Liquid-Cell Electron Microscopy of Adsorbed Polymers

Individual macromolecules of polystyrene sulfonate and poly(ethylene oxide) are visualized with nanometer resolution using transmission electron microscopy (TEM) imaging of aqueous solutions with and without added salt, trapped in liquid pockets between creased graphene sheets. Successful imaging with 0.3 s per frame is enabled by the sluggish mobility of the adsorbed molecules. This study finds, validating others, that an advantage of this graphene liquid-cell approach is apparently to retard sample degradation from incident electrons, in addition to minimizing background scattering because graphene windows are atomically thin. Its new application here to polymers devoid of metal-ion labeling allows the projected sizes and conformational fluctuations of adsorbed molecules and adsorption–desorption events to be analyzed. Confirming the identification of the observed objects, this study reports statistical analysis of datasets of hundreds of images for times up to 100 s, with variation of the chemical makeup of the polymer, the molecular weight of the polymer, and the salt concentration. This observation of discrete polymer molecules in solution environment may be useful generally, as the findings are obtained using an ordinary TEM microscope, whose kind is available to many researchers routinely.

Direct real-space investigation of adsorbed polymer dynamics, with single-polymer resolution using conventional transmission electron microscopy (TEM) (transmission liquid microscope) and graphene liquid cell, gives a time series of polymer images which enable statistical analysis of projected sizes, conformational rearrangements, and adsorption dynamics. This demonstrates the capability to image polymers in solution using a conventional TEM.

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Response to "Role of regulators in safe prescribing of opioids" [Letters]

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Trends in standardized mortality among individuals with schizophrenia, 1993-2012: a population-based, repeated cross-sectional study [Research]

BACKGROUND:

We examined mortality time trends and premature mortality among individuals with and without schizophrenia over a 20-year period.

METHODS:

In this population-based, repeated cross-sectional study, we identified all individual deaths that occurred in Ontario between 1993 and 2012 in persons aged 15 and over. We plotted overall and cause-specific age- and sex-standardized mortality rates (ASMRs), stratified all-cause ASMR trends by sociodemographic characteristics, and analyzed premature mortality using years of potential life lost. Additionally, we calculated mortality rate ratios (MRRs) using negative binomial regression with adjustment for age, sex, income, rurality and year of death.

RESULTS:

We identified 31 349 deaths among persons with schizophrenia, and 1 589 902 deaths among those without schizophrenia. Mortality rates among people with schizophrenia were 3 times higher than among those without schizophrenia (adjusted MRR 3.12, 95% confidence interval 3.06–3.17). All-cause ASMRs in both groups declined in parallel over the study period, by about 35%, and were higher for men, for those with low income and for rural dwellers. The absolute ASMR difference also declined throughout the study period (from 16.15 to 10.49 deaths per 1000 persons). Cause-specific ASMRs were greater among those with schizophrenia, with circulatory conditions accounting for most deaths between 1993 and 2012, whereas neoplasms became the leading cause of death for those without schizophrenia after 2005. Individuals with schizophrenia also died, on average, 8 years younger than those without schizophrenia, losing more potential years of life.

INTERPRETATION:

Although mortality rates among people with schizophrenia have declined over the past 2 decades, specialized approaches may be required to close the persistent 3-fold relative mortality gap with the general population.

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Cabinet shuffle brings "seismic shifts" to Indigenous affairs, health [News]

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Rebound adrenal insufficiency after withdrawal of ritonavir in a 65-year-old man using inhaled budesonide [Practice]

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Treating iron deficiency [Correction]

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Take-home naloxone [Practice]

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Addressing the scandal of early death among people with schizophrenia [Commentary]

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Contact dermatitis caused by methacrylates in nail products [Practice]

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Sensible approaches to manage the current opioid crisis [Letters]

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Cobwebs [Humanities]

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Combating antibiotic resistance: New drugs or alternative therapies? [News]

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Role of regulators in safe prescribing of opioids [Letters]

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Overweight or overfat? Many Canadians are both [News]

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BAFF augments IgA2 and IL-10 production by TLR7/8 stimulated total peripheral blood B cells

Class-switching of B cells to IgA can be induced via both T cell-dependent and T cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection. To this end total and naive peripheral blood B cells were stimulated with these factors for 6 days in the presence or absence of TLR7/8 agonist R848 (mimicking viral infection) or TLR9 agonist CpG-ODN (mimicking bacterial infection). We show that BAFF significantly augments IgA2 production in TLR7/8 stimulated mature, but not naïve B cells. In addition, BAFF augments IL-10 production and viability in TLR7/8 and TLR9 stimulated mature B cells. These data warrants further investigation of its role in immune regulation both in the periphery and mucosal tissues in early life or during disease.

This article is protected by copyright. All rights reserved

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Immune Reconstitution Inflammatory Syndrome and Cytomegalovirus Pneumonia Case Report: Highlights and Missing Links in Classification Criteria and Standardized Treatment

Background. Cytomegalovirus (CMV) pulmonary involvement is rarely associated with IRIS; therefore, limited information is available. Case Presentation. Here, we describe the case of a 43-year-old HIV-infected male who developed an unusual case of IRIS after cytomegalovirus (CMV) pneumonia. Clinically there was a progressive and paradoxical worsening of respiratory distress, despite being treated for CMV after initiation with antiretroviral therapy. Chest X-ray revealed disseminated infiltrates in both lungs; chest CT-scan showed generalized lung involvement and mediastinal adenopathy. Pulmonary biopsy confirmed CMV pneumonia with the observation of typical viral inclusions on pneumocytes. Conclusions. CMV pneumonia can be associated with the development of IRIS requiring treatment with immunosuppressant's and immunomodulatory drugs.

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Correlation between Tissue Characterization and Dynamic Expression of Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Conjunctival Filtering Bleb of Rats

Purpose. Using rat conjunctival bleb model, we correlated changes morphology and histology in the bleb with changes in MMP-2 and TIMP-2 levels. Methods. Filtering surgeries were performed on rats. Dynamic changes in morphology and histopathology were observed using HE staining. Expression of MMP-2 and TIMP-2 was determined by immunofluorescence microscopy and western blotting. Results. Well-elevated filtering blebs formed and persisted for an average of 12 days. Histological examination showed that inflammatory was dominant in postoperative days 1–3, and proliferating manifestation became the main sign 5 days later. Western blot showed that MMP-2 was downregulated 1 day after surgery, upregulated at 3 days, and observed with a peak at 7 days; then it persisted until 28 days. The difference was statistically significant (F = 280.18, ).TIMP-2 was upregulated 1 day after surgery and observed with a peak at 5 days; then it persisted until 28 days. The difference was statistically significant (F = 145.34, ). Conclusions. During the processes of conjunctival filtering bleb and scar formation in rats, the changes in MMP-2 and TIMP-2 levels in the filtering area, together with a corresponding proliferation of fibroblasts and the accumulation of collagen fibres, resulted in scarring of filtering blebs.

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Citalopram Ameliorates Impairments in Spatial Memory and Synaptic Plasticity in Female 3xTgAD Mice

Alzheimer's disease (AD) is the primary cause of dementia. There is no effective treatment. Amyloid-β peptide (Aβ) plays an important role in the pathogenesis and thus strategies suppressing Aβ production and accumulation seem promising. Citalopram is an antidepressant drug and can decrease Aβ production and amyloid plaques in transgenic mice of AD and humans. Whether citalopram can ameliorate memory deficit was not known yet. We tested the effects of citalopram on behavioral performance and synaptic plasticity in female 3xTgAD mice, a well-characterized model of AD. Mice were treated with citalopram or water from 5 months of age for 3 months. Citalopram treatment at approximately 10 mg/kg/day significantly improved spatial memory in the Morris water maze (MWM) test, while not affecting anxiety-like and depression-like behavior in 3xTgAD mice. Further, hippocampal long-term potentiation (LTP) impairment in 3xTgAD mice was reversed by citalopram treatment. Citalopram treatment also significantly decreased the levels of insoluble Aβ40 in hippocampal and cortical tissues in 3xTgAD mice, accompanied with a reduced amyloid precursor protein (APP). Together, citalopram treatment may be a promising strategy for AD and further clinical trials should be conducted to verify the effect of citalopram on cognition in patients with AD or mild cognitive impairment.

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Foodborne Pathogen Screening Using Magneto-fluorescent Nanosensor: Rapid Detection of E. Coli O157:H7

The overall goal of this protocol is to synthesize functional nanosensors for the portable, cost-effective, and rapid detection of specifically targeted pathogenic bacteria through a combination of magnetic relaxation and fluorescence emission modalities.

