bluuebunny/crossref_metadata_2025_split huggingface dataset:
2.1.6 [3 + 2] Cycloaddition as the Key Step
Authors: Raghunathan R. , Purushothaman S. 
Published: May 2016

Abstractα, β-Unsaturated carbonyl compounds, which act as dipolarophiles in [3 + 2]-cycloaddition reactions with azomethine ylides, have been used for the highly regio- and stereoselective construction of heterocycles such as spiro-fused pyrrolidines. Azomethine ylides generated from isatin (1H-indole-2,3-dione) and cyclic and acyclic α-amino acids are considered to be important 1,3-dipoles, since their cycloaddition to α, β-unsaturated carbonyl compounds leads to the formation of spiro[indoline-3,2′-pyrrolidin]-2-ones, which form the basic building units of several natural and biologically active compounds.
2.1.7 [4 + 2] Cycloaddition as the Key Step
Authors: Elliott M. , Jones D. H. 
Published: May 2016

Abstractα, β-Unsaturated carbonyl compounds are widely used as dienes and as dienophiles in [4 + 2] cycloadditions. This review covers those cycloaddition reactions in which a multicomponent reaction is used either in the formation of the α, β-unsaturated carbonyl compound or for the assembly of the final product. The review is organized according to the role of the carbonyl component (diene or dienophile) and whether it is introduced as a reagent or formed during the reaction.
2.1.4 Electron-Deficient Alkynes as Electrophiles
Authors: Shaabani A. , Sarvary A. , Shaabani S. 
Published: May 2016

AbstractThis chapter describes multicomponent reactions involving electron-deficient alkynes as electrophiles. The main focus is the addition of nucleophiles such as aza-aromatics, amines, and carbenes to electron-deficient alkynes in the presence of various suitable components such as CH-, NH-, and OH-acids, carbonyl and imine compounds, and electron-deficient alkenes. These multicomponent reactions result in the synthesis of various heterocyclic and open-chain organic products.
1.1.1 Hydroformylation of Alkenes
Authors: Bronger R. P. J. , Kamer P. C. J. , Vogt D. 
Published: May 2016

AbstractHydroformylation of alkenes is a mild and clean method for the functionalization of hydrocarbons and has grown to be among the most important homogeneously catalyzed reactions in industry. It is a 100% atom-economic reaction to prepare aldehydes that are important synthons for organic synthesis, and has wide functional group compatibility.In this review the focus is on the effects of various catalysts on the selective hydroformylation of both functionalized and unfunctionalized alkenes to produce high-value aldehydes. In particular, rhodium catalysts have undergone a remarkable development, while cobalt catalysts have remained more or less unchanged over the years, and palladium has recently been recognized as a suitable transition metal for hydroformylation.
1.1.5 Hydroformylation of Alkenes: Industrial Applications
Authors: de Vries J. G. 
Published: May 2016

AbstractAlkenes can be converted into aldehydes using a highly atom-efficient hydroformylation reaction in which carbon monoxide and hydrogen are added across the double bond. In this chapter industrial hydroformylation processes are described. Catalysts are based on cobalt with or without trialkylphosphine ligands, or rhodium with triarylphosphine ligands or monodentate or bidentate triaryl phosphite ligands. The products are raw materials for plasticizers and solvents.
1.1.6 Carbonylation of Alkenes
Authors: Clarke M. L. , Fuentes J. A. 
Published: May 2016

AbstractThis chapter provides a concise overview of metal-catalyzed additions to alkenes that involve carbon monoxide and another nucleophilic species, such as water or an alcohol. This is an important area of research in terms of several commodity chemical targets, with many papers devoted to the evolution and mechanistic interrogation of catalysts that are viable for industry. This chapter demonstrates that this class of reaction is synthetically useful for a wide range of possible target molecules. Such reactions include the formation of carboxylic acids, including the “profen” family of drugs by hydroxycarbonylation of vinylarenes, in which it is now possible to control both regioselectivity and, to a lesser degree, enantioselectivity. The alkoxycarbonylation of alkenes primarily refers to what is more strictly a hydroalkoxycarbonylation, where hydride and carbon monoxide are added across an alkene and then terminated with an alcohol. Both intermolecular and intramolecular variants of this reaction are discussed. Other variants of alkene carbonylation are those where a nucleophile attacks an alkene, with the other terminus being functionalized with a carboxylic acid derivative derived from carbon monoxide. A few examples are highlighted with typical experimental procedures that should aid the nonspecialist in conducting these reactions.
1.1.8 Addition of Carbon Dioxide to Alkenes and Other Unsaturated Hydrocarbons
Authors: Takaya J. , Iwasawa N. 
Published: May 2016

AbstractVarious transition-metal complexes promote CC bond-forming reactions of carbon dioxide with acyclic unsaturated hydrocarbons including alkenes, alkynes, 1,3-dienes, and allenes. These reactions provide efficient methods for the synthesis of carboxylic acids and their derivatives.
1.2.1 Carbonylation of Alkynes
Authors: Clarke M. L. , Fuentes J. A. 
Published: May 2016

AbstractThis chapter provides a concise overview of metal-catalyzed additions to alkynes that involve carbon monoxide and a nucleophilic species, such as water, an alcohol, a thiol, or an amine. Alkynes undergo very efficient hydroalkoxyesterifications of the type extensively studied in alkene carbonylation chemistry, but in this case giving unsaturated esters and seemingly by a different mechanism that allows for a wider range of reaction pathways. In this chapter, examples are presented where relatively subtle changes in substrate structure or competing pathways lead to a range of products; nucleophiles can add to alkynes in an intramolecular fashion prior to carbonylation, or external nucleophiles attack an alkyne to initiate a carbonylation. The carbonylation events can also be terminated in several different ways, especially under oxidative conditions. Several representative experimental procedures are given for the main classes of carbonylation covered.
1.3.3 Stereoselective Addition of Nitromethane
Authors: Ballini R. , Petrini M. 
Published: May 2016

AbstractNitromethane readily adds to carbonyl derivatives in a process known as the nitroaldol or Henry reaction. The enantioselective addition onto prochiral carbonyl groups can be carried out under asymmetric catalysis, mainly using copper and zinc complexes. Organocatalytic methods find only limited applications in nitroaldol reactions, being especially applied in diastereoselective processes and in the addition of nitromethane to activated ketone derivatives. The asymmetric aza version of the nitroaldol reaction (the aza-Henry reaction) with nitromethane is also possible using highly reactive N-acylaldimino derivatives. The latter electrophilic species can be freshly prepared before their utilization or generated in situ from suitable precursors. Finally, addition of nitromethane to N-sulfonylketimines and optically active N-sulfinylketimines readily provides an efficient entry to enantioenriched nitro amino compounds bearing a quaternary stereocenter.
1.1.2 Arylation Using a Palladium(II)/Palladium(IV) Catalyst System
Authors: Gandeepan P. , Chien-Hong C. 
Published: May 2016

AbstractAryl—aryl bonds are important structural motifs that are found in many natural products, bioactive compounds, and functional materials. Due to their application in various fields of organic and materials chemistry, continuous efforts have been made to develop attractive methods for their synthesis. In particular, aryl—aryl bond formation involving a palladium(II)/palladium(IV) catalyst system has received much attention in recent years. Compared to the traditional cross-coupling reactions and C—H arylation involving palladium(II)/palladium(0), biaryl formation via a palladium(IV) intermediate has high potential for application due to its insensitivity toward air and moisture, tolerance of various functional groups, lack of ligand requirement, and the very mild reaction temperature. In this chapter, arylation reactions using a palladium(II)/palladium(IV) catalyst system are reviewed.
Combinatorial effects of odorants on mouse behavior
Authors: Saraiva Luis R. , Kondoh Kunio , Ye Xiaolan , Yoon Kyoung-hye , Hernandez Marcus , Buck Linda B. 
Published: May 2016

Significance
Odor detection in the mouse nose is mediated by ∼1,000 different odorant receptors (ORs) and 14 trace amine-associated receptors (TAARs). Different OR combinations generate different odor perceptions. However, a few TAARs are associated with innate odor attraction or aversion, suggesting they signal through hard-wired neural circuits resistant to combinatorial receptor inputs. Contrary to this prediction, we find that different ligands for a given TAAR can be attractive or aversive, or instead neutral. In addition, some attractive and aversive odorants block one another’s behavioral effects. Odor blocking can occur without receptor antagonism in the nose and can require sensory input from one receptor. Thus, innate odor-induced behaviors can be context-dependent and modulated by interactions in the brain among signals derived from different receptors.
Intestinal dysbiosis and innate immune responses in axial spondyloarthritis
Authors: Ciccia Francesco , Ferrante Angelo , Triolo Giovanni 
Published: May 2016

Purpose of review
Inflammatory innate and adaptive immune cell responses to commensal bacteria underlie the pathogenesis of human chronic inflammatory diseases. Intestinal dysbiosis has been described in patients with spondyloarthritis (SpA) and seems to be correlated with histologic and immunologic alterations. Purpose of this review is to discuss the relationship occurring between intestinal dysbiosis and innate immune responses in patients with axial SpA.

Recent findings
Intestinal dysbiosis and differential activation of intestinal immune responses in patients with SpA have been demonstrated. Furthermore, innate cells that appear to be involved in the pathogenesis of SpA may control intestinal homeostasis through induction of apoptotic cell death and deletion of activated commensal bacteria-specific T cells.

Summary
Although the evidence shows that dysbiosis occurs in SpA, it is not clear the role of dysbiosis in regulating innate immune responses in SpA. Relationships between cause and effect remain to be answered.

Video abstract

http://links.lww.com/COR/A34.
Telomerase in hematologic malignancies
Authors: Bruedigam Claudia , Lane Steven W. 
Published: May 2016

Purpose of reviewThe activation of telomere maintenance pathways has long been regarded as a key hallmark of cancer and this has propelled the development of novel inhibitors of telomerase. In this review, we detail the background biology on telomere maintenance in health and disease, then concentrate on the recent preclinical and clinical development behind targeting telomerase in blood cancers.Recent findingsPreclinical and clinical studies have shown that imetelstat, a competitive inhibitor of telomerase, has activity in certain hematologic malignancies, in particular the myeloproliferative neoplasms and acute myeloid leukemia.SummaryTelomerase inhibition has shown remarkable efficacy in myeloid malignancies, and current and future preclinical and clinical studies are necessary to comprehensively investigate its underlying mechanism of action. Future work should identify the potential genetic susceptibilities to telomerase inhibition therapy, and evaluate rational combinations of telomerase inhibitors with chemotherapy and other novel agents. Robust preclinical evaluation is essential to best translate these new agents successfully into our clinical treatment algorithm for myeloid and other blood cancers.
Modulating cholesterol efflux capacity to improve cardiovascular disease
Authors: Brownell Nicholas , Rohatgi Anand 
Published: May 2016

Purpose of review
Low HDL-cholesterol (HDL-C) levels are predictive of incident atherosclerotic cardiovascular disease events. However, the use of medication to raise HDL-C levels has not consistently shown clinical benefit. As a result, studies have shifted toward HDL function, specifically cholesterol efflux, which has been inversely associated with prevalent subclinical atherosclerosis as well as subsequent atherosclerotic cardiovascular disease events. The purpose of this review is to summarize the effects of current medications and interventions on cholesterol efflux capacity.

Recent findings
Medications for cardiovascular health, including statins, fibrates, niacin, and novel therapeutics, are reviewed for their effect on cholesterol efflux. Differences in population studied and assay used are addressed appropriately. Lifestyle interventions, including diet and exercise, are also included in the review.

Summary
The modification of cholesterol efflux capacity (CEC) by current medications and interventions has been investigated in both large randomized control trials and smaller observational cohorts. This review serves to compile the results of these studies and evaluate CEC modulation by commonly used medications. Altering CEC could be a novel therapeutic approach to improving cardiovascular risk profiles.
A Pooled Analysis of Robotic Versus Laparoscopic Surgery for Total Mesorectal Excision for Rectal Cancer
Authors: Wang Yue , Zhao Guo-Hua , Yang Helen , Lin Jie 
Published: May 2016

Objective:
We conducted the meta-analysis to evaluate the safety and efficacy of robotic total mesorectal excision (RTME) compared with laparoscopic total mesorectal excision (LTME) in treatment of rectal cancer.

