Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Characterization of E. coli LptC: Interaction with LPS and a Synthetic Ligand

Lipopolysaccharide (LPS), the main cell‐surface molecular constituent of Gram‐negative bacteria, is synthesized in the inner membrane (IM) and transported to the outer membrane (OM) by the Lpt (lipopolysaccharide transport) machinery. Neosynthesized LPS is first flipped by MsbA across the IM, then transported to the OM by seven Lpt proteins located in the IM (LptBCFG), in the periplasm (LptA), and in the OM (LptDE). A functional OM is essential to bacterial viability and requires correct placement of LPS in the outer leaflet. Therefore, LPS biogenesis represents an ideal target for the development of novel antibiotics against Gram‐negative bacteria. Although the structures of Lpt proteins have been elucidated, little is known about the mechanism of LPS transport, and few data are available on Lpt–LPS binding. We report here the first determination of the thermodynamic and kinetic parameters of the interaction between LptC and a fluorescent lipo‐oligosaccharide (fLOS) in vitro. The apparent dissociation constant (Kd) of the fLOS–LptC interaction was evaluated by two independent methods. The first was based on fLOS capture by resin‐immobilized LptC; the second used quenching of LptC intrinsic fluorescence by fLOS in solution. The Kd values by the two methods (71.4 and 28.8 μm, respectively) are very similar, and are of the same order of magnitude as that of the affinity of LOS for the upstream transporter, MsbA. Interestingly, both methods showed that fLOS binding to LptC is mostly irreversible, thus reflecting the fact that LPS can be released from LptC only when energy is supplied by ATP or in the presence of a higher‐affinity LptA protein. A fluorescent glycolipid was synthesized: this also interacted irreversibly with LptC, but with lower affinity (apparent Kd=221 μM). This compound binds LptC at the LPS binding site and is a prototype for the development of new antibiotics targeting LPS transport in Gram‐negative bacteria.
Development of a theoretical framework describing relatives' involvement in palliative care.

BACKGROUND The present study is based on four earlier studies in which the authors classified the relative's involvement in palliative care into different categories and described the involvement as "involvement in the light" or "involvement in the dark". AIM The aim of the study was to develop a theoretical framework concerning the involvement of relatives based on an in-depth analysis of the results of the four earlier studies. METHOD Walker & Avant's (1995) strategies for theory construction were used for development of the framework. A number of different concepts, assumptions and statements about relatives' involvement were penetrated in an in-depth analysis. RESULTS From the concepts two theoretical "blocks" of the relatives' involvement were developed and these constitute the foundation for the framework. One is based on concrete descriptions of the concepts "to know", "to be" and "to do". The other describes how the concepts of "involvement in the light" and "involvement in the dark" differ. Factors that promoted involvement in the light were professional care based on humanistic values, a stronger sense of coherence on the part of relatives, an appropriate illness trajectory, and other available resources. The opposite was the case for those who were involved in the dark. Five assumptions successively developed which together form the theoretical framework. CONCLUSIONS An important conclusion that can be of importance in palliative care is that the manner in which the staff act toward the patient and relatives influence relatives' possibilities for involvement, patients' possibilities for an appropriate death, and the possibilities the staff have to give good care.
B‐lymphocyte subpopulations are equally susceptible to Epstein–Barr virus infection, irrespective of immunoglobulin isotype expression

While Epstein–Barr virus (EBV) is known to establish latency in the memory B‐cell compartment, there is controversy as to whether the memory or the naïve B cell is the initial target for infection. Here we have explored the infectability of the B‐cell subsets contained in peripheral blood and tonsils, as distinguished by their surface expression of the immunoglobulin isotypes that help to define naïve and memory pools. First we show that both CD21 and major histocompatibility complex (MHC) class II molecules – respectively, the major receptor and co‐receptor for EBV on B cells – are expressed at similar levels on blood and tonsillar B cells, irrespective of surface immunoglobulin class, indicating that each of the subsets demonstrate an equal potential, at least for infection. Then, following in vitro infection of total tonsillar B cells, we found that the relative frequencies of immunoglobulin (Ig)M‐, IgG‐ and IgA‐positive cells containing EBV‐encoded Epstein–Barr virus nuclear antigen 5 (EBNA5) protein at 48 hr were similar to those of the starting population. However, IgD expression was uniformly decreased, probably as a consequence of cellular activation. These data indicate that recirculating B cells have both the potential for, and susceptibility to, initial infection by EBV, irrespective of the immunoglobulin isotype expressed.
Room temperature crystal structure of the fast switching M159T mutant of the fluorescent protein dronpa

The fluorescent protein Dronpa undergoes reversible photoswitching reactions between the bright “on” and dark “off” states via photoisomerization and proton transfer reactions. We report the room temperature crystal structure of the fast switching Met159Thr mutant of Dronpa at 2.0‐Å resolution in the bright on state. Structural differences with the wild type include shifted backbone positions of strand β8 containing Thr159 as well as an altered A‐C dimer interface involving strands β7, β8, β10, and β11. The Met159Thr mutation increases the cavity volume for the p‐hydroxybenzylidene‐imidazolinone chromophore as a result of both the side chain difference and the backbone positional differences. Proteins 2015; 83:397–402. © 2014 Wiley Periodicals, Inc.
Assessment of Drug-Associated Extrapyramidal Symptoms in People With Intellectual Disability: A Comparison of an Informant-Based Scale With Clinical Rating Scales

Abstract Drug-associated extrapyramidal symptoms (EPS) in people with intellectual disability (ID) may be difficult to recognize, and clinicians' assessments may be hampered by lack of patients' capacities to adequately cooperate and by lack of reliable instruments to measure EPS in this population. Therefore, we compared assessments based on professional caregivers' observations with the informant-based validated Matson Evaluation of Drug Side Effects (MEDS) scale with assessments by clinicians using a set of clinical rating scales, most of which have not been validated for use in this population. We also compared 2 dyskinesia scales by replacing the widely used but not validated Abnormal Involuntary Movement Scale with the validated Dyskinesia Identification System Condensed User Scale (DISCUS) in half of the set of scales. We used linear regression to analyze associations between EPS as measured with MEDS and EPS as measured with the sets of scales at item and at scale level. Of the 30 MEDS items, 6 were associated with items of the other scales. At scale level, we found no significant associations. Comparison of the Abnormal Involuntary Movement Scale with the DISCUS indicated that the DISCUS may be preferable for use in people with ID. Results may be explained by shortcomings in education and training of caregivers and by lack of reliable assessments and rating scales for EPS in people with ID. We conclude that there is an urgent need for education and training of care professionals and clinicians in this area and for studies investigating the psychometric properties of rating scales.
Fighting Sudden Oak Death With Fire?

PORTLAND, OREGON-- A record number of ecologists--more than 4000--gathered here from 1 to 6 August for the 89th annual meeting of the Ecological Society of America. The meeting offered some possible good news about how to limit the spread of sudden oak death.
Neighborhood Socioeconomic Disadvantage and Access to Health Care∗

Most research on access to health care focuses on individual-level determinants such as income and insurance coverage. The role of community-level factors in helping or hindering individuals in obtaining needed care, however, has not received much attention. We address this gap in the literature by examining how neighborhood socioeconomic disadvantage is associated with access to health care. We find that living in disadvantaged neighborhoods reduces the likelihood of having a usual source of care and of obtaining recommended preventive services, while it increases the likelihood of having unmet medical need. These associations are not explained by the supply of health care providers. Furthermore, though controlling for individual-level characteristics reduces the association between neighborhood disadvantage and access to health care, a significant association remains. This suggests that when individuals who are disadvantaged are concentrated into specific areas, disadvantage becomes an “emergent characteristic” of those areas that predicts the ability of residents to obtain health care.
Activity of cefoperazone and two beta-lactamase inhibitors, sulbactam and clavulanic acid, against Bacteroides spp. correlated with beta-lactamase production

A total of 102 isolates of Bacteroides spp. were studied for beta-lactamase production and susceptibility to cefoperazone alone or in combination with either of the beta-lactamase inhibitors sulbactam and clavulanic acid. The geometric mean minimal inhibitory concentration of cefoperazone alone was 31.5 micrograms/ml and when combined with 10 micrograms of sulbactam per ml or 2 micrograms of clavulanic acid per ml was reduced to 5.4 and 9.2 micrograms/ml, respectively. When bacterial suspensions were tested for beta-lactamase production with nitrocefin, 91 (89.2%) of these isolates produced the enzyme. The geometric mean minimal inhibitory concentrations of cefoperazone rose only slightly for isolates with low or intermediate enzyme activity but rose significantly for those with high activity. The addition of EDTA to cefoperazone significantly more frequently enhanced the activity of cefoperazone against beta-lactamase-negative as opposed to beta-lactamase-positive isolates. Furthermore, EDTA resulted in synergistic activity of the cefoperazone-sulbactam combination on beta-lactamase-positive isolates for which the combination had previously not shown a synergistic effect. This study demonstrates the relationship between beta-lactamase production and the resistance of Bacteroides spp. to cefoperazone and shows that inhibition of these enzymes can reverse this resistance.
Pathologic criteria for nonalcoholic steatohepatitis: Interprotocol agreement and ability to predict liver‐related mortality

Since the initial description of nonalcoholic steatohepatitis (NASH), several sets of pathologic criteria for its diagnosis have been proposed. However, their interprotocol agreement and ability to predict long‐term liver‐related mortality (LRM) have not been demonstrated. In this study, we examined patients with biopsy‐proven nonalcoholic fatty liver disease (NAFLD) for whom liver biopsy slides and clinical and mortality data were available. Liver biopsy samples were evaluated for a number of pathologic features and were classified according to the presence or absence of NASH by (1) the original criteria for NAFLD subtypes, (2) the nonalcoholic fatty liver disease activity score (NAS), (3) the Brunt criteria, and (4) the current study's criteria. All NASH diagnostic criteria and individual pathologic features were tested for agreement and for their independent associations with LRM, which were determined with a Cox proportional hazards model. Two hundred fifty‐seven NAFLD patients with complete data were included. The diagnoses of NASH by the original NAFLD subtypes and by the current study's definition of NASH were in almost perfect agreement (κ = 0.896). However, their agreement was moderate with NAS (κ = 0.470 and κ = 0.511, respectively) and only fair to moderate with the Brunt criteria (κ = 0.365 and κ = 0.441, respectively). Furthermore, the agreement of the Brunt criteria with NAS was relatively poor (κ = 0.178). During the follow‐up (median = 146 months), 31% of the patients died (9% were LRM). After we controlled for confounders, a diagnosis of NASH by the original criteria for NAFLD subtypes [adjusted hazard ratio = 9.94 (95% confidence interval = 1.28‐77.08)] demonstrated the best independent association with LRM. Among the individual pathologic features, advanced fibrosis showed the best independent association with LRM [adjusted hazard ratio = 5.68 (95% confidence interval = 1.50‐21.45)]. Conclusion: The original criteria for NAFLD subtypes and the current study's criteria for NASH were in almost perfect agreement, but their level of agreement with the NAS and Brunt criteria was lower. A diagnosis of NASH by the original criteria for NAFLD subtypes demonstrated the best predictability for LRM in NAFLD patients. (HEPATOLOGY 2011;)
Feedback Control of Negative-Imaginary Systems

This paper investigates the robustness of positive-position feedback control of flexible structures with colocated force actuators and position sensors. In particular, the theory of negative-imaginary systems is used to reveal the robustness properties of multi-input, multi-output (MIMO) positive-position feedback controllers and related types of controllers for flexible structures. The negative-imaginary property of linear systems can be extended to nonlinear systems through the notion of counterclockwise input-output dynamics.
Leben nach Herzenslust? Lebensstil und Gesundheit aus psychologischer und pädagogischer Sicht

Die Zunahme chronischer Erkrankungen, der demographische Wandel und ein Mehr an Verantwortung des Einzelnen fur die eigene Gesundheit sind wesentliche Herausforderungen, denen sich unsere Gesellschaft in der Zukunft stellen muss. Leben nach Herzens Lust Â– Lebensstil und Gesundheit war daher das Jahresthema 2008 des Fachs Gesundheitspadagogik an der Padagogischen Hochschule Freiburg. In der vorliegenden Schrift ist ein Teil der Tagungs- und Kolloquiumsbeitrage zusammengefasst. Die einzelnen Beitrage ergrunden das Thema Lebensstil und Gesundheit aus padagogischer und psychologischer Perspektive. Sie zeigen dabei die Bedeutung der Wechselwirkung der drei Dimensionen Ressourcen, Orientierungen und gesundheitsrelevantes Verhalten fur den Lebensstil. Erganzt werden die Beitrage durch eine aktuelle Gegenstandsbestimmung der Disziplin » Gesundheitspadagogik «. Gesundheitspadagogik wie sie an der PH Freiburg verstanden wird, bedeutet »Gesundheitsforderung durch padagogische Settings« in Pravention, Intervention und Rehabilitation. Hierauf zielt auch die Vermittlung von Wissen- und Handlungskompetenzen fur Studierende im Studiengang Gesundheitspadagogik. (Verlag)
Reflection of a few-cycle laser pulse on a metal nano-layer: generation of phase dependent wake-fields

The reflection and transmission of a few-cycle femtosecond Ti:Sa laser pulse impinging on a metal nano-layer have been analyzed. The thickness of the layer was assumed to be of the order of 2 – 10 nm, and the metallic free electrons were represented by a surface current density at the plane boundary of a dielectric substrate. The target studied this way can be imagined for instance as a semi-transparent mirror produced by evaporating a thin aluminum layer on the surface of a glass plate. The exact analytical solution has been given for the system of the coupled Maxwell-Lorentz equations describing the dynamics of the surface current and the scattered radiation field. It has been shown that in general a non-oscillatory frozen-in wake-field appears following the main pulse with an exponential decay and with a definite sign of the electric field. The characteristic time of these wake-fields is inversely proportional with the square of the plasma frequency and with the thickness of the metal nano-layer, and can be larger then the original pulse duration. The magnitude of these wake-fields is proportional with the incoming field strength, and the definite sign of them is governed by the cosine of the carrier-envelope phase difference of the incoming ultrashort laser pulse. As a consequence, when we let such a wake-field excite the electrons of a secondary target (say an electron beam, a metal plate or a gas jet), we obtain 100 percent modulation depth in the electron signal in a given direction. This scheme can perhaps serve as a basis for the construction of a robust linear carrier-envelope phase difference meter.
The neuropsychology of anxiety.

This paper is a rough precis of a recent book (GRAY, 1982). It is concerned with the question: what are the brain structures which mediate the psychology as well as the neurology of anxiety? It is clear that, once you start asking questions about the brain, you have to work with animals for reasons that are familiar to everybody. But it is very difficult to start studying emotions in animals, because it is difficult to know what emotions animals experience and whether these are the same as the human emotions. So the first thing one has to look for is a kind of crutch or bridge to get you across from the human domain on one side to the animal domain on the other. Now in the case of anxiety we are quite fortunate in that there are certain drugs which are clinically very effective in controlling anxiety in human subjects. So one can take those drugs and apply them to animals to study their behavioral effects.
Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs.
Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2

RBF1, a Drosophila pRB family homolog, is required for cell cycle arrest and the regulation of E2F‐dependent transcription. Here, we describe the properties of RBF2, a second family member. RBF2 represses E2F transcription and is present at E2F‐regulated promoters. Analysis of in vivo protein complexes reveals that RBF1 and RBF2 interact with different subsets of E2F proteins. dE2F1, a potent transcriptional activator, is regulated specifically by RBF1. In contrast, RBF2 binds exclusively to dE2F2, a form of E2F that functions as a transcriptional repressor. We find that RBF2‐mediated repression requires dE2F2. More over, RBF2 and dE2F2 act synergistically to antagonize dE2F1‐mediated activation, and they co‐operate to block S phase progression in transgenic animals. The network of interactions between RBF1 or RBF2 and dE2F1 or dE2F2 reveals how the activities of these proteins are integrated. These results suggest that there is a remarkable degree of symmetry in the arrangement of E2F and RB family members in mammalian cells and in Drosophila.
Implications of endoplasmic reticulum stress, the unfolded protein response and apoptosis for molecular cancer therapy. Part I: targeting p53, Mdm2, GADD153/CHOP, GRP78/BiP and heat shock proteins

Background: In eukaryotes, endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are coordinately regulated to maintain steady-state levels and activities of various cellular proteins to ensure cell survival. Objective: This review (Part I of II) focuses on specific ERS and UPR signalling regulators, their expression in the cancer phenotype and apoptosis, and proposes how their implication in these processes can be rationalised into proteasome inhibition, apoptosis induction and the development of more efficacious targeted molecular cancer therapies. Method: In this review, we contextualise many ERS and UPR client proteins that are deregulated or mutated in cancers and show links between ERS and the UPR, their implication in oncogenic transformation, tumour progression and escape from immune surveillance, apoptosis inhibition, angiogenesis, metastasis, acquired drug resistance and poor cancer prognosis. Conclusion: Evasion of programmed cell death or apoptosis is a hallmark of cancer that enables tumour cells to proliferate uncontrollably. Successful eradication of cancer cells through targeting ERS- and UPR-associated proteins to induce apoptosis is currently being pursued as a central tenet of anticancer drug discovery.
From medical imaging data to 3D printed anatomical models

Anatomical models are important training and teaching tools in the clinical environment and are routinely used in medical imaging research. Advances in segmentation algorithms and increased availability of three-dimensional (3D) printers have made it possible to create cost-efficient patient-specific models without expert knowledge. We introduce a general workflow that can be used to convert volumetric medical imaging data (as generated by Computer Tomography (CT)) to 3D printed physical models. This process is broken up into three steps: image segmentation, mesh refinement and 3D printing. To lower the barrier to entry and provide the best options when aiming to 3D print an anatomical model from medical images, we provide an overview of relevant free and open-source image segmentation tools as well as 3D printing technologies. We demonstrate the utility of this streamlined workflow by creating models of ribs, liver, and lung using a Fused Deposition Modelling 3D printer.