Matrix Estimation for Individual Fairness

In recent years, multiple notions of algorithmic fairness have arisen. One such notion is individual fairness (IF), which requires that individuals who are similar receive similar treatment. In parallel, matrix estimation (ME) has emerged as a natural paradigm for handling noisy data with missing values. In this work, we connect the two concepts. We show that pre-processing data using ME can improve an algorithm's IF without sacrificing performance. Specifically, we show that using a popular ME method known as singular value thresholding (SVT) to pre-process the data provides a strong IF guarantee under appropriate conditions. We then show that, under analogous conditions, SVT pre-processing also yields estimates that are consistent and approximately minimax optimal. As such, the ME pre-processing step does not, under the stated conditions, increase the prediction error of the base algorithm, i.e., does not impose a fairness-performance trade-off. We verify these results on synthetic and real data.Comment: 23 pages, 3 figures, ICML 202

How the perceived neighbourhood environment influences active living in older dwellers of an Asian ultra-dense metropolis

The way older adults perceive their neighbourhood environment may determine their levels of physical activity. We examined the associations of perceived neighbourhood environmental attributes with accelerometry-assessed and self-reported physical activity and sedentary time in Hong Kong Chinese older adults. In doing so, we estimated the inter-relationships among perceived environmental attributes, the mediating role of physical activity in the environment-sedentary time nexus and the moderating role of sex. We used data from the Active Lifestyle and the Environment in Chinese Seniors (ALECS) project collected on older adults (N = 909; ≥65 years) living in neighbourhoods varying in walkability and socio-economic status (71 % response rate). Self-reported physical activity and perceived neighbourhood attributes were assessed with validated questionnaires. Accelerometer-based physical activity and sedentary time were collected in 402 participants. Older adults who perceived their neighbourhood to be walkable, safe, aesthetically pleasing and equipped with public sitting facilities engaged in more physical activity and less sedentary time. Curvilinear relations of perceived residential density and activity-friendly urban design features indicated that extreme levels of density may not be optimal for older adults to adopt an active lifestyle because they do not provide sufficient space for sitting facilities and greenery and do not result in better perceptions of neighbourhood walkability when compared to areas with moderate-to-high levels of density. Creative solutions for the incorporation of greenery and public places for sitting in megacities are needed

Beneficial Effect of Young Oocytes for Rabbit Somatic Cell Nuclear Transfer

Abstract This study was designed to examine the effect of the age of rabbit oocytes on the developmental potential of cloned embryos. The metaphase II oocytes used for nuclear transfer (NT) were collected at 10, 12, 14, and 16h post-hCG injection (hpi). The total number of oocytes collected per donor (21.4-23.7) at 12 to 16 hpi was similar, but significantly higher than that collected at 10 hpi (16.2). Additionally, a significant improvement in blastocyst development was achieved with embryos generated by electrically mediated cell fusion (56.0%), compared to those from nuclear injection (13.1 %) (Experiment 1). Markedly higher blastocyst development (45.8-54.5%) was also achieved with oocytes collected at 10-12 hpi than from those collected 14-16 hpi (8.3-14.3%) (Experiment 2). In Experiment 3, the blastocyst rates of NT embryos derived from oocytes harvested 12 hpi (39.2-42.8 %) were significantly higher than from those collected at 16 hpi (6.8-8.4 %) (p<0.05), regardless of the donor cell age. Kinase activity assays showed variable changes of activity in rabbit oocytes over the period of 10-16 hpi; however, there was no correlation with preimplantational development (blastocyst rate vs. MPF, R=0.326; blastocyst rate vs. MAPK, R=0.131). Embryo transfer of NT embryos utilizing 12 hpi oocytes resulted in one full-term but stillborn, and one live cloned rabbit; thus, an efficiency of 1.7 % (n=117) (Experiment 4). These results demonstrated that NT utilizing relatively young rabbit oocytes, harvested at 10-12h after hCG injection, was beneficial for the development of NT embryos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78139/1/clo.2008.0042.pd

Follicular Oocytes Better Support Development in Rabbit Cloning Than Oviductal Oocytes

This study was conducted to determine the effect of rabbit oocytes collected from ovaries or oviducts on the developmental potential of nuclear transplant embryos. Donor nuclei were obtained from adult skin fibroblasts, cumulus cells, and embryonic blastomeres. Rabbit oocytes were flushed from the oviducts (oviductal oocytes) or aspirated from the ovaries (follicular oocytes) of superovulated does at 10, 11, or 12-h post-hCG injection. The majority of collected oocytes were still attached to the sites of ovulation on the ovaries. We found that follicular oocytes had a significantly higher rate of fusion with nuclear donor cells than oviductal oocytes. There was no difference in the cleavage rate between follicular and oviductal groups, but morula and blastocyst development was significantly higher in the follicular group than in the oviductal group. Two live clones were produced in follicular group using blastomere and cumulus nuclear donors, whereas one live clone was produced in the oviductal group using a cumulus nuclear donor. These results demonstrate that cloned rabbit embryos derived from follicular oocytes have better developmental competence than those derived from oviductal oocytes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90481/1/cell-2E2011-2E0030.pd

Neighbourhood environment, physical activity, quality of life and depressive symptoms in Hong Kong older adults: a protocol for an observational study

