Dorsalization of the neural tube by the non-neural ectoderm

The patterning of cell types along the dorsoventral axis of the spinal cord requires a complex set of inductive signals. While the chordamesoderm is a well-known source of ventralizing signals, relatively little is known about the cues that induce dorsal cell types, including neural crest. Here, we demonstrate that juxtaposition of the non-neural and neural ectoderm is sufficient to induce the expression of dorsal markers, Wnt-1, Wnt-3a and Slug, as well as the formation of neural crest cells. In addition, the competence of neural plate to express Wnt-1 and Wnt-3a appears to be stage dependent, occurring only when neural tissue is taken from stage 8–10 embryos but not from stage 4 embryos, regardless of the age of the non-neural ectoderm. In contrast to the induction of Wnt gene expression, neural crest cell formation and Slug expression can be induced when either stage 4 or stage 8–10 neural plates are placed in contact with the non-neural ectoderm. These data suggest that the non-neural ectoderm provides a signal (or signals) that specifies dorsal cell types within the neural tube, and that the response is dependent on the competence of the neural tissue

Risk factors for Barrett’s esophagus among patients with gastroesophageal reflux disease: A community clinic-based case-control study

Objective: To measure the relative risks of Barrett’s esophagus (BE) associated with demographic factors, measures of adiposity and smoking among patients with gastroesophageal reflux disease (GERD). Methods: Patients newly diagnosed with specialized intestinal metaplasia (SIM) (n=197) were compared to patients with GERD (n= 418) in a community clinic-based case-control study. Case sub-groups included those with any visible columnar epithelium (VBE) (n=97), and those with a long segment (=2cm) of columnar epithelium (LSBE) (n=54). Results: Risks increased with older age (adjusted odds ratio (aOR) per decade for SIM=1.3, 95% confidence interval (CI)= 1.1-1.5; VBE aOR=1.4 ,CI=1.1-1.6; LSBE aOR=1.5, CI=1.2-1.9), male gender (SIM aOR=1.5, CI=1.1-2.2; VBE aOR=2.7, CI=1.6-4.5; LSBE aOR=3.9, CI=1.9- 8.1) and possibly Asian race. Increased risk of BE in particular was observed with high waist-tohip ratio (WHR, male high: =0.9, female high: =0.8) (SIM aOR=1.3, CI=0.9-2.1; VBE aOR=1.9, CI=1.0-3.5; LSBE aOR=4.1, CI=1.5-11.4). These associations were independent of body mass index (BMI) for the VBE and LSBE case groups but not for SIM which was the only case group in which BMI was a significant risk factor. Ever smoking cigarettes increased risk similarly for all case groups (SIM aOR=1.8, CI=1.2-2.6; VBE aOR=1.6, CI=1.0-2.6; LSBE aOR=2.6, CI=1.3- 4.9), although dose response relationship was not detected for duration or intensity of smoking. Conclusions: Older age, male gender and history of smoking increased risk of SIM and BE among GERD patients independent of other risk factors for BE. Central adiposity was most strongly related to risk of VBE and LSBE. These results may be useful in development of risk profiles for screening GERD patients

Proteomics Portrait of Archival Lesions of Chronic Pancreatitis

Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL), mild chronic pancreatitis (MCP), severe chronic pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) were subjected to proteomic analysis using a “label-free” comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma

Are ulcers a marker for invasive carcinoma in barrett's esophagus? data from a diagnostic variability study with clinical follow-up

We correlated follow-up information from 138 patients with Barrett's esophagus and varying degrees of dysplasia with the presence of ulcers. Methods A group of pathologist participants were asked to contribute patients’ initial biopsy slides showing Barrett's esophagus (BE) without dysplasia and with epithelial changes indefinite for dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma. From the initial 250 cases used for a diagnostic reproducibility study, follow-up information was available for 138 patients. Results There were 44 cases submitted as BE, 22 as BE with epithelial changes indefinite for dysplasia, 26 as BE with LGD, 33 as BE with HGD, and 13 as BE with adenocarcinoma. Ulcers were present in 35/138 cases (25%), including 3/44 cases of BE without dysplasia (7%), 2/22 cases of BE with epithelial changes indefinite for dysplasia (9%), 0/26 cases of BE with LGD (0%), 10/33 cases of BE with HGD (30%), and 7/13 cases of BE with adenocarcinoma (54%). On follow-up, there were no invasive carcinomas detected among the BE without dysplasia group (median follow-up = 38.5 months). Adenocarcinomas were detected in 4/22 cases (18%) submitted as BE with epithelial changes indefinite for dysplasia at 19, 55, 60, and 62 months and in 4/26 cases (15%) of BE with LGD at 9, 9, 11, and 60 months. None of these carcinomas occurred in cases in which an ulcer was present in the initial biopsy specimen. Among the 33 HGD cases, 20 (60%) were found to have adenocarcinoma on subsequent resection specimens. The presence of an ulcer with HGD increased the likelihood of finding carcinoma in the resection specimen, as 8/10 biopsies (80%) of HGD patients with ulcers had carcinoma, compared to 12/23 biopsies (52%) of HGD patients without ulcers. All of the cases interpreted as adenocarcinomas on biopsy were found either to have invasive carcinoma on esophageal resection or to have metastases that were demonstrated in unresectable patients. Conclusion If an ulcer accompanies HGD in a biopsy specimen from a patient with BE, it is likely that invasive carcinoma is also present at that time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75186/1/j.1572-0241.2002.05420.x.pd

Rigorous dimension estimates for Cantor sets arising in Zaremba theory

We address the question of the accuracy of bounds used in the study of Zaremba’s conjecture. Specifically, we establish rigorous estimates on the Hausdorff dimension of certain Cantor sets which arise in the analysis of Zaremba’s conjecture in [5, 18, 19, 23]

Order and the Virtual: Toward a Deleuzian Cosmology

None provided, have taken the following from the "Introduction" Order is a more or less explicit topic for any thinker who undertakes to write about nature. Even those who assert that randomness or chaos is the most fundamental trait of nature are obliged to account for the apparent permanence, organisation and structure we observe around us. No less is true for Gilles Deleuze, who champions the power of chaos through his work. On one reading, Deleuze’s chief impulse is to wrench loose the lynchpins of order; to ‘affirm chaos’ and disarticulate the law of excluded middle; to refuse jurisdiction to laws of nature and render provisional its every constant; to banish identity and negation alike. If we are to be left with no fixed point, we might ask, what remains of order? This study is nevertheless an examination of that notion in Deleuze’s natural philosophy. For me the counter-reading is much more productive and insightful. Deleuze is rather a firm believer in order, even there where he affirms chaos. If we could furnish a ‘Deleuzian Question’ par excellence, it would be; ‘Given that there are no fixed points, how is order expressed in the world?’ This question is implicitly reprised across the entirety of his work and inflected at each stage by fresh vocabulary coined to treat it anew, as though for each new Deleuzian territory a new phrasebook is required

Wi-Fi based people tracking in challenging environments

People tracking is a key building block in many applications such as abnormal activity detection, gesture recognition, and elderly persons monitoring. Video-based systems have many limitations making them ineffective in many situations. Wi-Fi provides an easily accessible source of opportunity for people tracking that does not have the limitations of video-based systems. The system will detect, localise, and track people, based on the available Wi-Fi signals that are reflected from their bodies. Wi-Fi based systems still need to address some challenges in order to be able to operate in challenging environments. Some of these challenges include the detection of the weak signal, the detection of abrupt people motion, and the presence of multipath propagation. In this thesis, these three main challenges will be addressed. Firstly, a weak signal detection method that uses the changes in the signals that are reflected from static objects, to improve the detection probability of weak signals that are reflected from the person’s body. Then, a deep learning based Wi-Fi localisation technique is proposed that significantly improves the runtime and the accuracy in comparison with existing techniques. After that, a quantum mechanics inspired tracking method is proposed to address the abrupt motion problem. The proposed method uses some interesting phenomena in the quantum world, where the person is allowed to exist at multiple positions simultaneously. The results show a significant improvement in reducing the tracking error and in reducing the tracking delay

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells