HOLOCENE GEOLOGY AND MULTI-PROXY PALEOENVIRONMENTAL RECONSTRUCTION OF THE SUNDA SHELF OFF THE EAST COAST OF PENINSULAR MALAYSIA

In May (2016), six 1.25 to 2.2 m long gravity cores were collected at water depths ranging from 68 m to 77 m along a transect crossing the incised Chao-Phraya paleo-river valley between Peninsular Malaysia and southern Vietnam, on the Sunda Shelf (southern South China Sea). The objective of this research is to use multiple proxies to make paleoenvironmental reconstructions of the cored sediments’ depositional environments. The six cores provided 130 samples selected for analysis of bulk sediment magnetic susceptibility (BMS), 66 for elemental analysis by means of x-ray fluorescence spectrometry (XRF), 52 for analysis of foraminiferal assemblages, and 10 for AMS radiocarbon dating. BMS data show that sediments near the base of the cores typically display higher magnetic susceptibility than sediments closer to the surface, although results vary between and within cores. Other studies show that variations in BMS magnitudes are a result of changes in terrestrial sediment flux during deposition. XRF data will help constrain origins on the cored sediment (e.g. terrestrial or marine). For example, aluminum is typically concentrated in aluminosilicates and can be used as a proxy for variations in grain size. Concentrations of calcium, when inversely correlated with aluminum, are commonly interpreted to derive from a different source (e.g., marine). Foraminiferal assemblages will be used as a proxy for environmental change in conjunction with BMS and XRF.Research and Creative Achievement Wee

Holocene Paleoenvironmental Reconstruction of Depositional Environments on the Sunda Shelf, Southwest South China Sea, using a Multidisciplinary Approach

The last glacial maximum, ca. 21,000 years ago, caused a fall in eustatic sea level of ca. 120 m below present. The low-gradient, shallow Sunda Shelf, Southeast Asia was subaerially exposed during this sea-level lowstand and experienced rising sea level thereafter. Sea level rose to a +1.3--5 m highstand ca. 6,500 cal yr BP, and then fell to modern sea level. The objective of this research is to characterize environmental change on the Sunda Shelf in response to the post-glacial rising eustatic sea level. To address this objective, six gravity cores were collected along a transect crossing the paleo-Chao Phraya incised river valley complex between peninsular Malaysia and southern Vietnam. Thirteen AMS radiocarbon samples, 130 bulk sediment magnetic susceptibility samples (BMS), 66 X-ray fluorescence spectrometry (XRF) samples, and 54 samples for the analysis of foraminiferal assemblages were used to characterize change in the depositional environments of the cored sediments. BMS, XRF, and foraminiferal analysis distinguish two main units. Unit 1 is found in the lower part of the cores and typically contains more terrestrial material than sediments further up-core as shown by higher BMS values, higher % Ti, % Al, % Fe, and lower indicators of marine influence, for example, lower % Ca, % planktonic foraminifera, and percentages of deeper water benthic foraminifera such as Heterolepa dutemplei. Unit 2 is characterized by a significant increase in % Ca, % Heterolepa dutemplei and % planktonic foraminifera ca. 6,500 cal yr BP. Unit 1 is consistent with shallower water depths and is part of a transgressive systems tract (TST, ca. 1 m thick) that terminates ca. 6,500 cal yr BP. Unit 2 represents the overlying highstand systems tract (HST, ca. 1 m thick) and is characterized by an increase in % planktonics, % Ca, and shifts in benthic foraminiferal assemblages, indicating deeper water conditions than the sediments below. This shift from a TST to a HST ca. 6500 cal yr BP is consistent with the Sunda Shelf sea-level record

Deletion of the Nucleotide Excision Repair Gene Ercc1 Reduces Immunoglobulin Class Switching and Alters Mutations Near Switch Recombination Junctions