INTRODUCTION: The neighbourhood environment can assist the adoption and maintenance of an active lifestyle and affect the physical and mental well-being of older adults. The psychosocial and behavioural mechanisms through which the environment may affect physical and mental well-being are currently poorly understood. AIM: This observational study aims to examine associations between the physical and social neighbourhood environments, physical activity, quality of life and depressive symptoms in Chinese Hong Kong older adults. METHODS AND ANALYSES: An observational study of the associations of measures of the physical and social neighbourhood environment, and psychosocial factors, with physical activity, quality of life and depressive symptoms in 900 Hong Kong older adults aged 65+ years is being conducted in 2012-2016. The study involves two assessments taken 6 months apart. Neighbourhood walkability and access to destinations are objectively measured using Geographic Information Systems and environmental audits. Demographics, socioeconomic status, walking for different purposes, perceived neighbourhood and home environments, psychosocial factors, health status, social networks, depressive symptoms and quality of life are being assessed using validated interviewer-administered self-report measures and medical records. Physical functionality is being assessed using the Short Physical Performance Battery. Physical activity and sedentary behaviours are also being objectively measured in approximately 45% of participants using accelerometers over a week. Physical activity, sedentary behaviours, quality of life and depressive symptoms are being assessed twice (6 months apart) to examine seasonality effects on behaviours and their associations with quality of life and depressive symptoms. ETHICS AND DISSEMINATION: The study received ethical approval from the University of Hong Kong Human Research Ethics Committee for Non-Clinical Faculties (EA270211) and the Department of Health (Hong Kong SAR). Data are stored in a password-protected secure database for 10 years, accessible only to the named researchers. Findings will be submitted for publication in peer-reviewed journals

siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells.</p> <p>Methods</p> <p>siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied <it>in vivo </it>by injection of the siRNA-transfected breast cancer cells into nude mice.</p> <p>The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined <it>in vitro </it>by MTT assay, FACS and SA-β-galactosidase staining.</p> <p>Results</p> <p>The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. <it>In vivo</it>, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 μM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 μM doxorubicin killed twice as many cancer cells, showing a cumulative effect of the two treatments.</p> <p>Conclusion</p> <p>The study demonstrated the potential of telomerase inhibition as an effective treatment for breast cancer. When used in conjunction to doxorubicin, it could potentiate the cytotoxic effect of the drug to breast cancer cells.</p

Simulated Microgravity Compromises Mouse Oocyte Maturation by Disrupting Meiotic Spindle Organization and Inducing Cytoplasmic Blebbing

In the present study, we discovered that mouse oocyte maturation was inhibited by simulated microgravity via disturbing spindle organization. We cultured mouse oocytes under microgravity condition simulated by NASA's rotary cell culture system, examined the maturation rate and observed the spindle morphology (organization of cytoskeleton) during the mouse oocytes meiotic maturation. While the rate of germinal vesicle breakdown did not differ between 1 g gravity and simulated microgravity, rate of oocyte maturation decreased significantly in simulated microgravity. The rate of maturation was 8.94% in simulated microgravity and was 73.0% in 1 g gravity. The results show that the maturation of mouse oocytes in vitro was inhibited by the simulated microgravity. The spindle morphology observation shows that the microtubules and chromosomes can not form a complete spindle during oocyte meiotic maturation under simulated microgravity. And the disorder of γ-tubulin may partially result in disorganization of microtubules under simulated microgravity. These observations suggest that the meiotic spindle organization is gravity dependent. Although the spindle organization was disrupted by simulated microgravity, the function and organization of microfilaments were not pronouncedly affected by simulated microgravity. And we found that simulated microgravity induced oocytes cytoplasmic blebbing via an unknown mechanism. Transmission electron microscope detection showed that the components of the blebs were identified with the cytoplasm. Collectively, these results indicated that the simulated microgravity inhibits mouse oocyte maturation via disturbing spindle organization and inducing cytoplasmic blebbing

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654

Production of Transgenic Pigs Mediated by Pseudotyped Lentivirus and Sperm

Sperm-mediated gene transfer can be a very efficient method to produce transgenic pigs, however, the results from different laboratories had not been widely repeated. Genomic integration of transgene by injection of pseudotyped lentivirus to the perivitelline space has been proved to be a reliable route to generate transgenic animals. To test whether transgene in the lentivirus can be delivered by sperm, we studied incubation of pseudotyped lentiviruses and sperm before insemination. After incubation with pig spermatozoa, 62±3 lentiviral particles were detected per 100 sperm cells using quantitative real-time RT-PCR. The association of lentivirus with sperm was further confirmed by electron microscopy. The sperm incubated with lentiviral particles were artificially inseminated into pigs. Of the 59 piglets born from inseminated 5 sows, 6 piglets (10.17%) carried the transgene based on the PCR identification. Foreign gene and EGFP was successfully detected in ear tissue biopsies from two PCR-positive pigs, revealed via in situ hybridization and immunohistochemistry. Offspring of one PCR-positive boar with normal sows showed PCR-positive. Two PCR-positive founders and offsprings of PCR-positive boar were further identified by Southern-blot analysis, out of which the two founders and two offsprings were positive in Southern blotting, strongly indicating integration of foreign gene into genome. The results indicate that incubation of sperm with pseudotyped lentiviruses can incorporated with sperm-mediated gene transfer to produce transgenic pigs with improved efficiency