317 research outputs found
Ocean shrimp report 1979 season
Statewide Pacific ocean shrimp, Pandalus jordani, landings
totaled 2,237.7 mt (4,922,857 lb), down 3,745 mt
(8,240,386 lb) from the 1978 catch of 5,983.3 mt
(13,163,243 lb). The 1979 landings are the lowest
since 1976 when 1,545.5 mt (3,400,191 lb) were landed. Area A (Eureka-Crescent City)landings dropped to 1,842.5 mt (4,053,605 lb) from 5,046.3 mt (11,101,895 lb) landed during the previous season. No landings were made in Area B-1 (Fort Bragg). Only 2.0 mt (4,385 lb) were reported caught in Area B-2 (Bodega Bay). Record landings of 393.1 mt
(864,867 lb) were made in Area C (Morro Bay-Avila), surpassing the previous record of 90.4 mt (199,000 lb) landed in 1953. In Area A a record 71 vessels, 34 double-rigged and 37 single-rigged, shrimped during the
season. Average catch per hour was a low .15 mt (338 lb) and .22 mt (490 1b) for single-rig and double-rig vessels, respectively. In Area C average catch per hour was .23 mt (508 lb) and .42 mt (924 lb) for single-rig and double-rig
vessels, respectively. Area A shrimp catches were dominated by 1-year-old shrimp throughout most of the season. The
age composition in Area C shifted predominately from 2-year-old shrimp in May and June to predominately 1-year-old shrimp in July, August, October, and November. Area A was closed for one month from July 15 to
August 15 because closure criteria of less than .16 mt
(350 lb) per hour for two consecutive weeks was met and year class composition exceeded 70% of 1-year-old shrimp. The season was closed October 14 when the catch per hour criterion was exceeded again. (18pp.
Determining benefits from B2B e-commerce : a strategic approach
A request from a powerful customer to exchange information electronically is an important external stimulus to the business strategy of a supplier. Prior research indicates that sub-optimal benefits, if any, are the typical result of such a stimulus. In this research, B2B ecommerce alignment between business strategy and IT strategy is proposed as a determinant of enhanced business benefits from electronic information exchange. A multiple case study approach in the Australian automotive industry is used to examine this proposition. As more electronic information is exchanged using a range of electronic modes, thus creating complex interorganizational systems, this research provides insights for suppliers about how to achieve greater benefits from B2B e-commerce.Una petición proveniente de un cliente poderoso para intercambiar información electrónicamente es un estímulo externo importante para la estrategia de negocios de un proveedor. Una investigación previa indica que los beneficios óptimos, si se producen, son el resultado de un estímulo así. En esta investigación, la alineación de comercio online B2B entre estrategias de negocios y estrategias de IT fueron propuestas como determinantes para obtener beneficios de intercambios de información electrónica. Un estudio de múltiples casos en la industria automotivacional australiana se usa para estudiar esta proposición. Conforme más información electrónica se intercambia usando un rango de métodos electrónicos, se crean complejos interorganismos, esta investigación proporciona pistas para cómo los proveedores pueden alcanzar mejores beneficios del comercio electrónico B2B
Ocean shrimp report 1980 season
Statewide Pacific ocean shrimp, Pandalus jordani, landings
totaled 2,033.1 mt (4,472,749 lb) down 204.6 mt (450,108 lb) from the 1979 catch of 2,237.7 m t (4,922,857 lb). The 1980 landings are the lowest since 1976 when 1,545.5 mt (3,400,191 lb) were landed. Area A (Eureka-Crescent City)
landings dropped to 1,234 mt (2,716,147 lb) from 1,842.5 mt
(4,053,605 lb) landed during the previous season. Area B-1 (Fort Bragg) landings totaled 79.3 mt (174,395 lb) from catches made during the last 9 days of the season. Only 100 lb were reported caught in Area B-2 (Bodega Bay). Record landings of 719.1 mt (1,582,107 lb were made in Area C (Morro Bay-Avila), surpassing the previous record of 391 mt
(864,667 lb) landed in 1979. In Area A a record 80 vessels, 34 double-rigged and 46 single-rigged, made shrimp deliveries during the season. Average catch per hour was a very low .ll mt (234 lb) and .20 mt (446 lb) for single-
rig and double-rig vessels, respectively. In Area C average
catch per hour was .25 mt (557 lb) and .21 mt (462 lb) for single-rig and double-rig vessels, respectively. Area A shrimp catches were dominated by 1-year-old shrimp in percent by number throughout the season. The age composition in Area C shifted from predominately 2-year-old shrimp
in April, May, and June to predominately 1-year-old shrimp
for the remainder of the season. Area A was closed for one month from June 1 to July 1 because closure criteria of less than .16 mt (350 lb) per hour for two consecutive weeks was met and year class composition exceeded 70% of year-old shrimp. The season was closed for the year on August 25 when
the catch per hour and percent 1-year-old shrimp criteria was exceeded again.
(22pp.
A 3D Heterotypic Breast Cancer Model Demonstrates a Role for Mesenchymal Stem Cells in Driving a Proliferative and Invasive Phenotype
Previous indirect 2D co-culture studies have demonstrated that mesenchymal stem cells (MSCs) promote breast cancer (BC) progression through secretion of paracrine factors including growth factors, cytokines and chemokines. In order to investigate this aspect of the tumour microenvironment in a more relevant 3D co-culture model, spheroids incorporating breast cancer cells (BCCs), both cell lines and primary BCCs expanded as patient-derived xenografts, and MSCs were established. MSCs in co-cultures were shown to enhance proliferation of estrogen receptor (ER)/progesterone receptor (PR)-positive BCCs. In addition, co-culture resulted in downregulation of E-cadherin in parallel with upregulation of the epithelial-mesenchymal transition (EMT)-relation transcription factor, SNAIL. Cytoplasmic relocalization of ski-related novel protein N (SnON), a negative regulator of transforming growth factor-beta (TGF-β) signalling, and of β-catenin, involved in a number of pathways including Wnt signalling, was also observed in BCCs in co-cultures in contrast to monocultures. In addition, the β-catenin inhibitor, 3-[[(4-methylphenyl)sulfonyl]amino]-benzoic acid methyl ester (MSAB), mediated reduced growth and invasion in the co-cultures. This study highlights the potential role for SnON as a biomarker for BC invasiveness, and the importance of interactions between TGF-β and Wnt signalling, involving SnON. Such pathways may contribute towards identifying possible targets for therapeutic intervention in BC patients
Crystal structure of the anthrax lethal factor
Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62772/1/414229a0.pd
Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma
Background and aims: Esophageal adenocarcinoma (EAC) is chemoresistant in the majority of cases. The tumor-promoting biology of cancer associated fibroblasts (CAF) make them a target for novel therapies. Phosphodiesterase type 5 inhibitors (PDE5i) have been shown to regulate the activated fibroblast phenotype in benign disease. We investigated the potential for CAF modulation in EAC using PDE5i to enhance the efficacy of chemotherapy. Methods: EAC fibroblasts were treated with PDE5i and phenotypic effects examined using immunoblotting, immunohistochemistry, gel contraction, transwell invasion, organotypics, single cell RNAseq and shotgun proteomics. The combination of PDE5i with standard-of-care chemotherapy (Epirubicin, 5-Fluorouracil and Cisplatin) was tested for safety and efficacy in validated near-patient model systems (3D tumor growth assays (3D-TGAs) and patient derived xenograft (PDX) mouse models). Results: PDE5i treatment reduced alpha-SMA expression in CAFs by 50% (p<0.05), associated with a significant reduction in the ability of CAFs to contract collagen-1 gels and induce cancer cell invasion, (p<0.05). RNAseq and proteomic analysis of CAF and EAC cell lines revealed PDE5i specific regulation of pathways related to fibroblast activation and tumor promotion. 3D-TGA assays confirmed the importance of stromal cells to chemoresistance in EAC, which could be attenuated by PDE5i. Chemotherapy+PDE5i in PDX-bearing mice was safe and significantly reduced PDX tumor volume (p<0.05). Conclusion: PDE5 is a candidate for clinical trials to alter the fibroblast phenotype in esophageal cancer. We demonstrate the specificity of PDE5i for fibroblasts to prevent transdifferentiation and revert the CAF phenotype. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient in vitro and in vivo PDX-based model systems
Targeting hypoxia regulated sodium driven bicarbonate transporters reduces triple negative breast cancer metastasis
Regions of low oxygen (hypoxia) are found in >50% of breast tumours, most frequently in the more aggressive triple negative breast cancer subtype (TNBC). Metastasis is the cause of 90% of breast cancer patient deaths. Regions of tumour hypoxia tend to be more acidic and both hypoxia and acidosis increase tumour metastasis. In line with this the metastatic process is dependent on pH regulatory mechanisms. We and others have previously identified increased hypoxic expression of Na+ driven bicarbonate transporters (NDBTs) as a major mechanism of tumour pH regulation. Hypoxia induced the expression of NDBTs in TNBC, most frequently SLC4A4 and SLC4A5. NDBT inhibition (S0859) and shRNA knockdown suppressed migration (40% reduction) and invasion (70% reduction) in vitro. Tumour xenograft metastasis in vivo was significantly reduced by NDBT knockdown. To investigate the mechanism by which NDBTs support metastasis, we investigated their role in regulation of phospho-signalling, epithelial-to-mesenchymal transition (EMT) and metabolism. NDBT knockdown resulted in an attenuation in hypoxic phospho-signalling activation; most notably LYN (Y397) reduced by 75%, and LCK (Y394) by 72%. The metastatic process is associated with EMT. We showed that NDBT knockdown inhibited EMT, modulating the expression of key EMT transcription factors and ablating the expression of vimentin whilst increasing the expression of E-cadherin. NDBT knockdown also altered metabolic activity reducing overall ATP and extracellular lactate levels. These results demonstrate that targeting hypoxia-induced NDBT can be used as an approach to modulate phospho-signalling, EMT, and metabolic activity and reduce tumour migration, invasion, and metastasis in vivo
SPECULOOS exoplanet search and its prototype on TRAPPIST
One of the most significant goals of modern science is establishing whether
life exists around other suns. The most direct path towards its achievement is
the detection and atmospheric characterization of terrestrial exoplanets with
potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs),
i.e. very-low-mass stars and brown dwarfs with effective temperatures lower
than 2700 K, represent a unique opportunity to reach this goal within the next
decade. The potential of the transit method for detecting potentially habitable
Earth-sized planets around these objects is drastically increased compared to
Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby
UCD would be amenable for a thorough atmospheric characterization, including
the search for possible biosignatures, with near-future facilities such as the
James Webb Space Telescope. In this chapter, we first describe the physical
properties of UCDs as well as the unique potential they offer for the detection
of potentially habitable Earth-sized planets suitable for atmospheric
characterization. Then, we present the SPECULOOS ground-based transit survey,
that will search for Earth-sized planets transiting the nearest UCDs, as well
as its prototype survey on the TRAPPIST telescopes. We conclude by discussing
the prospects offered by the recent detection by this prototype survey of a
system of seven temperate Earth-sized planets transiting a nearby UCD,
TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H.
Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure
Cohort profile : the Scottish Diabetes Research Network national diabetes cohort - a population-based cohort of people with diabetes in Scotland
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD
Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD
BACKGROUND: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. METHODS: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m2/yr) and those of the clinical end point (doubling of serum creatinine, GFR <15 ml/min per 1.73 m2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m2/yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero. RESULTS: There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [-0.05 to 0.03]; baseline UACR [-0.02 to 0.04]; CKD progression rate [-0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [-0.11 to -0.02]; CKD progression rate [0.01 to 0.15]). CONCLUSIONS: These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.</p
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