cssi/SciSciGPT-SciSciNet huggingface dataset:
Generative models of conformational dynamics.

Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term ‘generative’ refers to a model of the joint probability distribution over the behaviors of the constituent atoms. In the context of molecular modeling, generative models reveal the correlation structure between the atoms, and may be used to predict how the system will respond to structural perturbations. We begin by discussing traditional methods, which produce multivariate Gaussian models. We then discuss gamelan (GrAphical Models of Energy LANdscapes), which produces generative models of complex, non-Gaussian conformational dynamics (e.g., allostery, binding, folding, etc.) from long timescale simulation data.
Abstract 1056: Cancer avatars are sensitive diagnosticians of the pleural space

The identification of malignant cells in pleural fluid has critical prognostic and therapeutic implications but is frequently a diagnostic challenge. The first step in determining the cause of a suspected malignant pleural effusion, thoracentesis, has an unsatisfying low sensitivity (~60-70%). Patient-derived xenografts (PDX) retain the principal characteristics of the tumor of origin. However, there has been little progress in the application of these models to guide diagnostic and staging strategies. We assessed the feasibility, cellular yield and comparative diagnostic accuracy of pleural-derived xenografts in patients with effusions. An institutional review board-approved single-institution prospective registry of patients was used to identify patients undergoing diagnostic and/or therapeutic thoracentesis. Cells isolated from the pleural fluid of these patients were injected into NSG mice. A diagnosis of the cancer in the xenograft was confirmed by a staff pathologist with expertise in the correspondent cancer type. All of the cases that were clinically positive for tumor cells in the pleural space demonstrated tumor engraftment. Samples taken from patients with known benign etiologies did not result in tumor engraftment. The developed xenografts provided ample tissue that can be made available for extensive molecular testing, even in cases where the cytological samples consisted of very few cells. Critically, two of 10 cases resulted in engraftment of the tumor despite no evidence of malignant cells on cytological examination, indicating a 20% improvement in the statistical power of pleural-based xenografting for the detection of malignancy. Our study indicates that pleural-derived xenografts can enhance the sensitivity of malignant cell detection, reflecting the inherent limitations of cytological analyses of a few malignant cells. Moreover, the amplification of cellular material provides ample source material that can be used to satisfy the increasing demands for tissue-based molecular testing. To our knowledge, this is the first effort to effectively use patient-derived xenografts for the purpose of cancer staging and diagnosis. Citation Format: Gwendolyn B. Kuzmishin, Priyanka Gopal, Mohamed E. Abazeed. Cancer avatars are sensitive diagnosticians of the pleural space [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1056.
The role of the microbiota in infectious diseases

The human body is colonized by a diverse community of microorganisms collectively referred to as the microbiota. Here, we describe how the human microbiota influences susceptibility to infectious diseases using examples from the respiratory, gastrointestinal and female reproductive tract. We will discuss how interactions between the host, the indigenous microbiota and non-native microorganisms, including bacteria, viruses and fungi, can alter the outcome of infections. This Review Article will highlight the complex mechanisms by which the microbiota mediates colonization resistance, both directly and indirectly, against infectious agents. Strategies for the therapeutic modulation of the microbiota to prevent or treat infectious diseases will be discussed, and we will review potential therapies that directly target the microbiota, including prebiotics, probiotics, synbiotics and faecal microbiota transplantation. This Review discusses the role of the gut, respiratory tract and vaginal microbiota in susceptibility and resistance to infectious diseases.
Finite Plane Strain of Incompressible Elastic Solids by the Finite Element Method

The finite element method is extended to the problem of finite plane strain of elastic solids. A highly elastic body subjected to two-dimensional deformations is represented by an assembly of triangular elements of finite dimension. The displacement fields within each element are approximated by linear functions of the local coordinates. Non-linear stiffness relations involving generalised node forces and displacements are derived from energy considerations. For demonstration purposes, the non-linear stiffness equations are applied to the problems of finite simple shear and generalised shear. For finite simple shear, it is shown that these relations are in exact agreement with finite elasticity theory. Convergence rates of finite element representations of these problems are briefly examined.
Proton beam therapy for oligodendroglioma

Abstract With maximal safe surgical resection, radiation therapy, and chemotherapy, many patients with oligodendroglioma live for several years after diagnosis. Many of these survivors suffer long-term sequelae of radiation therapy, including neurocognitive decline, endocrine dysfunction, and secondary malignancy. Several clinicians and investigators have thus sought to eliminate or delay radiation therapy for these patients. Proton therapy utilizes the unique properties of the Bragg peak to decrease the overall integral dose to the brain and adjacent organs. Dosimetric studies and single arm trials suggest promising toxicity outcomes for proton therapy compared to photon therapy, however comparative trials are lacking. Overall, especially with continued technological advances to further the precision and understanding of dose delivery, proton therapy represents a promising way to decrease the late effects of radiation therapy for patients with oligodendroglioma.
Conjunctival HLA-DR Expression and Its Association With Symptoms and Signs in the DREAM Study.

Purpose Evaluation of dry eye disease (DED) relies on subjective symptoms and signs. We examined HLA-DR expression (HLA-DR%) in conjunctival cells, a minimally invasive biomarker with objective metrics, as an alternative method. Methods Dry Eye Assessment and Management (DREAM) study participants completed the Ocular Surface Disease Index questionnaire. Clinicians evaluated tear volume, tear breakup time, and corneal and conjunctival staining. Conjunctival impression cytology samples (n = 1049) were assessed for HLA-DR% in total cells (TCs), epithelial cells (ECs), and white blood cells (WBCs). Associations (categorized into 15%-25%, and >25%) with symptoms and signs were evaluated. Results The HLA-DR% varied markedly across samples. Over 40% had 25%, linear trend P = 0.009) and TCs (mean score 2.82 for 25%, linear trend P = 0.04) and in TCs was associated with higher corneal staining (mean score 3.59 for 25%, linear trend P = 0.03). HLA-DR% in WBCs did not correlated with signs (all P ≥ 0.58), and in TCs, ECs or WBCs were not associated with symptoms (P > 0.06). Conclusions The distribution of HLA-DR% in conjunctival cells reflects the heterogeneity of disease in DREAM participants. High percentages of samples with <5% positive cells indicate that HLA-DR% may not be a sensitive marker for DED in all patients. Translational Relevance High HLA-DR% in ECs in association with high conjunctival staining may identify a subgroup of DED patients prone to epithelial disease and possibly need a different approach from current standards of treatment.
BIOCHEMICAL AND CLINICAL SIGNIFICANCE OF APOLIPOPROTEINS AND LIPOPROTEIN FAMILIES

Recent advances in lipoprotein research have already produced a profound impact on the existing views about the definition and classification of plasma lipoproteins. The discovery of several apolipoproteins, the identification of discrete lipoprotein particles and the marked protein heterogeneity of density classes have become incompatible with the view that operationally-defined lipoproteins represent the fundamental chemical and metabolic entities of this system. To provide a new conceptual framework for the structural and functional complexity of lipoproteins, we have introduced the concept of lipoprotein families or particles as the fundamental components of the system. The individual, polydisperse families are characterized and identified solely on the basis of their apolipoprotein composition. The biochemical significance of this concept resides in its recognition of apolipoproteins as the most probable determinants of the structural integrity and functional specificity of lipoproteins. Due to their distinct chemical and immunologic properties, apolipoproteins also represent the most suitable markers for studying the metabolic interactions and fate of lipoprotein particles. The already available results on the quantification of apolipoproteins suggest that apolipoprotein profiles may be better markers than lipids for identifying the genetic and biochemical basis of dyslipoproteinemias. Clinically, the apolipoprotein profiles and lipoprotein families may provide new means for the differential diagnosis of dyslipoproteinemic states, for predicting the severity of atherosclerotic process and monitoring the progress of therapeutic interventions.
A Model-Based Prognostics Approach Applied to Pneumatic Valves

Within the area of systems health management, the task of prognostics centers on predicting when components will fail. Model-based prognostics exploits domain knowledge of the system, its components, and how they fail by casting the underlying physical phenomena in a physics-based model that is derived from first principles. Uncertainty cannot be avoided in prediction, therefore, algorithms are employed that help in managing these uncertainties. The particle filtering algorithm has become a popular choice for model-based prognostics due to its wide applicability, ease of implementation, and support for uncertainty management. We develop a general model-based prognostics methodology within a robust probabilistic framework using particle filters. As a case study, we consider a pneumatic valve from the Space Shuttle cryogenic refueling system. We develop a detailed physics-based model of the pneumatic valve, and perform comprehensive simulation experiments to illustrate our prognostics approach and evaluate its effectiveness and robustness. The approach is demonstrated using historical pneumatic valve data from the refueling system.
Cartilage and collagen mechanics under large-strain shear within in vivo and at supraphysiogical temperatures

