bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural analysis of emerin, an inner nuclear membrane protein mutated in X‐linked Emery–Dreifuss muscular dystrophy
Authors: Wolff Nicolas , Gilquin Bernard , Courchay Karine , Callebaut Isabelle , Worman Howard J. , Zinn-Justin Sophie
Published: July 2002

Like Duchenne and Becker muscular dystrophies, Emery–Dreifuss muscular dystrophy (EDMD) is characterized by myopathic and cardiomyopathic abnormalities. EDMD has the particularity of being linked to mutations in nuclear proteins. The X‐linked form of EDMD is caused by mutations in the emerin gene, whereas autosomal dominant EDMD is caused by mutations in the lamin A/C gene. Emerin colocalizes with lamin A/C in interphase cells, and binds in vitro to lamin A/C. Recent work suggests that lamin A/C might serve as a receptor for emerin. We have undertaken a structural analysis of emerin, and in particular of its N‐terminal domain, which is comprised in the emerin segment critical for binding to lamin A/C. We show that region 2–54 of emerin adopts the LEM fold. This fold was originally described in the two N‐terminal domains of another inner nuclear membrane protein called lamina‐associated protein 2 (LAP2). The existence of a conserved solvent‐exposed surface on the LEM domains of LAP2 and emerin is discussed, as well as the nature of a possible common target.
Radiation‐induced apoptosis in MOLT‐4 cells requires de novo protein synthesis independent of de novo RNA synthesis
Authors: Taylor Matthew Hiram , Buckwalter Matthew Ross , Stephenson Amen Craig , Hart Janet Leigh , Taylor Benjamin James , O'Neill Kim Leslie
Published: July 2002

We investigated the effects of inhibition of de novo RNA and protein synthesis in ionizing radiation (IR)‐induced apoptosis in the human T cell line MOLT‐4. We observed that pretreatment with cycloheximide inhibited IR‐induced apoptosis. However, pretreatment with actinomycin D did not inhibit apoptosis induced by IR. These results suggest that apoptosis induced by IR in MOLT‐4 cells requires de novo protein synthesis but not de novo RNA synthesis. This finding suggests that the mRNA encoding the proapoptotic protein(s) is stabilized to facilitate translation independent of de novo gene transcription in response to IR. Our results also indicate that translation of the required proapoptotic protein(s) occurs upstream of mitochondrial depolarization and after 2 h post‐IR.
Propagation of intercellular Ca2+ waves in mechanically stimulated articular chondrocytes
Authors: D'Andrea Paola , Vittur Franco
Published: July 2002

Intercellular Ca2+ signalling in primary cultures of articular chondrocytes was investigated with digital fluorescence video imaging. Mechanical stimulation of a single cell induced a wave of increased Ca2+ that was communicated to surrounding cells. Intercellular Ca2+ spreading was inhibited by 18α‐glycyrrhetinic acid, demonstrating the involvement of gap junctions in signal propagation. In the absence of extracellular Ca2+ mechanical stimulation failed to induce Ca2+ responses and communicated Ca2+ waves. Under these conditions Ca2+ microinjection induced intercellular waves involving the cells immediately surrounding the stimulated one. Mechanical stress induced Ca2+ influx in the stimulated, but not in the adjacent cells, as assessed by the Mn2+ quenching technique. Cell treatment with thapsigargin failed to block mechanically induced signal propagation, but significantly reduced the number of cells involved in the communicated Ca2+ wave. Similar results were obtained with the phospholipase C inhibitor U73122, which is known to prevent InsP3 generation. These results provide evidence that mechanical stimulation induces a cytosolic Ca2+ increase that may permeate gap junctions, thus acting as an intercellular messenger mediating cell‐to‐cell communication in articular chondrocytes.
Isolation and characterization of heparin‐ and phosphorylcholine‐binding proteins of boar and stallion seminal plasma. Primary structure of porcine pB1
Authors: Calvete Juan J , Raida Manfred , Gentzel Marc , Urbanke Claus , Sanz Libia , Töpfer-Petersen Edda
Published: July 2002

In the bovine, seminal plasma heparin‐binding proteins bind to sperm lipids containing the phosphorylcholine group and mediate the capacitating effects of heparin‐like glycosaminoglycans during sperm residence in the female genital tract. We report the characterization of heparin‐ and phosphorylcholine‐binding proteins of stallion and boar seminal plasma.
orse
eminal
lasma proteins HSP‐1 and HSP‐2, and boar protein pB1, belong to the same family as the bull heparin‐ and phosphorylcholine‐binding proteins BSP‐A1/2, BSP‐A3, and BSP‐30K. We have determined the amino acid sequence and posttranslational modifications of boar glycoprotein pB1. It contains 105 amino acids arranged into a mosaic structure consisting of a N‐terminal 18‐residue O‐glycosylated polypeptide followed by two tandemly organized 40–45‐residue fibronectin type II domains. pB1 displays 60–65% amino acid sequence similarity with its equine and bovine homologues. However, in their respective seminal plasmas, the BSP and the HSP proteins associate into 90–150‐kDa oligomeric complexes, whereas pB1 forms a 35–40‐kDa complex with spermadhesin AQN‐1. In addition, pB1 appears to be identical to the recently described leukocyte adhesion regulator of porcine seminal fluid pAIF‐1. Our results tie in with the hypothesis that homologous proteins from different mammalian species may display distinct biological activities, which may be related to species‐specific aspects of sperm physiology.
A truncated isoform of Ca2+/calmodulin‐dependent protein kinase II expressed in human islets of Langerhans may result from trans‐splicing
Authors: Breen Maria A. , Ashcroft Stephen J.H.
Published: July 2002

