Classification of Inflammatory Bowel Disease from Formalin‐Fixed, Paraffin‐Embedded Tissue Biopsies via Imaging Mass Spectrometry

Purpose: Discrimination between ulcerative colitis (UC) and Crohn's disease (CD) by histologic features alone can be challenging and often leads to inaccurate initial diagnoses in inflammatory bowel disease (IBD) patients. This is mostly due to an overlap of clinical and histologic features. However, exact diagnosis is not only important for patient treatment but it also has a socioeconomic impact. It is therefore important to develop and improve diagnostic tools complementing traditional histomorphological approaches. Experimental Design: In this retrospective proof-of-concept study, the utilization of MALDI imaging is explored in combination with multi-variate data analysis methods to classify formalin-fixed, paraffin-embedded (FFPE) colon biopsies from UC (87 biopsies, 14 patients), CD (71 biopsies, 14 patients), and normal colonic (21 biopsies, 14 patients) tissues. Results: The proposed method results in an overall balanced accuracy of 85.7% on patient and of 80.4% on sample level, thus demonstrating that the assessment of IBD from FFPE tissue specimens via MALDI imaging is feasible. Conclusions and Clinical Relevance: The results emphasize the high potential of this method to distinguish IBD subtypes in FFPE tissue sections, which is a prerequisite for further investigations in retrospective multicenter studies, as well as for a future implementation into clinical routine

Организация работ по ремонту и обслуживанию предпусковых подогревателей двигателей грузовых автомобилей в условиях ремонтной мастерской ООО «Сибтрейд»

В разделе объект и методы исследования выполнен аналитический обзор по теме работы и обоснован выбор темы выпускной работы бакалавра. В разделе расчеты и аналитика представлены необходимые инженерные расчеты, связанные с организацией работ по ремонту и обслуживанию предпусковых жидкостных подогревателей грузовых автомобилей. В разделе "Социальная ответственность" выявлены опасные и вредные факторы, а также мероприятия по их ликвидации.In the section of the object and methods of research, an analytical review of the topic of work was carried out and the choice of the topic of the bachelor's thesis was substantiated. The calculations and analytics section presents the necessary engineering calculations related to the organization of work on the repair and maintenance of pre-launch liquid heaters of trucks. n the section "Social responsibility" identified dangerous and harmful factors, as well as measures for their elimination

One Step at a Time: How Model Time Step Significantly Affects Convection‐Permitting Simulations

We show that there is a strong sensitivity of cloud microphysics to model time step in idealized convection-permitting simulations using the COnsortium for Small-scale MOdeling model. Specifically, we found a 53% reduction in precipitation when the time step is increased from 1 to 15 s, changes to the location of precipitation and hail reaching the surface, and changes to the vertical distribution of hydrometeors. The effect of cloud condensation nuclei perturbations on precipitation also changes both magnitude and sign with the changing model time step. The sensitivity arises because of the numerical implementation of processes in the model, specifically the so-called “splitting” of the dynamics (e.g., advection and diffusion) and the parameterized physics (e.g., microphysics scheme). Calculating one step at a time (sequential-update splitting) gives a significant time step dependence because large supersaturation with respect to liquid is generated in updraft regions, which strongly affect parameterized microphysical process rates—in particular, ice nucleation. In comparison, calculating both dynamics and microphysics using the same inputs of temperature and water vapor (hybrid parallel splitting) or adding an additional saturation adjustment within the dynamics reduces the time step sensitivity of surface precipitation by limiting the supersaturation seen by the microphysics, although sensitivity to time step remains for some processes

Microenvironment‐induced restoration of cohesive growth associated with focal activation of P ‐cadherin expression in lobular breast carcinoma metastatic to the colon

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E‐cadherin loss. Focal activation of P‐cadherin expression in tumor cells that are deficient for E‐cadherin occurs in a subset of ILCs. Switching from an E‐cadherin deficient to P‐cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52‐year‐old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E‐cadherin and P‐cadherin. CDH1 /E‐cadherin mutations were determined by next‐generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1 /E‐cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E‐cadherin‐negative and P‐cadherin‐negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter‐cryptal ILC cells switched to a P‐cadherin‐positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment‐induced EPS and conversion to cohesive growth

Проект узла гидрирования сернистых соединений

Конструирование аппарата для гидрирования сернистых соединений содержащихся в природном газе, а также исследование методов очистки природного газа.Designing an apparatus for hydrogenating sulfur compounds in natural gas, and studying methods for purifying natural gas