Partial least squares (PLS) have gained wide applications especially in chemometrics, metabolomics/metabonomics as well as bioinformatics. Here, we present libPLS, a library that integrates not only ...basic PLS modeling algorithms but also advanced and/or recently developed methods on model assessment, outlier detection, and variable selection. This package is featured in a set of Model Population Analysis (MPA)-type approaches that have not been integrated into a single package yet and thus functionally complement existing toolboxes. libPLS provides an integrated platform for developing PLS regression and/or linear discriminant analysis (PLS-LDA) models. It is written in MATLAB and freely available at www.libpls.net.
•Provide an integrated library for partial least squares regression and discriminant analysis.•Featured in model population analysis approaches.•Contain a series of versatile variable selection methods.
Asymmetric construction of halogenated quaternary carbon centers under mild reaction conditions remains challenging. Reported here is an unprecedented and highly stereoselective Brønsted base ...catalyzed 4+2 cycloaddition between either α‐chloro‐ or α‐bromoaldehydes and cyclic enones. The key intermediate, an α‐halogenated enolate, is susceptible to dehalogenation and can be stabilized and stereochemically controlled using bifunctional tertiary amines. This method provides facile access to a collection of optically pure bicyclic dihydropyrans having three contiguous stereocenters, including a halogen‐bearing quaternary carbon center. Of note, the product can be transformed in situ into densely functionalized spirocyclopropanes in a highly efficient and stereoselective manner.
Hello Halo! An unprecedented highly enantioselective, Brønsted base catalyzed 4+2 cycloaddition of α‐haloaldehydes and electron‐deficient cyclic enones has been developed. A series of fused bicyclic dihydropyrans featuring a halogenated quaternary stereocenter was synthesized in excellent yields with up to >99 % ee under mild reaction conditions. These products were further transformed into spirocyclopropanes having two vicinal all‐carbon quaternary centers.
Natural polymers, such as polysaccharides and proteins, have been widely studied for numerous biomedical applications because of their bioactivity, natural origin, and biodegradability. To address ...the different needs of a broad spectrum of biomedical applications, natural polymers are modified with or conjugated to small molecular compounds, synthetic and natural polymers, and inorganic nanomaterials and surfaces. Among these hybrid materials, polysaccharide–peptide conjugates have drawn much attention due to their design flexibility, biocompatibility, tunable degradability, and structure similarity to naturally occurring glycoproteins. In the past 20 years, polysaccharide–peptide conjugates have demonstrated the promising potential to address many long‐standing medical challenges. Thus, the design, conjugation chemistry and method, and biomedical applications of polysaccharide–peptide conjugates are summarized and discussed in this review. The conjugation techniques are reviewed from the view of the chemical reactions. Meanwhile, some inspiring examples of polysaccharide–peptide conjugates in biomedical applications, including drug delivery systems, nucleic acid delivery carriers, tissue engineering, and antimicrobial applications, are highlighted. Moreover, the outlook on the challenges and demands of polysaccharide–peptide conjugates is also elaborated.
Polysaccharide–peptide conjugates have been developed as a versatile material platform to combine the unique and complementary features of polysaccharides and peptides for a variety of applications in biomedical fields.
Sequence-derived structural and physiochemical features have been frequently used for analysing and predicting structural, functional, expression and interaction profiles of proteins and peptides. To ...facilitate extensive studies of proteins and peptides, we developed a freely available, open source python package called protein in python (propy) for calculating the widely used structural and physicochemical features of proteins and peptides from amino acid sequence. It computes five feature groups composed of 13 features, including amino acid composition, dipeptide composition, tripeptide composition, normalized Moreau-Broto autocorrelation, Moran autocorrelation, Geary autocorrelation, sequence-order-coupling number, quasi-sequence-order descriptors, composition, transition and distribution of various structural and physicochemical properties and two types of pseudo amino acid composition (PseAAC) descriptors. These features could be generally regarded as different Chou's PseAAC modes. In addition, it can also easily compute the previous descriptors based on user-defined properties, which are automatically available from the AAindex database.
The python package, propy, is freely available via http://code.google.com/p/protpy/downloads/list, and it runs on Linux and MS-Windows.
Supplementary data are available at Bioinformatics online.
A Review on Cable-driven Parallel Robots Qian, Sen; Zi, Bin; Shang, Wei-Wei ...
Chinese journal of mechanical engineering,
12/2018, Letnik:
31, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Cable-driven parallel robots (CDPRs) are categorized as a type of parallel manipulators. In CDPRs, flexible cables are used to take the place of rigid links. The particular property of cables ...provides CDPRs several advantages, including larger workspaces, higher payload-to-weight ratio and lower manufacturing costs rather than rigid-link robots. In this paper, the history of the development of CDPRs is introduced and several successful latest application cases of CDPRs are presented. The theory development of CDPRs is introduced focusing on design, performance analysis and control theory. Research on CDPRs gains wide attention and is highly motivated by the modern engineering demand for large load capacity and workspace. A number of exciting advances in CDPRs are summarized in this paper since it is proposed in the 1980s, which points to a fruitful future both in theory and application. In order to meet the increasing requirements of robot in different areas, future steps foresee more in-depth research and extension applications of CDPRs including intelligent control, composite materials, integrated and reconfigurable design.
The performance of Pd and Pt based catalysts for electrocatalysis is closely correlated with their surface structures and compositions. In this paper we developed an electrochemical route to ...synthesize novel bimetallic screw-like PdPt nanowires (PdPt NWs) with tunable composition. The surface of the as-synthesized screw-like nanowires is extremely rough, bounded with high-index facets and thus exhibits a high density of active sites. The particular surface structure together with the synergetic effect and electronic effect accounts for the enhanced catalytic activity and durability towards methanol and ethylene glycol electrooxidation (MOR and EGOR). The activity of PdPt NWs is highly dependent on their composition; Pd 1 Pt 1 NWs exhibit the highest catalytic activity for MOR that is 2.4-fold and 5.4-fold higher than that of the typical pure high-index Pt tetrahexahedrons (Pt THHs) and commercial Pt/C, respectively. It should be stressed that the initial activity of Pd 1 Pt 1 NWs towards EGOR is close to that of Pt THHs but the stability of the Pd 1 Pt 1 NWs can be significantly enhanced. In situ FTIR spectroscopic studies of the Pd 1 Pt 1 NWs have revealed that their ability towards CO-tolerance is highly improved, and their capability of cleaving the C–C bond of EG is greatly promoted. This study has shed new light on the structure and composition tuning of PdPt nanocatalysts with high performance, which is of great significance for direct alcohol fuel cells.
Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and ...select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients.
We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes.
CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival.
This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments.
ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. ...Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.
The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for ...intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.
Uniform experimental design in chemometrics Xu, Qing‐Song; Xu, Yuan‐Da; Li, Lan ...
Journal of chemometrics,
November 2018, 2018-11-00, 20181101, Letnik:
32, Številka:
11
Journal Article
Recenzirano
Experimental designs and modeling are very important in chemometrics and chemical engineering. There are many kinds of experimental designs, which include the fractional factorial design (including ...the orthogonal design), the optimal regression design, and the uniform design. The uniform experimental design can be regarded as a fractional factorial design with model uncertainty, a space filling design for computer experiments, a robust design against model specification, and a supersaturated design. This paper gives a brief introduction to the recent theoretical developments on uniform experimental design as well as its applications in chemometrics.
This paper gives a brief introduction to the recent theoretical developments on uniform experimental design as well as its applications in chemometrics.
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