Miracle-dz/UniFAR-FTUs huggingface dataset:
The quiet embryo hypothesis: Molecular characteristics favoring viability

It has been proposed that the viability of early mammalian embryos is associated with a metabolism that is “quiet” rather than “active” (Leese HJ, 2002:BioEssays 24:845–849). The data on which this hypothesis was based were largely drawn from measurements on the depletion and appearance of amino acids from the culture medium. Data on the de novo synthesis of protein in in vivo‐ and in vitro‐derived bovine embryos, as determined from the flux of radiolabeled methionine, have provided further support of the hypothesis and are interpreted to provide a new set of testable propositions that could illuminate the molecular basis of the quiet metabolism phenotype. The propositions are based on the premise that the extent of DNA damage, and the RNA and protein content of the immature oocyte, are key factors in determining whether the zygote progresses to the blastocyst stage. We propose that stochastic events and environmental stresses determine whether the condition of the genome, transcriptome, and proteome of the zygote will support development. Several molecular components are identified that may determine the viability of a zygote, and we speculate that the cellular response to unfavorable events or excessive DNA damage may be the premature activation of the embryonic genome and of apoptosis. Mol. Reprod. Dev. 74: 1345–1353, 2007. © 2007 Wiley‐Liss, Inc.
Reality-Check for DTN Routing Algorithms

Many applications of ad-hoc networks include intermittent connectivity. Anyone wishing to implement routing into her delay-tolerant network can select from a wide variation of options, but the choice is hard, as there is no strong comparative evidence to the relative performance of the algorithms. Every paper uses a different setting, mostly far from realistic. In our desire to improve the basis for decisions, we simulated a promising selection of DTN routing algorithms in three vastly different scenarios, all based on publicly available real-world traces. Using our open-source DTN simulator, we compare and analyse 11 routing techniques, then provide explanations for the behaviour and give advice for choosing a suitable mechanism. To our own surprise, the results challenge the conventional wisdom gained from synthetic simulations and poses the question whether the world is ready for DTNs.
A system for quantitative determination of cytotoxic activity of antisera to ascites tumor cells.

Criteria are described for recognizing early degenerative changes that occur when mouse ascites tumor cells are exposed to homologous or heterologous antisera. These permit determination of the same percentage of deformed cells, irrespective of whether or not vital staining dyes are used. When 10 million cells of the L4946 or E9514-A ascites tumors were incubated at 37° C. in 1 ml. modified Locke's buffer with excess complement, the percentage of deformed cells leveled out between 1 and 3 hours' incubation at a value determined by antibody concentration. A titration curve, of percentage cells deformed after 2 hours' incubation against antiserum concentration, gave the cytotoxic titer, i.e., the final concentration of antiserum giving 50 per cent plus one-half the control level of deformed cells. For a rabbit antiserum to L4946 cells, the cytotoxic titer was 1.24 parts per thousand, with a standard deviation of 21 per cent. A relationship between cytotoxic titer and cell concentration in the medium was demonstrated, and dependence on pH, osmolarity, and complement concentration were investigated. To relate cell deformation to cell death, serial dilutions of L4946 cells containing known percentages of deformed cells were inoculated into AKR mice and survival noted. The results indicate that the microscopic count underestimates the damage done to cells by antiserum. A method for estimating cell viability following inoculation of mice with tumor cells is described, which takes into account the period of temporary survival of mice dying from tumor, in addition to mere death or long-term survival.
Interjurisdictional Agreements in Metropolitan Areas

The utility of interjurisdictional cooperative efforts to provide public services within metropolitan areas is reassessed through an examination of interjurisdictional agreements in one middle-size metropolitan area, the Quad-City area of Iowa and Illinois. An extensive, complicated cooperative network is found to exist among jurisdictions, involving important public services. Many of the perceived limitations to voluntary cooperation are seen to be less compelling than much of the literature would indicate.
Kinematic Analysis of Hand Movements After Tendon Repair Surgery: A New Assessment Using Drawing Movements

Stenekes MW, Nicolai J-PA, Geertzen JHB, Mulder T: Kinematic analysis of hand movements after tendon repair surgery: a new assessment using drawing movements. Am J Phys Med Rehabil 2008;87:169–176. Objective:Although several hand outcome tests exist to judge skill level after hand injury, currently none give insight into how tasks are performed by looking at kinematic parameters. In this article, the clinical value of analyzing kinematic parameters related to the drawing of a triangle on a graphics tablet by healthy subjects and patients with hand injury is discussed. Design:In a first experiment 10 healthy subjects drew the triangles as accurately as possible at various speeds. In a second experiment, 67 healthy subjects and 12 patients with flexor tendon injury were measured repeatedly. Results:In the first experiment, the analysis showed a high linear correlation between speed and accuracy for each individual (Pearson correlation coefficient ≥0.762, P ≤ 0.01). The data led to a formula to standardize deviation for drawing speed, so that different measurements can be compared. In the second experiment, these two measurements correlated well (Pearson correlation coefficient = 0.909, P < 0.001), although a learning effect was noticed (5.4% improvement on average). In healthy subjects the dominant hand performed significantly better than the nondominant hand (P < 0.001). Patients performed significantly worse with their injured hand after 6 wks of dynamic splinting than did healthy subjects (P = 0.003). With their uninjured hand, they performed better than the controls. Six weeks after removal of the splint, no kinematic differences could be discovered between patients and controls. Conclusion:The results show that kinematic parameters of hand movements may be of additional value for assessing functional recovery from hand injury.
PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner

ABSTRACT A variant within the gene locus encoding PTPN22 (protein tyrosine phosphatase, non-receptor type 22) emerged as an important risk factor for auto-inflammatory disorders, including rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes, but at the same time protects from Crohn disease, one of the 2 main forms of inflammatory bowel diseases. We have previously shown that loss of PTPN22 results in decreased NLRP3 (NLR family pyrin domain containing 3) activation and that this effect is mediated via enhanced NLRP3 phosphorylation. However, it is unclear how phosphorylation of NLRP3 mediates its inhibition. Here, we demonstrate that loss of macroautophagy/autophagy abrogates the inhibitory effect on NLRP3 activation observed upon loss of PTPN22. Phosphorylated, but not nonphosphorylated NLRP3 is found in autophagosomes, indicating that NLRP3 phosphorylation mediates its inactivation via promoting sequestration into phagophores, the precursors to autophagosomes. This finding shows that autophagy and NLRP3 inflammasome activation are connected, and that PTPN22 plays a key role in the regulation of those 2 pathways. Given its role in inflammatory disorders, PTPN22 might be an attractive therapeutic target, and understanding the cellular mechanisms modulated by PTPN22 is of crucial importance.
Ketamine analgesic effect by continuous intravenous infusion in refractory cancer pain: considerations about the clinical research in palliative care.

BACKGROUND The literature has described the use of ketamine as an adjuvant treatment for opioid-refractory cancer pain. None of these studies have used the drug in a palliative care patient population. AIMS The primary objective of the study was to assess the efficacy of continuous intravenous infusion of ketamine in patients suffering from cancer pain refractory to opiates who had been admitted to palliative care units. Secondary objectives were to assess patients' satisfaction with and tolerance of ketamine. METHODS A randomized, double-blind, placebo-controlled study was designed, and the study setting included seven French adult palliative care units. Inclusion criteria were age ≥18 years, and cancer pain refractory to standard opiates. Evaluations were conducted at randomization (baseline), at ketamine or placebo introduction time (T0), and at 2 hours (T1), 24 hours (T2), and 48 hours (T3) after T0. The primary evaluation criterion was pain efficacy assessed using a patient self-rated Numeric Pain Intensity Scale (NPIS) at T1. The main secondary evaluation criteria were daily morphine dose, symptom evaluation (Edmonton Symptom Assessment Scale [ESAS]), and patient satisfaction (Pain Treatment Satisfaction Scale [PTSS]). RESULTS Twenty patients were analyzed (11 received ketamine and 9 received placebo). Self-reported pain did not differ between the two groups, as the symptoms continued to evolve during the study period. The tolerance for ketamine was satisfactory. CONCLUSION The present study did not confirm the efficacy of the ketamine-morphine combination in refractory cancer pain. The results suggest that specific populations could be "good responders" for this therapeutic approach. Further studies should be performed that take into account the difficulties of conducting clinical research in the palliative care context.
Market Orientation and Performance: A Meta-Analysis and Cross-National Comparisons

Quantitative evidence drawn from a meta-analysis of 56 studies (58 samples) conducted in 28 countries reveals that market orientation is a generic determinant of firm performance. However, stronger effects were found for studies set in large, mature markets and when market orientation was measured using Kohli, Jaworski and Kumar's (1993) MARKOR scale. The meta-analysis also revealed that the value of a market orientation weakens in proportion to the cultural distance separating the home market from the USA. This study thus extends previous research by: (1) providing evidence of measurement moderators that inhibit the generalization of results obtained from studies using different scales and performance variables; (2) establishing benchmark effect sizes for specific regions around the world; and (3) revealing that the managerial value of a market orientation is significantly affected by the cultural and economic characteristics of the host country.
Effects of Stable Flies (Diptera: Muscidae) on Weight Gains of Grazing Yearling Cattle

Abstract Differences in weight gains caused by stable flies, Stomoxys calcitrans (L.), on grazing yearling steer/calves averaged 0.2 kg per steer in a 3-yr study on canyon range pastures in West Central Nebraska. Stable fly numbers averaged 0.85 per front leg on treated calves and 3.64 per front leg on control calves. In 2 of the 3 yr after the grazing trials were completed, the calves were placed in a feedlot and fed a finishing ration. Compensatory gain did not occur in the feedlot after the stable fly stress was removed.
Exploring the Universe of Protein Structures beyond the Protein Data Bank

It is currently believed that the atlas of existing protein structures is faithfully represented in the Protein Data Bank. However, whether this atlas covers the full universe of all possible protein structures is still a highly debated issue. By using a sophisticated numerical approach, we performed an exhaustive exploration of the conformational space of a 60 amino acid polypeptide chain described with an accurate all-atom interaction potential. We generated a database of around 30,000 compact folds with at least of secondary structure corresponding to local minima of the potential energy. This ensemble plausibly represents the universe of protein folds of similar length; indeed, all the known folds are represented in the set with good accuracy. However, we discover that the known folds form a rather small subset, which cannot be reproduced by choosing random structures in the database. Rather, natural and possible folds differ by the contact order, on average significantly smaller in the former. This suggests the presence of an evolutionary bias, possibly related to kinetic accessibility, towards structures with shorter loops between contacting residues. Beside their conceptual relevance, the new structures open a range of practical applications such as the development of accurate structure prediction strategies, the optimization of force fields, and the identification and design of novel folds.
Profiling Younger Adults’ Communication About Aging

According to the Communicative Ecology Model of Successful Aging (CEMSA), how people talk about age can have implications for how they cope with aging later in life. However, most research on communication and successful aging has focused on older adults. In this study, we use latent class analysis to profile how younger adults (age 18–39) communicate about aging and examine how these profiles relate to their attitudes toward aging (affect, efficacy, anxiety, and perceptions of successful aging). Consistent with past research on older adults, we found three distinct profiles of communication behavior (disengaged, engaged, and bantering). An engaged profile was clearly associated with the most positive attitudes toward aging, while a disengaged profile was associated with the least positive attitudes. These findings suggest that patterns of talk about aging may start early in life, underscoring the importance of studying communication about aging across the lifespan.
Hierarchical subdivision of Arctic tundra based on vegetation response to climate, parent material and topography

Current land‐cover classifications used for global modelling portray Arctic tundra as one or two classes. This is insufficient for analysis of climate–vegetation interactions. This paper presents a simple three‐level vegetation‐map legend system useful for modelling at global, regional, and landscape scales. At the highest level (global scale: 107−108 km2) the Tundra Zone is divided into four subzones based on vegetation response to temperature along the latitudinal temperature gradient from north to south: (1) Cushion‐forb, (2) Prostrate Dwarf‐shrub, (3) Erect Dwarf‐shrub, and (4) Low Shrub subzones. The boundaries follow a modification of Yurtsev's phytogeographic subzones. Parent material and topography are also major considerations at global, regional, and landscape scales. Soil pH is a key variable for many ecosystem responses, and a division into acidic (pH 5.5 or less) and nonacidic soils is used. A conceptual mesotopographic gradient is used to characterize the influence of soil‐moisture and snow regimes. The example legend framework focuses on the Northern Alaska floristic subprovince, and could be expanded to other floristic provinces using local expert knowledge and available literature. Dominant plant functional types within each habitat type within the four subzones are also presented. Modellers could include or ignore different levels of resolution depending on the purpose of the model. The approach resolves conflicts in terminology that have previously been encountered between the Russian, North American, and Fennoscandian approaches to Arctic zonation.
Dance as a moving spirituality: A case study of Movement Medicine

This article describes dance as a moving spirituality through the case study of a specific practice called Movement Medicine. It addresses how a danced spirituality differs from other forms of spirituality, such as meditation and contemplation, and attempts to explore some of the aspects that make dance a unique medium for an embodied, lived and creative spirituality. ‘Feel good feelings’, as well as emerging from difficult emotions encountered on the dance floor, generate a sense of meaning which is translated to taking sustainable, socially just action. Through dance, different states of consciousness can be experienced through which ‘other’ knowledge is accessed and subsequently embodied. In these states, people can also meet and relate to spirit beings, and simultaneously express that relationship through the moving body. Finally, three qualities of dance are discussed, which contribute to concrete, lasting changes in existing life structures.
Identification of Occupational Cancer Risks in British Columbia: A Population-Based Case–Control Study of 769 Cases of Non-Hodgkin's Lymphoma Analyzed by Histopathology Subtypes

We have, as part of a program aimed at detecting occupational risk factors in British Columbia, collected lifetime occupational histories as well as information on lifetime cigarette smoking and alcohol consumption from 15,643 incident cancer cases, of whom 782 had a diagnosis of non-Hodgkin's lymphoma (NHL). Occupational risks for this cancer site are examined using a matched case–control study design, and the results are presented in this report for all cases and for histopathology subtypes. The results of our study indicate excess NHL risk, particularly for a number of occupations that involve exposures to electromagnetic fields, treated and fresh wood, metals, and solvents.
The roles of goal orientation, task-specific self-efficacy and motivation/emotion control in the academic performance of college students

The purpose of this research was to examine the types of emotional and motivational difficulties experienced by college age students and the types of emotional and motivational control strategies that they report using. Further, the study examined how goal orientation and self-efficacy beliefs influence students' motivational and emotional response to a difficult task. Finally, the study explored the interrelationships between goal orientation, self-efficacy beliefs, motivational and emotional response, motivation and emotion control strategy use, task persistence and academic achievement, to try to explain how volition control strategy use influences task persistence and academic achievement. Participants in the study (n = 186) completed questionnaires that measured learning and performance goals, self-efficacy, emotional and motivational difficulties, use of motivation and emotion control strategies, task persistence, and reading comprehension (as a measure of achievement). Results suggested that college-age students experience a range of emotional and motivational problems and use a variety of strategies to overcome those difficulties. Students reported having emotional problems more frequently than motivational problems, but they reported using motivation control strategies more frequently than emotional control strategies. Analyses also revealed that students high in learning goals were less likely to report motivational problems, more likely to report using volition control strategies, and more likely to persist. Students high in performance goals were more likely to report both emotional and motivational problems. Students high in selfefficacy were less likely to report both types of problems. Self-efficacy was also highly correlated with use of motivation control strategies, persistence, and achievement. Finally, the strongest predictor of task persistence and achievement was a lack of motivational problems. This suggests that self-efficacy and learning goals not only exert a direct effect on persistence and achievement, but also that they may exert an indirect effect on task engagement by protecting students from experiencing motivational problems. Theoretical and practical implications of these findings are discussed.
Differential role of the intermolecular base-pairs G292-C(75) and G293-C(74) in the reaction catalyzed by Escherichia coli RNase P RNA.

We present a systematic investigation of the thermodynamic and kinetic role of the intermolecular G292-C(75 )and G293-C(74 )Watson-Crick base-pairs in the reaction catalyzed by Escherichia coli RNase P RNA. Single turnover kinetics were analyzed for wild-type RNase P RNA and two variants with a single G to C exchange (C292 or C293), either acting on wild-type precursor tRNA (ptRNA) or derivatives carrying a complementary change at the tRNA 3'-end (G(74)CA or CG(75)A). Ground state binding of tRNA was studied using three different methods, including a novel fluorescence-based assay measuring equilibrium binding. We conclude that: (1) the role of the G293-C(74 )interaction is essentially confined to Watson-Crick base-pairing, with no indication for crucial tertiary contacts involving this base-pair; (2) the G293-C(74 )pair, although being as important for ptRNA ground state binding as G292-C(75), is much less crucial to catalytic performance than the G292-C(75) pair; (3) disruption of the G292-C(75 )base-pair results in preferential destabilization of enzyme transition-state complexes; and (4) the identity of the G292-C(75) pair, as part of the higher-order structural context consisting of coplanar G292-C(75)-A258 and G291-G259-A(76 )triples, contributes to high affinity binding of ptRNA and catalytic efficiency.
GMM Based Tests for Locally Misspecified Models

This paper shows that the standard Newey-West GMM based test is sensitive to the presence of locally misspecified alternatives. In particular, such test is shown to have incorrect size when the null model is locally contaminated, making the test spuriously reject the null hypothesis even when it is correct. After obtaining the distribution of the Newey-West test statistic under the misspecified alternative, the paper derives a Bera-Yoon modified test based on a restricted GMM estimator, which has the correct size under local misspecification. The paper can be seen as extending the likelihood based results of Saikkonen (1989), Davidson and MacKinnon (1987) and Bera and Yoon (1993) to the GMM framework, which does not require full specification of the underlying probabilistic model.
The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long‐term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4+ T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell‐intrinsic manner. Our data indicate that T cell‐expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell‐dependent B‐cell responses.