cssi/SciSciGPT-SciSciNet huggingface dataset:
Neuromodulation and Cognitive Performance: Recent Studies of Noradrenergic Locus Ceruleus Neurons in Behaving Monkeys

Publisher Summary Locus ceruleus (LC) neurons are phasically activated at short latencies selectively by target stimuli but not by other task events. This response is easily shifted to the new target cue after reversal training, confirming that these responses are driven by stimulus meaning. Optimal performance has been associated with an intermediate level of tonic LC discharge. In addition, phasic responses to target stimuli occur only during epochs of excellent task performance associated with intermediate tonic LC activity. A computational model of the LC explains the relationship between patterns of LC firing and task performance by changes in electrotonic coupling among LC neurons. Specifically, it demonstrates that an increase in coupling results in greater phasic responses to target but not nontarget cues and also produces lower spontaneous (tonic) activity. This model can predict possibility of modulated electrotonic coupling among LC neurons to be an important factor that regulates LC activity and its role in behavioral performance. This chapter describes recording of such LC neurons in monkeys during performance of a visual discrimination task. This task required animals to stably foveate a central fixation spot on a video monitor.
On sampling theorems for non bandlimited signals

It is well-known that certain non-bandlimited signals such as splines can be reconstructed from uniformly spaced samples similar to bandlimited signals. This usually requires noncausal IIR filters. We revisit this result and consider extensions such as derivative sampling theorems and pulse sampling theorems. It turns out that spline-like signals can often be reconstructed from joint sampling of amplitude and derivative using only FIR filters. We also briefly consider discrete time versions of these results.
A high‐order fully explicit flux‐form semi‐Lagrangian shallow‐water model

SUMMARY A new approach is proposed for constructing a fully explicit third-order mass-conservative semi-Lagrangian scheme for simulating the shallow-water equations on an equiangular cubed-sphere grid. State variables are staggered with velocity components stored pointwise at nodal points and mass variables stored as element averages. In order to advance the state variables in time, we first apply an explicit multi-step time-stepping scheme to update the velocity components and then use a semi-Lagrangian advection scheme to update the height field and tracer variables. This procedure is chosen to ensure consistency between dry air mass and tracers, which is particularly important in many atmospheric chemistry applications. The resulting scheme is shown to be competitive with many existing numerical methods on a suite of standard test cases and demonstrates slightly improved performance over other high-order finite-volume models. Copyright © 2014 John Wiley & Sons, Ltd.
Sensory Input Directs Spatial and Temporal Plasticity in Primary Auditory Cortex

The cortical representation of the sensory environment is continuously modified by experience. Changes in spatial (receptive field) and temporal response properties of cortical neurons underlie man...
Communicating Sensitive Scientific Issues: The Interplay Between Values, Attitudes, and Euphemisms in Communicating Livestock Slaughter

In demands for transparency in livestock production, how should the industry deal with communicating the sensitive topic of slaughter? This study examined the different effects of livestock slaughter transparency (via video) on slaughter and transparency attitudes based on people’s animal value orientation and the effects on the clarity and comfort of euphemisms. Findings indicated the video increased slaughter acceptance among all animal value orientations. All groups expected a high level of transparency from the industry regardless of the video. With respect to euphemisms, while slaughter was considered clearer, harvest was more comfortable.
Currents in contemporary bioethics: waiving informed consent to prenatal screening and diagnosis? Problems with paradoxical negotiation in surrogacy contracts.

Recently, an agonizing twist intersecting predictive genetic tests and surrogacy contracts made news headlines in Canada. The intended parents, a couple from British Columbia, instructed the surrogate mother with whom they were working to undergo First Trimester Screening and Chorionic Villi Sampling (CVS), which revealed the fetus likely had Down syndrome. The parents directed the surrogate to terminate the fetus or they would abdicate their parental claim upon birth. This story raised numerous legal and ethical questions relating to the transferability of decision making for prenatal screening, diagnostic tests, and the connected decision of termination when additional interested parties – the intended parents – are involved in the medical decision-making relationship. First, although the surrogate is the patient, what are the implications when the intended parents' wishes influence or even dictate the relationship between her and her obstetrician and genetic counselor? Second, if the intended parents' level of authority reaches explicit demands, may the intended parents ethically and legally require the surrogate to waive her right to informed consent for prenatal screening and diagnosis?
What Can Be Learned from Writing about Early Field Experiences

Abstract This paper describes the evolution of assignments in a course for students preparing to teach secondary science, mathematics, and agriculture science. We describe and analyze work done by preservice students in two different years to look for developing teacher knowledge, explicate how we have come to understand teacher knowledge as it was enacted in this particular context, and discuss how our self-study contributed to the growth of our knowledge as teacher educators.
Strontium and barium ions and guinea-pig ureter

