Miracle-dz/UniFAR-FTUs huggingface dataset:
Using Bioinformatics to Develop and Test Hypotheses: E. coli-Specific Virulence Determinants

Bioinformatics, the use of computer resources to understand biological information, is an important tool in research, and can be easily integrated into the curriculum of undergraduate courses. Such an example is provided in this series of four activities that introduces students to the field of bioinformatics as they design PCR based tests for pathogenic E. coli strains. A variety of computer tools are used including BLAST searches at NCBI, bacterial genome searches at the Integrated Microbial Genomes (IMG) database, protein analysis at Pfam and literature research at PubMed. In the process, students also learn about virulence factors, enzyme function and horizontal gene transfer. Some or all of the four activities can be incorporated into microbiology or general biology courses taken by students at a variety of levels, ranging from high school through college. The activities build on one another as they teach and reinforce knowledge and skills, promote critical thinking, and provide for student collaboration and presentation. The computer-based activities can be done either in class or outside of class, thus are appropriate for inclusion in online or blended learning formats. Assessment data showed that students learned general microbiology concepts related to pathogenesis and enzyme function, gained skills in using tools of bioinformatics and molecular biology, and successfully developed and tested a scientific hypothesis.
Diagnosis and management of early‐ and late‐onset cerebellar ataxia

Cerebellar ataxias represent a heterogeneous group of neurodegenerative disorders. Two main categories are distinguished: hereditary and sporadic ataxias. Sporadic ataxias may be symptomatic or idiopathic. The clinical classification of hereditary ataxias is nowadays being replaced by an expanding genotype‐based classification. A large spectrum of degenerative and metabolic disorders may also present with ataxia early or late in the course of disease. We present a diagnostic algorithm for the adult patient presenting with subacute cerebellar ataxia, based on family history and straightforward clinical characteristics of the patient. Along with the algorithm, an overview of the autosomal dominant, autosomal recessive, X‐linked, mitochondrial, symptomatic and idiopathic subtypes of cerebellar ataxia is presented. An appropriate diagnosis is of utmost importance to such considerations as prognosis, genetic counselling and possible therapeutic implications.
Secular Trends in Height in Different States of India in Relation to Socioeconomic Characteristics and Dietary Intakes

Background Information on adult height and associated secular trends in relation to socioeconomic characteristics based on a nationally representative sample is not available from India. Objective To assess the average adult height and secular trends in height in different states of India in relation to socioeconomic characteristics and dietary intakes according to data from the Third National Family Health Survey (NFHS 3). Methods Average heights and associated secular trends were analyzed for each state and in relation to socioeconomic variables. Bivariate and multiple regression analyses were performed to examine the association of socioeconomic factors and consumption of animal-source foods with height. Results Data from anthropometric measurements were available for 69,245 men and 118,796 women in the age group from 20 to 49 years. The average heights of adult men and women were 165 and 152 cm, respectively, with wide variation among states. Overall, there was a modest secular increase in height (0.50 cm per decade in men and 0.22 cm per decade in women), with a negative secular trend in some of the states. There were striking regional differences in the average heights and the secular trends in height. Similarly, higher socio-economic status was associated with greater height and a greater secular increase in height. Milk consumption had a positive association with height in men (r = 0.69, p < .001) and women (r = 0.63, p < .001) in various/different states. Conclusions The secular increase in height has been modest in India in spite of impressive economic growth. Consumption patterns of milk in different states may be related to the regional differences in height.
Chemotherapeutic drug‐induced apoptosis in human leukaemic cells is independent of the Fas (APO‐1/CD95) receptor/ligand system

The potential role of the Fas (CD95/APO‐1) receptor/ligand system in chemotherapeutic drug‐induced apoptosis was examined in a number of human leukaemic cell lines. Flow cytometric profiles of doxorubicin‐treated HL‐60, K562, U937 and Jurkat cells failed to show any significant increase in Fas or Fas ligand expression over 24 h, despite the induction of significant levels of apoptosis in these cells. Although preincubation of human leukaemic cells with a neutralizing anti‐Fas IgG antibody blocked anti‐Fas IgM‐induced apoptosis, this strategy failed to inhibit chemotherapeutic drug‐induced apoptosis. To determine whether recruitment of the Fas/Fas ligand complex during drug‐induced apoptosis was a cell‐specific event we utilized the CEM cell line. Doxorubicin treatment of CEM cells over 24 h failed to show any up‐regulation in Fas or Fas ligand protein levels as detected by flow cytometry. Furthermore, neutralizing anti‐Fas IgG Ab failed to inhibit chemotherapeutic drug‐induced apoptosis in CEM cells. The present studies do, however, demonstrate a role for anti‐Fas IgM Ab in producing a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs. Low‐dose anti‐Fas IgM treatment in combination with doxorubicin, methotrexate, camptothecin and etoposide produced an augmented cytoxicity in CEM cells. Taken together these observations demonstrate that although recruitment of the Fas/APO‐1/CD95 receptor/ligand system is not a necessary requirement for chemotherapeutic drug‐induced apoptosis, combination of anti‐Fas IgM and drug treatment produces a synergistic cytotoxic effect which may prove useful in the treatment of human leukaemias.
Added value of SPECT/CT over planar Tc-99m mebrofenin hepatobiliary scintigraphy in the evaluation of bile leaks

ObjectiveTo determine the added value of single-photon emission computed tomography/computed tomography (SPECT/CT) over planar hepatobiliary scintigraphy (HBS) in suspected cases of bile leak. Materials and methodsAn analysis of the data of all patients who had undergone HBS for suspected bile leak during the last 3 years was carried out. All patients had undergone an initial 45 min dynamic study after an intravenous injection of Tc-99m mebrofenin, following which they underwent multiple static imaging studies for up to 24 h and SPECT/CT imaging whenever needed. ResultsA total of 203 patients had undergone an HBS for evaluation of a suspected bile leak. HBS was positive for bile leak in 110 patients, among whom 42 had undergone additional SPECT/CT. In 32 patients SPECT/CT was useful in (i) defining the exact location of collection [intracapsular vs. extracapsular vs. intraparenchymal leak (n=18/25)], (ii) defining the extent of intraparenchymal collections (n=6/6), (iii) characterizing large abdominal collections (n=2/2), and (iv) characterizing suspected contamination (n=4/4), (v) suspected collection (n=0/3), (vi) and other miscellaneous conditions (n=2/2). Defining the extent and exact localization of collection can have therapeutic implications such as the accurate site of placement of the drain for drainage. In approximately one-third of the bile leak-positive HBS studies (32/110), SPECT/CT images were helpful for better characterization of biliary collection. In all, 76% (32/42) of the SPECT/CT studies were found to provide additional useful information over planar imaging. ConclusionHybrid SPECT/CT offers the unique advantage of combining the anatomical information from CT with the functional information provided by HBS. It is most useful in characterization of biliary collections, which give important scintigraphic evidence of the severity of bile leak with therapeutic implications such as placement of a drain or surgical exploration.
Towards a semantic PACS: Using Semantic Web technology to represent imaging data

The DICOM standard is ubiquitous within medicine. However, improved DICOM semantics would significantly enhance search operations. Furthermore, databases of current PACS systems are not flexible enough for the demands within image analysis research. In this paper, we investigated if we can use Semantic Web technology, to store and represent metadata of DICOM image files, as well as linking additional computational results to image metadata. Therefore, we developed a proof of concept containing two applications: one to store commonly used DICOM metadata in an RDF repository, and one to calculate imaging biomarkers based on DICOM images, and store the biomarker values in an RDF repository. This enabled us to search for all patients with a gross tumor volume calculated to be larger than 50 cc. We have shown that we can successfully store the DICOM metadata in an RDF repository and are refining our proof of concept with regards to volume naming, value representation, and the applications themselves.
Creating a Culture of Adaptive Accountability in an Organization

a work environment presented by a set of the interconnected actions having different difficulties of their performance. It influence on employees behavior in the work environment as regards taking by them accountability for the actions. Hence, a flexible, adaptive, and receptive to change culture of accountability should be created. It should promote adaptation of an employee’ accountability to change in the work environment. In other words, a culture of adaptive accountability should be formed that favors adaptation of taking accountability by employees for the actions to their abilities to perform the actions. Abstract: The three-step method for creating a culture of adaptive accountability in an organization is proposed. It is aimed to promote adaptation of taking accountability of employees for the changes in a work environment. The changes are engendered by variability of the organization’s objectives. The dynamic work environment is formed in the first step. It includes determination of the needed actions corresponding with the current objective of the organization, the action structure, and the actions-relevant skills, the difficulties in performance of the actions, and the extents of accountability for the actions that are correlated with the actions’ difficulties. Adaptation of taking accountability of employees for the actions to their aspiration and readiness to perform the actions is realized through a coordinated self-evaluation process in the second step. The employees evaluate their aspiration and readiness to perform the actions by examination of individual skills and the work environment. Aspiration of the employee to perform the action is induced by the condition implying more compensation for the action having the more extent of accountability. Readiness of the employee to perform the action is evaluated on the basis of the degree of difference between employee skills and the action-relevant skills. Adjustment of the employees’ compensations to their accountability for the actions is fulfilled by taking into consideration the extents of accountability for the actions in the third step.
Efficient and Confidentiality-Preserving Content-Based Publish/Subscribe with Prefiltering

Content-based publish/subscribe provides a loosely-coupled and expressive form of communication for large-scale distributed systems. Confidentiality is a major challenge for publish/subscribe middleware deployed over multiple administrative domains. Encrypted matching allows confidentiality-preserving content-based filtering but has high performance overheads. It may also prevent the use of classical optimizations based on subscriptions containment. We propose a support mechanism that reduces the cost of encrypted matching, in the form of a prefiltering operator using Bloom filters and simple randomization techniques. This operator greatly reduces the amount of encrypted subscriptions that must be matched against incoming encrypted publications. It leverages subscription containment information when available, but also ensures that containment confidentiality is preserved otherwise. We propose containment obfuscation techniques and provide a rigorous security analysis of the information leaked by Bloom filters in this case. We conduct a thorough experimental evaluation of prefiltering under a large variety of workloads. Our results indicate that prefiltering is successful at reducing the space of subscriptions to be tested in all cases. We show that while there is a tradeoff between prefiltering efficiency and information leakage when using containment obfuscation, it is practically possible to obtain good prefiltering performance while securing the technique against potential leakages.
SMAI-JCM SMAI Journal of Computational Mathematics Model Reduction And Neural Networks For Parametric PDEs

We develop a general framework for data-driven approximation of input-output maps between inﬁnite-dimensional spaces. The proposed approach is motivated by the recent successes of neural networks and deep learning, in combination with ideas from model reduction. This combination results in a neural network approximation which, in principle, is deﬁned on inﬁnite-dimensional spaces and, in practice, is robust to the dimension of ﬁnite-dimensional approximations of these spaces required for computation. For a class of input-output maps, and suitably chosen probability measures on the inputs, we prove convergence of the proposed approximation methodology. We also include numerical experiments which demonstrate the eﬀectiveness of the method, showing convergence and robustness of the approximation scheme with respect to the size of the discretization, and compare it with existing algorithms from the literature; our examples include the mapping from coeﬃcient to solution in a divergence form elliptic partial diﬀerential equation (PDE) problem, and the solution operator for viscous Burgers’ equation. 2020 Mathematics Subject Classiﬁcation. 65N75, 62M45, 68T05, 60H30, 60H15.
Conley's fundamental theorem for a class of hybrid systems

We establish versions of Conley's (i) fundamental theorem and (ii) decomposition theorem for a broad class of hybrid dynamical systems. The hybrid version of (i) asserts that a globally-defined "hybrid complete Lyapunov function" exists for every hybrid system in this class. Motivated by mechanics and control settings where physical or engineered events cause abrupt changes in a system's governing dynamics, our results apply to a large class of Lagrangian hybrid systems (with impacts) studied extensively in the robotics literature. Viewed formally, these results generalize those of Conley and Franks for continuous-time and discrete-time dynamical systems, respectively, on metric spaces. However, we furnish specific examples illustrating how our statement of sufficient conditions represents merely an early step in the longer project of establishing what formal assumptions can and cannot endow hybrid systems models with the topologically well characterized partitions of limit behavior that make Conley's theory so valuable in those classical settings.
Response of Grounding Electrodes to Impulsive Currents: An Experimental Evaluation

Experimental results for the transient behavior of grounding electrodes are presented to clarify fundamental aspects of the grounding response to lightning currents. It is shown that for fast current waves, the value of impulsive grounding impedance ZP of short electrodes is smaller than its low-frequency resistance R LF while electrodes longer than the effective length have a resistance value smaller than impulsive impedance. The values found for the ratio ZP/R LF in the experiments are lower than those resulting from numerical simulation for electrodes shorter than the effective length.
Forebrain ischemia studied using magnetic resonance imaging and spectroscopy

A combination of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) has been used to follow the time course of changes resulting from forebrain ischemia in the rat. The 31P MRS demonstrates that the level of high energy metabolites decreases significantly during the 10 min ischemic period but returns to normal after 1 h of reperfusion. MRI shows no change after 1 h of reperfusion but significant changes in the striatum after 24 h and in the hippocampus after 48 h. These changes correlate well with histopathology. Diabetic rats have shown the effect of hyperglycemia in accentuation of ischemic and post ischemic pH changes. Conversely, diabetic rats maintained severely hypoglycemic with insulin showed little variation in pH during or following the ischemic insult. The results emphasize the importance of both MRS and MRI in following the temporal profile and distribution of ischemic neuronal injury.
Model-based approaches to predict drug–drug interactions associated with hepatic uptake transporters: preclinical, clinical and beyond

Introduction: Membrane transporters have been recognized to play a key role in determining the absorption, distribution and elimination processes of drugs. The organic anion-transporting polypeptide (OATP)1B1 and OATP1B3 isoforms are selectively expressed in the human liver and are known to cause significant drug–drug interactions (DDIs), as observed with an increasing number of drugs. It is evident that DDIs involving hepatic transporters are capable of altering systemic, as well as tissue-specific, exposure of drug substrates resulting in marked differences in drug safety and/or efficacy. It is therefore essential to quantitatively predict such interactions early in the drug development to mitigate clinical risks. Areas covered: The role of hepatic uptake transporters in drug disposition and clinical DDIs has been reviewed with an emphasis on the current state of the models applicable for quantitative predictions. The readers will also gain insight into the in vitro experimental tools available to characterize transport kinetics, while appreciating the knowledge gaps in the in vitro–in vivo extrapolation (IVIVE), which warrant further investigation. Expert opinion: Static and dynamic models can be convincingly applied to quantitatively predict drug interactions, early in drug discovery, to mitigate clinical risks as well as to avoid unnecessary clinical studies. Compared to basic models, which focus on individual processes, mechanistic models provide the ability to assess DDI potential for compounds with systemic disposition determined by both transporters and metabolic enzymes. However, complexities in the experimental tools and an apparent disconnect in the IVIVE of transport kinetics have limited the physiologically based pharmacokinetic modeling strategies. Emerging data on the expression of transporter proteins and tissue drug concentrations are expected to help bridge these gaps. In addition, detailed characterization of substrate kinetics can facilitate building comprehensive mechanistic models.
Lipid Bilayers as Osmotic Response Elements

The importance of osmolarity in the regulation of a wide range of cellular functions and processes is well established. However, much less is known about the molecular mechanisms imparting sensitivity to osmotic forces to cells. The findings summarized in this brief review demonstrate that the principal structural element of all biomembranes, the lipid bilayer, provides a highly sensitive machinery for conveying information in the osmotic conditions of a cell to the relevant regulatory machineries. More specifically, osmotic shrinkage, swelling, as well as applied osmotic stress all have pronounced effects on the physical state and molecular interactions in the bilayer, influencing lipid packing and dynamics, and also altering the 2-dimensional (lateral) ordering in the membrane into compositionally distinct microdomains. Because of the cooperative behavior of lipid bilayers integrative regulation of the functions embedded in the different organelle membranes by the physical properties of lipids is possible. Organelle membranes should thus be understood as adaptive platforms harboring specialized metabolic pathways and functions, whose activities (physiological state) can be controlled by the physical state of the membrane lipids. Finally, it is important to keep in mind that virtually all biological macromolecules maintain a hydration shell. Living cells thus constitute highly complex supramolecular assemblies, their numerous components responding to osmotic forces in unison.
Development of additional autoimmune diseases in a multiethnic cohort of patients with systemic lupus erythematosus with reference to damage and mortality

Objectives: To determine the prevalence of other autoimmune diseases (AID) in black, Caucasian and South Asian patients with systemic lupus erythematosus (SLE) compared with the prevalence of these AID in the UK population, and to assess the impact of these additional AID on damage scores and mortality. Methods: The prevalence and chronology of development of additional AID in SLE patients was determined by case note review. Comparisons were made with prevalence data for AID in the general UK population. The impact of additional AID on mortality and damage scores at up to 10 years was determined in the index cases (patients who developed another AID either in the same year or within 5 years of onset of SLE) compared with controls matched for sex, age, ethnicity and year of onset of SLE. Results: There was no significant difference in the total number of AID that developed in patients from each ethnic group but differences in the frequency of some AID were noted. Mortality and damage scores were worse at 5 years in the study cases than the controls, particularly in the peripheral vascular category. Conclusion: Patients with SLE might develop other AID that could complicate management of SLE by having an adverse impact on damage scores and mortality.
Surgical time and severity of postoperative pain in dogs undergoing laparoscopic ovariectomy with one, two, or three instrument cannulas.

OBJECTIVE To determine whether number of instrument cannulas is associated with surgical time or severity of postoperative pain in dogs undergoing laparoscopic ovariectomy. DESIGN Randomized clinical trial. ANIMALS 18 healthy dogs. PROCEDURES Dogs were randomly assigned to undergo laparoscopic ovariectomy with 1, 2, or 3 instrument cannulas. Surgical time and intraoperative and postoperative complications were recorded. Severity of pain was monitored 2, 4, 8, 12, and 24 hours after surgery by means of pain scoring with a modified Melbourne Pain Scale and palpation of surgical sites with variably sized von Frey filaments. Owner-assessed postoperative comfort was also evaluated. RESULTS Surgical time was significantly longer with 1 cannula (mean ± SD, 29.7 ± 5.6 minutes) than with 2 cannulas (18.2 ± 4.4 minutes) or 3 cannulas (19.3 ± 3.4 minutes). Intraoperative complications included splenic puncture (2 dogs), pedicle hemorrhage (1 dog), and SC emphysema (1 dog); complication rates were not significantly different among groups. Total pain score was significantly lower for dogs with 2 cannulas than for dogs with 3 cannulas; total pain score for dogs with 1 cannula did not differ significantly from scores for dogs with 2 cannulas or 3 cannulas. Owner assessments of postoperative comfort and number of days pain medications were administered did not differ among groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that laparoscopic ovariectomy with 2 instrument cannulas, rather than with 1, resulted in shorter surgical times without increasing severity of postoperative pain.