Calcium/calmodulin‐dependent protein kinase II (CaM kinase II) has been proposed to play a key role in glucose stimulated insulin secretion. Using the rapid amplification of cDNA ends technique we amplified the 3′ end of the CaM kinase II γ gene from human islet RNA. A novel cDNA was detected composed of 5′ sequence from the human CaM kinase II γ gene joined to the 3′ end of the human signal recognition particle 72 (SRP72) gene. We predict that this mRNA species will code for a truncated form of CaM kinase II, designated γSRP, comprising the entire catalytic and regulatory domains of the protein and with a predicted molecular weight of 37 kDa. We mapped the human SRP72 gene to chromosome 18 and, as the CaM kinase II γ gene was previously mapped to human chromosome 10q22, we suggest this novel cDNA may have resulted from trans‐splicing.
Cloning and expression of an alternatively spliced mRNA encoding a soluble form of the human interleukin‐6 signal transducer gp1301
Authors: Diamant Marcus , Rieneck Klaus , Mechti Nadir , Zhang Xue-Guang , Svenson Morten , Bendtzen Klaus , Klein Bernard
Published: July 2002

Both gp130 and alternatively spliced sgp130 were also transcribed by the myeloma cell lines XG‐1, XG‐2, XG‐4, XG‐4CNTF XG‐6, XG‐7, XG‐9, XG‐10, U266 and RPMI 8226. However, XG‐4A cells derived from XG‐4 cells, but growing independently of exogenous IL‐6, did not transcribe sgp130 mRNA. A possible interference with intracrine stimulatory factors by alternatively spliced sgp130 needs to be further investigated.
The role of transient starch in acclimation to elevated atmospheric CO2
Authors: Ludewig Frank , Sonnewald Uwe , Kauder Friedrich , Heineke Dieter , Geiger Michael , Stitt Mark , Müller-Röber Bernd T , Gillissen Bernd , Kühn Christina , Frommer Wolf B
Published: July 2002

Although increased concentrations of CO2stimulate photosynthesis, this stimulation is often lost during prolonged exposure to elevated carbon dioxide, leading to an attenuation of the potential gain in yield. Under these conditions, a wide variety of species accumulates non‐structural carbohydrates in leaves. It has been proposed that starch accumulation directly inhibits photosynthesis, that the rate of sucrose and starch synthesis limits photosynthesis, or that accumulation of sugars triggers changes in gene expression resulting in lower activities of Rubisco and inhibition of photosynthesis. To distinguish these explanations, transgenic plants unable to accumulate transient starch due to leaf mesophyll‐specific antisense expression ofAGP Bwere grown at ambient and elevated carbon dioxide. There was a positive correlation between the capacity for starch synthesis and the rate of photosynthesis at elevated CO2concentrations, showing that the capability to synthesize leaf starch is essential for photosynthesis in elevated carbon dioxide. The results show that in elevated carbon dioxide, photosynthesis is restricted by the rate of end product synthesis. Accumulation of starch is not responsible for inhibition of photosynthesis. Although transgenic plants contained increased levels of hexoses, transcripts of photosynthetic genes were not downregulated and Rubisco activity was not decreased arguing against a role of sugar sensing in acclimation to high CO2.
2‐Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through Ca2+‐dependent and ‐independent mechanisms
Authors: Kondo Sachiko , Kondo Hironori , Nakane Shinji , Kodaka Tomoko , Tokumura Akira , Waku Keizo , Sugiura Takayuki
Published: July 2002

The molecular species compositions of monoacylglycerols obtained from various rat tissues were examined by reverse‐phase high‐performance liquid chromatography (HPLC) and gas chromatography‐mass spectrometry (GC‐MS) analyses. We confirmed that 2‐arachidonoylglycerol, an endogenous cannabinoid receptor agonist, is one of the most abundant molecular species of monoacylglycerols in the brain. Substantial amounts of 2‐arachidonoylglycerol were also found in the liver, spleen, lung and kidney, but the levels were considerably lower than that in the brain. We found that a small amount of 2‐arachidonoylglycerol was generated in a brain homogenate during incubation in the absence of Ca2+. Importantly, the generation of 2‐arachidonoylglycerol was markedly augmented in the presence of Ca2+, suggesting that Ca2+ plays a key role in regulation of the generation of 2‐arachidonoylglycerol in this tissue.
Site directed mutagenesis reduces the Na+ affinity of HKT1, an Na+ energized high affinity K+ transporter
Authors: Diatloff Eugene , Kumar Raman , Schachtman Daniel P
Published: July 2002

HKT1 encodes a high affinity Na+ coupled K+ transporter expressed in the cortical cells of Triticum aestivum roots. To identify regions of the protein involved in the binding and transport of Na+ and K+, mutations were introduced into a domain of HKT1 containing 16 amino acids that are highly conserved across a range of putative K+ transport proteins from different phyla. Two mutations had a significant effect on the functional characteristics of the transporter. A yeast growth assay showed that concentrations of NaCl between 2.5 to 50 mM stimulated the growth of yeast expressing HKT1 containing the E464Q substitution, but not the growth of yeast expressing HKT1. Kinetic analysis confirmed that the E464Q mutation lowered the affinity of HKT1 for Na+ but did not affect its affinity for K+. A second mutation in the same region F463L was created that also lowered the affinity of the transporter for Na+. The importance of these highly conserved amino acid residues is highlighted by the fact that they have remained conserved through evolution. The results of this mutational analysis suggest that this domain in HKT1 plays a role in the binding and transport of Na+.
HIV: from molecular recognition to tissue pathogenesis
Authors: Margolis Leonid
Published: July 2002

