Thermodynamic Analysis of Interacting Nucleic Acid Strands

Motivated by the analysis of natural and engineered DNA and RNA systems, we present the first algorithm for calculating the partition function of an unpseudoknotted complex of multiple interacting nucleic acid strands. This dynamic program is based on a rigorous extension of secondary structure models to the multistranded case, addressing representation and distinguishability issues that do not arise for single-stranded structures. We then derive the form of the partition function for a fixed volume containing a dilute solution of nucleic acid complexes. This expression can be evaluated explicitly for small numbers of strands, allowing the calculation of the equilibrium population distribution for each species of complex. Alternatively, for large systems (e.g., a test tube), we show that the unique complex concentrations corresponding to thermodynamic equilibrium can be obtained by solving a convex programming problem. Partition function and concentration information can then be used to calculate equilibrium base-pairing observables. The underlying physics and mathematical formulation of these problems lead to an interesting blend of approaches, including ideas from graph theory, group theory, dynamic programming, combinatorics, convex optimization, and Lagrange duality

Current outcomes of blunt open pelvic fractures: how modern advances in trauma care may decrease mortality.

Background:Open pelvic fracture, caused by a blunt mechanism, is an uncommon injury with a high mortality rate. In 2008, evidence-based algorithm for managing pelvic fractures in unstable patients was published by the Western Trauma Association (WTA). The use of massive transfusion protocols has become widespread as has the availability and use of pelvic angiography. The purpose of this study was to evaluate the outcome of open pelvic fractures in association with related advances in trauma care. Methods:A retrospective review was performed, at an American College of Surgeon verified level I trauma center, of patients with blunt open pelvic fractures from January 2010 to April 2016. The WTA algorithm, including massive transfusion protocol, and pelvic angiography were uniformly used. Data collected included injury severity score, demographic data, transfusion requirements, use of pelvic angiography, length of stay, and disposition. Data were compared with a similar study from 2005. Results:During the study period, 1505 patients with pelvic fractures were analyzed; 87 (6%) patients had open pelvic fractures. Of these, 25 were from blunt mechanisms and made up the study population. Patients in both studies had similar injury severity scores, ages, Glasgow Coma Scale, and gender distributions. Use of angiography was higher (44% vs. 16%; P=0.011) and mortality was lower (16% vs. 45%; P=0.014) than in the 2005 study. Conclusions:Changes in trauma care for patients with open blunt pelvic fracture include the use of an evidence-based algorithm, massive transfusion protocols and increased use of angioembolization. Mortality for open pelvic fractures has decreased with these advances. Level of evidence:Level IV

New light curves and ephemeris for the close eclipsing binary V963 PER

We have obtained CCD photometry in 2010-11 of V963 Per (=GSC3355 0394), which is a recently identified close binary star with unequal eclipse depths. The seven new eclipse timings yield an improved ephemeris, but we caution that secondary eclipse can be affected by variation of the light curve. This variation seems to be on a monthly timescale at the few percent level.Comment: 6 pages, 3 figure

Experimental library screening demonstrates the successful application of computational protein design to large structural ensembles

The stability, activity, and solubility of a protein sequence are determined by a delicate balance of molecular interactions in a variety of conformational states. Even so, most computational protein design methods model sequences in the context of a single native conformation. Simulations that model the native state as an ensemble have been mostly neglected due to the lack of sufficiently powerful optimization algorithms for multistate design. Here, we have applied our multistate design algorithm to study the potential utility of various forms of input structural data for design. To facilitate a more thorough analysis, we developed new methods for the design and high-throughput stability determination of combinatorial mutation libraries based on protein design calculations. The application of these methods to the core design of a small model system produced many variants with improved thermodynamic stability and showed that multistate design methods can be readily applied to large structural ensembles. We found that exhaustive screening of our designed libraries helped to clarify several sources of simulation error that would have otherwise been difficult to ascertain. Interestingly, the lack of correlation between our simulated and experimentally measured stability values shows clearly that a design procedure need not reproduce experimental data exactly to achieve success. This surprising result suggests potentially fruitful directions for the improvement of computational protein design technology

Crohn's disease activity index and Vienna classification - Is it worthwhile to calculate before surgery?

Background: Crohn's disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The `Crohn's disease activity index' (CDAI) and the `Vienna classification' (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed. Methods: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed. Results: VC behavior and location subtypes were associated with distinct types of surgery (i.e. `strictureplasty' in `stricturing disease', `colon surgery' in `colon involvement'), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 `surgical sites' 425 +/- 25 vs. 223.3 +/- 25) and complications (357.1 +/- 36.9 (with) vs. 244.4 +/- 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression. Conclusion: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications. Copyright (c) 2006 S. Karger AG, Base

Getting residents closer to public institutions through gamification

With the huge growth of mobile device users, in recent years, the need and the opportunity to create new digital services and platforms has arisen. These platforms and services not only make people’s daily life easier, but also facilitate and improve communication between institutions and people. Also, new ways of achieving the intended goals are being developed and tested. Gamification is an example, where institutions and people’s communication is encouraged through the offering of incentives/rewards that potentiate involvement with that particular institution. In practice, institutions offer rewards to participants who perform predetermined tasks, for recommendation, dissemination, evaluation or greater involvement of people with that particular institution. The concept of smart cities is also getting huge attention nowadays. Making a city “smart” is emerging as a strategy to mitigate the problems generated by the urban population growth and rapid urbanization. In this work, we propose a digital solution, in the form of a mobile application, which has as its main goal to improve city hall public services and people’s communication, bringing them closer. This is achieved using gamification techniques that aim to engage residents with city hall services. It is provided a report system that enables residents to communicate to the city hall services, some issues regarding their town that they wish to be solved, such as broken structures, clogged sewers, among others. The proposed system also has a lore that leads to extra motivation to complete missions, be part of player gatherings and events, and meet new people and to better explore the cities’ wonders. An admin platform for the maintenance and administration of the system is also proposed, to better help keeping the application’s content fresh and updated, allowing for a better user experience for the population. The proposed system is being prepared for testing in real environments, the simulation results, as showed in tThis work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT –Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/201

The structural history and mineralization controls of the world-class Geita Hill gold deposit, Geita Greenstone Belt, Tanzania

The Geita Hill gold deposit is located in the Archean Geita Greenstone Belt and is one of the largest gold deposits in East Africa. The Geita Greenstone Belt experienced a complex deformation and intrusive history that is well illustrated and preserved in and around the Geita Hill gold deposit. Deformation involved early stages of ductile shearing and folding (D1 to D5), during which episodic emplacement of large diorite intrusive complexes, sills, and dykes occurred. These ductile deformation phases were followed by the development of brittle-ductile shear zones and faults (D6 to D8). The last stages of deformation were accompanied by voluminous felsic magmatism involving the intrusion of felsic porphyry dykes, within the greenstone belt, and the emplacement of large granitic bodies now forming the margins of the greenstone belt. Early, folded lamprophyre dykes, and later lamprophyre dykes, crosscutting the folded sequence are common, although volumetrically insignificant. The gold deposit formed late during the tectonic history of the greenstone belt, post-dating ductile deformation and synchronous with the development of brittle-ductile shear zones that overprinted earlier structural elements. The main mineralizing process involved sulfide replacement of magnetite-rich layers in ironstone and locally the replacement of ferromagnesian phases and magnetite in the diorite intrusions. The intersection between the brittle-ductile (D6) Geita Hill Shear Zone and different structural elements of ductile origin (e.g., fold hinges), and the contact between banded ironstone and folded diorite dykes and sills provided the optimal sites for gold mineralization