particularly in the field of comparative political economy. We show that the generalized least squares approach of Parks produces standard errors that lead to extreme overconfidence, often underestimating variability by 50% or more. We also provide an alternative estimator of the standard errors that is correct when the error structures show complications found in this type of model. Monte Carlo analysis shows that these “panel-corrected standard errors” perform well. The utility of our approach is demonstrated via a reanalysis of one “social democratic corporatist” model.
On-line control, data collection, and reduction for chemical experiments at Berkeley☆

Abstract A small time-shared computer system has been developed at the Department of Chemistry, University of California at Berkeley. This system is primarily aimed at control, data collection and data reduction of on-line chemical experiments. A description of the interface between the computer and our microwave spectrograph is given as an example of the kind of computer-instrument interaction possible with this system. Several results in microwave spectroscopy are given and various methods of digitally filtering the data are discussed.
Exploring Ty1 retrotransposon RNA structure within virus-like particles

Ty1, a long terminal repeat retrotransposon of Saccharomyces, is structurally and functionally related to retroviruses. However, a differentiating aspect between these retroelements is the diversity of the replication strategies used by long terminal repeat retrotransposons. To understand the structural organization of cis-acting elements present on Ty1 genomic RNA from the GAG region that control reverse transcription, we applied chemoenzymatic probing to RNA/tRNA complexes assembled in vitro and to the RNA in virus-like particles. By comparing different RNA states, our analyses provide a comprehensive structure of the primer-binding site, a novel pseudoknot adjacent to the primer-binding sites, three regions containing palindromic sequences that may be involved in RNA dimerization or packaging and candidate protein interaction sites. In addition, we determined the impact of a novel form of transposon control based on Ty1 antisense transcripts that associate with virus-like particles. Our results support the idea that antisense RNAs inhibit retrotransposition by targeting Ty1 protein function rather than annealing with the RNA genome.
18F‐Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography Imaging in the Management of Merkel Cell Carcinoma: A Single‐Institution Retrospective Study

BackgroundMerkel cell carcinoma (MCC) is among the deadliest of cutaneous malignancies. A lack of consensus evaluation and treatment guidelines has hindered management of this disease. The utility of simultaneous positron emission tomography and computed tomography (PET/CT) has been demonstrated for
Orientation of the peptidoglycan chains in the sacculus of Escherichia coli

Summary The organization of chains of oligopeptidoglycan in the saccular wall is of critical importance in the study of the mechanism and physiology of prokaryotic wall growth. The electron microphotographs of De Pedro et al, present new findings and can be used to negate or at least raise questions about the previously accepted conclusion that the glycan chains are oriented transversely to the axis of rod-shaped Escherichia coli. This suggests caution in assuming that the glycan chains in the murein structure are parallel to each other and are perpendicular to the axis of the cell. These results should reopen the question of not only the orientation of the peptidoglycan chains, but the possibility of variability in orientation. Three classes of hypotheses about wall growth are reconsidered and problems with them are presented. The new results from De Pedro's laboratory and the experimental glycan chain length distribution argue against proposed systematic models. These include models that postulate belts or hoops stretched around the circumference of the cell and mechanisms that insert new chains of the length of presumptive “docking” strands in the stress-bearing wall. They are consistent, however, with the surface stress theory that proposes that random enzyme action together with physical forces are involved in the elongation of the rod-shaped Gram-negative wall.
“I Hate Everything About You”: A Qualitative Examination of Cyberbullying and On-Line Aggression in a College Sample

Due to highly innovative technologies such as the smart phone, cyberbullying and on-line aggression have increasingly affected individuals across the world. In this study, a broad symbolic interactionist approach is used to study both cyberbullying and on-line aggression. Cyberbullying is defined as repeated unwanted, hurtful, harassing, and/or threatening interaction through electronic communication media. On-line aggression is defined as hurtful, harassing, and/or threatening behavior that is not repeated. Undergraduate students at a Midwestern university (N = 221) were surveyed to determine the extent and nature of their cyberbullying and on-line aggression experiences. By using open ended questions to inquire about respondents' personal experiences with cyberbullying and on-line aggression, we identified three motivations for these acts, which included cyber sanctioning, power struggles, and entertainment.
Perceptions of Solicited Versus Unsolicited Self-Disclosure.

