bluuebunny/crossref_metadata_2025 huggingface dataset:
The regulated expression of an intrabody produces a mutant phenotype in Drosophila
Authors: Hassanzadeh Gh Gholamreza , Devoogdt Nick , Ghysen Alain , De Baetselier Patrick , Muyldermans Serge , Dambly-Chaudière Christine
Published: July 2002

Intrabodies show great promise for controlling gene expression. As an initial attempt to evaluate the intrabody technology in Drosophila, the gene poxn was used as target. Transgenic flies harboring different anti‐Poxn scFv genes integrated into various chromosomes were obtained. In one transformant, a phenocopy resembling the hypomorphic poxn
− phenotype was produced in embryos and larvae following induction of expression of α‐Poxn2 intrabody. The antisense approach was used as control. Parameters that can affect the success of intrabody technology are described.
Mutations at position 1122 in the catalytic domain of the mouse ras‐specific guanine nucleotide exchange factor CDC25Mm originate both loss‐of‐function and gain‐of‐function proteins
Authors: Carrera Vittorio , Moroni Andrea , Martegani Enzo , Volponi Celina , Cool Robbert H. , Alberghina Lilia , Vanoni Marco
Published: July 2002

The role of two residues within the catalytic domain of CDC25Mm, a mouse ras‐specific guanine nucleotide exchange factor (GEF), was investigated by site‐directed mutagenesis. The function of the mutant proteins was tested in vivo in both a Saccharomyces cerevisiae cdc25 complementation assay and in a mammalian fos‐luciferase assay, and in in vitro assays on human and yeast Ras proteins. Mutants CDC25 and CDC25 were shown to be (partly) inactive proteins, similar to their yeast homologs. Mutant CDC25 showed higher nucleotide exchange activity than the wild type protein on the basis of both in vitro and in vivo assays. Thus, alanine and valine substitutions at position 1122 within the GEF catalytic domain originate mutations with opposite biological properties, indicating an important role for position 1122 in GEF function.
The internal Cys‐207 of sorghum leaf NADP‐malate dehydrogenase can form mixed disulphides with thioredoxin
Authors: Goyer Aymeric , Decottignies Paulette , Lemaire Stephane , Ruelland Eric , Issakidis-Bourguet Emmanuelle , Jacquot Jean-Pierre , Miginiac-Maslow Myroslawa
Published: July 2002

The role of the internal Cys‐207 of sorghum NADP‐malate dehydrogenase (NADP‐MDH) in the activation of the enzyme has been investigated through the examination of the ability of this residue to form mixed disulphides with thioredoxin mutated at either of its two active‐site cysteines. The h‐type Chlamydomonas thioredoxin was used, because it has no additional cysteines in the primary sequence besides the active‐site cysteines. Both thioredoxin mutants proved equally efficient in forming mixed disulphides with an NADP‐MDH devoid of its N‐terminal bridge either by truncation, or by mutation of its N‐terminal cysteines. They were poorly efficient with the more compact WT oxidised NADP‐MDH. Upon mutation of Cys‐207, no mixed disulphide could be formed, showing that this cysteine is the only one, among the four internal cysteines, which can form mixed disulphides with thioredoxin. These experiments confirm that the opening of the N‐terminal disulphide loosens the interaction between subunits, making Cys‐207, located at the dimer contact area, more accessible.
Antisense oligonucleotides against receptor kinase GRK2 disrupt target selectivity of β‐adrenergic receptors in atrial myocytes
Authors: Wellner-Kienitz Marie-Cécile , Bender Kirsten , Brandts Bodo , Meyer Thomas , Pott Lutz
Published: July 2002

K+ channels composed of GIRK subunits are predominantly expressed in the heart and various regions of the brain. They are activated by βγ‐subunits released from pertussis toxin‐sensitive G‐proteins coupled to different seven‐helix receptors. In rat atrial myocytes, activation of K(ACh) channels is strictly limited to receptors coupled to pertussis toxin‐sensitive G‐proteins. Upon treatment of myocytes with antisense oligodesoxynucleotides against GRK2, a receptor kinase with Gβγ binding sites, in a fraction of cells, K(ACh) channels can be activated by β‐adrenergic receptors. Sensitivity to β‐agonist is insensitive to pertussis toxin treatment. These findings demonstrate a potential role of Gβγ binding proteins for target selectivity of G‐protein‐coupled receptors
The CCAAT‐box binding factor NF‐Y is required for the expression of phospholipid hydroperoxide glutathione peroxidase in human epidermoid carcinoma A431 cells
Authors: Huang Huei-Sheng , Chen Ching-Jiunn , Chang Wen-Chang
Published: July 2002

Promoter activation in the expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) gene in human epidermoid carcinoma A431 cells was studied in the present investigation. Luciferase reporter assays with plasmids carrying a 400 bp of the promoter DNA were performed to analyze the regulatory element in the proximal promoter of human PHGPx gene. Transient transfection with a series of 5′‐deletion and internal truncation mutants showed that the 5′‐flanking region spanning from −212 to −121 bp was important for the basal expression of PHGPx gene in A431 cells. A region from −170 to −140 bp was protected in DNase I footprinting assays and bound the nuclear proteins in electrophoretic mobility shift assays. This region, denoted FP3, contains the consensus recognition sites for AP‐2, CCAAT‐box and CRE. The oligonucleotide competitor with the mutation at CCAAT‐box could not eliminate the nuclear protein binding in gel‐shift assay and the site‐directed mutagenesis at the CCAAT‐box decreased the luciferase activity of PHGPx promoter for approximate 50% in reporter gene assays. Competition experiments indicate that the binding of nuclear factor to the FP3 region was abolished by oligodeoxyribonucleotide corresponding to NF‐Y/CP1 binding site to a greater extent than by those corresponding to sites for CTF/NFI and C/EBP. Taken together, the CCAAT‐box in the promoter ranging from −156 to −151 bp, bound to NF‐Y/CP1, was essential for the basal expression of human PHGPx gene in A431 cells.
A negatively charged region of the skeletal muscle ryanodine receptor is involved in Ca2+‐dependent regulation of the Ca2+ release channel
Authors: Hayek Salim M. , Zhao Jiying , Bhat Manjunatha , Xu Xuehong , Nagaraj Ramakrishnan , Pan Zui , Takeshima Hiroshi , Ma Jianjie
Published: July 2002

The ryanodine receptor/Ca2+ release channels from skeletal (RyR1) and cardiac (RyR2) muscle cells exhibit different inactivation profiles by cytosolic Ca2+. D3 is one of the divergent regions between RyR1 (amino acids (aa) 1872–1923) and RyR2 (aa 1852–1890) and may contain putative binding site(s) for Ca2+‐dependent inactivation of RyR. To test this possibility, we have deleted the D3 region from RyR1 (ΔD3‐RyR1), residues 1038–3355 from RyR2 (Δ(1038–3355)‐RyR2) and inserted the skeletal D3 into Δ(1038–3355)‐RyR2 to generate sD3‐RyR2. The channels formed by ΔD3‐RyR1 and Δ(1038–3355)‐RyR2 are resistant to inactivation by mM [Ca2+], whereas the chimeric sD3‐RyR2 channel exhibits significant inactivation at mM [Ca2+]. The ΔD3‐RyR1 channel retains its sensitivity to activation by caffeine, but is resistant to inactivation by Mg2+. The data suggest that the skeletal D3 region is involved in the Ca2+‐dependent regulation of the RyR1 channel.
Hypertrophic stimuli augment expression of cMG1/ERF‐1, a putative zinc‐finger motif transcription factor, in rat cardiomyocytes
Authors: Manabe Tomohiro , Fukuda Keiichi , Pan Jing , Nagasaki Koichi , Yamaguchi Ken , Ogawa Satoshi
Published: July 2002

We isolated the gene for cMG1/ERF‐1, a known putative zinc‐finger transcription factor, by differential display of mRNA extracted from cardiomyocytes with and without leukemia inhibitory factor (LIF) stimulation. LIF induced cMG1/ERF‐1 mRNA at 15 min, and levels peaked at 10‐fold initial levels at 30 min. cMG1/ERF‐1 expression was inhibited by AG490 (JAK2 inhibitor) and genistein, but was unaffected by PD98059 or wortmannin. Phenylephrine, angiotensin II and endothelin‐1 also induced cMG1/ERF‐1 expression. Mechanical stretch in vitro and acute pressure overload in vivo increased cMG1/ERF‐1 expression. To our knowledge, this is the first report showing that the cMG1/ERF‐1 gene can be induced by various hypertrophic stimuli, and that Janus kinase 2 is involved in this process.
Expression of brain Gi protein in the aging F344 rat following exposure to corticosterone
Authors: Maines Lynn W. , Polavarapu Rathnagiri , Lakoski Joan M.
Published: July 2002

G protein expression has been shown to be modulated by circulating plasma corticosterone in young animals. A loss of G protein expression regulation by corticosterone in the elderly could explain declines in the function of G protein‐coupled receptors and their effective signal transduction processes in the nervous system found in normal and pathological aging. In this study, adrenalectomized 3‐ and 18‐months‐old female Fischer 344 rats were exposed to low, moderate or high levels of plasma corticosterone to determine the effect of this hormone on Gi protein expression in the hippocampus and frontal cortex. Basal Gi protein expression, assessed by Western blot analysis, did not vary across age in either brain region. Hippocampal Gi protein levels increased following moderate and high corticosterone administration in the 3‐months old animals (125% ; P < 0.05) but not in the 18‐months old animals. In contrast, in the frontal cortex, Gi protein expression increased significantly in the 18‐months‐old group (93% ; P < 0.05) following exposure to high concentrations of corticosterone. These results suggest that steroid hormones, specifically corticosterone, may differentially modulate neurotransmitter‐G protein coupling in an age‐dependent manner.
Microbial and Enzymatic Polysaccharides
Authors: Kralj Slavko , Khandige Surabhi , Guan Rong , Boetkjaer Kenneth , Behabtu Natnael , Lenges Christian , Hennessey Susan , Sworn Graham
Published: December 2020

Polysaccharides are ubiquitous and the largest substantive material class in nature (eg, structural in plants (cellulose, starch), algae (alginate), and (microbes) and throughout history polysaccharides have found extensive use in many industrial applications, for example in packaging (paper and board), fiber and textiles (eg, cotton and viscose), adhesives, and even in early engineered thermoplastic materials (eg, cellulose esters). Sourced from nature and in general biocompatible, many polysaccharides have applications across various food and food additive applications. The broad functionality and general good compatibility are attractive properties increasingly desired as focus on sustainability is increasing.

This article will discuss the established product range of microbial polysaccharides utilized across a range of specialty applications such as food, personal care, and industrials. Product categories such as alginates, bacterial cellulose, curdlan, dextran, diutan, emulsan, fructan, gellan, pullulan, sceroglucan, succinoglycan, welan, and xanthan gum will be reviewed.

In addition, the emerging platform technology enzymatic polymerization is discussed with special focus on the transformational promise for this approach toward engineered polysaccharide structures. This approach allows for the rational and systematic design of polysaccharide materials controlling aspects such as molecular weight, branching, and particle morphology.
Well‐Defined Poly(Ester Amide)‐Based Homo‐ and Block Copolymers by One‐Pot Organocatalytic Anionic Ring‐Opening Copolymerization of N‐Sulfonyl Aziridines and Cyclic Anhydrides
Authors: Xu Jiaxi , Hadjichristidis Nikos
Published: December 2020

We report a new synthetic methodology for poly(ester amide)s by anionic ring‐opening copolymerization of N‐sulfonyl aziridines and cyclic anhydrides. Phosphazenes organocatalysts have been found to promote a highly‐active, controlled, and selective alternating copolymerization in the absence of any competitive side reaction (zwitterionic mechanism and exchange transacylations). Mechanistic studies have shown first‐order dependence of the copolymerization rate in N‐sulfonyl aziridines and phosphazenes, and zero‐order in cyclic anhydrides. This one‐pot methodology leads not only to homopolymers but also to poly(ester amide)‐based block copolymers. Two catalytic cycles involving ring‐opening alternating copolymerization of N‐sulfonyl aziridines with cyclic anhydrides and ring‐opening polymerization of N‐sulfonyl aziridines have been proposed to explain the one pot synthesis of poly(ester amide)‐based homo‐ and block copolymers.
Template‐Mediated Control over Polymorphism in the Vapor‐Assisted Formation of Zeolitic Imidazolate Framework Powders and Films
Authors: Tu Min , Kravchenko Dmitry E. , Xia Benzheng , Rubio‐Giménez Víctor , Wauteraerts Nathalie , Verbeke Rhea , Vankelecom Ivo F. J. , Stassin Timothée , Egger Werner , Dickmann Marcel , Amenitsch Heinz , Ameloot Rob
Published: December 2020

The landscape of possible polymorphs for some metal–organic frameworks (MOFs) can pose a challenge for controlling the outcome of their syntheses. Demonstrated here is the use of a template to control in the vapor‐assisted formation of zeolitic imidazolate framework (ZIF) powders and thin films. Introducing a small amount of either ethanol or dimethylformamide vapor during the reaction between ZnO and 4,5‐dichloroimidazole vapor results in the formation of the porous ZIF‐71 phase, whereas other conditions lead to the formation of the dense ZIF‐72 phase or amorphous materials. Time‐resolved in situ small‐angle X‐ray scattering reveals that the porous phase is metastable and can be transformed into its dense polymorph. This transformation is avoided through the introduction of template vapor. The porosity of the resulting ZIF powders and films was studied by N2 and Kr physisorption, as well as positron annihilation lifetime spectroscopy. The templating principle was demonstrated for other members of the ZIF family as well, including the ZIF‐7 series, ZIF‐8_Cl, and ZIF‐8_Br.
Enhanced photocatalytic performance by Y‐doped BiFeO3 particles derived from MOFs precursor based on band gap reduction and oxygen vacancies
Authors: Li Zhendong , Cheng Li , Zhang Ke , Wang Zhenhua
Published: December 2020

In order to improve the photocatalytic performance of BiFeO3, we prepared BiFeO3 nanoparticles doped with different molar concentrations of Y by thermal decomposition of MOFs precursor. The samples were characterized by XRD, TG, FESEM, XPS, UV‐vis, and PL. The results of XRD and XPS reveal that Y3+ have been successfully incorporated into BiFeO3 lattice. FESEM and UV‐vis results reveal that Y doping leads to a decrease in BiFeO3 particle size and band gap. PL shows that the recombination rate of photogenerated electron hole pairs of Bi0.95Y0.05FeO3 is the lowest. The influences of Y doping content on photocatalytic activity of BiFeO3 have been investigated. The results show that the best photocatalytic activity is Bi0.95Y0.05FeO3. Compared with pure BiFeO3, Bi0.95Y0.05FeO3 increased the degradation rate of MO by 1.3 times in 120 min. This may be due to the larger light response range and the lower photogenerated electron hole pairs recombination rate.
Influence of forming method of blending versus casting layer‐by‐layer on structural properties and packing performances of casein‐gelatin composite edible film under different appending proportion
Authors: Qian Fang , Gao Xiaoxi , Li Li , Safian Murad Mian , Mu Guangqing , Wu Xiaomeng
Published: December 2020

In order to obtain casein edible films with great packing performance, gelatin as the reinforcing additive with different ratios were loaded via two methods including layer‐ by‐ layer and blending. A comparative study on structure properties between double layers and blending films made from casein and gelatin was obtained by scanning electron microscopy and Fourier transform infrared spectroscopy. The difference between the films' packing characters were conducted by water vapor permeability (WVP), optical property, and mechanical properties (including tensile strength (TS) and elongation (EAB)). The results showed that the degree of films roughness increased and the structural stability decreased as the increase of gelatin additive ratio in both double layers and blending films. Thickness and WVP both displayed a trend of increasing first then decreasing at the dividing of gelatin instead of casein in 50%. Importantly, WVP values in double layers film with a largest value of 6.95 gm−1Pa−1s−1was higher than blending films, observably (P < 0.05). Additionally, TS in blending film was increased by 23.44% than double layers film under the gelatin additive proportion of 70%, and EAB value in double layers film was larger by 207.65% than blending film under the gelatin additive proportion of 10%.
Mitochondrial phylogeography reveals high haplotype diversity and unique genetic lineage in Indian dugongs (Dugong dugon)
Authors: Srinivas Yellapu , Pande Anant , Gole Swapnali , Jothi P.V.R. Prem , Magesh K. Madhu , Pathan Sameeha , Dudhat Sohini , Shekar Rukmini , Ghanekar Chinmaya , Kukadia Devanshi , Johnson Jeyaraj Antony , Mondol Samrat , Sivakumar Kuppusamy
Published: December 2020

India plays a significant role in dugong conservation by having the largest population within South Asia. The status of dugongs in India is largely unknown due to a paucity of reliable ecological data. This study generated mitochondrial control region sequences from ~10% of dugong individuals from existing populations within India. Furthermore, data generated in this study were compared with the global data to assess genetic lineages, population structure, and genetic diversity of Indian populations.

