Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structures of the BtuF Periplasmic-binding Protein for Vitamin B12 Suggest a Functionally Important Reduction in Protein Mobility upon Ligand Binding*

BtuF is the periplasmic binding protein (PBP) for the vitamin B12 transporter BtuCD, a member of the ATP-binding cassette (ABC) transporter superfamily of transmembrane pumps. We have determined crystal structures of Escherichia coli BtuF in the apo state at 3.0 Å resolution and with vitamin B12 bound at 2.0 Å resolution. The structure of BtuF is similar to that of the FhuD and TroA PBPs and is composed of two α/β domains linked by a rigid α-helix. B12 is bound in the “base-on” or vitamin conformation in a wide acidic cleft located between these domains. The C-terminal domain shares structural homology to a B12-binding domain found in a variety of enzymes. The same surface of this domain interacts with opposite surfaces of B12 when comparing ligand-bound structures of BtuF and the homologous enzymes, a change that is probably caused by the obstruction of the face that typically interacts with this domain by the base-on conformation of vitamin B12 bound to BtuF. There is no apparent pseudo-symmetry in the surface properties of the BtuF domains flanking its B12 binding site even though the presumed transport site in the previously reported crystal structure of BtuCD is located in an intersubunit interface with 2-fold symmetry. Unwinding of an α-helix in the C-terminal domain of BtuF appears to be part of conformational change involving a general increase in the mobility of this domain in the apo structure compared with the B12-bound structure. As this helix is located on the surface likely to interact with BtuC, unwinding of the helix upon binding to BtuC could play a role in triggering release of B12 into the transport cavity. Furthermore, the high mobility of this domain in free BtuF could provide an entropic driving force for the subsequent release of BtuF required to complete the transport cycle.
Pseudomonas aeruginosa biofilm infections in cystic fibrosis: insights into pathogenic processes and treatment strategies

Importance of the field: CF airway mucus can be infected by opportunistic microorganisms, notably Pseudomonas aeruginosa. Once organisms are established as biofilms, even the most potent antibiotics have little effect on their viability, especially during late-stage chronic infections. Better understanding of the mechanisms used by P. aeruginosa to circumvent host defenses and therapeutic intervention strategies is critical for advancing novel treatment strategies. Areas covered in this review: Inflammatory injury in CF lung, role of neutrophils in pathogenesis, P. aeruginosa biofilms, mucoidy and its relationship with poor airway oxygenation, mechanisms by which P. aeruginosa biofilms in the CF airway can be killed. What the reader will gain: An understanding of the processes that P. aeruginosa undergoes during CF airway disease and clues to better treat such infections in future. Take home message: The course of CF airway disease is a process involving host and microbial factors that often dictate frequency of pulmonary exacerbations, thus affecting the overall course. In the past decade significant discoveries have been made regarding the pathogenic processes used by P. aeruginosa to bypass the immune system. Many new and exciting features of P. aeruginosa now illuminate weaknesses in the organism that may render it susceptible to inexpensive compounds that force its own destruction.
Biomechanical Comparisons of Knee Stability After Anterior Cruciate Ligament Reconstruction Between 2 Clinically Available Transtibial Procedures

Background: Several trials have compared the clinical results between anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction procedures. However, it remains controversial whether the anatomic double-bundle procedure is superior to the single-bundle procedure. Hypothesis: The anatomic double-bundle procedure will be better than the single-bundle procedure at resisting anterior laxity, internal rotation laxity, and pivot-shift instability. Study Design: Controlled laboratory study. Methods: Eight cadaveric knees were tested in a 6 degrees of freedom rig using the following loading conditions: 90-N anterior tibialforce, 5-N·m internal and external tibial torques, and a simulated pivot-shift test. Tibiofemoral kinematics during the flexion-extension cycle were recorded with an optical tracking system for (1) intact, (2) anterior cruciate ligament–deficient knee, (3) anatomic double-bundle reconstruction, and (4) single-bundle reconstruction placed at 11 o’clock in the intercondylar notch. Results: There were significant reductions of anterior laxity of 3.5 mm at 20° of flexion, internal rotational laxity of 2.5° at 20° of flexion, and anterior translations (2 mm) and internal rotations (5°) in the simulated pivot-shift test in the double-bundle reconstruction com-pared with the single-bundle reconstruction. There were no significant differences between the 2 procedures for external rotation laxity. Conclusion: The postoperative anterior translation and internal rotation stability after anatomic double-bundle anterior cruciate ligament reconstruction were significantly better than after single-bundle reconstruction, in both static tests and the pivot shift. Clinical Relevance: Unlike previous laboratory studies, this work used clinical arthroscopic methods for anterior cruciate ligament reconstruction, and found that the anatomic reconstruction was superior to a single graft placed at 11 o’clock.
Exclusive olive oil consumption and 10-year (2004-2014) acute coronary syndrome incidence among cardiac patients: the GREECS observational study.

