Electrostatic Turbulence and Debye-scale Structures in Collisionless Shocks

We present analysis of more than 100 large-amplitude bipolar electrostatic structures in a quasi-perpendicular supercritical Earth's bow shock crossing, measured by the Magnetospheric Multiscale spacecraft. The occurrence of the bipolar structures is shown to be tightly correlated with magnetic field gradients in the shock transition region. The bipolar structures have negative electrostatic potentials and spatial scales of a few Debye lengths. The bipolar structures propagate highly oblique to the shock normal with velocities (in the plasma rest frame) of the order of the ion-acoustic velocity. We argue that the bipolar structures are ion phase space holes produced by the two-stream instability between incoming and reflected ions. This is the first identification of the ion two-stream instability in collisionless shocks

M1 Polarization Markers Are Upregulated in Basal-Like Breast Cancer Molecular Subtype and Associated With Favorable Patient Outcome

Background: Breast cancer heterogeneity is an essential element that plays a role in the therapy response variability and the patient’s outcome. This highlights the need for more precise subtyping methods that focus not only on tumor cells but also investigate the profile of stromal cells as well as immune cells. Objectives: To mine publicly available transcriptomic breast cancer datasets and reanalyze their transcriptomic profiling using unsupervised clustering in order to identify novel subsets in molecular subtypes of breast cancer, then explore the stromal and immune cells profile in each subset using bioinformatics and systems immunology approaches. Materials and Methods: Transcriptomic data from 1,084 breast cancer patients obtained from The Cancer Genome Atlas (TCGA) database were extracted and subjected to unsupervised clustering using a recently described, multi-step algorithm called Iterative Clustering and Guide-gene Selection (ICGS). For each cluster, the stromal and immune profile was investigated using ESTIMATE and CIBERSORT analytical tool. Clinical outcomes and differentially expressed genes of the characterized clusters were identified and validated in silico and in vitro in a cohort of 80 breast cancer samples by immunohistochemistry. Results: Seven unique sub-clusters showed distinct molecular and clinical profiles between the well-known breast cancer subtypes. Those unsupervised clusters identified more homogenous subgroups in each of the classical subtypes with a different prognostic profile. Immune profiling of the identified clusters showed that while the classically activated macrophages (M1) are correlated with the more aggressive basal-like breast cancer subtype, the alternatively activated macrophages (M2) showed a higher level of infiltration in luminal A and luminal B subtypes. Indeed, patients with higher levels of M1 expression showed less advanced disease and better patient outcomes presented as prolonged overall survival. Moreover, the M1 high basal-like breast cancer group showed a higher expression of interferon-gamma induced chemokines and guanylate-binding proteins (GBPs) involved in immunity against microbes. Conclusion: Adding immune profiling using transcriptomic data can add precision for diagnosis and prognosis and can cluster patients according to the available modalities of therapy in a more personalized approach

Exploiting gelatin nanocarriers in the pulmonary delivery of methotrexate for lung cancer therapy.

Gelatin has many merits that encourage its use in the pulmonary delivery of anticancer drugs. It is a biodegradable denatured protein which possesses several functional groups that could be modified. Additionally, it has balanced hydrophilic and hydrophobic characters, which facilitate the loading of chemotherapeutic agents. Accordingly, the purpose of the current work was to exploit this valuable biomaterial in the efficient pulmonary delivery of methotrexate in case of lung cancer. Gelatin nanoparticles were prepared via a desolvation method and the fabrication process was optimized using Box Behnken design of experiment. A comparative study on uptake of gelatin nanoparticles by lung adenocarcinoma cells and macrophages was implemented using flow cytometry. Investigation of the effect of different methotrexate loading techniques: encapsulation, post loading and chemical conjugation on the nanoparticles characteristics and cellular cytotoxicity was performed. Nano-in-microparticles were prepared by co-spray drying optimized nanoparticles with leucine. Results showed that Box Behnken design was able to optimize preparation parameters to yield uniform nanoparticles with suitable particle size for cancer cells uptake. The prepared nanoparticles demonstrated a preferential uptake by lung cancer cells. Additionally, methotrexate loaded nanoparticles demonstrated up to four fold significant reduction in methotrexate IC50. The spray dried gelatin nano-in microparticles demonstrated good aerosolization properties enabling lung deposition in the respirable airways. Thus, providing a promising platform for lung cancer therapy

Development, Optimisation, Validation and Inter-Laboratory Verification of a Reversed Phase HPLC Method for Quantification of Human Recombinant Insulin

HPLC methods for insulin in official monographs require extended runtimes and elevated temperatures. Inter-laboratory reproducibility of HPLC methods obtained from published literature is an on-going challenge, moreso for peptides. This paper serves as a step-by step guide to troubleshoot and establish a validated HPLC method for insulin at room temperature using simple UV detectors with minimal run times. A modified gradient reversed-phase HPLC was developed for the quantification of recombinant human insulin with UV detection at room temperature. An octadecylsilica column was used as the stationary phase while the mobile phase consisted of solution A: 1mmol sodium sulphate and 0.2% triethylamine in water and solution B: acetonitrile. The developed method was then validated using International Conference on Harmonisation (ICH) guidelines. The calibration curve was linear over a concentration range of 10-1000 μg/mL with correlation coefficient of 0.9993, with average recovery percent of 100.89 ± 1.4% and RSD recovery of 0.01. Insulin retention time was 3.84 ± 0.08 mins, while LOD and LOQ were estimated at 0.63 and 2.0 μg/mL respectively. The developed method conformed to the validation criteria of the ICH guidelines in our laboratories and other independent operator laboratories, and can serve as a rapid and effective method for quantifying insulin from any sample at room temperature using simple detectors

Localization for a matrix-valued Anderson model

We study localization properties for a class of one-dimensional, matrix-valued, continuous, random Schr\"odinger operators, acting on L^2(\R)\otimes \C^N, for arbitrary $N\geq 1$. We prove that, under suitable assumptions on the F\"urstenberg group of these operators, valid on an interval $I\subset \R$, they exhibit localization properties on $I$, both in the spectral and dynamical sense. After looking at the regularity properties of the Lyapunov exponents and of the integrated density of states, we prove a Wegner estimate and apply a multiscale analysis scheme to prove localization for these operators. We also study an example in this class of operators, for which we can prove the required assumptions on the F\"urstenberg group. This group being the one generated by the transfer matrices, we can use, to prove these assumptions, an algebraic result on generating dense Lie subgroups in semisimple real connected Lie groups, due to Breuillard and Gelander. The algebraic methods used here allow us to handle with singular distributions of the random parameters

Co-pyrolysis of Rice Husk with Underutilized Biomass Species: A Sustainable Route for Production of Precursors for Fuels and Valuable Chemicals

In this study, co-pyrolysis of rice husk with underutilized biomass, Napier grass and sago waste was carried out in a fixed bed reactor at 600 �C, 30 �C/min and 5 L/min nitrogen flowrate. Two-phase bio-oil (organic and aqueous) was collected and characterized using standard analytical techniques. 34.13–45.55 wt% total boil-oil yield was recorded using assorted biomass compared to pure risk husk biomass with 31.51 wt% yield. The organic phase consist mainly benzene derivatives with higher proportion in the oil from the co-pyrolysis process relative to the organic phase from the pyrolysis of the individual biomass while the aqueous phase in all cases was predominantly water, acids, ketones, aldehydes, sugars and traces of phenolics. This study has demonstrated a good approach towards increasing valorization of rice husk in a single reaction step for the production of high grade bio-oil, which can be transformed into fuel and valuable chemicals

Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts

Both canonical and non-canonical Wnt signaling pathway alterations have been documented in pulmonary disease pathogenesis and progression; therefore, they can be an attractive target for pharmaceutical management of severe asthma. Wnt/β-catenin signaling was shown to link early embryonic lung development impairment to later in life asthmatic airway remodeling. Here we explored the changes in Wnt signaling associated with asthma initiation and progression in epithelial and fibroblasts using a comprehensive approach based on in silico analysis and followed by in vitro validation. In summary, the in silico analysis showed that the bronchial epithelium of severe asthmatic patients showed a deranged balance between Wnt enhancer and Wnt inhibitors. A Th2-high phenotype is associated with upregulated Wnt-negative regulators, while inflammatory and neutrophilic severe asthmatics showed higher canonical Wnt signaling member enrichment. Most of these genes are regulators of healthy lung development early in life and, if disturbed, can make people susceptible to developing asthma early in life and prone to developing a severe phenotype. Most of the Wnt members are secreted, and their effect can be in an autocrine fashion on the bronchial epithelium, paracrine on nearby adjacent structural cells like fibroblasts and smooth muscles, or systemic in blood. Our results showed that canonical Wnt signaling is needed for the proper response of cells to proliferative stimuli, which puts cells under stress. Cells in response to this proliferative stress will activate the senescence mechanism, which is also dependent on Wnt signaling. Inhibition of Wnt signaling using FH535 inhibits both proliferation and senescence markers in bronchial fibroblasts compared to DMSO-treated cells. In fibroblasts from asthmatic patients, inhibition of Wnt signaling did not show that effect as the Wnt signaling is deranged besides other pathways that might be non-functional

Confounding patient factors affecting the proper interpretation of the periostin level as a biomarker in asthma development

Introduction: The proper use of serum periostin (POSTN) as a biomarker for asthma is hindered by inconsistent performance in different clinical settings. Objective: To explore patient’s factors that may affect POSTN expression locally and systematically and its utility as a biomarker for asthma development. Materials and Methods: Here we used bioinformatics analysis of publicly available transcriptomics data to confirm that POSTN is an asthma specific gene involved in core signaling pathways enriched in the bronchial epithelium during asthma. We then explored a large number of datasets to identify possible confounders that may affect the POSTN gene expression and consequently, its interpretation as a reliable biomarker for asthma. Plasma and saliva levels of POSTN were determined in locally recruited asthmatic patients (mild, moderate and severe) compared to healthy controls to confirm the bioinformatics findings. Results: Our bioinformatics results confirmed that POSTN was consistently upregulated in the bronchial epithelium in asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) bronchial epithelium. In asthma, its mRNA expression was affected by gender, sample anatomical site and type, steroid therapy, and smoking. In our cohort, plasma POSTN was upregulated in severe and non-severe asthmatic patients. Saliva POSTN was significantly higher in non-severe asthmatic patients compared to healthy and severe asthmatic patients (specifically those who are not on Xolair (omalizumab)). Patients’ BMI, inhaled steroid use and Xolair treatment affected POSTN plasma levels. Conclusion: Up to our knowledge, this is the first study examining the level of POSTN in the saliva of asthmatic patients. Both plasma and saliva POSTN levels can aid in early diagnosis of asthma. Saliva POSTN level was more sensitive than plasma POSTN in differentiating between severe and non-severe asthmatics. Patients’ characteristics like BMI, the use of inhaled steroids, or Xolair treatment should be carefully reviewed before any meaningful interpretation of POSTN level in clinical practice

Holographic phase diagram of quark-gluon plasma formed in heavy-ions collisions

The phase diagram of quark gluon plasma (QGP) formed at a very early stage just after the heavy ion collision is obtained by using a holographic dual model for the heavy ion collision. In this dual model colliding ions are described by the charged shock gravitational waves. Points on the phase diagram correspond to the QGP or hadronic matter with given temperatures and chemical potentials. The phase of QGP in dual terms is related to the case when the collision of shock waves leads to formation of trapped surface. Hadronic matter and other confined states correspond to the absence of trapped surface after collision. Multiplicity of the ion collision process is estimated in the dual language as area of the trapped surface. We show that a non-zero chemical potential reduces the multiplicity. To plot the phase diagram we use two different dual models of colliding ions, the point and the wall shock waves, and find qualitative agreement of the results.Comment: 33 pages, 14 figures, typos correcte

Critical Trapped Surfaces Formation in the Collision of Ultrarelativistic Charges in (A)dS

We study the formation of marginally trapped surfaces in the head-on collision of two ultrarelativistic charges in $(A)dS$ space-time. The metric of ultrarelativistic charged particles in $(A)dS$ is obtained by boosting Reissner-Nordstr\"om $(A)dS$ space-time to the speed of light. We show that formation of trapped surfaces on the past light cone is only possible when charge is below certain critical - situation similar to the collision of two ultrarelativistic charges in Minkowski space-time. This critical value depends on the energy of colliding particles and the value of a cosmological constant. There is richer structure of critical domains in $dS$ case. In this case already for chargeless particles there is a critical value of the cosmological constant only below which trapped surfaces formation is possible. Appearance of arbitrary small nonzero charge significantly changes the physical picture. Critical effect which has been observed in the neutral case does not take place more. If the value of the charge is not very large solution to the equation on trapped surface exists for any values of cosmological radius and energy density of shock waves. Increasing of the charge leads to decrease of the trapped surface area, and at some critical point the formation of trapped surfaces of the type mentioned above becomes impossible.Comment: 30 pages, Latex, 7 figures, Refs. added and typos correcte