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Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis reveal prototypical NADPH-dependent short-chain reductases with structural similarity to protozoan pteridine reductases that are potential drug targets., Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-dependent short-chain reductases that share their highest tertiary-structural similarity with protozoan pteridine reductases, which are being investigated for rational therapeutic development.

Subtalar arthroereisis has a controversial history and has previously been associated with high failure rates and excessive complications. A database search for outcomes of arthroereisis for the treatment of symptomatic paediatric flexible pes planus provided 24 articles which were included in this review, with a total of 2550 feet operated on. Post-operative patient-reported outcome measures recorded marked improvement. Patient satisfaction was reported as excellent in 79.9%, and poor in 5.3%. All radiological measurements demonstrated improvement towards the normal range following arthroereisis, as did hindfoot valgus, supination, dorsiflexion and Viladot grade. Complications were reported in 7.1% of cases, with a reoperation rate of 3.1%. Arthroereisis as a treatment for symptomatic paediatric flexible pes planus produces favourable outcomes and high patient satisfaction rates with a reasonable risk profile. There is still a great deal of negativity and literature highlighting the complications and failures of arthroereisis, especially for older implants. The biggest flaws in the collective literature are the lack of high-quality prospective studies, a paucity of long-term data and the heterogeneity of utilized outcome measures between studies. Cite this article: EFORT Open Rev 2021;6:118-129. DOI: 10.1302/2058-5241.6.200076

Introduction Reimers migration percentage (MP) is the gold standard for measuring hip displacement in children with cerebral palsy (CP). Hip surveillance registries proposed using the top of the Gothic arch (GA) as a modification in patients with acetabular dysplasia because the classical method (CM) described by Reimers may underestimate hip migration. The aim of this study is to assess the inter- and intra-observer reliability of the modified method (MM) versus the CM and identify their effect on the MP. Methods We performed a retrospective review of 50 children with CP, who had a hip radiograph at our institution between 1st April 2014 and 28th February 2018. All hip radiographs were carefully selected to show the presence of a GA. Four observers measured the MP using the CM and MM for each patient. Interclass coefficient was used to estimate inter- and intra-observer reliability. Results Inter-observer reliability was excellent for the CM with ICC 0.96 (95% CI 0.94 to 0.97) and good for the MM, ICC 0.78 (95% CI 0.51 to 0.89) p < 0.001. Intra-observer reliability was excellent for both methods raging from ICC 0.94 to 0.99 for the CM and ICC 0.89 to 0.95 for the MM. The mean MP was 19% for the CM and 28% for the MM (p < 0.001). Conclusion The CM is more reliable than the MM to measure hip migration in children with CP. If the CM is used and acetabular dysplasia with a GA are present on the hip radiograph, then a 9% hip migration underestimation should be considered on decisions for both referral and surgical management. Level of evidence II

Agricultural water demands can conflict with habitat needs in many North Coast watersheds. Understanding different water use patterns can help reduce conflict over limited supplies. We measured on-farm crop water use and conducted grower interviews to estimate the agricultural water demand in the upper Russian River and Navarro River watersheds. Annual agricultural water demand was less than 11% in the Russian River, and 2% in Navarro River, of the total annual discharge in each watershed. However, because demands are concentrated in the dry season when instream flows are at a minimum, these relatively small amounts can represent a significant constraint to stream habitat conditions. We have shared our study results in broad basin and community water resource planning efforts, including flow management of the Russian and Navarro rivers and implementation of the Sustainable Groundwater Management Act in the Ukiah Basin. Findings and recommendations from this study have influenced on-the-ground solutions to meet water demand in these watersheds, including construction of off-stream wintertime storage capacity to replace summertime stream diversions, and use of a municipal recycled water conveyance system as a replacement for summer diversions.

Osteopontin (OPN) also known by its official gene designation secreted phosphoprotein-1 (SPP1) is a fascinating, multifunctional protein expressed in a number of cell types that functions not only in intercellular communication, but also in the extracellular matrix (ECM). OPN/SPP1 possesses cytokine, chemokine, and signal transduction functions by virtue of modular structural motifs that provide interaction surfaces for integrins and CD44-variant receptors. In humans, there are three experimentally verified splice variants of OPN/SPP1 and CD44's ten exons are also alternatively spiced in a cell/tissue-specific manner, although very little is known about how this is regulated in the central nervous system (CNS). Post-translational modifications of phosphorylation, glycosylation, and localized cleavage by specific proteases in the cells and tissues where OPN/SPP1 functions, provides additional layers of specificity. However, the former make elucidating the exact molecular mechanisms of OPN/SPP1 function more complex. Flexibility in OPN/SPP1 structure and its engagement with integrins having the ability to transmit signals in inside-out and outside-in direction, is likely why OPN/SPP1 can serve as an early detector of inflammation and ongoing tissue damage in response to cancer, stroke, traumatic brain injury, pathogenic infection, and neurodegeneration, processes that impair tissue homeostasis. This review will focus on what is currently known about OPN/SPP1 function in the brain.