Abstract 1. 1. In guinea-pig ureteral smooth muscle, Sr2+ substitution for Ca2+ increased the duration and the number of spikes of an action potential and the duration of phasic contraction. 2. 2. The magnitudep of tension development was decreased in phasic contraction as well as in potassium-induced tonic contraction. Sr2+ activity could be inhibited by Mn2+. 3. 3. Ba2+ substitution was incapable of maintaining ureteral excitability, although contractile activity was preserved.
Understanding the Mechanism Behind Maternal Imprisonment and Adolescent School Dropout

This study empirically tested 3 mechanisms commonly suggested to disadvantage youths whose mothers are incarcerated in prison. An event history analysis of school dropout was conducted on a sample of 6,008 adolescents in a large city created by merging several Illinois state administrative data. Findings revealed that adolescents are indeed at greater risk of school dropout during the year(s) their mothers are incarcerated. Children who are removed from maternal guardianship and placed under the guardianship of a relative adult are observed to have higher odds of school dropout than children who remain under maternal guardianship after the mother's imprisonment. Lastly, attending a school in which maternal imprisonment is fairly common is not found to place adolescents at greater risk of school dropout after controlling for school quality.
Energy management via pricing in LQ dynamic games

This paper investigates the use of pricing mechanisms as a means to achieve a desired feedback control strategy among selfish agents in the context of HVAC resource allocation in buildings. We pose the problem of resource allocation as a linear-quadratic game with many dynamically coupled zone occupants(agents) and an uncoupled social planner. The social planner influences the game by choosing the quadratic dependence on control actions for each agent's cost function. We propose a neighborhood-based simplification of the dynamic game that results in a more realistic and scalable framework than is considered in standard dynamic game theory. In addition, we construct the pricing design problem as a convex feasibility problem and apply our method to an eight zone building model.
Ecological factors and screening in child protective services

Abstract The locality in which a child is reported as maltreated is one of the most powerful predictors of whether that allegation will be investigated. This study examined the relationship between ecological factors and screening decisions made by child protective services (CPS) workers from 12 sites in 5 states. Of community sociodemographic characteristics, the number of families with children under age 18 was the strongest predictor of the rate of screening in a local CPS office. Rate of investigation was also positively related to a higher proportion of contacts alleging neglect and the allied community professionals having a positive relationship with CPS. When sociodemographic and reporting variables were combined, the proportion of neglect cases was the far stronger predictor. At the case level, when controlling for locality, worker beliefs that the role of CPS was a broad one and a worker's statements that resource availability was not a factor in the worker decision making process were both positively related to that worker's decision to investigate specific allegations of maltreatment or allegations of injury to a child. Although much research has focused on case-related factors in the screening decision, the results of this study suggest that factors from other levels of the decision ecology should not be ignored.
Responses of older adults to theory-based nutrition newsletters.

Abstract Objective To evaluate the effect of a theory-based newsletter on knowledge, attitude, and behavior-change in older adults. Design Pretest-posttest, random assignment, and treatment-control design with 2 treatment groups: 1 that received newsletters-only and 1 that received newsletters with follow-up telephone interviews. Control group completed pretest-posttest surveys only. Subjects/setting Four hundred eighty men and women, aged 60 to 74 years, were recruited to participate in a home-based educational intervention using a patient list generated from a rural tertiary care hospital database, Geisinger Medical Center in Danville, Pa. Intervention Five nutrition newsletters designed using the nutrition communication model and adult learning theory principles were mailed biweekly. Telephone-interviews followed each of the 5 newsletters 10 to 14 days after distribution. Outcome measures Nutrition knowledge and interest, food behavior related to dietary fat, and stages of change for dietary fat and fiber. Statistical analyses performed Analysis of covariance was used to determine group differences in posttest outcome measures using pretest as covariate. Results In addition to achieving higher scores than the control group, the treatment groups were significantly different from each other in correct and perceived nutrition knowledge at posttest. Those in the treatment group receiving telephone calls scored higher (mean change=19.0% for correct and 20.3% for perceived) than those who received the newsletters only (mean change=12.5% for correct and 14.3% for perceived; P P P Applications/conclusions This study provides an example of the incorporation of a theoretical model in development and evaluation of newsletters. Home-delivered nutrition newsletters based on this model can communicate health and nutrition information to older adults. Consumers today have more opportunities than ever before to access nutrition information quickly and inexpensively. Newsletters can help dietetics professionals filter and limit what consumers must process, saving clients time and improving the accuracy of information obtained. Dietetics professionals in both clinical and community practice are uniquely positioned to provide highly focused and understandable information to consumers via a newsletter format. J Am Diet Assoc. 2000;100:656-664.
Digital signal processing concepts

Within the last few years, digital techniques have been extensively applied to the solution of signal processing problems. This paper briefly examines the relative merits of analog and digital signal processing techniques and then considers the conceptual issues involved in formulating the solution to a signal processing problem as a digital signal processor. Issues considered are the representation of a digital processor by a difference equation, formal solution of the difference equation, the system function corresponding to the processor, as well as the frequency response of the system.
Maximal dimensional partially ordered sets III: a characterization of Hiraguchi's inequality for interval dimension

