IT’S THE LITTLE THINGS: AN EXPLORATION OF SMALL RNAS AND SELFISH GENETIC ELEMENTS OF THE HUMAN BACTERIAL PATHOGENS COXIELLA BURNETII AND BARTONELLA BACILLIFORMIS

Coxiella burnetii is a Gram-negative gammaproteobacterium and zoonotic agent of Q fever in humans. Previous work in our lab has demonstrated that C. burnetii codes for several small RNAs (sRNAs) that are differentially expressed between in vivo and in vitro growth conditions. sRNAs serve as post-transcriptional regulatory effectors involved in the control of nearly all biological processes. We demonstrated that several of the identified sRNAs, namely Coxiella burnetii small RNA 3 (CbsR3), Cbsr13, and CbsR16, represent members of two novel families of miniature inverted-repeat transposable elements (MITEs), termed QMITE1 and QMITE2. Furthermore, we have characterized a highly expressed, infection-specific sRNA, CbsR12, and have determined that it is necessary for expansion of the C. burnetii intracellular niche in a human monocyte-derived alveolar macrophage cell line. We have determined that CbsR12 may participate in broad gene regulation by acting as an RNA sponge for the global regulatory RNA-binding protein CsrA. Additionally, CbsR12 is a trans-acting sRNA that targets transcripts of the carA, metK, and cvpD genes in vitro and in vivo. Bartonella bacilliformis is a Gram-negative alphaproteobacterium and the etiological agent of Carrión\u27s disease in humans. B. bacilliformis is spread between humans through the bite of female phlebotomine sand flies. As a result, the pathogen encounters significant environmental shifts during its life cycle, including changes in pH and temperature. Bacterial sRNAs can serve as a means of rapid regulation under shifting environmental conditions. We therefore performed total RNA-sequencing analyses on B. bacilliformis grown in vitro then shifted to one of ten distinct conditions that simulate various environments encountered by the pathogen during its life cycle. From this, we identified 160 sRNAs significantly expressed under at least one of the conditions tested. Northern blot analysis was used to confirm the expression of eight novel sRNAs. We also characterized a Bartonella bacilliformis group I intron (BbgpI) that disrupts an un-annotated tRNACCUArg gene and determined that the intron splices in vivo and self-splices in vitro. Furthermore, we verified the predicted molecular targeting of a sand fly-specific sRNA, Bartonella bacilliformis small RNA 9 (BbsR9), to transcripts of the ftsH, nuoF, and gcvT genes, in vitro

An Adversorial Approach to Enable Re-Use of Machine Learning Models and Collaborative Research Efforts Using Synthetic Unstructured Free-Text Medical Data

We leverage Generative Adversarial Networks (GAN) to produce synthetic free-text medical data with low re-identification risk, and apply these to replicate machine learning solutions. We trained GAN models to generate free-text cancer pathology reports. Decision models were trained using synthetic datasets reported performance metrics that were statistically similar to models trained using original test data. Our results further the use of GANs to generate synthetic data for collaborative research and re-use of machine learning models

Inflow cannula design for biventricular assist devices

Cardiovascular diseases are a leading cause of death throughout the developed world. With the demand for donor hearts far exceeding the supply, a bridge-to-transplant or permanent solution is required. This is currently achieved with ventricular assist devices (VADs), which can be used to assist the left ventricle (LVAD), right ventricle (RVAD), or both ventricles simultaneously (BiVAD). Earlier generation VADs were large, volume-displacement devices designed for temporary support until a donor heart was found. The latest generation of VADs use rotary blood pump technology which improves device lifetime and the quality of life for end stage heart failure patients. VADs are connected to the heart and greater vessels of the patient through specially designed tubes called cannulae. The inflow cannulae, which supply blood to the VAD, are usually attached to the left atrium or ventricle for LVAD support, and the right atrium or ventricle for RVAD support. Few studies have characterized the haemodynamic difference between the two cannulation sites, particularly with respect to rotary RVAD support. Inflow cannulae are usually made of metal or a semi-rigid polymer to prevent collapse with negative pressures. However suction, and subsequent collapse, of the cannulated heart chamber can be a frequent occurrence, particularly with the relatively preload insensitive rotary blood pumps. Suction events may be associated with endocardial damage, pump flow stoppages and ventricular arrhythmias. While several VAD control strategies are under development, these usually rely on potentially inaccurate sensors or somewhat unreliable inferred data to estimate preload. Fixation of the inflow cannula is usually achieved through suturing the cannula, often via a felt sewing ring, to the cannulated chamber. This technique extends the time on cardiopulmonary bypass which is associated with several postoperative complications. The overall objective of this thesis was to improve the placement and design of rotary LVAD and RVAD inflow cannulae to achieve enhanced haemodynamic performance, reduced incidence of suction events, reduced levels of postoperative bleeding and a faster implantation procedure. Specific objectives were: * in-vitro evaluation of LVAD and RVAD inflow cannula placement, * design and in-vitro evaluation of a passive mechanism to reduce the potential for heart chamber suction, * design and in-vitro evaluation of a novel suture-less cannula fixation device. In order to complete in-vitro evaluation of VAD inflow cannulae, a mock circulation loop (MCL) was developed to accurately replicate the haemodynamics in the human systemic and pulmonary circulations. Validation of the MCL’s haemodynamic performance, including the form and magnitude of pressure, flow and volume traces was completed through comparisons of patient data and the literature. The MCL was capable of reproducing almost any healthy or pathological condition, and provided a useful tool to evaluate VAD cannulation and other cardiovascular devices. The MCL was used to evaluate inflow cannula placement for rotary VAD support. Left and right atrial and ventricular cannulation sites were evaluated under conditions of mild and severe heart failure. With a view to long term LVAD support in the severe left heart failure condition, left ventricular inflow cannulation was preferred due to improved LVAD efficiency and reduced potential for thrombus formation. In the mild left heart failure condition, left atrial cannulation was preferred to provide an improved platform for myocardial recovery. Similar trends were observed with RVAD support, however to a lesser degree due to a smaller difference in right atrial and ventricular pressures. A compliant inflow cannula to prevent suction events was then developed and evaluated in the MCL. As rotary LVAD or RVAD preload was reduced, suction events occurred in all instances with a rigid inflow cannula. Addition of the compliant segment eliminated suction events in all instances. This was due to passive restriction of the compliant segment as preload dropped, thus increasing the VAD circuit resistance and decreasing the VAD flow rate. Therefore, the compliant inflow cannula acted as a passive flow control / anti-suction system in LVAD and RVAD support. A novel suture-less inflow cannula fixation device was then developed to reduce implantation time and postoperative bleeding. The fixation device was evaluated for LVAD and RVAD support in cadaveric animal and human hearts attached to a MCL. LVAD inflow cannulation was achieved in under two minutes with the suture-less fixation device. No leakage through the suture-less fixation device – myocardial interface was noted. Continued development and in-vivo evaluation of this device may result in an improved inflow cannulation technique with the potential for off-bypass insertion. Continued development of this research, in particular the compliant inflow cannula and suture-less inflow cannulation device, will result in improved postoperative outcomes, life span and quality of life for end-stage heart failure patients

Statistics of Random Permutations and the Cryptanalysis Of Periodic Block Ciphers

A block cipher is intended to be computationally indistinguishable from a random permutation of appropriate domain and range. But what are the properties of a random permutation? By the aid of exponential and ordinary generating functions, we derive a series of collolaries of interest to the cryptographic community. These follow from the Strong Cycle Structure Theorem of permutations, and are useful in rendering rigorous two attacks on Keeloq, a block cipher in wide-spread use. These attacks formerly had heuristic approximations of their probability of success. Moreover, we delineate an attack against the (roughly) millionth-fold iteration of a random permutation. In particular, we create a distinguishing attack, whereby the iteration of a cipher a number of times equal to a particularly chosen highly-composite number is breakable, but merely one fewer round is considerably more secure. We then extend this to a key-recovery attack in a "Triple-DES" style construction, but using AES-256 and iterating the middle cipher (roughly) a million-fold. It is hoped that these results will showcase the utility of exponential and ordinary generating functions and will encourage their use in cryptanalytic research.Comment: 20 page

Typografia w relacji człowiek–komputer. Kognitywne i estetyczne implikacje wyboru i sposobu prezentacji kroju fontów

The article discusses the typography in the context of literature concerning cognitive psychology. Scholars were interested in designers’ choices and their impact on the material’s readability and understanding by the reader. The Authors were also intrigued by researchers’ proposals on how typography can improve human–computer interaction. The text reconstructed, among others, the studies by Miles A. Tinker and Donald G. Patterson, Dan Boyarski, and David Beymer. The texts elaborates on text background or font color, as well as set out future research fields on the readability of on-screen texts.Artykuł omawia typografię w kontekście literatury dotyczącej psychologii kognitywnej. Badaczy interesowały wybory projektantów oraz wpływ tych wyborów na czytelność i zrozumienie materiału przez czytelnika, także zagadnienie, w jaki sposób typografia może poprawić interakcję między człowiekiem a komputerem. W tekście zrekonstruowano m.in. badania Milesa A. Tinkera i Donalda G. Pattersona, Dana Boyarskiego i Davida Beymera oraz przybliżono rozważania nad kolorem tła tekstu czy fontów

Offsetting of CO₂ emissions by air capture in mine tailings at the Mount Keith Nickel Mine, Western Australia: Rates, controls and prospects for carbon neutral mining

The hydrated Mg-carbonate mineral, hydromagnesite [Mg₅(CO₃)₄(OH)₂•4H₂O], precipitates within mine tailings at the Mount Keith Nickel Mine, Western Australia as a direct result of mining operations. We have used quantitative mineralogical data and δ¹³C, δ¹⁸O and F¹⁴C isotopic data to quantify the amount of CO₂fixation and identify carbon sources. Our radiocarbon results indicate that at least 80% of carbon stored in hydromagnesite has been captured from the modern atmosphere. Stable isotopic results indicate that dissolution of atmospheric CO₂ into mine tailings water is kinetically limited, which suggests that the current rate of carbon mineralization could be accelerated. Reactive transport modeling is used to describe the observed variation in tailings mineralogy and to estimate rates of CO₂ fixation. Based on our assessment, approximately 39,800 t/yr of atmospheric CO₂ are being trapped and stored in tailings at Mount Keith. This represents an offsetting of approximately 11% of the mine's annual greenhouse gas emissions. Thus, passive sequestration via enhanced weathering of mineral waste can capture and store a significant amount of CO₂. Recommendations are made for changes to tailings management and ore processing practices that have potential to accelerate carbonation of tailings and further reduce or completely offset the net greenhouse gas emissions at Mount Keith and many other mines

Displacing sedentary time: Association with cardiovascular disease prevalence

Purpose: Isotemporal substitution analysis offers new insights for public health, but has only recently been applied to sedentary behavior research. We aimed to quantify associations between the substitution of 10 minutes of sedentary behavior with 10 minutes of light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) and the prevalence of cardiovascular disease (CVD). Age was also explored as a potential effect modifier. Methods: We completed a secondary analysis of data from 1477 adults from the Health Survey for England (2008). Sedentary time, LPA and MVPA were measured using accelerometry. We applied isotemporal models to quantify the relationship with CVD prevalence of replacing 10 minutes of sedentary time with equivalent amounts of LPA or MVPA. Prevalence risk ratios (RR) with 95% confidence intervals (CI) are presented, adjusted for covariates. The role of age as an effect modifier was explored via age × MVPA and age × LPA interactions. CVD was defined as per the International Classification of Diseases. Results: The prevalence of CVD was 24%. The RR was 0.97 (95% CI: 0.96 to 0.99) for LPA and 0.88 (0.81 to 0.96) for MVPA. Substitution of approximately 50 minutes of LPA would be required for an association equivalent to 10 minutes of MVPA. The beneficial association of MVPA was attenuated with age, with a decrease in the relative risk reduction of ~7% per decade. Conclusions: Isotemporal substitution of sedentary time with LPA was associated with a trivial relative risk reduction for CVD, whereas the equivalent replacement with MVPA had a small beneficial relationship. With respect to CVD prevalence, MVPA might become decreasingly important in older individuals. Prospective studies are needed to investigate causality

Generative Adversarial Networks for Creating Synthetic Free-Text Medical Data: A Proposal for Collaborative Research and Re-use of Machine Learning Models

Restrictions in sharing Patient Health Identifiers (PHI) limit cross-organizational re-use of free-text medical data. We leverage Generative Adversarial Networks (GAN) to produce synthetic unstructured free-text medical data with low re-identification risk, and assess the suitability of these datasets to replicate machine learning models. We trained GAN models using unstructured free-text laboratory messages pertaining to salmonella, and identified the most accurate models for creating synthetic datasets that reflect the informational characteristics of the original dataset. Natural Language Generation metrics comparing the real and synthetic datasets demonstrated high similarity. Decision models generated using these datasets reported high performance metrics. There was no statistically significant difference in performance measures reported by models trained using real and synthetic datasets. Our results inform the use of GAN models to generate synthetic unstructured free-text data with limited re-identification risk, and use of this data to enable collaborative research and re-use of machine learning models

Environmental Exposure Conditions for Teflon FEP on the Hubble Space Telescope Investigated

The Hubble Space Telescope (HST) was launched into low Earth orbit on April 24,1990. During the first servicing mission in December 1993 (3.6 years after launch), multilayer insulation (MLI) blankets were retrieved from the two magnetic sensing systems located on the light shield. Retrieval of one of the solar arrays during this mission also provided MLI blanket material from the solar array drive arm. These MLI materials were analyzed in ground-based facilities, and results indicate that the space-facing outer layer of the MLI, aluminized Teflon FEP (DuPont; fluorinated ethylene propylene), was beginning to degrade. Close inspection of the FEP revealed through-the-thickness cracks in areas with the highest solar exposure and stress concentration. During the second servicing mission in February 1997 (6.8 years after launch), astronauts observed and documented severe cracking in the outer layer of the MLI blankets on both the solar-facing and anti-solar-facing surfaces. During this second mission, some material from the outer layer of the light shield MLI was retrieved and subsequently analyzed in ground-based facilities. After the second servicing mission, a Failure Review Board was convened by NASA Goddard Space Flight Center to address the MLI degradation problem on HST. Members of the Electro-Physics Branch of the NASA Glenn Research Center at Lewis Field participated on this board. To determine possible degradation mechanisms, board researchers needed to consider all environmental constituents to which the FEP MLI surfaces were exposed. On the basis of measurements, models, and predictions, environmental exposure conditions for FEP surfaces on HST were estimated for various time periods from launch in 1990 through 2010, the planned end-of-life for HST. The table summarizes these data including the number and temperature ranges of thermal cycles; equivalent Sun hours; fluence and absorbed radiation dose from solar event x rays; fluence and absorbed dose from solar wind protons and electrons trapped in Earth s magnetic field; fluence of plasma electrons and protons; and atomic oxygen fluence