Human joints, particularly those of extremities, experience a significant range of temperatures in vivo. Joint temperature influences the mechanics of both joint and cartilage, and the mechanics of cartilage can affect the temperature of both joint and cartilage. Thermal treatments and tissue repairs, such as thermal chondroplasty, and ex vivo tissue engineering may also expose cartilage to supraphysiological temperatures. Furthermore, although cartilage undergoes principally compressive loads in vivo, shear strain plays a significant role at larger compressive strains. Thus, we aimed to determine whether and how the bulk mechanical responses of cartilage undergoing large-strain shear change (1) within the range of temperatures relevant in vivo, and (2) both during and after supraphysiological thermal treatments. We completed large-strain shear tests (10 and 15%) at four thermal conditions: 24∘C and 40∘C to span the in vivo range, and 70∘C and 24∘C repeated after 70∘C to explore mechanics during and after potential treatments. We calculated the bulk mechanical responses (strain-energy dissipation densities, peak-to-peak shear stresses, and peak-effective shear moduli) as of function of temperature and used statistical methods to probe significant differences. To probe the mechanisms underlying differences we assessed specimens, principally the type II collagen, with imaging (second harmonic generation and transmission electron microscopies, and histology) and assessed the temperature-dependent mechanics of type II collagen molecules within cartilage using steered molecular dynamics simulations. Our results suggest that the bulk mechanical responses of cartilage depend significantly on temperature both within the in vivo range and at supraphysiological temperatures, showing significant reductions in all mechanical measures with increasing temperature. Using imaging and simulations we determined that one underlying mechanism explaining our results may be changes in the molecular deformation profiles of collagen molecules versus temperature, likely compounded at larger length scales. These new insights into the mechanics of cartilage and collagen may suggest new treatment targets for damaged or osteoarthritic cartilage.
A Three-Level Isolated AC–DC PFC Power Converter Topology With a Reduced Number of Switches

The main objective of this research work is to develop a new low-cost isolated three-level ac–dc power converter topology with a reduced number of switches. Existing three-level converter topologies change ac power to dc power while maintaining requirements set by international standards for power conversion. These types of converters have significant conduction losses due to high currents in the low-voltage side and high costs, mainly when using several active devices in series or in parallel to achieve high-voltage and high-power levels. The proposed topology replaces the conventional three-level converters in the secondary side by only two controlled devices and four diodes while still maintaining the basic functionality of a three-level converter. Furthermore, simulation results for a 25-kW case study and experimental results on a 900-W scale-down prototype demonstrate the feasibility of the proposed ideas.
Psychic Stock: Retail Inventory for Stimulating Demand

The supply-side or demand-servicing functions of inventory are well-known in the inventory, logistics, and retailing literature.However, this literature has yet to develop the demand-stimulating function of inventory.This paper introduces the concept of psychic stock, which is defined as retail inventory for stimulating demand.Operationally, psychic stock is measured as total inventory on hand minus the sum of cycle stock and safety stock.The consumer behavior theory is drawn upon to offer possible explanations for the impact of psychic stock on sales.
Inhibitory corticotropin-releasing factor neurons in the dorsomedial prefrontal cortex promote stress-resilient behavior in male rodents

Adaptive behavior in response to adverse experiences facilitates faster recovery and less time spent engaging in maladaptive behaviors that contribute to psychopathology, including anxiety, depression, and posttraumatic stress disorder. Dysregulation of activity in the prefrontal cortex (PFC) has been implicated in these disorders, with stress further exacerbating these negative effects. Corticotropin-releasing factor is an important regulator of the stress-response system and may have a differential involvement in individuals who are especially susceptible to negative stress-related outcomes. A recent study by Chen et al. (Chen P, Lou S, Huang ZH, Wang Z, Shan QH, Wang Y, Yang Y, Li X, Gong H, Jin Y, Zhang Z, Zhou Z. Neuron 106: 301-315, 2020) has identified a novel subtype of GABAergic CRF interneurons in the dorsomedial PFC that, upon activation, can promote active responses and resilient behavior in response to stress.
Profiling the research productivity of tenured information systems faculty at U.S. Institutions

How many articles in highly rated journals do Information Systems research faculty publish to earn tenure? Which journals are highly rated outlets? Tenure candidates, promotion and tenure committees, and those who are asked to write external letters are frequently called upon to answer such questions. When Dennis et al. (2006) examined all IS Ph.D. graduates entering academic careers, few faculty had published enough articles in 20 "elite" journals in six years to meet tenure research expectations at research-intensive schools. Our study builds on the dialog started by Dennis et al. In our study, we counted the number of journal articles at the point of tenure for faculty who earned tenure within five to seven years after their Ph.D. graduation date. We also examined the effect of acknowledging different sets of journals as highly rated on the publication rates of faculty who earned tenure. Specifically, we examined the effects of expanding on Dennis et al. by including MIS Quarterly, Information Systems Research, Journal of Management Information Systems, Journal of the AIS, Information Systems Journal, European Journal of Information Systems, Journal of Information Technology, and Journal of Strategic Information Systems in the journal basket. We also looked at the effect of acknowledging highly rated non-IS business journals and highly rated computer science and engineering journals. Finally, we present journal publication benchmarks based on these findings for different types of research institutions.
Enzymatic Assemblies of Thiophosphopeptides Instantly Target Golgi Apparatus and Selectively Kill Cancer Cells

Changing an oxygen atom of the phosphoester bond in phosphopeptides by a sulfur atom enables instantly targeting Golgi apparatus (GA) and selectively killing cancer cells by enzymatic self-assembly. Specifically, conjugating cysteamine S-phosphate to the C-terminal of a self-assembling peptide generates a thiophosphopeptide. Being a substrate of alkaline phosphatase (ALP), the thiophosphopeptide undergoes rapid ALP-catalyzed dephosphorylation to form a thiopeptide that self-assembles. The thiophosphopeptide enters cells via caveolin-mediated endocytosis and macropinocytosis and instantly accumulates in GA because of dephosphorylation and formation of disulfide bonds in Golgi by themselves and with Golgi proteins. Moreover, the thiophosphopeptide potently and selectively inhibits cancer cells (HeLa) with the IC50 (about 3 μM), which is an order of magnitude more potent than that of the parent phosphopeptide.
Engineering the Interface between Inorganic Nanoparticles and Biological Systems through Ligand Design

Nanoparticles (NPs) provide multipurpose platforms for a wide range of biological applications. These applications are enabled through molecular design of surface coverages, modulating NP interactions with biosystems. In this review, we highlight approaches to functionalize nanoparticles with "small" organic ligands (Mw < 1000), providing insight into how organic synthesis can be used to engineer NPs for nanobiology and nanomedicine.
Time Evolution of Quantum Effects.

For quantum effects $a$ and $b$ we define the $a$-evolution of $b$ at time $t$ denoted by $b(t\mid a)$. We interpret $b(t\mid a)$ as the influence that $a$ has on $b$ at time $t$ when $a$ occurs, but is not measured at time $t=0$. Using $b(t\mid a)$ we define the time-dependent sequential product $a[t]b$. This is interpreted as an effect that results from first measuring $a$ and then measuring $b$ after a time delay $t$. Various properties of $a[t]b$ are derived and it is shown that $a[t]b$ is constant in time if and only if $a$ and $b$ commute or $a$ is a multiple of a projection. These concepts are extended to observables for a quantum system. The ideas are illustrated with some examples.
Programs and Machines

This chapter discusses another way of formalizing the concept of effective calculability, namely register-machine programs. The main aim is to show that all general recursive partial functions are also computable by register machines. It provides half of a significant fact that formalizing the effective calculability concept by means of general recursiveness and formalizing the effective calculability concept by means of register machines lead to exactly the same class of partial functions. The register machines are capable of doing much more than might have been apparent initially from their very simple definition. The methods used here to obtain the equivalence of general recursiveness to register-machine computability are adaptable to obtaining equivalence between other formalizations of effective calculability.
Unilateral Presentation of Adult-Type Polycystic Kidney Disease in Children

Adult polycystic kidney disease is characterized by autosomal dominant inheritance, diffuse bilateral cystic kidney disease and onset during the young adult years. Relatively few cases of adult-type polycystic kidney disease in children have been reported. We describe a 4-year-old girl who appeared to have multiple, unilateral simple renal cysts by excretory urography and ultrasonography. There was no known familial renal cystic disease. When renal histology was consistent with adult-type polycystic kidney disease, screening nephrosonograms revealed that the mother also had the disease. We review 10 published cases of unilateral presentation of adult-type polycystic kidney disease in children. This report emphasizes the necessity of screening studies in parents of children with diffuse unilateral or bilateral cystic renal disease. Awareness of the unexpected unilateral presentation of adult-type polycystic kidney disease in children may allow a nonoperative diagnosis to be made.
A longitudinal analysis of stress in African American youth: Predictors and outcomes of stress trajectories

Few researchers have studied trajectories of stress over time in relation to psychosocial outcomes and behaviors among adolescents. A sample of African American adolescents were assessed longitudinally on perceived stress, psychological well-being, support, antisocial behaviors, and academic success. Patterns of stress over 4 time points were developed using a cluster-analytic approach. Differences among the trajectory clusters were examined using psychosocial outcomes and behaviors. Adolescents with chronic levels of stress reported more anxiety and depression, engaged in antisocial behaviors, and reported less active coping than youth in other trajectories. Adolescents with low levels of stress over time reported fewer psychological problems, perceived more social support, and were more likely to graduate from high school than those with higher stress levels over time. We also found that an increase in stress coincided with a lack of support and more psychological problems over time.
Red Cross Society in Imperial China, 1904-1912: A Historical Analysis

The Red Cross Society was introduced to China in the 1900s, when the nation was under the authoritarian reign of Qing dynasty. Famines and rebellions, along with the invasion of foreign military forces, created tremendous humanitarian crises that the corrupted imperial government was incapable to address. The Red Cross model was found to be a pragmatic solution by Chinese philanthropists. Using archived press releases, correspondences, and government statements, the study reconstructs the founding process of the first Chinese Red Cross organization from 1904 to 1912. The analysis reveals that the organization reflected the congruent interest of the imperial court and social elites in preserving the sovereignty and was therefore promoted by key players from both political and civil spheres. The trajectory of Red Cross movement in imperial China supports the synergism perspective of institutional theories. It demonstrates how micro-level factors such as leadership ties and alliances contribute to the interdependence of public and private sectors and facilitate the transformation of traditional charity to modern philanthropy.
Responsiveness to melatonin and its receptor expression in the aging circadian clock of mice

