Peak reduction technique in commutative algebra

The "peak reduction" method is a powerful combinatorial technique with applications in many different areas of mathematics as well as theoretical computer science. It was introduced by Whitehead, a famous topologist and group theorist, who used it to solve an important algorithmic problem concerning automorphisms of a free group. Since then, this method was used to solve numerous problems in group theory, topology, combinatorics, and probably in some other areas as well. In this paper, we give a survey of what seems to be the first applications of the peak reduction technique in commutative algebra and affine algebraic geometry.Comment: survey; 10 page

Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol.

LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and a number of pharmaceutical drugs. It is expressed in numerous cell types including T-cells, cancer cells and brain endothelial cells. However, mechanistic knowledge of how it functions and its interactions with lipids are unknown or limited due to inability of obtaining stable purified protein in sufficient quantities. Our data show that depleting cellular cholesterol reduced the Vmax but not the Km of the LAT1 mediated uptake of a model substrate into cells (L-DOPA). A soluble cholesterol analogue was required for the stable purification of the LAT1 with its chaperon CD98 (4F2hc,SLC3A2) and that this stabilised complex retained the ability to interact with a substrate. We propose cholesterol interacts with the conserved regions in the LAT1 transporter that have been shown to bind to cholesterol/CHS in Drosophila melanogaster dopamine transporter. In conclusion, LAT1 is modulated by cholesterol impacting on its stability and transporter activity. This novel finding has implications for other SLC7 family members and additional eukaryotic transporters that contain the LeuT fold

LAT1 (SLC7A5) and CD98hc (SLC3A2) complex dynamics revealed by single-particle cryo-EM

Solute carriers are a large class of transporters that play key roles in normal and disease physiology. Among the solute carriers, heteromeric amino-acid transporters (HATs) are unique in their quaternary structure. LAT1–CD98hc, a HAT, transports essential amino acids and drugs across the blood–brain barrier and into cancer cells. It is therefore an important target both biologically and therapeutically. During the course of this work, cryo-EM structures of LAT1–CD98hc in the inward-facing conformation and in either the substrate-bound or apo states were reported to 3.3–3.5 Å resolution [Yan et al. (2019), Nature (London), 568, 127–130]. Here, these structures are analyzed together with our lower resolution cryo-EM structure, and multibody 3D auto-refinement against single-particle cryo-EM data was used to characterize the dynamics of the interaction of CD98hc and LAT1. It is shown that the CD98hc ectodomain and the LAT1 extracellular surface share no substantial interface. This allows the CD98hc ectodomain to have a high degree of movement within the extracellular space. The functional implications of these aspects are discussed together with the structure determination

Eight Challenges of Servitization for the Configuration, Measurement and Management of Organisations

Purpose – There is an extensive research literature on servitisation and the related field of product-service systems that has emerged independently from different fields including engineering, management, design and environmental studies. The purpose of this paper is to conduct a structured literature review to explore, identify and synthesise the multi-disciplinary research challenges in the journey towards servitisation. Design/methodology/approach – The research approach is a systematic literature review using key word searches and citation tracking for research reported between 1990 and 2013 in research databases that cover the fields which have generated the body of knowledge. Findings – One of the key findings from the extant literature on servitisation is that it suffers from three fundamental weaknesses. First, numerous studies are conceptual in nature with limited practicality. Second, there are relatively few empirical studies, and often the findings relate to a single case study based on the insights of a limited number of senior managers. Third, often the dynamics are insufficiently studied in these organisations because data for most cases are collected post-event. Research limitations/implications – Based on the literature review and its shortfalls, this paper proposes a holistic framework of eight themes that require further attention from academic researchers in order that a more complete conceptual understanding of servitisation is developed to support practice. Practical implications – Each theme in the framework has an associated list of questions that can be addressed through research and presented to managers as a challenge agenda to improve their servitisation efforts. That servitisation is associated with differentiation and competitive advantage makes this a valuable approach for managing corporate performance. Originality/value – Research from multi-disciplinary sources is synergised in order to develop an overarching servitisation agenda that transcends domain-based boundaries. This paves the way for an approach to servitisation that is coherent and harmonious

Purification and Structural Characterization of Aggregation-Prone Human TDP-43 Involved in Neurodegenerative Diseases

© 2020 The Author(s) Mislocalization, cleavage, and aggregation of the human protein TDP-43 is found in many neurodegenerative diseases. As is the case with many other proteins that are completely or partially structurally disordered, production of full-length recombinant TDP-43 in the quantities necessary for structural characterization has proved difficult. We show that the full-length TDP-43 protein and two truncated N-terminal constructs 1-270 and 1-263 can be heterologously expressed in E. coli. Full-length TDP-43 could be prevented from aggregation during purification using a detergent. Crystals grown from an N-terminal construct (1-270) revealed only the N-terminal domain (residues 1-80) with molecules arranged as parallel spirals with neighboring molecules arranged in head-to-tail fashion. To obtain detergent-free, full-length TDP-43 we mutated all six tryptophan residues to alanine. This provided sufficient soluble protein to collect small-angle X-ray scattering data. Refining relative positions of individual domains and intrinsically disordered regions against this data yielded a model of full-length TDP-43