Multiple analyses suggest that the Indian dugong populations are part of a single genetic cluster, comprising South Asia, North‐west Indian Ocean, and South‐west Indian Ocean populations. Despite small population size, they retain high genetic diversity with unique mitochondrial DNA haplotypes within South Asia. Within India, novel haplotypes are observed from all dugong habitats sampled, with overall high haplotype diversity (0.85 ± 0.04) but low nucleotide diversity (0.005 ± 0.001). Indian populations exhibit genetic differentiation with higher within‐population variance (63.41%) than among populations (36.59%). Two of the haplotypes observed in India are shared with Sri Lanka, implying genetic connectivity between these populations.

The genetic data from Indian dugong populations provide critical insights into the identification of dugong corridors and important dugong conservation zones in India. We suggest site‐specific interventions, including the creation of new marine protected areas and boundary reorganization and expansion of other existing protected areas, to ensure population connectivity. In addition, simultaneous efforts towards seagrass meadow restoration, reduction of dugong mortalities, and community participation in dugong conservation are recommended for population recovery of this threatened marine herbivore.
Pharmacodynamics‐based approach for efficacious human dose projection of BMS‐986260, a small molecule transforming growth factor beta receptor 1 inhibitor
Authors: Parrish Karen E. , Swanson Jesse , Cheng Lihong , Luk Emily , Stetsko Paul , Smalley James , Shu Yue‐Zhong , Huang Jinwen , Pabalan Jonathan G. , Sun Yongnian , Zvyaga Tatyana , Cvijic Mary Ellen , Burke James , Borzilleri Robert , Murtaza Anwar , Augustine Karen , Yang Zheng
Published: December 2020

Transforming growth factor beta (TGF‐β) is a pleiotropic cytokine that has a wide array of biological effects. For decades, tumor biology implicated TGF‐β as an attractive therapeutic target due to its immunosuppressive effects. Toward this end, multiple pharmaceutical companies developed a number of drug modalities that specifically target the TGF‐β pathway. BMS‐986260 is a small molecule, selective TGF‐βR1 kinase inhibitor that was under preclinical development for oncology. In vivo studies across mouse, rat, dog, and monkey and cryopreserved hepatocytes predicted human pharmacokinetics (PK) and distribution of BMS‐986260. Efficacy studies of BMS‐986260 were undertaken in the MC38 murine colon cancer model, and target engagement, as measured by phosphorylation of SMAD2/3, was assessed in whole blood to predict the clinical efficacious dose. The human clearance is predicted to be low, 4.25 ml/min/kg. BMS‐986260 provided a durable and robust antitumor response at 3.75 mg/kg daily and 1.88 mg/kg twice‐daily dosing regimens. Phosphorylation of SMAD2/3 was 3.5‐fold less potent in human monocytes than other preclinical species. Taken together, the projected clinical efficacious dose was 600 mg QD or 210 mg BID for 3 days followed by a 4‐day drug holiday. Mechanism‐based cardiovascular findings in the rat ultimately led to the termination of BMS‐986260. This study describes the preclinical PK characterization and pharmacodynamics‐based efficacious dose projection of a novel small molecule TGF‐βR1 inhibitor.
A sensitive and efficient LC–MS/MS method for the bioanalysis of fosinopril diacid from human plasma and its application for a bioequivalence study in humans
Authors: Bhende Swati D. , Varanasi Murali Balaram , Abbulu Konde
Published: December 2020

Fosinopril diacid is an angiotensin converting enzyme inhibitor with efficient antihypertensive action. It is an active metabolic product formed in the body from hydrolysis of its prodrug Fosinopril. A sensitive, rapid method with high recovery for Fosinopril diacid from human plasma was developed. Solid‐phase extraction technique employing Waters Oasis SPE cartridges gave clean samples with very high recovery of 97%. The analyte along with its internal standard (Benazepril hydrochloride) were chromatographed on an XTerra RP8 column (4.6 × 50 mm, 5 μm) using methanol–ammonium acetate buffer (10 mm; 90:10, v/v) as the mobile phase. A triple quadrupole mass spectrometer equipped with electrospray ionization source operated in the negative ion mode was used for detection. Multiple reaction monitoring scan mode was used for monitoring the transitions from m/z 434.00 → 237.15 for Fosinopril diacid and m/z 423.10 → 174.00 for Benazepril hydrochloride. Beer–Lambert’s law was obeyed in the range of 0.50–1,500.00 ng/ml (r = 0.9993). The stability of the drugs in human plasma and in stock solution was proved by performing stability tests as per US Food and Drug Administration guidelines. The method was successfully applied for a bioequivalence study of Fosinopril diacid in 36 healthy, adult, male volunteers under fasting conditions.
Pyoderma gangrenosum confined to the irradiated chest wall of the reconstructed breast
Authors: Hammond Jacob B. , Pflibsen Lacey R. , Kruger Erwin A. , Casey William J. , Noland Shelley S. , Lettieri Salvatore C. , Rebecca Alanna M. , Struve Sara L. , Teven Chad M.
Published: December 2020

