Miracle-dz/UniFAR-FTUs huggingface dataset:
Shifting meiotic to mitotic spindle assembly in oocytes disrupts chromosome alignment

Mitotic spindles assemble from two centrosomes, which are major microtubule‐organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes, however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated from multiple acentriolar MTOCs that are sorted and clustered prior to completion of spindle assembly in an “inside‐out” mechanism, ending with establishment of the poles. We used HSET (kinesin‐14) as a tool to shift meiotic spindle assembly toward a mitotic “outside‐in” mode and analyzed the consequences on the fidelity of the division. We show that HSET levels must be tightly gated in meiosis I and that even slight overexpression of HSET forces spindle morphogenesis to become more mitotic‐like: rapid spindle bipolarization and pole assembly coupled with focused poles. The unusual length of meiosis I is not sufficient to correct these early spindle morphogenesis defects, resulting in severe chromosome alignment abnormalities. Thus, the unique “inside‐out” mechanism of meiotic spindle assembly is essential to prevent chromosomal misalignment and production of aneuploidy gametes.
Thematic Concentration as a Discriminating Feature of Text Types

Abstract Generally, human brains can grasp intuitively the gist of thematic content of different texts through comprehensive reading, and such human-like generalization process may be accomplished with a more exact basis. With three representative text types in Chinese and English from two comparative corpora as our focus, that is, LCMC (the Lancaster Corpus of Mandarin Chinese) and Frown (the Freiburg-Brown Corpus of American English), this study compares thematic characteristics of these texts with PAM (Partition around Medoids) and HA (Hierarchical Agglomerative) clustering via three quantitative indicators, namely, TC (Thematic Concentration), STC (Secondary Thematic Concentration) and PTC (Proportional Thematic Concentration). The results show that: (1) eigenvectors standing for the thematic characteristic of three text types can be clustered into their corresponding categories in both Chinese and English; (2) two contributing factors are identified for the clustering results. One is the differences of TC, STC and PTC values of three text types lying in different hierarchical levels; the other is the differences of the percentages of ‘thematic words’, especially nouns at the pre-h-point and pre-2 h-point domain in three text types. The characterization of three text types as thematic-intensive (Official Document), thematic-balanced (News) and thematic-dispersive (Fiction) bears a cross-linguistic similarity in both Chinese and English.
Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta).

OBJECTIVES The age at which females initiate their reproductive career is a critical life-history parameter with potential consequences on their residual reproductive value and lifetime fitness. The age at reproductive debut may be intimately tied to the somatic capacity of the mother to rear her young, but relatively little is known about the influence of age of first birth on milk synthesis within a broader framework of reproductive scheduling, infant outcomes, and other life-history tradeoffs. MATERIAL AND METHODS Our study investigated the predictors of age at first reproduction among 108 captive rhesus macaque (Macaca mulatta) females, and associations with their milk synthesis at peak lactation, infant mass, and ability to subsequently conceive and reproduce. RESULTS The majority of females reproduced in their fourth year (typical breeders); far fewer initiated their reproductive career one year earlier or one year later (respectively early and late breeders). Early breeders (3-year-old) benefited from highly favorable early life development (better juvenile growth, high dominance rank) to accelerate reproduction, but were impaired in milk synthesis due to lower somatic resources and their own continued growth. Comparatively, late breeders suffered from poor developmental conditions, only partially compensated by their delayed reproduction, and evinced compromised milk synthesis. Typical breeders not only produced higher available milk energy but also had best reproductive performance during the breeding and birth seasons following primiparity. DISCUSSION Here, we refine and extend our understanding of how life-history tradeoffs manifest in the magnitude, sources, and consequences of variation in age of reproductive debut. These findings provide insight into primate reproductive flexibility in the context of constraints and opportunities.
A Survey of Downlink Non-orthogonal Multiple Access for 5G Wireless Communication Networks

Non-orthogonal multiple access (NOMA) has been recognized as a promising multiple access technique for the next generation cellular communication networks. In this paper, we first discuss a simple NOMA model with two users served by a single-carrier simultaneously to illustrate its basic principles. Then, a more general model with multicarrier serving an arbitrary number of users on each subcarrier is also discussed. An overview of existing works on performance analysis, resource allocation, and multiple-input multiple-output NOMA are summarized and discussed. Furthermore, we discuss the key features of NOMA and its potential research challenges.
Thermal design and optimization

Introduction to Thermal System Design. Thermodynamics, Modeling, and Design Analysis. Exergy Analysis. Heat Transfer, Modeling, and Design Analysis. Applications with Heat and Fluid Flow. Applications with Thermodynamics and Heat and Fluid Flow. Economic Analysis. Thermoeconomic Analysis and Evaluation. Thermoeconomic Optimization. Appendices. Index.
The role of procalcitonin in acute heart failure patients

Acute dyspnoea is a common chief complaint in the emergency department and is mainly caused by cardiac and pulmonary underlying diagnoses. In patients with acute heart failure (AHF), an early initiation of adequate therapy is important to improve patient outcome. Clinical differentiation of pulmonary and cardiac underlying causes and of concomitant pathologies determines which therapeutic strategy is chosen.
The Urine Anion Gap in Context.

From its introduction in the late 1980s, the urine anion gap (UAG), calculated as [(Na+ + K+) – (Cl−)] has been used to roughly estimate whether urine ammonium is increased or decreased in the evaluation of hyperchloremic metabolic acidosis ([1][1],[2][2]). This is the context in which the use
Sex differences among Swedish adolescents in mother–child relationships in the intake of different food groups

The present study has explored mother–child relationships in the intake of different food groups and the sex differences in these relationships. A population-based sample of 471 mother–child pairs from Stockholm completed a dietary questionnaire to assess habitual dietary intake. Girls showed overall stronger correlations with their mothers' diet than boys did. The strongest correlations found, in both girls and boys, were for the intakes of fruit juice and sweet bakery goods (r 0·30–0·37, P < 0·001). There was a wide range in correlation strength between food groups. Milk/yoghurt and desserts showed no mother–child relationship at all. Breakfast cereals was the only food group with a significant sex interaction (P = 0·01; mothers–girls, r 0·30, P < 0·001; mothers–boys, r0·05, NS). There were significant positive correlations between mothers and daughters in the intake of all macronutrients, whereas none between mothers and sons (sex interactions: protein, P = 0·001; fat, P = 0·004; carbohydrates, P = 0·001). Mothers and daughters (r 0·29, P < 0·001), but not mothers and sons, showed significant correlation in total energy intake, (P = 0·001 for sex interaction). There were generally more differences between mothers and children than between boys and girls in the relative intake (percentage of energy) of different food groups. Since teenaged children have a similar intake of especially snack foods as their mothers, it could be meaningful to educate mothers when aiming at improving the diet of teenaged children, both boys and girls.
Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle.

BACKGROUND Accumulation of diacylglycerol (DAG) and sphingolipids is thought to promote skeletal muscle insulin resistance by altering cellular signaling specific to their location. However,the subcellular localization of bioactive lipids in human skeletal muscle is largely unknown. METHODS We evaluated subcellular localization of skeletal muscle DAGs and sphingolipids in lean individuals (n = 15), endurance-trained athletes (n = 16), and obese men and women with (n = 12) and without type 2 diabetes (n = 15). Muscle biopsies were fractionated into sarcolemmal, cytosolic, mitochondrial/ER, and nuclear compartments. Lipids were measured using liquid chromatography tandem mass spectrometry, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamp. RESULTS Sarcolemmal 1,2-DAGs were not significantly related to insulin sensitivity. Sarcolemmal ceramides were inversely related to insulin sensitivity, with a significant relationship found for the C18:0 species. Sarcolemmal sphingomyelins were also inversely related to insulin sensitivity, with the strongest relationships found for the C18:1, C18:0, and C18:2 species. In the mitochondrial/ER and nuclear fractions, 1,2-DAGs were positively related to, while ceramides were inversely related to, insulin sensitivity. Cytosolic lipids as well as 1,3-DAG, dihydroceramides, and glucosylceramides in any compartment were not related to insulin sensitivity. All sphingolipids but only specific DAGs administered to isolated mitochondria decreased mitochondrial state 3 respiration. CONCLUSION These data reveal previously unknown differences in subcellular localization of skeletal muscle DAGs and sphingolipids that relate to whole-body insulin sensitivity and mitochondrial function in humans. These data suggest that whole-cell concentrations of lipids obscure meaningful differences in compartmentalization and suggest that subcellular localization of lipids should be considered when developing therapeutic interventions to treat insulin resistance. FUNDING National Institutes of Health General Clinical Research Center (RR-00036), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK089170), NIDDK (T32 DK07658), and Colorado Nutrition Obesity Research Center (P30DK048520).
Atacicept as an investigated therapy for rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic, painful and debilitating autoimmune disease. Although the outcome for patients with RA has improved markedly in the past decades, adequate disease control cannot be achieved in a substantial proportion of patients. Since RA is a syndrome with different biological subsets, new drugs with a novel mechanism of action may represent a valuable addition to the current armamentarium. Areas covered: This review focuses on the pharmacodynamics and pharmacokinetics of atacicept. Furthermore, the article both summarises and comments on the drug’s efficacy and safety profile in RA patients. Expert opinion: Atacicept is designed to neutralise B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand, two cytokines involving B-cell function and survival. Two recent Phase II studies have demonstrated that atacicept was not effective in RA patients with an inadequate response to methotrexate or TNF antagonists. However, atacicept displayed significant biological activity, including reduction of Ig and rheumatoid factor levels. Adverse events were slightly more frequent among patients treated with atacicept compared with placebo. In contrast to patients with systemic lupus erythematosus, RA patients receiving atacicept did not show an increased susceptibility to infections. In view of its important impact on immunoglobulin-secreting cells, this drug might be a rational therapy for hematological diseases.
Compensation of Phase Noise in OFDM/OQAM Systems

We propose a time-domain phase noise (PN) compensation scheme for orthogonal frequency division multiplexing with offset quadrature amplitude modulation (OFDM/OQAM) systems. The proposed scheme fully explores the unique overlapped signal structure of OFDM/OQAM to perform symbol-wise phase noise approximation using discrete cosine transform basis. Numerical simulation results verify better performance of the proposed schemes.
Association of direct bilirubin level with postoperative outcome in critically ill postoperative patients

Background Hyperbilirubinemia is a common postoperative complication. Elevated direct bilirubin (D-Bil) and indirect bilirubin (I-Bil) levels are related to different pathophysiologies; therefore, their associations with outcomes also differ. However, there have been few comparative studies of such associations in postoperative patients. Methods This retrospective study compared the associations of postoperative D-Bil and I-Bil with outcomes. We included adult patients requiring postoperative intensive care for more than 48 hours between 2008 and 2013, except those undergoing liver operations. The number of patients was determined using a power calculation. D-Bil and I-Bil measurements were obtained on postoperative days (POD) 1 and 2. The primary outcome was defined as hospital mortality, with the number of ICU-free survival days (IFSD) at POD 28 as the secondary outcome. Results The study population consisted of 1,903 patients with a mortality rate of 2.2%. D-Bil at POD 1 was significantly higher in non-survivors than survivors (P = 0.001), but I-Bil at POD 1 showed no such relation (P = 0.209). Multivariate logistic analysis indicated that higher postoperative D-Bil was independently associated with increased postoperative mortality (POD 1: adjusted odds ratio [OR] = 2.32, P < 0.001; POD 2: adjusted OR = 1.95, P < 0.001), but I-Bil showed no such relation (POD 1: P = 0.913; POD 2: P = 0.209). Increased D-Bil was independently associated with decreased IFSD at POD 28 (POD 1: adjusted coefficient = −1.54, P < 0.001; POD 2: −1.84, P < 0.001). In contrast, increased I-Bil at POD 1 was independently associated with increased IFSD at POD 28 (POD 1: adjusted coefficient = +0.39, P = 0.021; POD 2: +0.33, P = 0.080). Conclusions D-Bil indices have a higher capability than I-Bil for predicting poorer outcomes in critically ill postoperative patients.
Sequence determinants of protein phase behavior from a coarse-grained model

Membraneless organelles important to intracellular compartmentalization have recently been shown to comprise assemblies of proteins which undergo liquid-liquid phase separation (LLPS). However, many proteins involved in this phase separation are at least partially disordered. The molecular mechanism and the sequence determinants of this process are challenging to determine experimentally owing to the disordered nature of the assemblies, motivating the use of theoretical and simulation methods. This work advances a computational framework for conducting simulations of LLPS with residue-level detail, and allows for the determination of phase diagrams and coexistence densities of proteins in the two phases. The model includes a short-range contact potential as well as a simplified treatment of electrostatic energy. Interaction parameters are optimized against experimentally determined radius of gyration data for multiple unfolded or intrinsically disordered proteins (IDPs). These models are applied to two systems which undergo LLPS: the low complexity domain of the RNA-binding protein FUS and the DEAD-box helicase protein LAF-1. We develop a novel simulation method to determine thermodynamic phase diagrams as a function of the total protein concentration and temperature. We show that the model is capable of capturing qualitative changes in the phase diagram due to phosphomimetic mutations of FUS and to the presence or absence of the large folded domain in LAF-1. We also explore the effects of chain-length, or multivalency, on the phase diagram, and obtain results consistent with Flory-Huggins theory for polymers. Most importantly, the methodology presented here is flexible so that it can be easily extended to other pair potentials, be used with other enhanced sampling methods, and may incorporate additional features for biological systems of interest. Author summary Liquid liquid phase separation (LLPS) of low-complexity protein sequences has emerged as an important research topic due to its relevance to membraneless organelles and intracellular compartmentalization. However a molecular level understanding of LLPS cannot be easily obtained by experimental methods due to difficulty of determining structural properties of phase separated protein assemblies, and of choosing appropriate mutations. Here we advance a coarse-grained computational framework for accessing the long time scale phase separation process and for obtaining molecular details of LLPS, in conjunction with state of the art enhanced sampling methods. We are able to capture qualitatively the changes of phase diagram due to specific mutations, inclusion of a folded domain, and to variation of chain length. The model is flexible and can be used with different knowledge-based potential energy functions, as we demonstrate. We expect a wide application of the presented framework for advancing our understanding of the formation of liquid-like protein assemblies.
Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis

Sunitinib based adjuvant chemotherapy combined with chloroquine (CQ) for the treatment of renal cell carcinoma (RCC) is in clinical trials; however, its anti-RCC effect and the mechanism remain unclear. In the present study, the anti-RCC effect of sunitinib with CQ and the underlying mechanism was investigated. An MTT assay demonstrated that CQ enhanced the proliferation inhibitory effect of sunitinib against the OS-RC-2 RCC cell line. CQ inhibited sunitinib-induced autophagy in OS-RC-2, which was evidenced by the inhibition of autophagic vacuoles, acidic vesicular organelle formation, light chain 3 (LC3)-II recruitment to the autophagosomes and the conversion of LC3-I to LC3-II, as induced by sunitinib. The inhibition of autophagy by CQ enhanced sunitinib-induced apoptosis, which was characterized by the activation of caspase-3, caspase-9, Bcl-2 and p53. Additionally, the exposure of OS-RC-2 cells to CQ and sunitinib resulted in the inhibition of AKT, tuberous sclerosis complex 2, mechanistic target of rapamycin and p70 ribosomal S6 kinase, which are associated with cell proliferation. In in vivo study, a combination of sunitinib with CQ in mice significantly reduced OS-RC-2 cell xenograft growth compared with the sunitinib alone group. In conclusion, the present study demonstrated that CQ may enhance the anti-RCC effect of sunitinib by inhibiting the autophagy induced by sunitinib, and enhance the rate of apoptosis. Inhibiting cell proliferation may also serve a role in the synergistic antitumor effect of sunitinib and CQ. These data suggest that combination therapy of sunitinib with CQ may be a promising strategy for adjuvant chemotherapy in RCC.
Proximal femoral nail antirotation and third-generation Gamma nail: which is a better device for the treatment of intertrochanteric fractures?

INTRODUCTION Proximal femoral nail antirotation (PFNA) and third-generation Gamma nail (Gamma 3) are widely used in the treatment of intertrochanteric fractures. However, it remains unclear which device achieves better clinical and radiographic outcomes when treating intertrochanteric fractures. METHODS This study comprised 239 patients with intertrochanteric fractures treated with either PFNA or Gamma 3 for a minimum of 12 months. During surgery, the operative time, image intensifier time and amount of blood loss were recorded. Following surgery, we assessed reduction quality and implant position. At the final follow-up, postoperative complications, including femoral shaft fracture, cutout, reoperation, pneumonia, urinary tract infection, cerebral infarction, cardiac infarction and decubital ulcer, were recorded. In addition, walking ability was assessed using the Parker-Palmer mobility score. RESULTS No difference was found in the operative time, image intensifier time and amount of blood loss between patients treated with PFNA and those treated with Gamma 3. The reduction quality of fractures treated with Gamma 3 was better than those treated with PFNA. However, there were no significant differences in implant position, walking ability and postoperative complications between the two groups. Although Gamma 3 resulted in better reduction quality, it did not provide any advantages in walking ability and postoperative complications when compared with PFNA. CONCLUSION Therefore, we conclude that both PFNA and Gamma 3 are safe and reliable devices for the treatment of intertrochanteric fractures.
End-Grafted Polymer Chains onto Inorganic Nano-Objects

Organic/inorganic nanohybrid materials have attracted particular scientific and technological interest because they combine the properties of the organic and the inorganic component. Inorganic nanoparticles exhibit interesting electrical, optical, magnetic and/or catalytic properties, which are related with their nano-scale dimensions. However, their high surface-to-volume ratio often induces agglomeration and leads to the loss of their attractive properties. Surface modification of the inorganic nano-objects with physically or chemically end-tethered polymer chains has been employed to overcome this problem. Covalent tethered polymer chains are realized by three different approaches: the “grafting to”, the “grafting from” and the “grafting through” method. This article reviews the synthesis of end-grafted polymer chains onto inorganic nanoparticles using “controlled/living” polymerization techniques, which allow control over the polymer characteristics and the grafting density of the end-tethered polymer chains.
Bayesian estimation in random effects meta‐analysis using a non‐informative prior

Pooling information from multiple, independent studies (meta‐analysis) adds great value to medical research. Random effects models are widely used for this purpose. However, there are many different ways of estimating model parameters, and the choice of estimation procedure may be influential upon the conclusions of the meta‐analysis. In this paper, we describe a recently proposed Bayesian estimation procedure and compare it with a profile likelihood method and with the DerSimonian–Laird and Mandel–Paule estimators including the Knapp–Hartung correction. The Bayesian procedure uses a non‐informative prior for the overall mean and the between‐study standard deviation that is determined by the Berger and Bernardo reference prior principle. The comparison of these procedures focuses on the frequentist properties of interval estimates for the overall mean. The results of our simulation study reveal that the Bayesian approach is a promising alternative producing more accurate interval estimates than those three conventional procedures for meta‐analysis. The Bayesian procedure is also illustrated using three examples of meta‐analysis involving real data. Copyright © 2016 John Wiley & Sons, Ltd.