Dramatic progress has been made recently in identifying both viral and cellular molecules responsible for binding and fusion of HIV‐1 to target cells. In vivo, HIV‐1 infection is transmitted by viruses that recognize chemokine receptor CCR5, while viruses isolated at later stages of HIV disease often recognize another chemokine receptor, CXCR4. It is still not understood how this molecular tropism of HIV‐1 is translated into the virus' ability to compromise normal cell functions, which results in impairment of lymphoid tissue and causes AIDS. Here, we discuss how the new molecular findings might relate to HIV pathogenesis in cells and tissues.
Identification and subcellular localization of a novel Cu,Zn superoxide dismutase of Mycobacterium tuberculosis
Authors: Wu C.H.Herbert , Tsai-Wu Jyy-Jih , Huang Yung-Tzung , Lin Ching-Yi , Lioua Gunn-Guang , Lee Feng-Jen S.
Published: July 2002

Periplasmic copper, zinc superoxide dismutases (Cu,ZnSOD) of several Gram‐negative pathogens have been shown to play an important role in protection against exogenous superoxide radicals and in determining virulence of the pathogens. Here we report the cloning and characterization of the sodC gene, encoding Cu,ZnSOD, from the Gram‐positive Mycobacterium tuberculosis. The predicted protein sequence contains 240 amino acids with a putative signal peptide at the N‐terminus and shows ∼25% identity to other bacterial sodC. Recombinant proteins of a full‐length sodC and a truncated form lacking the putative signal peptide were overexpressed in Escherichia coli and affinity purified. Renatured recombinant M. tuberculosis sodC protein possessed characteristics of a Cu,ZnSOD. Immunoblotting with an antiserum against the recombinant M. tuberculosis Cu,ZnSOD allowed detection of a single polypeptide in the lysate of M. tuberculosis. This polypeptide has a similar size as the recombinant protein without the putative signal peptide indicating that the endogenous Cu,ZnSOD in M. tuberculosis might be processed and secreted. Furthermore, immunogold electron microscopic image showed that Cu,ZnSOD is located in the periphery of M. tuberculosis. The enzymatic activity and subcellular localization of this novel Cu,ZnSOD suggest that it may play a role in determining virulence of M. tuberculosis.
Purification and characterization of rat hippocampal CA3‐dendritic spines associated with mossy fiber terminals
Authors: Kiebler Michael A , López-Garcı́a Juan Carlos , Leopold Philip L
Published: July 2002

We report a revised and improved isolation procedure for CA3‐dendritic spines, most of them still in association with mossy fiber terminals resulting in a 7.5‐fold enrichment over nuclei and a 29‐fold enrichment over myelin. Additionally, red blood cells, medullated fibers, mitochondria and small synaptosomes were significantly depleted. We show by high resolution electron microscopy that this subcellular fraction contains numerous dendritic spines with a rich ultrastructure, e.g. an intact spine apparatus, membranous organelles, free and membrane‐bound polyribosomes, endocytic structures and mitochondria. This improved experimental system will allow us to study aspects of post‐synaptic functions at the biochemical and molecular level.
Post‐translational processing of two α‐amylase inhibitors and an arcelin from the common bean, Phaseolus vulgaris
Authors: Young N.Martin , Thibault Pierre , Watson David C. , Chrispeels Maarten J.
Published: July 2002

Mass spectrometric methods were used to investigate the proteolytic processing and glycopeptide structures of three seed defensive proteins from Phaseolus vulgaris. The proteins were the α‐amylase inhibitors αAI‐1 and αAI‐2 and arcelin‐5, all of which are related to the seed lectins, PHA‐E and PHA‐L. The mass data showed that the proteolytic cleavage required for activation of the amylase inhibitors is followed by loss of the terminal Asn residue in αAI‐1, and in all three proteins, seven or more residues were clipped from the C‐termini, in the manner of the seed lectins. In most instances, individual glycoforms could be assigned at each Asn site, due to the unique masses of the plant glycopeptides. It was found that αAI‐1 and αAI‐2 differed significantly in their glycosylation patterns, despite their high sequence homology. These data complement the previous X‐ray studies of the α1‐amylase inhibitor and arcelin, where many of the C‐terminal residues and glycopeptide residues could not be observed.
Re‐evaluation of the primary structure of Ralstonia eutropha phasin and implications for polyhydroxyalkanoic acid granule binding
Authors: Hanley Steven Zachary , Pappin Darryl J.C , Rahman Dinah , White Andrew J , Elborough Kieran M , Slabas Antoni R
Published: July 2002

Sequence analysis of several cDNAs encoding the phasin protein of Ralstonia eutropha indicated that the carboxyl terminus of the resulting derived protein sequence is different from that reported previously. This was confirmed by: (1) sequencing of the genomic DNA; (2) SDS‐PAGE and peptide analysis of wild‐type and recombinant phasin; and (3) mass spectrometry of wild‐type phasin protein. The results have implications for the model proposed for the binding of this protein to polyhydroxyalkanoic acid granules in the bacterium.
Carotenoids inhibit DNA synthesis in human aortic smooth muscle cells
Authors: Carpenter Keri L.H , Hardwick Simon J , Albarani Valentina , Mitchinson Malcolm J
Published: July 2002

