cssi/SciSciGPT-SciSciNet huggingface dataset:
Medieval Russia, 980–1584: Ivan IV the Terrible

During the century preceding the reign of Ivan IV, the Muscovite princes had overseen an expansion of their territories, the development of political institutions to administer them, and the formation of a military organization to defend them. They had nurtured economic activities and molded social structures to support and operate their political and military establishments. They had, furthermore, exploited images and ideologies, expressed in a variety of cultural genres for purely ecclesiastical reasons or even to delimit princely authority, to legitimize and justify these developments. The result was that by the end of Vasily III's reign a centralized political structure had evolved in Muscovy. At its core was the dynasty. But it too had evolved so that the figure of the grand prince, followed by his eldest son and heir, assumed prominence over even his closest relatives. Although the latter princes remained politically significant as secondary heirs, they were steadily pushed to the periphery of the political structure, leaving the grand prince alone at its center. The grand prince was surrounded and assisted by members of other elite families, his highest-ranking courtiers. Administrative officials conducted the business of state and, more remotely, lower ranks of Moscow and provincial servicemen provided the personnel for civil and military posts. With this apparatus the grand princes had gradually tightened their control over key elements, such as the military, tax collection, and the judicial systems, which were essential to the establishment and maintenance of their authority in all areas of their expanding realm.
A Mixture of Wisharts (MOW) Model for Multifiber Reconstruction

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a noninvasive imaging technique that allows neural tissue architecture to be probed at a microscopic scale in vivo. By producing quantitative data on the motion of water molecules that naturally occurs in brain tissues as part of the physical diffusion process, DW-MRI can be used to map the fiber paths in the brain white matter. Estimating the local complex architecture in the presence of intra-voxel heterogeneity caused by multiple fiber pathways is of great importance and requires sophisticated modeling techniques.
Nuclear mechanical resilience but not stiffness is modulated by αII-spectrin

Spectrins are multi-domain, elastic proteins that provide elasticity to the plasma membrane of erythrocytes and select nucleated cells. Spectrins have also been found in the nucleus of non-erythrocytes, but their function remains to be uncovered. It has been hypothesized that a spring-like spectrin network exists within the lamina nucleoskeleton, however, experiments testing a spectrin network׳s mechanical impact on the nucleus are lacking. Here, we knock-down levels of nuclear αII-spectrin with the goal of disrupting this nucleoskeletal spectrin network. We mechanically test live cells with intranuclear particle tracking and compression assays to probe changes in nuclear mechanics with decreases in αII-spectrin. We show no changes in chromatin mechanics or in the stiffness of nuclei under compression. However, we do observe a reduction in the ability of nuclei with decreased αII-spectrin to recover after compression. These results establish spectrin as a nucleoskeletal component that specifically contributes to elastic recovery after compression.
The price of uncertainty in communication

We consider the problem of one-way communication when the recipient does not know exactly the distribution that the messages are drawn from, but has a “prior” distribution that is known to be close to the source distribution, a problem first considered by Juba et al. [5]. This problem generalizes the classical source coding problem in information theory, in which the receiver knows the source distribution exactly, that was first considered in Shannon's work [6]. This “uncertain priors” coding problem was intended to illuminate aspects of natural language communication, and has applications to adaptive compression schemes. We consider the question of how much longer the messages need to be in order to cope with the uncertainty that the sender and receiver have about the receiver's prior and the source distribution, respectively, as compared to the source coding problem. We obtain lower bounds for one-way communication using uncertain priors that are tight up to low-order terms. Specifically, we consider two variants of the uncertain priors problem. First, we consider the original setting of Juba et al. [5] in which the receiver is required to correctly recover the message with probability 1. We find that in this setting, the overhead of 2 log α + O(1) bits achieved by that scheme when the prior is α-close to the source is optimal up to an additive O(log log α) bits. We also consider a setting introduced in the work of Haramaty and Sudan [3], in which the receiver is permitted to fail to recover the message with some positive probability ϵ. In this setting, we find that the optimal overhead is essentially log α + log 1/ϵ bits by presenting both a variant of the coding scheme of Juba et al. with an overhead of log α+log 1/ϵ+1 bits, and a lower bound that matches up to an additive O(log log α) bits. Our lower bounds are obtained by observing that a worst-case, one-way communication complexity problem can be embedded in the sources and priors that any any uncertain priors coding scheme must address.
NIMG-11RADIOMIC SUBCLASSIFICATION OF GLIOBLASTOMA