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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy

Structures of supramolecular protein assemblies at atomic resolution are of high relevance because of their crucial roles in a variety of biological phenomena. Herein, we present a protocol to perform high-resolution structural studies on insoluble and non-crystalline macromolecular protein assemblies by magic-angle spinning solid-state nuclear magnetic resonance spectroscopy (MAS SSNMR).

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Incremental Value of Plaque Enhancement in Patients with Moderate or Severe Basilar Artery Stenosis: 3.0 T High-Resolution Magnetic Resonance Study

Aim. To investigate the clinical relevance of plaque's morphological characteristics and distribution pattern using 3.0 T high-resolution magnetic resonance imaging (HRMRI) in patients with moderate or severe basilar artery (BA) atherosclerosis stenosis. Materials and Methods. Fifty-seven patients (33 symptomatic patients and 24 asymptomatic patients) were recruited for 3.0 T HRMRI scan; all of them had >50% stenosis on the BA. The intraplaque hemorrhage (IPH), contrast-enhancement pattern, and distribution of BA plaques were compared between the symptomatic and asymptomatic groups. Factors potentially associated with posterior ischemic stroke were calculated by multivariate analyses. Results. Enhancement of BA plaque was more frequently observed in symptomatic than in asymptomatic patients (27/33, 81.8% versus 11/24, 45.8%; ). In multivariate regression analysis, plaque enhancement (OR = 7.193; 95% CI: 1.880–27.517; ) and smoking (OR = 4.402; 95% CI: 2.218–15.909; ) were found to be independent risk factors of posterior ischemic events in patients with BA stenosis >50%. Plaques were mainly distributed at the ventral site (39.3%) or involved more than two arcs (21.2%) in the symptomatic group but were mainly distributed at left (33.3%) and right (25.0%) sites in the asymptomatic group.

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Successful Treatment of Klebsiella pneumoniae Harboring a Klebsiella pneumoniae Carbapenemase Isolated from Lumbar Wound Infection and Blood in a Patient with Hardware Retention

Infections caused by carbapenem-resistant Enterobacteriaceae, especially carbapenemase producing Klebsiella pneumoniae, represent an urgent threat as outlined by the Centers for Disease Control and Prevention (CDC). We present a 66-year-old male with spinal stenosis who underwent elective L2-pelvis posterior spinal fusion at an outside institution and rapidly developed a complicated infection with Klebsiella pneumoniae harboring Klebsiella pneumoniae carbapenemase. This is the first described case of a patient with Klebsiella pneumoniae harboring Klebsiella pneumoniae carbapenemase causing postoperative lumbar wound infection and bacteremia, successfully treated with ceftazidime-avibactam in combination with additional synergistic antibacterials and without hardware removal.

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A Multiorgan Segmentation Model for CT Volumes via Full Convolution-Deconvolution Network

We propose a model with two-stage process for abdominal segmentation on CT volumes. First, in order to capture the details of organs, a full convolution-deconvolution network (FCN-DecNet) is constructed with multiple new unpooling, deconvolutional, and fusion layers. Then, we optimize the coarse segmentation results of FCN-DecNet by multiscale weights probabilistic atlas (MS-PA), which uses spatial and intensity characteristic of atlases. Our coarse-fine model takes advantage of intersubject variability, spatial location, and gray information of CT volumes to minimize the error of segmentation. Finally, using our model, we extract liver, spleen, and kidney with Dice index of 90.1 ± 1%, 89.0 ± 1.6%, and 89.0 ± 1.3%, respectively.

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Identification and Characterization of Oleaginous Yeast Isolated from Kefir and Its Ability to Accumulate Intracellular Fats in Deproteinated Potato Wastewater with Different Carbon Sources

The search for efficient oleaginous microorganisms, which can be an alternative to fossil fuels and biofuels obtained from oilseed crops, has been going on for many years. The suitability of microorganisms in this regard is determined by their ability to biosynthesize lipids with preferred fatty acid profile along with the concurrent utilization of energy-rich industrial waste. In this study, we isolated, characterized, and identified kefir yeast strains using molecular biology techniques. The yeast isolates identified were Candida inconspicua, Debaryomyces hansenii, Kluyveromyces marxianus, Kazachstania unispora, and Zygotorulaspora florentina. We showed that deproteinated potato wastewater, a starch processing industry waste, supplemented with various carbon sources, including lactose and glycerol, is a suitable medium for the growth of yeast, which allows an accumulation of over 20% of lipid substances in its cells. Fatty acid composition primarily depended on the yeast strain and the carbon source used, and, based on our results, most of the strains met the criteria required for the production of biodiesel. In particular, this concerns a significant share of saturated fatty acids, such as C16:0 and C18:0, and unsaturated fatty acids, such as C18:1 and C18:2. The highest efficiency in lipid biosynthesis exceeded 6.3 g L−1. Kazachstania unispora was able to accumulate the high amount of palmitoleic acid.

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Chronic Open Infective Lateral Malleolus Bursitis Management Using Local Rotational Flap

Background. Using a sinus tarsi rotational flap is an uncommon approach to treating chronic open infective lateral malleolus bursitis. Methods. We treated eight patients, including six males, using this approach. First, we debrided all the infected tissues and used a negative pressure wound closure system where needed. After acute infection had been controlled, the local rotational flap was used for cases where the wound could not be closed by a simple suture or bone exposure. The rotational flap was detached with a curved skin incision at the sinus tarsi next to the open wound and sutured to the defect, paying careful attention to the superficial peroneal nerve. The donor site was managed with a split-thickness skin graft. Results. The patients' mean age was 74.1 years. Six patients had a wound after suppurative infection, but two patients had ulcer-type bursitis. Six patients demonstrated full flap healing, but two patients had venous congestion necrosis. Conclusion. A sinus tarsi rotational flap is a useful method to ensure healing and coverage of chronic open lateral malleolus bursitis, especially for small to medium wounds with cavity and bone exposure.

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Biatractylolide Modulates PI3K-Akt-GSK3β-Dependent Pathways to Protect against Glutamate-Induced Cell Damage in PC12 and SH-SY5Y Cells

Biatractylolide, isolated from the ethyl acetate extract of Atractylodes macrocephala, has shown various pharmacological activities such as antitumor and antioxidant activities. In this work, we aim to study the protective effect of biatractylolide on glutamate-induced rat adrenal pheochromocytoma cell (PC12) and human bone marrow neuroblastoma cell line (SH-SY5Y) injury and preliminarily explore its mechanism. The results showed that glutamate was cytotoxic with an inhibitory concentration 50% (IC50) of 8.5 mM in PC12 and 10 mM in SH-SY5Y cells. In this work, the preincubation with biatractylolide (10, 15, and 20 M) observably improved cell viability, inhibited the apoptosis of cells induced by glutamate, and reduced the activity of LDH. AO staining revealed that apoptosis of cells was decreased. Additionally, the results of western blotting manifested that pretreatment with biatractylolide could downregulate GSK3 protein expression and upregulate p-Akt protein expression, thereby protecting PC12 and SH-SY5Y cells from injury. All these findings indicate that biatractylolide has a neuroprotective effect on glutamate-induced injury in PC12 and SH-SY5Y cells through a mechanism of the PI3K-Akt-GSK3-dependent pathways.

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Guanxintai Exerts Protective Effects on Ischemic Cardiomyocytes by Mitigating Oxidative Stress

Oxidative stress participates in numerous myocardial pathophysiological processes and is considered a therapeutic target for myocardial ischemia and heart failure. Guanxintai (GXT), a traditional Chinese medicine, is commonly used to treat cardiovascular disease on account of its numerous beneficial physiological activities, such as dilating coronary arteries, inhibiting platelet aggregation, and reducing the serum lipid content. However, the antioxidative properties of GXT and potential underlying mechanisms remain to be established. In the present study, we investigated the protective effects of GXT on ischemic cardiomyocytes and the associated antioxidative mechanisms, both in vivo and in vitro. Notably, GXT treatment reduced the degree of cardiomyocyte injury, myocardial apoptosis, and fibrosis and partially improved cardiac function after myocardial infarction. Furthermore, GXT suppressed the level of ROS as well as expression of NADPH oxidase (NOX) and phospho-p38 mitogen-activated protein kinase (MAPK) proteins. Our results collectively suggest that the protective effects of GXT on ischemic cardiomyocytes are exerted through its antioxidative activity of NOX inhibition.