Quiescent, serum‐starved human aortic smooth muscle cells were restimulated with 20% foetal calf serum in Dulbecco's modified Eagle medium, in the presence and absence of β‐carotene, canthaxanthin, zeaxanthin, lycopene, lutein or β‐cryptoxanthin, at final concentrations up to 23 μM. Concentration‐dependent inhibition of DNA synthesis, measured by [methyl‐3H]thymidine incorporation, was observed for the carotenoids, except for canthaxanthin and lutein which had no effect. Lycopene was the most potent of the carotenoids tested. The results suggest that antiproliferative effects of dietary carotenoids might be of significance in vivo.
Radiation target analysis indicates that phenylalanine hydroxylase in rat liver extracts is a functional monomer
Authors: Parniak Michael A , Davis Michael , Kaufman Seymour , Kempner Ellis S
Published: July 2002

The minimal enzymatically functional form of purified rat hepatic phenylalanine hydroxylase (PAH) is a dimer of identical subunits. Radiation target analysis of PAH revealed that the minimal enzymatically active form in crude extracts corresponds to the monomer. The ‘negative regulation' properties of the tetrahydrobiopterin cofactor in both crude and pure samples implicates a large multimeric structure, minimally a tetramer of PAH subunits. Preincubation of the samples with phenylalanine prior to irradiation abolished this inhibition component without affecting the minimal functional unit target sizes of the enzyme in both preparations. The characteristics of rat hepatic PAH determined by studies of the purified enzyme in vitro may not completely represent the properties of PAH in vivo.
Endoglin is expressed in the chicken vasculature and is involved in angiogenesis
Authors: Raab Ulla , Lastres Pedro , Arévalo Miguel A. , López-Novoa Jose M. , Cabañas Carlos , de la Rosa Enrique J. , Bernabéu Carmelo
Published: July 2002

Endoglin is a component of the transforming growth factor β (TGF‐β) receptor complex, highly expressed by endothelial cells. Mutations in the endoglin gene are responsible for hereditary hemorrhagic telangiectasia type 1 (HHT1), an autosomal dominant vascular disorder caused by a haploinsufficiency mechanism. Vascular lesions (telangiectasia and arteriovenous malformations) in HHT1 are associated with loss of the capillary network, suggesting the involvement of endoglin in vascular repair processes. Using the chick chorioallantoic membrane (CAM) as an angiogenic model, we have analyzed the expression and function of chicken endoglin. A pan‐specific polyclonal antibody (pAb) recognized chicken endoglin as demonstrated by immunostaining and Western blot analysis. In ovo treatment of chicken embryos with this pAb resulted in a significantly increased area of CAM. This effect was likely mediated by modulation of the ligand binding to endoglin as this pAb was able to inhibit TGF‐β1 binding. These results support the involvement of endoglin in the angiogenic process.
NO induces a cGMP‐independent release of cytochrome c from mitochondria which precedes caspase 3 activation in insulin producing RINm5F cells
Authors: Tejedo J , Bernabé J.C , Ramı́rez R , Sobrino F , Bedoya F.J
Published: July 2002

Exposure of RINm5F cells to interleukin‐1β and to several chemical NO donors such as sodium nitroprusside (SNP), SIN‐1 and SNAP induce apoptotic events such as the release of cytochrome c from mitochondria, caspase 3 activation, Bcl‐2 downregulation and DNA fragmentation. SNP exposure led to transient activation of soluble guanylate cyclase (sGC) and prolonged protein kinase G (PKG) activation but apoptotic events were not attenuated by inhibition of the sGC/PKG pathway. Prolonged activation of the cGMP pathway by exposing cells to the dibutyryl analogue of cGMP for 12 h induced both apoptosis and necrosis, a response that was abolished by the PKG inhibitor KT5823. These results suggest that NO‐induced apoptosis in the pancreatic β‐cell line is independent of acute activation of the cGMP pathway.
The management of the second stage of labor
Authors: O'Connell M.P , Tetsis A.V , Lindow S.W
Published: July 2002

Objective: To review obstetric practice in a single maternity hospital with respect to the assisted vaginal delivery rate. Method: A retrospective analysis of the hospital statistics, labor ward records, casenotes and management protocols with respect to the second stage of labor was performed in a single maternity unit in the UK; the study included 43 352 women who delivered a baby between the years of 1987 and 1997. The study looked at the rate of assisted vaginal deliveries, cesarean section, epidural in labor, and as well as the perinatal mortality rate. Results: In the 11‐year period of the study, 43 352 women delivered with a mean assisted vaginal delivery rate of 3.70%, cesarean section rate of 12.4% and an epidural rate of 31.5%. Conclusion: The management of the second stage of labor in this unit results in an assisted vaginal delivery rate significantly below the national average. The authors highlight the paucity of research in this important area of practice.
Colposcopic evaluation after a repeat atypical squamous cells of undetermined significance (ASCUS) smear
Authors: Gerber S , De Grandi P , Petignat P , Mihaescu A , Delaloye J.F
Published: July 2002

Objectives: Management of patients with atypical squamous cells of undetermined significance (ASCUS) remains controversial. We chose to repeat the Pap smear after four months. If ASCUS persisted in this second test, the patient was advised to undergo colposcopy. Our objective is to determine the clinical significance and the prediction of neoplasia among these patients through a colposcopic examination. Methods: Of 29 827 patients who had a Pap smear, ASCUS were detected in 1387 (5%) and persisted in the repeat smear of 225 (16%). Colposcopy and an additional Pap smear were performed on 186 patients. Results: Out of 186 colposcopic evaluations, 91 (49%) were normal and the patients had a negative Pap smear. Colposcopy was abnormal in 95/186 patients (51%) (Table 1). Histology of the directed biopsies revealed 38 (21%) low‐grade squamous intraepithelial lesions (LSIL) and 17 (9%) high‐grade squamous intraepithelial lesions (HSIL). Forty patients (21%) with normal biopsies had ASCUS for the third time in the Pap smear. Conclusions: Colposcopic evaluation after a repeated Pap smear with ASCUS is an appropriate cost‐effective management. Finding 30% of LSIL or HSIL justifies this additional investigation.
Obstetric outcome in uncomplicated prolonged pregnancy
Authors: Abotalib Z.M. , Soltan M.H. , Chowdhury N. , Adelusi B.
Published: July 2002

