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تقنية بلوكتشين في إنترنت الأشياء
يناقش الكتاب دمج تقنية البلوك تشين مع الإنترنت من الأشياء (IoT) لتشكيل ما يعرف بـB‑IoT، مركزا على البنية المعمارية، وأهم التقنيات، وقضايا الأمن والخصوصية في أنظمة IoT، ثم يستعرض التطبيقات العملية مثل خدمات ربط المركبات بالشبكة، وتبادل الكهرباء في السيارات، ومشاركة الركوب والتوثيق الإلكتروني عبر بلوك تشين. يحتوي على إطار تصميم نموذجي، ومشاريع تطبيقية (مثل محاكاة شبكة Ethereum محلية، وتطبيقات في سلسلة التوريد والتجارة التعاونية) يدمج بين الجوانب النظرية والعملية ليمنح الباحثين والمتخصصين فهما عميقا لكيفية استخدام البلوك تشين لتعزيز اللامركزية، الموثوقية، العدم قابلية التعديل، وقابلية التدقيق في نظم IoT، مع عرض اتجاهات مستقبلية ومجالات بحث واعدة في المجال.
BOOK
Development of a visual multiplex fluorescent LAMP assay for the detection of foot-and-mouth disease, vesicular stomatitis and bluetongue viruses
Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that can be used to amplify target genes at a constant temperature, and it has several advantages, including convenience, specificity and sensitivity. However, due to the special interpretation methods of this technology for reaction results, all the previously reported LAMP detection methods have been restricted to identifying a single target, which limits the application of this technology. In this study, we modified conventional LAMP to include a quencher-fluorophore composite probe complementary to the F1c segment of the inner primer FIP; upon strand separation, a gain in the visible fluorescent signal was observed. The probes could be labeled with different fluorophores, showing different colors at the corresponding wavelengths. Therefore, this multiplex LAMP (mLAMP) assay can simultaneously detect 1–3 target sequences in a single LAMP reaction tube, and the results are more accurate and intuitive. In this study, we comprehensively demonstrated a single-reaction mLAMP assay for the robust detection of three cattle viruses without nonspecific amplification of other related pathogenic cattle viruses. The detection limit of this mLAMP assay was as low as 526–2477 copies/reaction for the recombinant plasmids. It is expected that this mLAMP assay can be widely used in clinical diagnosis.
Journal Article
Diplomacy of quasi-alliances in the Middle East
Quasi-alliance refers to the ideation, mechanism and behavior of policy-makers to carry out security cooperation through informal political and security arrangements. As a \"gray zone\" between alliance and neutrality, quasi-alliance is a hidden national security statecraft. Based on declassified archives and secondary sources, this book probes the theory and practice of quasi-alliances in the Middle East. Four cases are chosen to test the hypotheses of quasi-alliance, one of which is the Anglo-French-Israeli quasi-alliance during the Suez Canal War of 1956.
Book
Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues
Background
Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.
Methods
We compared
ACE2
expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s
t
test. We also investigated the correlations between
ACE2
expression and immune signatures in various tissues using Pearson’s correlation test.
Results
ACE2
expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle.
ACE2
showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland.
ACE2
was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels,
ACE2
expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs,
ACE2
expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.
Conclusions
Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
Journal Article
Viral dynamics in mild and severe cases of COVID-19
Patients who had any of the following features at the time of, or after, admission were classified as severe cases: (1) respiratory distress (≥30 breaths per min); (2) oxygen saturation at rest ≤93%; (3) ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air ≤300 mm Hg; or (4) severe disease complications (eg, respiratory failure, requirement of mechanical ventilation, septic shock, or non-respiratory organ failure). Parameters did not differ significantly between the groups, except that patients in the severe group were significantly older than those in the mild group, as expected.4 No patient died from the infection. 23 (77%) of 30 severe cases received intensive care unit (ICU) treatment, whereas none of the mild cases required ICU treatment. All samples were collected according to WHO guidelines.5 The mean viral load of severe cases was around 60 times higher than that of mild cases, suggesting that higher viral loads might be associated with severe clinical outcomes.
Journal Article
Downregulation of miR‐491‐5p promotes gastric cancer metastasis by regulating SNAIL and FGFR4
Gastric cancer (GC) is among the most fatal cancers in China. MicroRNAs (miRNAs) are versatile regulators during GC development and progression. miR‐491‐5p has been demonstrated to act as a tumor suppressor in several types of cancer. However, the role of miR‐491‐5p in GC metastasis remains unknown. Here, we found that miR‐491‐5p was significantly decreased in GC tissues compared with adjacent non‐cancerous tissues, and low miR‐491‐5p level was associated with large tumor size. Overexpression of miR‐491‐5p significantly suppressed GC cell epithelial‐to‐mesenchymal transition (EMT) and tumor metastasis in vitro and in vivo. Mechanistically, SNAIL was identified as a direct target of miR‐491‐5p. The silencing of SNAIL phenocopied the tumor suppressive function of miR‐491‐5p, whereas re‐expression of SNAIL in GC cells rescued the EMT markers and cell migratory ability that were inhibited by miR‐491‐5p. In addition, miR‐491‐5p inhibited FGFR4 indirectly. Inhibition of FGFR4 also decreased the SNAIL level and impaired EMT and cell migration. Taken together, these findings indicate that downregulation of miR‐491‐5p promoted GC metastasis by inducing EMT via regulation of SNAIL and FGFR4. miR‐491‐5p is remarkably downregulated in gastric cancer. Restoration of miR‐491‐5p could effectively inhibited tumor growth and metastasis. We discovered that miR‐491‐5p directly targeted SNAIL and indirectly inhibited FGFR4, resulted in suppressed EMT and tumor metastasis.
Journal Article
MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer
Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU. Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Our results suggest that the restoration of microRNA‐375‐3p levels could be a future novel therapeutic strategy to modulate and enhance chemosensitivity to 5‐fluorouracil treatment in CRC.
Journal Article
A single mutation in the prM protein of Zika virus contributes to fetal microcephaly
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution [Ser139→Asn139 (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
Journal Article
Calculating the most likely intron splicing orders in S. pombe, fruit fly, Arabidopsis thaliana, and humans
Background
Introns have been shown to be spliced in a defined order, and this order influences both alternative splicing regulation and splicing fidelity, but previous studies have only considered neighbouring introns. The detailed intron splicing order remains unknown.
Results
In this work, a method was developed that can calculate the intron splicing orders of all introns in each transcript. A simulation study showed that this method can accurately calculate intron splicing orders. I further applied this method to real
S. pombe
, fruit fly,
Arabidopsis thaliana
, and human sequencing datasets and found that intron splicing orders change from gene to gene and that humans contain more not in-order spliced transcripts than
S. pombe
, fruit fly and
Arabidopsis thaliana
. In addition, I reconfirmed that the first introns in humans are spliced slower than those in
S. pombe
, fruit fly, and
Arabidopsis thaliana
genome-widely. Both the calculated most likely orders and the method developed here are available on the web.
Conclusions
A novel computational method was developed to calculate the intron splicing orders and applied the method to real sequencing datasets. I obtained intron splicing orders for hundreds or thousands of genes in four organisms. I found humans contain more number of not in-order spliced transcripts.
Journal Article