The present investigation examined perception of persons who emitted unsolicited self-disclosure as compared to perception of persons who emitted solicited self-disclosure. Sex differences were also examined. Subjects were 158 undergratuate students who were randomly assigned to listen to one of four audiotapes. The audiotaped vignette consisted of actors emitting either solicited or unsolicited self-disclosure. Subjects rated the actors on social skillfulness, social appropriateness, and interpersonal attraction. Unsolicited self-disclosers were rated as significantly less socially appropriate and interpersonally attractive. A significant interaction effect of disclosure mode by actor sex was also found for social skillfulness. The female was viewed as less socially skillful than the male when she failed to solicit disclosure. Explanations of these findings and their implications are discussed.
A Different Type of Medicine: Women's Experiences With Ophthalmic Diseases in Rural and Urban Tamil Nadu, India

I conducted a study to understand how urban and rural women conceptualized eye diseases in Tamil Nadu state 1 . I chose to examine eye diseases because ailments such as cataracts, glaucoma, refractive error, and diabetic retinopathy rank among the most serious diseases of Indian women. I collected observational, survey, and interview data to compare women from rural and urban areas. In line with my expectations, rural women were more likely to rely upon non-medical means of treatment than their urban counterparts. Contrary to expectations, however, I found that urban and rural Tamil women's overall dependence on nonmedical means was not excessive. Based on the study's findings, it appears that both urban and rural women express a marked preference for both traditional and modern medical treatments—a phenomenon that is known as medical pluralism. Rural participants expressed a greater interest in medical pluralism than their urban counterparts. The results of the study lead me to believe that medical plura...
Caregiver Perspectives on Transitions to Assisted Living and Memory Care

This study describes family caregivers' experiences moving relatives with Alzheimer's disease or related disorders (ADRD) from their homes to assisted living facilities (ALFs) and subsequently to memory care units (MCUs). We also examined how these experiences differed between caregiver dyad types, such as adult children caring for parents. In-depth interviews with 15 caregivers were transcribed verbatim. Grounded theory identified themes. Constant comparative analysis compared experiences of caregiver dyads. Most caregivers recognized the likely need for future specialized care at the time of the move to the ALF, but did not recall receiving information about transfer policies. The ALF move was harder for spouses, the MCU move for adult children. Assisted living facilities can improve support for caregivers facing a relative's MCU transition through education about advantages of MCU placement and information about transfer policies. Support needs during transitions may differ between adult children and spouses.
What's Next for Collection Management and Managers?

The realm of responsibility for most collection managers when dealing with gift stewardship within libraries focuses on managing donations of gifts in-kind. Fortunately, there is a significant amou...
Simulation of charge transport in a GaAs MESFET using the time dependent Schrodinger equation

Abstract The preliminary results of a numerical simulation of charge transport in a submicron size GaAs MESFET is described.
Fluorescence reflectance imaging of early processes of post-traumatic osteoarthritis in male and female mice

Osteophytes (0-3) 0.78 (0.51-1.00) 91.7% 96.7% 0.62 (0.39-0.86) 71.7% 80.0% Cysts (0-1) 1.00 (0.91-1.00) 100% 100% 1.00 (0.91-1.00) 100% 100% JSW (0-3) 0.63 (0.35-0.90) 71.7% 81.7% 0.34 (0.06-0.62) 45.0% 58.3% Composite score (0-7) 0.76 (0.48-1.00) 71.7% 81.7% 0.65 (0.41-0.89) 66.7% 66.7% Grade (‘none’, ‘developing’, ‘established’) 0.77 (0.56-0.98) 88.3% 95.0% 0.64 (0.43-0.85) 81.7% 86.7% Abstracts / Osteoarthritis and Cartilage 21 (2013) S63–S312 S190
Sediment Sources and Sedimentation Rates, Chincoteague Bay, Maryland and Virginia

ABSTRACT Chincoteague Bay receives an estimated 90,000 m3 of sediment annually, of which roughly half is sand and half mud. Sand is derived principally from the barrier, Assateague Island, with storm overwash being twice as effective as eolian transport in supplying sand to the bay. The mainland of Delmarva Peninsula is the primary source of mud-size sediment for the bay. Annual contribution of mud from shore erosion is approximately eight times that introduced by streams. Sediment transported from the Atlantic Ocean through the two active tidal inlets is important only in the immediate vicinity of the inlets. Present average rate of sedimentation in Chincoteague Bay estimated from annual sediment supply is 0.3 mm/yr. This is far less than the rate of 1.5 mm/yr, obtained from sediment thickness in borings in the bay and believed to represent average conditions over the past 5,000 years. The present anomalously low sedimentation rate and accompanying decline in salt-marsh growth are attributed to a decrease in ocean-derived sediment caused by the closing of former tidal inlets through Assateague Island. If this interpretation is correct, it underscores the wisdom of a recent decision against dune stabilization for prevention of storm overwash on Assateague Island. Overwash is a major means of providing sediment for landward accretion of barrier islands in response to relative sea-level rise. Elimination of storm overwash in the absence of sediment influx from the sea via tidal inlets almost certainly would have resulted in long-term net erosion on the lagoonal shore of Assateague Island.
Hypomorphic nuclear factor-κB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity

Background Human hypomorphic nuclear factor-κB essential modulator (NEMO) mutations cause diverse clinical and immunologic phenotypes, but understanding of their scope and mechanistic links to immune function and genotype is incomplete. Objective We created and analyzed a database of hypomorphic NEMO mutations to determine the spectrum of phenotypes and their associated genotypes and sought to establish a standardized NEMO reconstitution system to obtain mechanistic insights. Methods Phenotypes of 72 individuals with NEMO mutations were compiled. NEMO L153R and C417R were investigated further in a reconstitution system. TNF-α or Toll-like receptor (TLR)–5 signals were evaluated for nuclear factor-κB activation, programmed cell death, and A20 gene expression. Results Thirty-two different mutations were identified; 53% affect the zinc finger domain. Seventy-seven percent were associated with ectodermal dysplasia, 86% with serious pyogenic infection, 39% with mycobacterial infection, 19% with serious viral infection, and 23% with inflammatory diseases. Thirty-six percent of individuals died at a mean age of 6.4 years. CD40, IL-1, TNF-α, TLR, and T-cell receptor signals were impaired in 15 of 16 (94%), 6 of 7 (86%), 9 of 11 (82%), 9 of 14 (64%), and 7 of 18 (39%), respectively. Hypomorphism-reconstituted NEMO-deficient cells demonstrated partial restoration of NEMO functions. Although both L153R and C417R impaired TLR and TNF-α–induced NF-κB activation, L153R also increased TNF-α–induced programmed cell death with decreased A20 expression. Conclusion Distinct NEMO hypomorphs define specific disease and genetic characteristics. A reconstitution system can identify attributes of hypomorphisms independent of an individual's genetic background. Apoptosis susceptibility in L153R reconstituted cells defines a specific phenotype of this mutation that likely contributes to the excessive inflammation with which it is clinically associated.
Seesaw energy scale and the LSND anomaly

The most general, renormalizable Lagrangian that includes massive neutrinos contains 'right-handed neutrino' Majorana masses of order M. While there are prejudices in favor of M>>M{sub weak}, virtually nothing is known about the magnitude of M. I argue that the Liquid Scintillator Neutrino Detector (LSND) anomaly provides, currently, the only experimental hint: M{approx}1 eV. If this is the case, the LSND mixing angles are functions of the active neutrino masses and mixing and, remarkably, adequate fits to all data can be naturally obtained. I also discuss consequences of this 'eV-seesaw' for supernova neutrino oscillations, tritium beta-decay, neutrinoless double-beta-decay, and cosmology.
Transient Forward and Backward Whirl of Beam and Solid Rotors With Stiffening and Softening Effects

This paper describe the procedure of achieving unbalance response and stability of general accelerating solid rotor model rotors with variable cross-section on fluid film or rolling element bearings and seals with the casings mounted on foundations including stress stiffening and spin softening effects. The solid rotor analysis results are verified with beam analysis results wherever applicable.Copyright © 2011 by ASME
Party Polarization in the US Congress: Member Replacement and Member Adaptation

