cssi/SciSciGPT-SciSciNet huggingface dataset:
A Woman's Life: Pauline Wengeroff and Memoirs of a Grandmother

In 1908, Pauline Wengeroff published the first piece of writing by a woman in the history of Jewish literature to tell the story of a life and a family with historical consciousness and purpose. It is also the first account in this literature to make women, and men, the focus of inquiry. Shulamit Magnus's biography of this extraordinary woman lets readers share Wengeroff's life, her aspirations, and her disappointments, making a significant contribution both to women's history and to our understanding of the emergence and shape of Jewish modernity.
Synthesis of a Spiro[cyclohex-1,1‘-isobenzofuranyl] Dopamine Receptor Antagonist

Two syntheses of the novel CNS agent, 2-fluoro-4-(trans)-(4-(3‘H-spiro[cyclohex-1,1‘-isobenzofuran]-4-yl)-piperazin-1-yl)-benzonitrile, 1, are presented. The first relied on a reductive alkylation with low regioselectivity (1:1) but was sufficient for the preparation of kilogram quantities. The second used a selective ketone reduction of 3‘H-spiro[cyclohexane-1,1‘-isobenzofuran]-4-one, 8, with sodium borohydride to provide the cis-alcohol, 3‘H-spiro[cyclohexane-1,1‘-isobenzofuran]-(cis)-4-ol, 11. A simple process for the conversion of 11 to 1 is described. Regioselective reactions with 2,4-difluorobenzonitrile under mild conditions are described.
Blood, blood components, plasma, and plasma products

Abstract This review of 2018 publications identifies side effects of blood, blood components, and plasma products. In addition, albumin, blood transfusion (erythrocytes, granulocytes, and platelets), blood substitutes (hemoglobin-based oxygen carriers), plasma products (alpha1-antitrypsin, C1 esterase inhibitor concentrate, cryoprecipitate, and fresh frozen plasma), plasma substitutes (etherified starches, and gelatin), globulins (intravenous immunoglobulin, subcutaneous immunoglobulin, and anti-D immunoglobulin), coagulation proteins (factor I, factor II, factor VIIa, factor VIII, factor IX, prothrombin complex concentrate, antithrombin III, and von Willebrand factor/factor VIII concentrates), erythropoietin and derivatives, thrombopoietin and receptor agonists, transmission of infectious agents through blood donation, and stem cells are reviewed. This chapter informs the reader about newly recognized and published data in the blood product domain.
EPA's proposed transparency rule: Factors to consider, many; planets to live on, one.

> “In God we trust. All others bring data.” So reads a T-shirt sold by the American Statistical Association. This pithy quip encapsulates a fundamental principle of science: Scientists rely on evidence rather than authority. Indeed, “doubt has been considered essential to science since long before the scientific method was established in the 17th century” (1). Scientists seek reasons for why something should be believed as true, and those reasons involve data, the methods used to collect those data, and the logic connecting those data to conclusions. All other things being equal, absent the opportunity to fully inspect the data, methods, and logical connections of a study, scientists are less able to judge the validity of conclusions or the truth of propositions drawn from a study. As many of us heard from our middle school mathematics teachers, it is important to “show all your work.” Generating and evaluating the scientific evidence to form conclusions about the truth of a proposition is fundamental to the work of science. David B. Allison. Image courtesy of the University of Alabama at Birmingham. Notably, the Environmental Protection Agency (EPA) is not a scientist; it is a regulatory agency. EPA employs scientists and uses science to aid in its mission, but its primary mission is regulation and the protection of the environment and the public health, rather than simply drawing scientific conclusions. Regulatory decisions can, are, and should be informed by science. But science alone is not dispositive of regulatory decisions, and one should not conflate the role of scientists qua scientists with the role of scientists working in a regulatory process. Scientists working in a regulatory process must utilize the best information available to fulfill their charge of making decisions that benefit society, often under conditions of uncertainty. EPA proposed a rule in 2018 that … [↵][1]1To whom correspondence may be addressed. Email: allison{at}iu.edu. [1]: #xref-corresp-1-1
Perceived Barriers to the Adoption of Smart Farming Technologies in Piedmont Region, Northwestern Italy: The Role of User and Farm Variables

Smart Farming Technologies (SFTs) can increase the sustainability of agricultural production, based on a more precise and resource-efficient approach. However, previous studies pointed out a low level of SFTs adoption, often highlighting that technologies and innovations successfully adopted may be rejected by the users, who go back to the traditional practices even where benefits were being enjoyed. This study aimed at investigating the role played by individual variables, farming system characteristics, and perceived barriers in affecting the adoption of SFTs in a sample of Italian farm operators. Three-hundred and ten participants were administered a paper-and-pencil questionnaire addressing perceived economic, market and data management barriers in the adoption of SFTs. At the same time a set of user and farm-related variables was collected. The analyses showed that farm size and the perception of economic barriers affected the adoption of SFTs. Larger farms were more likely to adopt the SFTs investigated. The present results pointed out some critical aspects which may benefit from tailor-made interventions in terms of policies, work re-organization and/or operators’ training, to support and widen the use of SFTs in the Italian context.
Influence of Sexually Transmitted Infections in Pregnant Adolescents on Preterm Birth and Chorioamnionitis

Background Adolescents have an increased risk of preterm birth (PTB) and sexually transmitted infections (STIs). We examined the prevalence and impact of STIs (gonorrhea, chlamydia, and trichomonas) on PTB and chorioamnionitis in pregnant adolescents. Methods This retrospective cohort study utilized the first pregnancy delivered at an urban hospital among patients ≤ 19 years old over a 5-year period. Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) of the association between STIs and PTB (<37 weeks) and chorioamnionitis identified by clinical or placental pathology criteria. Results 739 deliveries were included. 18.8% (n = 139) of births were preterm. The overall prevalence of STIs during pregnancy was 16.5% (Chlamydia trachomatis: 13.1%, n = 97; Trichomonas vaginalis: 3.7%, n = 27; and Neisseria gonorrheae: 3.1%, n = 23). Detection of C. trachomatis, T. vaginalis, or N. gonorrheae was not associated with increased PTB. While infection with N. gonorrheae and C. trachomatis did not increase the likelihood of any chorioamnionitis, infection with T. vaginalis significantly increased the likelihood of any chorioamnionitis diagnosis (aPR 2.19, 95% CI 1.26-3.83). Conclusion In this adolescent population with a high rate of PTB, in whom most received appropriate STI treatment, we did not find an association between STI during pregnancy and an increased rate of PTB. However, an infection with T. vaginalis was associated with an increased likelihood of chorioamnionitis. Early detection of STIs may prevent adverse pregnancy outcomes. Continued vigilance in STI screening during pregnancy, including consideration of universal Trichomonas vaginalis screening, is merited in this high-risk population.
Pediatric diabetes and skin disease (PeDiSkin): A cross-sectional study in 369 children, adolescents and young adults with type 1 diabetes.

BACKGROUND The spectrum of skin disorders in children with type 1 diabetes (T1D) and their impact on affected persons are still incompletely understood. This study assessed the prevalence of skin diseases, cutaneous complications associated with T1D treatment and skin-related quality of life (QoL) in young T1D persons. METHODS Participation in this interdisciplinary, single-center, cross-sectional, observational study was offered to all persons with T1D ≤20 years. Participants were characterized by a detailed medical history, routine laboratory workup, thorough clinical examinations and an established QoL questionnaire. RESULTS Three hundred and sixty-nine persons were recruited (55% male; age 12.3 ± 4.4 years; HbA1c 7.4 ± 1.0%; mean ± SD). Continuous subcutaneous insulin infusion (CSII) was used by 72.4%, multiple daily injections (MDI) by 27.6% and continuous glucose monitoring (CGM) by 76%. Skin affections occurred in 91.8% of the study population. Device-associated lesions were most prevalent, including lipohypertrophy in 42.2% of MDI and 46.8% of CGM users and contact eczema associated with CSII or CGM in 14.2% and 18.3%, respectively. Diabetes-associated skin disorders and skin infections were rare or absent. Skin-related QoL impairment was low or absent in 95% of patients. CONCLUSIONS Skin diseases have a high prevalence and a broad spectrum in young persons with T1D. Eczematous reactions to CSII and CGM devices represent the most frequent skin complications. This highlights the need for regular skin checkups as an integral part of pediatric diabetes consultations and interdisciplinary cooperation for classification and treatment options.
Use of xenografts and allografts in scalp reconstruction.

PURPOSE OF REVIEW Scalp reconstruction requires a full array of reconstructive options given the complex anatomy and protection of vital structures. Not all patients qualify for advanced reconstructive options and therefore rely on short, effective procedures with minimal morbidity. This review aims to focus on xenografts and allografts to achieve an adequate reconstruction while minimizing morbidity. RECENT FINDINGS Although bovine xenografts have been used for many decades, there have been recent advances in porcine xenografts to aid in scalp defects. Similarly, new allogenic materials have emerged as additional tools in the armamentarium to promote wound healing. SUMMARY Both xenografts and allografts offer viable options for complex scalp reconstruction.
Rethinking Speech-Tort Remedies

Courts generally craft speech-tort jurisprudence as a binary proposition. Any time state tort law and the First Amendment come into potential conflict, courts typically hold either that the First Amendment comes into play and the defendant is completely exempt from traditional tort liability, or that it does not come into play and the plaintiff is entitled to the full complement of tort remedies. In other words, courts generally adopt an unspoken assumption that in speech-tort cases, liability and full tort remedies necessarily go hand-in-hand.This rigid approach, however, significantly limits courts’ ability to craft a nuanced balance between First Amendment and tort interests. In individual cases, it forces them to choose only one set of interests to be vindicated to the complete exclusion of the other, and on a jurisprudential level, it gives courts only the bluntest of instruments to tailor speech-tort doctrine to widely varying facts. Furthermore, the current approach exacerbates the distributional problem inherent to speech-tort cases: any time the First Amendment intervenes to completely invalidate a subset of common law tort liability, plaintiffs left without liability or remedy are effectively forced to subsidize the costs of free speech, the benefits of which are shared broadly by the public at large.In this Article, I argue that courts should incorporate a greater degree of remedial flexibility into speech-tort doctrine. Rather than simply adhere to an all-or-nothing approach, courts should consider intermediate approaches in which the First Amendment applies not to vitiate a finding of tort liability but merely to limit or eliminate the damages to which plaintiffs are entitled. These approaches allow courts to shape the complex balance of speech and tort interests with a scalpel rather than a chain saw, both on a case-by-case basis and on the broader level of doctrinal design.In recent years, this remedy-based approach to speech-tort jurisprudence has rarely been discussed by courts and commentators, while the shadow cast by the First Amendment over tort law has expanded well beyond the defamation context. This calcification of a rigid, binary approach to speech tort cases represents a significant lost opportunity for courts to design more sensible and equitable doctrines. By providing a detailed account of the benefits underlying the use of flexible remedies, evaluating potential critiques to such an approach, and laying out concrete examples of what a remedy-based regime might look like in practice, this Article seeks to rekindle judicial, legislative, and academic interest in adopting such approaches within speech-tort doctrine.
In situ leaching of copper: Challenges and future prospects

Abstract In situ leaching offers a potentially attractive way to extract copper from the subsurface without costly fragmentation and processing. Applicability of in situ leaching is limited to deposits where sufficient permeability exists and where the copper and gangue mineralogy is amenable to leaching. A key challenge from past projects is establishing uniform contact between the fluid and the formation in fractured environments, particularly if fractures become blocked by gypsum and jarosite precipitation during leaching. Previous projects have demonstrated that in situ leaching of copper sulfides is feasible by regenerating ferric iron using atmospheric bacteria cultures, pressurized oxygen gas, or chemical oxidants. Oilfield technologies, including polymer injection for permeability modification and nanoparticle tracers, may have future applications for diagnosing and mitigating short circuiting between wells. Geophysical techniques such as electrical resistance tomography have the potential to provide real-time data on lixiviant movement in the subsurface, thus aiding in both recovery optimization and environmental control. In this review, data from past copper in situ leaching projects are assembled, with a focus on recovery without prior permeability enhancement. The resulting database includes key operating variables from copper in situ leaching projects ranging from field scale pilots to commercial operations.
What Is Amblyopia

Amblyopia is defined primarily as a loss of acuity. In anisometropia, grating acuity, Snellen (optotype) acuity, and vernier acuity are degraded in proportion to each other. In strabismus, Snellen and vernier acuity are degraded more than grating acuity. The main problem in both cases is loss of binocular function, producing loss of stereoscopic vision. A number of other properties are also affected. There is uncertainty about the location of an object in space, a reduction in the ability to detect shapes, deficits in motion and direction perception, less ability to track several objects at once, reduced counting ability, and suppression of the image in one eye by the image in the other, to avoid the diplopia and confusion arising when the two eyes are looking in different directions. Some of these deficits are seen in the fellow as well as the amblyopic eye and in binocular viewing. There are also deficits in eye movements: poor fixation, a longer latency for saccades, inability to follow an object moving away from the nose smoothly, and slow inaccurate movements in visually guided reaches. These particularly affect reading so that an amblyope’s reading speed in both eyes is one-half to three-quarters of that of a normal person.
Tiltrotor analytic flight test and training support

Flight testing is used to determine basic air vehicle performance, handling qualities, avionics, and weapons suitability, as well as special mission applications like shipboard compatibility. Although basic flight testing is a required part of the acquisition cycle, it can be expensive and it may require a highly instrumented aircraft, plus a large test support team. The test team has limited capability to analyze aircraft characteristics early in the acquisition cycle. Aircraft in a grounded status for extended periods also make it difficult for test team members to get answers to specific questions relating to flight test applications. Tiltrotor models are available, but may have only a limited flight test support capability in specialized flight test scenarios. This paper reviews a generic model structure application to tiltrotor vehicle support for flight testing and training and presents some initial low speed model data applications. The generic model structure could also be used as the starting point for integrating a group of related technologies to greatly enhance future air vehicle acquisition, testing, and training.
The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution.

Abstract The three-dimensional structure of recombinant human lymphotoxin (residues 24-171 of the mature protein) has been determined by x-ray crystallography at 1.9-A resolution (Rcryst = 0.215 for I greater than 3 sigma (I)). Phases were derived by molecular replacement using tumor necrosis factor (TNF-alpha) as a search model. Like TNF-alpha, lymphotoxin (LT) folds to form a "jellyroll" beta-sheet sandwich. Three-fold related LT subunits form a trimer stabilized primarily by hydrophobic interactions. A cluster of 6 basic residues around the 3-fold axis may account for the acid lability of the trimer. Although the structural cores of TNF-alpha and LT are similar, insertions and deletions relative to TNF-alpha occur in loops at the "top" of the LT trimer and significantly alter the local structure and the overall shape trimer is highly conserved. The sites of two mutations (Asp-50 and Tyr-108) that abolish the cytotoxicity of LT are contained within poorly ordered loops of polypeptide chain that flank the cleft between neighboring subunits at the base of the molecule, suggesting that the receptor recognizes an intersubunit binding site.
Medieval Urban Environmental History

Medieval urban environmental history lies at the intersection of environmental history, urban history, and the history of public health. For many years, medieval towns were thought to be universally foul and filthy, a stereotype that remains common in both academic and popular histories. Since the 1920s, however, historians who work closely with the documentary evidence have challenged such a one-dimensional characterization. A growing body evidence from urban archaeological sites has created the potential for a more integrated, interdisciplinary approach to the study of urban ecosystems and waste management. Recent environmental scholarship has also focused on ‘urban footprints’ (the impact of cities on their supply hinterlands) and on the social construction of medieval attitudes to hygiene.
Genetic and physiological characterization of met15 mutants of Saccharomyces cerevisiae: a selective system for forward and reverse mutations.

One hundred and thirty-three spontaneous and induced mutants of the met15 locus in Saccharomyces cerevisiae were characterized with respect to temperature sensitivity, osmotic remediability, interallelic complementation, and suppressibility by amber and ochre suppressors. Forty mutants are osmotic remedial; 17 of these, and no others, are also temperature-sensitive. Seven of 133 mutations are suppressible by an amber suppressor and 11 are suppressible by an ochre suppressor. Seventy percent of the mutants exhibited interallelic complementation, suggesting that the functional gene product of the met15 gene is a multimeric protein. Relative map positions of 30 met15 were estimated from the frequencies of X-ray-induced mitotic reversion of various heteroallelic diploids. All complementing nonsense mutations are located near one end of the gene in contrast to other nonsense mutations which span most of the gene, thus relating the direction of translation of the mRNA with respect to the fine-structure map. Recombination studies indicated that two of 30 mutants contained deletions of the entire met15 locus.—It was established that a variety of mutational types, including missense, nonsense, and deletions, are recovered with this unique system in which both forward and reverse mutations can be selected on the basis of methyl mercury resistance and methionine requirement of the met15 mutants.
A Referee Method for the Determination of Total Calcium in Serum

The first referee method of analysis (a method of known accuracy) in clinical chemistry has been developed through the cooperation of scientists from the National Bureau of Standards and eight clinical chemistry laboratories. Subject to some limitations discussed in the text, calcium in serum can be determined by the referee method to within ±2% of the "true or absolute" value. The complete protocol, based on an atomic absorption spectrometric procedure, is described in detail.
Simulations to explore alternative sequencing rules

A flexible simulation system has been designed to permit investigation of sequencing rules in a large job shop, with continual input of new work. The objective is to understand what happens rather than to find optimum rules, with many conflicting measures of effectiveness: work in process, finished goods investment, delays, machine and labor utilization, and effort to implement. A few problem areas have been explored.
Right heart failure

Right ventricular failure (RVF) is a frequent and formidable clinical challenge in the intensive care unit, the operating room, the general ward, and the outpatient setting. The presence of RVF (1) carries substantial morbidity and mortality and (2) complicates the use of commonly employed treatment strategies in both inpatients and outpatients. In contrast to the left ventricle (LV), the right ventricle (RV) remains relatively understudied, and none of the major professional societies have published any guidelines on how to approach patients with RVF. Due to embryological, anatomical, physiological, biochemical, and electrophysiological differences between the RV and LV, paradigms that are important for the treatment of the failing LV cannot be extrapolated to RVF. However, with pulmonary hypertension (PH) having become a major area of scientific and clinical interest, recent studies have shed more light on the physiology of the normal RV and the pathophysiology of its failure. Using a comprehensive and evidence-based approach, this chapter will (1) highlight the pathophysiology of the failing RV; (2) discuss the etiologies of acute, chronic, and acute-on-chronic RVF; (3) describe invasive and noninvasive approaches that assist in diagnosis and risk stratification; and (4) emphasize treatment strategies for stable (chronic) and decompensated (acute) RVF.
Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis

Histologic, ultrastructural, chemical, and statistical methods were used to study liver biopsy and autopsy specimens from 43 patients who had primary sclerosing cholangitis (PSC), with or without chronic ulcerative colitis (CUC), and from 19 patients who had CUC without PSC. In all study groups, essentially the same abnormalities were found in the hepatic parenchyma outside the major bile ducts, although nondiagnostic tissue samples were observed also. Specimens from patients with extrahepatic PSC were indistinguishable from those from patients with combined extra- and intrahepatic PSC. Common findings included periductal fibrosis and inflammation, portal edema and fibrosis, focal proliferation of bile ducts and ductules, focal bile duct obliteration and loss of bile ducts, copper deposition, and cholestasis. Proliferation of bile ducts in some portal tracts and obliteration or absence of bile duct in others were the most characteristic changes. In most specimens, inflammatory changes appeared mild, yet biliary cirrhosis had developed in 34% of the patients. Specimens from patients with PSC, with or without CUC, more often contained bile and strikingly increased stainable copper (Grades 2 and 3) than did specimens from patients with CUC without PSC. Hepatic copper contents, measured by atomic absorption spectrophotometry, also were higher in specimens from patients with PSC. Study of PCS specimens by transmission electron microscopy and by energy-dispersive X-ray microanalysis revealed that most copper was sequestered in lipolysosomes. The recognition of strikingly similar morphologic features in many liver specimens from patients with either PSC or CUC or both suggests that the causes of these conditions are closely related.
Arousal response with aging: pupillographic study.

The performance of cognitive behaviors requires an activated, aroused cerebral cortex. Although studies have shown that there are decrements of cognitive functions in the elderly, changes in arousal with aging have not been fully studied. Our objective was to learn if there are attention–arousal changes associated with aging. Visual stimuli were presented to induce orienting responses or arousal reactions. Because changes in pupil size reflect changes in arousal, we recorded and compared pupillary responses of young and older normal participants using infared pupillography. During the 1 s that we recorded pupillary changes, we found major phases: a brief initial constriction (C1), then a maximal dilation (D1)—an arousal response, followed by constriction (C2), a habituation response. Although amplitude of these 3 phases was not different between the 2 groups, the interval between the D1 and C2 response was prolonged in the older group. Although the arousal response is not dramatically altered with aging, habituation appears to be delayed. ( JINS , 2000, 6 , 348–350.)
FEARS AND WORRIES OF YOUNG CHILDREN AS EXPRESSED IN A CONTEXTUAL PLAY SETTING

One hundred 5- and 6-year-old children were studied with a contextual play technique in order to gain insight into their fears and worries. Sex differences and differences relating to questioning procedure were examined. The discussion included the potential usefulness of the method and some implications for parents and teachers.
World at Total War: Global Conflict and the Politics of Destruction, 1937–1945 – Edited by Roger Chickering, Stig Förster, and Bernd Greiner

This book results from a conference in Hamburg in August 2001, the fifth and last in a series on the “road to total war.” It brings together twenty‐one essays, most by well‐established scholars in ...
Estrogen binding and estrogenic responses in normal human osteoblast‐like cells

A finite human cell line was established from trabecular bone explants obtained from a 48-year-old woman. These cells, designated BG688, were characterized as osteoblast-like in phenotype using the following independent criteria: (1) the presence of histochemically detectable alkaline phosphatase (AP) activity; (2) response to the calciotropic hormone 1,25-(OH)2D3 as assessed by increased AP activity; (3) synthesis and secretion of the osteoblast-specific marker bone gla protein; and (4) expression of alpha 1(I)-procollagen and alpha 1(III)-procollagen mRNAs in a pattern similar to that of other osteoblast-like cell lines. In addition to these classic osteoblast markers, BG688 cells also possess approximately 2400 high-affinity (Kd = 0.45 nM) 17 beta-estradiol (E2) binding sites per cell. The binding of E2 to these sites is specific, and of the steroid hormone agonists tested, E2 and diethylstilbestrol elicited the greatest amount of competition with radiolabeled E2. BG688 cells were also shown to respond to a physiologic concentration (10 nM) of E2. In vitro translation products of poly(A)+ RNA obtained from control and hormone-treated cells revealed a pleiotropic influence of E2 on the relative abundance of several mRNAs as assessed by two-dimensional gel electrophoretic analysis of their corresponding peptides. E2 also elicits a twofold increase in the steady-state concentration of alpha 1(I)-procollagen mRNA as demonstrated by northern blot hybridization. Thus, we here extend our previous data obtained in osteoblast-like osteosarcoma cells to indicate that a normal osteoblastic cell line is a target for the action of estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Lithium neuroprotection: molecular mechanisms and clinical implications.

Lithium has emerged as a neuroprotective agent efficacious in preventing apoptosis-dependent cellular death. Lithium neuroprotection is provided through multiple, intersecting mechanisms, although how lithium interacts with these mechanisms is still under investigation. Lithium increases cell survival by inducing brain-derived neurotrophic factor and thereby stimulating activity in anti-apoptotic pathways, including the phosphatidylinositol 3-kinase/Akt and the mitogen-activated protein kinase pathways. In addition, lithium reduces pro-apoptotic function by directly and indirectly inhibiting glycogen synthase kinase-3β activity and indirectly inhibiting N-methyl-D-aspartate (NMDA)-receptor-mediated calcium influx. Lithium-induced regulation of anti- and pro-apoptotic pathways alters a wide variety of downstream effectors, including β-catenin, heat shock factor 1, activator protein 1, cAMP-response-element-binding protein, and the Bcl-2 protein family. Lithium neuroprotection has a wide variety of clinical implications. Beyond its present use in bipolar mood disorder, lithium's neuroprotective abilities imply that it could be used to treat or prevent brain damage following traumatic injury, such as stroke, and neurodegenerative diseases such as Huntington's and Alzheimer's diseases.
Matrix metalloproteinase–13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance

Like bone mass, bone quality is specified in development, actively maintained postnatally, and disrupted by disease. The roles of osteoblasts, osteoclasts, and osteocytes in the regulation of bone mass are increasingly well defined. However, the cellular and molecular mechanisms by which bone quality is regulated remain unclear. Proteins that remodel bone extracellular matrix, such as the collagen-degrading matrix metalloproteinase (MMP)-13, are likely candidates to regulate bone quality. Using MMP-13-deficient mice, we examined the role of MMP-13 in the remodeling and maintenance of bone matrix and subsequent fracture resistance. Throughout the diaphysis of MMP-13-deficient tibiae, we observed elevated nonenzymatic cross-linking and concentric regions of hypermineralization, collagen disorganization, and canalicular malformation. These defects localize to the same mid-cortical bone regions where osteocyte lacunae and canaliculi exhibit MMP-13 and tartrate-resistant acid phosphatase (TRAP) expression, as well as the osteocyte marker sclerostin. Despite otherwise normal measures of osteoclast and osteoblast function, dynamic histomorphometry revealed that remodeling of osteocyte lacunae is impaired in MMP-13(-/-) bone. Analysis of MMP-13(-/-) mice and their wild-type littermates in normal and lactating conditions showed that MMP-13 is not only required for lactation-induced osteocyte perilacunar remodeling, but also for the maintenance of bone quality. The loss of MMP-13, and the resulting defects in perilacunar remodeling and matrix organization, compromise MMP-13(-/-) bone fracture toughness and postyield behavior. Taken together, these findings demonstrate that osteocyte perilacunar remodeling of mid-cortical bone matrix requires MMP-13 and is essential for the maintenance of bone quality.
On Nash-solvability in pure stationary strategies of finite games with perfect information which may have cycles

Abstract Let g be an n person positional game with perfect information modelled by a directed graph G =( V , E ) which is finite but may have directed cycles. A local cost function f ( i , e ) is given for every player i ∈ I and for every move e ∈ E . The players are allowed only pure stationary strategies, that is the move in any position is deterministic, and may depend only on this present position, not on the preceding positions or moves. In this case the resulting play p is a directed path which begins in the initial position v 0 and either (i) ends in a terminal position or (ii) results in a simple directed cycle. Given a play p , for each player i ∈ I the effective cost f ( i , p ) is defined as the sum of all local costs along the path f ( i , p )=Σ e ∈ p f ( i , e ) in case (i), or as f ( i , p )=+∞ in case (ii). The local cost function f and the corresponding game is called terminal if f ( i , e )=0, unless e is a terminal move. The players wish to minimize their effective costs, in particular they should avoid cycles. A game is called Nash-solvable if it has a Nash equilibrium in pure stationary strategies and properly Nash-solvable if the corresponding play results in a final position, not in a cycle. It is easy to demonstrate that already zero-sum games with two players may not be solvable. However, Nash-solvability turns into an exciting open problem under the following simple additional condition: (♣) all local costs are non-negative, that is f ( i , e )≥0 for all i ∈ I and e ∈ E , or under the seemingly weaker, but in fact equivalent, condition: (♠) Σ e ∈ c f ( i , e )≥0, for all i ∈ I and for each simple directed cycle c in G . In all examples, which we were able to analyze, games satisfying (♣) are properly Nash-solvable, yet, even the Nash-solvability of such games is an open problem. In this paper we prove proper Nash-solvability for the following special cases: (a) play-once games, that is the games in which every player controls only one position, (b) terminal games with two players, and (c) terminal games with only two terminal moves. We also show that in each of these cases a Nash equilibrium can be constructed in polynomial time in the size of the graph G .
Parasites as stressors: plasma cortisol responses of goats infected with the stomach worm Haemonchus contortus to exogenous corticotropin (ACTH).

Ten male, juvenile pigmy goats of similar age and weight were allocated randomly to two groups. Goats in one group were each inoculated with 20,000 infective larvae of Haemonchus contortus. The other group served as uninfected controls. Goats were housed together, and precautions were taken to avoid the creation of differential, between group, stressogenic circumstances. Body weights, nematode egg production, hematocrits, and clinical signs were monitored over a 61-day period following inoculation of larvae. On Days 59 and 61, adrenal response tests (ART) were conducted by measuring the levels of plasma cortisol before and 2 h after administration of porcine ACTH at the rate of 0.35 I.U. kg-1 body weight on Day 59 and 2.2 I.U. kg-1 on Day 61. Although the infections did not reduce body weights, they were 'heavy' on the basis of egg production, and led to significant reductions in packed erythrocyte volumes. There was no significant difference between the groups of goats in the responses to ART, indicating that the infections did not produce sufficient stress to reduce the ability of the adrenal cortex to respond to exogenous ACTH.
Detroit is a Blank Slate: Metaphors in the journalistic discourse of art and entrepreneurship in the City of Detroit

This paper presents an investigation of metaphoric language in the contemporary discourse of Detroit's “renewal.” News articles from local and national news sources from 2009–2011 provide evidence of critical and provocative metaphoric constructions found in the gentrification discourse of Detroit. As harbingers of gentrification, the discourse communities of artists and business entrepreneurs are the focus of this review. The author argues that metaphoric language in journalism must be critically evaluated and challenged to help ensure sustainable, equitable, and historically sensitive “renewal” of the city of Detroit and similar inner-city urban communities experiencing gentrification.
A loop configuration approach to automatic sketching of mechanisms

Sketching of mechanisms identified during the type synthesis process constitutes an important link with the subsequent dimensional synthesis process in the systematic design of mechanisms. A lack of reliable procedures for the automation of this sketching process is a hurdle towards computerization of the complete design process. In this paper, a simple and robust methodical procedure for automatically sketching every type of kinematic chain regardless of the number of links and degrees of freedom is presented. The development and application of this algorithm based on inter-loop relationship are demonstrated with the aid of several mechanism examples.
A correlation between the interstitial hole sizes in intermetallic compounds and the thermodynamic properties of the hydrides formed from those compounds

Abstract A correlation has been established between the stabilities of metal hydrides (measured in terms of the free energies of formation of the hydride phase per mole H 2 ) and the radii of tetrahedral holes in both hexagonal AB 5 (D2 d ) and cubic AB (B 2 ) intermetallic compounds. The correlation demonstrates that as the tetrahedral hole size increases, the stability increases. The results of this correlation show conclusively that hole size can be employed effectively in determining the stabilities of intermetallic compound-hydrogen phases. A model, which depends solely upon lattice parameters, was developed to compute the radii of tetrahedral holes in hexagonal AB 5 intermetallic compounds. A similar model, which requires a ratio of metallic radii in addition to the lattice parameter, has been employed to compute the radii of tetrahedral holes in the cubic AB intermetallic compounds. The thermodynamic and structural properties of hexagonal AB 5 -hydrogen systems and cubic AB-hydrogen systems have been compiled and are presented. The quantitative correlations are excellent. A change in valence of the A atom in the hexagonal AB 5 intermetallic compounds may have a significant effect on the stabilities of the hydride phases formed. In those cases where the B atoms were partially substituted in the hexagonal AB 6 and the cubic AB intermetallic compounds, a good correlation of stability with hole size was found. Gross deviations of the Ce-base AB 5 hydride data from the correlation line established by all the other AB 5 hydrides were observed. These were rationalized on the basis of well-documented stress-induced lattice contractions of Ce intermetallic compounds. The resulting contracted hole sizes of the CeNi 5 and CeCo 5 compounds modified the stability of their hydrides. These compound hydrides demonstrate a displaced but similar correlation to the other AB 5 hydrides, i.e . the smaller the hole size, the less stable is the system.
Detecting differential expressions in genechip microarray studies : A quantile approach

In this article we consider testing for differentially expressed genes in GeneChip studies by modeling and analyzing the quantiles of gene expression through probe level measurements. By developing a robust rank score test for linear quantile models with a random effect, we propose a reliable test for detecting differences in certain quantiles of the intensity distributions. By using a genomewide adjustment to the test statistic to account for within-array correlation, we demonstrate that the proposed rank score test is highly effective even when the number of arrays is small. Our empirical studies with real experimental data show that detecting differences in the quartiles for the probe level data is a valuable complement to the usual mixed model analysis based on Gaussian likelihood. The methodology proposed in this article is a first attempt to develop inferential tools for quantile regression in mixed models.
Probing Drug-Binding Pathways in P-Glycoprotein with Ensemble Docking

P-glycoprotein (P-gp) is one of the key members of the ATP-binding cassette (ABC) transporters family and the major contributor of multidrug resistance against a broad spectrum of drugs in cancer cells. Powered by ATP, P-gp acts as an efflux pump to export a diverse set of hydrophobic molecules, including drugs, out of the cell. These hydrophobic substrates are assumed to enter the translocation pathway of P-gp either via the intracellular side of the cell or directly from the cytoplasmic leaflet of the membrane. In order to characterize the mechanism, residues facilitating drug entry, and translocation, we have taken an approach combining the strengths of molecular dynamics (MD) and molecular docking. A 100 ns MD simulation of membrane-bound inward facing P-gp with Mg2+ and ATP was performed and subsequently used in ensemble docking. Doxorubicin, one of the drug substrates of P-gp, was docked into the defined active sites of 10,000 different snapshots representing the conformational flexibility of the protein in the membrane. Clustered docked poses identified the binding sites and yielded a picture of the sequence of binding events of the substrate within the translocation pathway. Interestingly, a few of the highly populated clusters were located within the region that interacts with the cytoplasmic leaflet of the membrane supporting the recruitment of the substrate laterally and directly from the membrane. Further MD simulations and energetic calculations of representative substrate poses are then used to characterize their real-time binding behavior and dynamics within the intracellular lumen and at the cytoplasmic leaflet of the membrane. This study, for the first time, explored and utilized the dynamic ensemble of conformations of P-gp in molecular docking and dissected important and complex features of its translocation pathway.
Inhibition of endothelial cell growth by a factor isolated from cartilage

