Optimization of van der Waals Energy for Protein Side-Chain Placement and Design

AbstractComputational determination of optimal side-chain conformations in protein structures has been a long-standing and challenging problem. Solving this problem is important for many applications including homology modeling, protein docking, and for placing small molecule ligands on protein-binding sites. Programs available as of this writing are very fast and reasonably accurate, as measured by deviations of side-chain dihedral angles; however, often due to multiple atomic clashes, they produce structures with high positive energies. This is problematic in applications where the energy values are important, for example when placing small molecules in docking applications; the relatively small binding energy of the small molecule is drowned by the large energy due to atomic clashes that hampers finding the lowest energy state of the docked ligand. To address this we have developed an algorithm for generating a set of side-chain conformations that is dense enough that at least one of its members would have a root mean-square deviation of no more than R Å from any possible side-chain conformation of the amino acid. We call such a set a side-chain cover set of order R for the amino acid. The size of the set is constrained by the energy of the interaction of the side chain to the backbone atoms. Then, side-chain cover sets are used to optimize the conformation of the side chains given the coordinates of the backbone of a protein. The method we use is based on a variety of dead-end elimination methods and the recently discovered dynamic programming algorithm for this problem. This was implemented in a computer program called Octopus where we use side-chain cover sets with very small values for R, such as 0.1 Å, which ensures that for each amino-acid side chain the set contains a conformation with a root mean-square deviation of, at most, R from the optimal conformation. The side-chain dihedral-angle accuracy of the program is comparable to other implementations; however, it has the important advantage that the structures produced by the program have negative energies that are very close to the energies of the crystal structure for all tested proteins

OS Support for Portable Bulk Synchronous Parallel Programs

Predictability -- the ability to foretell that an implementation will not violate a set of specified reliability and timeliness requirements -- is a crucial, highly desirable property of responsive embedded systems. This paper overviews a development methodology for responsive systems, which enhances predictability by eliminating potential hazards resulting from physically-unsound specifications. The backbone of our methodology is the Time-constrained Reactive Automaton (TRA) formalism, which adopts a fundamental notion of space and time that restricts expressiveness in a way that allows the specification of only reactive, spontaneous, and causal computation. Using the TRA model, unrealistic systems – possessing properties such as clairvoyance, caprice, infinite capacity, or perfect timing -- cannot even be specified. We argue that this "ounce of prevention" at the specification level is likely to spare a lot of time and energy in the development cycle of responsive systems -- not to mention the elimination of potential hazards that would have gone, otherwise, unnoticed. The TRA model is presented to system developers through the Cleopatra programming language. Cleopatra features a C-like imperative syntax for the description of computation, which makes it easier to incorporate in applications already using C. It is event-driven, and thus appropriate for embedded process control applications. It is object-oriented and compositional, thus advocating modularity and reusability. Cleopatra is semantically sound; its objects can be transformed, mechanically and unambiguously, into formal TRA automata for verification purposes, which can be pursued using model-checking or theorem proving techniques. Since 1989, an ancestor of Cleopatra has been in use as a specification and simulation language for embedded time-critical robotic processes.ARPA (F19628-92-C-0113); NSF (CDA-9308833

Using age, arterial lactate level and sequential organ failure assessment score in risk stratification of sepsis syndromes

Introduction: In low income countries, ICU places are limited and not all sepsis patients will benefit from ICU admission. Stratification is an important step to identify patients who require ICU treatment from patients who can be treated on general ward setting. Improper stratification results in increased length of stay, costs, morbidity and mortality. Objective: The aim of this study was to stratify the risk of mortality in patients with sepsis syndrome using age, arterial lactate level and SOFA score. Methods: In this prospective observational study, 250 patients with sepsis were enrolled and followed up until discharge. They were categorized into 2 groups according to 7-days mortality. Results: SOFA score (≥5) was the only good tool (AUC=0.722) while age (≥65 years) (AUC=0.650) and arterial lactate (≥3.25 mmol/L) (0.690) were fair tools to predict 7-days mortality. A new score “ALSOFA score” (≥10) was an excellent tool for prediction (AUC =0.912, 95%CI: 0.851 to 0.940, p<0.0001). It showed an excellent sensitivity (90.9%) and specificity (85.1%). Conclusion: In critically ill patients with sepsis syndromes, age, arterial lactate and SOFA score are fair tools of stratification. No single marker/score can be used alone to stratify such patients

Efficient Learning of Real Time One-Counter Automata

We present an efficient learning algorithm for languages accepted by deterministic real time one counter automata (ROCA). The learning algorithm works by first learning an initial segment, Bn, of the infinite state machine that accepts the unknown language and then decomposing it into a complete control structure and a partial counter. A new efficient ROCA decomposition algorithm, which will be presented in detail, allows this result. The decomposition algorithm works in O(n2log(n)) where nc is the number of states of Bn for some constant c. If Angluin's algorithm for learning regular languages is used to learn Bn and the complexity of this step is h(n, m) where m is the length of the longest counter example necessary for Angluin's algorithm, the complexity of our algorithm is thus O(h(n, m) + n2log(n)).Engineering and Applied Science

Thermal Equilibrium as an Initial State for Quantum Computation by NMR

We present a method of using a nuclear magnetic resonance computer to solve the Deutsch-Jozsa problem in which: (1) the number of molecules in the NMR sample is irrelevant to the number of qubits available to an NMR quantum computer, and (2) the initial state is chosen to be the state of thermal equilibrium, thereby avoiding the preparation of pseudopure states and the resulting exponential loss of signal as the number of qubits increases. The algorithm is described along with its experimental implementation using four active qubits. As expected, measured spectra demonstrate a clear distinction between constant and balanced functions.Comment: including 4 figure

Role of static fluid MR urography in detecting post urinary diversion complications

Aim of work: The aim of the study was to assess the diagnostic performance of static MR urography in detection of post cystectomy complications &amp; the ability of static fluid MR urography in visualization of urinary tract segments.Material &amp; methods: We prospectively reviewed 21 MR urograms with urinary diversion. The most common surgical procedures included Ileal conduit &amp; Ileocecal neobladder diversion.Material &amp; methods: Magnetic resonance urography examinations were performed with 1.5-T MR scanners. T2 weighted (static fluid) MR urography techniques were done, in addition to conventional T1- and T2-weighted axial and coronal sequences. Urinary tract was divided in different parts: pelvicalyceal systems, upper, mid and lower ureteric segments &amp; the reservoir or conduit Imaging features of the urinary collecting systems were evaluated for their visualization and complications detection.Results: T2-weighted MR urography could demonstrate 95% of urinary tract segments &amp; together with conventional MR sequences all urinary tract segments can be visualized. Urinary diversion related complications were encountered included in 15 patients (71.4%) &amp; no urological complications were seen in 6 patients (28.6%).Conclusion: Comprehensive T2-weighted MR urography is an effective imaging method for the visualization of the urinary system and detection of early and late postoperative complications in patients with urinary diversion.Keywords: MR urography, Urinary diversion, Cancer bladde

Age, Comorbidities, and Mortality Correlation in COVID-19 Patients: A Review

Background: The risk of death due to COVID-19 among hospitalized patients is known to be higher in older adults and those with underlying health conditions. Understanding the percentage of patients who are at increased risk of death due COVID-19 and how this varies between age groups will inform the healthcare community how to evaluate the risk of COVID-19, and better design healthcare and economic policies. Methods: We conducted a literature search for studies published between December 2019 until May 16, 2020 in PubMed, Embase, and Cochrane (CENTRAL). Descriptive statistics were performed. Results: We reviewed 14 studies of which 13 were retrospective and one was prospective. Eleven studies were conducted in Wuhan, China. A grand total of 11,938 COVID-19 confirmed patients were reviewed. Among these patients, 7637 (64%) were males. Our review reported hypertension (41%), diabetes (21%), cardiac diseases (14%), COPD (8%), chronic kidney disease (4%) and cerebrovascular disease (10%) as the most common underlying diseases among patients who died during hospitalization due to COVID-19. The total number of patients died in the hospital was 1744 (15%). Among patients who died in the hospital, 1% patients were 30-39 years, 16% patients were 40-59 years and 83% patients were more than 60 years of age. Conclusions: Older patients with underlying diseases appear to be at higher risk of mortality from COVID-19. Comorbidities are significant predictors of mortality in COVID-19 patients. There is an urgent need to know the epidemiology of the novel virus and characterize its potential impact

Accuracy of Gray‑scale and Three‑dimensional Power Doppler Ultrasound Parameters in the Diagnosis of Morbidly Adherent Placenta

Background: Morbidly adherent placenta (MAP) is usually associated with excess blood loss, bladder injuries, and hysterectomies.Aim: This study was designed to evaluate the accuracy of grayscale and three-dimensional (3D) power Doppler ultrasound parameters in the diagnosis of MAP. Subjects and Methods: Fifty pregnant women ≥28 weeks’ gestation with suspected MAP were included randomly in this prospective study. Two-dimensional (2D) transabdominal gray-scale ultrasound and 3D power Doppler scans were done for studied women to confirm placental location and findings suggestive of MAP. Intraoperative findings and histopathology results of removed uteri in the cases were managed by hysterectomies compared to preoperative sonographic findings using Student’s t-test and Mann–Whitney U-test for quantitative data, Chi-square test for qualitative data to detect the accuracy of 2D transabdominal gray-scale ultrasound and 3D power Doppler parameters in the diagnosis of MAP. Results: Best 2D gray scale ultrasound parameters for the detection of emergency hysterectomies in the studied cases were disruption of uterine serosa– bladder interface (81.8% sensitivity) and exophytic mass invading bladder (94.9% specificity, 66.7% positive predictive value (PPV), and 84.1% negative predictive value [NPV]). Best 3D power Doppler parameters for the detection of emergency hysterectomies in the studied cases were disruption of uterine serosa–bladder interface (90.9% sensitivity, 68.8% specificity, and 47% PPV) and crowded vessels over peripheral subplacental zone (93.2% NPV). Conclusion: 3D power Doppler is a useful complementary tool to 2D gray-scale ultrasound for antenatal diagnosis of MAP. Crowded vessels over peripheral sub-placental zone and disruption of uterine serosa–bladder interface were the best 3D power Doppler parameters for the detection of difficult placental separation, considerable intraoperative blood loss, and emergency hysterectomies in the studied cases.KEY WORDS: Three‑dimensional power Doppler, gray-scale, morbidly adherent placent