5,150 research outputs found
The depth of all Boolean functions
It is shown that every Boolean function of n arguments has a circuit of depth n+1 over the basis {f|f:{0,1}^2 -> {0,1}}
Two distinct aetiologies of cardia cancer, evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status
Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection
and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear.
Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach.
Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were
matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori
antibodies, pepsinogen I:II and gastrin.
Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and
gastric atrophy (pepsinogen I:II ,2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological
subtypes of non-cardia cancer were of similar proportions and both showed a positive association with
H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to
0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06
to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with
gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32
to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia
cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1).
Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic
gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa,
resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to
determining gastric versus oesophageal origin of cardia cancer
A universal size classification system for landslides
Size is a fundamental property of landslides, but it is described inconsistently within the scientific literature. There is currently no widely adopted size classification system applicable to all landslide types. A Scopus database search shows the most used landslide size descriptor is the term large, used to refer to landslides with volumes spanning ten orders of magnitude. Some size descriptors are unintuitive or potentially misleading (e.g. the term massive which describes a material property). We argue that a formal size classification scheme would encourage more consistent and logical usage of size descriptors and improve landslide science communication. To that end, we propose a size classification scheme suitable for all landslide types. The scheme provides a log scale of size classes for volume and area, with base units of cubic metre and square metre, respectively. In theory, there is no limit to the number of size classes possible. Six size descriptors are suggested, each spanning 3 orders of magnitude: very small (10−3–100 m3), small (10–103 m3), medium (103–106 m3), large (106–109 m3), giant (109–1012 m3), and monster (1012–1015 m3). Our system does not replace existing (or preclude future) classification systems for specific landslide types (e.g. snow avalanche) that use numerical size classes, and it maintains consistency with some commonly used descriptors. Whatever system is used, we encourage people to define the terms they use and to quantify size where possible, so that clearer meaning is given to the words used to describe landslide sizes
Reduction in jejunal fluid absorption in vivo through distension and cholinergic stimulation not attributable to enterocyte secretion
Jejunal fluid absorption in vivo was reduced by distension and by hydrostatic pressure and further declined on adding E. coli STa enterotoxin but no net fluid secretion was detected. Luminal atropine reduced pressure mediated reductions in fluid absorption to normal values but intravenous hexamethonium was without effect. A neural component to inhibition of absorption by pressure (though not stretch) may be mediated by axon reflexes within cholinergic neurons.Perfusion of cholinergic compounds also reduced net fluid absorption but did not cause secretion. In order to show that these actions were not secretory processes stimulated by cholinergic compounds that offset normal rates of absorption, these compounds were tested for their ability to cause net secretion in loops that were perfused with solutions in which choline substituted for sodium ion. In addition, these perfusates additionally contained E. coli STa enterotoxin or EIPA (ethyl-isopropyl-amiloride) to minimize absorption.In these circumstances, where it might be expected to do so if it were acting through a secretory rather than an absorptive mechanism, carbachol did not cause net fluid secretion. Cholinergic stimulation and pressure induced distension are thought to reduce net fluid absorption through inducing secretion but are found only to reduce fluid absorption.In conclusion, distension and cholinergic stimulation of the small intestine are two further circumstances in which fluid secretion is assumed to explain their action on fluid movement, as required by the enterocyte secretion model of secretion but, which like STa enterotoxin, instead are only able to reduce fluid absorption. This casts further doubt on the widespread validity of the enterocyte secretion model for fluid appearance in the lumen in diarrhoeal diseases
Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation
<b>Background</b>: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to
a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be
converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presence
of thiocyanate.
<b>Aims</b>: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating
the human proximal stomach.
<b>Methods</b>: The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary
amines under conditions simulating the proximal stomach. The N-nitrosamines formed were measured by gas
chromatography–ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured
amperometrically.
<b>Results</b>: In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating
species to nitric oxide. Addition of ascorbic acid reduced the amount of N-nitrosodimethylamine formed by
fivefold, N-nitrosomorpholine by .1000-fold, and totally prevented the formation of N-nitrosodiethylamine
and N-nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of Nnitrosodimethylamine,
N-nitrosodiethylamine and N-nitrosopiperidine formed by approximately 8-, 60- and
140-fold, respectively, compared with absence of ascorbic acid.
<b>Conclusion</b>: The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This
may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate
nitrosating species by reacting with oxygen in the lipid phase
Interplay between CCR7 and Notch1 axes promotes stemness in MMTV-PyMT mammary cancer cells
Background: Breast cancer is the major cause of cancer-related mortality in women. It is thought that quiescent stem-like cells within solid tumors are responsible for cancer maintenance, progression and eventual metastasis. We recently reported that the chemokine receptor CCR7, a multi-functional regulator of breast cancer, maintains the stem-like cell population. Methods: This study used a combination of molecular and cellular assays on primary mammary tumor cells from the MMTV-PyMT transgenic mouse with or without CCR7 to examine the signaling crosstalk between CCR7 and Notch pathways. Results: We show for the first time that CCR7 functionally intersects with the Notch signaling pathway to regulate mammary cancer stem-like cells. In this cell subpopulation, CCR7 stimulation activated the Notch signaling pathway, and deletion of CCR7 significantly reduced the levels of activated cleaved Notch1. Moreover, blocking Notch activity prevented specific ligand-induced signaling of CCR7 and augmentation of mammary cancer stem-like cell function. Conclusion: Crosstalk between CCR7 and Notch1 promotes stemness in mammary cancer cells and may ultimately potentiate mammary tumor progression. Therefore, dual targeting of both the CCR7 receptor and Notch1 signaling axes may be a potential therapeutic avenue to specifically inhibit the functions of breast cancer stem cells.Sarah T. Boyle, Krystyna A. Gieniec, Carly E. Gregor, Jessica W. Faulkner, Shaun R. McColl and Marina Kochetkov
Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori
Background & Aims:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods:H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects
A rising tide lifts all boats: the role of share and category changes in managing organic sales growth
The strategic objective of marketing activities is to drive business growth by promoting the firm’s products. Beyond merger and acquisition, organic growth can be targeted from two sources: Market Share Gain and Category Growth. Market share is often the focus for corporate objectives and used as a success measure. This research explores the relative impact of these two elements on firm growth across product category and addresses whether market share should be the main focus for all organisations. The study covers 39 consumer packaged goods’ categories from the UK and US, across 189 manufacturers over three to five years of data, post-2010. We show that firm growth through market share gain is likely to benefit small firms, and large firms’ growth is likely to be driven by category growth. The results provide empirical support in the area of business growth and how marketing plays a crucial role in this pursuit
Customer effort in value cocreation activities: improving quality of life and behavioral intentions of health care customers
Transformative service research is particularly relevant in health care where the firm and customer can contribute to individual as well as societal well-being. This article explores customer value cocreation in health care, identifying a hierarchy of activities representing varying levels of customer effort from complying with basic requirements (less effort and easier tasks) to extensive decision making (more effort and more difficult tasks). We define customer Effort in Value Cocreation Activities (EVCA) as the degree of effort that customers exert to integrate resources, through a range of activities of varying levels of perceived difficulty. Our findings underscore the importance of viewing health care service as taking place within the customer's service network that extends well beyond the customer-firm dyad to include other market-facing as well as public and private resources. Moreover, we demonstrate the transformative potential of customer EVCA linking customer EVCA to quality of life, satisfaction with service and behavioral intentions. We do so across three prevalent chronic diseasescancer, heart disease, and diabetes. Our findings highlight how an integrated care model has benefits for both customers and providers and can enhance customer EVCA
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