Synthesis of S-(1-diazo-2,2,2-Trifluorethyl) Cysteine Dioxide : A Potential Gutamine Antagonist

Compounds affecting the utilization of L-glutamine have a comparatively long history in the field of cancer chemotherapy. The Streptomyces antibiotics, azaserine (0-diazoacetyl-L-serine) and DON (6-diazo-5-oxo-L-norleucine) inhibit to varying extents those aminations in which glutamine serves as an amino group donor. This inhibition is achieved in at least one case by the glutamine antagonists alkylating the sulfhydryl group of the enzyme that catalyzes the amino group transfer of glutamine. A distinguishing feature of the diazo analogs of glutamine is the very reactive diazo group that enhances nucleophilic reactions on the adjacent carbon atom. Because of the increased reactivity created by the diazo group, the diazo analogs of glutamine irreversibly inhibit the glutamine requiring enzymes. Although having gone through exhaustive clinical tests, the L-glutamine antagonists, azaserine and DON, readily declined in interest because of their ineffectiveness in treatment of human malignancies. The recent success of L-asparaginase in the therapy of certain human neoplasms has prompted a reconsideration of compounds which can alter L-glutamine metabolism because: (1) L-glutamine is necessary in most mammalian systems, for the synthesis of L-asparagine; (2) both azaserine and azotomycin appear to be synergistic with L-asparaginase against the L5178Y mouse leukemia; and (3) L-asparaginase from E. coli (EC-2) of the form in clinical use in the United States has intrinsic L-glutaminase activity. EC-2 preparations appear to be more active against certain tumor cells than. guinea pig or agouti serum preparations that lack L-glutaminase activity. Whether this is due to the additional L-glutaminase activity remains to be proven. The purpose of making compounds which are structurally similar to the two antibiotics is threefold. These are to produce a compound which (1) is more active against the tumor, (2) is less toxic to the patient and (3) will help elucidate the mechanism and nature of its bonding to active sites of enzymes in various biological reactions. The history is divided into two parts; the first section deals with the importance of L-glutamine in metabolic and biosynthetic pathways, the second part concentrates on glutamine antagonists and their inhibitory effect with the biosynthesis or metabolic roles of the parent compound

Capital Punishment Reforms in Illinois: Comparing the Views of Police, Prosecutors, and Public Defenders

On 9 March 2011, Governor Patrick Quinn abolished capital punishment in Illinois stating that the state’s system of imposing the death penalty was inherently flawed. Quinn’s announcement followed an eleven-year effort to end the death penalty that began with a 2000 moratorium on executions imposed by then Governor George Ryan. This moratorium was the direct result of the appellate reversal of a series of death-row convictions. Prompted by these reversals, Ryan also created the Governor’s Commission on Capital Punishment to study the use of the death penalty in Illinois. As a result of this effort, comprehensive legislation was enacted to reform the Illinois death penalty system, and the Capital Punishment Reform Study Committee was formed to gauge the implementation and impact of the reforms. Working with the Committee, the authors’ surveyed 413 Illinois police departments, 102 Illinois State’s Attorneys’ Offices, and all 99 Public Defender’s Offices in an effort to determine the extent to which criminal justice agencies had implemented the requirements of the capital punishment reform legislation, and whether there were any significant barriers to the implementation of the legislative requirements. This paper reports the results of this inquiry, and argues that capital punishment ended in Illinois because of the complexity of the death penalty and the perceived inability to devise a system free of racial, geographic, and economic bias and not the failure of the criminal justice community to implement the reforms recommended by the Governor’s Commission on Capital Punishment

Organizational Approaches to Drug Law Enforcement by Local Police Departments in the United States: Specialized Drug Units and Participation in Multi-Agency Drug Task Forces

This paper examines the factors associated with the decision of local police departments in the United States to operate specialized drug units or to participate in multi-jurisdictional drug task forces. Combining data from the Law Enforcement Management and Administrative Statistics (LEMAS) Survey, the 2000 Census, and the Uniform Crime Report, we use both bivariate and multivariate methods to conduct the analysis. The findings indicate that county-level agencies, those with other formalized drug control efforts, high levels of violent crime, high degrees of task specialization and formalization, and high proportions of the resident population accounted for by renters were more likely to operate drug units, participate in multi-agency drug task forces, and allocate more officers per capita to these efforts

A fluorescence-activated cell sorting subsystem for the Imaging FlowCytobot

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Limnology and Oceanography: Methods 15 (2017): 94–102, doi:10.1002/lom3.10145.Recent advances in plankton ecology have brought to light the importance of variability within populations and have suggested that cell-to-cell differences may influence ecosystem-level processes such as species succession and bloom dynamics. Flow cytometric cell sorting has been used to capture individual plankton cells from natural water samples to investigate variability at the single cell level, but the crude taxonomic resolution afforded by the fluorescence and light scattering measurements of conventional flow cytometers necessitates sorting and analyzing many cells that may not be of interest. Addition of imaging to flow cytometry improves classification capability considerably: Imaging FlowCytobot, which has been deployed at the Martha's Vineyard Coastal Observatory since 2006, allows classification of many kinds of nano- and microplankton to the genus or even species level. We present in this paper a modified bench-top Imaging FlowCytobot (IFCB-Sorter) with the capability to sort both single cells and colonies of phytoplankton and microzooplankton from seawater samples. The cells (or subsets selected based on their images) can then be cultured for further manipulation or processed for analyses such as nucleic acid sequencing. The sorting is carried out in two steps: a fluorescence signal triggers imaging and diversion of the sample flow into a commercially available “catcher tube,” and then a solenoid-based flow control system isolates each sorted cell along with 20 μL of fluid.NSF Grant Number: OCE-11300140; WHOI internal support; NSERC through a Post-Graduate Masters awar

Pump-During-Probe Fluorometry of Phytoplankton: Group-Specific Photosynthetic Characteristics from Individual Cell Analysis

Saturating-flash fluorescence techniques are used to monitor the state of the photosynthetic apparatus in phytoplankton under natural conditions. At present these are bulk water measurements, which produce estimates of average properties of all the fluorescent particles present in a sample. Here we describe an improved approach for single-cell measurements of phytoplankton. We have combined individual- cell 'pump-during-probe' measurements of chlorophyll fluorescence induction on the time scale of 30 to 100 microseconds with flow cytometric characterization of each cell, to obtain population-specific photosynthetic characteristics. The results provide information about the potential quantum yield of photochemistry, the fraction of functional reaction centers, and the functional absorption cross section for photosystem 2

Inefficiency of classically simulating linear optical quantum computing with Fock-state inputs

Aaronson and Arkhipov recently used computational complexity theory to argue that classical computers very likely cannot efficiently simulate linear, multimode, quantum-optical interferometers with arbitrary Fock-state inputs [Aaronson and Arkhipov, Theory Comput. 9, 143 (2013)]. Here we present an elementary argument that utilizes only techniques from quantum optics. We explicitly construct the Hilbert space for such an interferometer and show that its dimension scales exponentially with all the physical resources. We also show in a simple example just how the Schr\"odinger and Heisenberg pictures of quantum theory, while mathematically equivalent, are not in general computationally equivalent. Finally, we conclude our argument by comparing the symmetry requirements of multiparticle bosonic to fermionic interferometers and, using simple physical reasoning, connect the nonsimulatability of the bosonic device to the complexity of computing the permanent of a large matrix.Comment: 7 pages, 1 figure Published in PRA Phys. Rev. A 89, 022328 (2014

Microzooplankton community structure investigated with imaging flow cytometry and automated live-cell staining

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Ecology Progress Series 550 (2016): 65-81, doi:10.3354/meps11687.Protozoa play important roles in grazing and nutrient recycling, but quantifying these roles has been hindered by difficulties in collecting, culturing, and observing these often-delicate cells. During long-term deployments at the Martha’s Vineyard Coastal Observatory (Massachusetts, USA), Imaging FlowCytobot (IFCB) has been shown to be useful for studying live cells in situ without the need to culture or preserve. IFCB records images of cells with chlorophyll fluorescence above a trigger threshold, so to date taxonomically resolved analysis of protozoa has presumably been limited to mixotrophs and herbivores which have eaten recently. To overcome this limitation, we have coupled a broad-application ‘live cell’ fluorescent stain with a modified IFCB so that protozoa which do not contain chlorophyll (such as consumers of unpigmented bacteria and other heterotrophs) can also be recorded. Staining IFCB (IFCB-S) revealed higher abundances of grazers than the original IFCB, as well as some cell types not previously detected. Feeding habits of certain morphotypes could be inferred from their fluorescence properties: grazers with stain fluorescence but without chlorophyll cannot be mixotrophs, but could be either starving or feeding on heterotrophs. Comparisons between cell counts for IFCB-S and manual light microscopy of Lugol’s stained samples showed consistently similar or higher counts from IFCB-S. We show how automated classification through the extraction of image features and application of a machine-learning algorithm can be used to evaluate the large high-resolution data sets collected by IFCBs; the results reveal varying seasonal patterns in abundance among groups of protists.This research was supported in part by NSF (grants OCE-1130140, OCE-1434440), NASA (grants NNX11AF07G and NNX13AC98G), the Gordon and Betty Moore Foundation (grants 934 and 2649), and the Woods Hole Oceanographic Institution’s Innovative Technology Program

Diatoms favor their younger daughters

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2012. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography 57 (2012): 1572-1578, doi:10.4319/lo.2012.57.5.1572.We used a time-lapse imaging approach to examine cell division in the marine centric diatom Ditylum brightwellii and observed that daughter cells who inherited their parents' hypothecal frustule half were more likely to divide before their sisters. This is consistent with observations in Escherichia coli of a bias between sister cells, where faster growth in one sister is thought to arise from its inheriting parental material with less oxidative damage. We also observed that hypothecal sisters in D. brightwellii were more likely to inherit a greater proportion of their parents' cellular material, similar to what has been seen in E. coli. We found a statistically significant correlation between the amount of parental material inherited by a hypothecal daughter and its relative division rate, indicating that this extra material inherited by the hypothecal daughter plays a role in its more rapid division. Furthermore, the intercept in this regression was greater than zero, indicating that other factors, such as differences in the quality of inherited material, also play a role. This similarity between two taxonomically distant microbes suggests that favoritism toward one daughter might occur broadly among unicellular organisms that reproduce asexually by binary fission. Such a bias in cell division might be advantageous, given model predictions that show that favoring one daughter at the expense of the other can result in higher population growth rates, increasing the chance that a cell's genotype will survive compared to a model where the daughters divide at equal rates.This research was funded in part by the Woods Hole Oceanographic Institution through an Ocean Life Institute Postdoctoral Scholarship to S.R.L. and by support to R.J.O. and H.M.S. from the Gordon and Betty Moore Foundation

Spawning and early development of captive yellowfin tuna (Thunnus albacares)

In this study we describe the courtship and spawning behaviors of captive yellowfin tuna (Thunnus albacares), their spawning periodicity, the influence of physical and biological factors on spawning and hatching, and egg and early-larval development of this species at the Achotines Laboratory, Republic of Panama, during October 1996 through March 2000. Spawning occurred almost daily over extended periods and at water temperatures from 23.3° to 29.7°C. Water temperature appeared to be the main exogenous factor controlling the occurrence and timing of spawning. Courtship and spawning behaviors were ritualized and consistent among three groups of broodstock over 3.5 years. For any date, the time of day of spawning (range: 1330 to 2130 h) was predictable from mean daily water temperature, and 95% of hatching occurred the next day between 1500 and 1900 h. We estimated that females at first spawning averaged 1.6−2.0 years of age. Over short time periods (<1 month), spawning females increased their egg production from 30% to 234% in response to shortterm increases in daily food ration of 9% to 33%. Egg diameter, notochord length (NL) at hatching, NL at first feeding, and dry weights of these stages were estimated. Water temperature was significantly, inversely related to egg size, egg-stage duration, larval size at hatching, and yolksac larval duration