Localized Centering: Reducing Hubness in Large-Sample Data

Hubness has been recently identified as a problematic phenomenon occurring in high-dimensional space. In this paper, we address a different type of hubness that occurs when the number of samples is large. We investigate the difference between the hubness in high-dimensional data and the one in large-sample data. One finding is that centering, which is known to reduce the former, does not work for the latter. We then propose a new hub-reduction method, called localized centering. It is an extension of centering, yet works effectively for both types of hubness. Using real-world datasets consisting of a large number of documents, we demonstrate that the proposed method improves the accuracy of k-nearest neighbor classification

A rapid screening with direct sequencing from blood samples for the diagnosis of Leigh syndrome

Large numbers of genes are responsible for Leigh syndrome (LS), making genetic confirmation of LS difficult. We screened our patients with LS using a limited set of 21 primers encompassing the frequently reported gene for the respiratory chain complexes I (ND1–ND6, and ND4L), IV(SURF1), and V(ATP6) and the pyruvate dehydrogenase E1α-subunit. Of 18 LS patients, we identified mutations in 11 patients, including 7 in mDNA (two with ATP6), 4 in nuclear (three with SURF1). Overall, we identified mutations in 61% of LS patients (11/18 individuals) in this cohort. Sanger sequencing with our limited set of primers allowed us a rapid genetic confirmation of more than half of the LS patients and it appears to be efficient as a primary genetic screening in this cohort

AJICAP Second Generation: Improved Chemical Site-Specific Conjugation Technology for Antibody-Drug Conjugate Production

The site-directed chemical conjugation of antibodies remains an area of great interest and active efforts within the antibody-drug conjugate (ADC) community. We previously reported a unique site modification using a class of immunoglobulin-G (IgG) Fc-affinity reagents to establish a versatile, streamlined, and site-selective conjugation of native antibodies to enhance the therapeutic index of the resultant ADCs. This methodology, termed “AJICAP,” successfully modified Lys248 of native antibodies to produce site-specific ADC with a wider therapeutic index than the Food and Drug Administration-approved ADC, Kadcyla. However, the long reaction sequences, including the reduction-oxidation (redox) treatment, increased. In this manuscript, we aimed to present an updated Fc-affinity-mediated site-specific conjugation technology named “AJICAP second generation” without redox treatment utilizing a "one-pot” antibody modification reaction. The stability of Fc affinity reagents was improved owing to structural optimization, enabling the production of various ADCs without aggregation. In addition to Lys248 conjugation, Lys288 conjugated ADCs with homogenous drug-to-antibody ratio of 2 were produced using this technology after a proper modification of the spacer linkage of Fc-affinity peptide reagents. These two conjugation technologies were used to produce over 20 ADCs from several combinations of antibodies and drug linkers. The in vivo profile of Lys248 and Lys288 conjugated ADCs was also compared. Furthermore, non-traditional ADC applications, such as antibody-protein conjugates and antibody-oligonucleotide conjugates, were performed. These results strongly indicate that this Fc affinity conjugation approach is a promising strategy for manufacturing site-specific antibody conjugates

Emergence of Home Blood Pressure-Guided Management of Hypertension Based on Global Evidence

status: publishe

The Accuracy in Measurement of Blood Pressure (AIM-BP) collaborative: Background and rationale

status: publishe