cssi/SciSciGPT-SciSciNet huggingface dataset:
Absence of Selection Against Aneuploid Mouse Sperm at Fertilization

Is there selection against aneuploid sperm during spermatogenesis and fertilization? To address this question, we used male mice doubly heterozygous for the Robertsonian (Rb) translocations Rb(6. 16)24Lub and Rb(16.17)7Bnr, which produce high levels of sperm aneuploid for chromosome 16, the mouse counterpart of human chromosome 21. The frequencies of aneuploid male gametes before and after fertilization were compared by analyzing approximately 500 meiosis II spermatocytes and approximately 500 first-cleavage zygotes using fluorescence in situ hybridization with a DNA painting probe mixture containing three biotin-labeled probes specific for chromosomes 8, 16, and 17 plus a digoxigenin-labeled probe specific for chromosome Y. Hyperhaploidy for chromosome 16 occurred in 20.0% of spermatocytes and in 21.8% of zygotes. Hypohaploidy for chromosome 16 occurred in 17.0% and 16.7% of spermatocytes and zygotes, respectively. In addition, there was no preferential association between chromosome 16 aneuploidy and either of the sex chromosomes, nor was there an elevation in aneuploidy for chromosomes not involved in the Rb translocations. These findings provide direct evidence that there is no selection against aneuploid sperm during spermiogenesis, fertilization, and the first cell cycle of zygotic development.
Species-Specific Secondary Metabolite Production in Marine Actinomycetes of the Genus Salinispora

Here we report associations between secondary metabolite production and phylogenetically distinct but closely related marine actinomycete species belonging to the genus Salinispora. The pattern emerged in a study that included global collection sites, and it indicates that secondary metabolite production can be a species-specific, phenotypic trait associated with broadly distributed bacterial populations. Associations between actinomycete phylotype and chemotype revealed an effective, diversity-based approach to natural product discovery that contradicts the conventional wisdom that secondary metabolite production is strain specific. The structural diversity of the metabolites observed, coupled with gene probing and phylogenetic analyses, implicates lateral gene transfer as a source of the biosynthetic genes responsible for compound production. These results conform to a model of selection-driven pathway fixation occurring subsequent to gene acquisition and provide a rare example in which demonstrable physiological traits have been correlated to the fine-scale phylogenetic architecture of an environmental bacterial community.
A rearrangement search strategy for determining propositional satisfiability

We present a simple algorithm for determining the satisfiability of propositional formulas in Conjunctive Normal Form. As the procedure searches for a satisfying truth assignment it dynamically rearranges the order in which variables are considered. The choice of which variable to assign a truth value next is guided by an upper bound on the size of the search remaining; the procedure makes the choice which yields the smallest upper bound on the size of the remaining search. We describe several upper bound functions and discuss the tradeoff between accurate upper bound functions and the overhead required to compute the upper bounds. Experimental data shows that for one easily computed upper bound the reduction in the size of the search space more than compensates for the overhead involved in selecting the next variable.
Loss of high-molecular-weight cytokeratin antigenicity in prostate tissue obtained by transurethral resections.

Abstract Objective.—Staining of prostatic basal cells for the expression of high-molecular-weight cytokeratin has been suggested as a way of distinguishing benign from malignant prostate glands. We evaluated the utility of high-molecular-weight cytokeratin in the diagnosis of malignancy in prostate specimens obtained in various ways. Design.—Prostate tissues obtained from needle biopsies, transurethral resections, and total prostatectomies were immunostained with monoclonal antibody 34βE12, an antibody directed against high-molecular-weight cytokeratins. Results.—Antiserum to high-molecular-weight cytokeratin only stained the basal cells in normal glands in 3 (12%) of 25 specimens obtained by transurethral resection. Other antigens, such as the alternate 10-nm filament protein vimentin, were unaffected and were detected in 100% of these specimens. However, keratin antigenicity in transurethral biopsies could be restored in these specimens by antigen retrieval in a low pH citrate buffer using a microwave h...
Post-surgical Pain Management

Why should we care about controlling pain in the postoperative period? Better pain control, depending on the agent(s) and modalities used, leads to benefits in terms of cardiovascular and respiratory complications as well as endocrine, immunologic, gastrointestinal, and hematological outcomes (Liu 2007). Another reason is that patients are often more concerned about being in pain than they are about the primary reason for being in the hospital. In addition, the quality of recovery is improved, and acute pain may become chronic/persistent if not treated properly (Carr 1999).
Panax Quinquefolius (American Ginseng) and Panax Notoginseng (Notoginseng) in Cancer Chemoprevention

The clinical management of cancer invariably involves diverse conventional modalities, including surgery, radiation, and chemotherapy. However, the complexity of human cancer requires some alternative management to improve the therapeutic efficacy of conventional treatment and/or the quality of life of cancer patients. Medicinal botanicals have recently gained more attention for cancer management. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources to develop ideal chemoprevention remains an essential step in advancing the treatment of cancer. In this chapter, potential roles of ginseng herbs, especially American ginseng and notoginseng, in cancer chemoprevention are presented. The major pharmacologically active constituents of ginsengs are ginsenosides, which can be mainly classified into protopanaxadiol and protopanaxatriol groups. The recognized active anticancer compounds from American ginseng and notoginseng are ginsenosides Rg3, Rh2, and protopanaxadiol. The structure-activity relationship between their chemical structures and pharmacological activities is discussed. Sugar molecules within a ginsenoside have a high impact on cancer cells. Anticancer activities increase with the decrease of sugar number. In addition, various steaming temperatures and time treatments of the ginseng herbs can change their ginsenoside profiles and enhance their anticancer activities. This heat treatment process may increase the role and efficacy of American ginseng and notoginseng in cancer chemoprevention.
Acute splenic responses in patients with ischemic stroke and intracerebral hemorrhage

Animal models provide evidence of spleen mediated post-stroke activation of the peripheral immune system. Translation of these findings to stroke patients requires estimation of pre-stroke spleen volume along with quantification of its day-to-day variation. We enrolled a cohort of 158 healthy volunteers and measured their spleen volume over the course of five consecutive days. We also enrolled a concurrent cohort of 158 stroke patients, measured initial spleen volume within 24 h of stroke symptom onset followed by daily assessments. Blood samples for cytokine analysis were collected from a subset of patients. Using data from healthy volunteers, we fit longitudinal quantile regression models to construct gender and body surface area based normograms of spleen volume. We quantified day-to-day variation and defined splenic contraction. Based on our criteria, approximately 40% of stroke patients experienced substantial post-stroke reduction in splenic volume. African Americans, older patients, and patients wi...
On the principles of equipresence and unification

In 1960, Truesdell and Toupin [1] proposed that in formulating constitutive equations for phenomenological theories in which there is more than one constitutive equation, the following principle, which they named the Principle of Equipresence, must be satisfied: A variable present as an independent variable in one constitutive equation should be so present in all. In explaining the application of this principle, they state “Let it not be thought that this principle would invalidate the classical separate theories in the cases for which they are intended, or that no separation of effects remains possible. Quite the reverse: The various principles of invariance, stated above, when brought to bear upon a general constitutive equation have the effect of restricting the manner in which a particular variable, such as the spin tensor or the temperature gradient, may occur. The classical separations may always be expected, in one form or another, for small changes—not as assumptions, but as proven consequences of invariance requirements. The principle of equipresence states, in effect, that no restrictions beyond those of invariance are to be imposed in constitutive equations”.
George Lippard’s The Quaker City: Disjointed Text, Dismembered Bodies, Regenerated Democracy

D. Berton Emerson, “George Lippard’s The Quaker City : Disjointed Text, Dismembered Bodies, Regenerated Democracy” (pp. 102–131) This essay argues that George Lippard’s The Quaker City (1844–1845), originally published in ten separate numbers, is best understood when read more consistently with Lippard’s own mid-production assessment: that he was producing two different books, a novel and its sequel. Doing so reveals that the target of Lippard’s unruly social protest transitions away from a nation-framed story featuring the seduction of an innocent woman and the moral degradation of a community in which such a crime would be possible, to a broader complaint in the sequel against the lack of democratic power and agency at the local level. I start by reconstructing the disjointed composition and publication-in-parts schedule of The Quaker City , along with some historical developments that might have led to its changed course, in order to highlight Lippard’s shifting design and the narrative’s vernacular aesthetics. Turning to the narrative, I explore how the shifting trajectory between novel and sequel becomes most compelling in Lippard’s treatment of printed texts/print culture and bodies/body politic, two entities frequently evoked in the cultivation and understanding of national (imagined) community. In Lippard’s imaginative revision, the sequel thus grapples with alternative political possibilities that discard faith in nation-scaled remedies and instead works through the complexities of a regenerated, localized democracy.
Neural control of the cardiovascular system during exercise. An integrative role for the vestibular system

Precise regulatory signals are required in order to adjust the cardiovascular and respiratory systems to meet the demands of exercise. Two neural mechanisms, central command and a reflex originating in contracting muscles, are known to play a large role in exercise-associated adjustments in cardiovascular and respiratory activity. The extent to which other regulatory reflexes, such as vestibulo-autonomic reflexes, are able to impact upon the cardiovascular and respiratory systems during exercise is largely unknown. Further, brain regions that may integrate these control mechanisms are only starting to be investigated. We propose that medullary brain nuclei may integrate both exercise and vestibular signals to produce a more coordinated, and therefore efficient, means of adaptation to exercise in a gravitational environment.
An Application of Mathematical Modelling to the Study of Reproductive Adaptations in the Yellow Fever Mosquito, Aedes Aegypti

Two reproductive parameters, maximum progeny production and age at maximum progeny production, were estimated for 13 strains of Aedes aegypti by fitting a mathematical model, namely, the gamma distribution function, to the age-specific reproductive curves of each strain. The formosus strains were found to have the lowest level of progeny production and require the longest period of time to reach this peak. Laboratory and “hybrid” strains reached the highest level of progeny production and did so in the shortest period of time. The typical strains were intermediate. The effect of these patterns of reproductive behavior on the intrinsic rate of increase and evolutionary strategies of this mosquito is discussed.
Westernization, Intuitive Eating, and BMI: An Exploration of Jordanian Adolescents:

The purpose of this study was to validate the Arabic-version of the adapted Marin Bidimensional Acculturation Scale and investigate the relationship between Westernization, intuitive eating, and bo...
Optical Bend Sensing for Wearable Goniometry: Exploring the Comfort/Accuracy Tradeoff

This paper explores some initial variables that impact the sensor signal and accuracy of a garment-integrated bend sensor used to measure the flexion and extension of the knee. An optical fiber bend sensor has been evaluated in garments of 6 sizes on an animatronic running mannequin. The resulting sensor signals are compared for correlation, signal-to-noise ratio, signal variability, and morphology. Subsequently, a knee-brace application is evaluated on the same signal parameters in repetitive donning and doffing trials for consistency between trials. The results show the impact of these variables on the amplitude, variability, and noise in the sensor signal.
Lactic Acidosis: Clinical Implications and Management Strategies

In hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment.
Arl13b Interacts With Vangl2 to Regulate Cilia and Photoreceptor Outer Segment Length in Zebrafish.

Purpose Mutations in the gene ARL13B cause the classical form of Joubert syndrome, an autosomal recessive ciliopathy with variable degrees of retinal degeneration. As second-site modifier alleles can contribute to retinal pathology in ciliopathies, animal models provide a unique platform to test how genetic interactions modulate specific phenotypes. In this study, we analyzed the zebrafish arl13b mutant for retinal degeneration and for epistatic relationships with the planar cell polarity protein (PCP) component vangl2.
Secrets of a Swahili Marriage

SUMMARY I am a cultural studies scholar with a primary interest in African discourse, and my research thus intersects with and draws on linguistic anthropology. I teach a course in literary ethnography and am interested in redeeming ethnography for African cultural studies, where it is still largely perceived as tainted by colonialism and orientalism. This piece of fiction draws on my fieldwork in Zanzibar and Zimbabwe, particularly my linguistic anthropological work on the instructions Swahili women give a bride about gender roles as they prepare her for an Islamic marriage and how they talk about their own experiences as Muslim wives, as well as on autoethnographic work on my experience as the wife of a Zanzibari man. [Ethnographic fiction, Swahili marriage, pregnancy, jealousy, Islam]
Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage: a meta-analysis.

Objective The efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs. Methods We searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model. Results Inclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management). Conclusion IAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.
EDUCATION DEVELOPMENT IN KENYA

In this chapter we examine formal education development in post-independence Kenya. We place particular emphasis on key challenges to providing education of sufficient quality to assure that all Kenyan students acquire the capacities they need to participate as productive citizens in their local, national, and global communities. Our focus is on national policy initiatives for education reform that were developed under successive government leaders.
Politics and historical imprisonment, 1930–2010

Theorists have argued that the increasing reliance on imprisonment in the late twentieth and the early twenty-first centuries is associated with a number of important social and political developments that began in the 1960s and 1970s. Despite the emphasis that has been placed on these historically contingent developments, scholars have yet to empirically examine whether the predictive power of recent political variables is restricted to the use of imprisonment in the late twentieth century. The current study addresses this gap in the literature by examining whether four political perspectives are able to account for the use of incarceration at the state level from 1930 to 2010. This study also examines whether the movement from the early to the late twentieth century changed the nature of the relationship between political considerations and jurisdictional reliance on imprisonment. The results indicate that the political party affiliation of elected officials, the public’s commitment to religious...
Prefrontal Cortex Stimulation Enhances Fear Extinction Memory in Humans.

Abstract Background Animal fear conditioning studies have illuminated neuronal mechanisms of learned associations between sensory stimuli and fear responses. In rats, brief electrical stimulation of the infralimbic cortex has been shown to reduce conditioned freezing during recall of extinction memory. Here, we translated this finding to humans with magnetic resonance imaging–navigated transcranial magnetic stimulation (TMS). Methods Subjects (N = 28) were aversively conditioned to two different cues (day 1). During extinction learning (day 2), TMS was paired with one of the conditioned cues but not the other. TMS parameters were similar to those used in rat infralimbic cortex: brief pulse trains (300 ms at 20 Hz) starting 100 ms after cue onset, total of four trains (28 TMS pulses). TMS was applied to one of two targets in the left frontal cortex, one functionally connected (target 1) and the other unconnected (target 2, control) with a human homologue of infralimbic cortex in the ventromedial prefrontal cortex. Skin conductance responses were used as an index of conditioned fear. Results During extinction recall (day 3), the cue paired with TMS to target 1 showed significantly reduced skin conductance responses, whereas TMS to target 2 had no effect. Further, we built group-level maps that weighted TMS-induced electric fields and diffusion magnetic resonance imaging connectivity estimates with fear level. These maps revealed distinct cortical regions and large-scale networks associated with reduced versus increased fear. Conclusions The results showed that spatiotemporally focused TMS may enhance extinction learning and/or consolidation of extinction memory and suggested novel cortical areas and large-scale networks for targeting in future studies.
Allergen-Specific Immunotherapies for Food Allergy

With rising prevalence of food allergy (FA), allergen-specific immunotherapy (AIT) for FA has become an active area of research in recent years. In AIT, incrementally increasing doses of inciting allergen are given with the goal to increase tolerance, initially through desensitization, which relies on regular exposure to allergen. With prolonged therapy in some subjects, AIT may induce sustained unresponsiveness, in which tolerance is retained after a period of allergen avoidance. Methods of AIT currently under study in humans include oral, sublingual, epicutaneous, and subcutaneous delivery of modified allergenic protein, as well as via DNA-based vaccines encoding allergen with lysosomal-associated membrane protein I. The balance of safety and efficacy varies by type of AIT, as well as by targeted allergen. Age, degree of sensitization, and other comorbidities may affect this balance within an individual patient. More recently, AIT with modified proteins or combined with immunomodulatory therapies has shown promise in making AIT safer and/or more effective. Though methods of AIT are neither currently advised by experts (oral immunotherapy [OIT]) nor widely available, AIT is likely to become a part of recommended management of FA in the coming years. Here, we review and compare methods of AIT currently under study in humans to prepare the practitioner for an exciting new phase in the care of food allergic patients in which improved tolerance to inciting foods will be a real possibility.
Quantifying the Complexity of Time Series With Applications to Postural Balance Studies of Parkinson's Patients

The article provides a quantitative assessment of the complexity of random time series via the tool of e-complexity. The methods is then applied to quantify differences in balance dynamics between ...
Resonance Raman Spectroscopy: Application of Tunable Lasers to the Study of the Molecular Mechanisms and Dynamics of Visual Excitation

Rod cells in the retinas of vertebrates are exquisitely sensitive pho-todetectors. In fact, a retinal rod cell can be excited by a single photon [1]. The photoreceptor molecule is rhodopsin, which consists of an 11-cis retinal chromophore and a 38,000 dal ton protein called opsin [for reviews, see 2,3]. The 11-cis retinal group is bound to a specific lysine side chain of opsin by a protonated Schiff base linkage (Fig. 1). WALD [4] showed that light isomerizes the 11-cis retinal group of rhodopsin to all-trans retinal, which no longer fits in the binding site for the chromophore. Several transient species in the photolysis of rhodopsin have been identified by their distinctive spectral properties (Fig. 2).
Evolution of secondary hematologic disorders: preMDS-->MDS-->sAML.

The myelodysplastic syndromes [MDS] and acute myelogenous leukemia [AML] occurring subsequent to toxic exposure constitute the clinically apparent secondary hematologic disorders [sHD]. The incidence of these disorders has significantly increased during the past 40 years. This increase is most likely to be due to at least two phenomena: 1) increased exposure of individuals to hemopoietic toxins as part of treatment for malignant or autoimmune diseases; and 2) the increasing age of our population. It is generally assumed that “spontaneous” myelodysplastic syndromes (no history of toxic exposure) in the elderly are actually the result of a lifetime accumulation of genetic damage resulting from repeated low level toxic exposures in the environment. Despite there being some differences in the frequency of specific chromosomal abnormalities between secondary MDS [sMDS] and spontaneous MDS, these two entities are similar in terms of stem cell involvement, the characteristics of the marrow and peripheral blood, and the clinical courses of these two syndromes. In this chapter these two “types” of MDS, will be considered as one.
Persepolis West (Fars, Iran): Report on the Fieldwork Carried out by the Iranian-Italian Joint Archaeological Mission in 2008–2009 (BAR-IS 2870)

Persepolis was the City of Persians, a concept that is in no way an idea of modern times. Greek authors such as Diodorus of Sicily in the first century BC describes Persepolis as a fortress encircl...
Drug-Induced Injury, Vascular, Congenital, Motility, Polyps, and Miscellaneous Disorders

A variety of drugs, ischemic and vascular conditions, congenital and acquired anatomic disorders can involve the colon. The clinical and pathological features of this heterogeneous group of entities are discussed. This chapter also discusses and illustrates motility disorders, polypoid lesions, and other conditions such as IgG4-related disease, melanosis coli, and endometriosis involving the colon.
The Role of Family Firms in Environmental Sustainability

Family firms are important and dynamic participants in the world economy. They account for two thirds of all businesses around the world, constitute between 70 and 95% of all business entities in m...
Adversity exposure and obesogenic food consumption in young children: The transgenerational role of emotion dysregulation.

Background Childhood adversity is linked with unhealthy eating behaviours and obesity, but the mechanisms underlying this association are unclear, specifically the transgenerational behavioural precursors that develop in early childhood. Objective To determine whether adversity predicts change in obesogenic food consumption through child emotion dysregulation, and whether caregiver emotion dysregulation modifies this association. Methods Participants included 190 low-income caregiver-child dyads (mean child age = 4.31 years [SD = 0.85]). Cumulative lifetime adversity exposure was assessed via study-created measure. The Difficulties with Emotion Regulation Scale and Emotion Regulation Checklist assessed caregiver and child emotion dysregulation, respectively. Children's obesogenic food consumption was assessed at two time points 6 months apart using a caregiver-report measure: the Children's Eating Habits Questionnaire. Moderated mediation models were tested using autoregressive structural equation modelling. Results Cumulative lifetime adversity was associated with child emotion dysregulation only when caregiver emotion dysregulation was high. Child emotion dysregulation in turn was associated with greater obesogenic food consumption 6 months later. Conclusions Among young children with caregivers high in emotion dysregulation, cumulative lifetime adversity was linked to an increase in obesogenic food consumption through child emotion dysregulation.
Characterizing the lipid-protein interface of the human serotonin transporter by crosslinking mass spectrometry

Altered serotonin (5-HT) levels contribute to disease states such as depression and anxiety. Synaptic serotonin concentration is partially regulated by the serotonin transporter (SERT), making this transporter an important therapeutic target. This study seeks to examine the lipid accessible domains of hSERT to provide critical information regarding the apo-state of this transporter in a lipid environment. Recombinant hSERT was inducibly expressed in a human cell line. Solubilized SERT was purified by affinity chromatography using a FLAG Tag and reconstituted into mixed lipid vesicles containing our photoactivatable lipid probe. The lipid-accessible domains of the reconstituted transporter in membranes in its apo-state were probed via photocrosslinking to azi-cholesterol followed by quadrupole time of flight liquid chromatography-mass spectrometry (QTOF-LC-MS). MS studies identified crosslinks in three transmembrane loops consistent with the known topology of SERT. Surprisingly, the amino- and carboxy-terminal domains were similarly crosslinked by cholesterol, suggesting that these regions may also be intimately associated with the lipid bilayer. The data presented herein assist in further refining our understanding of the topography of the apo-state of hSERT via analysis of lipid accessibility.
A Compendium of Sphere Path Integrals

We study 1-loop path integrals on $S^{d+1}$ for general massive, shift-symmetric and (partially) massless totally symmetric tensor fields. After reviewing the cases of massless fields with spin $s=1,2$, we provide a detailed derivation for path integrals of massless fields of arbitrary integer spins $s\geq 1$. Following the standard procedure of Wick-rotating the negative conformal modes, we find a higher spin analog of Polchinski's phase for any integer spin $s>2$. The derivations for low-spin ($s=0,1,2$) massive, shift-symmetric and partially massless fields are also carried out explicitly. Finally, we provide general prescriptions for general massive and shift-symmetric fields of arbitrary integer spins and general partially massless fields of arbitrary integer spins and depths.
The Effect of Ca(OH)2–Treated Ceramic Microspheres on the Mechanical Properties of High–Temperature Lightweight Cement Composites

The compressive strength and water permeability of high-temperature lightweight cementing materials containing sillimanite–based hollow microspheres as a filler can be improved by treating the surfaces of the microspheres with a Ca(OH)2–saturated solution at temperatures up to 200°C. The precipitation of an epitaxial layer formed by an interaction between a hot calcium hydroxide solution and the surface of the sphere plays an essential role in developing favorable bonding characteristics at the interfaces and in promoting the hydration of the cement matrix. The properties of the composites include a slurry density of 1015 psi (7.0 MPa), a water permeability of <10−4 Darcy, and a bulk density of <1.0 g/cc. It was observed that tobermorite-truscottite transformation and anorthite formation during autoclave exposure for 180 days in brine at 300°C results in slight strength reductions and increased water permeability.
Experimental exchange of paralogous domains in the MLH family provides evidence of sub-functionalization after gene duplication.

Baker's yeast contains a large number of duplicated genes; some function redundantly, whereas others have more specialized roles. We used the MLH family of DNA mismatch repair proteins as a model to better understand the steps that lead to gene specialization following a gene duplication event. We focused on two highly conserved yeast MLH proteins, Pms1 and Mlh3, with Pms1 having a major role in the repair of misincorporation events during DNA replication and Mlh3 acting to resolve recombination intermediates in meiosis to form crossovers. The baker's yeast Mlh3 and Pms1 proteins are significantly diverged (19% overall identity), suggesting that an extensive number of evolutionary steps, some major, others involving subtle refinements, took place to diversify the MLH proteins. Using phylogenetic and molecular approaches we provide evidence that all three domains (N-terminal ATP binding, linker, C-terminal endonuclease/MLH interaction) in the MLH protein family are critical for conferring pathway specificity. Importantly, mlh3 alleles in the ATP binding and endonuclease domains improved MMR functions in strains lacking the Pms1 protein and did not disrupt Mlh3 meiotic functions. This ability for mlh3 alleles to complement the loss of Pms1 suggests that an ancestral Pms1/Mlh3 protein was capable of performing both mismatch repair and crossover functions. Our strategy for analyzing MLH pathway specificity provides an approach to understand how paralogs have evolved to support distinct cellular processes.
Measurement of neurotransmitters excreted in the urine of behaviorally healthy dogs in home and boarding kennel conditions

Abstract Clinically relevant biomarkers have long been sought in behavioral medicine as a means to enhance diagnoses and treatment beyond the assessment of clinical symptoms. The monoamine neurotransmitters (NT) serotonin (5HT), dopamine (DA), norepinephrine (NE) and epinephrine (E), as well as glutamate (Glu) and gamma-aminobutyric acid (GABA) have been implicated in anxiety and other neuropsychiatric disorders. Analysis of urine presents the potential for noninvasive, high-throughput NT level evaluation. In this exploratory study, we evaluated a first-morning urine sample collected from 19 healthy dogs undergoing the stress of kennel boarding (Boarding) and 24 healthy dogs in the typical home environment (Home). NE (P
Computed Tomography Osteoabsorptiometry Evaluation of Cervical Endplate Subchondral Bone Mineral Density.

Study DesignBasic Science.ObjectivePoor subchondral bone mineral density (sBMD) has been linked with subsidence of cervical interbody devices or grafts, which are traditionally placed centrally on ...
La moral individual y la moral de las instituciones

espanolEste trabajo desarrolla la relacion entre la filosofia moral y la filosofia politica. Se sostiene que, de alguna manera, la filosofia politica es parte de la filosofia moral, en el sentido que la primera se preocupa del contenido de los estandares morales que rigen las relaciones de los individuos con las instituciones. Este seria el objeto de la “moral de las instituciones”, mientras que la asi llamada “moral individual” se ocuparia de los estandares que se aplican a los individuos. Sobre la base de una concepcion de la moral individual vinculada al contractualismo, y un desarrollo de la moral de las instituciones que sigue de cerca la teoria de la justicia de John Rawls, el trabajo se pregunta por el fundamento de la obligacion de cumplimiento de estandares definidos por instituciones y dirigidos a los individuos. Se pone al final especial atencion a la dificultad de fundamentar dicha obligacion en el caso de instituciones injustas. EnglishThis paper discusses the relationship between moral philosophy and political philosophy. It holds that political philosophy in some way is part of moral philosophy as the former deals with the content of moral standards governing the relations between individuals and institutions. That would be the purpose of the “morality of institutions,” while the so-called “individual morality” would inform the standards applicable to individuals. On the basis of a conception of individual morality as it relates to contractualism and a discussion of the morality of institutions that closely follows John Rawls’ theory of justice, the paper addresses the question of the foundations of the obligation to comply with institution-defined standards that are directed towards individuals. At the end, it focuses in particular on the difficulty of rationalizing that obligation in the case of unjust institutions.
Advanced methods comparisons of reaction rates in the purdue fast breeder blanket facility

A review of worldwide results revealed that reaction rates in the blanket region are generally underpredicted with the discrepancy increasing with penetration; however, these results vary widely. Experiments in the large uniform Purdue Fast Breeder Blanket Facility (FBBF) blanket yield an accurate quantification of this discrepancy. Using standard production code methods (diffusion theory with 50 group cross sections), a consistent Calculated/Experimental (C/E) drop-off was observed for various reaction rates. A 50% increase in the calculated results at the outer edge of the blanket is necessary for agreement with experiments. The usefulness of refined group constant generation utilizing specialized weighting spectra and transport theory methods in correcting this discrepancy was analyzed. Refined group constants reduce the discrepancy to half that observed using the standard method. The surprising result was that transport methods had no effect on the blanket deviations; thus, transport theory considerations do not constitute or even contribute to an explanation of the blanket discrepancies. The residual blanket C/E drop-off (about half the standard drop-off) using advanced methods must be caused by some approximations which are applied in all current methods. 27 refs., 3 figs., 1 tab.
Outside and Inside Hired CEOs: A Performance Surprise

We investigate the association between financial performance and CEO hiring source: internal promotion or external firm. This analysis includes all U.S. CEOs in established public firms from 1986 to 2005. The results show that in large firms, internal hires provide significantly higher median performance, equal chance of the highest performance, and lesser chance of low performance. Over our time period of study, external hires’ performance, relative to internal hires, has decreased significantly. Further, in 10 circumstances where it is commonly thought that external hires would excel, it is the inside hires who either excel or deliver performance comparable to external hires. In the aggregate, internally promoted CEOs are associated with at least 25.4% greater total financial performance than external hires. Overall, the results 1) reveal a deviation from boards’ expectations, and 2) are consistent with Merton’s (1987) observation that correction of an anomaly like this can only occur after a period of time sufficient for its statistical documentation.
Enabling resilience in the Internet of Things

This dissertation explores issues of resilience in pervasive Internet of Things (IoT) deployments. It discusses facilitating the classic observe-analyze-adapt loop by addressing problems with devices, networks, and applications. We discuss our experiences with two projects: the Safe Community Awareness and Alerting Network, which leverages pervasive devices to extend a smarter safer home to residents, and the Community Seismic Network, which creates a massive network of low-cost sensors for detecting earthquakes. We propose a middleware framework for improving resilient communications between devices and services, facilitating a scalable resilient multiprotocol data exchange, and supporting more resilient distributed applications.
Studies of heme-proteins

Abstract With increasing dilution in a medium of constant NaCl-concentration, horse-oxyhemoglobin spectra reveal red shifts in the γ-band, blue shifts in the indole band, and either red shifting or growth in a region centered at 270 mμ. The indole shifts appear to be uniquely associated with the reaction H4 ⇄ 2H2. The changes at 270 mμ appear to be unique to the reaction H2 ⇄ 2H1 Analysis of protein-concentration-difference spectra using these assignments provides a consistent picture of a two-step dissociation mechanism with equilibrium constants at 22 ° and in 1 n NaCl of K(H4 → H2) = 1.3 × 10−5 m and K(H2 → H1) = 1.9 × 10−5 m and no significant concentration of H3 under any circumstances. The γ-band changes contain contributions due to both dissociation processes and may measure interaction between protein conformation and electronic state of the heme group. Studies of the effect of varying salt at constant protein concentration (salt-dependent difference spectra) show shifts generally attributable to scattering effects at the γ-band though Mb(III)H2O demonstrates an effect in this band probably due to a local perturbation by ions of the iron ion. At salt concentrations of about 10−4 n NaCl but not above or below, there is an unusual shift at about 280 mμ attributable to a change in environment of a phenolic group. The Fischer-Cross method of concentration-difference spectra which is developed for hemoglobin is presented as the method of general choice for studies of the dissociation equilibria of this protein.
Sampling design and enumeration statistics for bacteria extracted from marine sediments.

The spatial and temporal distributions of marine bacteria were studied at both a muddy and a sandy subtidal site in North Inlet, S.C. The sampling design was hierarchical, since subsampling (by a dilution series) of the sediments was necessary to count bacterial cells using acridine orange epifluoresence microscopy. The cell count data fit a log-normal distribution. The abundance of bacteria was 1011 g−1 (dry weight) of mud and 109 g−1 (dry weight) of sand. Variance component analyses demonstrated that variation due to the subsampling procedures was always statistically significant. Thus the common practice of counting 20 fields from one filter preparation is inadequate for estimating the true bacterial population variance in marine sediments. It is recommended that replication of the subsampling level be performed. Standardization of data (by dry weight of sediment) decreased sampling variance at the mud site but not at the sand site, implying that bacteria are more homogeneously distributed in sand than in mud.
A suppressive role of STAT1 in lupus-like chronic graft versus host disease (IRM7P.479)

