A companion matrix approach to the study of zeros and critical points of a polynomial

In this paper, we introduce a new type of companion matrices, namely, D-companion matrices. By using these D-companion matrices, we are able to apply matrix theory directly to study the geometrical relation between the zeros and critical points of a polynomial. In fact, this new approach will allow us to prove quite a number of new as well as known results on this topic. For example, we prove some results on the majorization of the critical points of a polynomial by its zeros. In particular, we give a different proof of a recent result of Gerhard Schmeisser on this topic. The same method allows us to prove a higher order Schoenberg-type conjecture proposed by M.G. de Bruin and A. Sharma. © 2005 Elsevier Inc. All rights reserved.preprin

Laboratory aspects of assisted reproduction.

A number of advances have been made concerning the laboratory aspects of assisted reproduction. Intracytoplasmic sperm injection has revolutionised the treatment of male infertility. With the development of better embryo culture media, blastocyst transfer is now possible and is likely to reduce high-order multiple pregnancy in assisted reproduction treatment. Pre-implantation genetic diagnosis has become an alternative to prenatal diagnosis. The recent use of molecular biology techniques to detect small genetic defects in men with severe male-factor infertility has provided information for the better counselling of these patients. Other techniques that are being developed are likely to have a tremendous impact on assisted reproduction treatment. These include in vitro maturation, follicle culture, and oocyte/ovarian tissue cryopreservation. The current status of the developments in the laboratory aspects of assisted reproduction is reviewed in this article.published_or_final_versio

Immunomodulation in Administration of rAAV: Preclinical and Clinical Adjuvant Pharmacotherapies

Recombinant adeno-associated virus (rAAV) has attracted a significant research focus for delivering genetic therapies to target cells. This non-enveloped virus has been trialed in many clinical-stage therapeutic strategies but important obstacle in clinical translation is the activation of both innate and adaptive immune response to the protein capsid, vector genome and transgene product. In addition, the normal population has pre-existing neutralizing antibodies against wild-type AAV, and cross-reactivity is observed between different rAAV serotypes. While extent of response can be influenced by dosing, administration route and target organ(s), these pose concerns over reduction or complete loss of efficacy, options for re-administration, and other unwanted immunological sequalae such as local tissue damage. To reduce said immunological risks, patients are excluded if they harbor anti-AAV antibodies or have received gene therapy previously. Studies have incorporated immunomodulating or suppressive regimens to block cellular and humoral immune responses such as systemic corticosteroids pre- and post-administration of Luxturna® and Zolgensma®, the two rAAV products with licensed regulatory approval in Europe and the United States. In this review, we will introduce the current pharmacological strategies to immunosuppress or immunomodulate the host immune response to rAAV gene therapy

Extending the depth of field in a compound-eye imaging system with super-resolution reconstruction

Optical device miniaturization is highly desirable in many applications. Direct down-scaling of traditional imaging system is one approach, but the extent to which it can be minimized is limited by the effect of diffraction. Compound-eye imaging system, which utilizes multiple microlenses in image capture is a promising alternative. In this paper, we explore the possibility of an incorporation of phase masks in such a system to extend the depth of field. Simulation experiments are conducted to verify the feasibility of the system. © 2006 IEEE.published_or_final_versio

Scaffolding interaction in asynchronous online discussion through peer facilitation

This study aims to identify the peer facilitation techniques that could scaffold interaction in asynchronous online discussion forums. The findings of this study suggest that scaffolding interaction in asynchronous online discussion through peer facilitation could be achieved through the use of the following five peer facilitation techniques: "showing appreciation", "considering others' viewpoints", "general invitation to contribute", "questioning" and "challenging others' points".published_or_final_versio

Density estimates on composite polynomials

postprin

Towards accurate species-level metabarcoding of arthropod communities from the tropical forest canopy

Metabarcoding of arthropod communities can be used for assessing species diversity in tropical forests but the methodology requires validation for accurate and repeatable species occurrences in complex mixtures. This study investigates how the composition of ecological samples affects the accuracy of species recovery. Starting with field-collected bulk samples from the tropical canopy, the recovery of specimens was tested for subsets of different body sizes and major taxa, by assembling these subsets into increasingly complex composite pools. After metabarcoding, we track whether richness, diversity and most importantly composition of any size class or taxonomic subset is affected by the presence of other subsets in the mixture. Operational Taxonomic Units (OTUs) greatly exceeded the number of morphospecies in most taxa, even under very stringent sequencing read filtering. There was no significant effect on the recovered OTU richness of small and medium-sized arthropods when metabarcoded alongside larger arthropods, despite substantial biomass differences in the mixture. The recovery of taxonomic subsets was not generally influenced by the presence of other taxa, although with some exceptions likely due to primer mismatches. Considerable compositional variation within size and taxon-based subcommunities were evident resulting in high beta diversity among samples from within a single tree canopy, but this beta diversity was not affected by experimental manipulation. We conclude that OTU recovery in complex arthropod communities, with sufficient sequencing depth and within reasonable size ranges, is not skewed by variable biomass of the constituent species. This could remove the need for time-intensive manual sorting prior to metabarcoding. However, there remains a chance of taxonomic bias, which may be primer-dependent. There will never be a panacea primer; instead, metabarcoding studies should carefully consider whether the aim is broad-scale turnover, in which case these biases may not be important, or species lists, in which case separate PCRs and sequencing might be necessary. OTU number inflation remains an issue in metabarcoding and requires bioinformatic development, particularly in read filtering and OTU clustering, and/or greater use of species-identifying sequences generated outside of bulk sequencing

A general framework for searching in distributed data repositories

This paper proposes a general framework for searching large distributed repositories. Examples of such repositories include sites with music/video content, distributed digital libraries, distributed caching systems, etc. The framework is based on the concept of neighborhood; each client keeps a list of the most beneficial sites according to past experience, which are visited first when the client searches for some particular content. Exploration methods continuously update the neighborhoods in order to follow changes in access patterns. Depending on the application, several variations of search and exploration processes are proposed. Experimental evaluation demonstrates the benefits of the framework in different scenarios.published_or_final_versio

Viral gene therapy for paediatric neurological diseases: progress to clinical reality

In the era of genomic medicine, diagnoses of rare paediatric neurological diseases are increasing. Many are untreatable and life-limiting, leading to an exceptional increase in gene therapy development. It is estimated that 20 gene therapy products will have received approval from the US Food and Drug Administration by 2025. With viral gene therapy considered a potential single-dose cure for patients with spinal muscular atrophy type 1 as one example, and contemporaneously tragically resulting in the deaths of three male children with X-linked myotubular myopathy receiving high-dose gene therapy in 2020, what is the current state of gene therapy? What is behind the decades of hype around viral gene therapy and is it high impact, but high risk? In this review, we outline principles of viral gene therapy development and summarize the most recent clinical evidence for the therapeutic effect of gene therapy in paediatric neurological diseases. We discuss adeno-associated virus and lentiviral vectors, antisense oligonucleotides, emerging genetic editing approaches, and current limitations that the field still faces

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BackgroundExisting evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.Patients and methodsChemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.ResultsNinety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).ConclusionsWhile elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes