Persistent Decadal-Scale Rainfall Variability in the Tropical South Pacific Convergence Zone Through the Past Six Centuries

Modern Pacific decadal variability (PDV) has global impacts; hence records of PDV from the pre-instrumental period are needed to better inform models that are used to project future climate variability. We focus here on reconstructing rainfall in the western tropical Pacific (Solomon Islands; similar to 9.5 degrees S, similar to 160 degrees E), a region directly influenced by PDV, using cave deposits (stalagmite). A relationship is developed between delta O-18 variations in the stalagmite and local rainfall amount to produce a 600 yr record of rainfall variability from the South Pacific Convergence Zone (SPCZ). We present evidence for large (similar to 1.5 m), abrupt, and periodic changes in total annual rainfall amount on decadal to multidecadal timescales since 1423 +/- 5 CE (Common Era) in the Solomon Islands. The timing of the decadal changes in rainfall inferred from the 20th-century portion of the stalagmite delta O-18 record coincides with previously identified decadal shifts in PDV-related Pacific ocean-atmosphere behavior (Clement et al., 2011; Deser et al., 2004). The Solomons record of PDV is not associated with variations in external forcings, but rather results from internal climate variability. The 600 yr Solomon Islands stalagmite delta O-18 record indicates that decadal oscillations in rainfall are a persistent characteristic of SPCZ-related climate variability.Taiwan ROC NSCNTU 101-2116-M-002-009, 102-2116-M-002-016, 101R7625Geological Science

Growth and properties of ferromagnetic In(1-x)Mn(x)Sb alloys

We discuss a new narrow-gap ferromagnetic (FM) semiconductor alloy, In(1-x)Mn(x)Sb, and its growth by low-temperature molecular-beam epitaxy. The magnetic properties were investigated by direct magnetization measurements, electrical transport, magnetic circular dichroism, and the magneto-optical Kerr effect. These data clearly indicate that In(1-x)Mn(x)Sb possesses all the attributes of a system with carrier-mediated FM interactions, including well-defined hysteresis loops, a cusp in the temperature dependence of the resistivity, strong negative magnetoresistance, and a large anomalous Hall effect. The Curie temperatures in samples investigated thus far range up to 8.5 K, which are consistent with a mean-field-theory simulation of the carrier-induced ferromagnetism based on the 8-band effective band-orbital method.Comment: Invited talk at 11th International Conference on Narrow Gap Semiconductors, Buffalo, New York, U.S.A., June 16 - 20, 200

Prediction of Anisotropic Single-Dirac-Cones in Bi1−x{}_{1-x}Sbx{}_{x} Thin Films

The electronic band structures of Bi${}_{1-x}$Sb${}_{x}$ thin films can be varied as a function of temperature, pressure, stoichiometry, film thickness and growth orientation. We here show how different anisotropic single-Dirac-cones can be constructed in a Bi${}_{1-x}$Sb${}_{x}$ thin film for different applications or research purposes. For predicting anisotropic single-Dirac-cones, we have developed an iterative-two-dimensional-two-band model to get a consistent inverse-effective-mass-tensor and band-gap, which can be used in a general two-dimensional system that has a non-parabolic dispersion relation as in a Bi${}_{1-x}$Sb${}_{x}$ thin film system

Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study

IMPECCABLE: Integrated Modeling PipelinE for COVID Cure by Assessing Better LEads

The drug discovery process currently employed in the pharmaceutical industry typically requires about 10 years and $2–3 billion to deliver one new drug. This is both too expensive and too slow, especially in emergencies like the COVID-19 pandemic. In silico methodologies need to be improved both to select better lead compounds, so as to improve the efficiency of later stages in the drug discovery protocol, and to identify those lead compounds more quickly. No known methodological approach can deliver this combination of higher quality and speed. Here, we describe an Integrated Modeling PipEline for COVID Cure by Assessing Better LEads (IMPECCABLE) that employs multiple methodological innovations to overcome this fundamental limitation. We also describe the computational framework that we have developed to support these innovations at scale, and characterize the performance of this framework in terms of throughput, peak performance, and scientific results. We show that individual workflow components deliver 100 × to 1000 × improvement over traditional methods, and that the integration of methods, supported by scalable infrastructure, speeds up drug discovery by orders of magnitudes. IMPECCABLE has screened ∼ 1011 ligands and has been used to discover a promising drug candidate. These capabilities have been used by the US DOE National Virtual Biotechnology Laboratory and the EU Centre of Excellence in Computational Biomedicine

Coordinated hydrological regimes in the Indo-Pacific region during the past two millennia

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 25 (2010): PA1102, doi:10.1029/2009PA001871.Instrumental data suggest that major shifts in tropical Pacific atmospheric dynamics and hydrology have occurred within the past century, potentially in response to anthropogenic warming. To better understand these trends, we use the hydrogen isotopic ratios of terrestrial higher plant leaf waxes (δDwax) in marine sediments from southwest Sulawesi, Indonesia, to compile a detailed reconstruction of central Indo-Pacific Warm Pool (IPWP) hydrologic variability spanning most of the last two millennia. Our paleodata are highly correlated with a monsoon reconstruction from Southeast Asia, indicating that intervals of strong East Asian summer monsoon (EASM) activity are associated with a weaker Indonesian monsoon (IM). Furthermore, the centennial-scale oscillations in our data follow known changes in Northern Hemisphere climate (e.g., the Little Ice Age and Medieval Warm Period) implying a dynamic link between Northern Hemisphere temperatures and IPWP hydrology. The inverse relationship between the EASM and IM suggests that migrations of the Intertropical Convergence Zone and associated changes in monsoon strength caused synoptic hydrologic shifts in the IPWP throughout most of the past two millennia.This research was supported by the U.S. NSF, the Ocean and Climate Change Institute at WHOI, and a National Defense Science and Engineering Graduate Fellowship to J. Tierney

Prediction of pathological stage in patients with prostate cancer: a neuro-fuzzy model

The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR = 0.197, AUC = 0.582)

Ordered Patterns of Cell Shape and Orientational Correlation during Spontaneous Cell Migration

BACKGROUND: In the absence of stimuli, most motile eukaryotic cells move by spontaneously coordinating cell deformation with cell movement in the absence of stimuli. Yet little is known about how cells change their own shape and how cells coordinate the deformation and movement. Here, we investigated the mechanism of spontaneous cell migration by using computational analyses. METHODOLOGY: We observed spontaneously migrating Dictyostelium cells in both a vegetative state (round cell shape and slow motion) and starved one (elongated cell shape and fast motion). We then extracted regular patterns of morphological dynamics and the pattern-dependent systematic coordination with filamentous actin (F-actin) and cell movement by statistical dynamic analyses. CONCLUSIONS/SIGNIFICANCE: We found that Dictyostelium cells in both vegetative and starved states commonly organize their own shape into three ordered patterns, elongation, rotation, and oscillation, in the absence of external stimuli. Further, cells inactivated for PI3-kinase (PI3K) and/or PTEN did not show ordered patterns due to the lack of spatial control in pseudopodial formation in both the vegetative and starved states. We also found that spontaneous polarization was achieved in starved cells by asymmetric localization of PTEN and F-actin. This breaking of the symmetry of protein localization maintained the leading edge and considerably enhanced the persistence of directed migration, and overall random exploration was ensured by switching among the different ordered patterns. Our findings suggest that Dictyostelium cells spontaneously create the ordered patterns of cell shape mediated by PI3K/PTEN/F-actin and control the direction of cell movement by coordination with these patterns even in the absence of external stimuli

An energy transduction mechanism used in bacterial flagellar type III protein export

Flagellar proteins of bacteria are exported by a specific export apparatus. FliI ATPase forms a complex with FliH and FliJ and escorts export substrates from the cytoplasm to the export gate complex, which is made up of six membrane proteins. The export gate complex utilizes proton motive force across the cytoplasmic membrane for protein translocation, but the mechanism remains unknown. Here we show that the export gate complex by itself is a proton–protein antiporter that uses the two components of proton motive force, Δψ and ΔpH, for different steps of the protein export process. However, in the presence of FliH, FliI and FliJ, a specific binding of FliJ with an export gate membrane protein, FlhA, is brought about by the FliH–FliI complex, which turns the export gate into a highly efficient, Δψ-driven protein export apparatus