Machine Learning Uncovers the Universe's Hidden Gems: A Comprehensive Catalogue of CIV Absorption Lines in SDSS DR12

We assemble the largest CIV absorption line catalogue to date, leveraging machine learning, specifically Gaussian processes, to remove the need for visual inspection for detecting CIV absorbers. The catalogue contains probabilities classifying the reliability of the absorption system within a quasar spectrum. Our training set was a sub-sample of DR7 spectra that had no detectable CIV absorption in a large visually inspected catalogue. We used Bayesian model selection to decide between our continuum model and our absorption-line models. Using a random hold-out sample of 1301 spectra from all of the 26,030 investigated spectra in DR7 CIV catalogue, we validated our pipeline and obtained an 87% classification performance score. We found good purity and completeness values, both ~80%, when a probability of ~95% is used as the threshold. Our pipeline obtained similar CIV redshifts and rest equivalent widths to our training set. Applying our algorithm to 185,425 selected quasar spectra from SDSS DR12, we produce a catalogue of 113,775 CIV doublets with at least 95% confidence. Our catalogue provides maximum a posteriori values and credible intervals for CIV redshift, column density, and Doppler velocity dispersion. We detect CIV absorption systems with a redshift range of 1.37 $\!-\!$ 5.1, including 33 systems with a redshift larger than 5 and 549 absorbers systems with a rest equivalent width greater than 2 A at more than 95% confidence. Our catalogue can be used to investigate the physical properties of the circumgalactic and intergalactic media.Comment: 18 pages, 25 figures, 3 table

Compliance costs and disclosure requirement mandates: Some evidence

© 2015 Elsevier Ltd. This note contributes to the discussion on the compliance costs of disclosure requirements for publicly traded companies. Prior research tends to focus on audit cost increases when disclosure requirements are stricter. We add some evidence from the point of views of shareholders. Particularly, we contrast stock market reaction to the 2002 Sarbanes-Oxley (SOX) Act which significantly enhanced public company disclosure requirements, with the 2012 Jumpstart Our Business Startups (JOBS) Act which alleviated disclosure requirements for small firms. Contrary to popular belief that more disclosure rules impose regulatory burdens on firms and are costly to implement, we find that the stock market reacted positively toward rules that require more disclosure; whereas it reacted negatively toward rules that require less disclosure, even though those disclosure rules were initially designed to reduce the costs of compliance

An amine-reactive tetraphenylethylene derivative for protein detection in SDS-PAGE

A new aggregation-induced emission (AIE) compound 1,2-bis[4-(isothiocyanatomethyl)phenyl]-1,2-diphenylethene (2) was synthesized for use in SDS-PAGE. The molecule is practically nonemissive in solution but becomes highly emissive after reacting with the amine groups of the proteins by either the prestaining or poststaining method. The sensitivity of 2 achieved in the prestaining method is the same as that of Coomassie brilliant blue (CBB), while that observed in the poststaining method is higher than that of CBB. Excellent linear responses with the amount of protein were obtained in both cases. The detection of a mixture of proteins with different molecular weights was successfully achieved

The biological function of type I receptors of bone morphogenetic protein in bone

Bone morphogenetic proteins (BMPs) have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors (BMPRI and BMPRII). In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 (ALK2, also called type IA activin receptor), activin-like kinase 3 (ALK3, also called BMPRIA), and activin-like kinase 6 (ALK6, also called BMPRIB). The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future

The economic burden of influenza-associated outpatient visits and hospitalizations in China: a retrospective survey.

BACKGROUND: The seasonal influenza vaccine coverage rate in China is only 1.9 %. There is no information available on the economic burden of influenza-associated outpatient visits and hospitalizations at the national level, even though this kind of information is important for informing national-level immunization policy decision-making. METHODS: A retrospective telephone survey was conducted in 2013/14 to estimate the direct and indirect costs of seasonal influenza-associated outpatient visits and hospitalizations from a societal perspective. Study participants were laboratory-confirmed cases registered in the National Influenza-like Illness Surveillance Network and Severe Acute Respiratory Infections Sentinel Surveillance Network in China in 2013. Patient-reported costs from the survey were validated by a review of hospital accounts for a small sample of the inpatients. RESULTS: The study enrolled 529 outpatients (median age: eight years; interquartile range [IQR]: five to 20 years) and 254 inpatients (median age: four years; IQR: two to seven years). Among the outpatients, 22.1 % (117/529) had underlying diseases and among the inpatients, 52.8 % (134/254) had underlying diseases. The average total costs related to influenza-associated outpatient visits and inpatient visits were US$155 (standard deviation, SD US$ 122) and US$1,511 (SD US$ 1,465), respectively. Direct medical costs accounted for 45 and 69 % of the total costs related to influenza-associated outpatient and inpatient visits, respectively. For influenza outpatients, the mean cost per episode in children aged below five years (US$196) was higher than that in other age groups (US$ 129-153). For influenza inpatients, the mean cost per episode in adults aged over 60 years (US$2,735) was much higher than that in those aged below 60 years (US$ 1,417-1,621). Patients with underlying medical conditions had higher costs per episode than patients without underlying medical conditions (outpatients: US$186 vs. US$ 146; inpatients: US$1,800 vs. US$ 1,189). In the baseline analysis, inpatients reported costs were 18 % higher than those found in the accounts review (n = 38). CONCLUSION: The economic burden of influenza-associated outpatient and inpatient visits in China is substantial, particularly for young children, the elderly, and patients with underlying medical conditions. More widespread influenza vaccination would likely alleviate the economic burden of patients. The actual impact and cost-effectiveness analysis of the influenza immunization program in China merits further investigation

Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene

The myelin basic protein (MBP) gene encodes two families of proteins, the classic MBP constituents of myelin and the golli-MBPs, the function of which is less well understood. In this study, targeted ablation of the golli-MBPs, but not the classic MBPs, resulted in a distinct phenotype unlike that of knock-outs (KOs) of the classic MBPs or other myelin proteins. Although the golli KO animals did not display an overt dysmyelinating phenotype, they did exhibit delayed and/or hypomyelination in selected areas of the brain, such as the visual cortex and the optic nerve, as determined by Northern and Western blots and immunohistochemical analysis with myelin protein markers. Hypomyelination in some areas, such as the visual cortex, persisted into adulthood. Ultrastructural analysis of the KOs confirmed both the delay and hypomyelination and revealed abnormalities in myelin structure and in some oligodendrocytes. Abnormal visual-evoked potentials indicated that the hypomyelination in the visual cortex had functional consequences in the golli KO brain. Evidence that the abnormal myelination in these animals was a consequence of intrinsic problems with the oligodendrocyte was indicated by an impaired ability of oligodendrocytes to form myelin sheets in culture and by the presence of abnormal Ca^(2+) transients in purified cortical oligodendrocytes studied in vitro. The Ca^(2+) results reported in this study complement previous results implicating golli proteins in modulating intracellular signaling in T-cells. Together, all these findings suggest a role for golli proteins in oligodendrocyte differentiation, migration, and/or myelin elaboration in the brain

Feasibility of using quadriceps-strengthening exercise to improve pain and sleep in a severely demented elder with osteoarthritis – a case report

BACKGROUND: Osteoarthritis (OA) of the knee, which is prevalent among older adults in nursing homes, causes significant pain and suffering, including disturbance of nocturnal sleep. One nonpharmacologic treatment option is quadriceps-strengthening exercise, however, the feasibility of such a treatment for reducing pain from OA in severely demented elders has not been studied. This report describes our test of the feasibility of such an exercise program, together with its effects on pain and sleep, in a severely demented nursing home resident. CASE PRESENTATION: The subject was an elderly man with severe cognitive impairment (Mini-Mental Status Exam score 4) and knee OA (Kellgren-Lawrence radiographic grade 4). He was enrolled in a 5-week, 10-session standardized progressive-resistance training program to strengthen the quadriceps, and completed all sessions. Pain was assessed with the Western Ontario and MacMaster OA Index (WOMAC) pain subscale, and sleep was assessed by actigraphy. The patient was able to perform the exercises, with a revision to the protocol. However, the WOMAC OA pain subscale proved inadequate for measuring pain in a patient with low cognitive functioning, and therefore the effects on pain were inconclusive. Although his sleep improved after the intervention, the influence of his medications and the amount of daytime sleep on his nighttime sleep need to be considered. CONCLUSIONS: A quadriceps-strengthening exercise program for treating OA of the knee is feasible in severely demented elders, although a better outcome measure is needed for pain

Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein.

Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced Th1-type cytokine production, proliferation, and resistance to regulatory T cell (Treg)-mediated suppression. MEDI6383 enhanced the cytolytic activity of tumor-reactive T cells and reduced tumor growth in the context of an alloreactive human T cell:tumor cell admix model in immunocompromised mice. Consistent with the role of OX40 costimulation in the expansion of memory T cells, MEDI6383 administered to healthy nonhuman primates elicited peripheral blood CD4 and CD8 central and effector memory T-cell proliferation as well as B-cell proliferation. Together, these results suggest that OX40 agonism has the potential to enhance antitumor immunity in human malignancies

Linking the functions of unrelated proteins using a novel directed evolution domain insertion method

We have successfully developed a new directed evolution method for generating integral protein fusions comprising of one domain inserted within another. Creating two connections between the insert and accepting parent domain can result in the inter-dependence of the separate protein activities, thus providing a general strategy for constructing molecular switches. Using an engineered transposon termed MuDel, contiguous trinucleotide sequences were removed at random positions from the bla gene encoding TEM-1 β-lactamase. The deleted trinucleotide sequence was then replaced by a DNA cassette encoding cytochrome b562 with differing linking sequences at each terminus and sampling all three reading frames. The result was a variety of chimeric genes encoding novel integral fusion proteins that retained TEM-1 activity. While most of the tolerated insertions were observed in loops, several also occurred close to the termini of α-helices and β-strands. Several variants conferred a switching phenotype on Escherichia coli, with bacterial tolerance to ampicillin being dependent on the presence of haem in the growth medium. The magnitude of the switching phenotype ranged from 4- to 128-fold depending on the insertion position within TEM-1 and the linker sequences that join the two domains

A global assessment of the impact of school closure in reducing COVID-19 spread.

Prolonged school closure has been adopted worldwide to control COVID-19. Indeed, UN Educational, Scientific and Cultural Organization figures show that two-thirds of an academic year was lost on average worldwide due to COVID-19 school closures. Such pre-emptive implementation was predicated on the premise that school children are a core group for COVID-19 transmission. Using surveillance data from the Chinese cities of Shenzhen and Anqing together, we inferred that compared with the elderly aged 60 and over, children aged 18 and under and adults aged 19-59 were 75% and 32% less susceptible to infection, respectively. Using transmission models parametrized with synthetic contact matrices for 177 jurisdictions around the world, we showed that the lower susceptibility of school children substantially limited the effectiveness of school closure in reducing COVID-19 transmissibility. Our results, together with recent findings that clinical severity of COVID-19 in children is lower, suggest that school closure may not be ideal as a sustained, primary intervention for controlling COVID-19. This article is part of the theme issue 'Data science approach to infectious disease surveillance'