Democrats and Republicans in the US Congress are as ideologically consistent and distinct as they have been at any point in the past three decades. Since 1973, the Senate has become 29 percent more polarized and House polarization has increased 47 percent. This investigation of party polarization finds that member adaptation accounts for one-third of the total party polarization in both the House and Senate. Member replacement accounts for the other two-thirds, the lion's share of which has been the replacement of moderate southern Democrats by conservative Republicans. Republicans in both chambers are polarizing more quickly than Democrats. If the Democratic senators have taken one step toward their ideological home, House Democrats have taken two steps, Senate Republicans three steps and House Republicans four steps.
Phagocytic Cell Killing Mediated by Secreted Cytotoxic Factors of Vibrio cholerae

Vibrio cholerae strain VB1 secretes a number of enzymes into the outside medium that utilize ATP as a substrate. Such enzymes are found in the outside medium during the mid-log phase of growth, when the optical density at 650 nm is about 0.4, and they demonstrate nucleoside diphosphate kinase (Ndk), 5′ nucleotidase, and adenylate kinase (Ak) activities. We report that the filtered growth medium of V. cholerae , as well as the flowthrough fraction of a green Sepharose column during fractionation of the growth medium, had very little cytotoxicity by itself towards macrophages and mast cells but exhibited significant cytotoxicity in the presence of exogenous ATP. Such fractions, harboring 5′ nucleotidase, Ndk, and presumably other ATP-utilizing enzymes, demonstrated enhanced macrophage and mast cell death; periodate-oxidized-ATP (oATP)-treated macrophage and mast cells or such cells exposed to 0.1 mM Mg 2+ , where surface-associated P2Z receptors could not be activated, were not susceptible to subsequent ATP addition. Microscopic visualization of mast cells clearly demonstrated cell morphological changes such as swelling, vacuolization, and nuclear fragmentation following treatment with ATP and the growth medium of V. cholerae ; however, these effects were suppressed if the mast cells were pretreated with oATP. These results strongly imply that the secreted ATP-utilizing enzymes of V. cholerae modulate the external ATP levels of the macrophage and mast cells, leading to their accelerated death, presumably through activation of P2Z receptors. Thus, development of inhibitors for such enzymes may reduce the level of V. cholerae infection; alternatively, mutations in such genes may eliminate V. cholerae survival in the gut and contribute to a safer live vaccine.
Device mismatch and tradeoffs in the design of analog circuits

Random device mismatch plays an important role in the design of accurate analog circuits. Models for the matching of MOS and bipolar devices from open literature show that matching improves with increasing device area. As a result, accuracy requirements impose a minimal device area and this paper explores the impact of this constraint on the performance of general analog circuits. It results in a fixed bandwidth-accuracy-power tradeoff which is set by technology constants. This tradeoff is independent of bias point for bipolar circuits whereas for MOS circuits some bias point optimizations are possible. The performance limitations imposed by matching are compared to the limits imposed by thermal noise. For MOS circuits the power constraints due to matching are several orders of magnitude higher than for thermal noise. For the bipolar case the constraints due to noise and matching are of comparable order of magnitude. The impact of technology scaling on the conclusions of this work are briefly explored.
Robust adaptive feedforward control and achievable tracking for systems with time delays

A feedback/feedforward controller architecture is developed that characterises the achievable reference tracking of real time inputs for both minimum phase and non-minimum phase systems with time delays, when there are no modelling errors or external disturbances. This characterisation is obtained by factoring the plant into its minimum phase, non-minimum phase, and time delay components, which are used to design two feedforward controllers that inject signals into two points of the feedback loop. Design constraints are provided that determine both the types of signals that may be achieved, and the feedforward controllers that will generate that output. Of course, in practice, both modelling errors and external disturbances will be present. In this case, we develop robust analysis tools that both guide the feedback controller design process, and provide rigorous robust tracking performance that guarantees for the overall resulting closed-loop system. Robust methods for designing the feedforward controller...
Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience.

