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"Miller, Kenneth G."
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طريقة وارن بافيت
يقدم الكتاب الطريقة الأمثل للتعامل في بورصات الأسهم وهي التي استطاع من خلالها وارن بافيت تحقيق أرباح قدرها 42 مليار دولار ويمكن تلخيص تلك الطريق في تحديد الشركات شديدة التميز ذات التاريخ الطويل في تحقيق الأرباح والتى تديرها إدارات قوية ومتميزة وانتظار تدهور أسعار أسهم تلك الشركات مع الهبوط الشديد في الأسواق وعندئذ يتم شرائها … ثم الانتظار لبضعة سنوات لحين ارتفاع البورصه وعندئذ يتم البيع وفي ذلك الحين تكون قيمة الأسهم تضاعفت عدة مرات.
BOOK
Phanerozoic Record of Global Sea-Level Change
We review Phanerozoic sea-level changes [543 million years ago (Ma) to the present] on various time scales and present a new sea-level record for the past 100 million years (My). Long-term sea level peaked at 100 ± 50 meters during the Cretaceous, implying that ocean-crust production rates were much lower than previously inferred. Sea level mirrors oxygen isotope variations, reflecting ice-volume change on the 10⁴- to 10⁶-year scale, but a link between oxygen isotope and sea level on the 10⁷-year scale must be due to temperature changes that we attribute to tectonically controlled carbon dioxide variations. Sea-level change has influenced phytoplankton evolution, ocean chemistry, and the loci of carbonate, organic carbon, and siliciclastic sediment burial. Over the past 100 My, sea-level changes reflect global climate evolution from a time of ephemeral Antarctic ice sheets (100 to 33 Ma), through a time of large ice sheets primarily in Antarctica (33 to 2.5 Ma), to a world with large Antarctic and large, variable Northern Hemisphere ice sheets (2.5 Ma to the present).
Journal Article
A Novel Molecular Solution for Ultraviolet Light Detection in Caenorhabditis elegans
For many organisms the ability to transduce light into cellular signals is crucial for survival. Light stimulates DNA repair and metabolism changes in bacteria, avoidance responses in single-cell organisms, attraction responses in plants, and both visual and nonvisual perception in animals. Despite these widely differing responses, in all of nature there are only six known families of proteins that can transduce light. Although the roundworm Caenorhabditis elegans has none of the known light transduction systems, we show here that C. elegans strongly accelerates its locomotion in response to blue or shorter wavelengths of light, with maximal responsiveness to ultraviolet light. Our data suggest that C. elegans uses this light response to escape the lethal doses of sunlight that permeate its habitat. Short-wavelength light drives locomotion by bypassing two critical signals, cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG), that neurons use to shape and control behaviors. C. elegans mutants lacking these signals are paralyzed and unresponsive to harsh physical stimuli in ambient light, but short-wavelength light rapidly rescues their paralysis and restores normal levels of coordinated locomotion. This light response is mediated by LITE-1, a novel ultraviolet light receptor that acts in neurons and is a member of the invertebrate Gustatory receptor (Gr) family. Heterologous expression of the receptor in muscle cells is sufficient to confer light responsiveness on cells that are normally unresponsive to light. Our results reveal a novel molecular solution for ultraviolet light detection and an unusual sensory modality in C. elegans that is unlike any previously described light response in any organism.
Journal Article
Phytoplankton community disruption caused by latest Cretaceous global warming
Phytoplankton responses to a ∼350 kyr (kiloyear) long phase of gradual late Maastrichtian (latest Cretaceous) global warming starting at ∼66.4 Ma can provide valuable insights into the long-term influences of global change on marine ecosystems. Here we perform micropaleontological analyses on three cores from the New Jersey paleoshelf to assess the response of phytoplankton using cyst-forming dinoflagellates and benthic ecosystems using benthic foraminifera. Our records show that this latest Maastrichtian warming event (LMWE), characterized by a 4.0±1.3 ∘C warming of sea surface waters on the New Jersey paleoshelf, resulted in a succession of nearly monospecific dinoflagellate-cyst assemblages, dominated by the species Palynodinium grallator. This response, likely triggered by the combination of warmer and seasonally thermally stratified seas, appears to have been more intense at offshore sites than at nearshore sites. The LMWE, and related dinoflagellate response, is associated with an impoverished benthic ecosystem. A wider geographic survey of literature data reveals that the dominance of P. grallator is a marker for the LMWE throughout the northern midlatitudes. While the dinocyst assemblage returned to a stable, normal marine community in the last tens of thousands of years of the Maastrichtian, benthic foraminiferal diversity appears to have remained slightly suppressed. Increased ecosystem stress during the latest Maastrichtian potentially primed global ecosystems for the subsequent mass extinction following the Cretaceous Paleogene (K–Pg) boundary Chicxulub impact.
Journal Article
Antarctic role in Northern Hemisphere glaciation
Earth's climate underwent a major transition from the warmth of the late Pliocene, when global surface temperatures were ∼2° to 3°C higher than today, to extensive Northern Hemisphere glaciation (NHG) ∼2.73 million years ago (Ma). We show that North Pacific deep waters were substantially colder (4°C) and probably fresher than the North Atlantic Deep Water before the intensification of NHG. At ∼2.73 Ma, the Atlantic-Pacific temperature gradient was reduced to <1°C, suggesting the initiation of stronger heat transfer from the North Atlantic to the deep Pacific. We posit that increased glaciation of Antarctica, deduced from the 21 ± 10–meter sea-level fall from 3.15 to 2.75 Ma, and the development of a strong polar halocline fundamentally altered deep ocean circulation, which enhanced interhemispheric heat and salt transport, thereby contributing to NHG.
Journal Article
Stepwise transition from the Eocene greenhouse to the Oligocene icehouse
In the largest global cooling event of the Cenozoic Era, between 33.8 and 33.5 Myr ago, warm, high-CO
2
conditions gave way to the variable ‘icehouse’ climates that prevail today. Despite intense study, the history of cooling versus ice-sheet growth and sea-level fall reconstructed from oxygen isotope values in marine sediments at the transition has not been resolved. Here, we analyse oxygen isotopes and Mg/Ca ratios of benthic foraminifera, and integrate the results with the stratigraphic record of sea-level change across the Eocene–Oligocene transition from a continental-shelf site at Saint Stephens Quarry, Alabama. Comparisons with deep-sea (Sites 522 (South Atlantic) and 1218 (Pacific))
δ
18
O and Mg/Ca records enable us to reconstruct temperature, ice-volume and sea-level changes across the climate transition. Our records show that the transition occurred in at least three distinct steps, with an increasing influence of ice volume on the oxygen isotope record as the transition progressed. By the early Oligocene, ice sheets were ∼25% larger than present. This growth was associated with a relative sea-level decrease of approximately 105 m, which equates to a 67 m eustatic fall.
The Eocene–Oligocene transition is the largest global cooling in the Cenozoic period. A comparison of three independent proxies from the continental shelf and deep ocean reveals a three-step transition to cold glacial conditions, with ice sheets 25% larger than their present size.
Journal Article
Impact of Antarctic Circumpolar Current Development on Late Paleogene Ocean Structure
Global cooling and the development of continental-scale Antarctic glaciation occurred in the late middle Eocene to early Oligocene (∼38 to 28 million years ago), accompanied by deep-ocean reorganization attributed to gradual Antarctic Circumpolar Current (ACC) development. Our benthic foraminiferal stable isotope comparisons show that a large δ 13 C offset developed between mid-depth (∼600 meters) and deep (>1000 meters) western North Atlantic waters in the early Oligocene, indicating the development of intermediate-depth δ 13 C and O 2 minima closely linked in the modern ocean to northward incursion of Antarctic Intermediate Water. At the same time, the ocean's coldest waters became restricted to south of the ACC, probably forming a bottom-ocean layer, as in the modern ocean. We show that the modern four-layer ocean structure (surface, intermediate, deep, and bottom waters) developed during the early Oligocene as a consequence of the ACC.
Journal Article
Sentryn and SAD Kinase Link the Guided Transport and Capture of Dense Core Vesicles in Caenorhabditis elegans
Dense core vesicles (DCVs) can transmit signals by releasing neuropeptides from specialized synaptic regions called active zones. DCVs reach the active zone by motorized transport through a long axon. A reverse motor frequently interrupts progress by taking DCVs in the opposite direction. “Guided transport” refers to the mechanism by which outward movements ultimately dominate to bring DCVs to the synaptic region. After guided transport, DCVs alter their interactions with motors and enter a “captured” state. The mechanisms of guided transport and capture of DCVs are unknown. Here, we discovered two proteins that contribute to both processes in Caenorhabditis elegans. SAD kinase and a novel conserved protein we named Sentryn are the first proteins found to promote DCV capture. By imaging DCVs moving in various regions of single identified neurons in living animals, we found that DCV guided transport and capture are linked through SAD kinase, Sentryn, and Liprin-α. These proteins act together to regulate DCV motorized transport in a region-specific manner. Between the cell body and the synaptic region, they promote forward transport. In the synaptic region, where all three proteins are highly enriched at active zones, they promote DCV pausing by inhibiting transport in both directions. These three proteins appear to be part of a special subset of active zone-enriched proteins because other active zone proteins do not share their unique functions.
Journal Article
UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons
The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16’s organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-α). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(−) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADα (a SAD-1-interacting protein) in the CSS system. In an unc-16(−) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(−) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16’s organelle transport regulatory function.
Journal Article
Synapse-Assembly Proteins Maintain Synaptic Vesicle Cluster Stability and Regulate Synaptic Vesicle Transport in Caenorhabditis elegans
The functional integrity of neurons requires the bidirectional active transport of synaptic vesicles (SVs) in axons. The kinesin motor KIF1A transports SVs from somas to stable SV clusters at synapses, while dynein moves them in the opposite direction. However, it is unclear how SV transport is regulated and how SVs at clusters interact with motor proteins. We addressed these questions by isolating a rare temperature-sensitive allele of Caenorhabditis elegans unc-104 (KIF1A) that allowed us to manipulate SV levels in axons and dendrites. Growth at 20° and 14° resulted in locomotion rates that were ∼3 and 50% of wild type, respectively, with similar effects on axonal SV levels. Corresponding with the loss of SVs from axons, mutants grown at 14° and 20° showed a 10- and 24-fold dynein-dependent accumulation of SVs in their dendrites. Mutants grown at 14° and switched to 25° showed an abrupt irreversible 50% decrease in locomotion and a 50% loss of SVs from the synaptic region 12-hr post-shift, with no further decreases at later time points, suggesting that the remaining clustered SVs are stable and resistant to retrograde removal by dynein. The data further showed that the synapse-assembly proteins SYD-1, SYD-2, and SAD-1 protected SV clusters from degradation by motor proteins. In syd-1, syd-2, and sad-1 mutants, SVs accumulate in an UNC-104-dependent manner in the distal axon region that normally lacks SVs. In addition to their roles in SV cluster stability, all three proteins also regulate SV transport.
Journal Article