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease driven by genetic and environmental factors with unknown etiopathogenesis. The bm12→B6 chronic graft-versus-host disease (cGVHD) is a well-studied inducible mouse model of SLE. STAT1 is dynamically regulated during the course of immune and inflammatory responses. However, little is known about the role of STAT1 in autoimmune diseases. We induced cGVHD in B6.STAT1-KO and B6.WT mice by intraperitoneally injection of 1×108 splenocytes from bm12 mice. Mice were followed for autoimmune manifestations, such as mortality, skin rash, and renal involvement. Upon injection, WT mice developed anti-dsDNA autoantibodies starting at week 2 (as expected), with decline noted after week 4. In contrast, STAT1-deficient mice exhibited a prolonged and significant increase of anti-dsDNA autoantibody responses compared to WT mice (week 4 to week 8). Severe splenomegaly also developed in cGVHD STAT1-KO mice. Increased autoantibody titers were accompanied by increased proteinuria in mice lacking STAT1 due to immune complex deposition. Three months after injection, 40% of the STAT1-KO mice with cGVH disease were dead. Anti-dsDNA isotypes in cGVH diseased STAT1-KO mice were enhanced (IgG1 responses), but IgG3 responses were absent. STAT1 seems to suppress systemic autoimmunity by altering autoantibody isotype switching. Results from these studies may provide insights into the pathogenesis of STAT1 in SLE.
Chaos in blood flow control in genetic and renovascular hypertensive rats.

Hydrostatic pressure and flow in renal proximal tubules oscillate at 30–40 mHz in normotensive rats anesthetized with halothane. The oscillations originate in tubuloglomerular feedback, a mechanism...
Sample size methods for estimating HIV incidence from cross‐sectional surveys

Understanding HIV incidence, the rate at which new infections occur in populations, is critical for tracking and surveillance of the epidemic. In this article, we derive methods for determining sample sizes for cross-sectional surveys to estimate incidence with sufficient precision. We further show how to specify sample sizes for two successive cross-sectional surveys to detect changes in incidence with adequate power. In these surveys biomarkers such as CD4 cell count, viral load, and recently developed serological assays are used to determine which individuals are in an early disease stage of infection. The total number of individuals in this stage, divided by the number of people who are uninfected, is used to approximate the incidence rate. Our methods account for uncertainty in the durations of time spent in the biomarker defined early disease stage. We find that failure to account for this uncertainty when designing surveys can lead to imprecise estimates of incidence and underpowered studies. We evaluated our sample size methods in simulations and found that they performed well in a variety of underlying epidemics. Code for implementing our methods in R is available with this article at the Biometrics website on Wiley Online Library.
AGGRESSIVE THERAPY IS WARRANTED FOR GALLBLADDER CANCER

Untreated gallbladder cancer is a rapidly fatal disease. Over the years, however, the benefit of aggressive surgical therapy for this disease has been debated. This debate stems from the fact that gallbladder cancer is often metastatic to regional nodes and invasive of the liver at the time of discovery. Complete resection of this tumor, therefore, requires extensive procedures that, until recently, were associated with a very high morbidity and mortality. In this issue Maibenco et al. summarize the changing attitudes about this cancer. Their major message that radical resection of gallbladder cancers can provide long-term survival and cure deserves emphasis.
Regulation of expression of genes for enzymes of the mammalian urea cycle in permanent cell-culture lines of hepatic and non-hepatic origin

We present here the results of investigations conducted by ourselves and others on the regulation of the expression of genes encoding the enzymes of the mammalian urea cycle as manifest in cultured cells of both hepatic and extrahepatic origin. Upon consideration of the recently discovered discrete non-hepatic arginase genetic locus in man and our consequent hypothesis that the form of arginase thus transcribed in such extrahepatic cells functions principally in providing ornithine for protein anabolism and polyamine biosynthesis, rather than in detoxifying ammonia through urea formation, we have chosen instead to study permanent cell lines that are derived from liver and continue to perform a variety of hepatic functions in culture as experimental models for probing the molecular mechanisms underlying the control of ureagenesis within the mature liver cell. Of two such arginase-positive rat-hepatoma lines, we have characterized extensively in one (H4-II-E-C3) the mode of action of glucocorticoids in augmenting the cellular levels of this enzyme as well as of argininosuccinate synthetase. To this end, we have recently demonstrated that these stimulations are both mediated by binding of the hormones to classical cytoplasmic steroid receptors in a specific and saturable fashion and have thus concluded that the H4-II-E-C3 line will provide a suitable cell culture system for subsequent more detailed experiments from which the information garnered will continue to be relevant to the ureagenic pathway as modulated in the differentiated hepatocyte in vivo.
Clinical and Translational Scientist Career Success: Metrics for Evaluation

Despite the increased emphasis on formal training in clinical and translational research and the growth in the number and scope of training programs over the past decade, the impact of training on research productivity and career success has yet to be fully evalu- ated at the institutional level. In this article, the Education Evaluation Working Group of the Clinical and Translational Science Award Consortium introduces selected metrics and methods associated with the assessment of key factors that affect research career success. The goals in providing this information are to encourage more consistent data collection across training sites, to foster more rigorous and systematic exploration of factors associated with career success, and to help address previously identifi ed diffi culties in program evaluation. Clin Trans Sci 2012; Volume 5: 400-407