PyCoM: a python library for large-scale analysis of residue-residue coevolution data

The version currently archived on this institutional repository is an accepted manuscript, the PDF version of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.Data availability The data underpinning this publication can be accessed from Brunel University London's data repository under CC BY license: Coevolution matrix database https://brunel.figshare.com/articles/dataset/PyCoM_ProCoM_Database_of_coevolu tion_matrices/23735613 and protein database https://brunel.figshare.com/articles/dataset/PyCoM_ProCoM_Curated_UniProt_pro tein_database/23733309 .Availability and implementation PyCoM code is freely available from https://github.com/scdantu/pycom and PyCoMdb and the Jupyter Notebook tutorials are freely available from https://pycom.brunel.ac.uk .Supplementary information: Supplementary data are available at Bioinformatics online at https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/btae166/7635577#supplementary-data .Motivation: Computational methods to detect correlated amino acid positions in proteins have become a valuable tool to predict intra and inter-residue protein contacts, protein structures, and effects of mutation on protein stability and function. While there are many tools and webservers to compute coevolution scoring matrices, there is no central repository of alignments and coevolution matrices for large-scale studies and pattern detection leveraging on structural and biological annotation already available in UniProt. Results: We present a Python library, PyCoM, which enables users to query and analyse coevolution matrices and sequence alignments of 457,622 proteins, selected from UniProtKB/Swiss-Prot database (length ≤ 500 residues), from a pre-compiled coevolution matrix database (PyCoMdb). PyCoM facilitates the development of statistical analyses of residue coevolution patterns using filters on structural and biological annotation from UniProtKB/Swiss-Prot, with simple access to PyCoMdb for both novice and advanced users, supporting Jupyter Notebooks, Python scripts, and a web API access. The resource is open source and will help in generating data-driven computational models and methods to study and understand protein structures, stability, function, and design.This project made use of time on HPC granted via the UK High-End Computing Consortium for Biomolecular Simulation, HECBioSim (http://hecbiosim.ac.uk), supported by EPSRC (grant no. EP/R029407/1). Philipp Bibik was funded by Department of Computer Science, Brunel University London, summer internship programme

Surgical Outcome of Very Small Intracranial Aneurysms Utilizing the Double Clip Technique

OBJECTIVES: To report the outcome of patients with very small intracranial aneurysm (VSIA) undergoing surgical clipping using a double-clip technique. METHODS: This cross-sectional study was conducted in Namazi Hospital, the main referral neurovascular center in Southern Iran during a 6-year period from September 2010 to March 2016. All patients with VSIAs ( RESULTS: Operations were performed on 32 VSIAs in 26 patients with a mean +/- SD age of 55.7 +/- 10.1 years. Middle cerebral artery was the most common location for VSIA (50.0%). There was no neck remnant, and the complete occlusion rate was 100%. The rate of intraoperative aneurysm rupture was 30.8%, and none of the patients experienced rebleeding. The 6-month mortality rate was 0% in ruptured VSIAs and 6.25% in unruptured VSIAs. Most of the patients had favorable outcomes (88.5%), and the overall mortality rate was 11.5%. The rate of permanent neurologic deficit was 10.0% in ruptured and 12.5% in unruptured VSIAs. Multivariate logistic regression analysis revealed no association between baseline and clinical characteristics and outcome in this series. CONCLUSION: VSIAs are difficult to treat because of their small sizes; therefore, with a double-clip technique, one can reduce complications related to the treatment of small aneurysms.Peer reviewe

Outcome of decompressive craniectomy in comparison to nonsurgical treatment in patients with malignant MCA infarction

Background: Malignant cerebral infarction is a well-recognized disease, comprising 10-15% of all cases with cerebral infarction and causing herniation and death in 80% of cases. In this study, we compare the effects of decompressive craniectomy versus conventional medical treatment on mortality rate and functional and neurological outcome in patients with malignant MCA infarction. Methods: We performed a prospective case-control study on 60 patients younger than 80years of age suffering malignant MCA cerebral infarction. The case group underwent decompressive craniectomy in addition to routine aggressive medical care; while the control group received routine medical treatment. Patient outcome was assessed using Glasgow outcome scale and modified Rankin scale within three months of follow-up. The data were analyzed by SPSS version 16.0 software using Chi Square, One-way ANOVA and Mann-Whitney tests. Results: There were 27 male and 33 female patients with a mean age of 60.6 years (SD = 12.3). Glasgow outcome scale score averaged 2.93 in the surgical versus 1.53 in the medical group; this difference was significant (p = 0.001). Outcome in modified Rankin scale was also significantly lower in the surgical (3.27) versus medical (5.27) group (p <0.001). Surgery could decrease the mortality rate about 47%. Conclusion: In this study, decompressive craniectomy could decrease mortality rate, and improve neurological and functional outcome, and decrease long-term disability in patients with malignant MCA infarction.Peer reviewe

Engineered Protein Scaffolds as Tools for Studying Intracellular Proteins

Molecules that bind to targets with high specificity and affinity are used as therapeutic and diagnostic agents in medicine and research. Protein and non-protein ligands are used for introduction of mutations within the binding region to increase the binding affinity. Phage-display technology is used to screen multiple scaffolds against target proteins to select for high affinity binders. Scaffolds are displayed on phage particles and can be tested for binding to targets with standard binding assays. Various target proteins are encoded by essential genes to disrupt cellular proliferation and were identified as fitness genes in CRISPR screens. Altogether, utilizing the two technologies facilitates making and screening of binders to intracellular targets and accelerates the production of highly efficient synthetic binders. To develop and optimize the technique, the Sidhu lab generated 27 protein scaffold libraries that were tested against 25 target proteins and selected several variants for further analysis in mammalian cells.M.Sc

Unsteady-State Creep of an Asphalt Concrete

At present, an asphalt concrete, it seems, is the most widespread road material all over the world [...

Outcome of In-Hospital Rebleeding and Early Aneurysm Rupture at the Referral Center

Background and Aim: In-hospital rebleeding and early aneurysm rupture are major causes of mortality and morbidity in aneurysmal subarachnoid hemorrhage. Rebleeding may occur at the referring hospital, during transfer or at the referral neurovascular center prior to surgical or endovascular treatment. However, there has been no report regarding the rate of in-hospital rebleeding and early aneurysm rupture at the referral centers. This study aims to clarify the incidence, significance, management, and outcome of individuals who suffer in-hospital aneurysmal rebleeding and early aneurysm rupture at the referral hospital due to anterior circulation cerebral aneurysm to the time when its neck is visualized for clipping. Methods and Materials/Patients: Among 617 patients with anterior circulation cerebral aneurysms who underwent operation between September 2010 and September 2017 at Neurovascular Unit of Namazi Hospital (main referral neurovascular center in southern Iran), 22 suffered rebleeding since the time of neuroradiologic diagnosis of aneurysm to intraoperative visualization of aneurysm for neck dissection. A surgical technique for fast access and securing the aneurysm is described in this article, too. The patients’ demographics were collected via hospital records in a retrospective fashion. Six-month functional outcome was obtained via OPD records as well as phone calls. Utilizing Independent t test, 1-way ANOVA, Kruskal-Wallis and Mann-Whitney tests in SPSS22, the effect of each study variable was evaluated during 6 months follow-up period.  Results: Rebleeding occurred at different venues from CT angiography to frontal lobe retraction. Anterior communicating artery was the most common aneurysm to suffer in-hospital rebleeding and male gender was found as a risk factor. These patients have significantly higher bleeding amount and longer operative time (P<0.001), but still have a 68.2% chance of surviving with good functional recovery. Earlier in-hospital rebleedings are used to have worse outcomes (P=0.036 for GOS and 0.028 for mRS, respectively).  Conclusion: Patients with in-hospital rebleeding and early aneurysm rupture at the referral hospitals will have a considerable chance for favorable outcome if they undergo aggressive surgical management emergently

Erythropoietin Plus Methylprednisolone or Methylprednisolone in the Treatment of Acute Spinal Cord Injury: a Preliminary Report

Recent studies in animal models indicate that recombinant human erythropoietin (rhEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). We aimed to evaluate the effect of rhEPO plus methylprednisolone sodium succinate (MPSS) compared to MPSS alone to improve neurological function of patients after SCI in a randomized clinical trial. During a 15-month period 30 patients presenting to emergency departments of two university affiliated hospitals within less than 6 hours after acute SCI were randomized to two groups. Both groups received MPSS 30 mg/kg initially and 5.4 mg/kg every hour till 23 hours if admitted within 3 hours and till 47 hours if recruited within 3-6 hours after injury. Group EPO also received 500 unit/kg rhEPO on admission and another 500 unit/kg 24 hours later instead of placebo in group MPSS. Neurologic evaluation was performed on admission, 24, 48, 72 hours and one and 6 months later. Range of patients' age was 18-65 years. There was no significant difference between patients receiving two types of treatment in neurological exam on admission (P=0.125), 24 hours after admission (P=0.108) and 48 hours after admission (P=0.085). However, one week (P=0.046), one month (P=0.021) and six months (P=0.018) after admission these differences were significant. MPSS plus rhEPO started within 6 hours after acute spinal injury may be more effective than MPSS plus placebo in improvement of neurologic dysfunction. More studies with larger sample sizes are warranted

Modeling of Cyclic Strength for the Asphalt Concrete Considering Damage Accumulation

The expression is obtained for determination of cyclic tensile strength for asphalt concrete, which considers damage accumulation and history of loading, using the long-term strength curve for asphalt concrete obtained according to the test results of more than 110 samples to failure at stresses from 0.05 to 0.31 MPa and by introduction of damage kernel in this paper. Cyclic strength depends on the stress, parameters of long-term strength, frequency of loading, durations of loading and relax periods, and ratio of loading period to the long-term strength. Evaluation of accuracy for the obtained expression for the cyclic strength has been performed by comparison with the results of a series for experimental tests of asphalt concrete samples at a temperature of 22 °С and cyclic loading conditions. The stress is 0.31 MPa, and the durations of loading and relax periods are 5 and 60 s, respectively. Calculations performed with the obtained expressions at real road conditions (the stress is 0.31 MPa, and the durations of loading and relax periods are 0.1 and 9.9 s respectively) showed the possibility of its use for the prediction of fatigue (multicyclic) strength of an asphalt concrete pavement for a highway

Steady-State Creep of Asphalt Concrete

This paper reports the experimental investigation of the steady-state creep process for fine-grained asphalt concrete at a temperature of 20 ± 2 °С and under stress from 0.055 to 0.311 MPa under direct tension and was found to occur at a constant rate. The experimental results also determined the start, the end point, and the duration of the steady-state creep process. The dependence of these factors, in addition to the steady-state creep rate and viscosity of the asphalt concrete on stress is satisfactorily described by a power function. Furthermore, it showed that stress has a great impact on the specific characteristics of asphalt concrete: stress variation by one order causes their variation by 3–4.5 orders. The described relations are formulated for the steady-state of asphalt concrete in a complex stressed condition. The dependence is determined between stress intensity and strain rate intensity