cssi/SciSciGPT-SciSciNet huggingface dataset:
Phosphorylation of factor Va and factor VIIIa by activated platelets

Platelet activation leads to the incorporation of 32[PO4(2-)] into bovine coagulation factor Va and recombinant human factor VIII. In the presence of the soluble fraction from thrombin-activated platelets and (gamma-32P) adenosine triphosphate, radioactivity is incorporated exclusively into the M(r) = 94,000 heavy chain (H94) of factor Va and into the M(r) = 210,000 to 90,000 heavy chains as well into the M(r) = 80,000 light chain of factor VIII. Proteolysis of the purified phosphorylated M(r) = 94,000 factor Va heavy chain by activated protein C (APC) gave products of M(r) = 70,000, 24,000, and 20,000. Only the intermediate M(r) = 24,000 fragment contained radioactivity. Because the difference between the M(r) = 24,000 and M(r) = 20,000 fragments is located on the COOH-terminal end of the bovine heavy chain, phosphorylation of H94 must occur within the M(r) = 4,000 peptide derived from the carboxyl-terminal end of H94 (residues 663 through 713). Exposure of the radioactive factor VIII molecule to thrombin ultimately resulted in a nonradioactive light chain and an M(r) = 24,000 radioactive fragment that corresponds to the carboxyl-terminal segment of the A1 domain of factor VIII. Based on the known sequence of human factor VIII, phosphorylation of factor VIII by the platelet kinase probably occurs within the acidic regions 337 through 372 and 1649 through 1689 of the procofactor. These acidic regions are highly homologous to sequences known to be phosphorylated by casein kinase II. Results obtained using purified casein kinase II gave a maximum observed stoichiometry of 0.6 mol of 32[PO4(2-)]/mol of factor Va heavy chain and 0.35 mol of 32[PO4(2-)]/mol of factor VIII. Phosphoamino acid analysis of phosphorylated factor Va by casein kinase II or by the platelet kinase showed only the presence of phosphoserine while phosphoamino acid analysis of phosphorylated factor VIII by casein kinase II showed the presence of phosphothreonine as well as small amounts of phosphoserine. The platelet kinase responsible for the phosphorylation of the two cofactors was found to be inhibited by several synthetic protein kinase inhibitors. Finally, partially phosphorylated factor Va was found to be more sensitive to APC inactivation than its native counterpart. Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II-like kinase may downregulate the activity of the two cofactors.
Chronic Pain Status, Nicotine Withdrawal, and Expectancies for Smoking Cessation Among Lighter Smokers

Chronic pain and tobacco smoking are both highly prevalent and comorbid conditions, and chronic pain may pose a barrier to smoking cessation. The objective of this study was to test associations between chronic pain status and several smoking-related factors that have previously been shown to predict cessation outcomes. Daily smokers (N = 205) were recruited from the general population to complete an online survey of pain and tobacco smoking. Results indicated that smokers with chronic pain (vs. no chronic pain) consumed more cigarettes per day, scored higher on an established measure of tobacco dependence, reported having less confidence in their ability to quit, and endorsed expectations for experiencing greater difficulty and more severe nicotine withdrawal during future cessation attempts. Mediation analyses further indicated that the inverse association between chronic pain and abstinence self-efficacy was indirectly influenced by past cessation failures. These findings suggest that individuals with chronic pain may constitute an important subgroup of tobacco smokers who tend to experience lower confidence and greater difficulty when attempting to quit. Future research would benefit from replicating these findings among older and more diverse samples of heavier tobacco smokers, and extending this work to the study of prospective relations between chronic pain status and cessation-relevant processes/outcomes over the course of a quit attempt.
Perioperative do-not-resuscitate orders.

Recent advances in perioperative refusal of resuscitation center on goal-directed orders. Goal-directed orders permit patients to define perioperative resuscitation in terms of outcomes rather than procedures. A typical goal-directed order may state ‘The patient desires resuscitative efforts during surgery and in the postoperative care unit only if the adverse events are believed to be both temporary and reversible, in the clinical judgment of the attending anesthesiologists and surgeons.’ This review also discusses ways to use the ability to withdraw care as a way of honoring patients' wishes.
Inactivation of the miR-183/96/182 Cluster Decreases the Severity of Pseudomonas aeruginosa-Induced Keratitis

PURPOSE The microRNA-183/96/182 cluster (miR-183/96/182) plays important roles in sensory organs. Because the cornea is replete with sensory innervation, we hypothesized that miR-183/96/182 modulates the corneal response to bacterial infection through regulation of neuroimmune interactions. METHODS Eight-week-old miR-183/96/182 knockout (ko) mice and their wild-type littermates (wt) were used. The central cornea of anesthetized mice was scarred and infected with Pseudomonas aeruginosa (PA), strain 19660. Corneal disease was graded at 1, 3, and 5 days postinfection (dpi). Corneal RNA was harvested for quantitative RT-PCR. Polymorphonuclear neutrophils (PMN) were enumerated by myeloperoxidase assays; the number of viable bacteria was determined by plate counts, and ELISA assays were performed to determine cytokine protein levels. A macrophage (Mϕ) cell line and elicited peritoneal PMN were used for in vitro functional assays. RESULTS MicroRNA-183/96/182 is expressed in the cornea, and in Mϕ and PMN of both mice and humans. Inactivation of miR-183/96/182 resulted in decreased corneal nerve density compared with wt mice. Overexpression of miR-183/96/182 in Mϕ decreased, whereas knockdown or inactivation of miR-183/96/182 in Mϕ and PMN increased their capacity for phagocytosis and intracellular killing of PA. In PA-infected corneas, ko mice showed decreased proinflammatory neuropeptides such as substance P and chemoattractant molecules, MIP-2, MCP1, and ICAM1; decreased number of PMN at 1 and 5 dpi; increased viable bacterial load at 1 dpi, but decreased at 5 dpi; and markedly decreased corneal disease. CONCLUSIONS MicroRNA-183/96/182 modulates the corneal response to bacterial infection through its regulation of corneal innervation and innate immunity.
Sic Reinforced-Mosi2 Alloy Matrix Composites

MoSi2 based composites possess significant potential as high temperature structural materials. The present investigation constitutes an initial study of the fabrication and properties of MoSi2/silicide alloys and SiC particle reinforced-MoSi2 /silicide alloy matrix composites. Alloying disilicides (WSi2, Nb5Si2, Ta5Si2 ) and trisilicides (Mo5 Si3, W5Si3, Nb5Si3, Ta5Si3, Ti5Si3 ) were examined. Results indicated that at the 50/50 mole % alloying level, MoSi2 formed solid solutions with the alloying disilicides. Reaction of the MoSi2 /TaSi2 alloy with SiC was observed. An initial assessment of 50/50 mole % disilicide alloy oxidation behavior suggested an oxidation resistance inferior to that of pure MoSi2.
Patient Characteristics, Safety, and Tolerability with Telaprevir Treatment for HCV in the Clinic: a Retrospective, Multicenter Study

Background and Aims There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice.
Faster in-plane switching and reduced rotational viscosity characteristics in a graphene-nematic suspension

The in-plane switching (IPS) for a nematic liquid crystal (LC) was found to be considerably faster when the LC was doped with dilute concentrations of monolayer graphene flakes. Additional studies revealed that the presence of graphene reduced the rotational viscosity of the LC, permitting the nematic director to respond quicker in IPS mode on turning the electric field on. The studies were carried out with several graphene concentrations in the LC, and the experimental results coherently suggest that there exists an optimal concentration of graphene, allowing a reduction in the IPS response time and rotational viscosity in the LC. Above this optimal graphene concentration, the rotational viscosity was found to increase, and consequently, the LC no longer switched faster in IPS mode. The presence of graphene suspension was also found to decrease the LC's pretilt angle significantly due to the π-π electron stacking between the LC molecules and graphene flakes. To understand the π-π stacking interaction, th...
Mono- Versus Combination-Chemotherapy in Metastatic Breast Cancer

The conventional concept to deliver combination chemotherapy to patients with metastatic breast cancer has been questioned in the last years. The rationale for using a polydrug regimen was the assumption of a higher probability to achieve a remission (Falkson et al. 1991, Zinser et al. 1987). Besides others our prospectively-randomized multicenter trial comparing the treatments with 40 mg/m2 of epirubicin or with 40 mg/m2 of adriamycin or with 12 mg/m2 of mitoxantrone each in combination with 600 mg/m2 of cyclophosphamide shows that prognostic factors are more important than the chosen treatments for the outcome in metastatic breast cancer patients (Table 1, Fig. 1 and 2) (Heidemann et al. 1993).
Differential use of protein 4.1 translation initiation sites during erythropoiesis: implications for a mutation-induced stage-specific deficiency of protein 4.1 during erythroid development.

Expression of multiple protein 4.1 isoforms in erythroid progenitors and in a variety of nonerythroid tissues results from alternative pre- mRNA splicing. In 4.1 pre-mRNA, several translation initiation sites are present; synthesis of isoforms larger than 80 kD occurs when an upstream 5′ AUG is spliced in, whereas the 80-kD mature erythroid isoform is produced when the upstream AUG is spliced out and translation is initiated at the downstream AUG. During erythropoiesis, this splicing switch is developmentally regulated. We studied this developmental switch in hereditary elliptocytosis 4.1Alg, in which a DNA rearrangement involving the exon containing the downstream AUG results in loss of coding capacity for the 80-kD 4.1, leading to mature red blood cells deficient in 4.1 with decreased membrane mechanical stability. Analysis of erythroblast RNA by reverse transcriptase- polymerase chain reaction showed that, although it retained the upstream AUG, its coding region was approximately 2.2 kb, compared with approximately 2.5 kb of normal 4.1 mRNA, because of the deletion of exons, including the one that codes for the downstream AUG. Immunofluorescent microscopy and Western blot analysis documented protein 4.1 expression in HE 4.1Alg erythroblasts. These studies emphasize the crucial role of differentiation-regulated RNA splicing because, within the same erythroid tissue, the HE 4.1Alg phenotype did not appear until after the differentiation-associated splicing event.
Lattice Geometry and Crystal Symmetry

This chapter discusses lattice geometry and crystal symmetry. In defining lattice planes and other geometrical features, one can revert for simplicity to the space lattice, assuming that each lattice point in reality corresponds with a unit atomic group, for example, its center of gravity. A lattice plane is one passing through a sheet of lattice points. The chapter also discusses lattice direction and lattice spacing. It further discusses crystal symmetry, which is another consequence of the lattice formation underlying a crystal. In a lattice, it is natural for various directions to be geometrically equivalent, like the diagonals of a cubic cell. Therefore, in the crystal, provided that such directions are ones in which the unit atomic groups also have similar properties, it is natural for them to be equivalent both geometrically and physically, exhibiting similar electrical and thermal conductivities, refractive indices, or elastic moduli. Such full equivalence constitutes symmetry. The symmetry that a crystalline solid can possess is limited, one result being that crystals can be grouped according to their symmetry. First, those can be divided into seven major systems as a result of limitations imposed by lattice geometry; evidently a triclinic crystal cannot exhibit as many potential equivalent directions as a cubic crystal can. Next, each system can be subdivided into classes, arising because directions that are equivalent in the lattice may cease to be equivalent when the lattice points are replaced by unit atomic groups in the crystal.
Polymorphism of Trimeric Perfluoro-ortho-phenylene Mercury, [Hg(o-C6F4)]3

Three new modifications of trimeric perfluoro-ortho-phenylene mercury (2) have been investigated by single crystal X-ray diffraction. In each of these modifications, the molecules of 2 form extended stacks. Within each stack, the successive molecules are parallel and separated by approximately 3.3 - 3.4 A. The packing observed in the different structures is rationalized on the basis of secondary mercury-π interactions, mercuriophilic interactions and electrostatic interactions. Altogether, little preference is given for one particular type of interaction. The packing appears to be dominated by non-directional van der Waals interactions between molecules of 2 which are largely aromatic and whose overall polarizability is magnified by relativistic effects at the mercury(II) centers.
Effect of Direct Contact on the Phytotoxicity of Silver Nanomaterials.

The increasing use of silver nanomaterials (AgNMs) in consumer products will result in an increased amount entering the environment, where AgNMs were recently found to cause phytotoxicity in the model plant Lolium multiflorum. To better understand the causes of the phytotoxicity, we have designed a new set of experiments to study the effect of AgNM dissolution. Dissolution of AgNMs was measured over a 1-month period to determine if dissolution alone caused phytotoxicity. Very little dissolution was observed over the testing period, suggesting a different mechanism caused the majority of the toxicity. To further confirm this hypothesis, AgNMs were physically separated from the seeds and plants by a dialysis membrane. Toxicity was ameliorated in AgNM-exposed plants, showing that direct contact between AgNMs and plant seeds/roots is a required condition for the observed phytotoxicity in plant models. Probing further, a surface reactivity assay showed increased surface reactivity of silver nanoparticles (AgNP...
Personal Experience Versus Media Coverage: Testing the Issue Obtrusiveness Condition of Agenda-Setting Theory in a Developing Country

Issue obtrusiveness has long been considered a condition in agenda-setting effect of mass media. Public’s perceived salience of news issues has been found to be more strongly influenced by mass med...
Attitudes toward evidence-based clinical decision support tools to reduce exposure to ionizing radiation: The Canadian CT Head Rule

IntroductionProblem descriptionA large degree of variation in clinical practice exists among clinicians evaluating and treating individuals with minor brain injuries, resulting in variable consistency of the quality of care delivered in the United States (Institute of Medicine [IOM], 1999). The Amer
Learning History and Learning Language: Focusing on Language in Historical Explanations to Support English Language Learners

History is a language-based discipline. In this discipline, language plays a central role in understanding, reasoning, and explanation. Doing history entails engaging in close reading and evaluation of particular texts, reading across texts to establish intertextual links, constructing meaning by juxtaposing a series of texts, and writing arguments to support a particular interpretation of events, structures, themes, or metasystems (Leinhardt, Stainton, Virji, & Odoroff, 1994, Cognitive and instructional processes in the social sciences. Hillsdale, NJ: Lawrence Erlbaum Associates). Learning history requires teachers and students to engage with multiple kinds of texts deeply, fluently, and analytically
Simultaneous chaotic extensions for general operators on a Hilbert subspace

Abstract For an infinite-codimensional closed subspace M of a separable Hilbert space H, we show that every bounded linear operator A : M → H has a chaotic extension T : H → H . As a generalization of this result, we further show that for any uniformly bounded sequence of linear operators A n : M → H , there exists a bounded linear operator V : M ⊥ → H on the orthogonal complement M ⊥ of M that simultaneously extends all operators A n to chaotic operators A n + V : H → H .
Serving on a hospital board: A case study

