2,739 research outputs found

    TileProbe: modeling tiling array probe effects using publicly available data

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    Motivation: Individual probes on an Affymetrix tiling array usually behave differently. Modeling and removing these probe effects are critical for detecting signals from the array data. Current data processing techniques either require control samples or use probe sequences to model probe-specific variability, such as with MAT. Although the MAT approach can be applied without control samples, residual probe effects continue to distort the true biological signals

    Measuring geometric phases of scattering states in nanoscale electronic devices

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    We show how a new quantum property, a geometric phase, associated with scattering states can be exhibited in nanoscale electronic devices. We propose an experiment to use interference to directly measure the effect of the new geometric phase. The setup involves a double path interferometer, adapted from that used to measure the phase evolution of electrons as they traverse a quantum dot (QD). Gate voltages on the QD could be varied cyclically and adiabatically, in a manner similar to that used to observe quantum adiabatic charge pumping. The interference due to the geometric phase results in oscillations in the current collected in the drain when a small bias across the device is applied. We illustrate the effect with examples of geometric phases resulting from both Abelian and non-Abelian gauge potentials.Comment: Six pages two figure

    Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome

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    The human pangenome, a new reference sequence, addresses many limitations of the current GRCh38 reference. The first release is based on 94 high-quality haploid assemblies from individuals with diverse backgrounds. We employed a k-mer indexing strategy for comparative analysis across multiple assemblies, including the pangenome reference, GRCh38, and CHM13, a telomere-to-telomere reference assembly. Our k-mer indexing approach enabled us to identify a valuable collection of universally conserved sequences across all assemblies, referred to as “pan-conserved segment tags” (PSTs). By examining intervals between these segments, we discerned highly conserved genomic segments and those with structurally related polymorphisms. We found 60,764 polymorphic intervals with unique geo-ethnic features in the pangenome reference. In this study, we utilized ultra-conserved sequences (PSTs) to forge a link between human pangenome assemblies and reference genomes. This methodology enables the examination of any sequence of interest within the pangenome, using the reference genome as a comparative framework

    Novel non-heteroarylpyrimidine (HAP) capsid assembly modifiers have a different mode of action from HAPs in vitro

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    One of the most promising viral targets in current hepatitis B virus (HBV) drug development is the core protein due to its multiple roles in the viral life cycle. Here we investigated the differences in the mode of action and antiviral activity of representatives of six different capsid assembly modifier (CAM) scaffolds: three from the well-characterized scaffolds heteroarylpyrimidine (HAP), sulfamoylbenzamide (SBA), and phenylpropenamide (PPA), and three from novel scaffolds glyoxamide-pyrrolamide (GPA), pyrazolyl-thiazole (PT), and dibenzo-thiazepin-2-one (DBT). The target activity and antiviral efficacy of the different CAMs were tested in biochemical and cellular assays. Analytical size exclusion chromatography and transmission electron microscopy showed that only the HAP compound induced formation of aberrant non-capsid structures (class II mode of action), while the remaining CAMs did not affect capsid gross morphology (class I mode of action). Intracellular lysates from the HepAD38 cell line, inducibly replicating HBV, showed no reduction in the quantities of intracellular core protein or capsid after treatment with SBA, PPA, GPA, PT, or DBT compounds; however HAP-treatment led to a profound decrease in both. Additionally, immunofluorescence staining of compound-treated HepAD38 cells showed that all non-HAP CAMs led to a shift in the equilibrium of HBV core antigen (HBcAg) towards complete cytoplasmic staining, while the HAP induced accumulation of HBcAg aggregates in the nucleus. Our study demonstrates that the novel scaffolds GPA, PT, and DBT exhibit class I modes of action, alike SBA and PPA, whereas HAP remains the only scaffold belonging to class II inhibitors

    Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

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    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

    Atypical right diaphragmatic hernia (hernia of Morgagni), spigelian hernia and epigastric hernia in a patient with Williams syndrome: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Williams syndrome is rare genetic disorder resulting in neurodevelopmental problems. Hernias of the foramen of Morgagni are rare diaphragmatic hernias and they mostly present on the right side, in the anterior mediastinum. They are usually asymptomatic and are difficult to diagnose, especially in patients with learning disabilities.</p> <p>Case presentation</p> <p>This 49-year-old woman with Williams syndrome, cognitive impairment and aortic stenosis presented to physicians with right-sided chest pain. She had previously undergone repair of her right spigelian and epigastric hernia. Her abdominal examination was unremarkable. Chest X-ray suggested right-sided diaphragmatic hernia and pleural effusion for which she received treatment. The computed tomography scan showed a diaphragmatic hernia with some collapse/consolidation of the adjacent lung. Furthermore, the patient had aortic stenosis and was high risk for anaesthesia (ASA grade 3). She underwent successful laparoscopic repair of her congenital diaphragmatic hernia leading to a quick and uneventful postoperative recovery.</p> <p>Conclusion</p> <p>These multiple hernias suggest that patients with Williams syndrome may have some connective tissue disorder which makes them prone to develop hernias especially associated with those parts of the body which may have intracavity pressure variations like the abdomen. Diaphragmatic hernia may be the cause of chest pain in these patients. A computed tomography scan helps in early diagnosis, and laparoscopic repair helps in prevention of further complications, and leads to quick recovery especially in patients with learning disabilities. In the presence of significant comorbidities, a less invasive operative procedure with quick recovery becomes advisable.</p

    Full volume super-resolution imaging of thick mitotic spindle using 3D AO STED microscope

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    © 2019 Optical Society of America under the terms of the OSA Open Access Publishing. Stimulated emission depletion (STED) nanoscopy is one of a suite of modern optical microscopy techniques capable of bypassing the conventional diffraction limit in fluorescent imaging. STED makes use of a spiral phase mask to enable 2D super-resolution imaging whereas to achieve full volumetric 3D super-resolution an additional bottle-beam phase mask must be applied. The resolution achieved in biological samples 10 μm or thicker is limited by aberrations induced mainly by scattering due to refractive index heterogeneity in the sample. These aberrations impact the fidelity of both types of phase mask, and have limited the application of STED to thicker biological systems. Here we apply an automated adaptive optics solution to correct the performance of both STED masks, enhancing robustness and expanding the capabilities of this nanoscopic technique. Corroboration in terms of successful high-quality imaging of the full volume of a 15μm mitotic spindle with resolution of 50nm x 50nm x 150nm achieved in all three dimensions is presented

    Various Tumor-Mimicking Lesions in the Musculoskeletal System: Causes and Diagnostic Approach

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    Tumor-mimicking lesions in the musculoskeletal system can be defined as lesions mistaken as tumors due to the presence of palpation upon physical examination or a tumor-like appearance upon radiological examination. Moreover, tumor-mimicking lesions show diverse etiologies and anatomic locations. We illustrated the various tumor-mimicking lesions involving bone and soft tissue. In this review, the tumor-mimicking lesions were classified into those based on clinical examination and those based on radiological examination in musculoskeletal radiology. Awareness of the various causes of tumor-mimicking lesions, correctly obtaining clinical information, and the proper selection of imaging modality are important for the differentiation of tumor-mimicking lesions from true neoplasms
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