Dushnik and Miller defined the dimensions of a partially ordered set X,denoted dim X, as the smallest positive integer t for which there exist t linear extensions of X whose intersection is the partial ordering on X. Hiraguchi proved that if n >=2 and |X| @?2n+1, then dim X @? n. Bogart, Trotter and Kimble have given a forbidden subposet characterization of Hiraguchi's inequality by determining for each n >= 2, the minimum collection of posets @r"n such that if |X| = = 4, @r"n contains only the crown S^0"n - the poset consisting of all 1 element and n - 1 element subsets of an n element set ordered by inclusion. In this paper, we consider a variant of dimension, called interval dimension, and prove a forbidden subposet characterization of Hiraguchi's inequality for interval dimension: If n >=2 and |X 2n+1, the interval dimension of X is less than n unless X contains S^0"n.
Pertussis in adults. What physicians need to know.

Although there is increased awareness among physicians regarding their role in protecting adults against vaccine-preventable diseases, many physicians are unaware that adults develop pertussis. Studies of adults with prolonged cough have found that 20% to 25% have serologic evidence of recent pertussis infection. Investigations of outbreaks have documented that adults develop infection withBordetella pertussisand transmit the organism to susceptible children. Adults are the major reservoir of infection for children who may develop severe illness. Pediatric health care workers and patients infected with the human immunodeficiency virus might be at higher risk than the general population. Because most adults are susceptible to pertussis, physicians must consider pertussis in the differential diagnosis of patients with prolonged cough. Physicians who care for adults should be active in the diagnosis and treatment of pertussis, supportive of studies of the epidemiology of pertussis in adults, and interested in the development and testing of new diagnostic and preventive measures. (Arch Intern Med. 1991;151:1510-1512)
SEGREGATION KINETICS OF PARTICULATE SOLIDS SYSTEMS. I. INFLUENCE OF PARTICLE SIZE AND PARTICLE SIZE DISTRIBUTION.

Rates of segregation of initially randomly distributed mixtures of steel spheres of various sizes have been studied. Extent of segregation was determined by sampling the entire system and expressed as the standard deviation of the sample compositions from the mean composition of the system. The several idealized systems studied showed apparent first-order kinetics, and rate constants were determined as a function of particle size and particle size distribution. Segregation in these studies proceeded to an equilibrium state in which mixing and unmixing effects were balanced.
Phonetic variation in voiced obstruents in North-Central Peninsular Spanish

In Spanish, /b, d, [vvplosive]/ are usually spirantized to voiced approximants in all syllabic contexts after a continuant sound. However, in North-Central Peninsular Spanish (NCS), spirantization interacts with coda devoicing, yielding voiceless fricatives. In the majority of cases, coda /b, d, [vvplosive]/ occur in stressed syllables. This work examines whether or not stress is a factor in the likelihood of frication and devoicing of coda /b, d, [vvplosive]/ in this dialect. An acoustic study was conducted of nine native speakers from NCS. These speakers were tested on nonce words with /b, d, [vvplosive]/ in coda position in both stressed and unstressed syllables. Measurements were made of vowel and consonant duration, presence and absence of frication and voicing, and voicing duration. The results show that frication is more likely in stressed syllables than in unstressed syllables. This suggests that in stressed syllables, a higher subglottal pressure produces higher airflow across the glottis, thereby favoring frication. In turn, frication inhibits voicing due to conflicting aerodynamic requirements between the two. We conclude that stress is a factor in spirantization and that it may indirectly affect the voicing properties of /b, d, [vvplosive]/.
The eddy viscosity of turbulent equilibrium layers

Similarity laws for the mean flow and scaling laws for the turbulent motion are used in an attempt to obtain a general expression for the eddy viscosity of equilibrium layers. It is found that e=0.09 wτ2Δ/w*, in which wτ2 is a Reynolds stress representative for the region of overlap between the law of the wall and the velocity-defect law, while w* is the logarithmic slope of the mean velocity profile in that region. The distinction between wτ and w* is related to the strong inhomogeneity of the mean rate of strain in the inner layer. The results of the theory agree with experimental evidence obtained from transpired equilibrium layers.
Prehistoric deforestation at Chaco Canyon

Ancient societies are often used to illustrate the potential problems stemming from unsustainable land-use practices because the past seems rife with examples of sociopolitical “collapse” associated with the exhaustion of finite resources. Just as frequently, and typically in response to such presentations, archaeologists and other specialists caution against seeking simple cause-and effect-relationships in the complex data that comprise the archaeological record. In this study we examine the famous case of Chaco Canyon, New Mexico, during the Bonito Phase (ca. AD 860–1140), which has become a prominent popular illustration of ecological and social catastrophe attributed to deforestation. We conclude that there is no substantive evidence for deforestation at Chaco and no obvious indications that the depopulation of the canyon in the 13th century was caused by any specific cultural practices or natural events. Clearly there was a reason why these farming people eventually moved elsewhere, but the archaeological record has not yet produced compelling empirical evidence for what that reason might have been. Until such evidence appears, the legacy of Ancestral Pueblo society in Chaco should not be used as a cautionary story about socioeconomic failures in the modern world.
A speculation about the parallel ear asymmetries and sex differences in hearing sensitivity and otoacoustic emissions.

Abstract Hearing sensitivity and the prevalence of spontaneous otoacoustic emissions show parallel ear and sex differences in humans. Here it is proposed that these lateral asymmetries and sex differences may all result from differences in the ‘strength’ of the efferent inhibition delivered to individual cochleas. Specifically, it is proposed that the amount of efferent inhibition is relatively less in right ears and in females than in left ears and males. While it is unclear why or how ear asymmetries or sex differences would develop in the efferent system, by assuming that they do, one can begin to explain a number of basic facts of hearing. It is even possible that the lateral asymmetry in the efferent system may be related to the well-known cortical asymmetries that are believed to underlie speech perception, speech production, and other human abilities.
THE BIOLOGY OF HARVEYELLA MIRABILIS (CRYPTONEMIALES, RHODOPHYCEAE). VII. STRUCTURE AND PROPOSED FUNCTION OF HOST‐PENETRATING CELLS1

The parasitic red alga Harveyella mirabilis (Reinsch) Schmitz & Reinke was examined by light and electron microscopy to determine the structural mechanism involved in nutrient transfer. The host-penetrating rhizoidal cells are unique in possessing an extensive and apparently dynamic endomembrane system as well as other unique cytoplasmic inclusions. The membrane system consists of the plasmalemma, pinocytotic vesicles, multivesicular and concentric bodies, endoplasmic reticulum, dictyosomes, micro-body-like structures and an extensive vacuolar system. It is proposed that this system is active in the uptake and processing of host-derived nutrients. Plasmalemmal extensions (plasmalemmavilli) of Harveyella medullary cells may also function in nutrient uptake.
Design, construction, and performance of plastic heat exchangers for sub-Kelvin use

Abstract The ultimate temperature and cooling power of both the superfluid Stirling refrigerator (SSR) and the 3He–4He dilution refrigerator depend largely on the efficiency of their counterflow heat exchangers. This efficiency is limited mainly by the Kapitza boundary resistance at low temperatures. The usual method of overcoming this problem has been to increase the surface area of the heat exchangers. A different approach is to make the heat exchangers out of materials that have low Kapitza boundary resistance such as plastics. This article describes the design, construction, and performance of plastic heat exchangers that have been successfully used in our SSRs. Specifically, the paper includes a detailed description of our heat exchangers, step-by-step instructions on the construction of a plastic heat exchanger, and simple calculations of the performance of the heat exchanger under typical SSR operating conditions.
Caspase Inhibition Sensitizes Inhibitor of NF-κB Kinase β-deficient Fibroblasts to Caspase-independent Cell Death via the Generation of Reactive Oxygen Species

Cells lacking functional NF-kappaB die after ligation of some tumor necrosis factor (TNF) receptor family members through failure to express NF-kappaB-dependent anti-apoptotic genes. NF-kappaB activation requires the IkappaB kinase (IKK) complex containing two catalytic subunits named IKKalpha and IKKbeta that regulate distinct NF-kappaB pathways. IKKbeta is critical for classical signaling that induces pro-inflammatory and anti-apoptotic gene profiles, whereas IKKalpha regulates the non-canonical pathway involved in lymphoid organogenesis and B-cell development. To determine whether IKKalpha and IKKbeta differentially function in rescuing cells from death induced by activators of the classical and non-canonical pathways, we analyzed death after ligation of the TNF and lymphotoxin-beta receptors, respectively. Using murine embryonic fibroblasts (MEFs) lacking each of the IKKs, the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, and dominant negative Fas-associated death domain protein, we found that deletion of these kinases sensitized MEFs to distinct cell death pathways. MEFs lacking IKKalpha were sensitized to death in response to both cytokines that was entirely caspase-dependent, demonstrating that IKKalpha functions in this process. Surprisingly, death of IKKbeta-/- MEFs was not blocked by caspase inhibition, demonstrating that IKKbeta negatively regulates caspase-independent cell death (CICD). CICD was strongly activated by both TNF and lymphotoxin-beta receptor ligation in IKKbeta-/- MEFs and was accompanied by loss of mitochondrial membrane potential and the generation of reactive oxygen species. CICD was inhibited by the anti-oxidant butylated hydroxyanosole and overexpression of Bcl-2, neither of which blocked caspase-dependent apoptosis. Our findings, therefore, demonstrate that both IKKalpha and IKKbeta regulate cytokine-induced apoptosis, and IKKbeta additionally represses reactive oxygen species- and mitochondrial-dependent CICD.
Peritoneal dialysis in colistin intoxication: report of a case.