BACKGROUND: To identify clinically relevant glioblastoma (GBM) sub-classification/subtypes based on radiomic analysis. Integrated genomic analysis has already identified genomic subtypes of GBM as characterized by specific genomic aberrations and mutations. In our study, we seek to demonstrate a GBM sub-classification based on radiomic texture analysis that is both predictive and prognostic. METHODS: We retrospectively identified 80 GBM treatment naive patients from the Cancer Genome Atlas with corresponding MRI data in the Cancer Imaging Archive. We applied texture analysis (528 features) to each tumor. We extracted texture features and performed feature selection. Univariate and multivariate analysis were also performed. Clustering identified radiomic subclasses. RESULTS: Multiple texture features were associated with GBM and we were able to classify GBM into 4 subtypes. However, subclassification into 3 subclasses were associated with differences in patient progression free and overall survival. CONCLUSIONS: GBM subtypes based on radiomic texture signatures were identified that were both predictive and prognostic. These findings are important as this can help determine patient outcome based on imaging (obtained at the time of diagnosis before treatment); this can also help determine response to therapy at the pre-treatment stage to stratify patients and serve as imaging endpoints for clinical trials.
Breakdown of a Hybrid Swarm between Two Darters (Percidae), Etheostoma radiosum and Etheostoma spectabile, with Loss of One Parental Species

A local hybrid swarm between Etheostoma radiosum and Etheostoma spectabile, found in June 1985 in a short reach of Little Glasses Creek, southern Oklahoma, consisted by eye of 35% phenotypic E. radiosum, 18% phenotypic E. spectabile, and 47% hybrids. In July 1985, investigation of an additional longer reach downstream of the initial discovery site showed that hybrids also were present there, although fewer. Thus, in 1985 both parental species, and substantial numbers of hybrids, were present in approximately a 300 m reach of the stream. No further collections were made until 2003, when sampling in the former hybrid reach and substantially further downstream showed E. radiosum to be the only species of Etheostoma present, and neither E. spectabile nor hybrids (by eye) were detected. From 2003 to 2013 the reach was surveyed 11 times, with a total of 363 darters identified phenotypically as E. radiosum, and none as E. spectabile or hybrids. Of 20 individuals sampled in December 2011 for molecular analyses, 1...
Inducible and conditional transgenic mouse models of schizophrenia

Schizophrenia is a devastating disorder. Despite the advance in research techniques in the last couple of decades, the pathogenesis of the disorder still remains poorly understood. Given the lack of pathognomonic feature of the disease and difficulty to analyze molecular pathways in patients, animal models have been instrumental in advancing our understanding of the disease. Recent progress in genetics has identified candidate susceptibility genes for schizophrenia, and generation of new genetic animal models has begun to provide valuable insights into the disease development. However, the complex neurodevelopmental and heterogeneous nature of schizophrenia still poses tremendous challenges for creating credible mouse models. In this review, we will discuss how current genetic systems of temporal and conditional regulation of gene expression have shed lights on the functions of the candidate genes in mouse models of schizophrenia. We also consider the strength and weaknesses of each model. We will argue that further development of more sophisticated genetic animal models is crucial for clarifying the unknowns of schizophrenia.
Increasing Severity of Malnutrition Is Associated With Poorer 30-Day Outcomes in Patients Undergoing Hip Fracture Surgery.

OBJECTIVES Low serum albumin levels (hypoalbuminemia) have classically been used to identify malnutrition. The effect of increasing severity of malnutrition on postoperative outcomes in patients undergoing hip fracture surgery has not been well delineated on a large scale. DESIGN Retrospective. SETTING Multicenter. PATIENT/PARTICIPANTS A total of 12,373 patients undergoing hip fracture surgery from 2006 to 2013 National Surgery Quality Improvement Project data were identified. INTERVENTION Patient demographic, comorbidity, and preoperative laboratory data and complication, reoperation, and readmission data were collected. MAIN OUTCOME MEASUREMENTS Multivariate logistic regression was used to determine the effect of increasing severity of malnutrition on rates of 30-day postoperative complications, readmissions, and reoperations. RESULTS A total of 12,373 hip fractures met inclusion criteria. A total of 6506 (52.6%) patients had normal albumin levels (albumin ≥3.5 g/dL), 3205 (25.9%) patients were mildly malnourished (albumin 3.1-3.49 g/dL), 2265 (18.3%) were moderately malnourished (albumin 2.4-3.1 g/dL), and 397 (3.2%) patients were severely malnourished (albumin <2.4 g/dL). Mean age was similar between the 4 cohorts (P < 0.001). Severe malnutrition was associated with a 2-fold increase in the odds of postoperative complications and mortality when compared with mild malnutrition (P < 0.001). Increasing severity of malnutrition was associated with significantly longer lengths of stay and higher odds of experiencing a related readmission (P < 0.001). CONCLUSIONS Increasing severity of hypoalbuminemia is independently associated with poorer outcomes in the 30 days after hip fracture surgery. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Vitamin A, retinoids and breast cancer

Epidemiological investigations have indicated an inverse relationship between vitamin A intake and risk for developing cancer, and over the past several years an extensive effort has been directed towards understanding the mechanism by which vitamin A and retinoids (analogs of vitamin A) inhibit carcinogenesis.1,2
Moral dialogs and public opinion research

Abstract Etzioni’s article is thought provoking, and contains a series of arguments that would be useful lines of inquiry for scholars of public opinion. In many ways, these ideas link to, and can enrich existing areas of research on opinion formation, opinion change, and political behavior more broadly. Specifically, the elite vs. mass nature of these dialogs, the extent to which they are actual political discussions, and the impact of polarization on them are avenues where these ideas can inform broader understandings of public opinion, and vice versa. Etzioni’s arguments about the role of morals in political discussion and as agents of opinion change warrant further inquiry.
Panel Discussion: Management of Stages A1 and A2 Disease