Background Pulmonary large cell neuroendocrine carcinomas (LCNEC) are aggressive neoplasms with poor prognosis. The role of neoadjuvant and adjuvant therapies in these tumors remains uncertain. Methods We performed a retrospective review of a prospective database. Kaplan-Meier estimates of overall survival (OS) were determined and compared across prognostic factors using log-rank analysis and the Cox proportional hazards model. Results One hundred patients with resected LCNEC were identified from 1992 to 2008. Of these, 54% were male and 98% current or former smokers (mean 60.3 pack-years). Twenty-two patients received neoadjuvant platinum chemotherapy with a response rate of 68% (15 of 22). Eighty percent (80 of 100) underwent lobectomy and 11% (11 of 100) pneumonectomy with a 90% (90 of 100) complete resection (R0) rate. Seventy-one percent (71 of 100) were stage I-II, and 20 of 71 received platinum adjuvant chemotherapy. Mean OS was 40 months. Univariate factors associated with decreased OS included male gender ( p = 0.007), increasing tumor (T) stage ( p = 0.004), and stage III–IV disease ( p = 0.04). Stage IB patients fared significantly worse than IA ( p = 0.006). Multivariate analyses identified male gender (hazard ratio [HR] 2.3, p = 0.007), comorbid pulmonary disease (HR 2.3, p = 0.012), and pathologic stage (HR = 2.2, p = 0.011) as associated with risk of death. Univariate analysis in stage IB-IIIA completely resected (R0) patients receiving combination platinum-based induction and (or) adjuvant chemotherapy showed a trend toward improved OS (median survival 7.4 vs 2 years, p = 0.052). Conclusions The LCNEC has a high response rate to platinum-based neoadjuvant chemotherapy. Resected advanced-stage patients receiving combination neoadjuvant and (or) adjuvant chemotherapy may have a survival advantage. These therapies should be considered in resectable patients with LCNEC.
A low-loss Ka-band distributed MEMS 2-bit phase shifter using metal-air-metal capacitors

A two-bit wideband distributed CPW phase shifter has been developed on a 500 /spl mu/m quartz substrate for Ka-band operation. The design utilizes MEMS switches in a DMTL (Distributed MEMS Transmission Line) periodically loaded by MEMS switches and high Q (>250 at 30 GHz) metal-air-metal capacitors. The MEMS switches are actuated by a low 20 volt P-P AC bias voltage via a high-resistance bias line. Estimated spring constant and switching time of the MEMS switch is 30 N/m and /spl sim/9 /spl mu/s, respectively. The two-bit design results in a reflection coefficient better than -11.5 dB, an average insertion loss of -1.5 dB, and phase shifts of 89/spl deg/, 180/spl deg/, and 270/spl deg/ at 37.7 GHz. This is currently the lowest less distributed phase shifter at Ka-band frequencies.
Correspondences Among Parent, Teacher, and Student Perceptions of Adolescents' Learning Disabilities:

A group of 26 adolescents with learning disabilities (Grades 9 through 12), their parents, and their special education teachers were asked to rate the students' skills in each of 21 specific areas covering general ability, oral language, reading, written language, math, study skills, motivation, social skills, attention, and nonverbal skills. Correspondences in the absolute and relative ratings of parents, teachers, and students across the 21 skill areas were examined. The parents' ratings were consistent with those of the teachers in 16 areas and significantly lower than the teachers in 5 areas. The students' ratings were generally higher than those of their parents and teachers. The student-teacher differences were significant in 6 areas, whereas the student-parent differences were significant in 11 areas. Although generally lower in absolute terms than the ratings of their children, the parents' relative ratings were strikingly parallel to their children's ratings across skill areas (r= .80). Differenc...
THE PHYSICAL BASIS OF THE POSITIVE PHOTOTROPISM OF PHYCOMYCES

A physical basis is demonstrated, in the case of a cylindrical cell illuminated with parallel light from one side, for greater photochemical action in the half of the cell farthest from the source of light, when the cell is surrounded by a medium of refractive index less than that of the cell. Factors governing the balance and magnitude of unequal action of light in the two halves of the cell are: the refractive index of the cell, the cell radius, and the absorption coefficient of the intracellular pigment. A limiting value of absorption coefficient is deduced which cannot be exceeded in cells of a particular size showing positive phototropism. In terms of this mechanism the positive phototropism of Phycomyces in air is explained.
The Prehistory of Northern Chile: A Synthesis