Changing and pivoting the business model in software startups

In a company, its business strategy and business model undergo changes throughout its life. These changes can be induced or forced externally or they can result from a deliberate strategy to improve the business performance and to achieve success. Certain changes can lead to a major change in the business model of the company (i.e., a pivot). Such change or innovation in the business model can occur in various of its dimensions. According to Osterwalder and Pigneur, there are four epicenters of change and innovation to be taken into consideration. In this manuscript, fifteen Portuguese software startups were studied using essentially semi-structured interviews to gather the information. The data was processed with a software application for qualitative data analysis. The main results are related to a dynamic process of evolution and change of the business model in software startups. In particular, we have identified that the changes in the business elements that support the production of the value proposition (left-hand side of the Business Model Canvas) affect the elements that explain the strategy of delivering the value proposition to customers (right-hand side of the Business Model Canvas).This work was supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT Fundação para a Ciência e a Tecnologia within the Project Scope: UID/CEC/00319/2013

Stretchable liquid-crystal blue-phase gels

Liquid crystalline polymers are materials of considerable scientific interest and technological value to society [1-3]. An important subset of such materials exhibit rubber-like elasticity; these can combine the remarkable optical properties of liquid crystals with the favourable mechanical properties of rubber and, further, exhibit behaviour not seen in either type of material independently [2]. Many of their properties depend crucially on the particular mesophase employed. Stretchable liquid crystalline polymers have previously been demonstrated in the nematic, chiral nematic, and smectic mesophases [2,4]. Here were report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that may have its optical properties manipulated by an applied strain and, further, remains electro-optically switchable under a moderate applied voltage. We find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and new possibilities for low-voltage electro-optic devices.Comment: 15 pages, 6 figures, additional data and discussion included. Supplementary videos available from F. Castles on reques

Proximity curves for potential-based clustering

YesThe concept of proximity curve and a new algorithm are proposed for obtaining clusters in a finite set of data points in the finite dimensional Euclidean space. Each point is endowed with a potential constructed by means of a multi-dimensional Cauchy density, contributing to an overall anisotropic potential function. Guided by the steepest descent algorithm, the data points are successively visited and removed one by one, and at each stage the overall potential is updated and the magnitude of its local gradient is calculated. The result is a finite sequence of tuples, the proximity curve, whose pattern is analysed to give rise to a deterministic clustering. The finite set of all such proximity curves in conjunction with a simulation study of their distribution results in a probabilistic clustering represented by a distribution on the set of dendrograms. A two-dimensional synthetic data set is used to illustrate the proposed potential-based clustering idea. It is shown that the results achieved are plausible since both the ‘geographic distribution’ of data points as well as the ‘topographic features’ imposed by the potential function are well reflected in the suggested clustering. Experiments using the Iris data set are conducted for validation purposes on classification and clustering benchmark data. The results are consistent with the proposed theoretical framework and data properties, and open new approaches and applications to consider data processing from different perspectives and interpret data attributes contribution to patterns

XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk

Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Barbisan, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Poleri, Lucía Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Golijow, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

Electrically controlled long-distance spin transport through an antiferromagnetic insulator

Spintronics uses spins, the intrinsic angular momentum of electrons, as an alternative for the electron charge. Its long-term goal is in the development of beyond-Moore low dissipation technology devices. Recent progress demonstrated the long-distance transport of spin signals across ferromagnetic insulators. Antiferromagnetically ordered materials are however the most common class of magnetic materials with several crucial advantages over ferromagnetic systems. In contrast to the latter, antiferromagnets exhibit no net magnetic moment, which renders them stable and impervious to external fields. In addition, they can be operated at THz frequencies. While fundamentally their properties bode well for spin transport, previous indirect observations indicate that spin transmission through antiferromagnets is limited to short distances of a few nanometers. Here we demonstrate the long-distance, over tens of micrometers, propagation of spin currents through hematite (\alpha-Fe2O3), the most common antiferromagnetic iron oxide, exploiting the spin Hall effect for spin injection. We control the spin current flow by the interfacial spin-bias and by tuning the antiferromagnetic resonance frequency with an external magnetic field. This simple antiferromagnetic insulator is shown to convey spin information parallel to the compensated moment (N\'eel order) over distances exceeding tens of micrometers. This newly-discovered mechanism transports spin as efficiently as the net magnetic moments in the best-suited complex ferromagnets. Our results pave the way to ultra-fast, low-power antiferromagnet-insulator-based spin-logic devices that operate at room temperature and in the absence of magnetic fields