307 research outputs found
Quantum Superposition of Massive Objects and Collapse Models
We analyze the requirements to test some of the most paradigmatic collapse
models with a protocol that prepares quantum superpositions of massive objects.
This consists of coherently expanding the wave function of a
ground-state-cooled mechanical resonator, performing a squared position
measurement that acts as a double slit, and observing interference after
further evolution. The analysis is performed in a general framework and takes
into account only unavoidable sources of decoherence: blackbody radiation and
scattering of environmental particles. We also discuss the limitations imposed
by the experimental implementation of this protocol using cavity quantum
optomechanics with levitating dielectric nanospheres.Comment: 19 pages, 17 figure
Suppression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP-1 signalling in INS-1 cells
Aims/hypothesis: Mutations in genes encoding HNF-4α, HNF-1α and IPF-1/Pdx-1 are associated with, respectively, MODY subtypes-1, -3 and -4. Impaired glucose-stimulated insulin secretion is the common primary defect of these monogenic forms of diabetes. A regulatory circuit between these three transcription factors has also been suggested. We aimed to explore how Pdx-1 regulates beta cell function and gene expression patterns. Methods: We studied two previously established INS-1 stable cell lines permitting inducible expression of, respectively, Pdx-1 and its dominant-negative mutant. We used HPLC for insulin processing, adenovirally encoded aequorin for cytosolic [Ca2+], and transient transfection of human growth hormone or patch-clamp capacitance recordings to monitor exocytosis. Results: Induction of DN-Pdx-1 resulted in defective glucose-stimulated and K+-depolarisation-induced insulin secretion in INS-1 cells, while overexpression of Pdx-1 had no effect. We found that DN-Pdx-1 caused down-regulation of fibroblast growth factor receptor 1 (FGFR1), and consequently prohormone convertases (PC-1/3 and -2). As a result, DN-Pdx-1 severely impaired proinsulin processing. In addition, induction of Pdx-1 suppressed the expression of glucagon-like peptide 1 receptor (GLP-1R), which resulted in marked reduction of both basal and GLP-1 agonist exendin-4-stimulated cellular cAMP levels. Induction of DN-Pdx-1 did not affect glucokinase activity, glycolysis, mitochondrial metabolism or ATP generation. The K+-induced cytosolic [Ca2+] rise and Ca2+-evoked exocytosis (membrane capacitance) were not abrogated. Conclusions/interpretation: The severely impaired proinsulin processing combined with decreased GLP-1R expression and cellular cAMP content, rather than metabolic defects or altered exocytosis, may contribute to the beta cell dysfunction induced by Pdx-1 deficienc
Theory of decoherence in a matter wave Talbot-Lau interferometer
We present a theoretical framework to describe the effects of decoherence on
matter waves in Talbot-Lau interferometry. Using a Wigner description of the
stationary beam the loss of interference contrast can be calculated in closed
form. The formulation includes both the decohering coupling to the environment
and the coherent interaction with the grating walls. It facilitates the
quantitative distinction of genuine quantum interference from the expectations
of classical mechanics. We provide realistic microscopic descriptions of the
experimentally relevant interactions in terms of the bulk properties of the
particles and show that the treatment is equivalent to solving the
corresponding master equation in paraxial approximation.Comment: 20 pages, 4 figures (minor corrections; now in two-column format
Internally Electrodynamic Particle Model: Its Experimental Basis and Its Predictions
The internally electrodynamic (IED) particle model was derived based on
overall experimental observations, with the IED process itself being built
directly on three experimental facts, a) electric charges present with all
material particles, b) an accelerated charge generates electromagnetic waves
according to Maxwell's equations and Planck energy equation and c) source
motion produces Doppler effect. A set of well-known basic particle equations
and properties become predictable based on first principles solutions for the
IED process; several key solutions achieved are outlined, including the de
Broglie phase wave, de Broglie relations, Schr\"odinger equation, mass,
Einstein mass-energy relation, Newton's law of gravity, single particle self
interference, and electromagnetic radiation and absorption; these equations and
properties have long been broadly experimentally validated or demonstrated. A
specific solution also predicts the Doebner-Goldin equation which emerges to
represent a form of long-sought quantum wave equation including gravity. A
critical review of the key experiments is given which suggests that the IED
process underlies the basic particle equations and properties not just
sufficiently but also necessarily.Comment: Presentation at the 27th Int Colloq on Group Theo Meth in Phys, 200
Identification of functional insulin receptors on membranes from an insulin-producing cell line (RINm5F)
Acute appendicitis caused by endometriosis: a case report
<p>Abstract</p> <p>Introduction</p> <p>Endometriosis is a well-recognized gynecological condition in the reproductive age group. Surgical texts present the gynecological aspects of the disease in detail, but the published literature on unexpected manifestations, such as appendiceal disease, is inadequate. The presentation to general surgeons may be atypical and pose diagnostic difficulty. Thus, a definitive diagnosis is likely to be established only by the histological examination of a specimen.</p> <p>Case presentation</p> <p>We report a case of endometriosis of the appendix in a 25-year-old Caucasian woman who presented with symptoms of acute appendicitis and was treated by appendectomy, which resulted in a good outcome.</p> <p>Conclusions</p> <p>We discuss special aspects of acute appendicitis caused by endometriosis to elucidate the pathologic entity of this variant of acute appendicitis.</p
Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model
BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical
Protective Unfolded Protein Response in Human Pancreatic Beta Cells Transplanted into Mice
Background: There is great interest about the possible contribution of ER stress to the apoptosis of pancreatic beta cells in the diabetic state and with islet transplantation. Methods and Findings: Expression of genes involved in ER stress were examined in beta cell enriched tissue obtained with laser capture microdissection (LCM) from frozen sections of pancreases obtained from non-diabetic subjects at surgery and from human islets transplanted into ICR-SCID mice for 4 wk. Because mice have higher glucose levels than humans, the transplanted beta cells were exposed to mild hyperglycemia and the abnormal environment of the transplant site. RNA was extracted from the LCM specimens, amplified and then subjected to microarray analysis. The transplanted beta cells showed an unfolded protein response (UPR). There was activation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress, increased expression of ER chaperones and ERAD (ER-associated protein degradation) proteins. The other two arms of ER stress, PERK and ATF-6, had many down regulated genes. Downregulation of EIF2A could protect by inhibiting protein synthesis. Two genes known to contribute to apoptosis, CHOP and JNK, were downregulated. Conclusions: Human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins
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