Objective: To study and compare the obstetric outcome in term pregnancies and uncomplicated prolonged pregnancies. Methods: The study was a retrospective review of 596 cases. The case notes of 286 patients with uncomplicated prolonged pregnancies (≥ 42 weeks) and 310 patients with normal term pregnancies (37 to < 42 weeks) were analyzed. The Gold Stat package was used for statistical coding and analysis. Results: There was no fetal morbidity or mortality among the two groups. However, the number of previous abortions were significantly higher in prolonged pregnancies compared with term pregnancies. Similarly, fetal and placental weights, labor induction and operative delivery rates were significantly higher in prolonged pregnancies. However, there were no significant differences between the patients who were induced and those who had spontaneous labor among the prolonged pregnancies. Conclusions: There is no doubt that prolonged pregnancy may be associated with certain risks factors. However, there is no outcome variable to justify whether or not to induce those pregnancies which are prolonged.
The diagnosis and prognosis of molar pregnancy: The experience of the National Referral Centre in London
Authors: Paradinas F.J.
Published: July 2002

Since 1973, hCG follow up and treatment of patients with hydatidiform moles in the UK has been centralised. Registrations of moles have increased from 475 to 1248 in 2 years but histological review shows that first trimester non‐molar hydropic abortions (HAs) and complete moles (CMs) are often called partial moles (PMs) by pathologists. The introduction and widespread acceptance of the term PM in 1977, coincided with improvements in ultrasound which brought forward 6 weeks the average time of evacuation of CMs, when hydrops is not yet complete but partial and when vessels are present in most CMs, leading to erroneous diagnoses of PM.

Many true PMs are dismissed as HAs and often, HAs are called PMs. Valid diagnostic criteria for younger CMs and for PMs have been available for over 10 years and when used, PM is overwhelmingly associated with triploidy.

Reported diploid PMs are partly explained by misdiagnosed HAs, rare cases of Beckwith‐Widemann syndrome, CMs with partially developed hydrops, twin pregnancies and rare androgenetic CMs with fetal red cells in villi. A rare mole with “normal” diploid biparental karyotype probably exists but morphologically resembles CM.

CM and PM have widely different prognosis but the present diagnostic confusion means much of the published epidemiological, clinical and genetic information on PM based on suspect diagnostic criteria ia also suspect.
Voluntary and involuntary sterilization: denials and abuses of rights
Authors: Cook R.J , Dickens B.M
Published: July 2002

Laws that allow competent persons to make free and informed decisions for sterilization serve their entitlements to reproductive choice. Laws that allow others to consent to sterilization of disadvantaged persons who cannot freely consent risk oppression and denial of human rights. Laws that prohibit competent persons' choices for their own sterilization are comparably oppressive and violative of human rights to decide whether and how often to have children. Whether laws approach sterilization as a procedure done for patients, or to patients, is often ambivalent. Details of laws may indicate their liberating and oppressive potential. Programs offering inducements to persons to be sterilized may assist those who are disadvantaged to achieve their goals, but may appear to coerce those who, through poverty or dependency, cannot resist the inducement.
Knockdown of DNA methyltransferase 1 reduces DNA methylation and alters expression patterns of cardiac genes in embryonic cardiomyocytes
Authors: Fang Xiefan , Poulsen Ryan , Zhao Lu , Wang Jingjing , Rivkees Scott A. , Wendler Christopher C.
Published: July 2021

We previously found that DNA methyltransferase 3a (DNMT3a) plays an important role in regulating embryonic cardiomyocyte gene expression, morphology, and function. In this study, we investigated the role of the most abundant DNMT in mammalian cells, DNMT1, in these processes. It is known that DNMT1 is essential for embryonic development, during which it is involved in regulating cardiomyocyte DNA methylation and gene expression. We used siRNA to knock down DNMT1 expression in primary cultures of mouse embryonic cardiomyocytes. Immunofluorescence staining and multielectrode array were, respectively, utilized to evaluate cardiomyocyte growth and electrophysiology. RNA sequencing (RNA‐Seq) and multiplex bisulfite sequencing were, respectively, performed to examine gene expression and promoter methylation. At 72 h post‐transfection, reduction of DNMT1 expression decreased the number and increased the size of embryonic cardiomyocytes. Beat frequency and the amplitude of field action potentials were decreased by DNMT1 siRNA. RNA‐Seq analysis identified 801 up‐regulated genes and 494 down‐regulated genes in the DNMT1 knockdown cells when compared to controls. Pathway analysis of the differentially expressed genes revealed pathways that were associated with cell death and survival, cell morphology, cardiac function, and cardiac disease. Alternative splicing analysis identified 929 differentially expressed exons, including 583 up‐regulated exons and 308 down‐regulated exons. Moreover, decreased methylation levels were found in the promoters of cardiac genes Myh6, Myh7, Myh7b, Tnnc1, Tnni3, Tnnt2, Nppa, Nppb, mef2c, mef2d, Camta2, Cdkn1A, and Cdkn1C. Of these 13 genes, 6 (Myh6, Tnnc1, Tnni3, Tnnt2, Nppa, Nppb) and 1 (Cdkn1C) had increased or decreased gene expression, respectively. Altogether, these data show that DNMT1 is important in embryonic cardiomyocytes by regulating DNA methylation, gene expression, gene splicing, and cell function.
DMTs and Covid‐19 severity in MS: a pooled analysis from Italy and France
Authors: Sormani Maria Pia , Salvetti Marco , Labauge Pierre , Schiavetti Irene , Zephir Helene , Carmisciano Luca , Bensa Caroline , De Rossi Nicola , Pelletier Jean , Cordioli Cinzia , Vukusic Sandra , Moiola Lucia , Kerschen Philippe , Radaelli Marta , Théaudin Marie , Immovilli Paolo , Casez Olivier , Capobianco Marco , Ciron Jonathan , Trojano Maria , Stankoff Bruno , Créange Alain , Tedeschi Gioacchino , Clavelou Pierre , Comi Giancarlo , Thouvenot Eric , Battaglia Mario Alberto , Moreau Thibault , Patti Francesco , De Sèze Jérôme , Louapre Celine ,   the Musc‐19,   the Covisep study groups
Published: July 2021

We evaluated the effect of DMTs on Covid‐19 severity in patients with MS, with a pooled‐analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid‐19 severity was assessed by multivariate ordinal‐logistic models and pooled by a fixed‐effect meta‐analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti‐CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid‐19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled‐analysis confirms an increased risk of severe Covid‐19 in patients on anti‐CD20 therapies and supports the protective role of interferon.
Effect of Oxygen Impurity on Thermal Conduction Rate of Polycrystalline Si3N4
Authors: Dow Hwan Soo , Na Moonkyong , Jung Yeon Wook , Geun Jo Seung , Lee Jung Woo
Published: July 2021

Herein, the thermophysical properties and microstructures of the densified Si3N4, which are prepared by using MgO, Y2O3, and oxygen getter as sintering additives via conventional hot‐pressing sintering and followed by postheat treatment, are reported. Herein, it is found out that the sample using 5 mol.% of MgO, 2 mol.% of Y2O3, and 1.5 mol.% of Nb has the optimized thermal conductivity of 108 W m−1·K. Furthermore, increased rate of thermal conduction in the range of 10–15% is mainly originated from the decrease in the lattice oxygen contents of the grains in Si3N4 based on electron spin resonance (ESR) analysis.
Revealing the Mechanism behind the Catastrophic Failure of n‐i‐p Type Perovskite Solar Cells under Operating Conditions and How to Suppress It
Authors: Ding Changzeng , Yin Li , Zhang Lianping , Huang Rong , Fan Shizhao , Luo Qun , Lin Jian , Li Fangsen , Zhao Chun , Österbacka Ronald , Ma Chang‐Qi
Published: July 2021

The n‐i‐p type perovskite solar cells suffer unpredictable catastrophic failure under operation, which is a barrier for their commercialization. The fluorescence enhancement at Ag electrode edge and performance recovery after cutting the Ag electrode edge off prove that the shunting position is mainly located at the edge of device. Surface morphology and elemental analyses prove the corrosion of the Ag electrode and the diffusion of Ag+ ions on the edge for aged cells. Moreover, much condensed and larger Ag clusters are formed on the MoO3 layer. Such a contrast is also observed while comparing the central and the edge of the Ag/Spiro‐OMeTAD film. Hence, the catastrophic failure mechanism can be concluded as photon‐induced decomposition of the perovskite film and release reactive iodide species, which diffuse and react with the loose Ag clusters on the edge of the cell. The corrosion of the Ag electrode and the migration of Ag+ ions into Spiro‐OMeTAD and perovskite films lead to the forming of conducting filament that shunts the cell. The more condensed Ag cluster on the MoO3 surface as well as the blocking of holes within the Spiro‐OMeTAD/MoO3 interface successfully prevent the oxidation of Ag electrode and suppress the catastrophic failure.
Mechano‐Optical Sensors Fabricated with Multilayered Liquid Crystal Elastomers Exhibiting Tunable Deformation Recovery
Authors: Hisano Kyohei , Kimura Seiya , Ku Kyosun , Shigeyama Tomoki , Akamatsu Norihisa , Shishido Atsushi , Tsutsumi Osamu
Published: July 2021

Advances in tuning the mechanoresponsive behavior of liquid crystal elastomers have facilitated the development of next‐generation applications such as reconfigurable photonic/electronic materials, energy‐harvesting devices, and flexible sensors. However, the molecular‐level control of mechanical responses remains difficult, with limited tunability achieved for recovery processes after stimulus removal. Herein, a design concept is proposed for facilely tuning the recovery of both the macroscopic deformation and molecular orientation change of liquid crystal elastomers using layered materials that exhibit the desired mechanoresponsive behavior. Changing the layering materials (a polydimethylsiloxane film with elastic response to a polymethylpenten film with plastic response) alters the relaxation time from <1 s to >6 months. To demonstrate this concept, highly sensitive, stretchable mechano‐optical sensors with fast and ultraslow recovery times are developed that enable an applied strain to be quantitatively detected in real time or memorized with high spatial resolution, even with a conventional camera. This material design concept for arbitrarily controlling the recovery response can provide a platform for stimuli‐responsive applications.
Bioinspired Triboelectric Soft Robot Driven by Mechanical Energy
Authors: Liu Yuan , Chen Baodong , Li Wei , Zu Lulu , Tang Wei , Wang Zhong Lin
Published: July 2021

A sustainable power source is a key technical challenge for practical applications of electrically responsive soft robots, especially the required voltage is over several thousand volts. Here, a practicable new technology, triboelectric soft robot (TESR) system with the primary characteristics of power source from mechanical energy, is developed. At its heart is TESR with bioinspired architectures made of soft‐deformable body and two triboelectric adhesion feet, which is driven and accurately controlled through triboelectric effect, while reaching maximum crawling speeds of 14.9 mm s−1 on the acrylic surface. The characteristics of the TESR, including displacement and force, are tested and simulated under the power of a rotary freestanding triboelectric nanogenerator (RF‐TENG). Crawling of TESR is successfully realized on different materials surfaces and different angle slopes under the driven of RF‐TENG. Furthermore, a real‐time visual monitoring platform, in which TESR carries a micro camera to transmit images in a long narrow tunnel, is also achieved successfully, indicating that it can be used for fast diagnosis in an area inaccessible to human beings in the future. This study offers a new insight into the sustainable power source technologies suitable for electrically responsive soft robots and contributes to expanding the applicability of TENGs.
General Design Concept for Single‐Atom Catalysts toward Heterogeneous Catalysis
Authors: Guo Wenxin , Wang Zhiyuan , Wang Xiaoqian , Wu Yuen
Published: July 2021

As a new and popular material, single‐atom catalysts (SACs) exhibit excellent activity, selectivity, and stability for numerous important reactions, and show great potential in heterogeneous catalysis due to their high atom utilization efficiency and the controllable characteristics of the active sites. The composition and coordination would determine the geometric and electronic structures of SACs, and thus greatly influence the catalytic performance. Based on atom economy, rational design and controllable synthesis of SACs have become central tasks in the fields of low‐cost and green catalysis. Herein, an introduction to the recent progress in the precise synthesis of SACs including the regulation of the coordination structure and the choice of different systems is presented. Thereafter, the potentials of SACs in different applications are comprehensively summarized and discussed. Furthermore, a detailed discussion of the recent developments regarding the large‐scale preparation of SACs is provided, including the major issues and prospects for industrialization. Finally, the main challenges and opportunities of rapid large‐scale industrialization of SACs are briefly discussed.
T‐Cell‐Derived Nanovesicles for Cancer Immunotherapy
Authors: Hong Jihye , Kang Mikyung , Jung Mungyo , Lee Yun Young , Cho Yongbum , Kim Cheesue , Song Seuk Young , Park Chun Gwon , Doh Junsang , Kim Byung‐Soo
Published: July 2021

Although T‐cell therapy is a remarkable breakthrough in cancer immunotherapy, the therapeutic efficacy is limited for solid tumors. A major cause of the low efficacy is T‐cell exhaustion by immunosuppressive mechanisms of solid tumors, which are mainly mediated by programmed death‐ligand 1 (PD‐L1) and transforming growth factor‐beta (TGF‐β). Herein, T‐cell‐derived nanovesicles (TCNVs) produced by the serial extrusion of cytotoxic T cells through membranes with micro‐/nanosized pores that inhibit T‐cell exhaustion and exhibit antitumoral activity maintained in the immunosuppressive tumor microenvironment (TME) are presented. TCNVs, which have programmed cell death protein 1 and TGF‐β receptor on their surface, block PD‐L1 on cancer cells and scavenge TGF‐β in the immunosuppressive TME, thereby preventing cytotoxic‐T‐cell exhaustion. In addition, TCNVs directly kill cancer cells via granzyme B delivery. TCNVs successfully suppress tumor growth in syngeneic‐solid‐tumor‐bearing mice. Taken together, TCNV offers an effective cancer immunotherapy strategy to overcome the tumor's immunosuppressive mechanisms.
Optimization of Substrate Layer Material and Its Mechanical Properties for Piezoelectric Cantilever Energy Harvesting System
Authors: Kumar Akash , Singh Jagpreet
Published: July 2021

A cantilever piezoelectric energy harvester (PEH) is a popular choice to harvest energy for applications with natural or unnatural vibrations. Other than the choice of piezoelectric material, the substrate layer material also plays an important role to increase the energy harvesting in PEH. Earlier researches have emphasized on selecting a few substrate materials than all available in literature. However, we argue that the choice of the substrate material and its mechanical properties depend on the design of the PEH. We establish this fact by designing 20 different PEH models by varying the size of cantilever, substrate layer thickness, and types of the piezoelectric materials. These models are simulated in COMSOL with every known substrate material to select the best substrate material. We also propose a greedy approach to further increase the energy harvesting by optimizing the mechanical properties of the best substrate material. In all models, the best substrate material harvests at least 2 × more energy. The greedy approach increases energy harvesting in almost 50% of the models. Some of the substrate materials with optimized mechanical properties are reported in literature, however, this research opens up a discussion to manufacture new substrate materials to increase energy harvesting in PEH.
A practical approach for applying machine learning in the detection and classification of network devices used in building management
Authors: Touma Maroun , Witherspoon Shalisha , Witherspoon Shonda , Crawford‐Eng Isabelle
Published: July 2021

