Discovery of Multiple High-Velocity Narrow Circumstellar Na I D Lines in Nova V1280 Sco

We discovered multiple high-velocity (ranging from -900 to -650 km/s) and narrow (FWHM = 15 km/s) absorption components corresponding to both the D2 and the D1 lines of Na I on a high dispersion spectrum of V1280 Sco observed on 2009 May 9 (UT), 814 d after the V-band maximum. Subsequent observations carried out on 2009 June and July confirmed at least 11 distinct absorption components in both systems. Some components had deepened during the two months period while their HWHMs and wavelengths remained nearly constant. We suggest these high velocity components originate in cool clumpy gas clouds moving on the line of sight, produced in interactions between pre-existing cool circumstellar gas and high velocity gas ejected in the nova explosion. The optical region spectrum of V1280 Sco in 2009 is dominated by the continuum radiation and exhibits no forbidden line characterizing the nebular phase of typical novae. Permitted Fe II lines show doubly peaked emission profiles and some strong Fe II lines are accompanied by a blue shifted (about -255 km/s) absorption component. However, no high-velocity and narrow components corresponding to those of Na I could be detected in Fe II lines nor in the Balmer lines. The 255 km/s low velocity absorption component is most probably originating in the wind from the nova.Comment: Accepted for PASJ letter, 5 pages, 8 figure

U.S. Inflation Trends and the 2008 Recession

The U.S Federal Reserve Board uses long term inflation trends and projections to guide its policy decisions on controlling inflation. The objective of this study is to determine if the severe recession in 2008 altered the long term trend in inflation. Using the Consumer Price Index (CPI) as well as the Personal Consumption Expenditure Index (PCE) for our measures of inflation, we first divide the overall period of analysis into two nine year periods, 1999-2007 and 2009-2017, with 2008 the inflection point. Using linear regression with time as the independent variable, we develop regression coefficients (B) for both nine year periods and test the hypothesis that the 1999-2007 B coefficient is larger than the 2009-2017 B coefficient. If the hypothesis is correct, the difference in the B coefficients can be considered a proxy for the 2008 recession effect on trend inflation. We also run another test where a linear regression is run for the complete period but a dummy variable, D1, is added to the equation line with D1=1 for the 12 months in 2008. We test for a negative coefficient attached to D1, which indicates a downward shift in the regression line and provides another measure of the effect of the 08 recession on the inflation trend. Finally we test for a Phillips Curve effect on inflation trend in the 2009-2017 period. With U.S. unemployment reaching a rate around 4% during the last third of the 2009-2017 period, we run another trend regression but add the dummy variable D2 for the months in 2015, 2016, and 2017, in order to test for an upward shift in the inflation regression line. A positive coefficient attached to D2 would suggest the presence of the Phillips Curve affect.https://ecommons.udayton.edu/stander_posters/2122/thumbnail.jp

One-step isolation and biochemical characterization of a highlyactive plant PSII monomeric core

We describe a one-step detergent solubilization protocol for isolating a highly active form of Photosystem II (PSII) from Pisum sativum L. Detailed characterization of the preparation showed that the complex was a monomer having no light harvesting proteins attached. This core reaction centre complex had, however, a range of low molecular mass intrinsic proteins as well as the chlorophyll binding proteins CP43 and CP47 and the reaction centre proteins D1 and D2. Of particular note was the presence of a stoichiometric level of PsbW, a low molecular weight protein not present in PSII of cyanobacteria. Despite the high oxygen evolution rate, the core complex did not retain the PsbQ extrinsic protein although there was close to a full complement of PsbO and PsbR and partial level of PsbP. However, reconstitution of PsbP and PsbPQ was possible. The presence of PsbP in absence of LHCII and other chlorophyll a/b binding proteins confirms that LHCII proteins are not a strict requirement for the assembly of this extrinsic polypeptide to the PSII core in contrast with the conclusion of Caffarri et al. (2009)

Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10–15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously. Methods: A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher’s exact test was used to determine the association between the immunophenotypic markers and categorical variables. Results: Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki- 67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden. Conclusion: Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies

2,4-dinitrophenyl ether-containing chemodosimeters for the selective and sensitive 'in vitro' and 'in vivo' detection of hydrogen sulfide

[EN] Four probes (i.e. D1¿D4) for the selective and sensitive fluorogenic detection of HS2 have been prepared and characterised. HEPES (10 mM, pH 7.4)¿DMSO 99:1 v/v solutions of D1¿D4 are essentially non-fluorescent. Changes in the emission using D1¿D4 in the presence of anions (F2, Cl2, Br2, I2, N2 3 , CN2, SCN2, AcO2, CO22 3 , PO22 4 , SO22 4 , HS2 and OH2), biothiols (GSH, Cys, Hcy, Me ¿Cys and lipoic acid), reducing agents (SO22 3 and S2O22 3 ) and oxidants (H2O2) demonstrated that only HS2 is able to induce the appearance of intense emission bands in the 400¿ 520 nm range in the four probes. The selectivity observed was ascribed to a unique hydrogen sulfide-induced hydrolysis of the 2,4-dinitrophenyl ether moiety that yielded the corresponding free highly fluorescent alcohols. The potential detection of intracellular HS2 was also studied.Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEO/2009/016) is gratefully acknowledged. S.E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellow. L.E.S.F. also thanks the Carolina Foundation and UPNFM-Honduras for his doctoral grant.El Sayed Shehata Nasr, S.; De La Torre, C.; Santos Figueroa, LE.; Martínez-Máñez, R.; Sancenón Galarza, F.; Orzáez, M.; Costero, AM.... (2015). 2,4-dinitrophenyl ether-containing chemodosimeters for the selective and sensitive 'in vitro' and 'in vivo' detection of hydrogen sulfide. Supramolecular Chemistry. 27(4):244-254. https://doi.org/10.1080/10610278.2014.977286S24425427

GABAA Receptor β3 Subunit Expression Regulates Tonic Current in Developing Striatopallidal Medium Spiny Neurons

The striatum is a key structure for movement control, but the mechanisms that dictate the output of distinct subpopulations of medium spiny projection neurons (MSNs), striatonigral projecting and dopamine D1 receptor- (D1+) or striatopallidal projecting and dopamine D2 receptor- (D2+) expressing neurons, remains poorly understood. GABA-mediated tonic inhibition largely controls neuronal excitability and action potential firing rates, and we previously suggested with pharmacological analysis that the GABAA receptor β3 subunit plays a large role in the basal tonic current seen in D2+ MSNs from young mice (Ade et al., 2008; Janssen et al., 2009). In this study, we demonstrated the essential role of the β3 GABAA receptor subunit in mediating MSN tonic currents using conditional β3 subunit knock-out (β3f/fDrd2) mice. Cre-lox genetics were used to generate mice where Cre recombinase was expressed under the D2 receptor (Drd2) promoter. We show that while the wild-type MSN tonic current pattern demonstrates a high degree of variability, tonic current patterns from β3f/fDrd2 mice are narrow, suggesting that the β3 subunit is essential to striatal MSN GABA-mediated tonic current. Our data also suggest that a distinct population of synaptic receptors upregulate due to β3 subunit removal. Further, deletion of this subunit significantly decreases the D2+ MSN excitability. These results offer insight for target mechanisms in Parkinson’s disease, where symptoms arise due to the imbalance in striatal D1+ and D2+ MSN excitability and output

A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: The AIO KRK 0110 Trial/ML22011 Trial

<p>Abstract</p> <p>Background</p> <p>Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.</p> <p>Methods/Design</p> <p>The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m²bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m²BID for 14d (d1-14), irinotecan 200 mg/m²(d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.</p> <p>Conclusion</p> <p>The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01249638">NCT01249638</a></p> <p>EudraCT-No.: 2009-013099-38</p

Dopamine D1, D2 and mu-opioid receptors are co-expressed with adenylyl cyclase 5 and phosphodiesterase 7B mRNAs in striatal rat cells

El pdf es la versión post-print.Intracellular cAMP levels are regulated by cAMP synthesis and degradation rate. Nine isoforms of cAMP-synthesizing enzymes called adenylyl-cyclases (ACs) and eleven phosphodiesterases (PDEs) that degrade cyclic nucleotides have been identified. Both types of enzymes exhibit variations not only in their expression pattern distribution throughout the brain, but also in their regulatory characteristics. Different isoforms of ACs and PDEs may be co-expressed in a single cell, thus a gradient of cAMP intracellular levels is formed, which accounts for the diversity of cell responses. Among these isoforms, AC5 and PDE7B are highly expressed in striatum, where the cAMP pathway is implicated in diverse behavioural functions. Striatal AC5 is involved in drug reinforcing actions and motor activity. Less is known about the role of the PDE7B isoenzyme. We performed a double in situ hybridization analysis of the co-expression patterns of AC5 and PDE7B with μ-opioid-receptor (MOR), D1- and D2-receptor mRNAs to contribute to a better understanding in the regulation of cAMP levels under dopamine or opioidergic pathway activation in striatum. We found co-expression of AC5 and PDE7B mRNAs in caudate-putamen and nucleus accumbens; we also encountered that more than 50% of MOR, D2- and D1-expressing cells contained AC5 and PDE7B mRNAs. The presence of AC5 and PDE7B mRNAs in D1- and D2-containing cells suggests the participation of these enzymes in striatal functions involving dopaminergic pathways. Co-localization of both isoenzyme mRNAs with MOR expressing cells suggests their involvement in opioid reinforcing effects. © 2009 Elsevier B.V. All rights reserved.P. de G. is on sabbatical leave supported by Ministerio de Educación y Ciencia (SAB2005-0106). This research was supported by a grant from Ministerio de Educación y Ciencia (SAF2006-10243). Support from the Generalitat de Catalunya (Grup de Recerca de Qualitat 2005-SGR0758) is also acknowledged.Peer Reviewe