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Royal Jelly Inhibits Pseudomonas aeruginosa Adherence and Reduces Excessive Inflammatory Responses in Human Epithelial Cells

Pseudomonas aeruginosa is a Gram-negative bacterium and causes respiratory infection especially in elderly patients. Royal jelly has been used worldwide as a traditional remedy and as a nutrient; however, the effect against P. aeruginosa is unclear. The aim of this study was to analyze antibacterial, antiadherent, and anti-inflammatory effects of royal jelly against P. aeruginosa. Wild-type strain PAO1 and clinical isolates of P. aeruginosa were used for antibacterial assay and antiadherent assay to abiotic surface and epithelial cells, which are pharynx (Detroit 562) and lung (NCI-H292) epithelial cells. In anti-inflammatory assay, epithelial cells were pretreated with royal jelly before bacterial exposure to investigate its inhibitory effect on interleukin (IL-8) and macrophage inflammatory protein-3α/CCL20 overproduction. Although royal jelly did not have antibacterial activity at concentration of 50% w/v, antiadherent activity was confirmed on the abiotic surface and epithelial cells under concentration of 25%. Pretreatment with royal jelly significantly inhibited overproduction of IL-8 and CCL20 from both cells. These results demonstrated that royal jelly inhibits P. aeruginosa adherence and protects epithelial cells from excessive inflammatory responses against P. aeruginosa infection. Our findings suggested that royal jelly may be a useful supplement as complementary and alternative medicine for preventing respiratory infection caused by P. aeruginosa.

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A stress-induced cellular aging model with postnatal neural stem cells

A stress-induced cellular aging model with postnatal neural stem cells

Cell Death and Disease 8, e3041 (September 2017). doi:10.1038/cddis.2017.445

Authors: C-M Dong, X-L Wang, G-M Wang, W-J Zhang, L Zhu, S Gao, D-J Yang, Y Qin, Q-J Liang, Y-L Chen, H-T Deng, K Ning, A-B Liang, Z-L Gao & J Xu

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Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis

Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis

Cell Death and Disease 8, e3037 (September 2017). doi:10.1038/cddis.2017.394

Authors: Xiao Chen, Xin Zhi, Liehu Cao, Weizong Weng, Panpan Pan, Honggang Hu, Chao Liu, Qingjie Zhao, Qirong Zhou, Jin Cui & Jiacan Su

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LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer

LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer

Cell Death and Disease 8, e3039 (September 2017). doi:10.1038/cddis.2017.393

Authors: Hao-Zhe Cao, Xiao-Fang Liu, Wen-Ting Yang, Qing Chen & Peng-Sheng Zheng

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Acceleration of pancreatic tumorigenesis under immunosuppressive microenvironment induced by Reg3g overexpression

Acceleration of pancreatic tumorigenesis under immunosuppressive microenvironment induced by Reg3g overexpression

Cell Death and Disease 8, e3033 (September 2017). doi:10.1038/cddis.2017.424

Authors: Xiulan Liu, Zhongshi Zhou, Qi Cheng, Hongjie Wang, Hui Cao, Qianqian Xu, Yali Tuo, Li Jiang, You Zou, Hongyu Ren & Ming Xiang

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Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease

Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease

Cell Death and Disease 8, e3040 (September 2017). doi:10.1038/cddis.2017.436

Authors: Nunzio Ranaldo, Giuseppe Losurdo, Andrea Iannone, Mariabeatrice Principi, Michele Barone, Massimo De Carne, Enzo Ierardi & Alfredo Di Leo

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Abcb1a and Abcb1b genes function differentially in blood–testis barrier dynamics in the rat

Abcb1a and Abcb1b genes function differentially in blood–testis barrier dynamics in the rat

Cell Death and Disease 8, e3038 (September 2017). doi:10.1038/cddis.2017.435

Authors: Linlin Su, Yan C Cheng, Will M Lee, Min Zhang, Fangfang Yang, Bin Zhao, Daishu Han, Yixun Liu & Dahai Hu

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Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers

Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers

Cell Death and Disease 8, e3045 (September 2017). doi:10.1038/cddis.2017.440

Authors: Rimi Hamam, Dana Hamam, Khalid A Alsaleh, Moustapha Kassem, Waleed Zaher, Musaad Alfayez, Abdullah Aldahmash & Nehad M Alajez

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A Survey of the Use of Iterative Reconstruction Algorithms in Electron Microscopy

One of the key steps in Electron Microscopy is the tomographic reconstruction of a three-dimensional (3D) map of the specimen being studied from a set of two-dimensional (2D) projections acquired at the microscope. This tomographic reconstruction may be performed with different reconstruction algorithms that can be grouped into several large families: direct Fourier inversion methods, back-projection methods, Radon methods, or iterative algorithms. In this review, we focus on the latter family of algorithms, explaining the mathematical rationale behind the different algorithms in this family as they have been introduced in the field of Electron Microscopy. We cover their use in Single Particle Analysis (SPA) as well as in Electron Tomography (ET).

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