Abstract Background It is important for nurses to serve on hospital boards, largely to give voice to matters of quality and patient safety. Purpose Describe what one nurse was able to accomplish on a statewide board over time as chair of the board’s Quality and Patient Safety Committee. Methods The experience was analyzed using auto-ethnography and narrative analysis. Discussion After describing the organization, the paper summarizes the key issues on which the nurse took the lead, measures of success in the role, and learning acquired along the way. Conclusion The “system” orientation of nurses is an asset in getting hospital boards to view themselves as institutional champions of quality.
Endovascular and Open Repair of Ruptured Infrarenal Aortic Aneurysms at a Tertiary Care Center

Background The mortality of ruptured abdominal aortic aneurysms (rAAAs) has been reported as high as 90%. Loss of consciousness and a systolic blood pressure of Methods Retrospective review of all rAAAs presenting to a tertiary care center between January 1, 2000 and December 31, 2011 was performed. Patients were grouped based on the surgical approach (OR versus EVAR). Patient demographics, intraoperative details, and postoperative mortality and morbidity rates were compared. Statistical analyses were conducted with Stata, version 12. Results One hundred twenty-six patients presented with rAAA over the study period. Patients who declined repair ( n = 14) or died before repair ( n = 13) were excluded from this study. Of the 99 patients who underwent repair, 25 patients (25.3%) received EVAR and 74 (74.7%) underwent OR. One patient required conversion to OR from EVAR (1.0%). Overall, 30-day and 1-year mortality was 35.4% and 41.4%, respectively, with no difference seen between the 2 types of repair (30-day mortality: EVAR = 24.0%, OR = 39.2%, P = 0.17; 1-year mortality: EVAR = 32.0%, OR = 44.6%, P = 0.27). Major morbidity also did not differ between the 2 repair procedures (EVAR = 60.0%, OR = 60.8%, P = 0.94). However, patients undergoing EVAR had significantly less estimated blood loss (median: 0.3 vs. 3.0 L, P P = 0.0041). Furthermore, although there was no significant difference in length of overall hospital stay between the 2 groups (8.5 vs. 15 days in the OR group, P = 0.18), significantly more patients in the EVAR group were discharged to home (66.7% vs. 57.1% in the OR group, P = 0.03). Conclusions In contrast to recently published series, this series shows no differences in morbidity or mortality between EVAR or OR of rAAAs. EVAR is appropriate in stable patients with a rAAA and favorable anatomy.
R-Spondin chromosome rearrangements drive Wnt-dependent tumour initiation and maintenance in the intestine

Defining the genetic drivers of cancer progression is a key in understanding disease biology and developing effective targeted therapies. Chromosome rearrangements are a common feature of human malignancies, but whether they represent bona fide cancer drivers and therapeutically actionable targets, requires functional testing. Here, we describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo. We show that both Rspo2 and Rspo3 fusion events are sufficient to initiate hyperplasia and tumour development in vivo, without additional cooperating genetic events. Rspo-fusion tumours are entirely Wnt-dependent, as treatment with an inhibitor of Wnt secretion, LGK974, drives rapid tumour clearance from the intestinal mucosa without effects on normal intestinal crypts. Altogether, our study provides direct evidence that endogenous Rspo2 and Rspo3 chromosome rearrangements can initiate and maintain tumour development, and indicate a viable therapeutic window for LGK974 treatment of RSPO-fusion cancers.
Hidden Hearing Loss? No Effect of Common Recreational Noise Exposure on Cochlear Nerve Response Amplitude in Humans.

This study tested hypothesized relationships between noise exposure and auditory deficits. Retrospective assessment of potential associations between noise exposure history and performance on an audiologic test battery and prospective assessment of potential changes in performance after new recreational noise exposure were completed. METHODS: 32 participants (13M, 19F) with normal hearing (25-dB HL or better,0.25-8 kHz) were asked to participate in 3 pre- and post-exposure sessions including: otoscopy, tympanometry, distortion product otoacoustic emissions (DPOAEs) (f2 frequencies 1-8 kHz), pure-tone audiometry (0.25-8 kHz), Words-in-Noise (WIN) test, and electrocochleography (eCochG) measurements at 70, 80, and 90-dB nHL (click, and 1-4 kHz tone-bursts). The first session was used to collect baseline data, the second session was collected the day after a loud recreational event, and the third session was collected 1-week later. Of the 32 participants, 26 completed all 3 sessions. RESULTS: The retrospective analysis did not reveal statistically significant relationships between noise exposure history and any auditory deficits. The day after new exposure, there was a statistically significant correlation between noise “dose” and WIN performance overall, and within the 4-dB signal-to-babble ratio. In contrast, there were no statistically significant correlations between noise dose and changes in threshold, DPOAE amplitude, or AP amplitude the day after new noise exposure. Additional analyses revealed a statistically significant relationship between TTS and DPOAE amplitude at 6 kHz, with temporarily decreased DPOAE amplitude observed with increasing TTS. CONCLUSIONS: There was no evidence of auditory deficits as a function of previous noise exposure history, and no permanent change in audiometric, electrophysiologic, or functional measures after new recreational noise exposure. There were very few participants with TTS the day after exposure - a test time selected to be consistent with previous animal studies. The largest observed TTS was approximately 20-dB. The observed pattern of small TTS suggests little risk of synaptopathy from common, recreational noise exposure, and that we should not expect to observe changes in evoked potentials for this reason. No such changes were observed in this study. These data do not support suggestions that common, recreational noise exposure is likely to result in “hidden hearing loss”.
Linking in vitro estrogenicity to adverse effects in the inland silverside (Menidia beryllina).

High-throughput cell assays that detect and integrate the response of multiple chemicals acting via a common mode of action have the potential to enhance current environmental monitoring practices. Establishing the linkage between in vitro and in vivo responses is key to demonstrating that in vitro cell assays can be predictive of ecologically relevant outcomes. The present study investigated the potency of 17β-estradiol (E2), estrone (E1), nonylphenol (NP), and treated wastewater effluent using the readily available GeneBLAzer® estrogen receptor transactivation assay and 2 life stages of the inland silverside (Menidia beryllina). In vitro estrogenic potencies were ranked as follows: E2 > E1 >> NP. All 3 model estrogens induced vitellogenin and choriogenin expression in a dose-dependent manner in larvae and juveniles. However, apical effects were only found for E2 and E1 exposures of juveniles, which resulted in female-skewed sex ratios. Wastewater effluent samples exhibiting low in vitro estrogenicity (below the 10% effective concentration [EC10]), did not cause significant changes in M. beryllina. Significant induction of estrogen-responsive genes was observed at concentrations 6 to 26 times higher than in vitro responses. Gonadal feminization occurred at concentrations at least 19 to 26 times higher than the in vitro responses. These findings indicated that in vitro cell assays were more sensitive than the fish assays, making it possible to develop in vitro effect thresholds protective of aquatic organisms. Environ Toxicol Chem 2018;37:884-892. © 2017 SETAC.
Peer nominations and its relation to interactions in a computer game

Peer nomination has been one of the main tools used by social scientists to study the structure of social networks. Traditionally, the nominations are collected by asking participants to select a fixed number of peers, which in turn are all considered for the analysis with the same strength. In this paper, we explore several different ways of measuring the popularity of peers by taking into consideration not only the nominations themselves but their order and total quantity in the context of a computer social game. Using these different metrics, we explore the relationship between the nominations and the players' interactions through text messages while playing the game. Although all five proposed metrics can be used to find popular individuals among peers, they allow scientists to measure different characteristics of the individuals as shown by the correlations found between popularity scores and interaction variables.
Two-Person Relational Psychotherapy: Elementary School Age Youth

Children typically begin elementary school—primary education—at 5 years old, after kindergarten. Elementary school generally goes through the sixth grade, typically to 11 years old. In elementary school, children learn the basics of reading, math, science, and other subjects on which later learning will build. Socialization skills are an important aspect of this period. Granic and Patterson (Psychol Rev 113(1):101–131, 2006) eloquently stated, “Parents and children are confronted with a variety of daily tasks (e.g., clean-up time, playing games, problem solving when conflict arises, eating dinner together). From our perspective, the extent to which parents and children can flexibly and appropriately respond, emotionally, cognitively, and behaviorally, to shifts in contexts may tap a repertoire of alternative strategies that correspond to how children will adapt to future challenges at school and with peers.” Thus, during this age, the child’s most skilled way in communicating his or her affective states is initially through playing and making drawings, and later, in preadolescent years, verbal communication takes hold.
CT-Guided Biopsy

Computed tomography (CT) scanners are integral components of imaging facilities. CT scanners are widely available and can easily accommodate biopsy procedures. The high spatial and contrast resolution of CT images can help localize biopsy targets almost anywhere in the human body. CT fluoroscopy, when available, can help expedite procedures and make the biopsy process more efficient. This chapter outlines the equipment, advantages, disadvantages, applications, and techniques used in CT-guided and CT fluoroscopy-guided biopsies.
The Design of Montesquieu’s Considerations : Considerationson the causes of the greatness of the Romans and their decline*

Montesquieu's work on the Romans appeared in 1734, about midway between his other two great works, Persian Letters, and The Spirit of the Laws. Considerations, like Montesquieu' other two major works, contains parts linked by a "secret chain" or hidden design. Montesquieu takes his account of the Western Empire up to the time of its collapse under Arcadius and Honorius. A sympathetic study of republican Rome is, in fact, by its very nature an attack on the Bible, its leaders and its peoples. In particular, any effort to explain the causes of Rome's greatness and decline must reckon with the religious possibility. Montesquieu's radical teaching is not meant to have immediate practical consequences. Instead, it seeks to win the best minds both as colleagues in wisdom and as allies in the spiritual warfare necessary to preparing for whatever opportunities the future may bring.
Protein composition of the muscle mitochondrial reticulum during postnatal development.

Key points Muscle mitochondrial networks changed from a longitudinal, fibre parallel orientation to a perpendicular configuration during postnatal development. Mitochondrial dynamics, mitophagy and calcium uptake proteins were abundant during early postnatal development. Mitochondrial biogenesis and oxidative phosphorylation proteins were upregulated throughout muscle development. Postnatal muscle mitochondrial network formation is accompanied by a change in protein expression profile from mitochondria designed for co-ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism. Abstract Striated muscle mitochondria form connected networks capable of rapid cellular energy distribution. However, the mitochondrial reticulum is not formed at birth and the mechanisms driving network development remain unclear. In the present study, we aimed to establish the network formation timecourse and protein expression profile during postnatal development of the murine muscle mitochondrial reticulum. Two-photon microscopy was used to observe mitochondrial network orientation in tibialis anterior (TA) muscles of live mice at postnatal days (P) 1, 7, 14, 21 and 42, respectively. All muscle fibres maintained a longitudinal, fibre parallel mitochondrial network orientation early in development (P1-7). Mixed networks were most common at P14 but, by P21, almost all fibres had developed the perpendicular mitochondrial orientation observed in mature, glycolytic fibres. Tandem mass tag proteomics were then applied to examine changes in 6869 protein abundances in developing TA muscles. Mitochondrial proteins increased by 32% from P1 to P42. In addition, both nuclear- and mitochondrial-DNA encoded oxidative phosphorylation (OxPhos) components were increased during development, whereas OxPhos assembly factors decreased. Although mitochondrial dynamics and mitophagy were induced at P1-7, mitochondrial biogenesis was enhanced after P14. Moreover, calcium signalling proteins and the mitochondrial calcium uniporter had the highest expression early in postnatal development. In conclusion, mitochondrial networks transform from a fibre parallel to perpendicular orientation during the second and third weeks after birth in murine glycolytic skeletal muscle. This structural transition is accompanied by a change in protein expression profile from mitochondria designed for co-ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism.
Phonetic convergence and divergence in the American Midwest

The magnitude of phonetic convergence in word shadowing is affected by phonetic factors, including the shadowers’ phonetic distance from the model talker, and social factors, including the perceived prestige of the model talker’s variety. The current study explored the effects of these factors on phonetic convergence to the Northern dialect of American English by shadowers from the Midwestern United States. The shadowers read a set of target words to provide their baseline productions and then repeated the same target words after a native speaker of the Northern dialect. The target words contained stressed vowels that are phonetically shifted in the Northern dialect relative to other American English varieties. Phonetic convergence in word duration and vowel formant frequencies was observed for some vowel categories but not others. This phonetic selectivity was not driven by the acoustic distance between the shadowers’ baseline productions and the model talker’s productions. Phonetic convergence in word duration and vowel formant frequencies also varied depending on whether or not the shadowers were told where the model talker was from, leading to divergence for some dialect-specific features in the shadowing task. These findings provide additional evidence for the roles of phonetic and social factors in phonetic convergence. The magnitude of phonetic convergence in word shadowing is affected by phonetic factors, including the shadowers’ phonetic distance from the model talker, and social factors, including the perceived prestige of the model talker’s variety. The current study explored the effects of these factors on phonetic convergence to the Northern dialect of American English by shadowers from the Midwestern United States. The shadowers read a set of target words to provide their baseline productions and then repeated the same target words after a native speaker of the Northern dialect. The target words contained stressed vowels that are phonetically shifted in the Northern dialect relative to other American English varieties. Phonetic convergence in word duration and vowel formant frequencies was observed for some vowel categories but not others. This phonetic selectivity was not driven by the acoustic distance between the shadowers’ baseline productions and the model talker’s productions. Phonetic convergence in word d...
Peramorphosis, an evolutionary developmental mechanism in neotropical bat skull diversity.

Background The neotropical leaf‐nosed bats (Chiroptera, Phyllostomidae) are an ecologically diverse group of mammals with distinctive morphological adaptations associated with specialized modes of feeding. The dramatic skull shape changes between related species result from changes in the craniofacial development process, which brings into focus the nature of the underlying evolutionary developmental processes. Results In this study, we use three‐dimensional geometric morphometrics to describe, quantify, and compare morphological modifications unfolding during evolution and development of phyllostomid bats. We examine how changes in development of the cranium may contribute to the evolution of the bat craniofacial skeleton. Comparisons of ontogenetic trajectories to evolutionary trajectories reveal two separate evolutionary developmental growth processes contributing to modifications in skull morphogenesis: acceleration and hypermorphosis. Conclusion These findings are consistent with a role for peramorphosis, a form of heterochrony, in the evolution of bat dietary specialists.
How Do Interactions between Interfirm Real Options Affect Companies’ Investment Decisions

This study attempts to understand how CVC investment is related to subsequent acquisition activities. In particular, it investigates why the focal company chooses to acquire a technological new ven...
Evaluation and management of cauda equina syndrome in the emergency department.

Abstract Background Cauda equina syndrome (CES) may be a devastating disease with the potential for significant patient morbidity. It is essential for emergency clinicians to be aware of how to effectively diagnose and manage this condition. Objective This article provides a narrative review of the diagnosis and management of CES for the emergency clinician. Discussion Cauda equina syndrome is a rare but emergent condition associated with back pain. It can result in severe morbidity and can be due to a variety of causes, most commonly vertebral disc protrusion. Diagnosis is often delayed, which may result in a poor prognosis. Red flags and findings consistent with CES include bilateral neurogenic sciatica, reduced perineal sensation, altered bladder function leading to painless urinary retention, loss of anal tone, and loss of sexual function. In isolation, history and examination findings demonstrate poor sensitivity. Symptoms may occur either suddenly or gradually, and most patients do not present with all of these symptoms. Postvoid bladder volume assessments can assist in the evaluation, but the diagnosis typically involves magnetic resonance imaging (MRI) or computed tomography myelography if MRI is not available. Treatment relies upon surgical consultation and operative intervention for decompression. Conclusion Cauda equina syndrome can be a difficult diagnosis. However, knowledge of the history and examination findings, imaging, and treatment can assist the emergency clinician in optimizing management of this condition.
Modeling the Role of Sensory Feedback in Speech Motor Control and Learning.

Purpose While the speech motor system is sensitive to feedback perturbations, sensory feedback does not seem to be critical to speech motor production. How the speech motor system is able to be so ...
Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease.

Background Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial. Methods A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced. Results Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment. Conclusions In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.
Toba (Guaicuruan) hunter-gatherers in the Bolivian Chaco

Toba hunter-gatherers inhabited the dry savannas in the Manso plains of the Bolivian Chaco since precolonial times. Early on, Spaniards learned that these peoples (speakers of a language now classi...
Pseudotime Based Discovery of Breast Cancer Heterogeneity

Breast cancer is highly sporadic and heterogeneous in nature. Even the patients with same clinical stage do not cluster together in terms of genomic profiles such as mRNA expression. In order to prevent and cure breast cancer completely, it is essential to decipher the detailed heterogeneity of breast cancer at genomic level. Putting the cancer patients on a time scale, which represents the trajectory of cancer development, may help discover the detailed heterogeneity. This in turn would help establish the mechanisms for prevention and complete cure of breast cancer. The goal of this study is to discover the heterogeneity of breast cancer by ordering the cancer patients using pseudotime. This is achieved through two objectives: First, a computational framework is developed to place the cancer patients on a time scale, meaning construct a trajectory of cancer development, by inferring pseudotime from static mRNA expression data; Second, discovering breast cancer heterogeneity at different time periods of the trajectory using statistical and machine learning techniques. In this study, the trajectory of breast cancer progression was constructed using static mRNA expression profiles of 1072 breast cancer patients by inferring pseudotime. Three sets of key genes discovered using supervised machine learning techniques are used to develop the trajectories. The first set of genes are PAM50 genes which is available in literature. The second and third sets of genes were discovered in the present study using the clinical stages of breast cancer (Stage-I, Stage-II, Stage-III, and Stage-IV). The proposed computational framework has the capability of deciphering heterogeneity in breast cancer at a granular level. The results also show the existence of multiple parallel trajectories at different time periods of cancer development or progression.
Design Guidelines for Schematizing and Rendering Haptically Perceivable Graphical Elements on Touchscreen Devices

This paper explores the viability of new touchscreen-based haptic/vibrotactile interactions as a primary modality for perceiving visual graphical elements in eyes-free situations. For touchscreen-b...
Screening for Sexually Transmitted Infections During Hepatitis C Treatment to Predict Reinfection Among People With HIV.

Author(s): Hill, Lucas A; Martin, Natasha K; Torriani, Francesca J; Jain, Sonia; Qin, Huifang; Mathews, Wm Christopher; Cachay, Edward R | Abstract: BackgroundLittle is known about the risk of hepatitis C virus (HCV) reinfection among people with HIV (PWH) in the direct-acting antiviral (DAA) era. We evaluate HCV reinfection rates in the DAA era and characterize presustained virologic response (SVR) behavioral risk factors associated with reinfection among PWH at the University of California, San Diego (UCSD).MethodsObservational longitudinal cohort of PWH treated with DAAs between 2014 and July 2019 who achieved SVR and had at least 1 subsequent HCV viral load measurement. HCV reinfection was defined as new HCV viremia after SVR. We examined whether screening for sexually transmitted infections (STIs) and substance use during the pre-SVR period could identify patients at greater risk for reinfection using exact Poisson regression to compare reinfection incidence rates between those with and without pre-SVR STIs and positive urine drug screens.ResultsEight out of 200 PWH were reinfected with HCV a median ~26 weeks after SVR over 328.1 person-years of follow-up (PYFU), for an incidence rate of 2.44/100 PYFU. The observed HCV reinfection rate was highest among men who have sex with men who inject drugs (MSM IDU; 4.63/100 PFYU) and those aged 30-39 years (6.80/100 PYFU). Having a positive gonorrhea/chlamydia test during the pre-SVR period was a predictor of HCV reinfection.ConclusionsThe HCV reinfection rate in the DAA era is similar to the rate observed in the interferon era in San Diego in PWH. STI screening during HCV treatment may help determine those at higher risk for HCV reinfection.
Defects in The First Step of Lipoprotein Maturation Underlie The Synthetic Lethality of Escherichia coli Lacking The Inner Membrane Proteins YciB And DcrB.

ABSTRACT Nearly a quarter of the Escherichia coli genome encodes inner membrane proteins, of which approximately a third have unassigned or poorly understood functions. We had previously demonstrated that the synergy between the functional roles of the inner membrane-spanning YciB and the inner membrane lipoprotein DcrB is essential in maintaining cell envelope integrity. In yciB dcrB cells, the abundant outer membrane lipoprotein Lpp mislocalizes to the inner membrane, where it forms toxic linkages to peptidoglycan. Here, we report that the aberrant localization of Lpp in this double mutant is due to inefficient lipid modification at the first step in lipoprotein maturation. Both Cpx and Rcs signaling systems are upregulated in response to the envelope stress. The phosphatidylglycerol:preprolipoprotein diacylglyceryl transferase, Lgt, catalyzes the initial step in lipoprotein maturation. Our results suggest that the attenuation in Lgt-mediated transacylation in the double mutant is not a consequence of lowered phosphatidylglycerol levels. Instead, we posit that altered membrane fluidity, perhaps due to changes in lipid homeostasis, may lead to the impairment in Lgt function. Consistent with this idea, a dcrB null mutant is not viable when grown at low temperatures, conditions that impact membrane fluidity. Like the yciB dcrB double mutant, dcrB null-mediated toxicity can be overcome in distinct ways—by increased expression of Lgt, deletion of lpp, or removal of Lpp-peptidoglycan linkages. The last of these events leads to elevated membrane vesiculation and lipid loss, which may in turn impact membrane homeostasis in the double mutant. IMPORTANCE A distinguishing feature of Gram-negative bacteria is their double-membraned cell envelope, which presents a formidable barrier against environmental stress. In E. coli, more than a quarter of the cellular proteins reside at the inner membrane, but about a third of these proteins are functionally unassigned or their function is incompletely understood. Here, we show that the synthetic lethality underlying the inactivation of two inner membrane proteins, a small integral membrane protein (YciB) and a lipoprotein (DcrB), results from the attenuation of the first step of lipoprotein maturation at the inner membrane. We propose that these two inner membrane proteins, YciB and DcrB, play a role in membrane homeostasis in E. coli and related bacteria.
Design Properties of a 26 GHz Circularly Polarized Square Patch Antenna With Rectangular Slot

A square microstrip patch antenna with a diagonally symmetric rectangular slot is edge-fed with a 50 $\Omega$ microstrip line and designed to produce RHCP at 26 GHz. Rectangular slots with lengths from 1.1 mm to 1.7 mm and widths from 0.05 mm to 0.30 mm are considered. Increasing the size of the rectangular slot perimeter improves the impedance match between patch and feed line while reducing resonant frequency. Larger slots are shown to damage the axial ratio. A compromise slot size of 1.4 mm $\times 0.20$ mm is suggested with best axial ratio frequency at 24.6 GHz., a minimum axial ratio of 1.27 $\mathrm{dB}$ , and $S_{11}=-6$ . 53 $\mathrm{dB}$ at 24.68 GHz. This optimized patch element is designed for use in a $N\times N$ array for satellite communication.
Contribution heterogeneity and the dynamics of contributions in repeated public good games

Abstract Using data from four previous experiments, I examine the relationship between contribution heterogeneity and the changes in average contributions that occur from round to round. Specifically, I develop and test the hypothesis that when there is greater contribution heterogeneity in a particular round, average contributions will decrease more between the current round and the next round, all else being equal. I find strong support for my hypothesis with partner and stranger matching, and with and without belief elicitation about the average contributions of others. When beliefs are elicited, changes in average contributions tend to be positively associated with changes in average beliefs, but the relationship is not as strong as the one between changes in average contributions and contribution heterogeneity. In order to determine the driving force underlying the empirical relationship between contribution heterogeneity and changes in average contributions, I simulate contributions under different counterfactual assumptions about belief heterogeneity and contribution preference heterogeneity using one of the data sets. I compare the simulation models in terms of how well each matches the data. The simulations indicate that contribution preference heterogeneity is a stronger factor underlying the dynamics of contributions than belief heterogeneity.