Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic heterogeneity of AIDS‐related small non‐cleaved cell lymphoma

AIDS‐related small noncleaved cell lymphoma (AIDS‐SNCCL) includes Burkitt's lymphoma (BL) and high‐grade B‐cell Burkitt‐like lymphoma (BLL). Due to the marked polymorphism of AIDS‐related non‐Hodgkin's lymphomas (AIDS‐NHL), the morphologic distinction between these two types of lymphomas is frequently controversial, although it may bear clinical relevance. Although the molecular features of AIDS‐BL have been clarified to a certain extent, the genetic peculiarities of AIDS‐BLL have not been investigated in detail. In this study we have compared morphologic and genetic features of AIDS‐BL and AIDS‐BLL in a blind coded fashion. Molecular studies were focused on the genetic lesions known to be implicated in AIDS‐NHL, including alterations of c‐MYC, BCL‐6, p53, deletions of 6q, as well as infection by EBV and HHV‐8. Alterations of c‐MYC occurred in 10/10 AIDS‐BL, whereas they were restricted to 2/10 AIDS‐BLL (P < 0.01). Mutations of p53 were present in 5/10 AIDS‐BL, whereas they were consistently absent among AIDS‐BLL (n = 10; P < 0.05). Infection by EBV occurred in 30% of both AIDS‐BL and AIDS‐BLL. Rearrangements of BCL‐6, deletions of 6q and infection by HHV‐8 scored consistently negative in both AIDS‐BL and AIDS‐BLL. Based on the genetic lesions tested, the molecular profile of AIDS‐BLL appears to be closer to that of AIDS‐related diffuse large cell lymphoma (AIDS‐DLCL) than to that of AIDS‐BL. In contrast to AIDS‐BLL, however, AIDS‐DLCL carried rearrangements of BCL‐6 in a fraction of cases (2/9). This study, the largest of its kind reported so far, suggests that AIDS‐BL and AIDS‐BLL have a different molecular pathogenesis and that characterization of genetic lesions may help to distinguish between these two lymphomas.
Re-emergence of Bovine Brucellosis in Smallholder Dairy Farms in Urban Settings of Tanzania

Aims: Brucellosis infection was previously encountered in all livestock farming systems in Tanzania but reported to decline below 2% in smallholder dairy subsector due to the stringent calf-hood vaccination using S19 between 1979 and 1990. However, reports from the last decade indicated an increase of the infection in the smallholder dairy subsector. This prompted several researchers to conduct further studies in different urban settings to ascertain the disease and associated risk factors. This study aims to elucidate the magnitude of brucellosis in urban areas of Morogoro region and related risk factors in the advent of no control intervention in place. Presence of anti-brucella antibodies in dairy animals residing in urban areas may pose a threat to milk consumers in the cities as a significant proportion of the milk is sold informally. Therefore, generating this information will inform policy to formulate feasible intervention for controlling brucellosis in urban settings that indirectly will safeguard public health. Study Design: This was a cross-sectional survey. Place and Duration of Study: The study was conducted in Morogoro Municipality between May and September 2012. Original Research Article Shirima et al.; JALSI, 17(2): 1-7, 2018; Article no.JALSI. 40955 2 Methodology: The study was to determine the prevalence of anti-brucella antibodies in smallholder dairy cattle in urban settings of Tanzania. Milk Ring Test was used as a screening technique while Competitive Enzyme-Linked Immunosorbent Assay was a confirmatory test. A questionnaire was applied to each animal owner. A total of 104 respondents were interviewed to assess possible risk factors associated with re-emergence and transmission of brucellosis among dairy cattle. Results: 390 dairy cows from Morogoro Municipality were screened for Brucella circulating antibodies. Overall 35.4% (95%CI; 25.2-33.8) of milk samples tested positive based on MRT while seroprevalence was 21.3% (95% CI) based on c-ELISA. It was further revealed that abortion (p= 0.01) and herd size (0.05) were significantly associated with brucellosis seropositivity in cattle. Although 32% of herd owners vaccinate their cattle against several transboundary diseases, none vaccinated against brucellosis. Conclusions: From this study, there is evidence that collapse of the Tuberculosis and Brucellosis Control Programme has resulted into an increase of brucellosis within the smallholder dairy farmers within urban settings. This may pose a high risk to urban farmers and milk consumers thus attracting immediate response.
Predicting the Extension of Biomedical Ontologies

Developing and extending a biomedical ontology is a very demanding task that can never be considered complete given our ever-evolving understanding of the life sciences. Extension in particular can benefit from the automation of some of its steps, thus releasing experts to focus on harder tasks. Here we present a strategy to support the automation of change capturing within ontology extension where the need for new concepts or relations is identified. Our strategy is based on predicting areas of an ontology that will undergo extension in a future version by applying supervised learning over features of previous ontology versions. We used the Gene Ontology as our test bed and obtained encouraging results with average f-measure reaching 0.79 for a subset of biological process terms. Our strategy was also able to outperform state of the art change capturing methods. In addition we have identified several issues concerning prediction of ontology evolution, and have delineated a general framework for ontology extension prediction. Our strategy can be applied to any biomedical ontology with versioning, to help focus either manual or semi-automated extension methods on areas of the ontology that need extension.
Robust but delayed thalamocortical activation of dendritic-targeting inhibitory interneurons

GABA-releasing cortical interneurons are crucial for the neural transformations underlying sensory perception, providing “feedforward” inhibition that constrains the temporal window for synaptic integration. To mediate feedforward inhibition, inhibitory interneurons need to fire in response to ascending thalamocortical inputs, and most previous studies concluded that ascending inputs activate mainly or solely proximally targeting, parvalbumin-containing “fast-spiking” interneurons. However, when thalamocortical axons fire at frequencies that are likely to occur during natural exploratory behavior, activation of fast-spiking interneurons is rapidly and strongly depressed, implying the paradoxical conclusion that feedforward inhibition is absent when it is most needed. To address this issue, we took advantage of lines of transgenic mice in which either parvalbumin- or somatostatin-containing interneurons express GFP and recorded the responses of interneurons from both subtypes to thalamocortical stimulation in vitro. We report that during thalamocortical activation at behaviorally expected frequencies, fast-spiking interneurons were indeed activated only transiently because of rapid depression of their thalamocortical inputs, but a subset of layer 5 somatostatin-containing interneurons were robustly and persistently activated after a delay, due to the facilitation and temporal summation of their thalamocortical excitatory postsynaptic potentials. Somatostatin-containing interneurons are considered distally targeting. Thus, they are likely to provide delayed dendritic inhibition during exploratory behavior, contributing to the maintenance of a balance between cortical excitation and inhibition while leaving a wide temporal window open for synaptic integration and plasticity in distal dendrites.
Positron Emission Tomography for Predicting Pathologic Response After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

PurposeTo investigate whether before and after chemoradiotherapy (CRT) positron emission tomography (PET) predict for pathologic response after preoperative CRT in patients with locally advanced rectal adenocarcinoma. MethodsThirty-five patients who underwent pre-CRT and post-CRT PET scans before surgery were included. All patients were staged with endoscopic ultrasound or high resolution CT. CRT was given with 50.4 Gy at 1.8 Gy per fraction and concurrent 5-fluorouracil-based chemotherapy. Surgery occurred at a median of 46 days (range, 27 to 112 d) after completing CRT. The maximum standardized uptake value (SUVmax) and the metabolic tumor volume (MTV) using various minimum SUV thresholds (2, 2.5, 3) on the PET scans (MTV2.0, MTV2.5, MTV3.0) were determined. Post-CRT PET scans were done 3 to 5 weeks after completion of CRT. Pathologic response was assessed using the tumor regression grade (TRG) scale. Patients with complete or near-complete response (TRG=0 to 1) were considered pathologic responders. The pre-CRT and post-CRT PET scan SUVmax and MTV values were correlated with TRG. The &Dgr;SUVmax and &Dgr;MTV were correlated with TRG. ResultsNo correlation was seen with SUVmax (P=0.99), MTV2.0 (P=0.73), MTV2.5 (P=0.73), or MTV3.0 (P=0.31) on the pre-CRT PET between pathologic responders versus nonresponders. No correlation was noted between SUVmax (P=0.49), MTV2.0 (P=0.73), MTV2.5 (P=0.49), or MTV3.0 (P=0.31) on the post-CRT PET scan and pathologic response. Finally, the &Dgr;SUVmax (P=0.32), &Dgr;MTV2.0 (P=0.99), &Dgr;MTV2.5 (P=0.31), &Dgr;MTV3.0 (P=0.31) did not correlate with pathologic response. ConclusionsChanges seen on PET have limited value in predicting for pathologic response of rectal cancer after preoperative neoadjuvant therapy.
The Role of Stress Factors during Aging of the Immune System

