Estudio de prefactibilidad para la Instalación de una heladería especializada en la elaboración de helados congelados con nitrógeno líquido

The following prefeasibility study will determine the feasibility of implementing a specialized ice cream facility base on a liquid nitrogen freezing process in Lima Metropolitana. For this, the research problem was evaluated, establishing the objectives, and the scope. The subject was justified and the hypotheses were presented. Different theses found in the library of the University of Lima were used as references. It was necessary to implement a market research in order to determine the demand and interest from the target audience, therefor surveys were carried out. Based on the surveys and diferente relevant factors of the study such as proximity to the target audience, polarization, security and others, the location of the ice cream facility was determined. The size of the business was also determined analyzing factors such as market, resources, investment, etc. An analysis of all the activities and processes that will be carried out in the facilities for the proper functioning of the service was performed. Having this analysis, the personnel that would be in charge of each of the activities and their specific functions were determined. A compilation of all the income and expenses that the business would have was made in order to perform a financial evaluation of the service.En el siguiente trabajo se determinará la factibilidad de implementar una heladería de congelamiento con nitrógeno líquido en Lima Metropolitana Se asume que la heladería comenzaría a operar en el año 2021, en un estado de “normalidad” tras la aprobación y distribución de una vacuna contra el COVID-19. Para ello se evaluó la problemática de la investigación, estableciendo los objetivos, y el alcance. Se justificó el tema y se plantearon hipótesis. Diferentes tesis encontradas en la biblioteca de la Universidad de Lima fueron utilizadas como referencia. Fue necesario realizar un estudio de mercado para determinar la demanda e interés por parte del público objetivo, para lo que se llevaron a cabo encuestas. Asimismo, basándonos en la encuesta y en distintos factores relevantes en el estudio como cercanía al mercado, polarización, seguridad, entre otros, se determinó la localización del local. Tambien se determinó el tamaño del negocio utilizando factores como mercado, recursos, inversión, etc. Se realizó un análisis de todas las actividades y procesos que se realizaran en las instalaciones para el buen funcionamiento del servicio. Teniendo este análisis, se determinó el personal que estaría a cargo de cada una de las actividades y cuales serian sus funciones especificas. Luego, se realizo un compilación de todos los ingresos y egresos que tendría el negocio para así realizar una evaluación financiera del servicio a brindar

Seven mutations of the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM

Transglutaminase 2 transamidation activity during first-phase insulin secretion: natural substrates in INS-1E.

Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent transamidating and G protein activity. Previously, we reported that tgm2 -/- mice have an impaired insulin secretion and that naturally occurring TG2 mutations associated with familial, early-onset type 2 diabetes, show a defective transamidating activity. Aim of this study was to get a better insight into the role of TG2 in insulin secretion by identifying substrates of TG2 transamidating activity in the pancreatic beta cell line INS-1E. To this end, we labeled INS-1E that are capable of secreting insulin upon glucose stimulation in the physiologic range, with an artificial acyl acceptor (biotinamido-pentylamine) or donor (biotinylated peptide), in basal condition and after stimulus with glucose for 2, 5, and 8 min. Biotinylated proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. In addition, subcellular localization of TG2 in human endocrine pancreas was studied by electron microscopy. Among several TG2's transamidating substrates in INS-1E, mass spectrometry identified cytoplasmic actin (a result confirmed in human pancreatic islet), tropomyosin, and molecules that participate in insulin granule structure (e.g., GAPDH), glucose metabolism, or [Ca(2+)] sensing (e.g., calreticulin). Physical interaction between TG2 and cytoplasmic actin during glucose-stimulated first-phase insulin secretion was confirmed by co-immunoprecipitation. Electron microscopy revealed that TG2 is localized close to insulin and glucagon granules in human pancreatic islet. We propose that TG2's role in insulin secretion may involve cytoplasmic actin remodeling and may have a regulative action on other proteins during granule movement. A similar role of TG2 in glucagon secretion is also suggested

Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene

7 páginas, 3 figuras, 2 tablas.Glucokinase is essential for glucose-stimulated insulin release from the pancreatic beta-cell, serving as glucose sensor in humans. Inactivating or activating mutations of glucokinase lead to different forms of glucokinase disease, i.e. GCK-monogenic diabetes of youth, permanent neonatal diabetes (inactivating mutations), and congenital hyperinsulinism, respectively. Here we present a novel glucokinase gene (GCK)-activating mutation (p.E442K) found in an infant with neonatal hypoglycemia (1.5 mmol/liter) and in two other family members suffering from recurrent hypoglycemic episodes in their childhood and adult life. In contrast to the severe clinical presentation in the index case, functional studies showed only a slight activation of the protein (relative activity index of 3.3). We also report on functional studies of two inactivating mutations of the GCK (p.E440G and p.S441W), contiguous to the activating one, that lead to monogenic diabetes of youth. Interestingly, adult family members carrying the GCK pE440G mutation show an unusually heterogeneous and progressive diabetic phenotype, a feature not typical of GCK-monogenic diabetes of youth. In summary, we identified a novel activating GCK mutation that although being associated with severe neonatal hypoglycemia is characterized by the mildest activation of the glucokinase enzyme of all previously reportedThis work was supported by grants (to A.L.C.-M. and N.C.-V.) from Ministerio de Ciencia e Innovación, Dirección General de Investigación Científica y Técnica (SAF2005-08014; SAF2006-12863) and Junta de Andalucía (SAS/PI-024/2007; SAS/PI-0236/2009)Peer reviewe

Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?

Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson–Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter’s syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR

No sign of proliferative retinopathy in 15 patients with permanent neonatal diabetes with a median diabetes duration of 24 years

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