With the increasing deployment of smart buildings and infrastructure, supervisory control and data acquisition (SCADA) devices and the underlying IT network have become essential elements for the proper operations of these highly complex systems. Of course, with the increase in automation and the proliferation of SCADA devices, a corresponding increase in surface area of attack on critical infrastructure has increased. Understanding device behaviors in terms of known and understood or potentially qualified activities vs unknown and potentially nefarious activities in near‐real time is a key component of any security solution. In this paper, we investigate the challenges with building robust machine learning models to identify unknowns purely from network traffic both inside and outside firewalls, starting with missing or inconsistent labels across sites, feature engineering and learning, temporal dependencies and analysis, and training data quality (including small sample sizes) for both shallow and deep learning methods. To demonstrate these challenges and the capabilities we have developed, we focus on Building Automation and Control networks (BACnet) from a private commercial building system. Our results show that “Model Zoo” built from binary classifiers based on each device or behavior combined with an ensemble classifier integrating information from all classifiers provides a reliable methodology to identify unknown devices as well as determining specific known devices when the device type is in the training set. The capability of the Model Zoo framework is shown to be directly linked to feature engineering and learning, and the dependency of the feature selection varies depending on both the binary and ensemble classifiers as well.
Demonstration of Spider‐Eyes‐Like Intelligent Antennas for Dynamically Perceiving Incoming Waves
Authors: Wang Zhedong , Qian Chao , Cai Tong , Tian Longwei , Fan Zhixiang , Liu Jian , Shen Yichen , Jing Li , Jin Jianming , Li Er-Ping , Zheng Bin , Chen Hongsheng
Published: July 2021

Obtaining a full view and complete information of the surrounding dynamics is of great significance for a plethora of applications in sensing, imaging, navigation, and orientation. However, conventional spatial spectrum methods heavily rely on a priori knowledge with a trial‐and‐error solution fashion, leading to a great challenge to estimate complete information in volatile scenarios. Inspired by the mechanism of the jumping spider (Salticidae), here a universal detection approach driven by an intelligent antenna array, with the usage of amplitude‐only information as inputs, is introduced. The applied machine learning method can process the received time‐varying signals in one single feed‐forward computation, bypassing a heavy recline on prior knowledge of the array structure. As a demonstration, a compact eight‐port antenna array is designed for simultaneous attainments of frequency, direction of arrival, and polarization, covering the entire microwave X band. Both the simulated and experimental results show that the average accuracies for the azimuth angle, elevation angle, and polarization are up to 98%, with a millisecond detection time. Different from conventional methods, the strategy herein does not involve a complex beamforming network and a time‐consuming trial‐and‐error solution fashion, allowing a big step toward a miniaturized, integrated, and cost‐effective detector.
Measuring Youth Empowerment: An Item Response Theory Analysis of the Sociopolitical Control Scale for Youth
Authors: Powell Kristen Gilmore , Peterson N. Andrew , Treitler Peter C. , Lardier David T. , Rashid Mariam , Reid Robert J.
Published: July 2021

Sociopolitical control (SPC) has been identified as a key element of the intrapersonal component of psychological empowerment. The Sociopolitical Control Scale (SPCS) is a widely used measure and has been modified for use among youth (SPCS‐Y). In light of the emerging interest in SPC among youth within community‐based research, this study applied item response theory (IRT) to examine the psychometric properties of the SPCS‐Y and to explore a brief version. Data were collected between 2006 and 2013 from a convenience sample of high school students (N = 1,808), located in a midsized, economically disadvantaged urban community in the northeastern United States. Findings indicate that the two subscales, leadership competence, and policy control, were unidimensional and items functioned well. Most items functioned particularly well at low and moderate levels of the construct, but a few were able to capture higher levels of the construct. Based on our IRT analyses of the performance of items on the subscales, we selected items to create a brief version of the SPCS‐Y (BSPCS‐Y) and performed structural equation modeling for further examination. Results provide empirical evidence to support the reliability and validity of the SPCS‐Y and suggest a brief version based on high‐performing items is possible.
Second instance of co‐occurring 22q11.2 deletion syndrome and Williams syndrome
Authors: Uhles Crescenda L. , Barnes Shirelle , Uddin Naseem , Umaña Luis A.
Published: July 2021

We present an 18‐month‐old male with Tetralogy of Fallot, retrognathia, short stature, global developmental delay, and dysmorphic features who was found to have dual diagnoses of both Williams syndrome and 22q11.2 deletion syndrome (22q11.2DS). To our knowledge, this is the second case of such a co‐occurrence documented in the medical literature. Our patient presents with a blended physical phenotype of these two conditions and a behavioral phenotype that is distinct from what is typically observed in either disorder alone. We compare our patient's phenotype to the previously reported case and to the typical phenotypes for each individual condition. Additionally, we discuss why the occurrence of these two disorders together seems to be so rare, and the benefit of a genetics evaluation to an inpatient service team and the patient.
Ganzheitliche Betrachtung in der Materialentwicklung: Wasser‐Elektrolyse als Fallbeispiel
Authors: Klemenz Sebastian , Stegmüller Andreas , Yoon Songhak , Felser Claudia , Tüysüz Harun , Weidenkaff Anke
Published: July 2021

Angesichts des steigenden ökologischen Bewusstseins zielt die Materialentwicklung in erster Linie auf die Verbesserung der Leistung und Effizienz innovativer und komplexerer Materialien ab. Eine Leistungsbewertung von Werkstoffen sollte jedoch wesentliche Aspekte von Materialien einbeziehen: Umweltauswirkungen, wirtschaftliche Zwänge, technische Machbarkeit usw. Daher wollen wir die Einbeziehung von Nachhaltigkeitskriterien bereits während des Materialdesignprozesses anstoßen. Mit einem solchen ganzheitlichen Designansatz ist es wahrscheinlicher, dass neue Produkte die Anforderungen der Kreislaufwirtschaft erfüllen, als wenn traditionelle Entwicklungsstrategien verfolgt werden. Am Beispiel von Katalysatoren für die Wasserelektrolyse präsentieren wir eine auf experimentellen Daten basierende Modellierungsmethode zur ganzheitlichen Bewertung von Prozessen.