Regarding Stage A prostatic cancer, there seem to be three principle concerns and I hope that as we hear more from our discussants some of these problems will be illuminated.
Hepatitis D Virus Infection: Role of Hepatitis B and the Current Updates on Management

Hepatitis D virus (HDV) discovery was linked to hepatitis B virus (HBV), where it was named as delta antigen and thereafter found to be the smallest RNA virus but a genome by itself depending of hepatitis B in its life cycle. It uses hepatitis B surface antigen as envelope and uses similar mechanism to enter the hepatocyte. Once inside the hepatocyte, it uses the host cell enzymes to replicate. HDV has eight genotypes with variation in geographic location and clinical severity. Also, certain HBV genotypes are linked with higher viral load and lower remission rates. Chronic hepatitis D (CHD) can result from either coinfection or superinfection of HBV, the latter associated with higher rate of progression to CHD. Pegylated interferon has been the mainstay treatment for CHD for many years with discouraging virological response around 25%. Recent trails of new medications including myrcludex B, lonafarnib, and nucleic acid polymers show some promising results awaiting further larger trials.
The Molecular Pathogenesis of Dupuytren Disease: Review of the Literature and Suggested New Approaches to Treatment.

Background Ever since the classification of Dupuytren disease into the proliferative, involutional, and residual stages, extensive research has been performed to uncover the molecular underpinnings of the disease and develop better treatment modalities for patients. The aim of this article is to systematically review the basic science literature pertaining to Dupuytren disease and suggest a new approach to treatment. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using the MEDLINE database to identify basic science literature on Dupuytren pathophysiology falling under 1 or more of the following categories: (1) Molecular alterations, (2) Structural alterations, and (3) Genetic predisposition. Results A total of 177 articles were reviewed of which 77 studies met inclusion criteria. Articles were categorized into respective sections outlined in the study methods. Conclusion The pathophysiological changes involved in Dupuytren's disease can be divided into a number of molecular and structural alterations with genetic predisposition playing a contributory role. Understanding these changes can allow for the development of biologics which may disrupt and halt the disease process.
An Accurate and Robust Algorithm for Performance Evaluation of Exponential Serial Lines with Finite Buffers

Calculation of performance metrics as functions of machine and buffer parameters is one of the most important problems in production system research. In this paper, we study serial production lines with finite buffers and machines following the exponential reliability model. While such systems are characterized by continuous-time Markov processes, exact analysis is all but impossible due to high state space dimensionality. To overcome this problem, a recursive aggregation-based algorithm is proposed by representing a multi-machine line by a number of two-machine lines. Numerical experiments are used to justify the convergence of the algorithm and to evaluate the accuracy of the calculated performance metrics. The results show that the proposed algorithm significantly improve the approximation accuracy, compared to two commonly used aggregation-based methods in the literature.
Exploring the impact of connected and autonomous vehicles on freeway capacity using a revised Intelligent Driver Model

ABSTRACTConnected and autonomous vehicle (CAV) technologies are expected to change driving/vehicle behavior on freeways. This study investigates the impact of CAVs on freeway capacity using a micro...
The Queen and Her Royal Court: A Content Analysis of Doing Gender at a Tulip Queen Pageant

Evidence indicates that privilege is made and reproduced in the family. There, however, has been little investigation in the field of beauty pageantry and how pageant winners represent themselves and their community. Using content analysis, this study aims to better understand how privilege is reproduced for girls who are on royal court and how the girls represent themselves in media interviews. Findings show that the girls on royal court presented themselves in media interview as having common traits and discourses about the community. The texts show the girls to have a common lifelong aspiration for being on royal court, having parents with similar employment status and occupational positions, similar involvement in extra-curricular and co-curricular activities, common aspirations to earn a college degree, and a common religious identity. As a qualitative study, the findings from this study are not intended to be generalizable, but to be transferable and extendable to future research on class reproduction and gender performance.
E-235 Use of 45 mg twice daily ticagrelor with 81 mg aspirin for endovascular treatment of unruptured intracranial aneurysms: a single center experience