The structure-specific endonuclease ERCC1-XPF is an essential component of the nucleotide excision DNA repair pathway. ERCC1-XPF nicks double-stranded DNA immediately adjacent to 3′ single-strand regions. Substrates include DNA bubbles and flaps. Furthermore, ERCC1 interacts with Msh2, a mismatch repair (MMR) protein involved in class switch recombination (CSR). Therefore, ERCC1-XPF has abilities that might be useful for antibody CSR. We tested whether ERCC1 is involved in CSR and found that Ercc1−/− splenic B cells show moderately reduced CSR in vitro, demonstrating that ERCC1-XPF participates in, but is not required for, CSR. To investigate the role of ERCC1 in CSR, the nucleotide sequences of switch (S) regions were determined. The mutation frequency in germline Sμ segments and recombined Sμ-Sγ3 segments cloned from Ercc1−/− splenic B cells induced to switch in culture was identical to that of wild-type (WT) littermates. However, Ercc1−/− cells show increased targeting of the mutations to G:C bp in RGYW/WRCY hotspots and mutations occur at sites more distant from the S–S junctions compared with WT mice. The results indicate that ERCC1 is not epistatic with MMR and suggest that ERCC1 might be involved in processing or repair of DNA lesions in S regions during CSR

Deep ACS Imaging in the Globular Cluster NGC 6397: The Cluster Color Magnitude Diagram and Luminosity Function

We present the CMD from deep HST imaging in the globular cluster NGC 6397. The ACS was used for 126 orbits to image a single field in two colors (F814W, F606W) 5 arcmin SE of the cluster center. The field observed overlaps that of archival WFPC2 data from 1994 and 1997 which were used to proper motion (PM) clean the data. Applying the PM corrections produces a remarkably clean CMD which reveals a number of features never seen before in a globular cluster CMD. In our field, the main sequence stars appeared to terminate close to the location in the CMD of the hydrogen-burning limit predicted by two independent sets of stellar evolution models. The faintest observed main sequence stars are about a magnitude fainter than the least luminous metal-poor field halo stars known, suggesting that the lowest luminosity halo stars still await discovery. At the bright end the data extend beyond the main sequence turnoff to well up the giant branch. A populous white dwarf cooling sequence is also seen in the cluster CMD. The most dramatic features of the cooling sequence are its turn to the blue at faint magnitudes as well as an apparent truncation near F814W = 28. The cluster luminosity and mass functions were derived, stretching from the turn off down to the hydrogen-burning limit. It was well modeled with either a very flat power-law or a lognormal function. In order to interpret these fits more fully we compared them with similar functions in the cluster core and with a full N-body model of NGC 6397 finding satisfactory agreement between the model predictions and the data. This exercise demonstrates the important role and the effect that dynamics has played in altering the cluster IMF.Comment: 43 pages including 4 tables and 12 diagrams. Figures 2 and 3 have been bitmapped. Accepted for publication in the Astronomical Journa

A proteogenomic signature of age-related macular degeneration in blood

© 2022. The Author(s). Funding Information: The authors acknowledge the contribution of the Icelandic Heart Association (IHA) staff to the AGES-RS, as well as the involvement of all study participants. We thank the IAMDGC consortium for supplying us with their GWAS summary statistics data. National Institute on Aging (NIA) contracts N01-AG-12100 and HHSN271201200022C for V.G. financed the AGES study; retinal image collection and AMD readings were funded by the NIH Intramural Research Program (ZIAEY000401). V.G. received a funding from the NIA (1R01AG065596), and IHA received a support from Althingi (the Icelandic Parliament). The Icelandic Research Fund (IRF) funded V.E. and Va.G. with grants 195761-051, 184845-053, and 206692-051, while Va.G. received a postdoctoral research grant from the University of Iceland Research Fund Funding Information: The study was supported by the Novartis Institute for Biomedical Research. M.T., N.F., S.P., X.L., R.E., Y.Z., S.J., C.L.H., S.M.L., J.L., C.L.G., A.A.N., B.L., R.P., Z.L., L.L.J., T.E.W., Q.Z., Q.H., and J.R.L. are employees and stockholders of Novartis. All other authors have no conflict of interests to declare. Publisher Copyright: © 2022, The Author(s).Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.Peer reviewe

