Impact of inter-correlated initial binary parameters on double black hole and neutron star mergers

The distributions of the initial main-sequence binary parameters are one of the key ingredients in obtaining evolutionary predictions for compact binary (BH-BH / BH-NS / NS-NS) merger rates. Until now, such calculations were done under the assumption that initial binary parameter distributions were independent. Here, we implement empirically derived inter-correlated distributions of initial binary parameters primary mass (M1), mass ratio (q), orbital period (P), and eccentricity (e). Unexpectedly, the introduction of inter-correlated initial binary parameters leads to only a small decrease in the predicted merger rates by a factor of 2 $-$ 3 relative to the previously used non-correlated initial distributions. The formation of compact object mergers in the isolated classical binary evolution favors initial binaries with stars of comparable masses (q = 0.5 $-$ 1) at intermediate orbital periods (log P (days) = 2 $-$ 4). New distributions slightly shift the mass ratios towards smaller values with respect to the previously used flat q distribution, which is the dominant effect decreasing the rates. New orbital periods only negligibly increase the number of progenitors. Additionally, we discuss the uncertainty of merger rate predictions associated with possible variations of the massive-star initial mass function (IMF). We argue that evolutionary calculations should be normalized to a star formation rate (SFR) that is obtained from the observed amount of UV light at wavelength 1500{\AA} (SFR indicator). In this case, contrary to recent reports, the uncertainty of the IMF does not affect the rates by more than a factor of 2. Any change to the IMF slope for massive stars requires a change of SFR in a way that counteracts the impact of IMF variations on the merger rates. In contrast, we suggest that the uncertainty in cosmic SFR at low metallicity can be a significant factor at play.Comment: accepted for publication in A&

Barium and Calcium Stimulate Secretion from Digitonin-Permeabilized Bovine Adrenal Chromaffin Cells by Similar Pathways

We compared the characteristics of secretion stimulated by EGTA-buffered Ba 2+ - and Ca 2+ -containing solutions in digitonin-permeabilized bovine adrenal chromaffin cells. Half-maximal secretion occurred at approximately 100 Μ M Ba 2+ or 1 Μ M Ca 2+ . Ba 2+ -stimulated release was not due to release of sequestered intracellular Ca 2+ because at a constant free Ba 2+ concentration, increasing unbound EGTA did not diminish the extent of release due to Ba 2+ . The maximal extents of Ba 2+ - and Ca 2+ -dependent secretion in the absence of MgATP were identical. MgATP enhanced Ba 2+ -induced secretion to a lesser extent than Ca 2+ -induced secretion. Half-maximal concentrations of Ba 2+ and Ca 2+ , when added together to cells, yielded approximately additive amounts of secretion. Maximal concentrations of Ba 2+ and Ca 2+ when added together to cells for 2 or 15 min were not additive. Tetanus toxin inhibited Ba 2+ - and Ca 2+ -dependent secretion to a similar extent. Ba 2+ , unlike Ca 2+ , did not activate polyphosphoinositide-specific phospholipase C. These data indicate that (1) Ba 2+ directly stimulates exocytosis, (2) Ba 2+ -induced secretion is stimulated to a lesser extent than Ca 2+ -dependent secretion by MgATP, (3) Ba 2+ and Ca 2+ use similar pathways to trigger exocytosis, and (4) exocytosis from permeabilized cells does not require activation of polyphosphoinositide-specific phospholipase C.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66323/1/j.1471-4159.1992.tb09771.x.pd

Effects of Osmolality and Ionic Strength on Secretion from Adrenal Chromaffin Cells Permeabilized with Digitonin

Hyperosmotic solutions inhibit exocytosis of catecholamine from adrenal chromaffin cells at a step after Ca 2+ entry into the cells. The possibility that the inhibition resulted from an inability of shrunken secretory granules to undergo exocytosis was investigated in cells with plasma membranes permeabilized by digitonin. The osmoticants and salts used in this study rapidly equilibrated across the plasma membrane and bathed the intracellular organelles. When sucrose was the osmoticant, secretion was not significantly inhibited unless the osmolality was raised above 1,000 mOs. When the osmolality was raised with the tetrasaccharide stachyose or a low-molecular-weight maltodextrin fraction (average size a tetrasaccharide), one-half maximal inhibition occurred at 900–1,000 mOs. Prior treatment of permeabilized cells with Ca 2+ in hyperosmotic solution did not result in enhanced secretion when cells were restored to normal osmolality. Increased concentrations of potassium glutamate or sodium isethionate were more potent than carbohydrate in inhibiting secretion. Half-maximal inhibition occurred at 600–700 mOs or when the ionic strength was approximately doubled. The inhibition by elevated potasium glutamate also occurred when the osmolality was kept constant with sucrose. Increasing the ionic strength did not alter the Ca 2+ sensitivity of the secretory response. Reducing the ionic strength by substituting sucrose for salt reduced the Ca 2+ concentration required for half-maximal stimulated secretion from approximately 1.2 Μ M . Chromaffin granules, the secretory granules, are known to shrink in hyperosmotic solution. The experiments indicate that shrunken chromaffin granules can undergo exocytosis and suggest that in intact cells elevated ionic strength rather than chromaffin granule shrinkage contributes to the inhibition of secretion by hyperosmotic solutions. The experiments place limits on the possible osmotic mechanisms that could be involved in exocytosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66041/1/j.1471-4159.1986.tb08502.x.pd

Phorbol Esters Enhance Exocytosis from Chromaffin Cells by Two Mechanisms

Treatment with phorbol esters such as 12- O -tet-radecanoylphorbol acetate (TPA) rapidly enhances [ 3 H]norepinephrine secretion from digitonin-permeabilized adrenal chromaffin cells. When TPA treatment was prolonged for several hours, a second distinct enhancing effect was observed. This later enhancement was most prominent at intracellular Ca 2+ concentrations of 3–30 ΜM , and did not require the continued presence of membrane-bound protein kinase C for its expression. The effect could be elicited by as little as 30-min exposure to TPA, followed by several hours in TPA- free medium. This effect of TPA was blocked by actinomycin D and cycloheximide, indicating a requirement for RNA and protein synthesis. Similar effects were seen when intact cells that had been pretreated with TPA were stimulated to secrete by depolarizing concentrations of K + . Thus, protein kinase C enhances secretion by two mechanisms. One is rapid and probably reflects the effects of immediate protein phosphorylation. The other occurs over several hours and requires gene transcription and protein synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66341/1/j.1471-4159.1990.tb13302.x.pd

Arachidonic Acid Release and Catecholamine Secretion from Digitonin-Treated Chromaffin Cells: Effects of Micromolar Calcium, Phorbol Ester, and Protein Alkylating Agents

The relationship between catecholamine secretion and arachidonic acid release from digitonin-treated chromaffin cells was investigated. Digitonin renders permeable the plasma membranes of bovine adrenal chromaffin cells to Ca 2+ , ATP, and proteins. Digitonin-treated cells undergo exocytosis of catecholamine in response to micromolar Ca 2+ in the medium. The addition of micromolar Ca 2+ to digitonin-treated chromaffin cells that had been prelabeled with [ 3 H]arachidonic acid caused a marked increase in the release of [ 3 H]arachidonic acid. The time course of [ 3 H]arachidonic acid release paralleled catecholamine secretion. Although [ 3 H]arachidonic acid release and exocytosis were both activated by free Ca 2+ in the micromolar range, the activation of [ 3 H]arachidonic acid release occurred at Ca 2+ concentrations slightly lower than those required to activate exocytosis. Pretreatment of the chromaffin cells with N -ethylmaleimide (NEM) or p -bromophenacyl bromide (BPB) resulted in dose-dependent inhibition of 10 Μ M Ca 2+ -stimulated [ 3 H]arachidonic acid release and exocytosis. The IC 50 of NEM for both [ 3 H]arachidonic acid release and exocytosis was 40 Μ M. The IC 50 of BPB for both events was 25 Μ M. High concentrations (5–20 m M ) of Mg 2+ caused inhibition of catecholamine secretion without altering [ 3 H]arachidonic acid release. A phorbol ester that activates protein kinase C, 12- O -tetradecanoylphorbol-13-acetate (TPA), caused enhancement of both [ 3 H]arachidonic acid release and exocytosis. The findings demonstrate that [ 3 H]arachidonic acid release is stimulated during catecholamine secretion from digitonin-treated chromaffin cells and they are consistent with a role for phospholipase A 2 in exocytosis from chromaffin cells. Furthermore the data suggest that protein kinase C can modulate both arachidonic acid release and exocytosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65534/1/j.1471-4159.1985.tb07140.x.pd

Kinetic and Spectroscopic Characterization of the H178A Methionyl Aminopeptidase from \u3cem\u3eEscherichia coli\u3c/em\u3e

To gain insight into the role of the strictly conserved histidine residue, H178, in the reaction mechanism of the methionyl aminopeptidase from Escherichia coli (EcMetAP-I), the H178A mutant enzyme was prepared. Metal-reconstituted H178A binds only one equivalent of Co(II) or Fe(II) tightly with affinities that are identical to the WT enzyme based on kinetic and isothermal titration calorimetry (ITC) data. Electronic absorption spectra of Co(II)-loaded H178A EcMetAP-I indicate that the active site divalent metal ion is pentacoordinate, identical to the WT enzyme. These data indicate that the metal binding site has not been affected by altering H178. The effect of altering H178 on activity is, in general, due to a decrease in kcat. The kcat value for Co(II)-loaded H178A decreased 70-fold toward MGMM and 290-fold toward MP-p-NA compared to the WT enzyme, while kcat decreased 50-fold toward MGMM for the Fe(II)-loaded H178A enzyme and 140-fold toward MP-p-NA. The Km values for MGMM remained unaffected, while those for MP-p-NA increased approximately 2-fold for Co(II)- and Fe(II)-loaded H178A. The kcat/Km values for both Co(II)- and Fe(II)-loaded H178A toward both substrates ranged from ∼50- to 580-fold reduction. The pH dependence of log Km, log kcat, and log(kcat/Km) of both WT and H178A EcMetAP-I were also obtained and are identical, within error, for H178A and WT EcMetAP-I. Therefore, H178A is catalytically important but is not required for catalysis. Assignment of one of the observed pKa values at 8.1 for WT EcMetAP-I was obtained from plots of molar absorptivity at λmax(640) vs pH for both WT and H178A EcMetAP-I. Apparent pKa values of 8.1 and 7.6 were obtained for WT and H178A EcMetAP-I, respectively, and were assigned to the deprotonation of a metal-bound water molecule. The data reported herein provide support for the key elements of the previously proposed mechanism and suggest that a similar mechanism can apply to the enzyme with a single metal in the active site

Strongly Secure and Efficient Data Shuffle On Hardware Enclaves

Mitigating memory-access attacks on the Intel SGX architecture is an important and open research problem. A natural notion of the mitigation is cache-miss obliviousness which requires the cache-misses emitted during an enclave execution are oblivious to sensitive data. This work realizes the cache-miss obliviousness for the computation of data shuffling. The proposed approach is to software-engineer the oblivious algorithm of Melbourne shuffle on the Intel SGX/TSX architecture, where the Transaction Synchronization eXtension (TSX) is (ab)used to detect the occurrence of cache misses. In the system building, we propose software techniques to prefetch memory data prior to the TSX transaction to defend the physical bus-tapping attacks. Our evaluation based on real implementation shows that our system achieves superior performance and lower transaction abort rate than the related work in the existing literature.Comment: Systex'1

The Relationship Between Arachidonic Acid Release and Catecholamine Secretion from Cultured Bovine Adrenal Chromaffin Cells

Increased arachidonic acid release occurred during activation of catecholamine secretion from cul- tured bovine adrenal medullary chromaffin cells. The nicotinic agonist l,l-dimethyl-4-phenylpiperazinium (DMPP) caused an increased release of prcincubated [ 3 H]arachidonic acid over a time course which corre- sponded to the stimulation of catecholamine secretion. Like catecholamine secretion, the DMPP-induced [ 3 H]arachidonic acid release was calcium-dependent and was blocked by the nicotinic antagonist mecamylamine. Depolarization by elevated K + , which induced catechol amine secretion, also stimulated arachidonic acid release. Because arachidonic acid release from cells probably re- sults from phospholipase A 2 activity, our findings indicate that phospholipase A 2 may be activated in chromaffin cells during secretion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66068/1/j.1471-4159.1984.tb06690.x.pd

Cholinergic Stimulation of Inositol Phosphate Formation in Bovine Adrenal Chromaffin Cells: Distinct Nicotinic and Muscarinic Mechanisms

The ability of cholinergic agonists to activate phospholipase C in bovine adrenal chromaffin cells was examined by assaying the production of inositol phosphates in cells prelabeled with [ 3 H]inositol. We found that both nicotinic and muscarinic agonists increased the accumulation of [ 3 H]inositol phosphates (mainly inositol monophos-phate) and that the effects mediated by the two types of receptors were independent of each other. The production of inositol phosphates by nicotinic stimulation required extracellular Ca 2+ and was maximal at 0.2 m M Ca 2+ . Increasing extracellular Ca 2+ from 0.22 to 2.2 m M increased the sensitivity of inositol phosphates formation to stimulation by submaximal concentrations of 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) but did not enhance the response to muscarine. Elevated K + also stimulated Ca 2+ -dependent [ 3 H]inositol phosphate production, presumably by a non-receptor-mediated mechanism. The Ca 2+ channel antagonists D600 and nifedipine inhibited the effects of DMPP and elevated K + to a greater extent than that of muscarine. Ca 2+ (0.3–10 Μ M ) directly stimulated the release of inositol phosphates from digitonin-permeabilized cells that had been prelabeled with [ 3 H]inositol. Thus, cholinergic stimulation of bovine adrenal chromaffin cells results in the activation of phospholipase C by distinct muscarinic and nicotinic mechanisms. Nicotinic receptor stimulation and elevated K + probably increased the accumulation of inositol phosphates through Ca 2+ influx and a rise in cytosolic Ca 2+ . Because Ba 2+ caused catechol-amine secretion but did not enhance the formation of inositol phosphates, phospholipase C activation is not required for exocytosis. However, diglyceride and wyo -inositol 1,4,5-trisphosphate produced during cholinergic stimulation of chromaffin cells may modulate secretion and other cellular processes by activating protein kinase C and/or releasing Ca 2+ from intracellular stores.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65738/1/j.1471-4159.1987.tb01037.x.pd

Effects of Tetanus Toxin on Catecholamine Release from Intact and Digitonin-Permeabilized Chromaffin Cells

Tetanus exotoxin inhibited Ca 2+ -dependent cate-cholamine secretion in a dose-dependent manner in digito-nin-permeabilized chromaffin cells. The inhibition was specific for tetanus exotoxin and the B fragment of tetanus toxin; the C fragment had no effect. Inhibition required the introduction of toxin into the cell, and was not seen when intact cells were preincubated with the toxin or toxin fragments. The degree of inhibition was related to the length of preincubation with toxin, as well as the concentration of toxin used. A short preincubation with toxin was sufficient to inhibit secretion, and the continued presence of toxin in the incubation medium was not required during the incubation with Ca 2+ . The inhibition of secretion by tetanus toxin or the B fragment was not overcome with increasing Ca 2+ concentrations. Tetanus toxin also inhibited catechol-amine secretion enhanced by phorbol ester-induced activation of protein kinase C. Thus, the toxin or a proteolytic fragment of the toxin can enter digitonin-permeabilized cells to interact with a component of the Ca 2+ -dependent exocytotic pathway to inhibit secretion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66452/1/j.1471-4159.1988.tb01059.x.pd