Materials and Methods:
A systematic search of Medline, Embase databases, and the Cochrane Library was performed to identify studies that compared RTME versus LTME for rectal cancer and were published up to July 2014. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, the fixed or random effect model was used for the meta-analysis. Outcomes of interest and related outcomes were evaluated.

Results:
Eight studies were included in the meta-analysis. These studies involved a total of 1229 patients, 554 of whom underwent RTME and 675 of whom underwent LTME. The meta-analysis showed that RTME had lower conversion rate and positive rate of circumferential resection margins, and lesser incidence of erectile dysfunction.

Conclusions:
Our study suggests that RTME for rectal cancer appears to be a safe, feasible, and minimally invasive alternative to its laparoscopic counterpart. But the long-term outcomes between the 2 techniques need to be further examined.
Scalable Design of paired CRISPR Guide RNAs for Genomic Deletion
Authors: Pulido-Quetglas Carlos , Aparicio-Prat Estel , Arnan Carme , Polidori Taisia , Hermoso Toni , Palumbo Emilio , Ponomarenko Julia , Guigo Roderic , Johnson Rory 
Published: May 2016

AbstractUsing CRISPR/Cas9, diverse genomic elements may be studied in their endogenous context. Pairs of single guide RNAs (sgRNAs) are used to delete regulatory elements and small RNA genes, while longer RNAs can be silenced through promoter deletion. We here present CRISPETa, a bioinformatic pipeline for flexible and scalable paired sgRNA design based on an empirical scoring model. Multiple sgRNA pairs are returned for each target. Any number of targets can be analyzed in parallel, making CRISPETa equally appropriate for studies of individual elements, or complex library screens. Fast run-times are achieved using a precomputed off-target database. sgRNA pair designs are output in a convenient format for visualisation and oligonucleotide ordering. We present a series of pre-designed, high-coverage library designs for entire classes of non-coding elements in human, mouse, zebrafish,DrosophilaandC. elegans. Using an improved version of the DECKO deletion vector, together with a quantitative deletion assay, we test CRISPETa designs by deleting an enhancer and exonic fragment of theMALAT1oncogene. These achieve efficiencies of ≥50%, resulting in production of mutant RNA. CRISPETa will be useful for researchers seeking to harness CRISPR for targeted genomic deletion, in a variety of model organisms, from single-target to high-throughput scales.
Gating mass cytometry data by deep learning
Authors: Li Huamin , Shaham Uri , Stanton Kelly P. , Yao Yi , Montgomery Ruth , Kluger Yuval 
Published: May 2016

AbstractMass cytometry or CyTOF is an emerging technology for high-dimensional multiparameter single cell analysis that overcomes many limitations of fluorescence-based flow cytometry. New methods for analyzing CyTOF data attempt to improve automation, scalability, performance, and interpretation of data generated in large studies. Assigning individual cells into discrete groups of cell types (gating) involves time-consuming sequential manual steps, untenable for larger studies. We introduce DeepCyTOF, a standardization approach for gating, based on deep learning techniques. DeepCyTOF requires labeled cells from only a single sample. It is based on domain adaptation principles and is a generalization of previous work that allows us to calibrate between a target distribution and a source distribution in an unsupervised manner. We show that Deep-CyTOF is highly concordant (98%) with cell classification obtained by individual manual gating of each sample when applied to a collection of 16 biological replicates of primary immune blood cells, even when measured accross several instruments. Further, DeepCyTOF achieves very high accuracy on the semi-automated gating challenge of the FlowCAP-I competition as well as two CyTOF datasets generated from primary immune blood cells: (i)14 subjects with a history of infection with West Nile virus (WNV), (ii) 34 healthy subjects of different ages. We conclude that deep learning in general, and DeepCyTOF specifically, offers a powerful computational approach for semi-automated gating of CyTOF and flow cytometry data.
Nonessential nucleoporins Nup2, Nup60 and Nup84 are required for normal meiosis inSaccharomyces cerevisiae
Authors: Chu Daniel B. , Burgess Sean M. 
Published: May 2016