This study determined the effect of age on the efficacy of melatonin treatment to phase shift circadian activity rhythms and on melatonin receptor expression in the suprachiasmatic nucleus (SCN) an...
Extracellular matrix elasticity and topography: Material‐based cues that affect cell function via conserved mechanisms

Chemical, mechanical, and topographic extracellular matrix (ECM) cues have been extensively studied for their influence on cell behavior. These ECM cues alter cell adhesion, cell shape, and cell migration and activate signal transduction pathways to influence gene expression, proliferation, and differentiation. ECM elasticity and topography, in particular, have emerged as material properties of intense focus based on strong evidence these physical cues can partially dictate stem cell differentiation. Cells generate forces to pull on their adhesive contacts, and these tractional forces appear to be a common element of cells' responses to both elasticity and topography. This review focuses on recently published work that links ECM topography and mechanics and their influence on differentiation and other cell behaviors. We also highlight signaling pathways typically implicated in mechanotransduction that are (or may be) shared by cells subjected to topographic cues. Finally, we conclude with a brief discussion of the potential implications of these commonalities for cell based therapies and biomaterial design.
A low-cost approach for testing embedded rf passive circuits based on oscillation principle

In this paper, a low-cost method for testing RF passive filters embedded in an RF substrate is proposed. As compared to a conventional test method the proposed method reduces the test-setup cost by around 35%. This method does not require any vector network analyzer (VNA) and allows the testing of embedded RF filters without any external test stimulus. A calibration technique is presented for an efficient implementation of the proposed method at the production floor. The core principle of the method is to include embedded passive filters through substrate surface probes into an external RF amplifier located on the probe card, such that this inclusion causes the RF amplifier to oscillate. RF filters are tested by measuring the changes in the oscillation frequency of the proposed test-setup. Hence, the test-setup cost reduces substantially. The test method with the calibration technique is demonstrated by simulations and measurements.
Geospatial Methods for Reducing Uncertainties in Environmental Health Risk Assessment: Challenges and Opportunities

As in many studies involving disparate data and methodologies, environmental health risk assessment research is prone to errors and uncertainties. Unfortunately, uncertainties associated with the r...
A note on the excitation of nerve pathways

LetS denote the intensity of a stimulus, ν the frequency of discharge of a fiber, and ν T the integral frequency of discharge of a nerve pathway. The relation between ν T andS can be derived when the relation between ν andS, as well as the distribution function of the fiber thresholds are given. It is investigated under what conditions the functions ν T (S) and ν(s) will be both of the same exponential form, and it is shown that this can happen only ifS exceeds the highest threshold of the pathway.
Visualization of a highly organized intranuclear network of filaments in living mammalian cells.

For 30 years, the mammalian cell nucleus has been hypothesized to contain a filamentous framework, the nuclear matrix or karyoskeleton, which regulates nuclear structure and function. However, such an organized network of filaments has never been observed in living cells. Here we show that human Cdc14B phosphatase in living cells tightly associates with long filaments that begin at the nucleolar periphery and extend to the nuclear envelope, frequently making close connections with nuclear pore complexes. We demonstrate that Cdc14B contains a bipartite signal that directs it to the intranuclear filaments, and we also detect a small amount of Cdc14B on interphase and mitotic centrosomes. Furthermore, we show that Cdc14B is critical for the maintenance of proper nuclear structure together with polo-like kinase Plk1. This work provides the first direct evidence for the existence of an intranuclear filamentous framework in living mammalian cells and implicates Cdc14B in the control of mammalian nuclear architecture. Cell Motil. Cytoskeleton 59:94–108, 2004. © 2004 Wiley-Liss, Inc.
Competency Is Not Guaranteed by the Letters That Follow Your Name: A Response to My Critics:

This article is a formal response to those that authored critiques of the author1's research. Each author has provided a thoughtful and critical perspective highlighting the perceived merits and demerits of the research questions posed, theoretical assumptions underlying the inquiry, study design and methodology, and interpretations garnered from summarized findings. In the end, no sound evidence was presented that refutes suggestions that the educational background of child welfare workers is a poor predictive variable of their performance. Regardless, taken together, the insights and criticisms of my colleagues provide other researchers with a foundation for better answering the questions the authors pose. These include questions about the efficacy of Title IV-E educational programs, what factors are predicative of competent child welfare practice, the means and mechanisms by which practice and worker competency is evaluated, and who has a right or privilege to receive specialized child welfare educatio...
Chronic prenatal ethanol exposure alters the normal ontogeny of choline acetyltransferase activity in the rat septohippocampal system.

In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown to be especially sensitive to the effects of prenatal ethanol exposure, exhibiting neuronal loss and alterations in neuritic process elaboration. We have characterized the influence of chronic prenatal ethanol treatment (CPET) on the postnatal expression of choline acetyltransferase (ChAT) In the hippocampus and the septal area that contains neurons that provide the primary cholinergic innervation to the hippocampus. On gestation days 1–22, pregnant rats were either fed an ethanol-containing liquid diet, pair-fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In Chow control animals, the ontogenetic progression of ChAT activity in the septal area and hippocampus was characterized by a significant period of upregulation during the 2nd and 3rd postnatal weeks, exhibiting an approximate 5-fold increase (septal area) and 7-fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure reduced septal and hippocampal ChAT activity levels, compared with those of pair-fed offspring. ChAT activity reached control levels by P21 in ethanol-exposed pups, suggesting that the earlier decline in activity may reflect a delay in the ontogenetic upregulation. In addition, there was a trend toward increased septal and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This liquid diet-stimulated increase may mask the effects of ethanol on early postnatal ChAT expression in the septohippocampal system. The results suggest that prenatal ethanol exposure may influence factors that regulate the developmental expression of ChAT in the septohippocampal system. In addition, we found a close relationship between the effects of CPET on litter birthweight and subsequent postnatal body and brain weight measures, but not between litter birthweight and ChAT activity from individual animals. This may imply that the influence of ethanol exposure on ChAT activity is independent of its effects on postnatal brain or body growth. Such an observation of neurochemical dysfunction in the absence of morphological indices frequently used to diagnose alcohol-related deficits could have potential clinical significance, both in the diagnostic and therapeutic realms.
Comparative disposition and biotransformation of naphthalene in fresh- and seawater-acclimated striped bass (Morone saxatilis).

1. The disposition and biotransformation of naphthalene in striped bass (Morone saxatilis) acclimated to either fresh- or seawater have been determined.2. The 24-h total concentration factor did not significantly differ between the freshwater (283 ± 7 ± 61 ± 5 [± SD]) and seawater (245 ± 5 ± 44 ± 4)-acclimated bass. At both salinities, the viscera/gonad and liver accumulated large concentrations of residues, whereas the skin retained the largest total residue mass.3. During the 24-h depuration period, the freshwater-acclimated bass depurated 45% of retained residue and the seawater-acclimated bass depurated 85% of retained residue.4. Naphthalene was primarily excreted unchanged (>99% in freshwater-acclimated bass and > 88% in seawater-acclimated bass), but small amounts of 1,2-dihydro-1,2-dihydroxynaphthalene and 1- and/or 2-naphthylsulphate were formed.
Do practicing clinicians agree with expert ratings of neonatal intensive care unit quality measures

Do practicing clinicians agree with expert ratings of neonatal intensive care unit quality measures?
Group Reminiscing Therapy with Elderly Clients

A co-led reminiscing time-limited group in a residential geriatric setting is described. Theory related to normal aging with its concomitant developmental tasks and its relationship to the progress...
Optical reflectance studies of conducting polymers on the metal-insulator boundary

Abstract Recent progress in the processing of polyaniline protonated with camphor sulfonic acid (PANI-CSA) and polypyrrole doped with PFg (PPy-PF 6 ) has provided opportunities to investigate the nature of the metallic state and associated metal-insulator (M-I) transition in conducting polymers. We present the reflectance spectra of such materials over a wide spectral range from 0.002 eV to 6eV, yielding a wealth of information on the electronic states near the Fermi Energy (E F ) and the electronic structure over a wide energy range. A quantitative analysis of spectra in terms of the localization modified Drude model leads to the conclusion that heavily doped conducting polymers are disordered metals near the M-I boundary. The optical spectra of such improved materials are compared with those obtained from conventionally prepared materials. While the structurally improved materials show distinct metallic signatures indicative of delocalized electronic states at E F , the optical spectra of the conventional materials indicate that the states near E F are localized due to severe disorder in the context of Anderson localization ( Fermi glass ). The two categories of samples show different charge dynamics in the far-infrared, consistent with theoretical predictions.
A consistent operator solution for the thirring model

The Thirring model is examined with the interacting currents redefined to be limits of non-local expressions, as proposed by Johnson. The most general solution to the new equation of motion is obtained as an operator functional of a canonical free field, its current, and the current of the interacting field. Since the latter also satisfies the free field wave equation, this is then an exploit solution for the interacting field operator. It is shown that this solution is completely consistent in the sense that the operator representative of a product is equal to the product of the operator representatives. The Hilbert space is defined, some renormalized matrix element are calculated, and the results are compared with those obtained using the conventional, inconsistent formalism, and with Johnson’s results.
Dynamics of the intermediate state in nonequilibrium superconductors

We report experimental measurements of the voltage response of current-biased superconducting thin films excited by 30-ps-FWHM (full width at half-maximum) pulsed laser radiation. Experiments performed with Pb and Sn films irradiated by a full train of laser pulses provide direct evidence for the existence of a nonstationary intermediate state. The state was observed during the superconducting-to-normal transition, as well as during the recovery of the film from the nonequilibrium normal state into the superconducting state. Single-pulse laser experiments enabled us to study the superconducting-to-normal transition in detail. Depending on the optical power, both triangular and quadruangular voltage pulses were observed. The triangular pulses had amplitudes dependent on the laser power and reflected the transition to the intermediate state, where superconducting and normal domains coexisted. The quadrangular pulses were associated with the full transition into the normal state. Very short triangular voltage pulses with full widths of the order of hundreds of picoseconds and rise times as short as about 100 ps were observed for thin Pb films illuminated by a low, near-threshold, laser power. The pulse rise time was almost constant and it only depended weakly on the film thickness, while the pulse width and the fall time were verymore » sensitive to the optical input power as well as other experimental conditions (e.g., film thickness, Pb-substrate interface). The pulse decay was determined to be linear. The linear decay reflects a geometric relaxation of the intermediate state. An experiment performed with a stretched laser pulse (about 470 ps FWHM) demonstrated an initial thresholding effect and indicated that the subsequent voltage is proportional to the time integral of the laser pulse (optical energy).« less
Free‐energy correlation for catalysis of outer sphere electron‐transfer reactions by noncoordinated pyridine derivatives

Recent experimental data concerning the rate constants and their free energy of the outer sphere electron-transfer reactions, as catalyzed by noncoordinated pyridine derivatives in aqueous solution, are examined for possible correlation. For the electron transfer reactions between V or Eu and the bipyridyl derivatives, such as N,N'-dimethyl-4,4′-bipyridyl (paraquat) or diquat, the data are correlated quite well by the Marcus equation. The electron exchange rate constant, 5 × 107M−1·s−1, for an organic radical ion and its parent molecule obtained from semiquinones or their related compounds can be applied to these pyridine derivatives. However, in some cases such as electron transfer from paraquat or diquat cation radical to Co(en), positive departures from the Marcus model are observed. These positive departures are interpreted in terms of interaction between the molecular orbitals of electron donors and electron acceptors in the transition state.
An In-Vivo Study of Normal Wrist Kinematics

The motion of the hand relative to a reference frame embedded in the radius is described using the screw displacement axis (SDA) concept. A three-dimensional sonic digitizer was utilized in a study of the dominant wrist of 15 normal subjects to determine the location and orientation of the SDAs based on the endpoints of flexion-extension motion (FEM) and radial-ulnar deviation (RUD) of the hand. The length of the common perpendicular between the SDAs of FEM and RUD was as large as 6 mm in some individuals; however, in some subjects the FEM SDA was distal of the RUD SDA while in others it was proximal. Considering the group of 15 subjects, the SDAs of FEM and RUD for the normal group nearly intersect in the head of the capitate in the neutrally positioned wrist and forearm.
Direct generation of acyclic polypropionate stereopolyads via double diastereo- and enantioselective iridium-catalyzed crotylation of 1,3-diols: beyond stepwise carbonyl addition in polyketide construction.

Under the conditions of transfer hydrogenation employing the cyclometalated iridium catalyst (R)-I derived from [Ir(cod)Cl]2, allyl acetate, 4-cyano-3-nitrobenzoic acid, and the chiral phosphine ligand (R)-SEGPHOS, α-methylallyl acetate engages 1,3-propanediol (1a) and 2-methyl-1,3-propanediol (1b) in double carbonyl crotylation from the alcohol oxidation level to deliver the C2-symmetric and pseudo-C2-symmetric stereopolyads 2a and 3a, respectively, with exceptional control of anti-diastereoselectivity and enantioselectivity. Notably, the polypropionate stereopentad 3a is formed predominantly as 1 of 16 possible stereoisomers. Desymmetrization of 3a is readily achieved upon iodoetherification to form pyran 4. The direct generation of 3a enables a dramatically simplified approach to previously prepared polypropionate substructures, as demonstrated by the synthesis of C19–C27 of rifamycin S (eight steps, originally prepared in 26 steps) and C19–C25 of scytophycin C (eight steps, originally prepared in 15 s...
The response criterion, the stimulus configuration, and the relationship between brightness contrast and brightness constancy*

Four experiments were designed to investigate the nature of the relationship between brightness contrast and brightness constancy while controlling the response criterion, the area of the surround, the stimulus configuration, and the mode of appearance of the modulus target. Ten Os in each of the four experiments estimated the apparent whiteness or brightness of targets with different contrast ratios. All targets were viewed at several illumination levels. Most constancy (whiteness and brightness) functions displayed shallow slopes that reflected a good approximation to constancy. The functions within Experiments I, III, and IV were vertically displaced and parallel; those in Experiment II were vertically displaced and increased in slope. This suggests that decreasing the contrast ratio had no effect on the tendency towards constancy when the area of the surround was greater than that of the target but resulted in a decrease in constancy when the area of the surround was equal to that of the target.
Presentation of Untreated Systemic Mastocytosis as Recurrent, Pulseless-Electrical-Activity Cardiac Arrests Resistant to Cardiac Pacemaker

Recurrent, pulseless-electrical-activity (PEA) cardiac arrests were the novel presentation of untreated systemic mastocytosis in an 85-year-old woman who lacked cutaneous findings of mastocytosis. Despite prior implantation of a dual-chamber cardiac pacemaker 3 weeks previously for similar spells, she experienced a PEA arrest accompanied by flushing, increased urinary N-methylhistamine excretion and serum tryptase values on the day of presentation to our clinic. Bone marrow biopsy findings conducted to rule out breast cancer metastases showed 30% mast cell infiltration, aberrant expression of CD25 and a positive c-kit Asp816Val mutation. Treatment with a combination of H1 and H2 receptor blockers reduced flushing and eliminated hypotension. Maintenance medication included aspirin, cetirizine, ranitidine, montelukast, oral cromolyn sodium and an epinephrine autoinjector (as needed). At 6-month follow-up, the patient remained free of PEA arrests, flushing, or any clinical signs of mastocytosis or mast cell degranulation. PEA cardiac arrests may therefore be a presenting sign of untreated systemic mastocytosis.
Vaccination with embryonic stem cells protects against lung cancer: is a broad-spectrum prophylactic vaccine against cancer possible?

The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC). Naive C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF) in order to provide immunostimulatory adjuvant activity. Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC). ESC-induced anti-tumor immunity was not due to a non-specific “allo-response” as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8+ T effector responses, Th1 cytokine response, higher intratumoral CD8+ T effector/CD4+CD25+Foxp3+ T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL) response because in vivo depletion of CD8+ T lymphocytes completely abrogated the protective effect of vaccination. Importantly, this vaccination strategy also suppressed the development of lung cancer induced by the combination of carcinogen administration and chronic pulmonary inflammation. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, perhaps more importantly, could represent a first step toward the development of prophylactic cancer vaccines.
The role of an active-site lysyl residue of spinach phosphoribulokinase as explored by site-directed mutagenesis.

Based on selective labeling by ATP analogues, Lys68 of the Calvin Cycle enzyme phosphoribulokinase (PRK) from spinach has been assigned to the active-site region [Miziorkoet al. (1990),J. Biol. Chem. 265, 3642–3647]. The equivalent position is occupied by lysyl or arginyl residues in the PRK from both prokaryotic and eukaryotic sources, suggesting a requirement for a basic residue at this location. To examine this possibility, we have replaced Lys68 of the spinach enzyme with arginyl, glutaminyl, alanyl, or glutamyl residues by site-directed mutagenesis. All of the mutant enzymes retain substantial kinase activity; and even in the case of the radical substitution by glutamate, theK m values for ATP and ribulose 5-phosphate are not perturbed significantly. Glutamate at position-68 may destabilize tertiary structure, because the yield of this mutant protein from transformedE. coli is quite low compared to that of the other proteins in this series. Despite the active-site proximity of Lys68, our results show that this residue does not play a key role in catalysis or substrate binding.
The Mood Stabilizers Valproic Acid and Lithium Enhance Mesenchymal Stem Cell Migration via Distinct Mechanisms

Mesenchymal stem cells (MSCs) show high potential for the therapy of several human diseases; however, the effectiveness of MSC transplantation has been hampered by the relatively poor migratory capacity of these cells toward disease target sites. This study investigated whether treatment of MSCs with two mood stabilizers—valproic acid (VPA) and lithium—would enhance cell migration and, if so, to explore the mechanisms underlying their effects. Short-term (3 h) exposure of MSCs to a relatively high concentration (2.5 mM) of VPA markedly increased the transcript and protein levels of CXC chemokine receptor 4 (CXCR4). VPA-induced CXCR4 expression required inhibition of histone deacetylases (HDACs), including the HDAC1 isoform, and involved histone hyperacetylation at the promoter region of the CXCR4 gene. Notably, VPA treatment enhanced stromal cell-derived factor-1α (SDF-1α)-mediated MSC migration, which was completely blocked by AMD3100, a CXCR4 antagonist. Treatment of MSCs with lithium (2.5 mM for 1 day) selectively elevated the transcript and protein levels of matrix metalloproteinase-9 (MMP-9) and its enzymatic activity; these effects were mimicked by inhibition or gene silencing of glycogen synthase kinase-3β (GSK-3β). Lithium treatment also potentiated SDF-1α-dependent MSC migration across the extracellular matrix, which was suppressed by two MMP-9 inhibitors, doxycycline and GM6001. Combining VPA and lithium treatment further increased MSC migration. Overall, VPA and lithium stimulated MSC migration through distinct targets and mediators: HDAC-CXCR4 and GSK-3β-MMP-9, respectively.