Abstract An endothelial cell growth inhibitor (EGI), which affects proliferation of vascular endothelial cells, has been isolated from a 1 M guanidine hydrochloride extract of bovine cartilage by ion exchange chromatography on CM-Sephadex C-25. Two peaks of EGI activity were observed, both of which eluted in positions separate from a peak of trypsin inhibitory activity. Using bovine endothelial cells in culture, we have demonstrated that EGI is not cytotoxic, but rather affects the cell cycle. The average population doubling time increased from 24 h for cells grown in control media to 40 h when cells were grown in the presence of 2 μg EGI/ml of culture medium. The trypsin inhibitor isolated from cartilage had no effect on endothelial cell proliferation. As predicted by segmented regression analysis of the growth curves, we have shown that EGI remains active in the media for a period of 3 days. An appendix of the statistical treatment of the data by segmented regression analysis is presented.
Visible light diffraction by a monolayer periodic array of UV laser dye Bis-MSB doped polystyrene spheres

Abstract Visible light diffraction by a monolayer periodic array is investigated. The planar array with two-dimensional single crystalline structure was made by UV laser dye Bis-MSB doped polystyrene spheres with diameter of 2.6 μm. The diffraction patterns with 6, 12, 18, 24, 30, 36 spots from visible light (λ = 632.8 nm) show that the array has high diffractive efficiency and uniformity. The number of spots in the diffraction patterns were modulated by the size of the Gaussian beam based simply on Z-scanning. We analyze array diffraction with Gaussian optics and array theory.
Characterization of L-arginine and aminoguanidine uptake into isolated rat choroid plexus: differences in uptake mechanisms and inhibition by nitric oxide synthase inhibitors.

Recent reports suggest that nitric oxide (NO) may contribute to several neurodegenerative diseases, e.g., focal cerebral ischemia, N-methyl-D-aspartate-mediated neurotoxicity, and experimental autoimmune encephalomyelitis. Accordingly, an understanding of the CNS transport processes of NO synthase (NOS) inhibitors has important therapeutic implications. The objective of the present study was to characterize the in vitro transport processes governing the uptake of L-[14C]arginine and the NOS inhibitor [14C]aminoguanidine in rat choroid plexus tissue. Consistent with previous reports, the uptake of L-[14C]arginine was mediated by both saturable and nonsaturable processes and was inhibited by the NOS inhibitors NG-methyl-L-arginine, NG-amino-L-arginine, and N5-imidoethyl-L-ornithine. L-[14C]Arginine uptake was not inhibited by aminoguanidine or NG-nitro-L-arginine. Because aminoguanidine is an organic cation that bears some structural similarity to L-arginine, aminoguanidine might be transported by either an organic cation transporter or by the basic amino acid transporter governing arginine uptake. However, there was no evidence of a saturable uptake process for [14C]aminoguanidine in isolated rat choroid plexus, in contrast to that observed for L-[14C]arginine.
Axenic culture of Tyrophagus putrescentiae in a chemically deffined diet and determination of essential amino acids

Abstract A chemically defined axenic diet has been formulated for the acarid mite, Tyrophagus putrescentiae . With the use of this diet, the essentiality or non-essentiality of amino acids for the species was determined by the indirect method using glucose-UL 14 C in the diet and also by deletion of some individual amino acids from the diet. Essential amino acids were threonine, valine, methionine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, lysine, arginine, and histidine, the classical ten amino acids essential in the nutrition of the rat.
Photoexcitations of the Si−4 anion. Theoretical study

Abstract Some stable and metastable (autodetaching) excited states of the Si − 4 anions are characterized with the use of the first-order correlation orbital method and the coupled-cluster method. There are three doublet states of the anion, X 2 B 2g , 2 B 1g and 2 B 1u , which lie below the electron ejection threshold. All other states have total energy higher than the energy of the neutral cluster.
External form and internal anatomy of Holsteins and Jerseys.

Body weights, external dimensions, and postmortem measures of internal body dimensions or weights of organs and glands of Holsteins and Jerseys were used to establish norms, interrelationships of traits, and effects of sire and inbreeding on changes in external form. Sires differed in nearly all measures of external body form. Sire effects increased with advancing age whereas effects of inbreeding (greater than 12.5, 3.0 to 12.4, or less than 3.0% of inbreeding) declined. Skeletal dimensions were smallest in the greater than 12.5% inbred group. Differences due to inbreeding were largest at 3 and 6 mo of age and in first lactation. Body heights and head dimensions were nearer to mature size at 3 and 6 mo than other measures. In both breeds, most rapid development was between 3 and 6 mo, but Jersey matured 1 to 2% faster. Age (2 to 3, 4 to 5, 6 to 10, greater than 10 yr) was significant for most postmortem measurements. Correlations among measures of external form were .30 to .93. Correlations between external form and internal features or between internal dimensions and organs were lower. External and internal features were positively correlated, but few external features showed strong enough association with internal features for use as predictors of size of organs, glands, or digestive capacity.