Purpose: Despite extensive research, an effective and safe treatment for diffuse intrinsic pontine glioma (DIPG) has not been established. In this study, we investigate the therapeutic potential of combination therapy with histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors against DIPG.Methods: We used RNA sequencing data from DIPG patient samples to evaluate the expression of the carbonic anhydrase family and the activity of the hypoxia signaling pathway. Next, we performed a synergy screen using CA9 inhibitor SLC-0111 and the HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. We selected the SLC-0111/HDACi combination showing the highest synergy, and its effects on cell proliferation, invasion, and migration were evaluated. We also measured changes in histone acetylation, apoptosis, cell cycle, and intracellular pH.Results: CA9 was significantly upregulated in human DIPG samples. Furthermore, pathways downstream of CA9 were found to be activated when compared to normal brain tissue. The synergy screen revealed that the combination of SLC-0111 and pyroxamide was most effective at inhibiting DIPG cell proliferation. Furthermore, this combination reduced cell migration and invasion potential while enhancing histone acetylation with subsequent reduction of cell population in S Phase. Finally, the SLC-0111 and pyroxamide combination showed greater reduction of intracellular pH as compared to each agent alone.Conclusion: Our in vitro data suggest that the combination of SLC-0111 and pyroxamide shows promise in the treatment of experimental DIPG. Based on these findings, further investigation of this combination therapy in preclinical models is warranted.

RationaleSevere viral respiratory infections are often characterised by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain poorly understood.ObjectivesTo identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity.MethodsPreclinical murine models of influenza A virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.ResultsOxidised cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte/macrophage infiltration to the lung during influenza A virus (IAV) and SARS-CoV-2 infection. Both IAV and SARS-CoV-2 infection upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidised cholesterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC). Loss-of-function mutation of Gpr183 or treatment with a GPR183 antagonist reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist significantly attenuated the severity of SARS-CoV-2 infection and viral loads. Analysis of single-cell RNA-sequencing data on bronchoalveolar lavage samples from healthy controls and COVID-19 patients with moderate and severe disease revealed thatCH25H,CYP7B1andGPR183are significantly upregulated in macrophages during COVID-19.ConclusionThis study demonstrates that oxysterols drive inflammation in the lungviaGPR183 and provides the first preclinical evidence for the therapeutic benefit of targeting GPR183 during severe viral respiratory infections.

Behavior Trees (BTs) were invented as a tool to enable modular AI in computer games, but have received an increasing amount of attention in the robotics community in the last decade. With rising demands on agent AI complexity, game programmers found that the Finite State Machines (FSM) that they used scaled poorly and were difficult to extend, adapt and reuse. In BTs, the state transition logic is not dispersed across the individual states, but organized in a hierarchical tree structure, with the states as leaves. This has a significant effect on modularity, which in turn simplifies both synthesis and analysis by humans and algorithms alike. These advantages are needed not only in game AI design, but also in robotics, as is evident from the research being done. In this paper we present a comprehensive survey of the topic of BTs in Artificial Intelligence and Robotic applications. The existing literature is described and categorized based on methods, application areas and contributions, and the paper is concluded with a list of open research challenges.

The up-operators $u_i$ and down-operators $d_i$ (introduced as Schur operators by Fomin) act on partitions by adding/removing a box to/from the $i$th column if possible. It is well known that the $u_i$ alone satisfy the relations of the (local) plactic monoid, and the present authors recently showed that relations of degree at most 4 suffice to describe all relations between the up-operators. Here we characterize the algebra generated by the up- and down-operators together, showing that it can be presented using only quadratic relations., 13 pages

BACKGROUND: Amputation at the transfemoral (TF) level reduces the rate of successful prosthetic fitting, functional outcome, and quality of life (QoL) compared with transtibial amputation. The TF socket interface is considered the most critical part of the prosthesis, but socket discomfort is still the most common user complaint. Direct Socket for transfemoral prosthesis users is a novel interface fabrication process where the socket is shaped and laminated directly on the residual limb and delivered in a single visit. OBJECTIVE(S): The aim of this study was to investigate if prosthetic users' quality of life (QoL), comfort, and mobility with a Direct Socket TF interface were comparable to their experience with their previous prostheses. METHODOLOGY: The pre/post design prospective cohort study included 47 subjects. From this cohort, 36 subjects completed the 6-months follow-up (mean age 58 years, 27 males). Outcomes at baseline included EQ-5D-5L®, PLUS-M™, CLASS, ABC, AMPPRO, and TUG. At 6-weeks and 6-months, subjects repeated all measures. Seven Certified Prosthetist (CP) investigators performed observations and data collection at six different sites (from July 2018 to April 2020). FINDINGS: Results showed significant improvement in all outcome measures for the 36 subjects that completed both 6-weeks and 6-months follow-ups. CLASS sub-scales showed significantly improved stability, suspension, comfort, and socket appearance. Improvement in K-Level and less use of assistive devices were observed with the AMPPRO instrument, indicating improved user mobility and performance. QoL was also increased, as measured in Quality-Adjusted-Life-Years (QALY) from the EQ-5D-5L. CONCLUSION: Evidence from the findings demonstrate that the Direct Socket TF system and procedure can be a good alternative to the traditional method of prosthetic interface delivery. Layman's Abstract After lower limb amputation, the goal for most people is to regain mobility and independence and return to normal daily activities. Typically, people with transfemoral amputation are less likely to receive a prosthesis or fully use a prosthesis as compared to people with transtibial amputation. Moreover, their quality of life is also lower. The Direct Socket TF method is a new way of fabricating a prosthetic socket for users with above-knee amputation, enabling fabrication directly onto the residual limb and delivery of the socket in a single visit. In this study, we wanted to understand how the effect of Direct Socket TF on prosthetic 'user's quality of life, health, mobility level, and balance would compare to their previous prosthesis. This new Direct Socket TF procedure was implemented in six different prosthetic clinics across the United States and used by 36 prosthetic users for six months. Our first article on this study describes increased user satisfaction with their new interface and the single visit service model. This second article on the same clinical investigation documents the significant improvement in outcomes compared to their original interface in terms of quality of life, confidence, mobility, comfort, stability, and activity level. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/36065/27923 Direct Socket TF – Summary (YouTube): https://www.youtube.com/watch?v=-fvVFqjgxjo How To Cite: Walker J, Marable W.R, Smith C, Sigurjónsson B.Þ, Atlason I.F, Johannesson G.A. Clinical outcome of transfemoral direct socket interface (part 2). Canadian Prosthetics & Orthotics Journal. 2021;Volume 4, Issue 1, No.6. https://doi.org/10.33137/cpoj.v4i1.36065 Corresponding Author: Anton Johannesson, PhDTeamOlmed, Kistagången 12, 164 40 Kista, Stockholm, Sweden.E-mail: ajohannesson@teamolmed.seORCID: https://orcid.org/0000-0001-8729-458X

Background The majority of undergraduate anatomy learning has shifted online, or to a mixture of virtual and face-to-face teaching, due to the COVID-19 pandemic. Cadaveric shortages have also influenced the need for alternative methods of anatomical education. This study examines the current literature on the use of extended reality technologies (XR) such as Virtual reality (VR), Augmented reality (AR), and Mixed reality (MR) for anatomy teaching and explores its potential for implementation in medical education. Methods A literature review was performed of PubMed, ProQuest, Science Direct, and Springer databases. Included studies were assessed for user satisfaction, perceived effectiveness, cost, acceptability and side effects. Results The database search identified 1687 papers, of which 45 papers were included in this review. Both AR and VR had high rates of satisfaction and acceptability as a supplementary teaching aid amongst undergraduate participants. AR was found to have higher effectiveness than VR. VR is more expensive than AR. Results and comparisons were limited due to short length of study. Conclusions VR is a popular choice with undergraduates as an aid to supplement teaching, in spite of the associated cost and side effects such as nausea. AR has shown the most potential for independent study. Larger and long-term studies are required to determine true effectiveness, and consideration of the clinical relevance of these technologies.

Fast changing tasks in unpredictable, collaborative environments are typical for medium-small companies, where robotised applications are increasing. Thus, robot programs should be generated in short time with small effort, and the robot able to react dynamically to the environment. To address this we propose a method that combines context awareness and planning to learn Behavior Trees (BTs), a reactive policy representation that is becoming more popular in robotics and has been used successfully in many collaborative scenarios. Context awareness allows to infer from the demonstration the frames in which actions are executed and to capture relevant aspects of the task, while a planner is used to automatically generate the BT from the sequence of actions from the demonstration. The learned BT is shown to solve non-trivial manipulation tasks where learning the context is fundamental to achieve the goal. Moreover, we collected non-expert demonstrations to study the performances of the algorithm in industrial scenarios., Comment: Submitted to RO-MAN 2022

Modern industrial applications require robots to be able to operate in unpredictable environments, and programs to be created with a minimal effort, as there may be frequent changes to the task. In this paper, we show that genetic programming can be effectively used to learn the structure of a behavior tree (BT) to solve a robotic task in an unpredictable environment. Moreover, we propose to use a simple simulator for the learning and demonstrate that the learned BTs can solve the same task in a realistic simulator, reaching convergence without the need for task specific heuristics. The learned solution is tolerant to faults, making our method appealing for real robotic applications.

Industrial robots can solve very complex tasks in controlled environments, but modern applications require robots able to operate in unpredictable surroundings as well. An increasingly popular reactive policy architecture in robotics is Behavior Trees but as with other architectures, programming time still drives cost and limits flexibility. There are two main branches of algorithms to generate policies automatically, automated planning and machine learning, both with their own drawbacks. We propose a method for generating Behavior Trees using a Genetic Programming algorithm and combining the two branches by taking the result of an automated planner and inserting it into the population. Experimental results confirm that the proposed method of combining planning and learning performs well on a variety of robotic assembly problems and outperforms both of the base methods used separately. We also show that this type of high level learning of Behavior Trees can be transferred to a real system without further training., Comment: Submitted to IEEE/RSJ IROS 2021

The task undertaken in this paper is to discover a means by which the practice of literary criticism can derive an imperative for activism that confronts and changes the social conditions it critiques. The case of Karl Marx’s use of world literature in his critique of capitalism and the state, set within the history of the development of continental philosophy, is explored through a close-reading of its interterxtuality. Particular attention is paid to Marx’s use of quotations from and allusions to world literature, including Homer, Sophocles, Virgil, Shakespeare, Cervantes, Goethe and Heine, to register the harmful inversions caused by an economy based on money and commodities. If literature registers the contradictions of its time in its form and content, then the urge to resolve those contradictions sits restless in literature. When Marx inserts literature into his theoretical texts, he transfers into his text the impulse of the contradiction to resolve itself. Similarly, literary criticism is well-placed to unfold clear, obvious and necessary logic which leads to activism.

Gait phase recognition is of great importance in the development of assistance-as-needed robotic devices, such as exoskeletons. In order for a powered exoskeleton with phase-based control to determine and provide proper assistance to the wearer during gait, the user&rsquo, s current gait phase must first be identified accurately. Gait phase recognition can potentially be achieved through input from wearable sensors. Deep convolutional neural networks (DCNN) is a machine learning approach that is widely used in image recognition. User kinematics, measured from inertial measurement unit (IMU) output, can be considered as an &lsquo, image&rsquo, since it exhibits some local &lsquo, spatial&rsquo, pattern when the sensor data is arranged in sequence. We propose a specialized DCNN to distinguish five phases in a gait cycle, based on IMU data and classified with foot switch information. The DCNN showed approximately 97% accuracy during an offline evaluation of gait phase recognition. Accuracy was highest in the swing phase and lowest in terminal stance.

Dieser Text beschreibt, auf welche Weise die folgenden Unterrichtsentwürfe zum Thema "Das gute Leben" für Innovation im Deutschunterricht sorgen.

Hip arthroscopy for femoroacetabular impingement syndrome (FAI) has been shown to be beneficial in the short- to medium-term though outcomes vary between individuals. Multiple factors have been suggested to affect outcomes including pre-operative mental health disorders. We undertook a systematic review to assess the evidence relating to the effect of pre-existing mental health disorders on the outcomes following hip arthroscopy for FAI. Following PRISMA guidelines, a multi-database search was undertaken using three key concepts: ‘mental health’, ‘FAI’ and ‘hip arthroscopy’. Results were screened and data extracted from relevant studies. A total of six studies met the inclusion criteria including 2248 hips, all published between 2017 and 2019. All studies were of evidence level III or IV with reasonable methodological quality. One study demonstrated pre-operative depression to be related to altered pain reduction in the short-term following surgery. Three studies reported inferior outcomes in the medium-term (1–2 years) in those with worse mental health. One study demonstrated an increased risk of persistent pain 2 years following surgery and one a reduced chance of returning to active military service following surgery in those with worse mental health. Despite inferior outcomes individuals with mental health disorders did still benefit from surgery in general. In conclusion, the presence of pre-existing poor mental health is associated with inferior outcomes in the medium-term following arthroscopic surgery for FAI. Surgeons should consider screening patients for mental health disorders before surgery and counselling them appropriately as to the potential for less satisfactory surgical outcomes.

Se describe un mecanismo inusual de infarto de miocardio como complicación del síndrome aórtico agudo, dado por la compresión del tronco de la arteria coronaria izquierda por un hematoma generado a partir de un desgarro intimal por encima de la cúspide aórtica sin extensión hacia la aorta ascendente. Se detecta una disección crónica tipo B con compromiso del arco distal, implementando el tratamiento global de la aorta torácica.

We study the problem of robot interaction with mechanisms that afford one degree of freedom motion, e.g., doors and drawers. We propose a methodology for simultaneous compliant interaction and estimation of constraints imposed by the joint. Our method requires no prior knowledge of the mechanisms' kinematics, including the type of joint, prismatic or revolute. The method consists of a velocity controller that relies on force/torque measurements and estimation of the motion direction, the distance, and the orientation of the rotational axis. It is suitable for velocity controlled manipulators with force/torque sensor capabilities at the end-effector. Forces and torques are regulated within given constraints, while the velocity controller ensures that the end-effector of the robot moves with a task-related desired velocity. We give proof that the estimates converge to the true values under valid assumptions on the grasp, and error bounds for setups with inaccuracies in control, measurements, or modeling. The method is evaluated in different scenarios involving opening a representative set of door and drawer mechanisms found in household environments. QC 20160323

We study a representation of the (local) plactic monoid given by Schur operators u i , which act on partitions by adding a box in column i (if possible). In particular, we give a complete list of the relations that hold in the algebra of Schur operators.

La diabetes es una enfermedad con elevado riesgo cardiovascular. El objetivo fue evaluar la mortalidad intrahospitalaria y en el seguimiento a largo plazo de los pacientes diabeticos con infarto agudo de miocardio tratados con angioplastia primaria y determinar sus predictores. Material y metodos: Se incluyeron de forma retrospectiva 866 pacientes durante enero de 1993 y diciembre de 2013. Se evaluaron 100 sujetos con diagnostico de diabetes. La mediana de seguimiento fue de 121 meses. Resultados: De los 100 pacientes diabeticos evaluados (11.56% del total), el 86% fueron hombres y el 50% tenian mas de 50 anos. El 76% estaba en Killip-Kimball 1 al ingreso y el 16% en Killip-Kimball 4. La localizacion mas frecuente fue la anterior y el 65% presentaba lesion de 2 o mas vasos coronarios. Se observo una mortalidad intrahospitalaria del 15%, cuyo unico predictor resulto el Killip-Kimball de ingreso. La mortalidad alejada fue del 35%, y solamente la edad, el Killip-Kimball al ingreso y el uso de Inhibidores de la enzima convertidora de angiotensina resultaron variables con significacion estadistica. A diferencia de la poblacion diabetica, el Killip-Kimball al ingreso no se asocio significativamente a la mortalidad alejada en no diabeticos. Conclusion: Esta poblacion de pacientes diabeticos se caracterizo por ser mas anosa y por presentar lesion de 2 o mas vasos coronarios. El shock cardiogenico fue la unica variable predictora independiente de mortalidad intrahospitalaria y, junto con la edad y el uso de inhibidores de la enzima convertidora de angiotensina, de mortalidad en el seguimiento a largo plazo

Fragility fractures, those fractures which result from low level trauma, have a large and growing socio-economic cost in countries with aging populations. Bone-density-based assessment techniques are vital for identifying populations that are at higher risk of fracture, but do not have high sensitivity when it comes to identifying individuals who will go on to have their first fragility fracture. We are developing Spatially Offset Raman Spectroscopy (SORS) as a tool for retrieving chemical information from bone non-invasively in vivo. Unlike X-ray-based techniques SORS can retrieve chemical information from both the mineral and protein phases of the bone. This may enable better discrimination between those who will or will not go on to have a fragility fracture because both phases contribute to bone's mechanical properties. In this study we analyse excised bone with Raman spectroscopy and multivariate analysis, and then attempt to look for similar Raman signals in vivo using SORS. We show in the excised work that on average, bone fragments from the necks of fractured femora are more mineralised (by 5-10%) than (cadaveric) non-fractured controls, but the mineralisation distributions of the two cohorts are largely overlapped. In our in vivo measurements, we observe similar, but as yet statistically underpowered, differences. After the SORS data (the first SORS measurements reported of healthy and diseased human cohorts), we identify methodological developments which will be used to improve the statistical significance of future experiments and may eventually lead to more sensitive prediction of fragility fractures. © 2015 The Authors. Journal of Raman Spectroscopy Published by John Wiley & Sons, Ltd.

In this work we propose a method for integrating motion planning and in-hand manipulation. Commonly addressed as a separate step from the final execution, in-hand manipulation allows the robot to reorient an object within the end-effector for the successful outcome of the goal task. A joint achievement of repositioning the object and moving the manipulator towards its desired final pose saves time in the execution and introduces more flexibility in the system. We address this problem using a pivoting strategy (i.e. in-hand rotation) for repositioning the object and we integrate this strategy with a path planner for the execution of a complex task. This method is applied on a Baxter robot and its efficacy is shown by experimental results. QC 20210324

In this survey, we review the field of human shoulder functional kinematic representations. The central question of this review is to evaluate whether the current approaches in shoulder kinematics can meet the high-reliability computational challenge. This challenge is posed by applications such as robot-assisted rehabilitation. Currently, the role of kinematic representations in such applications has been mostly overlooked. Therefore, we have systematically searched and summarised the existing literature on shoulder kinematics. The shoulder is an important functional joint, and its large range of motion (ROM) poses several mathematical and practical challenges. Frequently, in kinematic analysis, the role of the shoulder articulation is approximated to a ball-and-socket joint. Following the high-reliability computational challenge, our review challenges this inappropriate use of reductionism. Therefore, we propose that this challenge could be met by kinematic representations, that are redundant, that use an active interpretation and that emphasise on functional understanding.

Herpes simplex virus type 1 (HSV-1) is a significant human pathogen that infects a large portion of the human population. Cells deploy a variety of defenses to limit the extent to which the virus can replicate. One such factor is the promyelocytic leukemia (PML) protein, the nucleating and organizing factor of nuclear domain 10 (ND10). PML responds to a number of stimuli and is implicated in intrinsic and innate cellular antiviral defenses against HSV-1. While the role of PML in a number of cellular pathways is controlled by post-translational modifications, the effects of phosphorylation on its antiviral activity toward HSV-1 have been largely unexplored. Consequently, we mapped phosphorylation sites on PML, mutated these and other known phosphorylation sites on PML isoform I (PML-I), and examined their effects on a number of PML’s activities. Our results show that phosphorylation at most sites on PML-I is dispensable for the formation of ND10s and colocalization between PML-I and the HSV-1 regulatory protein, ICP0, which antagonizes PML-I function. However, inhibiting phosphorylation at sites near the SUMO-interaction motif (SIM) of PML-I impairs its ability to respond to HSV-1 infection. Overall, our data suggest that PML phosphorylation regulates its antiviral activity against HSV-1.

Objectives The objective was to compare the rates of antimicrobial susceptibility in strains of Escherichia coli isolated from uncomplicated cystitis cases presenting to the emergency department (ED) of a tertiary care center to those reported on that institution's hospital-wide antibiogram. The hypothesis was that cases of uncomplicated cystitis presenting to the ED will exhibit higher antimicrobial susceptibility than is reported by the hospital-wide antibiogram. Methods A retrospective chart review of patients who were diagnosed with uncomplicated cystitis in the ED of a large, academic tertiary care center was conducted. Due to an error in the implementation of a new electronic medical record system at this institution in 2009, all urine samples with any abnormality were reflexively sent for culture. The authors were then able to review and record the antibiotic susceptibility patterns of all cultures that grew E. coli. Exclusion criteria included fever, subsequent hospital admission, treatment of suspected pyelonephritis, receiving current cystitis treatment, male sex, indwelling catheters, recent surgery or hospitalization, or asymptomatic for cystitis. Culture isolate antimicrobial susceptibility was then compared with the hospital-wide antibiogram of the same period. Empiric treatment regimens were also recorded as secondary data. Results Greater susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX; 80% vs. 71%), cefazolin (97% vs. 87%), and ciprofloxacin (89% vs. 73%) was found in our population than was published in the hospital antibiogram. These differences were shown to be statistically significant using Fisher's exact test (p