Ring contraction in synthesis of functionalized carbocycles

Carbocycles are a key and widely present structural motif in organic compounds. The construction of structurally intriguing carbocycles, such as highly-strained fused rings, spirocycles or highly-functionalized carbocycles with congested stereocenters, remains challenging in organic chemistry. Cyclopropanes, cyclobutanes and cyclopentanes within such carbocycles can be synthesized through ring contraction. These ring contractions involve re-arrangement of and/or small molecule extrusion from a parental ring, which is either a carbocycle or a heterocycle of larger size. This review provides an overview of synthetic methods for ring contractions to form cyclopropanes, cyclobutanes and cyclopentanes en route to structurally intriguing carbocycles

Metadata Service to Enable Display of Rich Artifacts in Machine Learning Pipelines

Cloud-based machine learning (ML) platforms enable ML practitioners to build, rebuild, and serve multiple machine learning models in production environments. Proper ML metadata tracking and management is important to enable large-scale experimentation and to provide traceability and verifiability for modern production ML. This disclosure describes a ML metadata service to manage the lifecycle of metadata consumed and produced by ML pipelines. The ML metadata service enables logging detailed metadata as artifacts, capturing metadata as typed artifacts, and capturing a ML pipeline in an intuitive workflow graph. The metadata service enables provision of a ML dashboard that displays visualizations of a ML workflow along with the relevant metadata for each type of entity and supports queries for models and/or datasets that meet specific criteria

Stereoselective synthesis of cyclobutanes by contraction of pyrrolidines

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by a nitrogen extrusion process, the stereospecific synthesis of cyclobutanes involves a radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and a concise, formal synthesis of the cytotoxic natural product piperarborenine B is reported

Delayed maintenance modelling considering speed restriction for a railway section

The deterioration of track geometry depends on several factors of which the speed of the train is one. Imposing a speed restriction can slow down the track deterioration and allows a longer survival time before a serious condition is achieved. Preventive maintenance delays can be authorized during the survival time. However, speed restrictions also reduce the system throughput. On the other hand, a longer interval between preventive maintenance activities has a lower maintenance action cost and it also enables grouping the maintenance activities to save set-up costs as well as system down time. If the repair delay is too long, it may cause unacceptable conditions on the track and lead to higher maintenance costs and accidents. Therefore, it is interesting to assess the effect of a speed restriction on the delayed maintenance strategies for a railway track section. We want to solve a maintenance optimization problem to find the optimal tuning of the maintenance delay time and imposition of a speed restriction. To this aim, a delayed maintenance model is developed, in which track deterioration depends on the train speed and the number of passing trains. The model is used to determine an optimal speed restriction strategy and a preventive repair delay for the optimization of the system benefit and unavailability. Coloured Petri Nets (CPN) are adopted to model the maintenance and operation of the railway track section. The CPN model describes the gradual track deterioration as a stochastic process. Different speed restriction policies and maintenance delay strategies are modelled and activated by the observed component states. Monte Carlo simulations are carried out to estimate the maintenance cost, the system benefit and the system downtime under different policies. Numerical results show the maintenance decision variable trade-off

Numerical Algebraic Geometry: A New Perspective on String and Gauge Theories

The interplay rich between algebraic geometry and string and gauge theories has recently been immensely aided by advances in computational algebra. However, these symbolic (Gr\"{o}bner) methods are severely limited by algorithmic issues such as exponential space complexity and being highly sequential. In this paper, we introduce a novel paradigm of numerical algebraic geometry which in a plethora of situations overcomes these short-comings. Its so-called 'embarrassing parallelizability' allows us to solve many problems and extract physical information which elude the symbolic methods. We describe the method and then use it to solve various problems arising from physics which could not be otherwise solved.Comment: 36 page

One-Pot Synthesis of Biocompatible CdSe/CdS Quantum Dots and Their Applications as Fluorescent Biological Labels

We developed a novel one-pot polyol approach for the synthesis of biocompatible CdSe quantum dots (QDs) using poly(acrylic acid) (PAA) as a capping ligand at 240°C. The morphological and structural characterization confirmed the formation of biocompatible and monodisperse CdSe QDs with several nanometers in size. The encapsulation of CdS thin layers on the surface of CdSe QDs (CdSe/CdS core–shell QDs) was used for passivating the defect emission (650 nm) and enhancing the fluorescent quantum yields up to 30% of band-to-band emission (530–600 nm). Moreover, the PL emission peak of CdSe/CdS core–shell QDs could be tuned from 530 to 600 nm by the size of CdSe core. The as-prepared CdSe/CdS core–shell QDs with small size, well water solubility, good monodispersity, and bright PL emission showed high performance as fluorescent cell labels in vitro. The viability of QDs-labeled 293T cells was evaluated using a 3-(4,5-dimethylthiazol)-2-diphenyltertrazolium bromide (MTT) assay. The results showed the satisfactory (>80%) biocompatibility of as-synthesized PAA-capped QDs at the Cd concentration of 15 μg/ml

Perforated acute appendicitis resulting from appendiceal villous adenoma presenting with small bowel obstruction: a case report

<p>Abstract</p> <p>Background</p> <p>A villous adenoma is an extremely rare benign tumour in the appendix, in contrast to other benign appendiceal lesions. The clinical features are usually asymptomatic. Acute appendicitis is the most common complication with the lesion obstructing the orifice of the appendiceal lumen. Thus, a villous adenoma is usually found during surgical intervention for acute appendicitis. Mechanical obstruction induced by acute perforated appendicitis has been previously reported. Acute appendicitis caused by a villous adenoma presenting with acute intestinal obstruction has not been previously reported.</p> <p>Case presentation</p> <p>A 78-year-old woman presented to our Emergency Department with diffuse abdominal pain and tenderness. The abdominal plain film and computed tomography revealed an intestinal obstruction. After surgical intervention, the ruptured appendix was shown to be associated with intestinal obstruction. The post-operative pathologic diagnosis was an appendiceal villous adenoma.</p> <p>Conclusions</p> <p>This is the first report describing an appendiceal villous adenoma, which is an occasional cause of perforated acute appendicitis, presenting as a complete intestinal obstruction. We emphasize that in elderly patients without a surgical history, the occult cause of complete intestinal obstruction must be determined. If an appendiceal tumour is diagnosed, an intra-operative frozen section is suggested prior to selecting a suitable method of surgical intervention.</p

Cell Encapsulation in Sub-mm Sized Gel Modules Using Replica Molding

For many types of cells, behavior in two-dimensional (2D) culture differs from that in three-dimensional (3D) culture. Among biologists, 2D culture on treated plastic surfaces is currently the most popular method for cell culture. In 3D, no analogous standard method—one that is similarly convenient, flexible, and reproducible—exists. This paper describes a soft-lithographic method to encapsulate cells in 3D gel objects (modules) in a variety of simple shapes (cylinders, crosses, rectangular prisms) with lateral dimensions between 40 and 1000 μm, cell densities of 105 – 108 cells/cm3, and total volumes between 1×10−7 and 8×10−4 cm3. By varying (i) the initial density of cells at seeding, and (ii) the dimensions of the modules, the number of cells per module ranged from 1 to 2500 cells. Modules were formed from a range of standard biopolymers, including collagen, Matrigel™, and agarose, without the complex equipment often used in encapsulation. The small dimensions of the modules allowed rapid transport of nutrients by diffusion to cells at any location in the module, and therefore allowed generation of modules with cell densities near to those of dense tissues (108 – 109 cells/cm3). This modular method is based on soft lithography and requires little special equipment; the method is therefore accessible, flexible, and well suited to (i) understanding the behavior of cells in 3D environments at high densities of cells, as in dense tissues, and (ii) developing applications in tissue engineering

Reproductive factors and oesophageal cancer in Chinese women: a case-control study

<p/> <p>Background</p> <p>Previous studies showed that sex hormone might play a role in the development of oesophageal cancer in Western countries. However, evidence from Chinese populations is still lacking.</p> <p>Methods</p> <p>We performed a hospital-based case-control study in Guangzhou, China. From June 2006 to May 2009, face-to-face interviews were conducted on 73 cases and 157 controls. Cases were Chinese females with newly diagnosed primary oesophageal cancer. Controls were hospitalized individuals without cancer and frequency matched by age groups. The interviews included questions about childbearing and menarche history, together with potential confounders. Unconditional logistic regression was used to estimate the risk of factors.</p> <p>Results</p> <p>Women who had given birth before were not at increased risk compared to childless women (adjusted OR = 1.17, 95% CI: 0.48 ~ 2.85). The risk of oesophageal cancer increased with age at first birth: the adjusted OR for women first giving birth at age 25 or later was 2.02 (95% CI: 1.01 ~ 4.04) compared with those reporting their first birth before age 22. History of spontaneous abortion was not significantly associated with increased risk (adjusted OR = 1.37, 95% CI: 0.49 ~ 3.83). No significant association was observed between menstrual variables (age at menarche, age at menopause, and years of menstruation) and risk of oesophageal cancer.</p> <p>Conclusions</p> <p>Giving birth at later age may increase the risk of oesophageal cancer in women. Further studies in Chinese populations with larger sample sizes are still needed.</p

A high-throughput and sensitive method to measure Global DNA Methylation: Application in Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Genome-wide changes in DNA methylation are an epigenetic phenomenon that can lead to the development of disease. The study of global DNA methylation utilizes technology that requires both expensive equipment and highly specialized skill sets.</p> <p>Methods</p> <p>We have designed and developed an assay, <it>CpG</it>lobal, which is easy-to-use, does not utilize PCR, radioactivity and expensive equipment. <it>CpG</it>lobal utilizes methyl-sensitive restriction enzymes, HRP Neutravidin to detect the biotinylated nucleotides incorporated in an end-fill reaction and a luminometer to measure the chemiluminescence. The assay shows high accuracy and reproducibility in measuring global DNA methylation. Furthermore, <it>CpG</it>lobal correlates significantly with High Performance Capillary Electrophoresis (HPCE), a gold standard technology. We have applied the technology to understand the role of global DNA methylation in the natural history of lung cancer. World-wide, it is the leading cause of death attributed to any cancer. The survival rate is 15% over 5 years due to the lack of any clinical symptoms until the disease has progressed to a stage where cure is limited.</p> <p>Results</p> <p>Through the use of cell lines and paired normal/tumor samples from patients with non-small cell lung cancer (NSCLC) we show that global DNA hypomethylation is highly associated with the progression of the tumor. In addition, the results provide the first indication that the normal part of the lung from a cancer patient has already experienced a loss of methylation compared to a normal individual.</p> <p>Conclusion</p> <p>By detecting these changes in global DNA methylation, <it>CpG</it>lobal may have a role as a barometer for the onset and development of lung cancer.</p