BACKGROUND The present study evaluated the association between long-term, exclusive olive oil consumption, in cooking preparation or as a dressing, and the 10-year (2004-2014) incidence of acute coronary syndrome (ACS) among cardiac patients. METHODS From October 2003 to September 2004, a sample of 2172 ACS consecutive patients from six major Greek hospitals were enrolled. During 2013-2014, the 10-year follow-up was performed in 1918 patients (88% participation rate). The development of fatal or nonfatal ACS was recorded through medical records or hospital registries. Among other dietary components, added fats (i.e. olive oil, butter, margarine and seed oils) consumption at baseline examination was assessed using a semi-quantitative food frequency questionnaire. RESULTS Non-exclusive olive oil consumption on a daily basis was associated with an adverse effect on the ACS incidence after taking into account various potential confounders [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.05-1.86, P = 0.024]. However, significant interactions between olive oil consumption and body mass index (BMI) (P = 0.082) and educational level (P = 0.054) led to further stratified analysis. Using BMI as strata (i.e. ≤29.9 versus >29.9 kg m(-2)), the above association remained significant only in obese patients (OR = 1.80, 95% CI = 1.03-3.12, P = 0.038), whereas, on examining the education status (i.e. ≤9 versus >9 years of school), a significant association was observed only among the higher educated patients (OR = 1.83, 95% CI = 1.01-3.32, P = 0.047). CONCLUSIONS Exclusive use of olive oil, either as a salad dressing or in cooking, should be promoted through the dietary management of ACS patients, with the aim of reducing the likelihood of recurrent cardiac episodes.
OpenFlow and services in the cloud: Core network demonstrator

Considering the growth of customers craving for complex services like IPTV, cloud storage, and online gaming, traditional networking is quickly becoming an obsolete technology. The new networking paradigm, Software Defined Networking (SDN), in combination with the recent communication protocol, OpenFlow, brings a new perspective to the operator and cloud provider's core networks by providing new autonomous tools. This paper proposes and evaluates a new SDN control mechanism that allows the definition of dedicated connectivity service within an operator network, making it possible to easily provide and support cloud services to the end user. It takes advantage of the combination of SDN and Cloud Computing, and further benefits the automation of both technologies, which empowers the operator to provide faster services to its users, such as virtual machine instantiation with automatic network creation. The evaluation of the proposed approach shows that the most time consuming phase is the installation of the OpenFlow rules in the network: in a network of 128 nodes, it takes around 250msec to both install and remove connections.
Deubiquitylating Enzyme UBP64 Controls Cell Fate through Stabilization of the Transcriptional Repressor Tramtrack

ABSTRACT Protein ubiquitylation plays a central role in multiple signal transduction pathways. However, the substrate specificity and potential developmental roles of deubiquitylating enzymes remain poorly understood. Here, we show that the Drosophila ubiquitin protease UBP64 controls cell fate in the developing eye. UBP64 represses neuronal cell fate but promotes the formation of nonneuronal cone cells. Using a proteomics approach, we identified the transcriptional repressor Tramtrack (TTK) as a primary UBP64 substrate. In common with TTK, reduced UBP64 levels lead to a loss of cone cells, supernumerary photoreceptors, and mechanosensory bristle cells. Previously, it was demonstrated that the blockade of neuronal cell fate was relieved by SINA-dependent ubiquitylation and degradation of TTK. We found that UBP64 counteracts SINA function by deubiquitylating TTK, leading to its stabilization and thereby promoting a nonneuronal cell fate. Mass spectrometric mapping revealed that SINA ubiquitylates multiple sites dispersed throughout TTK, which are duly deubiquitylated by UBP64. This observation suggests that both E3 SINA and UBP64 use a scanning mechanism to (de)ubiquitylate TTK. We conclude that the balance of TTK ubiquitylation by SINA and deubiquitylation by UBP64 constitutes a specific posttranslational switch controlling cell fate.
Using Northern Sotho as medium of instruction in vocational training

Currently, the official MoI in all CFET is English: learners are taught in English, they have to learn in English (that is, master complex concepts and principles, understand how complicated systems function, read text books in English), and they have to demonstrate their knowledge, understanding and skills in their selected fields of study in English (i.e. write tests and exams in English). However, learners’ are generally not proficient enough in English to perform these tasks effectively, and their educational performance is therefore not satisfactory (see the opening paper of the Le3o conference). The use of English as MoI, in fact, operates as an obstacle to effective educational development at the colleges. Le3o therefore wants to construct the case for using Northern Sotho as MoI, arguing on theoretical as well as empirical grounds that such a decision will contribute towards improving educational performance in the CFET and, subsequently, lead to more competitive performance in the workplace.
Identification of novel microRNA genes in freshwater and marine ecotypes of the three‐spined stickleback (Gasterosteus aculeatus)

The three‐spined stickleback (Gasterosteus aculeatus L.) is an important model organism for studying the molecular mechanisms of speciation and adaptation to salinity. Despite increased interest to microRNA discovery and recent publication on microRNA prediction in the three‐spined stickleback using bioinformatics approaches, there is still a lack of experimental support for these data. In this paper, high‐throughput sequencing technology was applied to identify microRNA genes in gills of the three‐spined stickleback. In total, 595 miRNA genes were discovered; half of them were predicted in previous computational studies and were confirmed here as microRNAs expressed in gill tissue. Moreover, 298 novel microRNA genes were identified. The presence of miRNA genes in selected ‘divergence islands’ was analysed and 10 miRNA genes were identified as not randomly located in ‘divergence islands’. Regulatory regions of miRNA genes were found enriched with selective SNPs that may play a role in freshwater adaptation.
Insights from curve fitting models in mouse dynamics authentication systems

In this work, we investigate the impact of various curve smoothing approaches on the performance of prediction tasks using mouse movement sequences as inputs in the setting of user authentication. We make use of three time-series forecasting modelling techniques as alternatives and we perform a comparison. We demonstrate our findings for the Balabit challenge mouse movement dataset.
Willingness to undergo HIV testing among factory workers in Surabaya, Indonesia

Abstract The objective of this study is to investigate workers' perceptions of HIV testing in the workplace in Indonesia. In a cross-sectional study, we used a self-administered questionnaire in Surabaya, Indonesia. A convenient sample of 536 workers was chosen from two factories with similar sample characteristics from March through June 2008. Of these workers, 433 (response rate: 80.8%) answered questions about their willingness to undergo HIV testing. More than 40% of workers were willing to undergo HIV testing. Not knowing where to get tested (adjusted odds ratio [AOR] = 0.40, confidence interval [CI] = 0.18–0.89) and not feeling the need to be tested for HIV (AOR = 0.02, CI = 0.01–0.04) were negatively associated with willingness to undergo HIV testing. HIV prevention in the workplace needs to reach out to individuals who are not willing to undergo HIV testing – workers unaware of where to get tested for HIV and not feeling the need to get tested – through education, information, and communication in the workplace in light of the stigma and discrimination associated with HIV. High-impact voluntary counseling and testing (VCT) strategies need to be quickly developed to improve HIV prevention and access to care in the workplace.
Removal of phenols from wastewater by soluble and immobilized tyrosinase

An enzymatic method for removal of phenols from industrial wastewater was investigated. Phenols in an aqueous solution were removed after treatment with mushroom tyrosinase. The reduction order of substituted phenols is catechol > p‐cresol > p‐chlorophenol > phenol > p‐methoxyphenol. In the treatment of tyrosinase alone, no precipitate was formed but a color change from colorless to dark‐brown was observed. The colored products were removed by chitin and chitosan which are available abundantly as shellfish waste. In addition, the reduction rate of phenols was observed to be accelerated in the presence of chitosan. Tyrosinase, immobilized by using amino groups in the enzyme on cation exchange resins, can be used repeatedly. By treatment with immobilized tyrosinase, 100% of phenol was removed after 2 h, and the activity was reduced very little even after 10 repeat treatments. © 1993 John Wiley & Sons, Inc.
Be Careful What You Wish For

Learning at work is usually seen as beneficial for the professional and personal lives of workers. In this article, we propose that learning’s relationship to worker well-being may be more complicated. We posit that learning can become a burden (instead of always being a benefit) in occupations that are learning intensive and tightly associated with the postindustrial economy. Results of analyses using data from the General Social Survey suggest that learning lessens work–family conflict by increasing job satisfaction, but at the same time, learning makes work–family conflict worse by leading people to work longer hours and exacerbating work-related stress.
Good foundations: prediction of degree success in non-traditional students

This paper reports the findings of a qualitative comparative analysis of factors affecting the success of mature, local and non-traditional Foundation students at Durham University. The study reports the findings from analysing 234 cases of students who progressed to degrees at Durham University from the Foundation Centre and considers the effect of a range of inputs including the students' age, sex, origin, qualifications prior to entry, conscientiousness, program of study and average score on the foundation program on their degree outcomes. One of the purposes of the study was to inform subsequent admissions and teaching and learning policies to support retention. Given the diverse nature of the students on the foundation program, traditional statistical methods were considered unlikely to identify the nuances within the data. Consequently a case-led approach was thought to be more appropriate and the data was analysed using crisp set Qualitative Comparative Analysis (csQCA).
Crystal Structures of the GCaMP Calcium Sensor Reveal the Mechanism of Fluorescence Signal Change and Aid Rational Design*S⃞