AbstractThe nuclear pore complex (NPC) selectively transports cargo between the nucleus and the cytoplasm. The inner nuclear membrane (INM) face of the NPC also serves as a hub where gene silencing and DNA repair are spatially coordinated. InSaccharomyces cerevisiae, partitioning of active and silenced chromatin at subtelomeric regions depends on the boundary activity of nonessential nucleoporin proteins Nup2 and Nup60, along with Htz1, the histone variant H2A.Z. The INM is also important for the chromosome events of meiosis since Ndj1-mediated telomere attachment and clustering at the INM is required for efficient homolog pairing, recombination, and segregation. Here we tested possible meiotic roles for Nup2, Nup60, Htz1, and other nonessential nucleoporins by analyzing the effects of deletion mutations on sporulation, spore viability and possible phenotypic epistasis withndj1Δ. DeletingNUP2,NUP60, andHTZ1reduced spore viability compared to wild-type (WT). A detailed analysis of spore lethality indicated that homolog nondisjunction in these mutants was elevated compared to WT, yet unlikendj1Δ, this was not the predominant cause of spore death. DeletingNUP84reduced meiosis I nuclear divisions, while deletingNUP53,NUP100, andNUP157had no effect on sporulation, spore viability, or the kinetics of meiosis I progression. Surprisingly,nup2Δ ndj1Δuniquely failed to undergo meiosis I nuclear divisions, suggesting Nup2 and Ndj1 function in partially redundant pathways or create a poisonous intermediate. The meiosis I division was also delayed by 2 hours innup2Δcompared to WT pointing to a specialized role for Nup2 in the meiotic program.
Improving occupational health by modelling indoor pollutant distribution
Authors: Pitarma Rui , Lourenço Miguel , Ramos João 
Published: May 2016

Purpose
Indoor environments are characterized by several pollutant sources. Some of these can be sufficiently characterized through the prediction of the airflow and pollutant distribution patterns. The purpose of this study was to simulate, analyze and compare different locations of known pollutant source inside a ventilated room.

Design/methodology/approach
Computational fluid dynamics modelling approach was used to analyze the prediction of the airflow and pollutant distribution patterns for different locations of known pollutant source inside a ventilated room by mixing ventilation.

Findings
Distinct areas of poor air quality, perfectly identified by concentration fields, were given. The indoor air quality obtained by the different simulated conditions was analyzed and compared.

Research limitations/implications
Pollutant concentration was not measured in the validation experiments (qualitative validation based on the velocity fields).

Practical implications
Once the contaminant concentration fields are calculated based on the source location, the model is very useful to choose the best place to install any pollutant indoor equipment to preserve breathing zones.

Originality/value
Providing an effective indoor air quality assessment to prevent exposure risk. The results would be useful for making decisions to optimize the design procedure, such as establish the best location to install polluting equipment, occupied areas and their interdependence with ventilation systems. In addition, this tool also helps to choose the best location and correct set point adjustment for the pollutant sensors.
Sustainable healthcare design
Authors: Sagha Zadeh Rana , Xuan Xiaodong , Shepley Mardelle M. 
Published: May 2016

Purpose
Healthcare projects face multiple obstacles in achieving sustainability. This paper aims to provide information regarding the energy consumption of healthcare facilities, to identify barriers to sustainability and to suggest methods to improve the effectiveness of these buildings.

Design/methodology/approach
This study investigates sustainability in healthcare buildings by examining national databases about energy use and energy savings. The authors then initiate a dialogue on this topic by interviewing experts in healthcare planning and design regarding the implications of this data, challenges to sustainability and potential solutions to these challenges.

Findings
An analysis of data from the Energy Information Administration revealed that healthcare facilities rank second among building types in the USA in energy use per square foot and rank fourth in total energy use. Data from the US Green Building Council showed that only 1 per cent of healthcare buildings are registered with the Leadership in Energy and Environmental Design rating system, and 0.4 per cent have achieved certification, which is low compared with other building types.

Research limitations/implications
Research and discussion must continue engaging all stakeholders to interpret the data and identify transformative solutions to facilitate sustainable healthcare design construction and operation.

Practical implications
It is important to approach sustainability in healthcare from social, economic, environmental and health-related perspectives. The authors identify five major barriers to sustainable healthcare design and construction and discuss 12 practical solutions.

Originality/value
Given the energy demands of healthcare buildings, facilitating their sustainability has the potential to make a significant difference in national energy use. Empirical research and evidence-based design can potentially help to accelerate sustainability by clarifying impacts and documenting the economic and operational returns on investment.