This manuscript reviews current evidence suggesting that aging of the immune system (immunosenescence) may be closely related to chronic stress and stress factors. Healthy aging has been associated with emotional distress in parallel to increased cortisol to dehydroepiandrosterone (DHEA) ratio. The impaired DHEA secretion together with the increase of cortisol results in an enhanced exposure of lymphoid cells to deleterious glucocorticoid actions. The lack of appropriated growth hormone signaling during immunosenescence is also discussed. It follows that altered neuroendocrine functions could be underlying several immunosenescence features. Indeed, changes in both innate and adaptive immune responses during aging are also similarly reported during chronic glucocorticoid exposure. In addition, chronically stressed elderly subjects may be particularly at risk of stress‐related pathology because of further alterations in both neuroendocrine and immune systems. The accelerated senescent features induced by chronic stress include higher oxidative stress, reduced telomere length, chronic glucocorticoid exposure, thymic involution, changes in cellular trafficking, reduced cell‐mediated immunity, steroid resistance, and chronic low‐grade inflammation. These senescent features are related to increased morbidity and mortality among chronically stressed elderly people. Overall, these data suggest that chronic stress leads to premature aging of key allostatic systems involved in the adaptation of the organisms to environmental changes. Stress management and psychosocial support may thus promote a better quality of life for elderly people and at the same time reduce hospitalization costs.
DNS authentication as a service: preventing amplification attacks

We present the first defence against DNS-amplification DoS attacks, which is compatible with the common DNS servers configurations and with the (important standard) DNSSEC. We show that the proposed DNS-authentication system is efficient, and effectively prevents DNS-based amplification DoS attacks abusing DNS name servers. We present a game-theoretic model and analysis, predicting a wide-spread adoption of our design, sufficient to reduce the threat of DNS amplification DoS attacks. To further reduce costs and provide additional defences for DNS servers, we show how to deploy our design as a cloud based service.
HF-driven currents in the polar ionosphere

Ionospheric heaters located in the polar-regions (EISCAT, HAARP, HIPAS) have generated waves in the ULF/ELF/VLF range by modulating the auroral electrojet at D/E region altitudes in a concept termed by the EISCAT group as the Polar Electrojet (PEJ) antenna. The PEJ antenna requires an ionospheric heater located under regions of naturally driven D/E region currents, such as in the auroral or equatorial electrojet. In a simplified fashion the PEJ antenna operates as following: In the presence of an electrojet current periodic electron heating in the Hall dominated region of the lower ionosphere reduces the conductivity of the heated spot building oscillatory polarization charges at the boundaries. This acts as an essentially Horizontal Electric Dipole (HED) at the modulation frequency. The HED excites the Earth-Ionosphere Waveguide (EIW) from above while the current closes by launching upwards helicon (whistler) waves carrying field-aligned current. A major problem with the PEJ is its reliance in the presence and strength of the electrojet current. This restricts not only the location of the heater but makes their generation highly unpredictable. We will present theoretical/computational results indicating that modulated HF heating can generate ionospheric currents in the ULF/ELF range even in the absence of electrojet currents. The new concept relies in using HF heating of the F-region to modulate the electron temperature and has been given the name Ionospheric Current Drive (ICD). The ICD is a two-step process: First, the pressure gradient associated with anomalous or collisional F-region electron heating drives a local diamagnetic current that acts as an antenna to inject mainly Magneto-Sonic (MS) waves in the ionospheric plasma. Second, the electric field associated with the MS wave drives Hall currents when it reaches the E region of the ionosphere. The Hall currents act as a secondary antenna that inject waves in the Earth-Ionosphere Waveguide (EIW) below and Shear Alfven (SA) waves upwards towards the conjugate regions. We will examine the scaling and limitations of the concept with simulation and suggest proof-of-principle experiments using the HAARP ionospheric heater. We will discuss the implications of freeing the ionospheric ULF/ELF generation from the requirement of electrojet availability and strength.
Identification of dendritic antigen-presenting cells in the zebrafish