Pyoderma gangrenosum (PG) is a diagnosis of exclusion worsened by surgical debridement. This report presents two atypical manifestations of PG in the reconstructed breast, whereby the disease is only confined to the irradiated chest wall tissue bed, sparing the abdominal donor sites and the contralateral reconstructed breast.
Tuning the Molecular Packing of Self‐Assembled Amphiphilic PtII Complexes by Varying the Hydrophilic Side‐Chain Length
Authors: Herkert Lorena , Selter Philipp , Daniliuc Constantin G. , Bäumer Nils , Palakkal Jasnamol P. , Fernández Gustavo , Hansen Michael Ryan
Published: December 2020

Understanding the relationship between molecular design and packing modes constitutes one of the major challenges in self‐assembly and is essential for the preparation of functional materials. Herein, we have achieved high precision control over the supramolecular packing of amphiphilic PtII complexes by systematic variation of the hydrophilic side‐chain length. A novel approach of general applicability based on complementary X‐ray diffraction and solid‐state NMR spectroscopy has allowed us to establish a clear correlation between molecular features and supramolecular ordering. Systematically increasing the side‐chain length gradually increases the steric demand and reduces the extent of aromatic interactions, thereby inducing a gradual shift in the molecular packing from parallel to a long‐slipped organization. Notably, our findings highlight the necessity of advanced solid‐state NMR techniques to gain structural information for supramolecular systems where single‐crystal growth is not possible. Our work further demonstrates a new molecular design strategy to modulate aromatic interaction strengths and packing arrangements that could be useful for the engineering of functional materials based on PtII and aromatic molecules.
Sb6O7(SO4)2: A Promising Ultraviolet Nonlinear Optical Material with an Enhanced Second‐Harmonic‐Generation Response Activated by SbIII Lone‐Pair Stereoactivity
Authors: Wei Qi , He Chao , Wang Kui , Duan Xiao‐Fang , An Xing‐Tao , Li Jin‐Hua , Wang Guo‐Ming
Published: December 2020

The stereochemical activity of lone pairs (SCALP) in a cation favors the formation of acentric materials and can enhance the second‐harmonic‐generation (SHG) response and/or the birefringence. By introducing functional SbIII into sulfates, an anhydrous sulfate of Sb6O7(SO4)2 (1) is explored. Sb3+ cations are in seesaw configurations and in‐phase aligned in a 3D asymmetric dense structure. Compound 1 exhibits an enhanced phase‐matching SHG response, a moderate birefringence, a wide transparency window, and considerable environmental stabilities, which result in it being a promising UV nonlinear optical (NLO) material. Theoretical studies reveal that the stereoactive lone pairs on Sb3+ cations make the predominant contribution to the SHG effect. This work will attract more interest from scientists for research into SCALP‐cation‐based NLO materials.
Analysis of Mobility Effects in Particle‐Gas Flows by Particle‐Resolved LBM‐DEM Simulations
Authors: Rosemann Tony , Reinecke Simon R. , Kruggel‐Emden Harald
Published: December 2020

Particle‐resolved direct numerical simulations are performed to simulate the flow through particle assemblies that are either static or freely moving to demonstrate the influence of particle mobility. To obtain a comprehensive understanding for this influence essential parameters such as the Reynolds number, solids volume fraction, particle‐fluid density ratio, collision parameters and particle shape are varied. The influence of particle mobility is assessed by evaluating the particle‐fluid forces, the particle ensemble structure and particle velocities. It is found that the ability of existing correlations for static particle systems to predict drag and lift forces correctly in dynamic particle‐gas flows is limited and that drift forces perpendicular to the drag force play an important role.
CFD‐DEM simulation of wall sheeting and particles charge in fluidized beds
Authors: Kazemi Saman , Zarghami Reza , Mostoufi Navid , Sotudeh‐Gharebagh Rahmat
Published: December 2020

The effect of the electrostatic charge of particles was investigated in fluidized beds with conductive and nonconductive walls. For this purpose, changes in the wall surface charge density and particle contact time near the wall were examined. Computational fluid dynamics/discrete element method (CFD‐DEM) was utilized to simulate the accumulation of particle and wall‐induced electrostatic charges in a quasi‐two‐dimensional fluidized bed. Particles and walls were initially considered neutral and gained charge with time. The simulations showed that aggregated particles are formed due to the presence of the opposite electrostatic charges. Agglomerates are produced by joining the aggregated particles together. Agglomerates have a layered‐like structure and are made of positive and negative particles. Accumulation of these agglomerates and aggregated particles on the wall forms wall sheeting, which has a layered‐like structure. In other words, particles do not accumulate on the wall individually. A significant accumulation of particles near the wall was seen in the presence of electrostatic charges compared with the neutral bed. Also, the contact time of particles on the wall in the conductive case was more prolonged than in the nonconductive case. The results indicate that the CFD‐DEM approach is a helpful technique for predicting particles behaviour in the presence of the electrostatic charge.
Nye tray vs sieve tray: A comparison based on computational fluid dynamics and tray efficiency
Authors: Abbasnia Sadegh , Nasri Zarrin , Shafieyoun Vali , Golzarijalal Mohammad
Published: December 2020