A patient with acute renal failure secondary to an overdose of colistin is presented. Peritoneal dialysis was used in an attempt to reduce the serum colistin level. Most previous reports have indicated that dialysis is not an effective way of removing colistin from the serum; there have been no published reports of the use of dialysis specifically for colistin intoxication. In our patient serum colistin was reduced from 16 to 4 μg per milliliter during the initial dialysis, with a further reduction to 2 μg per milliliter during a second dialysis. Renal function was markedly impaired until after the second dialysis, but thereafter gradually improved. Subsequent measurements of renal function have been normal.
Dynamical Dimension of Defects in Spatiotemporal Chaos

We utilize the dynamical fluctuations in spatiotemporal chaotic systems to elucidate the dynamical role of topological defects. We find that each defect in a representative defect-mediated system is associated with one to two degrees of dynamical freedom. Furthermore, we find that a significant fraction of the total degrees of freedom is {ital not} associated with the defects, and, in fact, appear to be related to the background phase turbulence. This new understanding of defect-mediated chaos provides hope that these complicated systems may be amenable to reduced statistical descriptions. {copyright} {ital 1998} {ital The American Physical Society }
Some supplementary attributes in the classification of Chlorococcum species.

Seventeen species of the chlorophycean genus Chlorococcum have been studied comparatively in axenic culture with the purpose of exploring the value of certain supplementary attributes in facilitating identification. The algae were cultivated under standard conditions in defined media. Such attributes as colony characteristics, changes in color and cellular morphology with increasing age, inhibition in the light by organic compounds such as acetate, pyruvate and certain pentose sugars, and differential sensitivity to antibiotic agents were studied and found useful in distinguishing the species of the genus Chlorococcum.
AWclust: point-and-click software for non-parametric population structure analysis

Background Population structure analysis is important to genetic association studies and evolutionary investigations. Parametric approaches, e.g. STRUCTURE and L-POP, usually assume Hardy-Weinberg equilibrium (HWE) and linkage equilibrium among loci in sample population individuals. However, the assumptions may not hold and allele frequency estimation may not be accurate in some data sets. The improved version of STRUCTURE (version 2.1) can incorporate linkage information among loci but is still sensitive to high background linkage disequilibrium. Nowadays, large-scale single nucleotide polymorphisms (SNPs) are becoming popular in genetic studies. Therefore, it is imperative to have software that makes full use of these genetic data to generate inference even when model assumptions do not hold or allele frequency estimation suffers from high variation.
Yeast ornithine decarboxylase and antizyme form a 1:1 complex in vitro: Purification and characterization of the inhibitory complex

Abstract Saccharomyces cerevisiae antizyme (AZ) resembles mammalian AZ in its mode of synthesis by translational frameshifting and its ability to inhibit and facilitate the degradation of ornithine decarboxylase (ODC). Despite many studies on the interaction of AZ and ODC, the ODC:AZ complex has not been purified from any source and thus clear information about the stoichiometry of the complex is still lacking. In this study we have studied the yeast antizyme protein and the ODC:AZ complex. The far UV CD spectrum of the full-length antizyme shows that the yeast protein consists of 51% β-sheet, 19% α-helix, and 24% coils. Surface plasmon resonance analyses show that the association constant (KA) between yeast AZ and yeast ODC is 6 × 107 (M−1). Using purified His-tagged AZ as a binding partner, we have purified the ODC:AZ inhibitory complex. The isolated complex has no ODC activity. The molecular weight of the complex is 90 kDa, which indicates a one to one stoichiometric binding of AZ and ODC in vitro. Comparison of the circular dichroism (CD) spectra of the two individual proteins and of the ODC:AZ complex shows a change in the secondary structure in the complex.
Tree mortality rates and tree population projections in Baltimore, Maryland, USA

Based on re-measurements (1999 and 2001) of randomly-distributed permanent plots within the city boundaries of Baltimore, Maryland, trees are estimated to have an annual mortality rate of 6.6% with an overall annual net change in the number of live trees of -4.2%. Tree mortality rates were significantly different based on tree size, condition, species, and Land use. Morus alba, Ailanthus altissima, and trees in small diameter classes, poor condition, or in transportation or commercial - industrial land uses exhibited relatively high mortality rates. Trees in medium- to low-density residential areas exhibited low mortality rates. The high mortality rate for A. altissima is an artifact of this species distribution among land use types (24% were in the transportation land use). Based on a new tree population projection model that incorporates Baltimore's existing tree population and annual mortality estimates, along with estimates of annual tree growth, Baltimore's urban forest is projected to decline in both number of trees and canopy area over the next century. Factors affecting urban tree mortality are discussed.
Born globals, the choice of globalization strategy, and the market's perception of performance

Abstract This paper analyzes which characteristics of born global firms determine their choice for international entry mode. Using a logistic regression analysis, we study 124 newly public firms in the United States that undertake 261 international joint ventures or international acquisitions within the first 6 years of their founding. We find that the market responds positively to announcements of international expansions by born global firms, and that larger, more profitable, and more liquid firms have a higher propensity to engage in joint ventures rather than acquisitions. We also find that the market favors firms that announce joint ventures, rewarding them with significantly positive abnormal returns. Furthermore, while we find that cultural similarity affects mode choice, it does not affect the market's reaction to the announcements.
Self-consistent properties of the electron distribution at a metal surface

Abstract The work function, surface energy, charge density, and potential are computed self-consistently for the semi-infinite electron gas model of a metal surface. Careful attention is given to quantum density oscillations. A procedure of Kohn and Sham for the inhomogeneous electron gas is used to treat exchange and correlation effects. Results are compared with experimental data.
Direct observation of structure-function relationship in a nucleic acid–processing enzyme

The relationship between protein three-dimensional structure and function is essential for mechanism determination. Unfortunately, most techniques do not provide a direct measurement of this relationship. Structural data are typically limited to static pictures, and function must be inferred. Conversely, functional assays usually provide little information on structural conformation. We developed a single-molecule technique combining optical tweezers and fluorescence microscopy that allows for both measurements simultaneously. Here we present measurements of UvrD, a DNA repair helicase, that directly and unambiguously reveal the connection between its structure and function. Our data reveal that UvrD exhibits two distinct types of unwinding activity regulated by its stoichiometry. Furthermore, two UvrD conformational states, termed “closed” and “open,” correlate with movement toward or away from the DNA fork.
Water diffusion coefficient measurements in deposited silica coatings by the substrate curvature method

Abstract The diffusion of water in silica coatings deposited by evaporation and physical vapor deposition (sputtering) is studied using the substrate curvature measurement technique. The diffusion of water into the coatings induced a swelling, which in turn caused bending (curvature) of the silicon substrate. The curvature change was measured in situ during a humidity increase from 0% to 95% at room temperature. The diffusivity of water in the sputtered silica coating was measured to be 10 × 10−12 cm2/s and achieved equilibrium in about 10 min. The diffusion of water in the evaporated silica coating achieved equilibrium in about 2 min. Because the coatings exhibited very short equilibration times, the impact of a non-instantaneous humidity change on the calculated diffusion coefficients was also examined.
Structure of the human κ-opioid receptor in complex with JDTic

Here we report the crystal structure of the humank-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 Aresolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human k-OR. Modelling of other important k-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 59-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure-activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for k-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human k-OR.
Genome-wide evaluation for quantitative trait loci under the variance component model

The identity-by-descent (IBD) based variance component analysis is an important method for mapping quantitative trait loci (QTL) in outbred populations. The interval-mapping approach and various modified versions of it may have limited use in evaluating the genetic variances of the entire genome because they require evaluation of multiple models and model selection. In this study, we developed a multiple variance component model for genome-wide evaluation using both the maximum likelihood (ML) method and the MCMC implemented Bayesian method. We placed one QTL in every few cM on the entire genome and estimated the QTL variances and positions simultaneously in a single model. Genomic regions that have no QTL usually showed no evidence of QTL while regions with large QTL always showed strong evidence of QTL. While the Bayesian method produced the optimal result, the ML method is computationally more efficient than the Bayesian method. Simulation experiments were conducted to demonstrate the efficacy of the new methods.
Circadian rhythm in blood glucose level of chickens.

Abstract 1. 1. The blood glucose levels of young chickens were sampled during alternating periods of darkness and light. 2. 2. A significant difference between the blood glucose levels of birds sampled during hours of darkness and light was found.
The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth

Although numerous molecules required for limb bud formation have recently been identified, the molecular pathways that initiate this process and ensure that limb formation occurs at specific axial positions have yet to be fully elucidated. Based on experiments in the chick, Fgf8 expression in the intermediate mesoderm (IM) has been proposed to play a critical role in the initiation of limb bud outgrowth via restriction of Fgf10 expression to the appropriate region of the lateral plate mesoderm. Contrary to the outcome predicted by this model, ablation of Fgf8 expression in the intermediate mesoderm before limb bud initiation had no effect on initial limb bud outgrowth or on the formation of normal limbs. When their expression patterns were first elucidated, both Fgf4 and Fgf8 were proposed to mediate critical functions of the apical ectodermal ridge (AER), which is required for proper limb bud outgrowth. Although mice lacking Fgf4 in the AER have normal limbs, limb development is severely affected in Fgf8 mutants and certain skeletal elements are not produced. By creating mice lacking both Fgf4 and Fgf8 function in the forelimb AER, we show that limb bud mesenchyme fails to survive in the absence of both FGF family members. Thus, Fgf4 is responsible for the partial compensation of distal limb development in the absence of Fgf8. A prolonged period of increased apoptosis, beginning at 10 days of gestation in a proximal–dorsal region of the limb bud, leads to the elimination of enough mesenchymal cells to preclude formation of distal limb structures. Expression of Shh and Fgf10 is nearly abolished in double mutant limb buds. By using a CRE driver expressed in both forelimb and hindlimb ectoderm to inactivate Fgf4 and Fgf8, we have produced mice lacking all limbs, allowing a direct comparison of FGF requirements in the two locations.
Estimation of multi-output production functions in commercial fisheries

Abstract Measuring the productivity of vessels in a multi-species fishery can be problematic. Typical regression techniques are not capable of handling multiple outputs while Data Envelopment Analysis (DEA) tends to ignore the stochastic nature of production. Applied economists have devoted considerable time to this problem and have developed several methods of dealing with the issue of multiple output technologies in commercial fisheries. Our paper contributes to this literature by providing another method for estimating production functions of vessels operating in multi-species fisheries. We utilize a two-stage model – with data from the West Coast Limited Entry Groundfish Trawl Fishery – using DEA to aggregate output in the first stage. This aggregate index is then used as the dependent variable in a regression framework, allowing for the estimation of the return to different inputs in fisheries production. This provides information that may be particularly important for fisheries managers.
Dynamical localization in spiral microlasers with unidirectional emission

High-Q modes with unidirectional emission are present in spiral-shaped microresonators despite completely chaotic ray dynamics. We demonstrate that formation of such modes is due to dynamical localization, and develop the theory of this effect
Simulation of Multidimensional Binary Random Fields with Application to Modeling of Two-Phase Random Media

This paper proposes a methodology for simulation of binary random fields with application to the problem of generating sample realizations of two-phase random media. The methodology is based on the concept of nonlinear transformations with memory of Gaussian random fields. The simulation is performed according to the autocorrelation function of the binary field which contains considerable information about the microstructural characteristics of the medium. The determination of the probabilistic characteristics of the underlying Gaussian field is achieved through an iterative procedure that was introduced in a previous paper by the same authors in one dimension and is extended here to multiple dimensions. Limiting cases and alternative mappings are also presented. The capabilities of the methodology are demonstrated in a series of examples.
Current Role of Anti-Angiogenic Strategies for Glioblastoma

Glioblastoma, an incurable, malignant, and highly vascular tumor, is a seemingly ideal target for anti-angiogenic therapies such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. Phase II trials in recurrent glioblastoma demonstrated bevacizumab was associated with clinical benefits, including decreases in brain edema and corticosteroids use resulting from reduced vascular permeability, as well as radiographic responses in 25 %–40 % of patients. In newly diagnosed disease, a phase III trial (AVAglio) showed adding bevacizumab to standard chemoradiotherapy improved progression free survival (PFS), with preservation of quality of life, and reduced corticosteroids use, but did not improve overall survival (OS). Another similar phase III trial (RTOG 0825) found similar PFS and OS trends, but suggested that the addition of bevacizumab resulted in more frequent cognitive decline compared with standard chemoradiotherapy. However, interpretation of those findings is limited by the fact that progressing patients were not evaluated, and patients remained longer on study in the bevacizumab arm. It is possible that the observed cognitive decline represented unrecognized tumor progression, rather than deleterious bevacizumab effects. Regardless, even if real, it is difficult to ascertain how improvements in PFS and quality of life compare with the associated economic costs and increased toxicities of bevacizumab, in the setting of no survival benefit. Further studies in recurrent disease are being conducted; preliminary results of a randomized trial showed favorable results with the combination with CCNU, and final results are awaited. Meanwhile, outside the realm of clinical trials, the current trend appears to be to reserve bevacizumab for use in recurrent disease, or for patients with moderate or severe neurologic symptoms, either in the newly diagnosed or recurrent setting. Further research efforts are needed to determine optimal candidates for this treatment from a molecular standpoint, as well as to develop imaging tools capable of accurately identifying response and progression, and to establish new drug combinations that could result in unquestionable clinical benefit and improved survival in these patients.
Fermionic string field theory

Abstract A spacetime Lorentz-invariant, gauge-fixed field theory for the NSR fermionic string is formulated using BRST gauge fixing. It is shown that, in order for the fields not to violate the spin statistics theorem, the states must be G -parity even.
PLASMA INHIBITOR OF PLATELET FUNCTION IN |[beta]|-THALASSEMIA

Patients with homozygous B-thalassemia of ten have moderate to severe epistaxis and/or a petechial rash with normal platelet count, PT and PTT. For this reason we have studied platelet function (P1 F). Pre-transfusion evaluation included: Duke bleeding time (BT), PF3 release (Stypven), aggregation (epinephrine, ADP, collagen), PT, PTT and platelet count. PI F was abnormal in 13/30 patients(43%) studied: 10/13 had recurrent epistaxis and/or petechial rashes. 3 had minimal symptoms; 13/13 had abnormal aggregation with epinephrine, 10/13 with ADP, and 10/13 with collagen; only 1 also had slightly low PF3 release; BT was abnormal in 3/13. At time of study platelet count was normal in all, PT and PTT in most; none were receiving anti-aggregating drugs. Patients' platelets were isolated, washed by Ardlie buffer method, lysed and analyzed spectophotomet-rically for iron. No iron deposition in platelets was detected by this method. In other experiments, donor platelets were washed or gel-filtered to render them free of donor plasma; test plasma was then added to platelets and platelet aggregation assays were performed. Normal donor platelets were abnormal when tested in plasma from patients with abnormal P1 F; platelets from 3 patients with abnormal P1 F functioned normally in normal plasma but abnormally in “abnormal” plasma. Abnormalities of platelet aggregation are detectable in 1/2 symptomatic patients. Our data suggest that the P1 F abnormalities detected in β-thalassemia may be due to a plasma Inhibitor, rather than an intrinsic platelet defect.
Tumor Necrosis Factor α Activates the Human Plasminogen Activator Inhibitor-1 Gene through a Distal Nuclear Factor κB Site

Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of plasminogen activation and likely plays important roles in coronary thrombosis and arteriosclerosis. Tumor necrosis factor-α (TNFα) is one of many recognized physiological regulators of PAI-1 expression and may contribute to elevated plasma PAI-1 levels in sepsis and obesity. Although TNFα is a potent inducer of PAI-1 expression in vitro and in vivo, the precise location of the TNFα response site in the PAI-1 promoter has yet to be determined. Transient transfection studies using luciferase reporter constructs containing PAI-1 promoter sequence up to 6.4 kb failed to detect a response to TNFα. Moreover, TNFα failed to induce expression of enhanced green fluorescent protein under the control of a 2.9-kb human PAI-1 promoter in transgenic mice, although endogenous murine PAI-1 was strongly induced. These data suggested that the TNFα response element in the PAI-1 gene is remote from the proximal promoter region. In this study, seven candidate regulatory regions were identified using cross-species sequence homology analysis as well as DNase I-hypersensitive site analysis. We identified a 5′ distal TNFα-responsive enhancer of the PAI-1 gene located 15 kb upstream of the transcription start site containing a conserved NFκB-binding site that mediates the response to TNFα. This newly recognized site is fully capable of binding NFκB subunits p50 and p65, whereas overexpression of the NFκB inhibitor IκB prevents TNFα-induced activation of this enhancer element.
River pollution by anticholinesterase agents

Abstract The effects of effluent discharged into the Blue River, near its confluence with the Missouri River in Kansas City, Missouri, by a manufacturer of organophosphate and carbamate pesticides were investigated. Since these pesticides act as nerve poisons by inhibiting the neurotransmitter modulating enzyme acetylcholinesterase (AChE) in the nervous system, poisoning of fishes was diagnosed by measurement of brain-AChE in fishes collected from the Missouri River upstream and downstream from the mouth of the Blue River. Other fish were exposed to diluted effluent in glass jars and their brain-AChE measured to determine combined poisoning potential of compounds present. Fishes immediately downstream repeatedly had lower brain-AChE activity than fishes upstream, and fish exposed to diluted effluent had lower brain-AChE activity than unexposed fish. Chemical analyses showed substantial amounts of AChE-inhibiting pesticides in the effluent relative to their toxicities. These data indicate the effluent is a contributing factor in the reduced brain-AChE activity of Missouri River fishes, and that brain-AChE measurement in fishes is a sensitive and reliable indicator of such pollution.
Distribution of single‐axon recurrent inhibitory post‐synaptic potentials in a single spinal motor nucleus in the cat.

1. The distribution of recurrent Renshaw inhibition was examined in the medial gastrocnemius motor nucleus of the cat by measurement of single-axon recurrent inhibitory post-synaptic potentials (recurrent i.p.s.p.s) in motoneurones supplying medial gastrocnemius produced by single impulses of antidromically stimulated single motor axons supplying the same muscle. 2. Stimulated motor-axon-recorded-motoneurone pairs were classified as 'close' if both contributed their axons to the same portion of the ventral roots (L7 rostral, L7 caudal or S1). Alternatively, they were classified as 'distant' if their axons were in different portions of these ventral roots. 3. Both the incidence and amplitude of 'close-pair' recurrent i.p.s.p.s were shown to be significantly larger than the corresponding values for 'distant-pair' recurrent i.p.s.p.s. 4. The results provided evidence of a strong topographic effect on the distribution of recurrent Renshaw inhibition within a single spinal motor nucleus. This finding is discussed in relation to the roles of topographic and species specificity in determining the organization of recurrent inhibition and to the partitioned distribution of monosynaptic Ia excitation in single motor nuclei.