Northern Chile, part of the south central Andes, consists of two main ecological subareas: extreme northern Chile, including the western valleys, and the Atacama Desert and oases. Different ecological conditions obtain in each subarea: puna, altiplano, and precordillera in the highlands; valleys, the desert, and oases in the intermediate zone; and coastal environments along the Pacific shores. In prehistoric times, all these environments were very interconnected. There are three different cultural traditions in the local prehistory: the early hunting and gathering tradition (10,000–4000 B.P.), the Chinchorro Tradition (7500–2500 B.P.), and the Altiplano or Andean Tradition (3000–0 B.P.). This proposed sequence is described, with emphasis on the early Chinchorro adaptations, including the important patterns of mummification, and its possible relation to tropical forest groups of the Amazon basin; and the Pre-Tiwanaku and later Tiwanaku and Inca developments, in relation to the circum-Titicaca region. The data presented in the paper are further developed to explore ideas and hypotheses for future research.
Comparison of Treatment Outcomes Associated With Early Versus Late Treatment of Mandible Fractures: A Retrospective Chart Review and Analysis

Purpose We conducted outcomes assessment for all patients who had undergone treatment of mandible fractures at Tufts Medical Center across the 2 specialties of oral and maxillofacial surgery and otolaryngology. The aim of the present study was to determine whether a correlation existed between the development of postoperative complications and late treatment of mandible fractures (defined as treatment provided >48 hours after the time of injury). Patients and Methods All patients with mandible fractures treated at Tufts Medical Center between January 1, 2003 and January 1, 2008, underwent chart review to document the relevant data, including the time of fracture, time of treatment, and complications recorded during postoperative follow-up. The only patients included in the review were those who had follow-up data with good documentation. Results Our dataset included 92 patients, with a mean age of 28.74 years. The injury scores, compared between the early and late treatment and complication and noncomplication groups, were equivocal. Of our 92 treated patients, 19 (20.7%) had ≥1 postoperative complication. Of the 19 patients with any complication, 10 had undergone early treatment and 9 had been treated after 48 hours. Of our late treatment group, 25% developed ≥1 complication. The overall complication rate for the early group was 18%. Conclusions Our study did not reveal a statistically significant difference in the development of postoperative complications after mandible fracture repair between the early and late treatment groups. Our study seemed to have a result similar to that of some of the earlier studies investigating the same variable.
Pathway recognition and augmentation by computational analysis of microarray expression data

Motivation: We present a system, QPACA (Quantitative Pathway Analysis in Cancer) for analysis of biological data in the context of pathways. QPACA supports data visualization and both fine- and coarse-grained specifications, but, more importantly, addresses the problems of pathway recognition and pathway augmentation. Results: Given a set of genes hypothesized to be part of a pathway or a coordinated process, QPACA is able to reliably distinguish true pathways from non-pathways using microarray expression data. Relying on the observation that only some of the experiments within a dataset are relevant to a specific biochemical pathway, QPACA automates selection of this subset using an optimization procedure. We present data on all human and yeast pathways found in the KEGG pathway database. In 117 out of 191 cases (61%), QPACA was able to correctly identify these positive cases as bona fide pathways with p-values measured using rigorous permutation analysis. Success in recognizing pathways was dependent on pathway size, with the largest quartile of pathways yielding 83% success. In cross-validation tests of pathway membership prediction, QPACA was able to yield enrichments for predicted pathway genes over random genes at rates of 2-fold or better the majority of the time, with rates of 10-fold or better 10--20% of the time. Availability: The software is available for academic research use free of charge by email request. Contact: [email protected] Supplementary information: Data used in the paper may be downloaded from http://www.jainlab.org/downloads.html
Mothers' Labeling Responses to Infants' Gestures Predict Vocabulary Outcomes.

