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The Angolan Government is developing mechanisms to reduce gender inequalities in the world of work, breaking cultural and traditional barriers, such as women's nature of being a wife, mother, caregiver and domestic worker. Thus, the objective of this work was to understand the impact of the glass ceiling effect in the work context of Angolan women. The aim was also to identify whether Angolan women perceive discrimination in the workplace, whether there is a gender pay gap, whether there is a balance between private life and work and whether there are differences between public and private organizations. A basic or generic qualitative study was carried out, which includes description, interpretation and understanding of recurring patterns. Eleven women participated in the study and as an inclusion criterion, Angolan women working in public or private companies were chosen. As a collection technique, individual semi-structured interviews were carried out, which lasted around 30 to 40 minutes. The interviews were recorded with the consent of the interviewees. The data collected was analyzed according to content analysis techniques. The results showed that the majority of interviewees had difficulties in locating the question, taking into account what they perceive as discrimination, that is, there is no way that a situation that is already naturalized can be discrimination; divergences were identified between public and private organizations and it was noted that there is greater segregation of women, which leaves them in the condition of having to choose between two spheres (family or work). All interviewees stated that they had equal pay between genders. It can be concluded that the glass ceiling effect impacts the work context of Angolan women in a less hostile way, being considered more as a protection and not as a discriminatory factor. [ABSTRACT FROM AUTHOR]

Background: Schizoaffective psychosis is a severe and chronic psychiatric disorder defined by the presence of mood symptoms, like mania and/or depression and schizophrenia, such as hallucinations and/or delusions. Aims: We aim to find out whether there is a correlation between schizoaffective psychosis and being homeless. Method: To do so, a literature search was carried out in the PubMed platform in April 2022, using the keywords 'schizoaffective' and 'homeless'. Results: In this review, 28 articles from this search were included. Intrinsic characteristics, rates of psychiatric readmission, prediction of homelessness, medication noncompliance, and substance use were explored, as they were the main themes of the results. Conclusions: The homeless population suffers from great diagnostic variability and the diagnosis schizoaffective psychosis is still evolving contributing to such diagnostic and treatment difficulties. Their frequent visits to the healthcare services, especially emergency room leads to consequent interaction with multiple healthcare professionals, resulting in a myriad of diagnoses, with clinical remission and therapeutic goals not being attained. More studies are necessary for a better evaluation of this super difficult population. [ABSTRACT FROM AUTHOR]

In this paper, we study an automatic hypothesis generation (HG) problem, which refers to the discovery of meaningful implicit connections between scientific terms, including but not limited to diseases, chemicals, drugs, and genes extracted from databases of biomedical publications. Most prior studies of this problem focused on the use of static information of terms and largely ignored the temporal dynamics of scientific term relations. Even when the dynamics were considered in a few recent studies, they learned the representations for the scientific terms, rather than focusing on the term-pair relations. Since the HG problem is to predict term-pair connections, it is not enough to know with whom the terms are connected, it is more important to know how the connections have been formed (in a dynamic process). We formulate this HG problem as a future connectivity prediction in a dynamic attributed graph. The key is to capture the temporal evolution of node-pair (term-pair) relations. We propose an inductive edge (node-pair) embedding method named T-PAIR, utilizing both the graphical structure and node attribute to encode the temporal node-pair relationship. We demonstrate the efficiency of the proposed model on three real-world datasets, which are three graphs constructed from Pubmed papers published until 2019 in Neurology, Immunotherapy, and Virology, respectively. Evaluations were conducted on predicting future term-pair relations between millions of seen terms (in the transductive setting), as well as on the relations involving unseen terms (in the inductive setting). Experiment results and case study analyses show the effectiveness of the proposed model. [ABSTRACT FROM AUTHOR]

IL-2 remains a promising candidate for immunotherapy of cancer, but its use is hampered by systemic toxicities. In this issue of Immunity , Tichet, Hanahan, and colleagues demonstrate that an IL-2 variant fused to an anti-PD-1 antibody overcomes these limitations to promote impressive tumor control. This approach may be a path to treat tumors that do not respond to anti-PD-1 monotherapy. [ABSTRACT FROM AUTHOR]

When amphibians thermoregulate, they face a fundamental trade-off between the ability to maintain activity and an increased rate of dehydration at higher temperatures. Canopy coverage affects both the thermal and hydric conditions of the environment and can therefore influence amphibian thermoregulation. Frogs require proper conditions to thermoregulate to successfully grow, survive, and reproduce. But while we know how canopy and environmental variables typically affect operative temperature, less is known about effects on amphibian water loss rates. In this study, we measure the effect of canopy coverage on the conditions available for thermoregulation at a breeding pond of the California red-legged frog, Rana draytonii. We use agar frog models to estimate the thermal and hydric capacities frogs would experience in locations with different canopy coverage and microhabitats. At each site, we deployed models under four microhabitat treatments: wet/sun, wet/shade, dry/sun, and dry/shade. We modeled how environmental variables affected operative temperature and evaporative water loss from agar frogs. We found positive effects of air temperature, the sun treatment, and reduced canopy cover on operative temperature, and negative direct or indirect effects of these variables on evaporative water loss, consistent with the hypothesized trade-off between thermoregulatory behavior to increase temperature and the increased desiccation risk due to higher water loss. Additionally, our results indicate that the availability of wet microhabitats can allow frogs to reduce water loss, potentially mitigating the risk of desiccation when thermoregulating to achieve higher operative temperatures. Our findings suggest, that with access to proper microhabitats, amphibians can mitigate the fundamental trade-off and receive benefits of thermoregulating at high temperatures. • We investigated environmental effects on frog body temperature and water loss. • We placed agar frog models in locations with variable canopy coverage and microhabitats. • Air temperature, sun, and lower canopy cover increased operative body temperature. • Thermoregulating at higher body temperatures increases water loss. • Water access and higher humidity decrease evaporative water loss. [ABSTRACT FROM AUTHOR]

Many universities offer one or more courses on leadership that include followership as a topic. A few have offered a complete course on followership. However, there is little information on postsecondary followership training. This chapter explores the unique issues of introducing followership to students, many of whom have been told their entire lives that leadership is everything. This chapter highlights followership courses and programs at institutions that offer them, and explores the delivery of current practices, with suggestions for increasing efficacy. [ABSTRACT FROM AUTHOR]

Case: A 60-year-old man presented with left hip pain, and a radiograph showed reduced joint space. During the surgical procedure for a total hip replacement, a proximal femur mass was identified and biopsy was subsequently interpreted as grade 2 chondrosarcoma. A wide resection was needed, but he developed local recurrence after 2 years and was treated with an external hemipelvectomy. Conclusions: Chondrosarcoma does not always present with a classical clinical picture or imaging, and it can be misdiagnosed. Practitioners should be highly suspicious of malignant disease as a cause for hip pain even if there is no direct indication of a neoplasm such as chondrosarcoma. [ABSTRACT FROM AUTHOR]

The development of cancer immunotherapies has been guided by advances in our understanding of the dynamics between tumor cells and immune populations. An emerging consensus is that immune control of tumors is mediated by cytotoxic CD8+ T cells, which directly recognize and kill tumor cells. The critical role of T cells in tumor control has been underscored by preclinical and clinical studies that observed that T cell presence is positively correlated with patient response to checkpoint blockade therapy. However, the vast majority of patients do not respond or develop resistance, frequently associated with exclusion of T cells from the tumor microenvironment. This review focuses on tumor cell–intrinsic alterations that blunt productive anti-tumor immune responses by directly or indirectly excluding effector CD8+ T cells from the tumor microenvironment. A comprehensive understanding of the interplay between tumors and the immune response holds the promise for increasing the response to current immunotherapies via the development of rational novel combination treatments. [ABSTRACT FROM AUTHOR]

The laser implantation–named technique aims to address the tribological problems frequently seen on tool surfaces during hot stamping. It is based on the creation of elevated dome- or ring-shaped hard structures on the surface of tool steels by a localized dispersing of hard particles. Therefore, a combination of the two distinct approaches that are normally used in surface technology for optimizing friction and wear, i.e., surface texturing and surface material optimization, are realized in one processing step. In experimental studies, a localized dispersing of TiB2 particles in the surface layer of the hot work tool steel X38CrMoV5-3 was considered and compared with punctual laser–remelted textures. The structures (micro-) hardness was measured at top- and cross-sections. With the aid of a scanning electron microscope, energy dispersive X-ray spectroscopy and X-ray diffraction the interaction between the hard particles and the substrate material were studied. From the results, an optimal parameter range was identified for laser implantation. To the investigation's end, the implant geometry was measured by optical microscopy and white light microscopy. Furthermore, a mathematic model was introduced, which allows a prediction of the implant geometry as a response to the laser parameters. It was shown that the implantation of TiB2 particles leads to a significant hardness increase up to 1600 HV1 due to the dispersion of initial particles and an in situ precipitation of new titanium-rich phases. It was possible to create defect-free dome- and ring-shaped microstructures on the surfaces. It was also shown that the implants geometry highly depends on the applied laser parameters. The applied central composite design shows a good agreement with the experimental results. [ABSTRACT FROM AUTHOR]

Abstract The pathogenic Escherichia coli strain may be responsible for foodborne infections in humans. This study was carried out to evaluate the presence of Escherichia coli and verify the occurrence of virulence genes in mussels (Mytella falcata) and oysters (Crassostrea brasiliana) collected from natural banks of the Estuary Lagunar Complex of Cananéia in the State of São Paulo, southeastern Brazil. A total of 150 shellfish samples (75 mussels and 75 oysters) were collected from June 2016 to February 2017. Total coliforms and Escherichia coli were determined using the most probable number (MPN) procedure. Colonies of Escherichia coli were biochemically characterized. The positive samples were submitted to molecular identification of species and posterior genetic sequencing for identifying Escherichia coli pathotypes. Escherichia coli was detected in 48 samples (32%) in concentrations ranging from <3 to <927 MPN/g. From 240 colonies tested biochemically, ninety-three were positive and submitted to molecular analyses. Fourty-eight colonies were confirmed as Escherichia coli by presenting PhoA gene and six (12.5%) were identified as enteropathogenic Escherichia coli (EPEC) by presenting eaeA gene and by sequencing of positive amplicons. Phylogenetic analyses revealed that the Brazilian samples were grouped in clades along with other EPEC isolates. These results are the first to indicate the presence of EPEC in shellfish in Brazil. Highlights • Escherichia coli were detected in shellfish samples in concentrations up to <927 MPN/g. • First detection of EPEC strain in shellfish in Brazil. • EPEC strains circulating in the assessed aquatic environment are very similar to those found in Uruguay and Brazil. [ABSTRACT FROM AUTHOR]

Highlights • Localized dispersing of TiB2 in AISI D2 allows the formation of elevated textures. • The elevated surface features (implants) show hardness values up to 1800 HV1. • Hardness values result from dispersed particles and in-situ precipitated particles. • Implants show diameters from 150 µm up to 350 µm and heights up to 30 µm. Abstract AISI D2 is one of the most applied cold-working tool steel for deep drawing operations, due to the materials good toughness and high wear resistance. However, since the lubricant-free deep drawing as well as the processing of high strength and ultra-high strength steel sheets remaining ongoing trends in the automotive industry, the tool surfaces need to be improved regarding their friction and wear behavior. For this purpose elevated micro textures can be applied. Since protruded micro features are predominantly affected by wear, a structuring process enabling the formation of suitable textures with high wear resistance is needed. In this paper surface texturing at microscale was conducted by laser implantation. This technique allows the fabrication of highly wear resistant, separated and elevated features (implants) on steel surfaces via a discontinuous dispersing of ceramic particles by pulsed laser radiation. The aim of this study was to investigate the techniques potential for the creation of wear resistant elevated micro features on AISI D2 tool steel surfaces by the application of TiB 2 particles. The laser parameters (pulse power and length) were varied and a comparative material analysis on AISI D2 laser remelted spots and TiB 2 localized dispersed zones was examined. High-speed camera recordings allowed the description of the particle insertion mechanism from pre-coatings during laser processing. Mechanical properties were analyzed by (micro-) hardness measurements at top and cross sections. The microstructure was investigated by optical microscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The implants geometrical properties (diameter, height, depth) were investigated by white light interferometry and optical microscopy. The experiments reveal that a pulsed laser remelting of AISI D2 leads to a significant hardness drop due to high retained austenite (γ R) contents. Contrary, a localized dispersing of TiB 2 particles leads to defect free dome- or ring-shaped elevated features with hardness values up to 1800 HV1. The high hardness values result from the dispersed TiB 2 particles and an in-situ precipitation of new hard particle phases, which lead to a reduction of the γ R content within the matrix. [ABSTRACT FROM AUTHOR]

Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy. Highlights Canonical WNT signaling plays a central role in embryogenesis, tissue homeostasis, and wound repair. Deregulated WNT signaling is involved in virtually all stages of oncogenesis. Impaired anticancer immunity as a result of aberrant WNT signaling is emerging as a key contributor to tumor progression and resistance to treatment. Activation of canonical WNT signaling hampers T cell-mediated anticancer immune responses by multiple mechanisms including immune exclusion. [ABSTRACT FROM AUTHOR]

Abstract Although dietary decision-making is regulated by multiple interacting neural controllers, their impact on dietary treatment success in obesity has only been investigated individually. Here, we used fMRI to test how well interactions between the Pavlovian system (automatically triggering urges of consumption after food cue exposure) and the goal-directed system (considering long-term consequences of food decisions) predict future dietary success achieved in 39 months. Activity of the Pavlovian system was measured with a cue-reactivity task by comparing perception of food versus control pictures, activity of the goal-directed system with a food-specific delay discounting paradigm. Both tasks were applied in 30 individuals with obesity up to five times: Before a 12-week diet, immediately thereafter, and at three annual follow-up visits. Brain activity was analyzed in two steps. In the first, we searched for areas involved in Pavlovian processes and goal-directed control across the 39-month study period with voxel-wise linear mixed-effects (LME) analyses. In the second, we computed network parameters reflecting the covariation of longitudinal voxel activity (i.e. principal components) in the regions identified in the first step and used them to predict body mass changes across the 39 months with LME models. Network analyses testing the link of dietary success with activity of the individual systems as reference found a moderate negative link to Pavlovian activity primarily in left hippocampus and a moderate positive association to goal-directed activity primarily in right inferior parietal gyrus. A cross-paradigm network analysis that integrated activity measured in both tasks revealed a strong positive link for interactions between visual Pavlovian areas and goal-directed decision-making regions mainly located in right insular cortex. We conclude that adaptation of food cue processing resources to goal-directed control activity is an important prerequisite of sustained dietary weight loss, presumably since the latter activity can modulate Pavlovian urges triggered by frequent cue exposure in everyday life. Highlights • Dietary decision-making is regulated by multiple interacting neural controllers. • Their impact on dietary success in obesity has only been investigated individually. • We assessed the impact of interactions between Pavlovian and goal-directed systems. • Longitudinal interactions are better predictor than activity of individual systems. • Goal-directed controllers presumably reduce Pavlovian urges triggered by food cues. [ABSTRACT FROM AUTHOR]

Organic carbon in atmospheric particles comprises a large fraction of chromatographically unresolved compounds, often referred to as humic-like substances (HULIS), which influence particle properties and impact climate, human health, and ecosystems. To better understand its composition, a two-dimensional (2D) offline method combining size-exclusion (SEC) and reversed-phase liquid chromatography (RP-HPLC) using a new spiked gradient profile is presented. It separates HULIS into 55 fractions of different size and polarity, with estimated ranges of molecular weight and octanol/water partitioning coefficient (log-P) from 160-900 g/mol and 0.2-3.3, respectively. The distribution of HULIS within the 2D size versus polarity space is illustrated with heat maps of ultraviolet absorption at 254 nm. It is found to strongly differ in a small example set of samples from a background site near Leipzig, Germany. In winter, the most intense signals were obtained for the largest molecules (>520 g/mol) with low polarity (log-P ∼ 1.9), whereas in summer, smaller (225-330 g/mol) and more polar (log-P ∼ 0.55) molecules dominate. The method reveals such differences in HULIS composition in a more detailed manner than previously possible and can therefore help to better elucidate the sources of HULIS in different seasons or at different sites. Analyzing Suwannee river fulvic acid as a common HULIS surrogate shows a similar polarity range, but the sizes are clearly larger than those of atmospheric HULIS. [ABSTRACT FROM AUTHOR]

Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α1-adrenergic blockade (prazosin; 75 κg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/dtmax, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α1-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN. [ABSTRACT FROM AUTHOR]

Dendritic cells are crucial for anti-tumor immune responses due to their ability to activate cytotoxic effector CD8+ T cells. Canonically, in anti-tumor immunity, dendritic cells activate CD8+ T cells in a process termed cross-presentation. Recent studies have demonstrated that another type of antigen presentation, MHC-dressing, also serves to activate CD8+ T cells against tumor cell-derived antigens. Understanding MHC-dressing's specific contributions to anti-tumor immunity can open up novel therapeutic avenues. In this review, we summarize the early studies that identified MHC-dressing as a relevant antigen presentation pathway before diving into a deeper discussion of the biology of MHC-dressing, focusing in particular on which dendritic cell subsets are most capable of performing MHC-dressing and how MHC-dressing compares to other forms of antigen presentation. We conclude by discussing the implications MHC-dressing has for anti-tumor immunity. • Tumor-specific CD8+ T cells can be primed via MHC-dressing. • Both subsets of conventional dendritic cells can utilize MHC-dressing to prime CD8+ T cells. • The dendritic cell activation state, determined by tumor-derived factors, affects the ability of dendritic cells to prime CD8+ T cells via MHC-dressing. [ABSTRACT FROM AUTHOR]

Melanoma metastases can be categorized by gene expression for the presence of a T-cell--inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer--testis antigens. Therapies are being pursued to trigger immune infiltration into non--T-cell--inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored. To address this question, 266 melanomas from The Cancer Genome Atlas (TCGA) were categorized by the presence or absence of a T-cell--inflamed gene signature. These two subsets were interrogated for cancer--testis, differentiation, and somatic mutational antigens. No statistically significant differences were observed, including density of NSSMs. Focusing on hypothetical HLA-A2+ binding scores, 707 peptides were synthesized, corresponding to all identified candidate neoepitopes. No differences were observed in measured HLA-A2+ binding between inflamed and noninflamed cohorts. Twenty peptides were randomly selected from each cohort to evaluate priming and recognition by human CD8+ T cells in vitro with 25% of peptides confirmed to be immunogenic in both. A similar gene expression profile applied to all solid tumors of TCGA revealed no association between T-cell signature and NSSMs. Our results indicate that lack of spontaneous immune infiltration in solid tumors is unlikely due to lack of antigens. Strategies that improve T-cell infiltration into tumors may therefore be able to facilitate clinical response to immunotherapy once antigens become recognized. [ABSTRACT FROM AUTHOR]

An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient. [ABSTRACT FROM AUTHOR]

Checkpoint blockade therapy has been proven to be highly active across many cancer types but emerging evidence indicates that the therapeutic benefit is limited to a subset of patients in each cancer entity. The presence of CD8+ T cells within the tumor microenvironment or the invasive margin of the tumor, as well as the up-regulation of PD-L1, have emerged to be the most predictive biomarkers for clinical benefit in response to checkpoint inhibition. Although the up-regulation of immune inhibitory mechanisms is one mechanism of immune escape, commonly used by T-cellinflamed tumors, exclusion of an anti-tumor specific T-cell infiltrate displays another even more potent mechanism of immune escape. This review will contrast the mechanisms of immunogenic, T-cell-inflamed, and the novel concept of non-immunogenic, non-T-cell-inflamed, adaptive immune escape. [ABSTRACT FROM AUTHOR]

The article presents a report from a January 31 to February 2, 2016 conference in Berlin, Germany on the 20th-century history of Judaism and the labor movement hosted by the Ludwig Rosenberg Kolleg college and the academy of the Jewish museum of Berlin. Topics of presentations delivered included political, historical, and economic histories of French, American, and Israeli Jewish communities, the role of Ada Maimon née Fischmann in founding the women's labor movement of Eretz Israel, and the views on Soviet communism held by Jewish socialist Fritz Sternberg.

Acquired dysfunction of tumor-reactive T cells is one mechanism by which tumors can evade the immune system. Identifying and correcting pathways that contribute to such dysfunction should enable novel anticancer therapy design. During cancer growth, T cells show reduced NF-κB activity, which is required for tumor rejection. Impaired T cell--intrinsic NF-κB may create a vicious cycle conducive to tumor progression and further T cell dysfunction. We hypothesized that forcing T cell--intrinsic NF-κB activation might break this cycle and induce tumor elimination. NF-κB was activated in T cells by inducing the expression of a constitutively active form of the upstream activator IκB kinase β (IKKβ). T cell-restricted constitutively active IKKβ augmented the frequency of functional tumor-specific CD8+ T cells and improved tumor control. Transfer of constitutively active IKKβ-transduced T cells also boosted endogenous T cell responses that controlled pre-established tumors. Our results demonstrate that driving T cell-intrinsic NF-κB can result in tumor control, thus identifying a pathway with potential clinical applicability. [ABSTRACT FROM AUTHOR]

Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P = 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR. [ABSTRACT FROM AUTHOR]

Defining perceptual similarity metrics for odorant comparisons is crucial to understanding the mechanism of olfactory perception. Current methods in olfaction rely on molecular physicochemical features or discrete verbal descriptors (floral, burnt, etc.) to approximate perceptual (dis)similarity between odorants. However, structural or verbal descriptors alone are limited in modeling complex nuances of odor perception. While structural features inadequately characterize odor perception, language-based discrete descriptors lack the granularity needed to model a continuous perception space. We introduce data-driven approaches to perceptual metrics learning (PMeL) based on two key insights: a) by combining physicochemical features with the user's perceptual feedback, we can leverage both structural and perceptual attributes of odors to define dissimilarity, and b) instead of discrete labels, user's perceptual feedback can be gathered as relative similarity comparisons, such as "Does molecule-A smell more like molecule-B, or molecule-C?" These triplet comparisons are easier even for non-experts users and offer a more effective representation of the continuous perception space. Experimental results on several defined tasks show the effectiveness of our approach in evaluating perceptual dissimilarity between odorants. Finally, we investigate how closely our model, trained on non-expert feedback, aligns with the expert's similarity judgments. Our effort aims to reduce reliance on expert annotations. [ABSTRACT FROM AUTHOR]

Understanding and controlling the growth and stability of molecular thin films on solid surfaces is necessary to develop nanomaterials with well-defined physical properties. As a prominent model system in organic electronics, we investigate the post-growth dewetting kinetics of the fullerene C60 on mica with real-time and in situ X-ray scattering. After layer-by-layer growth of C60, we find a thermally-activated post-growth dewetting, where the smooth C60-layer breaks up into islands. This clearly shows that growth is kinetically limited before the system moves over an activation barrier into an energetically favored configuration. From the temperaturedependent dewetting kinetics we find an effective activation barrier of 0.33 eV, which describes both the temperaturedependent macroscopic changes in the surface morphology and the microscopic processes of inter- and intralayer diffusion during dewetting. [ABSTRACT FROM AUTHOR]

Blood flow restriction (BFR) training (also known as Kaatsu training) is an increasingly common practice employed during resistance exercise by athletes attempting to enhance skeletal muscle mass and strength. During BFR training, blood flow to the exercising muscle is mechanically restricted by placing flexible pressurizing cuffs around the active limb proximal to the working muscle. This maneuver results in the accumulation of metabolites (e.g., protons and lactic acid) in the muscle interstitium that increase muscle force and promote muscle growth. Therefore, the premise of BFR training is to simulate and receive the benefits of high-intensity resistance exercise while merely performing low-intensity resistance exercise. This technique has also been purported to provide health benefits to the elderly, individuals recovering from joint injuries, and patients undergoing cardiac rehabilitation. Since the seminal work of Alam and Smirk in the 1930s, it has been well established that reductions in blood flow to exercising muscle engage the exercise pressor reflex (EPR), a reflex that significantly contributes to the autonomic cardiovascular response to exercise. However, the EPR and its likely contribution to the BFR-mediated cardiovascular response to exercise is glaringly missing from the scientific literature. Inasmuch as the EPR has been shown to generate exaggerated increases in sympathetic nerve activity in disease states such as hypertension (HTN), heart failure (HF), and peripheral artery disease (PAD), concerns are raised that BFR training can be used safely for the rehabilitation of patients with cardiovascular disease, as has been suggested. Abnormal BFR-induced and EPR-mediated cardiovascular complications generated during exercise could precipitate adverse cardiovascular or cerebrovascular events (e.g., cardiac arrhythmia, myocardial infarction, stroke and sudden cardiac death). Moreover, although altered EPR function in HTN, HF, and PAD underlies our concern for the widespread implementation of BFR, use of this training mechanism may also have negative consequences in the absence of disease. That is, even normal, healthy individuals performing resistance training exercise with BFR are potentially at increased risk for deleterious cardiovascular events. This review provides a brief yet detailed overview of the mechanisms underlying the autonomic cardiovascular response to exercise with BFR. A more complete understanding of the consequences of BFR training is needed before this technique is passively explored by the layman athlete or prescribed by a health care professional. [ABSTRACT FROM AUTHOR]

In this paper, a novel approach for field coupled inline transitions between different waveguides is proposed. The immittance inverting characteristics of these transitions are simultaneously utilized for filter design. Based on scattering parameters, an exact relation is derived between the desired inverter constants and the even and odd mode characteristic impedances. The well-known approximation introduced by Cohn is improved. Further it will be shown that the introduced inline transitions can be effectively modeled with a contra-directional symmetrical coupler. The description of the field coupled waveguide transitions as inverters allows a “straight on design method” for general field coupled structures and accelerates the optimization process. The integration of the inline transitions into the filter design is applied for two different types of transitions, namely, the transition between a parallel-plate waveguide and a rectangular waveguide (RWG) and the transition between a microstrip line and a RWG, using a ridged waveguide section for the coupling. For both configurations a third-order bandpass filter was realized by using three coupled waveguide resonators. Two of the coupling structures were made up of inline transitions. To verify the approach and quantify losses, a filter was fabricated and its scattering parameters measured. With this new approach low-loss waveguide filters can be integrated into a planar RF circuit while minimizing space. No delicate manufacturing processes are required. [ABSTRACT FROM PUBLISHER]

In this paper, we perform a comparative analysis between two computational methods for virtual stent deployment: a novel fast virtual stenting method, which is based on a spring–mass model, is compared with detailed finite element analysis in a sequence of in silico experiments. Given the results of the initial comparison, we present a way to optimise the fast method by calibrating a set of parameters with the help of a genetic algorithm, which utilises the outcomes of the finite element analysis as a learning reference. As a result of the calibration phase, we were able to substantially reduce the force measure discrepancy between the two methods and validate the fast stenting method by assessing the differences in the final device configurations. [ABSTRACT FROM AUTHOR]

Melanoma treatment is being revolutionized by the development of effective immunotherapeutic approaches. These strategies include blockade of immune-inhibitory receptors on activated T cells; for example, using monoclonal antibodies against CTLA-4, PD-1, and PD-L1 (refs 3, 4, 5). However, only a subset of patients responds to these treatments, and data suggest that therapeutic benefit is preferentially achieved in patients with a pre-existing T-cell response against their tumour, as evidenced by a baseline CD8+ T-cell infiltration within the tumour microenvironment. Understanding the molecular mechanisms that underlie the presence or absence of a spontaneous anti-tumour T-cell response in subsets of cases, therefore, should enable the development of therapeutic solutions for patients lacking a T-cell infiltrate. Here we identify a melanoma-cell-intrinsic oncogenic pathway that contributes to a lack of T-cell infiltration in melanoma. Molecular analysis of human metastatic melanoma samples revealed a correlation between activation of the WNT/β-catenin signalling pathway and absence of a T-cell gene expression signature. Using autochthonous mouse melanoma models we identified the mechanism by which tumour-intrinsic active β-catenin signalling results in T-cell exclusion and resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy. Specific oncogenic signals, therefore, can mediate cancer immune evasion and resistance to immunotherapies, pointing to new candidate targets for immune potentiation. [ABSTRACT FROM AUTHOR]

During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN). The mechanisms sustaining the pressor response during PEMI in HTN are unknown. In six chronically instrumented canines, hemodynamic responses were observed during rest, mild exercise (3.2 km/h), MMA, and PEMI in the same animals before and after the induction of HTN [Goldblatt two kidney, one clip (2K1C)]. In controls, MAP, CO and HR increased with MMA (+52 ± 6 mmHg, +2.1 ± 0.3 l/min, and +37 ± 7 beats per minute). After induction of HTN, MAP at rest increased from 97 ± 3 to 130 ± 4 mmHg, and the metaboreflex responses were markedly attenuated (+32 ± 5 mmHg, +0.6 ± 0.2 l/min, and +11 ± 3 bpm). During PEMI in HTN, HR and CO were not sustained, and MAP fell to normal recovery levels. We conclude that the attenuated metaboreflex-induced HR, CO, and MAP responses are not sustained during PEMI in HTN. [ABSTRACT FROM AUTHOR]

Muscle metaboreflex-induced increases in mean arterial pressure (MAP) during submaximal dynamic exercise are mediated principally by increases in cardiac output. To what extent, if any, the peripheral vasculature contributes to this rise in MAP is debatable. In several studies, we observed that in response to muscle metaboreflex activation (MMA; induced by partial hindlimb ischemia) a small but significant increase in vascular conductance occurred within the nonischemic areas (calculated as cardiac output minus hindlimb blood flow and termed nonischemic vascular conductance; NIVC). We hypothesized that these increases in NIVC may stem from a metaboreflex-induced release of epinephrine, resulting in β2-mediated dilation. We measured NIVC and arterial plasma epinephrine levels in chronically instrumented dogs during rest, mild exercise (3.2 km/h), and MMA before and after β-blockade (propranolol; 2 mg/kg), α1-blockade (prazosin; 50 μg/kg), and α1 + β-blockade. Both epinephrine and NIVC increased significantly from exercise to MMA: 81.9 ± 18.6 to 141.3 ± 22.8 pg/ml and 33.8 ± 1.5 to 37.6 ± 1.6 ml•min-1 •mmHg-1, respectively. These metaboreflex-induced increases in NIVC were abolished after β-blockade (27.6 ± 1.8 to 27.5 ± 1.7 ml•min-1•mmHg-1) and potentiated after α1-blockade (36.6 ± 2.0 to 49.7 ± 2.9 ml•min-1•mmHg-1), while α1 + β-blockade also abolished any vasodilation (33.7 ± 2.9 to 30.4 ± 1.9 ml•min-1•mmHg-1). We conclude that MMA during mild dynamic exercise induces epinephrine release causing β2-mediated vasodilation. [ABSTRACT FROM AUTHOR]

This paper presents a methodology for modeling the deployment of implantable devices used in minimally invasive vascular interventions. Motivated by the clinical need to perform preinterventional rehearsals of a stent deployment, we have developed methods enabling virtual device placement inside arteries, under the constraint of real-time application. This requirement of rapid execution narrowed down the search for a suitable method to the concept of a dynamic mesh. Inspired by the idea of a mesh of springs, we have found a novel way to apply it to stent modeling. The experiments conducted in this paper investigate properties of the stent models based on three different spring types: lineal, semitorsional, and torsional springs. Furthermore, this paper compares the results of various deployment scenarios for two different classes of devices: a stent graft and a flow diverter. The presented results can be of a high-potential clinical value, enabling the predictive evaluation of the outcome of a stent deployment treatment. [ABSTRACT FROM PUBLISHER]

Highlights: [•] In the combined treatment, BOD5/COD increases from 0.3 to 0.9, with 95% COD removal. [•] Chromium and zinc concentrations decrease by cathodic reduction during EC+AO process. [•] [Fe] varies during EC due to the cycles of iron hydroxide formation and precipitation. [•] The combined EC+AO process resulted in very high removals of all forms of nitrogen. [ABSTRACT FROM AUTHOR]

In 2011 the European Court of Justice issued a decision regarding the patentability of technologies derived from human embryonic stem cells. The finding will have an impact on the framework of stem cell research within the European Union and its Member States and has already triggered several political initiatives regarding the funding of research with human embryonic stem cells on the European level as well as a renewed public debate. This article will take a short look at the case history and the findings of the court. It offers some critical comments regarding the findings' consistency with European and international regulations on intellectual property rights as well as some considerations on the possible impact of the case for other fields of law. [ABSTRACT FROM AUTHOR]

Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance. [ABSTRACT FROM AUTHOR]

OBJECTIVE-Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to investigate the relationship between hepatic insulin clearance (HIC) and different components ofmetabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome. RESEARCH DESIGN AND METHODS-Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were calculated. RESULTS-Both HIC indices showed lower values in subjects with metabolic syndrome (P, 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 6 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI 0.97-1.31], P = 0.12, and HICISR 1.38 [0.88-2.17], P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 [0.92-1.36], P = 0.26, and HICISR 1.31 [0.74-2.33] P = 0.36), although point estimates reached no statistical significance. CONCLUSIONS-HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects. [ABSTRACT FROM AUTHOR]

Muscle metaboreflex activation (MMA) during submaximal dynamic exercise in normal individuals increases mean arterial pressure (MAP) via increases in cardiac output (CO) with little peripheral vasoconstriction. The rise in CO occurs primarily via increases in heart rate (HR) with maintained or slightly increased stroke volume. When the reflex is sustained during recovery (postexercise muscle ischemia, PEMI), HR declines yet MAP remains elevated. The role of CO in mediating the pressor response during PEMI is controversial. In seven chronically instrumented canines, steady-state values with MMA during mild exercise (3.2 km/h) were observed by reducing hindlimb blood flow by ~60% for 3-5 min. MMA during exercise was followed by 60 s of PEMI. Control experiments consisted of normal exercise and recovery. MMA during exercise increased MAP, HR, and CO by 55.3 ± 4.9 mmHg, 42.5 ± 6.9 beats/min, and 2.5 ± 0.4 l/min, respectively. During sustained MMA via PEMI, MAP remained elevated and CO remained well above the normal recovery levels. Neither MMA during dynamic exercise nor during PEMI significantly affected peripheral vascular conductance. We conclude that the sustained increase in MAP during PEMI is driven by a sustained increase in CO not peripheral vasoconstriction. [ABSTRACT FROM AUTHOR]

Summary: Proteolytic activity of the mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) paracaspase is required for survival of the activated B cell subtype of diffuse large B cell lymphoma (ABC-DLBCL). We have identified distinct derivatives of medicinal active phenothiazines, namely mepazine, thioridazine, and promazine, as small molecule inhibitors of the MALT1 protease. These phenothiazines selectively inhibit cleavage activity of recombinant and cellular MALT1 by a noncompetitive mechanism. Consequently, the compounds inhibit anti-apoptotic NF-κB signaling and elicit toxic effects selectively on MALT1-dependent ABC-DLBCL cells in vitro and in vivo. Our data provide a conceptual proof for a clinical application of distinct phenothiazines in the treatment of ABC-DLBCL. [ABSTRACT FROM AUTHOR]

The hyaluronan-mediated motility receptor (HMMR/Rhamm) is overexpressed in numerous tumor types, including acute lymphoid leukemia and acute myeloid leukemia (AML). Several studies have reported the existence of T-cell responses directed against HMMR in AML patients that are linked to better clinical outcome. Therefore, we explored the use of HMMR-specific TCRs for transgenic expression in lymphocytes and their in vivo impact on HMMR+ solid tumors and disseminated leukemia. We obtained TCRs via an in vitro priming approach in combination with CD137-mediated enrichment. Recipient lymphocytes expressing transgenic TCR revealed the specific tumor recognition pattern seen with the original T cells. Adoptive transfer experiments using a humanized xenograft mouse model resulted in significantly retarded solid tumor outgrowth, which was enhanced using IL-15-conditioned, TCR-transgenic effector memory cells. These cells also showed an increased potency to retard the outgrowth of disseminated AML, and this was further improved using CD8-enriched effector memory cells. To define a safe clinical setting for HMMR-TCR gene therapy, we analyzed transgenic T-cell recognition of hematopoietic stem cells (HSCs) and found on-target killing of HLA-A2+ HSCs. Our findings clearly limit the use of HMMR-TCR therapy to MHC-mismatched HSC transplantation, in which HLA-A2 differences can be used to restrict recognition to patient HSCs and leukemia. [ABSTRACT FROM AUTHOR]

Schatz, T. R., Spranger, T., Kubik, V. & Knopf, M. (2011). Exploring the enactment effect from an information processing view: What can we learn from serial position analyses? Scandinavian Journal of Psychology 52, 509-515. The focus of the present article was to analyze processes that determine the enactment and age effect in a multi-trial free recall paradigm by looking at the serial position effects. In an experimental study (see ), the performance-enhancing effect of enactive encoding and repeated learning was tested with older and younger participants. As expected, there was a steady improvement of memory performance as a function of repeated learning regardless of age. In addition, enactive encoding led to a better memory performance than verbal encoding in both age groups. Furthermore, younger adults outperformed the elderly regardless of type of encoding. Analyses in the present article show that encoding by enacting seems to profit especially from remembering the last items of a presented list. Regarding age differences, younger outperformed older participants in nearly all item positions. The performance enhancement after task repetition is due to a higher amount of recalled items in the middle positions in a subject performed task (SPT) and a verbal task (VT) as well as the last positions of a learned list in VT. [ABSTRACT FROM AUTHOR]

Fractures of the calcaneus are still severe injuries of the lower extremities which is reflected in the above average times of disability and the very different results of treatment compared to other fractures of the lower extremities. Therefore therapeutic decision-making for these patients requires, besides knowledge of the current treatment options, an individual and patient-orientated assessment. Various studies have shown that accurate reconstruction of the subtalar joint leads to a better outcome in these patients which will strengthen the importance of intraoperative digital 3D imaging techniques in the future. [ABSTRACT FROM AUTHOR]

Various kinds of normative judgments are an integral part of everyday life. We extended the scrutiny of social cognitive neuroscience into the domain of legal decisions, investigating two groups, lawyers and other academics, during moral and legal decision-making. While we found activation of brain areas comprising the so-called ‘moral brain’ in both conditions, there was stronger activation in the left dorsolateral prefrontal cortex and middle temporal gyrus particularly when subjects made legal decisions, suggesting that these were made in respect to more explicit rules and demanded more complex semantic processing. Comparing both groups, our data show that behaviorally lawyers conceived themselves as emotionally less involved during normative decision-making in general. A group × condition interaction in the dorsal anterior cingulate cortex suggests a modulation of normative decision-making by attention based on subjects’ normative expertise. [ABSTRACT FROM PUBLISHER]

Schatz, T.R., Spranger, T. & Knopf, M. (2010). Is there a memory profit after repeated learning of subject-performed actions? Comparing direct and long-term memory performance level as a function of age. Scandinavian Journal of Psychology 51, 465-472. The present two studies investigated the possibility for improvement and maintenance of episodic memory in young and older adults. In a first study, the performance-enhancing effect of two separate as well as combined learning devices, enactive encoding and repeated learning, was tested. With a time lag of one week, four different series of 30 action phrases were encoded either verbally or by enacting them symbolically. Memory was assessed in four immediate free recall tests. In a second study, the maintenance of the memory profit was tested in an unexpected fifth session half a year later. As expected, there was a steady improvement of memory performance as a function of repeated learning in study one. This holds true regardless of age. In addition, enactive encoding led to a better memory performance than verbal encoding in both age groups. Moreover, younger adults outperformed the elderly regardless of type of encoding. The combination of the two learning devices was not efficient enough to eliminate aging effects in episodic memory. However, memory flexibility is demonstrated also in the elderly. In the long-term follow-up, maintenance of learning and memory could be found in all participant groups. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a software system that integrates different computational paradigms to solve cognitive tasks of different levels. The system has been employed to empower research on very different platforms ranging from simple two-wheeled structures with only a few cheap sensors, to complex two-legged humanoid robots, with many actuators, degrees of freedom and sensors. It is flexible and adjustable enough to be used in part or as a whole, to target different research domains projects and questions, including Evolutionary Robotics, RoboCup and Artificial Language Evolution on Autonomous Robots (ALEAR, an EU funded cognitive systems project). In contrast to many other frameworks, the system is such that researchers can quickly adjust the system to different problems and platforms, while allowing maximum reuse of components and abstractions, separation of concerns and extensibility. [Copyright &y& Elsevier]