Miracle-dz/UniFAR-FTUs huggingface dataset:
BoolNet - an R package for generation, reconstruction and analysis of Boolean networks

MOTIVATION As the study of information processing in living cells moves from individual pathways to complex regulatory networks, mathematical models and simulation become indispensable tools for analyzing the complex behavior of such networks and can provide deep insights into the functioning of cells. The dynamics of gene expression, for example, can be modeled with Boolean networks (BNs). These are mathematical models of low complexity, but have the advantage of being able to capture essential properties of gene-regulatory networks. However, current implementations of BNs only focus on different sub-aspects of this model and do not allow for a seamless integration into existing preprocessing pipelines. RESULTS BoolNet efficiently integrates methods for synchronous, asynchronous and probabilistic BNs. This includes reconstructing networks from time series, generating random networks, robustness analysis via perturbation, Markov chain simulations, and identification and visualization of attractors. AVAILABILITY The package BoolNet is freely available from the R project at http://cran.r-project.org/ or http://www.informatik. uni-ulm.de/ni/mitarbeiter/HKestler/boolnet/ under Artistic License 2.0. CONTACT hans.kestler@uni-ulm.de SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer

Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413–26) and can reach values of 1.3–1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664–77, Courdi et al 1994 Br. J. Radiol. 67 800–4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the αref/βref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE = 1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study—based on in vitro data since human tissue RBE values are scarce and have large uncertainties—can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume.
A Systematic Review of p53 as a Prognostic Factor of Survival in Squamous Cell Carcinoma of the Four Main Anatomical Subsites of the Head and Neck

Objectives: To summarize existing evidence about whether the presence of mutant or upregulated p53 is a prognostic factor for patients presenting with squamous cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity. Method: Relevant articles were identified using strict criteria for systematic searches. Associations between mutant or upregulated p53 versus wild-type or low/undetectable p53 in relation to overall survival and DFS were summarized by extracting or deriving hazard ratio (HR) estimates. Random-effects meta-analyses were used to account for between-study heterogeneity and to summarize the effect of p53 across studies. Results: The meta-analyses gave a statistically significant pooled HR for overall survival in oral cavity [pooled HR, 1.48; 95% confidence interval, (95% CI), 1.03-2.11], and for disease-free survival in oral cavity (pooled HR, 1.47; 95% CI, 1.12-1.93) and in oropharynx (pooled HR, 0.45; 95% CI, 0.27-0.73). Despite attempts to limit it, between-study heterogeneity was large in the majority of meta-analyses and the prognostic value of p53 was generally inconsistent and inconclusive across studies. Conclusion: The meta-analysis results highlight that current evidence about the prognostic value of p53 in patients with squamous cell carcinaoma of the head and neck is inconclusive. Large heterogeneity exists across studies in study-level and patient-level characteristics, making it difficult to ascertain a clear picture. Future studies are required in which p53 expression is investigated in a more standardized and biologically informative manner. In particular, prospectively planned individual patient data meta-analyses are needed to establish the prognostic importance of p53 for specific subgroups of patients undergoing specific treatments. Cancer Epidemiol Biomarkers Prev; 19(2); 574–87
Serial verb constructions in Chinese: A HPSG account

The present paper gives an account of Serial Verb Constructions (SVCs) in Mandarin Chinese. After a typological presentation of the phenomenon, we give an overview of the Chinese data with examples of the semantic variations of SVCs. The inventory of SVC types is classified according to causal and temporal relations between the components. We also discuss the pragmatic conditions on the use of SVCs as well as alternative, semantically equivalent constructions. A HPSG-analysis is proposed for marked SVCs, which uses the interaction between aspect marking and the set of possible subordinative relations to deduce the extra-lexical meaning of the construction. Particular attention is payed to the syntactically peculiar SVC with shared internal arguments, which is accounted for by a non-cancellation approach to valence requirements.
Protein Components of the Purified Sodium Channel from Rat Skeletal Muscle Sarcolemma

Abstract: Sensitive detection systems have been used to study the protein components of the sodium channel purified from rat skeletal muscle sarcolemma. This functional, purified sodium channel contains at least three subunits on 7–20% gradient sodium dodecyl sulfate (SDS)‐polyacrylamide gel electrophoresis: a large glycoprotein which migrates anomalously in the high‐molecular‐weight range, a 45,000 molecular weight polypeptide, and a third protein often seen as a doublet at 38,000. The large glycoprotein runs as a diffuse band and stains very poorly with Coomassie blue, but is adequately visualized with silver staining or iodination followed by autoradiography. This glycoprotein exhibits anomalous electrophoretic behavior in SDS‐polyacrylamide gels. The apparent molecular weight of the center of the band varies from ∼230,000 on 13% acrylamide gels to ∼130,000 on 5% gels; on 7–20% gradient gels a value of 160,000 is found. Plots of relative migration versus gel concentration suggest an unusually high apparent free solution mobility. Lectin binding to purified channel peptides separated by gel electrophoresis indicates that the large glycoprotein is the only subunit that binds either concanavalin A or wheat germ agglutinin, and this component has high binding capacity for both lectins. The smaller channel components run consistently at 45,000 and 38,000 molecular weight in a variety of gel systems and do not appear to be glycosylated.
In Vitro Emergence of High Persistence upon Periodic Aminoglycoside Challenge in the ESKAPE Pathogens

ABSTRACT Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. —are collectively referred to as the “ESKAPE bugs. ” They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro. We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence.
Hepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3

Chronic infection with hepatitis C virus (HCV) affects 130 million people worldwide and is a major cause of liver cirrhosis and liver cancer. After translation of the HCV RNA genome into a polyprotein, 2 viral proteases process its non-structural protein (NS) region. While the essential chymotrypsin-like serine protease NS3–4A mediates all cleavages downstream of NS3, the NS2–3 cysteine protease catalyzes a vital cleavage at the NS2/3 site. Protease activity of NS2–3 has been described to require, besides NS2, the N-terminal 181 aa of NS3. The latter domain corresponds to the NS3 serine protease domain and contains a structural Zn2+-binding site with functional importance for both viral proteases. The catalytic triad of the NS2–3 protease resides in NS2; the role of the NS3 part in proteolysis remained largely undefined. Here we report a basal proteolytic activity for NS2 followed by only 2 amino acids of NS3. Basal activity could be dramatically enhanced by the NS3 Zn2+-binding domain (NS3 amino acids 81–213) not only in cis but also in trans which, however, required a more extended N-terminal part of NS3 downstream of NS2 in cis. Thus, this study defines for the first time (i) NS2 as a bona fide protease, (ii) NS3 as its regulatory cofactor, and (iii) functional subdomains in NS3 that cooperate in NS2 protease activation. These findings give new mechanistic insights into function and regulation of the NS2 protease and have important implications for the development of anti-HCV therapeutics.
The Coffin–Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1

Exocytosis of neurotransmitters and hormones occurs through the fusion of secretory vesicles with the plasma membrane. This highly regulated process involves key proteins, such as SNAREs, and specific lipids at the site of membrane fusion. Phospholipase D (PLD) has recently emerged as a promoter of membrane fusion in various exocytotic events potentially by providing fusogenic cone-shaped phosphatidic acid. We show here that PLD1 is regulated by ribosomal S6 kinase 2 (RSK2)-dependent phosphorylation. RSK2 is activated by a high K+-induced rise in cytosolic calcium. Expression of inactive RSK2 mutants or selective knockdown of endogenous RSK2 dramatically affects the different kinetic components of the exocytotic response in chromaffin cells. RSK2 physically interacts with and stimulates PLD activity through the phosphorylation of Thr-147 in the PLD1 amino-terminal phox homology domain. Expression of PLD1 phosphomimetic mutants fully restores secretion in cells depleted of RSK2, suggesting that RSK2 is a critical upstream signaling element in the activation of PLD1 to produce the lipids required for exocytosis. We propose that PLD-related defects in neuronal and endocrine activities could contribute to the effect observed after the loss-of-function mutations in Rsk2 that lead to Coffin–Lowry syndrome, an X-linked form of growth and mental retardation.
A randomized, double-blind controlled comparison of nefazodone and paroxetine in the treatment of depression: safety, tolerability and efficacy in continuation phase treatment

We investigated the safety, tolerability and efficacy of nefazodone and paroxetine in the continuation phase of treatment of depression. The study comprised a double-blind, parallel-group comparison over 4 months, of patients who had previously improved following random allocation to nefazodone or paroxetine during an 8-week acute treatment study. Assessments included Clinical Global Impression Scales, Hamilton Rating Scales for Depression and Anxiety, Montgomery-Asberg Depression Rating Scale and the Patient Global Assessment Scale, in addition to a review of reported adverse events, vital sign measurements, electrocardiograms and clinical laboratory tests. One hundred and eight patients participated in the continuation study (53 received paroxetine, 55 nefazodone) and 73 completed treatment. No clinically relevant differences in antidepressant efficacy were seen. Headache and somnolence were the most common reported adverse events in both treatment groups. Both nefazodone and paroxetine maintain their efficacy in continuation treatment, and both are generally well tolerated.
Applying Governance Principles to Systematic Conservation Decision-Making in Queensland

The literature on the science-policy interface suggests that stakeholders' perceptions of environmental planning and decision-making processes can affect the uptake of conservation plans. Despite calls for more and better stakeholder engagement in conservation planning there is currently no empirical evidence on participants' perceptions of such processes. We asked participants of a conservation planning process and other key informants to evaluate their engagement experiences using normative governance principles (legitimacy, inclusiveness, fairness, accountability, integration, adaptability, transparency and capability). We analysed a large-scale case-study of species prioritization in Queensland, Australia. Conceptually, our systematic use of governance principles to interrogate perceptions of engagement showcased the utility of this analytical approach to uncover important issues influencing science-policy uptake. Empirically, we showed that there remains considerable debate about how a normative conservation planning process should be. Our data revealed different interpretations of species prioritization, ranging from a deliberative process to define priorities in biodiversity conservation, to a technical, expert-based process. Matters of 'who' was included affected stakeholders' perceptions of species prioritization. Perceived limitations of 'how' the process was conducted were also important, affected by the: (1) institutional culture of the Queensland Government; (2) lack of transparency; (3) limited flexibility to incorporate both emerging data and participants' suggestions in programme management; and (4) limited capability for implementation. These empirical data support existing evidence from studies in the broader field of collaborative planning. We draw from this literature to suggest how conservation planners can overcome the barriers to the uptake of prioritization priorities identified in or research. Copyright C) 2016 John Wiley & Sons, Ltd and ERP Environment
Prediction Model Students' Performance in Online Discussion Forum

Prediction is one of the most popular topic in Education Data Mining. Prediction is related to students' performance, which can be accurately observed through Educational Data Mining. Online discussion forum can utilize prediction modeling techniques to identify key predictors of students' academic performance by monitoring the progress of students with fully use of online discussion forum. In this paper, a new model in E-learning to predict students' performance in online discussion forum was proposed. This research was participated to 165 students in English for Librarians course by extracting and analyzing online discussion forum data from E-learning log in Open University, Indonesia. The result from analysis is used to determine which features in online discussion forum as the key indicator to predict students' performance. Course module instance list viewed, discussion created, discussion subscription created, discussion subscription deleted, discussion viewed, module course viewed, post created, post deleted, post updated, some content has been posted and user report viewed were the features to predicting students' performance.
The Balance of Nuclear Import and Export Determines the Intracellular Distribution and Function of Tomato Heat Stress Transcription Factor HsfA2

ABSTRACT Tomato heat stress transcription factor HsfA2 is a shuttling protein with dominant cytoplasmic localization as a result of a nuclear import combined with an efficient export. Besides the nuclear localization signal (NLS) adjacent to the oligomerization domain, a C-terminal leucine-rich motif functions as a nuclear export signal (NES). Mutant forms of HsfA2 with a defective or an absent NES are nuclear proteins. The same is true for the wild-type HsfA2 if coexpressed with HsfA1 or in the presence of export inhibitor leptomycin B (LMB). Fusion of the NES domain of HsfA2 to HsfB1, which is a nuclear protein, caused export of the HsfB1-A2NES hybrid protein, and this effect was reversed by the addition of LMB. Due to the lack of background problems, Chinese hamster ovary (CHO) cells represent an excellent system for expression and functional analysis of tomato Hsfs. The results faithfully reflect the situation found in plant cells (tobacco protoplasts). The intriguing role of NLS and NES accessibility for the intracellular distribution of HsfA2 is underlined by the results of heat stress treatments of CHO cells (41°C). Despite the fact that nuclear import and export are not markedly affected, HsfA2 remains completely cytoplasmic at 41°C even in the presence of LMB. The temperature-dependent conformational transition of HsfA2 with shielding of the NLS evidently needs intramolecular interaction between the internal HR-A/B and the C-terminal HR-C regions. It is not observed with the HR oligomerization domain (HR-A/B region) deletion form of HsfA2 or in HsfA2-HsfA1 hetero-oligomers.
Cholesteric Liquid Crystals with a Broad Light Reflection Band

The cholesteric‐liquid‐crystalline structure, which concerns the organization of chromatin, collagen, chitin, or cellulose, is omnipresent in living matter. In technology, it is found in temperature and pressure sensors, supertwisted nematic liquid crystal displays, optical filters, reflective devices, or cosmetics. A cholesteric liquid crystal reflects light because of its helical structure. The reflection is selective – the bandwidth is limited to a few tens of nanometers and the reflectance is equal to at most 50% for unpolarized incident light, which is a consequence of the polarization‐selectivity rule. These limits must be exceeded for innovative applications like polarizer‐free reflective displays, broadband polarizers, optical data storage media, polarization‐independent devices, stealth technologies, or smart switchable reflective windows to control solar light and heat. Novel cholesteric‐liquid‐crystalline architectures with the related fabrication procedures must therefore be developed. This article reviews solutions found in living matter and laboratories to broaden the bandwidth around a central reflection wavelength, do without the polarization‐selectivity rule and go beyond the reflectance limit.
Effects of 8-Week in-Season Upper and Lower Limb Heavy Resistance Training on The Peak Power, Throwing Velocity, and Sprint Performance of Elite Male Handball Players

Hermassi, S, Chelly, MS, Tabka, Z, Shephard, RJ, and Chamari, K. Effects of 8-week in-season upper and lower limb heavy resistance training on the peak power, throwing velocity, and sprint performance of elite male handball players. J Strength Cond Res 25(9): 2424-2433, 2011—The aims of this study were to test the potential of in-season heavy upper and lower limb strength training to enhance peak power output (Wpeak), vertical jump, and handball related field performance in elite male handball players who were apparently already well trained, and to assess any adverse effects on sprint velocity. Twenty-four competitors were divided randomly between a heavy resistance (HR) group (age 20 ± 0.7 years) and a control group (C; age 20 ± 0.1 years). Resistance training sessions were performed twice a week for 8 weeks. Performance was assessed before and after conditioning. Peak power (Wpeak) was determined by cycle ergometer; vertical squat jump (SJ) and countermovement jump (CMJ); video analyses assessed velocities during the first step (V1S), the first 5 m (V5m), and between 25 and 30 m (Vpeak) of a 30-m sprint. Upper limb bench press and pull-over exercises and lower limb back half squats were performed to 1-repetition maximum (1RM). Upper limb, leg, and thigh muscle volumes and mean thigh cross-sectional area (CSA) were assessed by anthropometry. Wpeak (W) for both limbs (p < 0.001), vertical jump height (p < 0.01 for both SJ and CMJ), 1RM (p < 0.001 for both upper and lower limbs) and sprint velocities (p < 0.01 for V1S and V5m; p < 0.001 for Vpeak) improved in the HR group. Upper body, leg, and thigh muscle volumes and thigh CSA also increased significantly after strength training. We conclude that in-season biweekly heavy back half-squat, pull-over, and bench-press exercises can be commended to elite male handball players as improving many measures of handball-related performance without adverse effects upon speed of movement.
Consumer Preferences for Natural Beef

The FDA received petitions to more clearly define the content of the natural label or even prohibit its use. Against this background, we conducted an online choice experiment to determine consumer preferences for boneless USDA Choice ribeye steaks. We also determined if providing consumers with information regarding the legal definition of natural had an impact on consumer preferences. Results indicate that natural labeling has a positive impact on consumer utility when consumers were not aware of the definition of natural; this impact was not found when consumers were informed of the definition of natural.