Holocene Paleoenvironmental Reconstruction of Depositional Environments on the Sunda Shelf , Southwest South China Sea , using a Multidisciplinary Approach

The last glacial maximum , ca. 21 , 000 years ago , caused a fall in eustatic sea level of ca. 120 m below present. The low-gradient , shallow Sunda Shelf , Southeast Asia was subaerially exposed during this sea-level lowstand and experienced rising sea level thereafter. Sea level rose to a +1.3--5 m highstand ca. 6 , 500 cal yr BP , and then fell to modern sea level. The objective of this research is to characterize environmental change on the Sunda Shelf in response to the post-glacial rising eustatic sea level. To address this objective , six gravity cores were collected along a transect crossing the paleo-Chao Phraya incised river valley complex between peninsular Malaysia and southern Vietnam. Thirteen AMS radiocarbon samples , 130 bulk sediment magnetic susceptibility samples (BMS) , 66 X-ray fluorescence spectrometry (XRF) samples , and 54 samples for the analysis of foraminiferal assemblages were used to characterize change in the depositional environments of the cored sediments. BMS , XRF , and foraminiferal analysis distinguish two main units. Unit 1 is found in the lower part of the cores and typically contains more terrestrial material than sediments further up-core as shown by higher BMS values , higher % Ti , % Al , % Fe , and lower indicators of marine influence , for example , lower % Ca , % planktonic foraminifera , and percentages of deeper water benthic foraminifera such as Heterolepa dutemplei. Unit 2 is characterized by a significant increase in % Ca , % Heterolepa dutemplei and % planktonic foraminifera ca. 6 , 500 cal yr BP. Unit 1 is consistent with shallower water depths and is part of a transgressive systems tract (TST , ca. 1 m thick) that terminates ca. 6 , 500 cal yr BP. Unit 2 represents the overlying highstand systems tract (HST , ca. 1 m thick) and is characterized by an increase in % planktonics , % Ca , and shifts in benthic foraminiferal assemblages , indicating deeper water conditions than the sediments below. This shift from a TST to a HST ca. 6500 cal yr BP is consistent with the Sunda Shelf sea-level record

Holocene Paleoenvironmental Reconstruction of Depositional Environments on the Sunda Shelf, Southwest South China Sea, using a Multidisciplinary Approach

The last glacial maximum, ca. 21,000 years ago, caused a fall in eustatic sea level of ca. 120 m below present. The low-gradient, shallow Sunda Shelf, Southeast Asia was subaerially exposed during this sea-level lowstand and experienced rising sea level thereafter. Sea level rose to a +1.3--5 m highstand ca. 6,500 cal yr BP, and then fell to modern sea level. The objective of this research is to characterize environmental change on the Sunda Shelf in response to the post-glacial rising eustatic sea level. To address this objective, six gravity cores were collected along a transect crossing the paleo-Chao Phraya incised river valley complex between peninsular Malaysia and southern Vietnam. Thirteen AMS radiocarbon samples, 130 bulk sediment magnetic susceptibility samples (BMS), 66 X-ray fluorescence spectrometry (XRF) samples, and 54 samples for the analysis of foraminiferal assemblages were used to characterize change in the depositional environments of the cored sediments. BMS, XRF, and foraminiferal analysis distinguish two main units. Unit 1 is found in the lower part of the cores and typically contains more terrestrial material than sediments further up-core as shown by higher BMS values, higher % Ti, % Al, % Fe, and lower indicators of marine influence, for example, lower % Ca, % planktonic foraminifera, and percentages of deeper water benthic foraminifera such as Heterolepa dutemplei. Unit 2 is characterized by a significant increase in % Ca, % Heterolepa dutemplei and % planktonic foraminifera ca. 6,500 cal yr BP. Unit 1 is consistent with shallower water depths and is part of a transgressive systems tract (TST, ca. 1 m thick) that terminates ca. 6,500 cal yr BP. Unit 2 represents the overlying highstand systems tract (HST, ca. 1 m thick) and is characterized by an increase in % planktonics, % Ca, and shifts in benthic foraminiferal assemblages, indicating deeper water conditions than the sediments below. This shift from a TST to a HST ca. 6500 cal yr BP is consistent with the Sunda Shelf sea-level record

HOLOCENE GEOLOGY AND MULTI-PROXY PALEOENVIRONMENTAL RECONSTRUCTION OF THE SUNDA SHELF OFF THE EAST COAST OF PENINSULAR MALAYSIA

In May (2016) , six 1.25 to 2.2 m long gravity cores were collected at water depths ranging from 68 m to 77 m along a transect crossing the incised Chao-Phraya paleo-river valley between Peninsular Malaysia and southern Vietnam , on the Sunda Shelf (southern South China Sea). The objective of this research is to use multiple proxies to make paleoenvironmental reconstructions of the cored sediments' depositional environments. The six cores provided 130 samples selected for analysis of bulk sediment magnetic susceptibility (BMS) , 66 for elemental analysis by means of x-ray fluorescence spectrometry (XRF) , 52 for analysis of foraminiferal assemblages , and 10 for AMS radiocarbon dating. BMS data show that sediments near the base of the cores typically display higher magnetic susceptibility than sediments closer to the surface , although results vary between and within cores. Other studies show that variations in BMS magnitudes are a result of changes in terrestrial sediment flux during deposition. XRF data will help constrain origins on the cored sediment (e.g. terrestrial or marine). For example , aluminum is typically concentrated in aluminosilicates and can be used as a proxy for variations in grain size. Concentrations of calcium , when inversely correlated with aluminum , are commonly interpreted to derive from a different source (e.g. , marine). Foraminiferal assemblages will be used as a proxy for environmental change in conjunction with BMS and XRF

Estimating disability incidence rates for long term care insurance

This paper uses data from the 1999 NLTCS and NHIS surveys to compute Long Term Care (LTC) prevalence rates. We develop several triggers, evaluate a test of cognitive ability, and compute prevalence rates for each trigger. We develop a model to compute LTC incidence rates based on the prevalence data. We find that incidence is a strictly increasing function of age and that there is a sharp increase in incidence rates starting at age ninety

Mechanism of nucleic acid sensing in retinal pigment epithelium (RPE): RIG-I mediates type I interferon response in human RPE

Age-related macular degeneration (AMD), a degenerative disease of the outer retina, is the leading cause of blindness among the elderly. A hallmark of geographic atrophy (GA), an advanced type of non-neovascular AMD (dry AMD), is photoreceptor and retinal pigment epithelium (RPE) cell death. Currently, there are no FDA-approved therapies for GA due to a lack of understanding of the disease-causing mechanisms. Increasing evidence suggests that chronic inflammation plays a predominant role in the pathogenesis of dry AMD. Dead or stressed cells release danger signals and inflammatory factors, which causes further damage to neighboring cells. It has been reported that type I interferon (IFN) response is activated in RPE cells in patients with AMD. However, how RPE cells sense stress to initiate IFN response and cause further damage to the retina are still unknown. Although it has been reported that RPE can respond to extracellularly added dsRNA, it is unknown whether and how RPE detect and sense internally generated or internalized nucleic acids. Here, we elucidated the molecular mechanism by which RPE cells sense intracellular nucleic acids. Our data demonstrate that RPE cells can respond to intracellular RNA and induce type I IFN responses via the RIG-I (DExD/H-box helicase 58, DDX58) RNA helicase. In contrast, we showed that RPE cells were unable to directly sense and respond to DNA through the cGAS-STING pathway. We demonstrated that this was due to the absence of the cyclic GMP-AMP synthase (cGAS) DNA sensor in these cells. The activation of IFN response via RIG-I induced expression of cell death effectors and cause barrier function loss in RPE cells. These data suggested that RPE-intrinsic pathways of nucleic acid sensing are biased toward RNA sensing