Introduction Stent assisted coiling (SAC) and Flow diverter (FD) placement are commonly used techniques for the treatment of unruptured intracranial aneurysms (UIA). Stents and FDs require dual antiplatelet therapy (DAPT ) to prevent in-stent thrombosis. The selection of medications is mainly operator dependent. Cardiovascular literature suggests that the use of Aspirin 81 mg in conjunction with low dose Ticagrelor (45 mg twice daily) is superior than the use of Clopidogrel 75 mg and Aspiring 325 mg. Methods We performed a retrospective chart review of patients who underwent treatment of UIA at our institution using SAC or FD from 2016–2019. The patients who are on anticoagulation or did not have a pre-procedure P2Y12 inhibition assay were excluded. The patient group receiving Brilinta 45 mg twice daily with aspirin 81 mg daily (Group 1) was compared with the patient group receiving Plavix 75 mg daily with aspirin 325 mg daily (Group 2). The primary outcome was defined as intraoperative or acute (during hospitalization) postoperative stroke. Secondary outcomes included ischemic stroke after discharge within one year from treatment, and differences in P2Y12 inhibition assay values between the two groups. Results A total of 111 patients were identified that met the inclusion criteria, 42 (37.8%) in Group 1, and 69 in Group 2 (62.2%) protocol. There was no significant difference in the primary outcome between the two groups; Group 1, (2 patients,4.7%), and Group 2 (1 patient,1.4%) (p=0.11). All the primary end point events in both groups were related to FD. Clinically significant ischemic stroke after discharge within one year was also not significantly different (2 patients (4.7%) in Group 1 Vs. 3 patients (4.3%) in Group 2, p=0.277). The P2Y12 inhibition assay level was significantly lower in Group 1, when compared to Group 2 (71.6 Vs 94.8, p=0.027). There was no significant difference in the number of patients achieving a therapeutic value for the P2Y12 inhibition assay value ( Conclusion Lower preoperative P2Y12 assay values from the use of 45 mg twice daily Ticagrelor with 81 mg Aspirin for treatment of UIAs with SAC or FD placement did not result in decreased rates of perioperative stroke or delayed stroke rates within 1 year of surgery when compared to the well established use of Clopidogrel 75 mg and Aspirin 325 mg. Disclosures T. Mehta: None. K. Masood: None. M. Ghannnam: None. A. Grande: None. R. Tummala: None. B. Jagadeesan: None.
The idiosyncrasies of everyday digital lives: Using the Human Screenome Project to study user behavior on smartphones

Most methods used to make theory-relevant observations of technology use rely on self-report or application logging data where individuals' digital experiences are purposively summarized into aggregates meant to describe how the average individual engages with broadly defined segments of content. This aggregation and averaging masks heterogeneity in how and when individuals actually engage with their technology. In this study, we use screenshots (N > 6 million) collected every five seconds that were sequenced and processed using text and image extraction tools into content-, context-, and temporally-informative "screenomes" from 132 smartphone users over several weeks to examine individuals' digital experiences. Analyses of screenomes highlight extreme between-person and within-person heterogeneity in how individuals switch among and titrate their engagement with different content. Our simple quantifications of textual and graphical content and flow throughout the day illustrate the value screenomes have for the study of individuals' smartphone use and the cognitive and psychological processes that drive use. We demonstrate how temporal, textual, graphical, and topical features of people's smartphone screens can lay the foundation for expanding the Human Screenome Project with full-scale mining that will inform researchers' knowledge of digital life.
A Screen for Small Molecules to Target Candida albicans Biofilms

The human fungal pathogen Candida albicans can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 "drug-like" small molecules and identified 45 compounds that inhibited biofilm formation. These 45 compounds were then tested for their abilities to disrupt mature biofilms and for combinatorial interactions with fluconazole, amphotericin B, and caspofungin, the three antifungal drugs most commonly prescribed to treat Candida infections. In the end, we identified one compound that moderately disrupted biofilm formation on its own and four compounds that moderately inhibited biofilm formation and/or moderately disrupted mature biofilms only in combination with either caspofungin or fluconazole. No combinatorial interactions were observed between the compounds and amphotericin B. As members of a diversity library, the identified compounds contain "drug-like" chemical backbones, thus even seemingly "weak hits" could represent promising chemical starting points for the development and the optimization of new classes of therapeutics designed to target Candida biofilms.
Cosmological Advection Flows in the Presence of Primordial Black Holes as Dark Matter and Formation of First Sources.

In the inflation-based cosmology the dark matter (DM) density component starts moving with respect to the universal expansion at ${z}_{\mathrm{eq}}\ensuremath{\sim}3200$ while baryons remain frozen until ${z}_{\mathrm{rec}}\ensuremath{\sim}1100$. It has been suggested that in this case postlinear corrections to the evolution of small fluctuations would result, for the standard $\mathrm{\ensuremath{\Lambda}}$-dominated cold DM (CDM) model, in delayed formation of early objects as supersonic advection flows develop after recombination, so baryons are not immediately captured by the DM gravity on small scales. We develop the hydrodynamical description of such two-component advection and show that, in the supersonic regime, the advection within irrotational fluids is governed by the gradient of the difference of the kinetic energies of the two (DM and baryonic here) components. We then apply this formalism to the case where DM is made up of LIGO-type black holes (BHs) and show that there the advection process on scales relevant for early structure collapse will differ significantly from the earlier discussed (CDM) case because of the additional granulation component to the density field produced during inflation. The advection here will lead efficiently to the common motion of the DM and baryon components on scales relevant for collapse and formation of first luminous sources. This leads to early collapse, making it easier to explain the existence of supermassive BHs observed in quasars at high $zg7$. The resultant net advection rate reaches minimum around $\ensuremath{\lesssim}{10}^{9}\text{ }\text{ }{M}_{\ensuremath{\bigodot}}$ and subsequently rises to a secondary maximum near the typical mass of $\ensuremath{\sim}{10}^{12}\text{ }\text{ }{M}_{\ensuremath{\bigodot}}$, which may be an important consideration for formation of galaxies at $z\ensuremath{\lesssim}(a\text{ }\mathrm{few})$.
The hierarchical construction of value

Here we argue that the assignment of subjective value to potential outcomes at the time of decision-making is an active process, in which individual features of a potential outcome of varying degrees of abstraction are represented hierarchically and integrated in a weighted fashion to produce an overall value judgment. We implicate the lateral orbital and medial prefrontal cortex in this function, situating these areas more broadly within a hierarchical integration process that takes place throughout the cortex for the ultimate purpose of valuing options to guide decisions.
Evidence for recent climate change and carbon dioxide influence on plant based aero-allergens in the Northern Hemisphere

BACKGROUND AND AIM: Recent and projected assessments of climate change and carbon dioxide may influence plant based aero-allergen characteristics related to pollen load and pollen seasonality METHO...
Thermodynamics of alpha-chymotrypsin-inhibitor complex formation. Effects of structural modification of the inhibitor.

Abstract Temperature dependence studies, at a slightly acid pH, on the competitive water analogue inhibitors of α-chymotrypsin show that complex formation is independent of temperature and that binding is primarily entropy-driven. The inhibitors of this type studied here were tertiary amyl alcohol and 3-pentanone. In addition, studies on another class of inhibitor are presented. These competitive inhibitors consist of a benzene ring with different functional groups attached. The compounds are benzene, toluene, benzyl alcohol, benzaldehyde, and benzoate ion. Such inhibitors are similar to the substrate methyl hippurate in that the ΔH0 values for complex formation are quite negative while ΔS0 values may range from slightly positive to quite negative. Compounds of this type give rise to very large negative values for the change in heat capacity, ΔCp, for the complex-forming step, suggesting that considerable conformational change takes place in the enzyme during the process. This is in striking contrast to the first mentioned water analogue inhibitors where ΔCp is equal to zero. In addition it is shown that ΔCp for the formation of the ES complex from diethylglutarate which does not contain an aromatic nucleus is also very close to zero; this implies that the proposed conformational change brought about by the aromatic substrates and inhibitors does not take place in the absence of an aromatic ring, and suggests that a charge transfer complex may be involved in triggering the aforementioned conformational change. Examples are produced to show that comparison of association constants at a single temperature can be very misleading. Evidence is presented which indicates that there is no charge neutralization when complex formation with an anion such as benzoate takes place, but that there is a truly enormous change in heat capacity. It is suggested that the aliphatic alcohol and ketone may well bind at a slightly different site or portion of the enzyme than that with which the aromatic inhibitors combine. It is further proposed that both of these sites may be used to help bind a substrate such as methyl hippurate by means of a two-point hydrophobic attachment. The hydrophobic binding of the aromatic portion of the substrate molecule is probably exothermic, while the binding of the aliphatic portion of the alcohol component may not make a significant contribution to the enthalpy change. The ratio of inhibitor to enzyme in the enzyme-inhibitor complex is unity for all types of inhibitors studied.
Identification of quantitative trait loci controlling sucrose content in soybean (Glycine max)

Sucrose is a primary constituent of soybean (Glycine max) seed; however, little information concerning the inheritance of seed sucrose in soybean is available. The objective of this research was to use molecular markers to identify genomic regions significantly associated with quantitative trait loci (QTL) controlling sucrose content in a segregating F2 population. DNA samples from 149 F2 individuals were analyzed with 178 polymorphic genetic markers, including RFLPs, SSRs, and RAPDs. Sucrose content was measured on seed harvested from each of 149 F2:3 lines from replicated field experiments in 1993 and 1995. Seventeen marker loci, mapping to seven different genomic regions, were significantly associated with sucrose variation at P<0.01. Individually, these markers explained from 6.1% to 12.4% of the total phenotypic variation for sucrose content in this population. In a combined analysis these genomic regions; explained 53% of total variation for sucrose content. No significant evidence of epistasis among QTLs was observed. Comparison of our QTL mapping results for sucrose content and those previously reported for protein and oil content (the other major seed constituents in soybean), suggests that seed quality traits are inherited as clusters of linked loci or that `major' QTLs with pleiotropic effects may control all three traits. Of the seven genomic regions having significant effects on sucrose content, three were associated with significant variation for protein content and three were significantly associated with oil content.
Glucose phosphorylation. Site-directed mutations which impair the catalytic function of hexokinase.

Recent studies from this and other laboratories have resulted in the cloning and sequencing of hexokinases from a variety of tissues including yeast, human kidney, rat brain, rat liver, and mouse hepatoma. Significantly, studies on the hepatoma enzyme conducted in this laboratory (Arora, K.K., Fanciulli, M., and Pedersen, P.L. (1990) J. Biol. Chem. 265, 6481-6488) resulted also in its overexpression in Escherichia coli in active form. We have now used site-directed mutagenesis for the first time in studies of hexokinase to evaluate the role of amino acid residues predicted to interact with either glucose or ATP. Four amino acid residues (Ser-603, Asp-657, Glu-708, and Glu-742) believed to interact with glucose were mutated to alanine or glycine, whereas a lysine residue (Lys-558) thought to be directly involved in binding ATP was mutated to either methionine or arginine. Of all the mutations in residues believed to interact with glucose, the Asp-657----Ala mutation is the most profound, reducing the hexokinase activity to a level less than 1% of the wild type. The relative Vmax values for Ser-603----Ala, Glu-708----Ala, and Glu-742----Ala enzymes are 6, 10, and 6.5%, respectively, of the wild-type enzyme. Glu-708 and Glu-742 mutations increase the apparent Km for glucose 50- and 14-fold, respectively, while the Ser-603----Ala mutation decreases the apparent Km for glucose 5-fold. At the putative ATP binding site, the relative Vmax for Lys-558----Arg and Lys-558----Met enzymes are 70 and 29%, respectively, of the wild-type enzyme with no changes in the apparent Km for glucose. No changes were observed in the apparent Km for ATP with any mutation. These results support the view that all 4 residues predicted to interact with glucose from earlier x-ray studies may play a role in binding and/or catalysis. The Asp-657 and Ser-603 residues may be involved in both, while Glu-708 and Glu-742 clearly contribute to binding but are not essential for catalysis. In contrast, Lys-558 appears to be essential neither for binding nor catalysis.
Thermodynamics of A:G Mismatch Poly(dG) Synthesis by Human Immunodeficiency Virus 1 Reverse Transcriptase*

Human immunodeficiency virus 1 (HIV-1) reverse transcriptase has been found to conduct error-prone synthesis on DNA and RNA templates. We find here that tolerance of an A:G mispair with poly(rA) as template is particularly strong, such that extensive poly(dG) synthesis is conducted. This type of extensive misincorporation is not observed with several reference DNA polymerases. Surprisingly, HIV reverse transcriptase processivity and kcat for dGMP misincorporation and normal dTMP incorporation are about the same. However, the Km value for dGTP in poly(dG) synthesis is approximately 1000-fold higher than the Km for dTTP in poly(dT) synthesis. Comparison of thermodynamic parameters for dGMP misincorporation and normal dNMP incorporation indicates a lower energy of activation for dGMP misincorporation than for normal dNMP incorporation. Entropy of activation (delta S*) for normal dTMP incorporation is positive (approximately 10 cal/kmol), whereas delta S* for dGMP misincorporation is negative (-36 cal/kmol). Since differences in delta S* are usually considered to reflect differences in solvation for the transition state complex, these results are consistent with the interpretation that the active site of HIV reverse transcriptase is flexible enough to misincorporate dGMP without the usual dispersion of water molecules.
Identifying conflicts in overconstrained temporal problems

We describe a strong connection between maximally satisfiable and minimally unsatisfiable subsets of constraint systems. Using this relationship, we develop a two-phase algorithm, employing powerful constraint satisfaction techniques, for the identification of conflicting sets of constraints in infeasible constraint systems. We apply this technique to overconstrained instances of the Disjunctive Temporal Problem (DTP), an expressive form of temporal constraint satisfaction problems. Using randomly-generated benchmarks, we provide experimental results that demonstrate how the algorithm scales with problem size and constraint density.
The Palomar Supernova Search

The Palomar Supernova Search was initiated by F. Zwicky when the 18-in. Schmidt Telescope was put into operation in 1936. At that time only 20 supernovae had been discovered worldwide since 1885 when the first supernova of modern times was found in M31. The introduction of the 18-in. Schmidt lead to a rapid increase in the rate of discovery; a particularly notable event was Zwicky’s discovery of the SN 1937c in IC 4182 which led to Baade and Minkowski’s delineation of the evolution of the spectrum and light curve characteristic of a type I supernova.
Combined effects of climate change and bank stabilization on shallow water habitats of chinook salmon.

Significant challenges remain in the ability to estimate habitat change under the combined effects of natural variability, climate change, and human activity. We examined anticipated effects on shallow water over low-sloped beaches to these combined effects in the lower Willamette River, Oregon, an area highly altered by development. A proposal to stabilize some shoreline with large rocks (riprap) would alter shallow water areas, an important habitat for threatened Chinook salmon (Oncorhynchus tshawytscha), and would be subject to U.S. Endangered Species Act-mandated oversight. In the mainstem, subyearling Chinook salmon appear to preferentially occupy these areas, which fluctuate with river stages. We estimated effects with a geospatial model and projections of future river flows. Recent (1999-2009) median river stages during peak subyearling occupancy (April-June) maximized beach shallow water area in the lower mainstem. Upstream shallow water area was maximized at lower river stages than have occurred recently. Higher river stages in April-June, resulting from increased flows predicted for the 2080s, decreased beach shallow water area 17-32%. On the basis of projected 2080s flows, more than 15% of beach shallow water area was displaced by the riprap. Beach shallow water area lost to riprap represented up to 1.6% of the total from the mouth to 12.9 km upstream. Reductions in shallow water area could restrict salmon feeding, resting, and refuge from predators and potentially reduce opportunities for the expression of the full range of life-history strategies. Although climate change analyses provided useful information, detailed analyses are prohibitive at the project scale for the multitude of small projects reviewed annually. The benefits of our approach to resource managers include a wider geographic context for reviewing similar small projects in concert with climate change, an approach to analyze cumulative effects of similar actions, and estimation of the actions' long-term effects.
Cost effectiveness and health sector reform

