Статті в журналах: "Bcnam"

1

Diallo, Chiaka, H. Frederick W. Rattunde, Vernon Gracen, Aboubacar Touré, Baloua Nebié, Willmar Leiser, Daniel K. Dzidzienyo, et al. "Genetic Diversification and Selection Strategies for Improving Sorghum Grain Yield Under Phosphorous-Deficient Conditions in West Africa." Agronomy 9, no. 11 (November 11, 2019): 742. http://dx.doi.org/10.3390/agronomy9110742.

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Sorghum, a major crop for income generation and food security in West and Central Africa, is predominantly grown in low-input farming systems with serious soil phosphorus (P) deficiencies. This study (a) estimates genetic parameters needed to design selection protocols that optimize genetic gains for yield under low-phosphorus conditions and (b) examines the utility of introgressed backcross nested association mapping (BCNAM) populations for diversifying Malian breeding materials. A total of 1083 BC1F5 progenies derived from an elite hybrid restorer “Lata-3” and 13 diverse donor accessions were evaluated for yield and agronomic traits under contrasting soil P conditions in Mali in 2013. A subset of 298 progenies were further tested under low-P (LP) and high-P (HP) conditions in 2014 and 2015. Significant genetic variation for grain yield was observed under LP and HP conditions. Selection for grain yield under LP conditions was feasible and more efficient than the indirect selection under HP in all three years of testing. Several of the BCNAM populations exhibited yields under LP conditions that were superior to the elite restorer line used as a recurrent parent. The BCNAM approach appears promising for diversifying the male parent pool with introgression of diverse materials using both adapted Malian breed and unadapted landrace material from distant geographic origins as donors.

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2

Le Sourd, Marie. "The Bandung Center for New Media Arts: Local Commitment and International Collaboration." Leonardo 39, no. 4 (August 2006): 315–18. http://dx.doi.org/10.1162/leon.2006.39.4.315.

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The article focuses on the Bandung Center for New Media Arts (BCNMA), an autonomous cultural space set up in 2001 by three Indonesian artists and architects. The BCNMA aims to encourage a dialogue with circles outside the art world and to offer greater dynamic possibilities for experimental forms of expressions. The Indonesian sociopolitical context after 1998 has had a great influence on the nature, development and methodologies used by this center. The case study of the Third Asia-Europe Art Camp, coorganized in 2005 by the BCNMA and the Asia-Europe Foundation, also highlights how international projects are developed by the BCNMA while taking into consideration the local cultural networks and creative environment.

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3

Collec, Emmanuel, Marie-Christine Lecomte, Wassim El Nemer, Yves Colin, and Caroline Le Van Kim. "Novel role for the Lu/BCAM–spectrin interaction in actin cytoskeleton reorganization." Biochemical Journal 436, no. 3 (May 27, 2011): 699–708. http://dx.doi.org/10.1042/bj20101717.

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Lu/BCAM (Lutheran/basal cell-adhesion molecule) is a laminin 511/521 receptor expressed in erythroid and endothelial cells, and in epithelial tissues. The RK573–574 (Arg573-Lys574) motif of the Lu/BCAM cytoplasmic domain interacts with αI-spectrin, the main component of the membrane skeleton in red blood cells. In the present paper we report that Lu/BCAM binds to the non-erythroid αII-spectrin via the RK573–574 motif. Alanine substitution of this motif abolished the Lu/BCAM–spectrin interaction, enhanced the half-life of Lu/BCAM at the MDCK (Madin–Darby canine kidney) cell surface, and increased Lu/BCAM-mediated cell adhesion and spreading on laminin 511/521. We have shown that the Lu/BCAM–spectrin interaction mediated actin reorganization during cell adhesion and spreading on laminin 511/521. This interaction was involved in a laminin 511/521-to-actin signalling pathway leading to stress fibre formation. This skeletal rearrangement was associated with an activation of the small GTP-binding protein RhoA, which depended on the integrity of the Lu/BCAM laminin 511/521-binding site. It also required a Lu/BCAM–αII-spectrin interaction, since its disruption decreased stress fibre formation and RhoA activation. We conclude that the Lu/BCAM–spectrin interaction is required for stress fibre formation during cell spreading on laminin 511/521, and that spectrin acts as a signal relay between laminin 511/521 and actin that is involved in actin dynamics.

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4

Kannan, Kalpana, Cristian Coarfa, Pei-Wen Chao, Liming Luo, Yan Wang, Amy E. Brinegar, Shannon M. Hawkins, Aleksandar Milosavljevic, Martin M. Matzuk, and Laising Yen. "Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma." Proceedings of the National Academy of Sciences 112, no. 11 (March 2, 2015): E1272—E1277. http://dx.doi.org/10.1073/pnas.1501735112.

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High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. Excessive genomic rearrangements, which are expected to create fusion oncogenes, are the hallmark of this cancer. Here we report a cancer-specific gene fusion between BCAM, a membrane adhesion molecule, and AKT2, a key kinase in the PI3K signaling pathway. This fusion is present in 7% of the 60 patient cancers tested, a significant frequency considering the highly heterogeneous nature of this malignancy. Further, we provide direct evidence that BCAM-AKT2 is translated into an in-frame fusion protein in the patient’s tumor. The resulting AKT2 fusion kinase is membrane-associated, constitutively phosphorylated, and activated as a functional kinase in cells. Unlike endogenous AKT2, whose activity is tightly regulated by external stimuli, BCAM-AKT2 escapes the regulation from external stimuli. Moreover, a BCAM-AKT2 fusion gene generated via chromosomal translocation using the CRISPR/Cas9 system leads to focus formation in both OVCAR8 and HEK-293T cell lines, suggesting that BCAM-AKT2 is oncogenic. Together, the results indicate that BCAM-AKT2 expression is a new mechanism of AKT2 kinase activation in HGSC. BCAM-AKT2 is the only fusion gene in HGSC that is proven to translate an aberrant yet functional kinase fusion protein with oncogenic properties. This recurrent genomic alteration is a potential therapeutic target and marker of a clinically relevant subtype for tailored therapy of HGSC.

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5

Yu, Hyunkyung, Nathalie Bellocq, Youngeun Ha, Hyunuk Kim, Yunyeon Kim, Bu-Nam Jeon, Léo Marx, et al. "Abstract 1760: The antibody-drug conjugate GENA-111 conjugated to auristatin F shows therapeutic potency in BCAM positive epithelial cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 1760. http://dx.doi.org/10.1158/1538-7445.am2022-1760.

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Abstract Antibody-drug conjugates (ADCs) are considered as promising cancer treatment modalities that combine the selectivity of antibodies and the cytotoxic properties of payloads using chemical linkers. However, despite their success, ADCs still suffer from drawbacks, e.g., systemic toxicity, which limit their potential clinical applications. The systemic toxicity of an ADC is mainly related to the stability of its linker, and to the selectivity of its antibody towards the targeted antigen expressed on cancer cells. Lu/BCAM (Lutheran/basal cell adhesion molecule) is a member of the immunoglobulin superfamily and is a receptor for laminin, a protein that facilitates cell adhesion, migration, and invasion. A growing number of studies show that BCAM plays an essential role in tumor progression and is overexpressed on epithelial cancers e.g., skin cancer. Here we describe GENA-111, a human monoclonal anti-BCAM IgG4 (S228P) antibody that binds to human BCAM with high affinity, and that is significantly internalized by BCAM-positive tumor cells. We also describe the GENA-111-auristatin F ADC, wherein the GENA-111 antibody has been armed with an auristatin F derivative using a new linker technology and a stabilized thiol maleimide conjugation. This new linker technology comprises a cleavable peptidic sequence that facilitates multidrug attachment and the production of ADCs with tailored drug-to-antibody ratios (DARs). Cytotoxic drugs are rapidly and selectively released from the linker by the carboxypeptidase activity of Cathepsin B. In vitro cytotoxicity examination showed the potent cytotoxic effects of this GENA-111-auristatin F ADC on BCAM-expressing tumor cells, with a positive correlation between cytotoxicity and BCAM expression. Moreover, this ADC was also shown to significantly reduce the growth of tumor cells, including A431, T47D, and Huh7. The GENA-111-auristatin F ADC was evaluated in a xenograft mouse model established by subcutaneous injection of A431 cells, a BCAM positive human skin cancer cell line. The results of this study will be presented and discussed. Taken together, our data suggest that an ADC targeting BCAM e.g., GENA-111-auristatin F, might be a promising treatment strategy for BCAM positive epithelial cancer patients. Citation Format: Hyunkyung Yu, Nathalie Bellocq, Youngeun Ha, Hyunuk Kim, Yunyeon Kim, Bu-Nam Jeon, Léo Marx, Mathilde Pantin, Hyunjin Yoo, Seungmin Byun, Joo-Yeon Chung, Mi Young Cha, Patrick Garrouste, Frédéric Lévy. The antibody-drug conjugate GENA-111 conjugated to auristatin F shows therapeutic potency in BCAM positive epithelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1760.

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6

Rahuel, Cécile, Anne Filipe, Léa Ritie, Wassim El Nemer, Natacha Patey-Mariaud, Dominique Eladari, Jean-Pierre Cartron, Patricia Simon-Assmann, Caroline Le Van Kim та Yves Colin. "Genetic inactivation of the laminin α5chain receptor Lu/BCAM leads to kidney and intestinal abnormalities in the mouse". American Journal of Physiology-Renal Physiology 294, № 2 (лютий 2008): F393—F406. http://dx.doi.org/10.1152/ajprenal.00315.2007.

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Lutheran blood group and basal cell adhesion molecule (Lu/BCAM) has been recognized as a unique receptor for laminin α5chain in human red blood cells and as a coreceptor in epithelial, endothelial, and smooth muscle cells. Because limited information is available regarding the function of this adhesion glycoprotein in vivo, we generated Lu/BCAM-null mice and looked for abnormalities in red blood cells as well as in kidney and intestine, two tissues showing alteration in laminin α5chain-deficient mice. We first showed that, in contrast to humans, wild-type murine red blood cells failed to express Lu/BCAM. Lu/BCAM-null mice were healthy and developed normally. However, although no alteration of the renal function was evidenced, up to 90% of the glomeruli from mutant kidneys exhibited abnormalities characterized by a reduced number of visible capillary lumens and irregular thickening of the glomerular basement membrane. Similarly, intestine analysis of mutant mice revealed smooth muscle coat thickening and disorganization. Because glomerular basement membrane and smooth muscle coat express laminin α5chain and are in contact with cell types expressing Lu/BCAM in wild-type mice, these results provide evidence that Lu/BCAM, as a laminin receptor, is involved in vivo in the maintenance of normal basement membrane organization in the kidney and intestine.

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7

Karabay, Onder, Mustafa Hasbahceci, and Huseyin Kadioglu. "Impact of breast cancer awareness month on detection of breast cancer in a private hospital." Journal of International Medical Research 46, no. 2 (March 29, 2017): 619–25. http://dx.doi.org/10.1177/0300060517699988.

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Objective Breast cancer awareness month increases public awareness in association with increased rates of screening and new diagnoses. This study aimed to evaluate the effect of breast cancer awareness month on primary diagnosis of breast cancer. Methods Asymptomatic women with the intention of breast cancer screening were included. The non-BCAM (Breast cancer awareness month) group were screened from February to September 2016 and the BCAM group during October 2016. Ultrasound and mammography were performed in all women and in those aged ≥ 40 years, respectively. A BIRADS (Breast Imaging Reporting And Data Systems) score of ≥4 and solid palpable masses without features suggestive of malignancy and/or the physician’s preference were regarded as indications for histopathological analysis. Requirement for histopathological analysis and detection of breast cancer were identified as the main variables. Results There were 198 women with a mean age of 49.3 ± 9.5 years. Sixty-nine and 129 women were in the non-BCAM and BCAM groups, respectively. Percutaneous biopsy was performed in seven (10.1%) and three patients (2.3%) in the non-BCAM and BCAM groups, respectively ( P = 0.035). Pathological examinations were benign. Conclusion Although public awareness campaigns lead to increased rates of screening, they may lose their impact on detecting breast cancer because of widespread use of routine screening programs.

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8

Wautier, Marie-Paule, Wassim El Nemer, Pierre Gane, Jean-Didier Rain, Jean-Pierre Cartron, Yves Colin, Caroline Le Van Kim та Jean-Luc Wautier. "Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin α5 chain and Lu/BCAM". Blood 110, № 3 (1 серпня 2007): 894–901. http://dx.doi.org/10.1182/blood-2006-10-048298.

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Abstract Patients with polycythemia vera (PV) have a JAK2 (a cytosolic tyrosine kinase) mutation and an increased risk of vascular thrombosis related to red blood cell (RBC) mass and platelet activation. We investigated functional RBC abnormalities that could be involved in thrombosis. RBC adhesion to human umbilical vein endothelial cells (HUVECs) was measured by a radiometric technique and in a flow system by video microscopy, and adhesion molecule expression was determined using specific antibodies (against CD36, CD49d, ICAM-4, Lu/BCAM, CD147, and CD47) and flow cytometry in a group of 38 patients with PV and a group of 36 healthy volunteers. Adhesion of PV RBCs was 3.7-fold higher than that of normal RBCs (P < .001). Adhesion was inhibited when PV RBCs were incubated with anti-Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) or when HUVECs were treated with anti-laminin α5 and to a lesser extent with anti-α3 integrin. Lu/BCAM was constitutively phosphorylated in PV RBCs. Transfection of K562 cells with JAK2 617V>F resulted in increased expression and phosphorylation of Lu/BCAM. Phosphorylation of Lu/BCAM increases RBC adhesion. Our results indicate that JAK2 mutation might be linked to Lu/BCAM modification and increased RBC adhesiveness, which may be a factor favoring thrombosis in PV.

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9

Andrei, Graciela, Rebecca Sienaert, Chris McGuigan, Erik De Clercq, Jan Balzarini, and Robert Snoeck. "Susceptibilities of Several Clinical Varicella-Zoster Virus (VZV) Isolates and Drug-Resistant VZV Strains to Bicyclic Furano Pyrimidine Nucleosides." Antimicrobial Agents and Chemotherapy 49, no. 3 (March 2005): 1081–86. http://dx.doi.org/10.1128/aac.49.3.1081-1086.2005.

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ABSTRACT Varicella-zoster virus (VZV) is responsible for primary infections as well as reactivations after latency in the dorsal root ganglia. The treatment of such infections is mandatory for immunocompromised patients and highly recommended for elderly patients with herpes zoster infections (also called zona or shingles). The treatment of choice is presently based on four molecules, acyclovir (ACV), valaciclovir, famciclovir, and (in Europe) brivudine (BVDU). We present here our data on the antiviral activity of a new class of potent and selective anti-VZV compounds, bicylic pyrimidine nucleoside analogues (BCNAs), against a broad variety of clinical isolates and different drug-resistant virus strains. The results show that the BCNAs are far more potent inhibitors than ACV and BVDU against clinical VZV isolates as well as the VZV reference strains Oka and YS. The BCNAs were not active against ACV- and BVDU-resistant VZV strains bearing mutations in the viral thymidine kinase gene but kept their inhibitory potential against virus strains with mutations in the VZV DNA polymerase gene. Mutant virus strains selected in the presence of the BCNAs were solely cross-resistant to drugs, such as ACV and BVDU, that depend for their antiviral action on metabolic activation by the viral thymidine kinase.

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Klei, T. R. L., D. Z. de Back, P. J. Asif, P. J. J. H. Verkuijlen, M. Veldthuis, P. C. Ligthart, J. Berghuis, et al. "Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte aging." Blood Advances 2, no. 1 (January 3, 2018): 14–24. http://dx.doi.org/10.1182/bloodadvances.2017013094.

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Key Points The Lu/BCAM adhesion molecule is gradually activated during erythrocyte aging due to loss of sialic acid on glycophorin-C. Upon activation, Lu/BCAM engages a sialic acid–dependent interaction with the extracellular matrix protein laminin-α5.

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11

Yasmin, Rojoba, and Russell Deaton. "Logical computation with self-assembling electric circuits." PLOS ONE 17, no. 12 (December 7, 2022): e0278033. http://dx.doi.org/10.1371/journal.pone.0278033.

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Inspired by self-assembled biological growth, the Circuit Tile Assembly Model (cTAM) was developed to provide insights into signal propagation, information processing, and computation in bioelectric networks. The cTAM is an abstract model that produces a family of circuits of different sizes that is amenable to exact analysis. Here, the cTAM is extended to the Boolean Circuit Tile Assembly Model (bcTAM) that implements a computationally complete set of Boolean gates through self-assembled and self-controlled growth. The proposed model approximates axonal growth in neural networks and thus, investigates the computational capability of dynamic biological networks, for example, in growing networks of axons. Thus, the bcTAM models the effect of electrical activity on growth and shows how that growth might implement Boolean computations. In this sense, given a set of input voltages, the bcTAM is a system that is able to monitor and make decisions about its own growth.

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Soffer, Arad, Adnan Mahly, Krishnanand Padmanabhan, Jonathan Cohen, Orit Adir, Eidan Loushi, Yaron Fuchs, Scott E. Williams, and Chen Luxenburg. "Apoptosis and tissue thinning contribute to symmetric cell division in the developing mouse epidermis in a nonautonomous way." PLOS Biology 20, no. 8 (August 15, 2022): e3001756. http://dx.doi.org/10.1371/journal.pbio.3001756.

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Mitotic spindle orientation (SO) is a conserved mechanism that governs cell fate and tissue morphogenesis. In the developing epidermis, a balance between self-renewing symmetric divisions and differentiative asymmetric divisions is necessary for normal development. While the cellular machinery that executes SO is well characterized, the extrinsic cues that guide it are poorly understood. Here, we identified the basal cell adhesion molecule (BCAM), a β1 integrin coreceptor, as a novel regulator of epidermal morphogenesis. In utero RNAi-mediated depletion of Bcam in the mouse embryo did not hinder β1 integrin distribution or cell adhesion and polarity. However, Bcam depletion promoted apoptosis, thinning of the epidermis, and symmetric cell division, and the defects were reversed by concomitant overexpression of the apoptosis inhibitor Xiap. Moreover, in mosaic epidermis, depletion of Bcam or Xiap induced symmetric divisions in neighboring wild-type cells. These results identify apoptosis and epidermal architecture as extrinsic cues that guide SO in the developing epidermis.

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13

Naguib, Marwa, Nicolás Feldman, Paulina Zarodkiewicz, Holly Shropshire, Christina Biamis, Omar M. El-Halfawy, Julia McCain, et al. "An evolutionary conserved detoxification system for membrane lipid–derived peroxyl radicals in Gram-negative bacteria." PLOS Biology 20, no. 5 (May 17, 2022): e3001610. http://dx.doi.org/10.1371/journal.pbio.3001610.

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How double-membraned Gram-negative bacteria overcome lipid peroxidation is virtually unknown. Bactericidal antibiotics and superoxide ion stress stimulate the transcription of the Burkholderia cenocepacia bcnA gene that encodes a secreted lipocalin. bcnA gene orthologs are conserved in bacteria and generally linked to a conserved upstream gene encoding a cytochrome b561 membrane protein (herein named lcoA, lipocalin-associated cytochrome oxidase gene). Mutants in bcnA, lcoA, and in a gene encoding a conserved cytoplasmic aldehyde reductase (peroxidative stress-associated aldehyde reductase gene, psrA) display enhanced membrane lipid peroxidation. Compared to wild type, the levels of the peroxidation biomarker malondialdehyde (MDA) increase in the mutants upon exposure to sublethal concentrations of the bactericidal antibiotics polymyxin B and norfloxacin. Microscopy with lipid peroxidation–sensitive fluorescent probes shows that lipid peroxyl radicals accumulate at the bacterial cell poles and septum and peroxidation is associated with a redistribution of anionic phospholipids and reduced antimicrobial resistance in the mutants. We conclude that BcnA, LcoA, and PsrA are components of an evolutionary conserved, hitherto unrecognized peroxidation detoxification system that protects the bacterial cell envelope from lipid peroxyl radicals.

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Bartolucci, Pablo, Vicky Chaar, Julien Picot, Dora Bachir, Anoosha Habibi, Christine Fauroux, Frédéric Galactéros, Yves Colin, Caroline Le Van Kim, and Wassim El Nemer. "Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation." Blood 116, no. 12 (September 23, 2010): 2152–59. http://dx.doi.org/10.1182/blood-2009-12-257444.

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Abstract Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level.

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15

Nishimura, Yoshito, and Jared D. Acoba. "Impact of Breast Cancer Awareness Month on Public Interest in the United States between 2012 and 2021: A Google Trends Analysis." Cancers 14, no. 10 (May 21, 2022): 2534. http://dx.doi.org/10.3390/cancers14102534.

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Breast Cancer Awareness Month (BCAM) has a long history of over 30 years, established in 1985 to occur every October, and the National Breast Cancer Foundation now leads the operation. There have been no studies to evaluate the impact of the BCAM on public awareness of breast cancer. We analyzed the impact of BCAM on public awareness of breast cancer in the U.S. from 2012 to 2021 using the relative search volume (RSV) of Google Trends as a surrogate. We also analyzed the impact of Lung Cancer Awareness Month (LCAM) and Prostate Cancer Awareness Month (PCAM) on public awareness of lung and prostate cancer, respectively, to see differences in their effectiveness among the health observances for the top three most common cancers in the U.S. We performed a joinpoint regression analysis to identify statistically significant time points of a change in trend. There were joinpoints around BCAM for “Breast cancer” every year from 2012 to 2021, with a significant increase in the weekly RSVs from 21.9% to 46.7%. Except for 2013 and 2015 for “Lung cancer”, when significant increases in the RSV at 1.8% and 1.2% per week were observed around LCAM, no joinpoints were noted around LCAM or PCAM. These results imply that BCAM has successfully improved the public awareness of breast cancer in the U.S. compared to other representative health observances, likely due to the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.

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Maciaszek, Jamie L., Biree Andemariam, and George Lykotrafitis. "A-Kinase Anchoring Proteins Mediate Healthy and Sickle Red Blood Cell Adhesion To Endothelial Laminin-5." Blood 122, no. 21 (November 15, 2013): 968. http://dx.doi.org/10.1182/blood.v122.21.968.968.

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Abstract Introduction Healthy and pathological human red blood cells (RBCs) express surface adhesion receptors which mediate interactions with the endothelium, platelets, and white blood cells. The adhesive properties of RBCs are defined by the density and distribution of adhesion receptors, and the binding force to specific ligands. In sickle cell disease (SCD), cytoadherence of RBCs to the vascular endothelium and subendothelial matrix is thought to be a major contributor to and possibly the primary cause of vasculopathy in SCD1. Painful vaso-occlusive episodes (VOEs), the hallmark of SCD, result from the blockage of small vessels. Here, we establish a molecular-level technique, based on atomic force microscopy (AFM), to measure the binding force between a specific ligand and its corresponding receptor on a single RBC. Using AFM, we can compare the frequency and localization of adhesion receptors present on the membrane of RBCs collected from healthy human volunteers and SCD patients. We focused on the interaction between basal cell adhesion molecule and its isoform Lutheran (BCAM/Lu) on the RBC and the subendothelial matrix protein laminin-5. Sickle RBCs (SS RBCs) overexpress BCAM/Lu and are more adherent to laminin-5 than healthy RBCs. Importantly, by using a flow adhesion assay, Hines et al2 demonstrated that the interaction between BCAM/Lu and laminin-5 is mediated by cyclic adenosine monophosphate (cAMP) which activates protein kinase A (PKA) and BCAM/Lu receptors. Because PKA binding can be mediated by A-kinase anchoring proteins (AKAPs), which sequester PKA to subcellular sites3, here we investigate whether AKAPs play a role in BCAM/Lu receptor activation on RBCs from healthy volunteers and SCD patients. Methods Peripheral blood RBCs were collected from consenting healthy volunteers (n=5) and individuals with SCD (n=4). RBCs were separated from whole blood using centrifugation. AFM was employed to quantify the frequency of active BCAM/Lu receptors on a single RBC. Molecular interactions were quantified by recording force v. distance curves between a laminin-5 functionalized probe and a 1μm2 area of the RBC surface with a lateral resolution of 30nm. Detected binding forces represent adhesive events between BCAM/Lu and laminin-5, which translate to the percentage of active BCAM/Lu receptors on the RBC surface. To detect the presence of AKAPs, RBCs were treated with St-Ht31 inhibitor peptide (83nM bath), which inhibits the interaction between the regulatory subunits of PKA and AKAP in cells. As a negative control, RBCs were treated with St-Ht31P control peptide (83nM bath), which is the inactive form of the St-Ht31 inhibitor peptide. Results Our experiments reveal that following treatment with St-Ht31, the frequency of active BCAM/Lu receptors is significantly lower on healthy RBCs (from 5.71±1.23% to 3.15±1.09%; p<0.05) and even more in SS RBCs (from 7.19±1.42% to 2.02±0.37%; p<0.0001). Treatment with St-Ht31P control peptide did not change the frequency of active BCAM/Lu receptors on healthy RBCs (5.92±1.09%) or SS RBCs (6.49±1.27%) as compared to baseline measurements. Conclusions Importantly, using St-Ht31, we confirm the presence of AKAPs as scaffold proteins which can modulate the adhesion of BCAM/Lu adhesion receptors on the SS RBC to laminin-5. PKA binding can be mediated by AKAPs, which sequester PKA to specific subcellular sites through binding to regulatory subunits3. Each AKAP contains two classes of binding sites: an anchoring motif, which binds the regulatory subunit of PKA, and a targeting domain, which directs the subcellular localization of the PKA-AKAP complex through association with structural proteins, membranes, or other components. This finding provides evidence for a new paradigm in AKAP adhesive signaling in RBCs and a potential new pharmacologic target for the prevention and treatment of VOEs in SCD. References: 1. Hillery CA, Panepinto JA. Pathophysiology of stroke in sickle cell disease. Microcirculation. 2004;11(2):195-208. 10.1080/10739680490278600. 2. Hines PC, Zen Q, Burney SN, et al. Novel epinephrine and cyclic amp-mediated activation of bcam/lu-dependent sickle (ss) rbc adhesion. Blood. 2003;101(8):3281-3287. 10.1182/blood-2001-12-0289. 3. Benovic JL. Novel β2-adrenergic receptor signaling pathways. Journal of Allergy and Clinical Immunology. 2002;110(6, Supplement):S229-S235. http://dx.doi.org/10.1067/mai.2002.129370. Disclosures: No relevant conflicts of interest to declare.

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Chitneni, Satish K., Jan Balzarini, Sofie Celen, Natalia Dyubankova, Alfons M. Verbruggen, and Guy M. Bormans. "Synthesis and biological evaluation of carbon-11-labeled acyclic and furo[2,3-d]pyrimidine derivatives of bicyclic nucleoside analogues (BCNAs) for structure–brain uptake relationship study of BCNA tracers." Journal of Labelled Compounds and Radiopharmaceuticals 51, no. 3 (2008): 159–66. http://dx.doi.org/10.1002/jlcr.1494.

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18

De Grandis, Maria, Marie Cambot, Marie-Paule Wautier, Bruno Cassinat, Christine Chomienne, Yves Colin, Jean-Luc Wautier, Caroline Le Van Kim, and Wassim El Nemer. "JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway." Blood 121, no. 4 (January 24, 2013): 658–65. http://dx.doi.org/10.1182/blood-2012-07-440487.

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Abstract Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.

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QIAO, Zenglin, Xinchao ZHAO, and Lingyu WU. "A Review of Evolutionary Deep Neural Architecture Search with Performance Predictor." Bulletin of Chinese Applied Mathematics 1, no. 1 (December 28, 2023): 1–9. http://dx.doi.org/10.48014/bcam.20230822002.

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Automated design of deep neural networks using performance predictor has become a hot topic in current research. Neural architecture search (NAS) methods can be used to enable automatic design of neural network structures by defining different search spaces, search strategies, or optimization strategies. Evolutionary computation by many researchers as the search strategy for NAS, which is called evolutionary NAS (ENAS) . However, ENAS is time-consuming in evaluating the performance of network structures, which hinders the development of ENAS. Therefore, predicting network architecture performance using performance predictor can improve ENAS search speed and save computational resources. This paper summarizes several ENAS methods that utilize performance predictor, and discusses an outlook on search space, search strategies, and the future directions of ENAS assisted by performance predictor.

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Hao, Du, and G. Raab Clemens. "Complete Reduction Systems for Airy Functions." Bulletin of Chinese Applied Mathematics 1, no. 1 (December 28, 2023): 10–21. http://dx.doi.org/10.48014/bcam.20230724002.

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The computation of indefinite integrals in some kinds of “closed form”, the so-called symbolic integration, is an important and basic research subarea of computer algebra. After implementing Risch’s algorithm partly, it was realized that efficient algorithms can be achieved in parallel integration. One of the most famous algorithms is the Risch-Norman algorithm. However, this approach relies on an analytic with heuristic degree bounds. Norman’s completion-based approach provides an alternative for finding the numerator of the integral avoiding heuristic degree bounds. However, depending on the differential field and on the selected ordering of terms, it may happen that the completion process does not terminate and yields an infinite number of reduction rules. We apply Norman’s approach to the differential fields generated by Airy functions, which play an important role in physics. By fixing adapted orderings and analyzing the process in the concrete case, we present two complete reduction systems for Airy functions by finitely many formulae to denoting infinitely many reduction rules.

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El Nemer, Wassim, Marie-Paule Wautier, Cécile Rahuel, Pierre Gane, Patricia Hermand, Frédéric Galactéros, Jean-Luc Wautier, Jean-Pierre Cartron, Yves Colin та Caroline Le Van Kim. "Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell α4β1integrin: role in adhesion of sickle red blood cells to endothelial cells". Blood 109, № 8 (7 грудня 2006): 3544–51. http://dx.doi.org/10.1182/blood-2006-07-035139.

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Abstract The Lutheran (Lu) blood group and basal cell adhesion molecule (BCAM) antigens are both carried by 2 glycoprotein isoforms of the immunoglobulin superfamily representing receptors for the laminin α5 chain. In addition to red blood cells, Lu/BCAM proteins are highly expressed in endothelial cells. Abnormal adhesion of red blood cells to the endothelium could potentially contribute to the vaso-occlusive episodes in sickle cell disease. Considering the presence of integrin consensus-binding sites in Lu/BCAM proteins, we investigated their potential interaction with integrin α4β1, the unique integrin expressed on immature circulating sickle red cells. Using cell adhesion assays under static and flow conditions, we demonstrated that integrin α4β1 expressed on transfected cells bound to chimeric Lu-Fc protein. We showed that epinephrine-stimulated sickle cells, but not control red cells, adhered to Lu-Fc via integrin α4β1 under flow conditions. Antibody-mediated activation of integrin α4β1 induced adhesion of sickle red cells to primary human umbilical vein endothelial cells; this adhesion was inhibited by soluble Lu-Fc and vascular cell adhesion molecule-1 (VCAM-1)–Fc proteins. This novel interaction between integrin α4β1 in sickle red cells and endothelial Lu/BCAM proteins could participate in sickle cell adhesion to endothelium and potentially play a role in vaso-occlusive episodes.

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Chien, Ai C., Rahima Zennadi, Laura M. De Castro, and Marilyn J. Telen. "Adhesive Characteristics of Hemoglobin SC Red Blood Cells." Blood 106, no. 11 (November 16, 2005): 3780. http://dx.doi.org/10.1182/blood.v106.11.3780.3780.

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Abstract Hemoglobin (Hb)-S containing red blood cells (RBCs) adhere abnormally to the vascular wall; this phenomenon is postulated to contribute to vaso-occlusive crisis and serious tissue damage. Patients homozygous for Hb S experience the most severe form of SCD, whereas heterozygous patients carrying Hb S and another hemoglobin variant, Hb C, experience somewhat milder clinical courses. Laminin is the extracellular matrix protein to which SS RBCs bind most avidly and is the ligand for the BCAM/Lu receptor. αvβ3 integrin is one of the major integrins on endothelial cells (ECs) and is the counter-receptor for LW on SS RBCs. Epinephrine activates both LW and BCAM/Lu on SS RBCs and thereby induces increased SS RBC adhesion to both ECs and laminin via a cAMP-dependent pathway. We have now compared the adhesive properties of Hb SC RBCs to SS RBCs. We measured the expression of RBC adhesion receptors, BCAM/Lu and LW, and assayed adhesion of SC RBCs to laminin and ECs (with and without prior stimulation of RBCs by epinephrine). Blood samples from Hb SC and SS patients in steady state and from normal controls (Hb AA) were collected into citrate tubes and were washed to remove plasma and buffy coat before use. The levels of BCAM/Lu and LW expression on RBCs were measured by flow cytometry using monoclonal antibodies to BCAM/Lu and anti-LW. SC RBCs expressed higher levels of BCAM/Lu (MFI 476.2, n=13) than did SS RBCs (MFI 332.3, n=33) and AA RBCs (MFI=225.5, n=16), but none of these differences were statistically significant (all p values >0.05). The levels of LW expression were also similar on AA, SC, and SS RBCs. Adhesion to laminin and ECs was measured as previously described, in a graduated height flow chamber. Non-treated, sham-treated, and epinephrine-treated RBCs were each infused into a flow chamber fitted with a slide coated with laminin or ECs. After washing at a constant rate, adherent RBCs were quantitated at points of different shear stresses. Adhesion of SC RBCs to laminin (mean of 53.1 cells/mm2 at 1 dyne/cm2, n=9) was lower than that of SS RBCs (mean of 69.0 cells/mm2 at 1 dyne/cm2, n=6, p=0.459) but was markedly higher than the adhesion seen with AA RBCs (mean of 0.03 cells/mm2 at 1 dyne/cm2, n=3, SC vs AA p=0.011). A positive correlation was found between BCAM/Lu expression and SC RBC adhesion to laminin (r=0.638, p=0.047). While epinephrine induced an increase in SC RBC adhesion to laminin in only 10% of all SC patient samples tested (compared to 50% of SS patients), epinephrine upregulated SC RBC adhesion to ECs approximately 10-fold in all samples tested (n=3). We conclude that SC RBCs represent an intermediate adhesive phenotype compared to AA and SS RBCs. While BCAM/Lu-mediated adhesion to laminin was lower on SC RBCs than on SS RBCs, unstimulated BCAM/Lu adhesive function was strikingly enhanced in relation to AA RBCs. Most importantly, epinephrine uniformly increased SC RBC adhesion to ECs, suggesting that in Hb SC disease, physiological stress may induce SC RBC adhesion and vaso-occlusive crises by mechanisms similar to those postulated to occur as a result of stress in Hb SS disease.

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Liu, Na, Ping Li, Jie Wang, Dan-dan Chen, Wei-jia Sun, Ping-ping Guo, Xue-hui Zhang, and Wei Zhang. "Psychometric properties of the Breast Cancer Awareness Measurement among Chinese women: a cross-sectional study." BMJ Open 10, no. 3 (March 2020): e035911. http://dx.doi.org/10.1136/bmjopen-2019-035911.

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ObjectivesTo perform the cross-cultural adaption of the Breast Cancer Awareness Measurement (BCAM) and to test its psychometric properties among Chinese women.DesignThis is a cross-sectional study.SettingsThis study was conducted in communities, schools and institutions in Changchun, Jilin Province, China.ParticipantsA total of 328 women voluntarily participated in and completed the Chinese version of the BCAM (C-BCAM), resulting in an effective response rate of 91.1%.Primary and secondary outcome measuresPsychometric properties, including item analysis (the extreme group comparison and item-total correlations), content validity (item-level content validity index (I-CVI) and scale-level content validity index (S-CVI)), construct validity (exploratory factor analysis (EFA) and confirmatory factor analysis (CFA)) and internal consistency (Cronbach’s α and test–retest reliability), were measured.ResultsThe C-BCAM has excellent internal consistency (Cronbach’s α=0.90), with alpha coefficients of 0.88, 0.84 and 0.94 for its three domains. The test–retest reliability coefficient was 0.72. The I-CVI ranged from 0.86 to 1.00, and the S-CVI was 0.92. CFA showed that the three-factor model explained 51.56% of the total variance, with a good model fit (likelihood ratio χ2/df=1.86, incremental fit index=0.94, comparative fit index=0.94, goodness-of-fit index=0.84, adjusted goodness-of-fit index=0.80, standardised root mean square error of approximation=0.06 and root mean square residual=0.05).ConclusionsThe C-BCAM has satisfactory validity and reliability and is a culturally appropriate and reliable tool for evaluating breast cancer awareness among Chinese women. This reliable instrument can help researchers and health professionals evaluate women’s knowledge about the symptoms and risk factors of breast cancer and identify their barriers to seeking medical help. It also helps healthcare providers identify women with poor breast cancer awareness and encourage them to perform screening practice.

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Kridl, Jean C., David W. McCarter, Ronald E. Rose, Donna E. Scherer, Deborah S. Knutzon, Sharon E. Radke, and Vic C. Knauf. "Isolation and characterization of an expressed napin gene fromBrassica rapa." Seed Science Research 1, no. 4 (December 1991): 209–19. http://dx.doi.org/10.1017/s0960258500000921.

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AbstractAn expressed napin storage protein gene fromBrassica rapa, BcNA1, has been cloned and sequenced. The gene is a member of a family of four to seven napin genes inB. rapaand is highly expressed in developing seeds. An expression cassette containing the DNA flanking the napin coding region of BcNA1 has been engineered and demonstrated to function appropriately, as compared with the gene's endogenous expression, in transgenic rapeseed using the β-glucuronidase reporter gene. TheB. rapaBcNA1 gene and aB. napusnapin gene, gNa, share extremely high nucleotide homology not only throughout their coding regions, but over a DNA locus comprising 4.3 kb. We suggest the gNa gene was contributed by the originalB. rapaprogenitor of the amphidiploidB. napus.

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25

Wilson, Jo Ellen, Leanne Boehm, Lauren R. Samuels, Deborah Unger, Martha Leonard, Christianne Roumie, E. Wesley Ely, Robert S. Dittus, Sumi Misra, and Jin H. Han. "Use of the brief Confusion Assessment Method in a veteran palliative care population: A pilot validation study." Palliative and Supportive Care 17, no. 5 (March 19, 2019): 569–73. http://dx.doi.org/10.1017/s1478951518001050.

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AbstractObjectiveMany patients with advanced serious illness or at the end of life experience delirium, a potentially reversible form of acute brain dysfunction, which may impair ability to participate in medical decision-making and to engage with their loved ones. Screening for delirium provides an opportunity to address modifiable causes. Unfortunately, delirium remains underrecognized. The main objective of this pilot was to validate the brief Confusion Assessment Method (bCAM), a two-minute delirium-screening tool, in a veteran palliative care sample.MethodThis was a pilot prospective, observational study that included hospitalized patients evaluated by the palliative care service at a single Veterans’ Administration Medical Center. The bCAM was compared against the reference standard, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Both assessments were blinded and conducted within 30 minutes of each other.ResultWe enrolled 36 patients who were a median of 67 years (interquartile range 63–73). The primary reasons for admission to the hospital were sepsis or severe infection (33%), severe cardiac disease (including heart failure, cardiogenic shock, and myocardial infarction) (17%), or gastrointestinal/liver disease (17%). The bCAM performed well against the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, for detecting delirium, with a sensitivity (95% confidence interval) of 0.80 (0.4, 0.96) and specificity of 0.87 (0.67, 0.96).Significance of ResultsDelirium was present in 27% of patients enrolled and never recognized by the palliative care service in routine clinical care. The bCAM provided good sensitivity and specificity in a pilot of palliative care patients, providing a method for nonpsychiatrically trained personnel to detect delirium.

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Johnson, Clarissa E., and Marilyn J. Telen. "Hydroxyurea Therapy Increases Expression of BCAM/LU and Adhesion to Laminin in Children with Sickle Cell Disease." Blood 112, no. 11 (November 16, 2008): 4806. http://dx.doi.org/10.1182/blood.v112.11.4806.4806.

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Abstract Vaso-occlusion is the major cause of morbidity and mortality in sickle cell disease. The tendency of red blood cells (RBCs) to adhere to extracellular matrix molecules and the vascular endothelium is believed to be a significant contributor to the vaso-occlusive process. Some published studies have shown that hydroxyurea decreases sickle (SS) RBC adhesion to some ligands, although the mechanism by which this occurs is not completely understood. SS RBCs demonstrate increased expression of several adhesion molecules, especially BCAM/LU, and also conserve functional signaling pathways that are associated with upregulation of adhesion. BCAM/LU mediates adhesion to the extracellular matrix protein laminin. We hypothesized that patients responsive to hydroxyurea (HU) therapy would exhibit reduced adhesion to laminin as well as a decrease in adhesion molecule expression. Our subjects included patients with Hb SS between the ages of 5 to 18. They were divided into three groups: children not receiving HU therapy (n = 3); children receiving HU therapy for over 6 months (n = 5), and children initially not receiving HU but who were initiating therapy at the time of study enrollment (n = 5). Adhesion to laminin was examined using a graduated height flow chamber to quantitate the adhesion of SS RBCs. Expression of adhesion molecules was analyzed by western blot and densitometry, using monoclonal antibody to BCAM/LU. We found that HU therapy was associated with significantly increased expression of BCAM/LU (HU: 145.8 ± 14.0 SEM; no HU: 60.8 ± 11.0 SEM densitometry units, p = .0014). This somewhat unexpected finding confirms results published earlier this year by Odievre et al. (2008). Adhesion to laminin was also increased for patients on HU (HU: 9.3 ± 5.9; no HU: .3 ± .3, p=.2), although this increase was not significant, given the variability in adhesion seen among patients and the small number of subjects. Nevertheless, the increase in adhesion corresponded to the increase in BCAM/LU expression. In contrast, adhesion to endothelial cells was decreased, although not significantly, in patients on HU (HU: 38.1 ± 38; no HU: 127.2 ± 122.5, p=.6). Our findings thus confirm earlier published data showing that HU increases the expression of BCAM/LU measured by flow cytometry and further shows that this increased expression is associated with increased adhesion to laminin but not to endothelial cells. Potential mechanisms by which HU affects adhesion molecule expression and activity merit further investigation, as does the physiologic role of these alterations. Comparison of results from patient-matched pre-treatment and post-treatment samples should also help define the effects of HU. Figure Figure

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Bru, Jean-Bernard, and Carlos Pérez. "BCAM, the Basque Center for Applied Mathematics." EMS Newsletter 2018-9, no. 109 (September 3, 2018): 42–45. http://dx.doi.org/10.4171/news/109/10.

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Dass, M. L. A., T. A. Bielicki, G. Thomas, T. Yamamoto, and K. Okazaki. "Convergent-bceam diffraction studies on lead zirconate titanate Ceramics." Proceedings, annual meeting, Electron Microscopy Society of America 44 (August 1986): 482–83. http://dx.doi.org/10.1017/s0424820100143961.

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Lead zirconate titanate, Pb(Zr,Ti)O3 (PZT), ceramics are ferroelectrics formed as solid solutions between ferroelectric PbTiO3 and ant iferroelectric PbZrO3. The subsolidus phase diagram is shown in figure 1. PZT transforms between the Ti-rich tetragonal (T) and the Zr-rich rhombohedral (R) phases at a composition which is nearly independent of temperature. This phenomenon is called morphotropism, and the boundary between the two phases is known as the morphotropic phase boundary (MPB). The excellent piezoelectric and dielectric properties occurring at this composition are believed to.be due to the coexistence of T and R phases, which results in easy poling (i.e. orientation of individual grain polarizations in the direction of an applied electric field). However, there is little direct proof of the coexistence of the two phases at the MPB, possibly because of the difficulty of distinguishing between them. In this investigation a CBD method was found which would successfully differentiate between the phases, and this was applied to confirm the coexistence of the two phases.

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McGuigan, Christopher, Marco Migliore, Geoffrey Henson, Joseph Patti, Graciela Andrei, Robert Snoeck, and Jan Balzarini. "Design, Synthesis and Evaluation of Novel Anti-VZV BCNAs." Antiviral Research 78, no. 2 (May 2008): A29. http://dx.doi.org/10.1016/j.antiviral.2008.01.047.

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Ribeiro, Thaissa Saraiva, Matheus Arrais Gonçalves, Geraldo Narciso da Rocha Filho, and Leyvison Rafael Vieira da Conceição. "Functionalized Biochar from the Amazonian Residual Biomass Murici Seed: An Effective and Low-Cost Basic Heterogeneous Catalyst for Biodiesel Synthesis." Molecules 28, no. 24 (December 7, 2023): 7980. http://dx.doi.org/10.3390/molecules28247980.

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This study presents the synthesis of a basic heterogeneous catalyst based on sodium functionalized biochar. The murici biochar (BCAM) support used in the process was obtained through the pyrolysis of the murici seed (Byrsonimia crassifolia), followed by impregnation of the active phase in amounts that made it possible to obtain concentrations of 6, 9, 12, 15 and 18% of sodium in the final composition of the catalyst. The best-performing 15Na/BCAM catalyst was characterized by Elemental Composition (CHNS), Thermogravimetric Analysis (TG/DTG), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and Energy Dispersion X-ray Spectroscopy (EDS). The catalyst 15Na/BCAM was applied under optimal reaction conditions: temperature of 75 °C, reaction time of 1.5 h, catalyst concentration of 5% (w/w) and MeOH:oil molar ratio of 20:1, resulting in a biodiesel with ester content of 97.20% ± 0.31 in the first reaction cycle, and maintenance of catalytic activity for five reaction cycles with ester content above 65%. Furthermore, the study demonstrated an effective catalyst regeneration process, with the synthesized biodiesels maintaining ester content above 75% for another five reaction cycles. Thus, the data indicate a promising alternative to low-cost residual raw materials for the synthesis of basic heterogeneous catalysts.

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Drusbosky, Leylah, Amy Meacham, Elizabeth Wise, Edward W. Scott, and Christopher R. Cogle. "Bone Marrow Endothelial Cells Protect Acute Myeloid Leukemia From Chemotherapy By Direct Contact: The BCAM/Laminin/VLA5 Axis As a Potential Therapeutic Target." Blood 122, no. 21 (November 15, 2013): 2546. http://dx.doi.org/10.1182/blood.v122.21.2546.2546.

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Abstract Causes of refractory acute myeloid leukemia (AML) are unknown, but may be related to the bone marrow (BM) vascular network given the close relationship between hematopoiesis and the vasculature. We hypothesized that endothelial cells (ECs) provide a protective advantage to AML cells. To test this hypothesis, we first cultured human AML cells with and without primary bone marrow endothelial cells (BMECs). Co-cultures of AML cells and BMECs were then exposed to increasing doses of cytarabine chemotherapy. There was a 2-fold decrease in leukemia cell death of AML cells when adhered to BMECs compared to non-adhered (30% vs. 60%, P < 0.0001). Even irradiated BMECs protected AML cells from cytarabine chemotherapy. To identify adhesion molecules mediating this protective effect, we analyzed cell membranes and supernatants of the cytarabine-treated co-cultures using protein microarrays. After cytarabine exposure, the Lutheran blood group glycoprotein basal cell adhesion molecule (BCAM) was upregulated in both human AML cells and BMECs. Prior work has shown BCAM as a receptor for Laminin and VLA5. As AML cells are known to express VLA5, we hypothesized that blocking BCAM may represent a novel therapeutic strategy. Blocking BCAM with neutralizing antibodies resulted in a 75% increase in non-adherent AML cells. Together, these in vitro results support the concept that ECs may be a protective reservoir for AML cells, at a minimum by means of adhesion molecules. BCAM represents a viable target. Because of the complex nature of the leukemia microenvironment, we sought to test this concept in vivo. Prior intravital efforts have focused on calvaria bone, which may over-represent the endosteal niche and under-represent the vascular niche due to the very close approximation of bone surfaces. Therefore, we created an intravital animal model of human AML to track single AML cells in the bone marrow of mouse long bones. In brief, we irradiated NOD/scid/IL2Rγnull (NSG) mice, drilled a window on the tibia surface, xenotransplanted fluorescently tagged human AML cells via IV injection, and then analyzed the tibias by fluorescent microscopy for the presence of AML cells at various time points after transplant. Initially the AML cells homed to endosteal surfaces of the bone marrow as early as one day after transplant. Over time, the AML cells lining the endosteum remained as single cells or very small clusters of a few cells. However, in the central marrow region the AML cells proliferated into massive clusters around blood vessels. Ongoing experiments are being performed to determine the disruption and resurgence of AML cells after chemotherapy and blockade of adhesion molecules. In sum, ECs protect human AML cells from chemotherapy by direct contact and the BCAM/Laminin/VLA5 axis may be a therapeutic target. Using our unique intravital imaging model of bone marrow in long bones, the endosteal niche appears to be the first site of homing and engraftment while the vascular niche appears to be the site for leukemia proliferation/progression. Disclosures: No relevant conflicts of interest to declare.

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Hines, Patrick C., Qin Zen, Sharran N. Burney, Deborah A. Shea, Kenneth I. Ataga, Eugene P. Orringer, Marilyn J. Telen, and Leslie V. Parise. "Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion." Blood 101, no. 8 (April 15, 2003): 3281–87. http://dx.doi.org/10.1182/blood-2001-12-0289.

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Abstract The vasoocclusive crisis is the major clinical feature of sickle cell anemia, which is believed to be initiated or sustained by sickle (SS) red blood cell (RBC) adhesion to the vascular wall. SS RBCs, but not unaffected (AA) RBCs, adhere avidly to multiple components of the vascular wall, including laminin. Here we report a novel role for epinephrine and cyclic adenosine monophosphate (cAMP) in the regulation of human SS RBC adhesiveness via the laminin receptor, basal cell adhesion molecule/Lutheran (BCAM/Lu). Our data demonstrate that peripheral SS RBCs contain greater than 4-fold more cAMP than AA RBCs under basal conditions. Forskolin or the stress mediator epinephrine further elevates cAMP in SS RBCs and increases adhesion of SS RBCs to laminin in a protein kinase A (PKA)–dependent manner, with the low-density population being the most responsive. Epinephrine-stimulated adhesion to laminin, mediated primarily via the β2-adrenergic receptor, occurred in SS RBC samples from 46% of patients and was blocked by recombinant, soluble BCAM/Lu, implicating this receptor as a target of cAMP signaling. Thus, these studies demonstrate a novel, rapid regulation of SS RBC adhesion by a cAMP-dependent pathway and suggest that components of this pathway, particularly PKA, the β2-adrenergic receptor, and BCAM/Lu, should be further explored as potential therapeutic targets to inhibit SS RBC adhesion.

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Redden, Miles D., Daniel W. Shike, and Joshua C. McCann. "335 Metabolizable protein requirement of lightweight beef calves." Journal of Animal Science 97, Supplement_2 (July 2019): 136. http://dx.doi.org/10.1093/jas/skz122.241.

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Abstract The objective was to assess the metabolizable protein (MP) requirements of lightweight beef steers. The 2016 Beef Cattle Nutrient Requirements Model (BCNRM) prediction of MP requirements in lightweight beef steers (less than 250 kg) is limited by available performance data in beef calves. Fall born Angus × Simmental crossbred steers (n = 172; BW = 153 kg) were weaned at 70 d of age (± 26 d), backgrounded 73 d, implanted with Component TE-IS, blocked by BW as light (96–163 kg) or heavy (163–215 kg), and assigned to one of four treatments for 56 d. Treatment diets provided MP at: 0.59 (MP1), 0.69 (MP2), 0.85 (MP3), and 0.91 kg per d (MP4) based on observed DMI. Energy was similar across all treatments at 2.14 Mcal/kg ME. Shrunk body weights were collected on d 0 and 56 to estimate performance. Dry matter intake was affected (P < 0.01) by treatment and increased (linear; P < 0.01) with greater provision of MP. As a percent of shrunk body weight, DMI averaged 2.8% and tended (linear; P = 0.07) to increase with MP. Based on observed DMI, ADG for MP1, MP2, MP3, and MP4 was predicted using the BCNRM at 1.15, 1.55, 1.99, and 1.98 kg, respectively. Observed ADG increased quadratically (P = 0.01) with MP1, MP2, MP3, and MP4 gaining 1.86, 2.13, 2.3, and 2.3 kg, respectively. Final BW increased (quadratic; P = 0.02) with greater MP as MP1, MP2, MP3, and MP4 were 258, 273, 282, and 284 kg, respectively. Gain:feed increased quadratically (P = 0.04) with observed values for MP1, MP2, MP3, and MP4 being 0.323, 0.357, 0.359, and 0.360, respectively. Steer ADG response exceeded BCNRM predictions by 29%. Data suggest MP requirements of lightweight beef steers (BW = 213 kg) are 0.85 kg per d to achieve 2.3 kg ADG when fed a 2.14 Mcal/kg ME diet.

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Yang, Ruoli, Yaowen Hu, Ye Yao, Ming Gao, and Runmin Liu. "Fruit Target Detection Based on BCo-YOLOv5 Model." Mobile Information Systems 2022 (July 7, 2022): 1–8. http://dx.doi.org/10.1155/2022/8457173.

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After the birth of deep learning, artificial intelligence has entered a vigorous period of rapid development. In this process of rising and growing, we have made one achievement after another. When deep learning is applied to fruit target detection, due to the complex recognition background, large similarity between models, serious texture interference, and partial occlusion of fruits, the fruit target detection rate based on traditional methods is low. In order to solve these problems, a BCo-YOLOv5 network model is proposed to recognize and detect fruit targets in orchards. We use YOLOv5s as the basic model for feature image extraction and target detection. This paper introduces BCAM (bidirectional cross attention mechanism) into the network and adds BCAM between the backbone network and the neck network of the YOLOv5s basic model. BCAM uses weight multiplication strategy and maximum weight strategy to build a deeper position feature relationship, which can better assist the network in detecting fruit targets in fruit images. After training and testing the network, the map BCo-YOLOv5 network model reaches 97.70%. In order to verify the detection ability of the BCo-YOLOv5 network to citrus, apple, grape, and other fruit targets, we conducted a large number of experiments BCo-YOLOv5 network. The experimental results of the BCo-YOLOv5 network show that this method can effectively detect citrus, apple, and grape targets in fruit images, and the fruit target detection method based on BCo-YOLOv5 network is better than most orchard fruit detection methods.

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Li, Ali, Rui Wang, Liyuan Liu, Lei Xu, Fei Wang, Fei Chang, Lixiang Yu, Yujuan Xiang, Fei Zhou, and Zhigang Yu. "BCRAM: A Social-Network-Inspired Breast Cancer Risk Assessment Model." IEEE Transactions on Industrial Informatics 15, no. 1 (January 2019): 366–76. http://dx.doi.org/10.1109/tii.2018.2825345.

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36

Murphy, Meghan M., Mohamed A. Zayed, Allyson Evans, Carol E. Parker, Kenneth I. Ataga, Marilyn J. Telen, and Leslie V. Parise. "Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU." Blood 105, no. 8 (April 15, 2005): 3322–29. http://dx.doi.org/10.1182/blood-2004-07-2881.

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Abstract Vaso-occlusion is a hallmark of sickle cell disease. Agonist-induced activation of sickle red blood cells (SS RBCs) promotes their adhesion to vascular proteins, potentially contributing to vasoocclusion. Previously, we described a cyclic adenosine monophosphate (cAMP)-dependent increase in SS RBC adhesion to laminin. Here, we investigated whether Rap1, a small guanosine triphosphatase (GTPase) known to promote integrin-mediated adhesion in other cells, was involved in this signaling pathway. We found that agonists known to induce cAMP signaling promoted the GTP-bound, active state of Rap1 in SS RBCs. The cAMP-dependent exchange factor Epac (exchange protein directly activated by cAMP) is a likely upstream activator of Rap1, since Epac is present in these cells and the Epac-specific cAMP analog 8CPT-2-Me (8-(4-cholorophenylthio)-2′-O-methyl-cAMP) activated Rap1 and promoted SS RBC adhesion to laminin. This 8CPT-2-Me-stimulated adhesion was integrin independent, since it was insensitive to RGD peptide or antibodies against the only known integrin on SS RBCs, α4β1. However, this adhesion was completely inhibited by either a soluble version of basal cell adhesion molecule/Lutheran (BCAM/LU) or a BCAM/LU adhesion-blocking anti-body. Surprisingly, 8CPT-2-Me-activated Rap1 did not promote SS RBC adhesion to a known α4β1 ligand, vascular cell adhesion molecule 1 (VCAM-1). These results demonstrate that Epac-induced Rap1 activation in SS RBCs promotes BCAM/LU-mediated adhesion to laminin. Thus, Epac-mediated Rap1 activation may represent an important signaling pathway for promoting SS RBC adhesion. (Blood. 2005;105:3322-3329)

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37

El Nemer, W., Y. Colin, and C. Le Van Kim. "Role of Lu/BCAM glycoproteins in red cell diseases." Transfusion Clinique et Biologique 17, no. 3 (September 2010): 143–47. http://dx.doi.org/10.1016/j.tracli.2010.06.002.

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38

Elshami, Mohamedraed, Hanan Abu Kmeil, Maymona Abu-Jazar, Ibtisam Mahfouz, Dina Ashour, Ansam Aljamal, Nada Mohareb, et al. "Breast Cancer Awareness and Barriers to Early Presentation in the Gaza-Strip: A Cross-Sectional Study." Journal of Global Oncology, no. 4 (December 2018): 1–13. http://dx.doi.org/10.1200/jgo.18.00095.

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Purpose Timely detection of breast cancer (BC) is important to reduce its related deaths. Hence, high awareness of its symptoms and risk factors is required. This study aimed to assess the awareness level of BC among females in Gaza. Materials and Methods A cross-sectional study was performed during September and October 2017 in Gaza, Palestine. Stratified sampling was used to recruit patients from four hospitals and seven high schools. The validated Breast Cancer Awareness Measure (BCAM) was used to assess confidence and behavior in relation to breast changes, awareness of BC symptoms and risk factors, barriers to seek medical help, and knowledge of BC screening. Women (age ≥ 18 years) visiting or admitted to any of the four hospitals, and female adolescents (age 15 to 17 years) in any of the seven schools, were recruited for face-to-face interviews to complete the BCAM. Results Of 3,055 women approached, 2,774 participants completed the BCAM questionnaire (response rate, 90.8%); 1,588 (57.2%) were adults, and 1,186 (42.8%) were adolescents. Of these, 1,781 (64.2%) rarely (or never) checked their breasts, and 909 (32.8%) were not confident to notice changes. In total, 1,675 (60.4%) were aware of the availability of BC screening programs. The overall mean ± standard deviation score for awareness of BC symptoms was 5.9 ± 2.9 of 11, and that of risk factors 7.5 ± 3.1 of 16. Feeling scared was the most reported barrier to seeking advice reported among women (n = 802; 50.2%), whereas feeling embarrassed was the most reported in adolescents (n = 745; 62.8%). Conclusion Awareness of BC symptoms, risk factors, and screening programs is suboptimal in Gaza. Educational interventions are necessary to increase public awareness of BC and to train local female breast surgeons to address barriers to early detection.

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De Brevern, Alexandre G., Aline Floch, and Connie M. Westhoff. "Un modèle structural 3D complet de la protéine Lutheran (BCAM)." Transfusion Clinique et Biologique 28, no. 4 (November 2021): S108. http://dx.doi.org/10.1016/j.tracli.2021.08.316.

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40

Colin, Y., C. Rahuel, M. P. Wautier, W. El Nemer, A. Filipe, J. P. Cartron, C. Le Van Kim, and J. L. Wautier. "Red cell and endothelial Lu/BCAM beyond sickle cell disease." Transfusion Clinique et Biologique 15, no. 6 (December 2008): 402–5. http://dx.doi.org/10.1016/j.tracli.2008.07.011.

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41

Latini, Flavia Roche Moreira, André Uchimura Bastos, Carine Prisco Arnoni, Janaína Guilhem Muniz, Rosangela Medeiros Person, Wilson Baleotti, José Augusto Barreto, Lilian Castilho, and Janete Maria Cerutti. "DARC (Duffy) and BCAM (Lutheran) reduced expression in thyroid cancer." Blood Cells, Molecules, and Diseases 50, no. 3 (March 2013): 161–65. http://dx.doi.org/10.1016/j.bcmd.2012.10.009.

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42

Pertenbreiter, Florian, and Chris Meier. "Synthesis and Properties of CycloSal-phosphatetriesters of Fluorescent Bicyclic Nucleoside Analogues (BCNAS)." Antiviral Research 82, no. 2 (May 2009): A62. http://dx.doi.org/10.1016/j.antiviral.2009.02.149.

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43

Akiyama, Hirotada, Yoshimasa Iwahana, Mikiya Suda, Atsunori Yoshimura, Hiroyuki Kogai, Ai Nagashima, Hiroko Ohtsuka, Yuko Komiya, and Fumio Tashiro. "The FBI1/Akirin2 Target Gene, BCAM, Acts as a Suppressive Oncogene." PLoS ONE 8, no. 11 (November 6, 2013): e78716. http://dx.doi.org/10.1371/journal.pone.0078716.

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44

Derudas, Marco, Maurizio Quintiliani, Christopher McGuigan, Andrea Brancale, Geoffrey Henson, and Jan Balzarini. "Design, Synthesis, and Biological Evaluation of Novel Fluoro Derivatives of BCNA." Antiviral Research 82, no. 2 (May 2009): A57. http://dx.doi.org/10.1016/j.antiviral.2009.02.135.

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45

Wautier, Jean-Luc, and Marie-Paule Wautier. "Cellular and Molecular Aspects of Blood Cell–Endothelium Interactions in Vascular Disorders." International Journal of Molecular Sciences 21, no. 15 (July 27, 2020): 5315. http://dx.doi.org/10.3390/ijms21155315.

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In physiology and pathophysiology the molecules involved in blood cell–blood cell and blood cell–endothelium interactions have been identified. Platelet aggregation and adhesion to the walls belonging to vessels involve glycoproteins (GP), GP llb and GP llla and the GP Ib–IX–V complex. Red blood cells (RBCs) in normal situations have little interaction with the endothelium. Abnormal adhesion of RBCs was first observed in sickle cell anemia involving vascular cell adhesion molecule (VCAM)-1, α4β1, Lu/BCAM, and intercellular adhesion molecule (ICAM)-4. More recently RBC adhesion was found to be increased in retinal-vein occlusion (RVO) and in polycythemia vera (PV). The molecules which participate in this process are phosphatidylserine and annexin V in RVO, and phosphorylated Lu/BCAM and α5 laminin chain in PV. The additional adhesion in diabetes mellitus occurs due to the glycated RBC band 3 and the advanced glycation end-product receptors. The multiligand receptor binds advanced glycation end products (AGEs) or S100 calgranulins, or β-amyloid peptide. This receptor for advanced glycation end products is known as RAGE. The binding to RAGE-activated endothelial cells leads to an inflammatory reaction and a prothrombotic state via NADPH activation and altered gene expression. RAGE blockade is a potential target for drugs preventing the deleterious consequences of RAGE activation.

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Klei, Thomas R. L., Jill J. Dalimot, Boukje M. Beuger, Martijn Veldthuis, Fatima Ait Ichou, Paul J. J. H. Verkuijlen, Iris M. Seignette, et al. "The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation." Blood Advances 4, no. 24 (December 16, 2020): 6218–29. http://dx.doi.org/10.1182/bloodadvances.2020003077.

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Abstract Senescence of erythrocytes is characterized by a series of changes that precede their removal from the circulation, including loss of red cell hydration, membrane shedding, loss of deformability, phosphatidyl serine exposure, reduced membrane sialic acid content, and adhesion molecule activation. Little is known about the mechanisms that initiate these changes nor is it known whether they are interrelated. In this study, we show that Ca2+-dependent K+ efflux (the Gardos effect) drives erythrocyte senescence. We found that increased intracellular Ca2+ activates the Gardos channel, leading to shedding of glycophorin-C (GPC)–containing vesicles. This results in a loss of erythrocyte deformability but also in a marked loss of membrane sialic acid content. We found that GPC-derived sialic acid residues suppress activity of both Lutheran/basal cell adhesion molecule (Lu/BCAM) and CD44 by the formation of a complex on the erythrocyte membrane, and Gardos channel–mediated shedding of GPC results in Lu/BCAM and CD44 activation. This phenomenon was observed as erythrocytes aged and on erythrocytes that were otherwise prone to clearance from the circulation, such as sickle erythrocytes, erythrocytes stored for transfusion, or artificially dehydrated erythrocytes. These novel findings provide a unifying concept on erythrocyte senescence in health and disease through initiation of the Gardos effect.

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47

Sun, Weimin, Guangcheng Zhang, Ling Pan, Helin Li, and Aihua Shi. "Synthesis, Characterization, and Flocculation Properties of Branched Cationic Polyacrylamide." International Journal of Polymer Science 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/397027.

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A water soluble branched cationic polyacrylamide (BCPAM) was synthesized using solution polymerization. The polymerization was initiated using potassium diperiodatocuprate, K5[Cu(HIO6)2](Cu(III)), initiating the self-condensing vinyl copolymerization of acrylamide and acryloxyethyltrimethyl ammonium chloride (DAC) monomer. The resulting copolymer was characterized by the use of Fourier-transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Its flocculation properties were evaluated with standard jar tests of sewage. The effects of initiator concentration, monomer concentration, reaction temperature, and the mass ratio of monomers on intrinsic viscosity and flocculation properties of the product were determined using single-factor experiments and orthogonal experiment.

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De Clercq, Erik. "FV-100 for the Treatment of Varicella-Virus (VZV) Infections: Quo Vadis?" Viruses 14, no. 4 (April 7, 2022): 770. http://dx.doi.org/10.3390/v14040770.

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The bicyclic nucleoside analogue (BCNA) Cf1743 and its orally bioavailable prodrug FV-100 have unique potential as varicella-zoster virus (VZV) inhibitors to treat herpes zoster (shingles) and the therewith associated pain, including post-herpetic neuralgia (PHN). The anti-VZV activity of Cf1743 depends on a specific phosphorylation by the VZV-encoded thymidine kinase (TK). The target of antiviral action is assumed to be the viral DNA polymerase (or DNA synthesis in the virus-infected cells).

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Finkelshtein, Alin, Neta Shlezinger, Olga Bunis, and Amir Sharon. "Botrytis cinerea BcNma is involved in apoptotic cell death but not in stress adaptation." Fungal Genetics and Biology 48, no. 6 (June 2011): 621–30. http://dx.doi.org/10.1016/j.fgb.2011.01.007.

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50

Janeba, Zlatko, Antonín Holý, Radek Pohl, Robert Snoeck, Graciela Andrei, Erik De Clercq, and Jan Balzarini. "Synthesis and biological evaluation of acyclic nucleotide analogues with a furo[2,3-d]pyrimidin-2(3H)-one base." Canadian Journal of Chemistry 88, no. 7 (July 2010): 628–38. http://dx.doi.org/10.1139/v10-054.

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As a part of a broader structure–activity relationship (SAR) study of bicyclic nucleoside analogues (BCNAs) [anti-varicella-zoster virus (anti-VZV) and anti-human cytomegalovirus (anti-HCMV) agents], a novel series of 2-(phosphonomethoxy)ethyl (PME) substituted furo[2,3-d]pyrimidin-2(3H)-ones was synthesized. The target acyclic nucleotide analogues were prepared by Sonogashira coupling of protected 5-iodo-1-[2-(phosphonomethoxy)ethyl]uracil with various 1-alkynes, followed by in situ Cu(I)-promoted intramolecular cyclization and standard removal of the isopropyl ester groups. None of the prepared PME analogues were active at subtoxic concentrations against VZV thymidine kinase competent (TK+), VZV thymidine kinase deficient (TK–), HCMV, or any other viruses tested.

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