Nye and sieve trays were hydrodynamically simulated and compared. The simulations were performed in a Eulerian‐Eulerian framework under unsteady (transient) conditions at industrial scale. Conducted on an air‐water system, the simulations included three dimensions and two phases. The velocity distribution across the tray, the height of clear liquid, the froth height, and the pressure drop were investigated and compared with experimental data. Péclet number was calculated using hydrodynamic and geometric parameters. The tray efficiencies were also predicted to further compare the two trays. The results showed that the liquid flow was steadier on the Nye tray rather than the sieve tray, possibly because of the special structure of the liquid and gas inlets for the Nye tray.
Safety, Tolerability, and Pharmacokinetics of PF‐06823859, an Anti–Interferon β Monoclonal Antibody: A Randomized, Phase I, Single‐ and Multiple‐Ascending‐Dose Study
Authors: Neelakantan Srividya , Oemar Barry , Johnson Kristen , Rath Natalie , Salganik Mikhail , Berman Gabe , Pelletier Kathleen , Cox Lori , Page Karen , Messing Dean , Tarabar Sanela
Published: December 2020

This double‐blind, randomized, placebo‐controlled, dose‐ascending, first‐in‐human study (NCT02766621) assessed the safety, tolerability, and pharmacokinetics (PK) of PF‐06823859, an anti–interferon β monoclonal antibody. Healthy subjects were randomized to single ascending doses (SADs) of intravenous PF‐06823859 30, 100, 300, 900, or 2000 mg or placebo; to multiple ascending doses (MADs) of subcutaneous PF‐06823859 100 or 300 mg or placebo (once every 2 weeks for a total of 3 doses); or to MAD of intravenous PF‐06823859 600 mg or placebo (once every 3 weeks or once every 4 weeks for a total of 2 doses). The incidence, severity, and causal relationship of adverse events (AEs) were assessed, along with immunogenicity and PK. In total, 62 subjects were randomized to treatment (SAD, n = 35; MAD, n = 27). There were 76 treatment‐emergent all‐causality AEs in the SAD (PF‐06823859: n = 25; placebo: n = 4) and MAD (PF‐06823859: n = 40; placebo: n = 7) cohorts. In the SAD cohorts, all treatment‐emergent all‐causality AEs were mild in severity; 4 AEs of moderate severity were identified in the MAD cohorts. No dose‐limiting AEs, serious AEs, treatment‐related discontinuations, dose reductions, or deaths occurred. PF‐06823859 exposure increased dose‐proportionally, with half‐life values ranging between 23 and 35 days. The estimated subcutaneous bioavailability was 43% to 44%. Immunogenicity incidence rates were low (antidrug antibodies, 12.5%; neutralizing antibodies, 2.1%). No immunogenically related clinical responses of concern were observed. In conclusion, PF‐06823859 demonstrated an acceptable safety, tolerability, and PK profile that supports clinical development for treating disorders associated with increased interferon β levels, such as dermatomyositis or systemic lupus erythematosus.
Trained immunity as a novel approach against COVID‐19 with a focus on Bacillus Calmette–Guérin vaccine: mechanisms, challenges and perspectives
Authors: Sohrabi Yahya , Dos Santos Jéssica Cristina , Dorenkamp Marc , Findeisen Hannes , Godfrey Rinesh , Netea Mihai G , Joosten Leo AB
Published: December 2020

COVID‐19 is a severe health problem in many countries and has altered day‐to‐day life in the whole world. This infection is caused by the SARS‐CoV‐2 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID‐19. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette–Guérin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non‐specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID‐19. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS‐CoV‐2 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID‐19 severity.
A corner truncated fractal slot ultrawide spectrum sensing antenna for wireless cognitive radio sensor network
Authors: Goswami Pankaj Kumar , Goswami Garima
Published: December 2020

Due to the scarcity of the radio frequency spectrum, the emergent network sharing technique elicits the efficient use of licensed unutilized spectrum. Here, an ultra‐wideband (UWB) microstrip antenna is proposed for wireless cognitive radio sensor network (WCRSN). The antenna is uniquely designed for large spectrum scanning of channel vacancies in licensed frequency bands. Software‐defined radios (SDR) govern the algorithmic controls on spectrum sensing and channel interface using an appropriate antenna. The antenna comprises the effects of fractal slot patch and electromagnetic bandgap (EBG) ground structures on 12 × 18 × 1.6 mm3 FR4 (relative dielectric constant of 4.4) substrate. Circular polarization is achieved through corner truncation to make antenna orientation free in wireless sensing networks. The measured |S11| parameter offers 0.75‐ to 12‐GHz wide spectrum sensing with 2.51‐dBi average gain. The antenna is unique in compactness and includes lower edge bands of frequencies (0.75–3.1 GHz) along with UWB (3.1–12.0 GHz) for a very wide range scanning to utilize vacant channel opportunity in WCRSN through SDR. The proposed structure is experimented and validated for real‐time wideband scanning of the frequency spectrum within the operating limit as per the allotted FCC standard.
Anion Directed Selective Synthesis of Supramolecular Metallocycles and Related Coordination Dimers
Authors: Sturm Lisa , Göb Christian R. , Oppel Iris M.
Published: December 2020

The reaction of C3‐symmetric tris‐(2‐pyridinylene‐N‐oxide)triaminoguanidinium salts ([H3L]X) and zinc(II) in presence of thiocyanate and different carboxylate ions as co‐ligands yields in a series of different coordination compounds. Supramolecular metallocycles and carboxylate‐bridged dimers are defined by two fundamentally different binding motifs. By adjusting the co‐ligands’ stoichiometry, metallocycles and carboxylate‐bridged compounds can be synthesized selectively. Furthermore, the occupation of the metallocycles with co‐ligands can also be controlled that way. Directed synthesis of these metallocycles is essential for further application in host‐guest chemistry due to their cavities and porosity in the solid state.
The value of including families in the treatment of anorexia nervosa
Authors: Treasure Janet , Parker Stacey , Oyeleye Oyenike , Harrison Amy
Published: December 2020

The aim of this paper is to consider family and wider carer involvement in the treatment of anorexia nervosa, and how this can be used to add value to services. We discuss widely adopted interventions involving the family that have been manualised and studied in trials that have outcome measures that are of relevance to illness costs. The therapeutic targets of these interventions range from a focus on feeding to the wellbeing of the whole family. The theoretical models that underpin interventions involving the family/wider carers include both intra and interpersonal processes, with the exception of family‐based therapy, which in its original form holds an agnostic stance towards aetiology. Although formal evaluation of the cost effectiveness of these interventions is minimal, there is evidence that involving the family can reduce bed use and improve the wellbeing of both patients and family members. Moreover, for the most part, these interventions are acceptable to patients and carers. Finally, we consider how these approaches can be disseminated and scaled up more widely into services.
Hydrothermal alteration and mineralization of Baiyun gold deposit in Liaodong Peninsula, North China Craton
Authors: Zhang Zhichao , Wang Yuwang , Li Dedong , Wang Wei , Li Shenghui , Qiu Jinzhu , Lai Chunkit , Li Xiang
Published: December 2020

Baiyun deposit is a large gold deposit in the Liaodong Peninsula (North China Craton), containing over 31.7 t of gold. Silicic alteration, K‐feldspar alteration, and pyritization are well developed and closely related with mineralization in Baiyun deposit. Based on field and optical microscopic observations, the alteration styles include quartz + K‐feldspar zone, pyrite + sericite +quartz zone, and chlorite zone from orebody outward. In this study, the quartz, K‐feldspar, and pyrite of pre‐ore, syn‐ore stages 1 and 2 were selected for LA‐ICP‐MS trace element analysis and electron probe microanalysis (EPMA) to reveal the alteration‐mineralization link. Results show that the albite was altered to mainly K‐feldspar and minor secondary quartz at syn‐ore stage 1. Fluid‐rock reaction of the silicic‐potassic alteration may have decreased the fluid oxygen fugacity (fO2), which triggered the gold precipitation. Most of invisible gold occurred in the form of solid solution. At syn‐ore stage 2, albite altered to mainly quartz and minor K‐feldspar. The syn‐ore stage 1 K‐feldspar also altered to minor secondary quartz at syn‐ore stage 2. In addition, the release of sulphur from the syn‐ore stage 1 pyrite was likely another trigger for the gold precipitation. Most of syn‐ore stage 2 invisible gold occurred as nano‐particles. The ore‐forming fluids consist mainly of primary magmatic fluids mixed with minor metamorphic fluids. The ore metals may have sourced mainly from the magmatic fluid and the sillimanite‐mica schist of the Gaixian Formation.
Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study
Authors: Eksteen Bertus , Bowlus Christopher L. , Montano‐Loza Aldo J. , Lefebvre Eric , Fischer Laurent , Vig Pamela , Martins Eduardo Bruno , Ahmad Jawad , Yimam Kidist K. , Pockros Paul J. , Feld Jordan J. , Minuk Gerald , Levy Cynthia
Published: December 2020

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C‐C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC. This was a single‐arm, open‐label, exploratory study of CVC in adults with a clinical diagnosis of PSC, serum alkaline phosphatase (ALP) ≥1.5 times the upper limit of normal (ULN), with or without inflammatory bowel disease, across eight sites in the United States and Canada. The primary endpoint was percent change in ALP over 24 weeks; key secondary efficacy endpoints were proportion of participants who achieved ALP normalization and overall response (decrease to <1.5 times the ULN or 50% decrease). Of the 24 participants, 20 completed the study. The mean age was 43 years, 50% were female, and the mean body mass index was 25 kg/m2. From a median ALP baseline of 369 U/L (range: 173, 1,377 U/L), a median absolute reduction of 49.5 U/L (range: −460, 416 U/L) was achieved at week 24, corresponding to a median reduction of 18.0% (range: −46%, 89%). No participant achieved ALP normalization or a 50% decrease; 2 participants (10%) achieved a reduction in ALP to < 1.5 times the ULN, and 4 had ≥25% increase. Twenty participants (83.3%) reported at least one adverse event; most were mild to moderate in severity. The most frequent events were rash, fatigue, and dizziness. Conclusion: After 24 weeks of CVC treatment, adults with PSC achieved a modest reduction (median 18%) in the surrogate endpoint of ALP. CVC was well tolerated, and no new safety signals were observed. ClinicalTrials.gov identifier: NCT02653625.
Separate signaling events control TCR downregulation and T cell activation in primary human T cells
Authors: van der Donk Lieve E. H. , Ates Louis S. , van der Spek Jet , Tukker Laura M. , Geijtenbeek Teunis B. H. , van Heijst Jeroen W. J.
Published: December 2020

Introduction

T‐cell antigen receptor (TCR) interaction with cognate peptide:MHC complexes trigger clustering of TCR:CD3 complexes and signal transduction. Triggered TCR:CD3 complexes are rapidly internalized and degraded in a process called ligand‐induced TCR downregulation. Classic studies in immortalized T‐cell lines have revealed a major role for the Src family kinase Lck in TCR downregulation. However, to what extent a similar mechanism operates in primary human T cells remains unclear.

Methods

Here, we developed an anti‐CD3‐mediated TCR downregulation assay, in which T‐cell gene expression in primary human T cells can be knocked down by microRNA constructs. In parallel, we used CRISPR/Cas9‐mediated knockout in Jurkat cells for validation experiments.

Results

We efficiently knocked down the expression of tyrosine kinases Lck, Fyn, and ZAP70, and found that, whereas this impaired T cell activation and effector function, TCR downregulation was not affected. Although TCR downregulation was marginally inhibited by the simultaneous knockdown of Lck and Fyn, its full abrogation required broad‐acting tyrosine kinase inhibitors.

Conclusions

These data suggest that there is substantial redundancy in the contribution of individual tyrosine kinases to TCR downregulation in primary human T cells. Our results highlight that TCR downregulation and T cell activation are controlled by different signaling events and illustrate the need for further research to untangle these processes.
The progress of magnetic sensor applied in biomedicine: A review of non‐invasive techniques and sensors
Authors: Li Yongying , Cheng Hui , Alhalili Zahrah , Xu Guiying , Gao Guo
Published: December 2020

With the rapid development of sensing technology, it has attracted tremendous interests in the field of biomedicine because of its good biocompatibility, reliability, and safety. In comparison to other sensors, magnetic sensor has a broad application prospect in biomedical field due to its high sensitivity, small size, and intriguing non‐invasive detection property. The purpose of this review is to discuss the applications of magnetic sensors in the biomedical field. First, some widely used magnetic sensors are reviewed based on their working principle and characteristics. Then, the applications of magnetic sensors in biomedical field are introduced from the aspects of magnetic label‐based bioassays, detection of biological movement, and biology magnetism. Finally, the future development direction and prospect of magnetic sensors in biomedical field are prospected. This review will provide a general outlook for the applications of magnetic sensors in biomedicine.
Amoebic colitis: A case series of a recurring missed diagnosis
Authors: Abasszade Joshua Haron , Little Robert , Yeaman Fiona , Robertson Marcus , Bell Sally
Published: December 2020

Entamoeba histolytica, a pathogenic protozoan that causes amoebiasis, remains the second leading cause of death from parasitic infections worldwide. We present a case series of patients presenting to metropolitan tertiary gastroenterology units in Melbourne, Australia, highlighting the complexities of diagnosing amoebic colitis and the potential for misdiagnosis. These cases illustrate four key lessons in the identification of amoebic colitis: (i) obtaining a thorough travel and exposure history, (ii) having a high index of suspicion, (iii) understanding the limitations of available investigations, and (iv) being aware that amoebic colitis may masquerade as other common conditions.
Fully automated detection and differentiation of pandemic and endemic coronaviruses (NL63, 229E, HKU1, OC43 and SARS‐CoV‐2) on the hologic panther fusion
Authors: Cordes Anne K. , Rehrauer William M. , Accola Molly A. , Wölk Benno , Hilfrich Birgitta , Heim Albert
Published: December 2020

The hologic panther fusion (PF) platform provides fully automated CE marked diagnostics for respiratory viruses, including the recently discovered severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) by a transcription mediated amplification (TMA) assay, but not for the endemic human coronaviruses (hCoV). Therefore, a laboratory developed test (LDT) comprising a multiplexed reverse transcription polymerase chain reaction (RT‐PCR) protocol that detects and differentiates the four hCoV NL63, 229E, HKU1, and OC43 was adapted on the PF. The novel CE marked Aptima SARS‐CoV‐2 TMA and the LDT for hCoV were validated with 321 diagnostic specimens from the upper and lower respiratory tract in comparison to two SARS‐CoV‐2 RT‐PCRs (PF E‐gene RT‐PCR and genesig RT‐PCR, 157 specimens) or the R‐GENE hCoV/hParaFlu RT‐PCR (164 specimens), respectively. For the endemic hCoV, results were 96.3% concordant with two specimens discordantly positive in the PF and four specimens discordantly positive in the R‐GENE assay. All discordantly positive samples had Ct values between 33 and 39. The PF hCoV LDT identified 23 hCoV positive specimens as NL63, 15 as 229E, 15 as HKU1, and 25 as OC43. The Aptima SARS‐CoV‐2 TMA gave 99.4% concordant results compared to the consensus results with a single specimen discordantly positive. Moreover, 36 samples from proficiency testing panels were detected and typed correctly by both novel methods. In conclusion, the SARS‐CoV‐2 TMA and the LDT for hCoV enhanced the diagnostic spectrum of the PF for all coronaviruses circulating globally for a multitude of diagnostic materials from the upper and lower respiratory tract.
Interspecific differences, plastic, and evolutionary responses to a heat wave in three co‐occurring Daphnia species
Authors: Vanvelk Héléne , Govaert Lynn , van den Berg Edwin M. , Brans Kristien I. , De Meester Luc
Published: December 2020

Many studies document genetic and phenotypic trait changes of species in response to climate change, or document how evolution of individual species can impact population abundances and community composition. An integration of population and community‐level responses requires, however, a multiple species approach. Here we quantify among‐ and within‐species differences in thermal tolerance and life‐history traits in three co‐occurring Daphnia species upon exposure to a naturally occurring heat wave. Populations of randomly isolated clones of Daphnia magna, Daphnia pulicaria, and Daphnia galeata from the same pond were exposed to a natural heat wave in outdoor mesocosms. We subsequently conducted a common garden experiment in the laboratory using clonal lineages isolated at the end of the mesocosm selection experiment, at two rearing temperatures, measuring thermal tolerance and life‐history traits. We find pronounced plasticity responses to higher rearing thermal regime in each study species. We observe only few significant microevolutionary responses involving evolution of plasticity in D. pulicaria. Yet in terms of effect size, evolutionary trait change within species contributes more than 25% to total trait change in response to the heat wave for a majority of the trait × species combinations. The relative importance of intraspecific to interspecific variation varies widely among traits. Our results show that the relative importance of interspecific variation, phenotypic plasticity, and evolutionary trait change differs strongly depending on the set of species and traits studied. Taking into account this variation at different levels of biological organization is important to predict community‐wide responses to global change.