The World Bank's 1993 World Development Report (WDR): Investing in Health makes extensive use of the concept the global burden of disease to measure the state of health of a population and, together with the related concept of cost-effectiveness, to judge which interventions to improve health deserve the highest priority for public action. These criteria are not always understood, in part because of uncertainty over their meaning and in part because they may appear to conflict with other criteria which are widely accepted in the health sector. By focusing on six questions, this paper seeks to clarify WDR has to say on the subject, and to illustrate how these ideas are relevant to health care reform.
Faculty development in tobacco cessation: training health professionals and promoting tobacco control in developing countries.

Issues. Cessation programs are essential components of comprehensive tobacco control. Health-care providers, especially physicians, have major responsibility for role modeling and promoting cessation. For successful, sustainable cessation training programs, countries need health-care professionals with knowledge and skills to deliver and teach tobacco cessation. Approach. Review literature relevant to faculty development in tobacco cessation and discuss its strategic potential in tobacco control. Key Findings. Faculty development is essential for sustainable tobacco cessation training programs, and a potentially powerful strategy to shift professional and societal norms towards cessation and support of comprehensive tobacco control in countries with normative tobacco use and underdeveloped tobacco control programs. Implications. Medical faculty are in a key position to influence tobacco cessation and control programs because of their roles as educators and researchers, receptivity to innovation and, influence on competencies and standards for medical education and practice. Faculty development programs must consider the number and type of faculty, and tobacco cessation curricula needed. Faculty development fosters the ability to institutionalise cessation education for students and community practitioners. Academic faculty are often leaders in their professional disciplines, influential in establishing clinical practice standards, and technical experts for government and other key health organisations. Conclusion. Training health-care professional faculty to become knowledgeable and committed to tobacco cessation opens opportunities to promote cessation and shift professional and societal norms away from tobacco use. [Muramoto ML, Lando H. Faculty development in tobacco cessation: Training health professionals and promoting tobacco control in developing countries. Drug Alcohol Rev 2009;28:498–506]
Comparison of plasma FSH concentration in boars and gilts from lines selected for ovulation rate and embryonal survival, and litter size and estimation of (co)variance components for FSH and ovulation rate.

The objective of this research was to determine whether plasma concentration of FSH was genetically correlated with ovulation rate and thus was a useful trait for indirect selection. Blood samples were collected from 619 animals from five lines of pigs. Line I was selected for increased index of ovulation rate and embryonal survival, and Line C was its randomly selected control. Pigs sampled from Lines I and C were from generations 12 and 13. Pigs from three additional lines that were derived from eighth-generation pigs of Lines I and C also were used. These lines were Line C2, a randomly selected control derived from Line C, Line COL, derived from Line C, and Line IOL, derived from Line I; each of these lines was selected an additional five generations for increased ovulation rate and increased litter size. A single blood sample was collected from each pig between 46 to 63 (d 58), 86 to 98 (d 90), 110 to 133 (d 124), and 147 to 153 (d 150) d of age. The heritability of ovulation rate was .28 and heritabilities of plasma concentration of FSH at d 58, 90, 124, and 150 were .41, .25, .12, and 0, respectively. Genetic correlations between ovulation rate and d-58, d-90, and d-124 plasma concentration of FSH were .31, .23, and 0, respectively. Line I gilts had greater estimated breeding values for plasma concentration of FSH at d 58 and 90 than Line C gilts (P < .01). Line COL gilts had greater estimated breeding values for plasma concentration of FSH at d 58 than Line C2 gilts (P < .01). Line I boars had greater estimated breeding values for plasma concentration of FSH at d 90 than Line C boars (P < .05). Even though genetic correlations were low, selection for increased plasma concentration of FSH was estimated to be 93% as effective in changing ovulation rate as direct selection because selection for FSH can be practiced in both sexes. Thus, selection for increased plasma concentration of FSH seems to be a practical method for increasing ovulation rate in pig breeding programs without using laparoscopy.
Bakhtinian ‘Journalization’ and the Mid‐Victorian Literary Marketplace

This paper forms part of a Literature Compass cluster on Modern Book History. The full cluster is made up of the following articles: ‘Between Then and Now: Modern Book History’, Kate Longworth, Literature Compass 4 (2007), 10.1111/j.1741-4113.2007.00474.x. ‘Ezra Pound's Cantos: A Compact History of Twentieth-Century Authorship, Publishing and Editing’, Mark Byron, Literature Compass 4 (2007), 10.1111/j.1741-4113.2007.00475.x. ‘ “The Making of the Book”: Roy Fisher, the Circle Press and the Poetics of Book Art’, Matthew Sperling, Literature Compass 4 (2007), 10.1111/j.1741-4113.2007.00476.x. ‘Bakhtinian “Journalization” and the Mid-Victorian Literary Marketplace’, Dallas Liddle, Literature Compass 4 (2007), 10.1111/j.1741-4113.2007.00477.x. ‘Manuscript in Print: The Materiality of Alternative Comics’, Emma Tinker, Literature Compass 4 (2007), 10.1111/j.1741-4113.2007.00478.x. ‘Lost in a World of Books: Reading and Identity in Pre-War Japan’, Susan C. Townsend, Literature Compass 4 (2007), 10.1111/j.1741-4113.2007.00479.x. *** In now-famous remarks on ‘novelization’, M. M. Bakhtin theorized a mechanism by which one literary genre influences the content and structure of other genres. The popular and critical success of the novel form demonstrates its specific discursive advantages over other genres, which recognize these advantages and often attempt to copy or adapt to them. Though the influence Bakhtin describes goes only one way – the novel ‘novelizes’ other genres – novelization is not an isolated phenomenon, but an example or case study within Bakhtin's larger ‘Galilean’ conception of genre interaction. Parallel cases should therefore exist: in other literary markets and moments in book history we should expect great artistic, popular, or financial success by one genre to lead contemporary writers to adopt elements of the successful genre, or to adjust their practices in response to it. This prediction is particularly important because for Bakhtin genres are more than outward conventions; they are ‘form-shaping ideologies’ with inherent knowledges and ways of thinking. Adopting or adapting a new genre requires a writer to change not simply forms, but also attitudes, assumptions, and worldview. My paper hypothesizes a Bakhtinian moment of genre influence in Great Britain in and immediately after 1855, triggered by the sudden rise in the perceived power of newspaper press discourse. Factors including the apparent political power wielded by the press during the Crimean War, and the repeal of the newspaper stamp, with its resulting proliferation of apparently successful new journals, combined to raise the perceived cultural, financial, and political status of newspaper discourse in this period dramatically. I consider critically the evidence for a resulting ‘journalization’ of other discourse genres between 1855 and 1860, reflected partly by a sudden proliferation of journalist characters and considerations of journalism in British fiction and poetry of this period.
Compress knee arthroplasty has 80% 10-year survivorship and novel forms of bone failure.

Background Compliant, self-adjusting compression technology is a novel approach for durable prosthetic fixation of the knee. However, the long-term survival of these constructs is unknown.
The Dynamics of Arachidonic Acid Liberation and Prolactin Release: A Comparison of Thyrotropin-Releasing Hormone, Angiotensin II, and Neurotensin Stimulation in Perifused Rat Anterior Pituitary Cells*

The dynamics of arachidonic acid (AA) liberation and PRL release were highly correlated in perifused rat anterior pituitary cells during stimulation by three different neuropeptides: TRH, angiotensin II (AII), and neurotensin (NT). After preincubation of these cells with 1 microCi [3H]AA, a 20-min perifusion with AII (100 nM), TRH (100 nM), or NT (1 microM) elicited a sharp initial increase in PRL release and [3H]AA efflux, which rapidly subsided (within 6 min) to less elevated levels of PRL release and AA liberation. The plateau responses were sustained throughout the remainder of the 20-min treatment period; after the cessation of neuropeptide perifusion, the responses rapidly returned to basal levels. AII and TRH elicited a greater initial stimulation of PRL release and AA liberation, whereas NT resulted in less pronounced initial responses and a greater plateau of sustained PRL release and AA liberation. Dopamine (DA; 500 nM) or calcium-depleted medium (containing 60 microM EGTA) evenly attenuated the stimulation of PRL release throughout exposure to the neuropeptides; however, the initial stimulation of AA efflux by AII and TRH was relatively resistant to inhibition by DA or calcium-depleted medium. In contrast, the stimulation of AA liberation by NT was abolished by DA or calcium-dependent medium. These results establish that the time course of AA liberation is complimentary to that of PRL release during stimulation by AII, TRH, and NT and support a possible role for AA liberation and metabolism as one of the mechanisms that participates in the regulation of PRL release. A lesser ability of NT to elicit functional and biochemical responses to intracellular calcium mobilization is postulated as an explanation for the observed differences among AII, TRH, and NT effects on PRL release and AA liberation.
Three-dimensional wave patterns in long air cavities on a horizontal plane

Abstract Significant drag reduction of large displacement vessels can be achieved by applying multi-wave air cavities arranged on the hull bottom. Waves generated on the air–water interface of air cavities impose requirements on the dimensions of a hull recess that accommodates the air cavity. An approximate model for calculating wave patterns in the critical upstream part of long air cavities in a simplified, horizontal-plane geometry is presented in this paper. The influence of the recess planform boundaries and other factors on the wave patterns is studied parametrically. Some hydrodynamic aspects of multi-wave air cavities are discussed.