The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca2+-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaM and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.
Dynamic multi-user transmission for efficient dimensioning in Green LTE-A uplink networks

In this paper, we propose a dynamic multi-user transmission strategy for the uplink of MU-MIMO LTE-Advanced networks with 2 transmit antennas at the user equipment (UE) and 4 receive antennas at the eNB. For this purpose, we define transmission modes that enable, depending on the position of the UE in the cell and the transmission reliability, the multiplexing of 1 to 4 UEs on the same radio resource block (RB). Each UE selects an adequate transmission mode to optimize one of the following metrics: the RB sharing, the individual benefit in rate, the power consumption or the sharing-benefit efficiency. Based on this dynamic multi-user strategy, we propose an efficient dimensioning for the LTE bandwidth that fairly distributes the radio and spatial resources in all the sector. Numerical results show that the sharing-benefit efficiency metric provides the best trade-off between the achievable reliable rate and the RB sharing and it maximizes indeed, the number of fairly distributed transmitting UEs in the sector.
Traumatic Wound Debridement: A Comparison of Irrigation Methods

Objectives: To test wound debridement efficacy and soft tissue damage produced by high-pressure pulsatile lavage (HPPL), suction irrigation, and bulb syringe irrigation. Design: Randomized trial in an in vitro model. Setting: Medical school orthopaedic department. Patients/Participants: No patients were used in this study. Intervention: Beef flank steaks (100-g ± 10-g) were divided into 8 test groups and incised uniformly. Four test groups were contaminated with 2 g of rock dust and 4 were not. The specimens were then treated as follows: nothing (control), bulb irrigation, suction irrigation, or HPPL. Main Outcome Measurements: Runoff from the irrigation was collected, filtered, lyophilized, and ashed to allow for quantitative determination of organic and inorganic material removed from the wound by each irrigation method. Digital photographs of the tissue samples were subjected to blinded grading on a scale of 1 to 5 to assess macroscopic soft tissue damage. Results: Qualitatively, tissue samples treated with HPPL consistently received worse grades for tissue damage than samples in any other experimental group. Quantitative soft tissue damage analysis revealed that significantly more organic material was removed from samples treated with HPPL (141.3 ± 58.9 mg) than those treated with bulb syringe (50.7 ± 28.6 mg) or suction irrigation (108.7 ± 174.5 mg). Surprisingly, significantly less inorganic contaminant was removed from tissue samples treated with HPPL (1549.6 ± 77.3 mg) than those treated with bulb syringe (1834.9 ± 39.1 mg) or suction irrigation (1827 ± 39.4 mg). Conclusions: There has been some concern regarding damage produced by HPPL. According to our quantitative soft tissue damage data, tissue treated by HPPL was damaged significantly more than tissue treated with bulb syringe or suction irrigation. Our qualitative tissue damage grade data showed that HPPL treated test groups appeared more damaged than other irrigation groups. Surprisingly, HPPL removed significantly less inorganic contaminant than other debridement methods, and it is proposed that HPPL may drive some contaminants deeper into the tissue rather than removing them. This study seems to support the concept that suction and sharp debridement, as practiced by most surgeons, may remove foreign bodies well without the use of HPPL.
Recombinant Adenovirus Induces Maturation of Dendritic Cells via an NF-κB-Dependent Pathway

ABSTRACT Recombinant adenovirus (rAd) infection is one of the most effective and frequently employed methods to transduce dendritic cells (DC). Contradictory results have been reported recently concerning the influence of rAd on the differentiation and activation of DC. In this report, we show that, as a result of rAd infection, mouse bone marrow-derived immature DC upregulate expression of major histocompatibility complex class I and II antigens, costimulatory molecules (CD40, CD80, and CD86), and the adhesion molecule CD54 (ICAM-1). rAd-transduced DC exhibited increased allostimulatory capacity and levels of interleukin-6 (IL-6), IL-12p40, IL-15, gamma interferon, and tumor necrosis factor alpha mRNAs, without effects on other immunoregulatory cytokine transcripts such as IL-10 or IL-12p35. These effects were not related to specific transgenic sequences or to rAd genome transcription. The rAd effect correlated with a rapid increase (1 h) in the NF-κB–DNA binding activity detected by electrophoretic mobility shift assays. rAd-induced DC maturation was blocked by the proteasome inhibitorNα-p-tosyl-l-lysine chloromethyl ketone (TLCK) or by infection with rAd-IκB, an rAd-encoding the dominant-negative form of IκB. In vivo studies showed that after intravenous administration, rAds were rapidly entrapped in the spleen by marginal zone DC that mobilized to T-cell areas, a phenomenon suggesting that rAd also induced DC differentiation in vivo. These findings may explain the immunogenicity of rAd and the difficulties in inducing long-term antigen-specific T-cell hyporesponsiveness with rAd-transduced DC.