In mammals, dendritic cells (DCs) form the key link between the innate and adaptive immune systems. DCs act as immune sentries in various tissues and, upon encountering pathogen, engulf and traffic foreign antigen to secondary lymphoid tissues, stimulating antigen-specific T lymphocytes. Although DCs are of fundamental importance in orchestrating the mammalian immune response, their presence and function in nonmammalian vertebrates is largely unknown. Because teleosts possess one of the earliest recognizable adaptive immune systems, we sought to identify antigen-presenting cells (APCs) in the zebrafish to better understand the potential origins of DCs and their evolutionary relationship to lymphocytes. Here we present the identification and characterization of a zebrafish APC subset strongly resembling mammalian DCs. Rare DCs are present in various adult tissues, and can be enriched by their affinity for the lectin peanut agglutinin (PNA). We show that PNAhi myeloid cells possess the classical morphological features of mammalian DCs as revealed by histochemical and ultrastructural analyses, phagocytose-labeled bacterial preparations in vivo, and exhibit expression of genes associated with DC function and antigen presentation, including il12, MHC class II invariant chain iclp1, and csf1r. Importantly, we show that PNAhi cells can activate T lymphocytes in an antigen-dependent manner. Together, these studies suggest that the cellular constituents responsible for antigen presentation are remarkably conserved from teleosts to mammals, and indicate that the zebrafish may serve as a unique model to study the origin of APC subsets and their evolutionary role as the link between the innate and adaptive immune systems.
Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins

Ullrich congenital muscular dystrophy is a severe genetically and clinically heterogeneous muscle disorder linked to collagen VI deficiency. The pathogenesis of the disease is unknown. To assess the potential role of mitochondrial dysfunction in the onset of muscle fiber death in this form of dystrophy, we studied biopsies and myoblast cultures obtained from patients with different genetic defects of collagen VI and variable clinical presentations of the disease. We identified a latent mitochondrial dysfunction in myoblasts from patients with Ullrich congenital muscular dystrophy that matched an increased occurrence of spontaneous apoptosis. Unlike those in myoblasts from healthy donors, mitochondria in cells from patients depolarized upon addition of oligomycin and displayed ultrastructural alterations that were worsened by treatment with oligomycin. The increased apoptosis, the ultrastructural defects, and the anomalous response to oligomycin could be normalized by Ca2+ chelators, by plating cells on collagen VI, and by treatment with cyclosporin A or with the specific cyclophilin inhibitor methylAla3ethylVal4-cyclosporin, which does not affect calcineurin activity. Here we demonstrate that mitochondrial dysfunction plays an important role in muscle cell wasting in Ullrich congenital muscular dystrophy. This study represents an essential step toward a pharmacological therapy of Ullrich congenital muscular dystrophy with cyclosporin A and methylAla3ethylVal4 cyclosporin.
Designing fuzzy net controllers using GA optimization

As plant specifications become complicated, more robust controller design methodologies are needed. A genetic algorithm optimizer, which utilizes natural evolution strategies, offers a promising technology that supports optimization of the parameters of fuzzy logic and other parameterized non-linear controllers. This paper shows how GAs can effectively and efficiently optimize the performance of parameterized non-linear controllers, such as fuzzy net controllers in a multiprocessor simulation environment. Our results demonstrate the advantage of a Computer-Aided System Design technique for rapid prototyping of control systems. <<ETX>>
Production of Monoclonal Antibodies

This unit describes the production of monoclonal antibodies beginning with immunization and cell fusion and selection. Support protocols are provided for screening primary hybridoma supernatants for antibodies of desired specificity, establishment of stable hybridoma lines, cloning of these B cell lines by limiting dilution to obtain monoclonal lines, and preparation of cloning/expansion medium (thymocyte‐conditioned medium).
Biologically-inspired Edge Detection Through Surround Modulation

Edges are key components of any visual scene to the extent that we can recognise objects merely by their silhouettes. The human visual system captures edge information through neurons in the visual cortex that are sensitive to both intensity discontinuities and particular orientations. The “classical approach” assumes that these cells are only responsive to the stimulus present within their receptive fields, however, recent studies demonstrate that surrounding regions and inter-areal feedback connections influence their responses significantly. In this work we propose a biologically-inspired edge detection model in which orientation selective neurons are represented through the first derivative of a Gaussian function resembling double-opponent cells in the primary visual cortex (V1). In our model we account for four kinds of surround, i.e. full, far, isoand orthogonal-orientation, whose contributions are contrast-dependant. The output signal from V1 is pooled in its perpendicular direction by larger V2 neurons employing a contrast-variant centre-surround kernel. We further introduce a feedback connection from higher-level visual areas to the lower ones. The results of our model on two benchmark datasets show a big improvement compared to the current non-learning and biologically-inspired state-of-the-art algorithms while being competitive to the learningbased methods.
Quality of Life, Anxiety and Depression among Patients with Chronic Obstructive Pulmonary Disease and their Spouses

Chronic obstructive pulmonary disease (COPD) could have a negative impact on quality of life (QoL) and is associated with anxiety and depression in both patients and informal caregivers. The aim of this study was to examine the relationships between anxiety, depression and QoL of both Jordanian patients with COPD and their spouses. The selected design used in this study was a cross-sectional, descriptive, correlational design. A total of 67 patients and spouses were interviewed in 2011, using self-administered questionnaires. Descriptive statistical analysis was applied. Bivariate correlation analysis was undertaken to examine the relationship between variables. The results showed that patients and spouses with high levels of anxiety and depression reported a poor QoL. Patients had a lower QoL than their spouses. A better understanding of patient and spouse psychological wellbeing and QoL will provide nurses with the information needed in terms of developing strategies for reducing patients’ and spouses’ anxiety and depression and thus improve their QoL. The health-service agencies and government should improve policy by improving family-centred services for both patients and spouses.
Site‐Specific Dephosphorylation of Tau of Apolipoprotein E‐Deficient and Control Mice by M1 Muscarinic Agonist Treatment

Abstract : Apolipoprotein E (apoE)‐deficient mice have memory deficits that are associated with synaptic loss of basal forebrain cholinergic projections and with hyperphosphorylation of distinct epitopes of the microtubuleassociated protein tau. Furthermore, treatment of apoEdeficient mice with the M1 selective agonist 1‐methylpiperidine‐4‐spiro‐(2'‐methylthiazoline) [AF 150(S)] abolishes their memory deficits and results in recovery of their brain cholinergic markers. In the present study, we used a panel of anti‐tau monoclonal antibodies to further map the tau epitopes that are hyperphosphorylated in apoE‐deficient mice and examined the effects of prolonged treatment with AF 150(S). This revealed that tau of apoE‐deficient mice contains a distinct, hyperphosphorylated “hot spot” domain which is localized N‐terminally to the microtubule binding domain of tau, and that AF150(S) has an epitope‐specific tau dephosphorylating effect whose magnitude is affected by apoE deficiency. Accordingly, epitopes which reside in the hyperphosphorylated “hot spot” are dephosphorylated by AF 150(S) in apoE‐deficient mice but are almost unaffected in the controls, whereas epitopes which flank this tau domain are dephosphorylated by AF150(S) in both mice groups. In contrast, epitopes located at the N and C terminals of tau are unaffected by AF150(S) in both groups of mice. These findings suggest that apoE deficiency results in hyperphosphorylation of a distinct tau domain whose excess phosphorylation can be reduced by muscarinic treatment.
Mitogen‐activated protein kinase expression and activation does not differentiate benign from malignant mesothelial cells

In vitro studies of malignant mesothelioma (MM) cells have suggested activation of mitogen‐activated protein kinase (MAPK) in response to asbestos exposure. The objective of this study was to investigate protein expression (level) and phosphorylation status (activity) of the extracellular‐regulated kinase (ERK), the c‐Jun amino‐terminal kinase (JNK), and the high‐osmolarity glycerol response kinase (p38) in vivo through the analysis of fresh frozen reactive mesothelium (RM) and MM specimens.