Twenty-nine infants aged 1;1 and their mothers were videotaped while interacting with toys for 18 minutes. Six experimental stimuli were presented to elicit infant communicative bids in two communicative intent contexts - proto-declarative and proto-imperative. Mothers' verbal responses to infants' gestural and non-gestural communicative bids were coded for object and action labels. Relations between maternal labeling responses and infants' vocabularies at 1;1 and 1;5 were examined. Mothers' labeling responses to infants' gestural communicative bids were concurrently and predictively related to infants' vocabularies, whereas responses to non-gestural communicative bids were not. Mothers' object labeling following gestures in the proto-declarative context mediated the association from infants' gesturing in the proto-declarative context to concurrent noun lexicons and was the strongest predictor of subsequent noun lexicons. Mothers' action labeling after infants' gestural bids in the proto-imperative context predicted infants' acquisition of action words at 1;5. Findings show that mothers' responsive labeling explain specific relations between infants' gestures and their vocabulary development.
Some new methods for the evaluation of medical school sex education curricula.

To develop new measures to evaluate medical school sex education curricula and to determine what skills a physician needs to assist patients with sexual problems 24 2nd-year medical students 14 of whom had completed a 4-week sexuality course completed a 15-minute interview with a simulated patient then filled out the Forced Choice Guilt Inventory (FCGI) and the Sex Knowledge and Attitude Test (SKAT). Additional measures used were the Sex Content Scale (SCS) and the Patient Response Form (PRF). Contrary to expectations the SCS ratio and peak scores were negatively correlated with the SKAT knowledge scale. The negative correlation between the PRF score and the FCGI suggests that the less guilty about sex the subject was the more positive the patient felt about his interview performance. No other significant correlations were observed between scores on the interview and on the written tests. Correlations between the FCGI and the several SKAT scales and intercorrelations among the latter were significant and in the expected direction. Finally no significant difference between medical students who had taken the sexuality course and those who had not was found; none of these instruments was able to identify any effect of the course. Although these results are suggestive of either deficiencies in the program or lack of discrimination in the instruments further research is necessary both to confirm the study results and to establish the validity of the instruments and methods used.
RARE EARTH ELEMENT (REE) ANALYSIS OF VERTEBRATE FOSSILS FROM THE UPPER CRETACEOUS CARBONATE MARINE FORMATIONS OF WESTERN AND CENTRAL ALABAMA, USA: TAPHONOMIC AND PALEOENVIRONMENTAL IMPLICATIONS

Rare earth element (REE) analysis of vertebrate fossils has previously been used to answer a number of stratigraphic, taphonomic, and paleoenvironmental questions concerning the depositional environments of Cretaceous siliciclastic marine and freshwater formations. In this study, vertebrate fossils from Upper Cretaceous formations of Alabama were analyzed to determine if REE analyses could be equally effective at resolving taphonomic and paleoenvironmental questions in marine carbonate strata. Results indicate that these fossils possess unique REE signatures, although they are not as distinctive as those of siliciclastic formations. REE data can also be used, with limitations, for stratigraphic assignment of vertebrate fossils as well as indicating relative paleobathymetry. Furthermore, differences in REE signatures between certain taxonomic groups and REE concentrations in different osteological material are observed. In conclusion, findings herein indicate that REE analysis of vertebrate fossils from carbonate deposits can be effective for paleoenvironmental and regional paleogeographic studies.
Online Learning of Spacecraft Simulation Models

Spacecraft simulation is an integral part of NASA mission planning, real-time mission support, training, and systems engineering. Existing approaches that power these simulations cannot quickly react to the dynamic and complex behavior of the International Space Station (ISS). To address this problem, this paper introduces a unique and efficient method for continuously learning highly accurate models from realtime streaming sensor data, relying on an online learning approach. This approach revolutionizes NASA simulation techniques for space missions by providing models that quickly adapt to real-world feedback without human intervention. A novel regional sliding-window technique for online learning of simulation models is proposed that regionally maintains the most recent data. We also explore a knowledge fusion approach to reduce predictive error spikes when confronted with making predictions in situations that are quite different from training scenarios. We demonstrate substantial error reductions up to 74% in our experimental evaluation on the ISS Electrical Power System and discuss the early deployment of our software in the ISS Mission Control Center (MCC) for ground-based simulations.