Risky Businesses: A Micro-Level Spatiotemporal Analysis of Crime, Place, & Business Establishment Type

Continuing advances in the fields of environmental criminology and geographical information sciences are facilitating place-based research. One of the current trends in environmental criminology is the focus on micro-level `places\u27 including street segments, property lots, and specific kinds of buildings and facilities in understanding crime patterns and the opportunity structure that permits crime. Despite important findings on the concentration of crime in urban areas, there continues to be substantial gaps in our knowledge about micro-level spatiotemporal patterns of crime. These gaps in micro-level environmental criminology research have primarily been a result of the lack of access to data, availability of ancillary data (land-use & business establishment data), accuracy of geocoded crime data, and availability of existing theory and methods to study crime at micro-levels. Interestingly, many studies indicate that crimes are clustered at neighborhood level, but the entire neighborhood is rarely (if ever) criminogenic and only specific parts of neighborhoods contain high concentrations of crime. Prior studies incorrectly assume that the relationships between crime, population, land-use, and business establishment types are both homogenous and spatially stationary. Environmental criminologists using Pareto\u27s 80/20 concept pointed out that not all parks are full of drug users/dealers, not all high schools have high rates of delinquency, not all bars contain high rates of assault, and not all parking lots have high rates of auto theft. In fact neighborhoods contain hot spots (high density crime areas) and cold spots (low density crime areas), bad streets and good streets, and good and bad businesses. By undertaking a micro-level spatiotemporal framework, this dissertation research is intended to promote understanding of the patterns of violent crimes and the opportunity factors that contribute to these crimes in neighborhoods, street segments, property lots and business establishment types. The integration of environmental criminological theory and novel spatial analyses at the street segment and property lot level should help criminology/criminal justice scholars and practitioners to better understand the spatial and temporal processes in the `magma\u27 that fuels today\u27s hot spots

Chemical and physical influences on aerosol activation in liquid clouds: a study based on observations from the Jungfraujoch, Switzerland

A simple statistical model to predict the number of aerosols which activate to form cloud droplets in warm clouds has been established, based on regression analysis of data from four summertime Cloud and Aerosol Characterisation Experiments (CLACE) at the high-altitude site Jungfraujoch (JFJ). It is shown that 79 % of the observed variance in droplet numbers can be represented by a model accounting only for the number of potential cloud condensation nuclei (defined as number of particles larger than 80 nm in diameter), while the mean errors in the model representation may be reduced by the addition of further explanatory variables, such as the mixing ratios of O3, CO, and the height of the measurements above cloud base. The statistical model has a similar ability to represent the observed droplet numbers in each of the individual years, as well as for the two predominant local wind directions at the JFJ (northwest and southeast). Given the central European location of the JFJ, with air masses in summer being representative of the free troposphere with regular boundary layer in-mixing via convection, we expect that this statistical model is generally applicable to warm clouds under conditions where droplet formation is aerosol limited (i.e. at relatively high updraught velocities and/or relatively low aerosol number concentrations). A comparison between the statistical model and an established microphysical parametrization shows good agreement between the two and supports the conclusion that cloud droplet formation at the JFJ is predominantly controlled by the number concentration of aerosol particles

ISSUES IN REFORMING TARIFF-RATE IMPORT QUOTAS IN THE AGREEMENT ON AGRICULTURE IN THE WTO

Contents: The Economics of Tariff Rate Quotas and the Effects of Trade Liberalization; TRQs and GATT Rules; An Overview of Tariffs, Quotas and Imports Worldwide; TRQs in the European Union; U.S. TRQs for Sugar, Tobacco and Peanuts; Dairy TRQs in the United States; Tariff Rate Quota Implementation and Administration by Developing Countries; Management of Tariff Rate Quotas in Korea and Japan; Tariff Rate Quota Administration in Canadian Agriculture; The Case of Australia and New Zealand Facing TRQs; The 1999 WTO Panel Report on the EU's Common Market Organization for Bananas; AssessmentInternational Relations/Trade,

Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem- and progenitor cells in acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is a life-threatening stem cell disease characterized by uncontrolled proliferation and accumulation of myeloblasts. Using an advanced RNAi screen-approach in an AML mouse model we have recently identified the epigenetic ‘reader’ BRD4 as a promising target in AML. In the current study, we asked whether inhibition of BRD4 by a small-molecule inhibitor, JQ1, leads to growth-inhibition and apoptosis in primary human AML stem- and progenitor cells. Primary cell samples were obtained from 37 patients with freshly diagnosed AML (n=23) or refractory AML (n=14). BRD4 was found to be expressed at the mRNA and protein level in unfractionated AML cells as well as in highly enriched CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in all patients examined. In unfractionated leukemic cells, submicromolar concentrations of JQ1 induced major growth-inhibitory effects (IC50 0.05-0.5 μM) in most samples, including cells derived from relapsed or refractory patients. In addition, JQ1 was found to induce apoptosis in CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in all donors examined as evidenced by combined surface/Annexin-V staining. Moreover, we were able to show that JQ1 synergizes with ARA-C in inducing growth inhibition in AML cells. Together, the BRD4-targeting drug JQ1 exerts major anti-leukemic effects in a broad range of human AML subtypes, including relapsed and refractory patients and all relevant stem- and progenitor cell compartments, including CD34+/CD38− and CD34+/CD38+ AML cells. These results characterize BRD4-inhibition as a promising new therapeutic approach in AML which should be further investigated in clinical trials

Chemical characterization of atmospheric ions at the high altitude research station Jungfraujoch (Switzerland)

The ion composition at high altitude (3454 m a.s.l.) was measured with an atmospheric pressure interface time-of-flight mass spectrometer (APi-TOF) during a period of 9 months, from August 2013 to April 2014. The negative mass spectra were dominated by the ions of sulfuric, nitric, malonic, and methanesulfonic acid (MSA) as well as SO5. The most prominent positive ion peaks were from amines. The other cations were mainly organic compounds clustered with a nitrogen-containing ion, which could be either NH4+ or an aminium. Occasionally the positive spectra were characterized by groups of compounds each differing by a methylene group. In the negative spectrum, sulfuric acid was always observed during clear sky conditions following the diurnal cycle of solar irradiation. On many occasions we also saw a high signal of sulfuric acid during nighttime when clusters up to the tetramer were observed. A plausible reason for these events could be evaporation from particles at low relative humidity. A remarkably strong correlation between the signals of SO5 and CH3SO3- was observed for the full measurement period. The presence of these two ions during both the day and the night suggests a non-photochemical channel of formation which is possibly linked to halogen chemistry. Halogenated species, especially Br- and IO3-, were frequently observed in air masses that originated mainly from the Atlantic Ocean and occasionally from continental areas based on back trajectory analyses. We found I2O5 clustered with an ion, a species that was proposed from laboratory and modeling studies. All halogenated ions exhibited an unexpected diurnal behavior with low values during daytime. New particle formation (NPF) events were observed and characterized by (1) highly oxygenated molecules (HOMs) and low sulfuric acid or (2) ammonia-sulfuric acid clusters. We present characteristic spectra for each of these two event types based on 26 nucleation episodes. The mass spectrum of the ammonia-sulfuric acid nucleation event compares very well with laboratory measurements reported from the CLOUD chamber. A source receptor analysis indicates that NPF events at the Jungfraujoch take place within a restricted period of time of 24-48 h after air masses have had contact with the boundary layer. This time frame appears to be crucial to reach an optimal oxidation state and concentration of organic molecules necessary to facilitate nucleation.Peer reviewe

Single electron Sensitive Readout (SiSeRO) X-ray detectors: Technological progress and characterization

Single electron Sensitive Read Out (SiSeRO) is a novel on-chip charge detector output stage for charge-coupled device (CCD) image sensors. Developed at MIT Lincoln Laboratory, this technology uses a p-MOSFET transistor with a depleted internal gate beneath the transistor channel. The transistor source-drain current is modulated by the transfer of charge into the internal gate. At Stanford, we have developed a readout module based on the drain current of the on-chip transistor to characterize the device. Characterization was performed for a number of prototype sensors with different device architectures, e.g. location of the internal gate, MOSFET polysilicon gate structure, and location of the trough in the internal gate with respect to the source and drain of the MOSFET (the trough is introduced to confine the charge in the internal gate). Using a buried-channel SiSeRO, we have achieved a charge/current conversion gain of >700 pA per electron, an equivalent noise charge (ENC) of around 6 electrons root mean square (RMS), and a full width half maximum (FWHM) of approximately 140 eV at 5.9 keV at a readout speed of 625 Kpixel/s. In this paper, we discuss the SiSeRO working principle, the readout module developed at Stanford, and the characterization test results of the SiSeRO prototypes. We also discuss the potential to implement Repetitive Non-Destructive Readout (RNDR) with these devices and the preliminary results which can in principle yield sub-electron ENC performance. Additional measurements and detailed device simulations will be essential to mature the SiSeRO technology. However, this new device class presents an exciting technology for next generation astronomical X-ray telescopes requiring fast, low-noise, radiation hard megapixel imagers with moderate spectroscopic resolution.Comment: To appear in SPIE Proceedings of Astronomical Telescopes + Instrumentation, 202

The high-speed X-ray camera on AXIS

AXIS is a Probe-class mission concept that will provide high-throughput, high-spatial-resolution X-ray spectral imaging, enabling transformative studies of high-energy astrophysical phenomena. To take advantage of the advanced optics and avoid photon pile-up, the AXIS focal plane requires detectors with readout rates at least 20 times faster than previous soft X-ray imaging spectrometers flying aboard missions such as Chandra and Suzaku, while retaining the low noise, excellent spectral performance, and low power requirements of those instruments. We present the design of the AXIS high-speed X-ray camera, which baselines large-format MIT Lincoln Laboratory CCDs employing low-noise pJFET output amplifiers and a single-layer polysilicon gate structure that allows fast, low-power clocking. These detectors are combined with an integrated high-speed, low-noise ASIC readout chip from Stanford University that provides better performance than conventional discrete solutions at a fraction of their power consumption and footprint. Our complementary front-end electronics concept employs state of the art digital video waveform capture and advanced signal processing to deliver low noise at high speed. We review the current performance of this technology, highlighting recent improvements on prototype devices that achieve excellent noise characteristics at the required readout rate. We present measurements of the CCD spectral response across the AXIS energy band, augmenting lab measurements with detector simulations that help us understand sources of charge loss and evaluate the quality of the CCD backside passivation technique. We show that our technology is on a path that will meet our requirements and enable AXIS to achieve world-class science.Comment: 17 pages, 11 figures, submitted to Proceedings of SPIE Optics + Photonics 202

Structural studies suggest aggregation as one of the modes of action for teixobactin

Teixobactin is a new promising antibiotic that targets cell wall biosynthesis by binding to lipid II and has no detectable resistance thanks to its unique but yet not fully understood mechanism of operation. To aid in the structure-based design of teixobactin analogues with improved pharmacological properties, we present a 3D structure of native teixobactin in membrane mimetics and characterise its binding to lipid II through a combination of solution NMR and fast (90 kHz) magic angle spinning solid state NMR. In NMR titrations, we observe a pattern strongly suggesting interactions between the backbone of the C-terminal “cage” and the pyrophosphate moiety in lipid II. We find that the N-terminal part of teixobactin does not only act as a membrane anchor, as previously thought, but is actively involved in binding. Moreover, teixobactin forms a well-structured and specific complex with lipid II, where the N-terminal part of teixobactin assumes a b conformation that is highly prone to aggregation, which likely contributes to the antibiotic's high bactericidal efficiency. Overall, our study provides several new clues to teixobactin's modes of action

A Census of the High-Density Molecular Gas in M82

We present a three-pointing study of the molecular gas in the starburst nucleus of M82 based on 190 - 307 GHz spectra obtained with Z-Spec at the Caltech Submillimeter Observatory. We present intensity measurements, detections and upper limits, for 20 transitions, including several new detections of CS, HNC, C2H, H2CO, and CH3CCH lines. We combine our measurements with previously-published measurements at other frequencies for HCN, HNC, CS, C34S, and HCO+ in a multi-species likelihood analysis constraining gas mass, density and temperature, and the species' relative abundances. We find some 1.7 - 2.7 x 10^8 M_sun of gas with n_H2 between 1 - 6 x 10^4 cm^-3 and T > 50 K. While the mass and temperature are comparable to values inferred from mid-J CO transitions, the thermal pressure is a factor of 10 - 20 greater. The molecular interstellar medium is largely fragmented and is subject to ultraviolet irradiation from the star clusters. It is also likely subject to cosmic rays and mechanical energy input from the supernovae, and is warmer on average than the molecular gas in the massive star formation regions in the Milky Way. The typical conditions in the dense gas in M82's central kpc appear unfavorable for further star formation; if any appreciable stellar populations are currently forming, they are likely biased against low mass stars, producing a top-heavy initial mass function.Comment: 15 pages (using emulateapj.cls), 6 figures, Astrophysical Journal, in pres

Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments