cssi/SciSciGPT-SciSciNet huggingface dataset:
Conditional resampling improves sensitivity and specificity of single cell CRISPR regulatory screens

Mapping gene-enhancer regulatory relationships is key to unraveling molecular disease mechanisms based on GWAS associations in non-coding regions. Recently developed CRISPR regulatory screens (CRSs) based on single cell RNA-seq (scRNA-seq) are a promising high-throughput experimental approach to this problem. However, the analysis of these screens presents significant statistical challenges, including modeling cell-level gene expression and correcting for sequencing depth. Using a recent large-scale CRS and its original analysis as a case study, we demonstrate weaknesses in existing analysis methodology, which lead to false positives as well as false negatives. To address these challenges, we propose SCEPTRE: analysis of single cell perturbation screens via conditional resampling. This novel method infers gene-enhancer associations by modeling the stochastic assortment of CRISPR gRNAs among cells instead of the gene expression, remaining valid despite arbitrary misspecification of the gene expression model. Applying SCEPTRE to the large-scale CRS, we demonstrate improvements in both sensitivity and specificity. We also discover 217 regulatory relationships not found in the original study, many of which are supported by existing functional data.
The impact of U.S. refugee policy change & political rhetoric on nonprofit service providers’ emotional well-being

This study examines how U.S. refugee policy changes from 2014 to 2018 affected the emotional well-being of nonprofit service providers. Participants identified the general political climate, includ...
Effects of general anesthetics on synaptic transmission and plasticity.

General anesthetics depress excitatory and/or enhance inhibitory synaptic transmission principally by modulating the function of glutamatergic or GABAergic synapses, respectively, with relative anesthetic agent-specific mechanisms. Synaptic signaling proteins, including ligand- and voltage-gated ion channels, are targeted by general anesthetics to modulate various synaptic mechanisms including presynaptic neurotransmitter release, postsynaptic receptor signaling, and dendritic spine dynamics to produce their characteristic acute neurophysiological effects. As synaptic structure and plasticity mediate higher-order functions such as learning and memory, long-term synaptic dysfunction following anesthesia may lead to undesirable neurocognitive consequences depending on specific anesthetic agent and the vulnerability of population. Here we review the cellular and molecular mechanisms of transient and persistent general anesthetic alterations of synaptic transmission and plasticity.
Developing Complex Societies in Southeast Asia: Using Archaeological and Historical Evidence

A number of archaeologists are making significant advances in the historical archaeology of Southeast Asia. The papers presented in this issue, and the one that preceded it, provide new insights and exciting directions for future research.
Extracting speed, heading and turn-rate measurements from extended objects using the EM algorithm

In active sonar and radar target tracking, measurements consist of position and often Doppler. Tracking algorithms use these measurements over time to estimate target state comprising position, velocity and turn rate. In most cases there is an underlying assumption in the tracking algorithm that the target is a “point target” (i.e. the target has no physical extent). Another common assumption is that, at most, one measurement per scan originates from the target. For certain combinations of transmitted waveform and target type, the resolution of the waveform is such that the target is “overresolved” (i.e. the error in the measurements is small enough that the spatial characteristics of the target can be measured). For such cases the point target assumption must be replaced with an extended target assumption. This work provides a methodology to exploit the extended nature of the target for the case of a rigid target whose spatial characteristics are fixed with respect to the line of motion. By employing a combination of the expectation maximization (EM) algorithm and allowing more than one measurement per scan to originate from the target, a measurement conversion technique is developed. This technique converts a single scan of rawmeasurements that include position and Doppler into an estimate of target position, velocity, heading and turn rate.
The Elastic Rod Provides a Model for DNA and Its Functions

The processes of transcription and replication are catalysed by processive enzyme complexes which move translationally along the DNA helix, unwinding the DNA helix ahead of the complex and reforming a duplex helix behind the complex (Gamper and Hearst 1982; Cook et al. 1994). These processes are known to torsionally stress DNA.
Berkshire Downs: Racing’s Non-Success Story

This article provides a short history of Berkshire Downs, a former thoroughbred track located in Hancock Massachusetts. The article provides information on how the track was established and the reasons for its ultimate demise.
A cold-sensitive cytoplasmic mutation of Saccharomyces cerevisiae affecting assembly of the mitochondrial 50S ribosomal subunit.

A cytoplasmic mutant of Saccharomyces cerevisiae (E23-1) has been isolated that is resistant to erythromycin and cold sensitive for growth on nonfermentable carbon sources at 18°. Genetic analysis has shown that both of these properties probably result from a single mutation at the rib2 locus which maps close to or within the gene for the 21S rRNA of the mitochondrial 50S ribosomal subunit. Electrophoresis of total RNA extracted from purified mitochondria demonstrated that the 21S and 14S rRNA species from both mutant and wild-type cells were present in roughly equimolar quantities regardless of growth temperature. The mutant is therefore not defective in the synthesis of the 21S rRNA. Sucrose gradient analysis of the mitochondrial ribosomes in Mg2+-containing buffers revealed that approximate values for the ratio of 50S to 37S subunits were 1:1 for wild-type cells grown at either 18° or 32°, 0.5:1 for the mutant grown at 32° and 0.2:1 for the mutant grown at 18°. The subunit ratios were approximately 1:1 when Ca2+-containing buffers were used, however, In alls cases, 50S particles from the mutant grown at 18° lacked or contained markedly reduced amounts of two distinctive protein components that were present in the mutant at 32° and in the wild-type at both temperatures. In addition, no intact 21S RNA could be recovered from the mitochondrial ribosomes of the mutant grown at the restrictive temperature, even in the presence of Ca2+. These findings indicate that mitochondrial 50S ribosomal subunits produced by the mutant at 18° are structurally defective and raise the possibility that the defect results from an alteration in the gene for 21S rRNA.
Constancy of the relation between floc size and density in San Francisco Bay

The size and density of fine-sediment aggregates, or flocs, govern their transport and depositional properties. While the mass and volume concentrations of flocs can be measured directly or by optical methods, they must be determined simultaneously to gain an accurate density measurement. Results are presented from a tidal cycle study in San Francisco Bay, where mass concentration was determined directly, and volume concentration was measured in 32 logarithmically spaced size bins by laser-diffraction methods. The relation between floc size and density is investigated assuming a constant primary particle size and fractal floc dimension. This relation is validated with measurements from several sites throughout San Francisco Bay. The constancy of this relation implies a uniform primary particle size throughout the Bay, as well as uniform aggregation/disaggregation mechanisms (which modify fractal dimension). The exception to the relation is identified during near-bed measurements, when advected flocs mix with recently resuspended flocs from the bed, which typically have a higher fractal dimension than suspended flocs. The constant relation for suspended flocs simplifies monitoring and numerical modeling of suspended sediment in San Francisco Bay.
Muon Tomography Algorithms for Nuclear Threat Detection

In this article on Muon Tomography we report our work on the development of an intelligent pattern detection system for materials with high atomic numbers (Z) for Homeland Security application. Muons are naturally produced in the upper atmosphere by primary cosmic rays and are used as passive probes of a cargo volume. By sensing the incoming and outgoing tracks and measuring the momentum of each muon for a probed volume one may derive the scattering parameters. A statistical algorithm is being used to estimate scattering densities of the material in each unit volume (voxel) of the probed target. The article describes the algorithm and some results from our simulation experiments.
Physical and chemical studies on ceruloplasmin. IX. The role of galactosyl residues in the clearance of ceruloplasmin from the circulation.

Abstract The survival time in plasma of incompletely desialylated ceruloplasmin, labeled with 64Cu or with tritium, was studied in the rat. Removal of less than 20% of the terminal sialic acid, with consequent exposure of the penultimate galactosyl residues, resulted in the rapid disappearance from the circulation of more than 50% of the injected dose. Statistical analysis of the experimental results by means of the Poisson distribution equation supports the estimate that the exposure of no more than 2 galactosyl residues is sufficient to effect prompt clearance of ceruloplasmin from the circulation. Examination of the specificity of the two neuraminidase preparations used in this study revealed that each of the enzymes possessed a preferential affinity for different sialic acid residues, although the results from each were statistically predictable. Consequently, the removal of any 2 sialic acid residues from 1 molecule of ceruloplasmin appears to be incompatible with the continued survival of that molecule in the circulation.
PHOSPHATASES IN EPIPHYSEAL CARTILAGE; THEIR POSSIBLE ROLE IN TISSUE SYNTHESIS.

An attempt is made to delineate three phosphatase systems in the epiphyseal mechanism of the rabbit, dog, and human being. Of particular interest is inorganic pyrophosphatase since it is present in substantial amount only in the proliferating cell zone. Some of its properties are described. An explanation of its functional significance to the growth mechanism is suggested.
Strange stars: Which is the ground stage of QCD at finite baryon number

Witten's conjecture about strange quark matter (`Strange Matter') being the ground state of QCD at finite baryon number is presented and stars made of strange matter (`Strange Stars') are compared to neutron stars. The only observable way in which a strange star differs from a neutron star is in its early thermal history and a detailed study of strange star cooling is reported and compared to neutron star cooling. One concludes that future detection of thermal radiation from the compact object produced in the core collapse of SN 1987A could present the first evidence for strange matter.
Cu‐Catalyzed Azide‐Alkyne Cycloaddition: Preparation of Tris((1‐Benzyl‐1H‐1,2,3‐Triazolyl)Methyl)Amine

Tripropargylamine Benzyl azide Copper(II) acetate, monohydrate Sodium ascorbate Keywords: Cu-catalyzed azide-alkyne cycloaddition; tris((1-benzyl-1H-1,2,3-triazolyl)methyl)amine; off-cycle ligated-copper species; tripropargylamine
The effect of modulation amplitude on electron-excited auger data from titanium

Abstract The effects of the distortion due to large modulation amplitudes on the electron-excited Auger spectra of titanium have been studied using a cylindrical mirror analyzer. It is found that the normal derivative Auger data are very sensitive, both in magnitude and shape, to the value of the amplitude. The peak-to-peak signal strengths behave in a very complex manner and there is no simple way of relating the various values. Since the background is essentially eliminated in the derivative data, the Auger spectrum, itself, is obtained in the electron energy distribution by integrating the differential spectrum. It is shown that the magnitude and shape of these spectra are better behaved as a function of the modulation amplitude. The strengths of these features vary almost linearly with amplitude and the effect of distortion is simply to broaden the features. Auger area values obtained by double integration over the Auger structure in the derivative spectrum are shown to follow the predicted linear relation with the modulation amplitude. This simple relationship allows relative elemental surface concentration measurements to be made with enormous improvements in signal-to-noise ratio while maintaining the ability to exactly correct for potential modulation distortion.
Cheddar Cheese Made from Pasteurized Milk Homogenized at Various Pressures

Summary Cheese of the Cheddar type was made from either standardized Jersey milk or unstandardized Holstein milk homogenized at 0, 500, 1,000, and 2,000 p.s.i. Increasing homogenization pressures resulted in progressive decreases in elasticity of curd, slower whey expulsion, lower fat losses in whey, lower color intensity of cheese, and less oiling off. Analysis of variance showed nonsignificance with respect to breed differences and to differences in flavor scores of the ripened cheese. The differences in body and texture scores were found to be significant between the 0.1 and 0.05 level of probability of chance occurrence, with 500 and 1,000 p.s.i. resulting in a superior body and texture.
Advanced Radiation-Resistant Ceramic Composites

Ceramic matrix composites (CMC’s), particularly silicon carbide (SiC) fiber-reinforced SiC-matrix (SiC/SiC) composites, have been studied for advanced nuclear energy applications for more than a decade. The perceived potentials for advanced SiC/SiC composites include the ability to operate at temperature regimes much higher than heat-resistant alloys, the inherent low inducedactivation nuclear properties, and the tolerance against neutron irradiation at high temperatures. This paper reviews the recent research and development of the advanced radiation-resistant SiC/SiC composites for nuclear applications. Additionally, remaining general and specific technical issues for SiC/SiC composites for nuclear applications are discussed.
Abstract 1018: Inhibition of BET bromodomain targets genetically diverse glioblastoma.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Epigenetic regulations have been increasingly recognized as an integral part of tumor biology and attractive therapeutic targets. The bromodomain and extra-terminal domain (BET) proteins specifically recognize acetylated lysine residues on histone tails. BET bromodomain inhibition with a first-in-class inhibitor JQ1 reduces expression of a broad spectrum of growth promoting and antiapoptotic genes, including c-Myc, resulting in suppression of several hematopoietic cancers and NUT midline carcinoma. We and other groups have previously reported the critical role of c-Myc in glioblastoma stem cells. Here, we demonstrated broad antineoplastic effects of JQ1 both in ex vivo cultures and orthotopic models using a panel of glioblastoma tumors carrying different genetic lesions. JQ1 induced marked cell cycle arrest and apoptosis in association with p21WIP1/CIP1 induction and hTERT, Bcl-2 and Bcl-xL reduction. Consistent with previous studies, JQ1 decreased c-Myc expression in glioblastoma. However, exogenous c-Myc did not significantly protect glioblastoma from JQ1, unlike the observations in hematopoietic cancers. Cells genetically engineered for Akt hyperactivation or p53/Rb inactivation did not compromise JQ1 efficacy, suggesting that these signaling pathways commonly altered in glioblastoma may not confer resistance to JQ1. Taken together, our results suggest potentially broad therapeutic utility of BET bromodomain inhibition for treating genetically diverse glioblastoma tumors. Citation Format: Jialiang Wang, Zhixiang Cheng. Inhibition of BET bromodomain targets genetically diverse glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1018. doi:10.1158/1538-7445.AM2013-1018
The Perception of obesity by normal-weight versus obese school-age children

There appears to be little difference between obese and normal weight children in their perceptions of obese individuals. Both groups of children endorse negative stereotypes of obese persons when information about body type is the only available cue. However, these stereotypes may be somewhat negated in the minds of both groups when the obese person is physically attractive and/or is in a position of authority.
Effects of anticholinergic medication on memory in schizophrenia.

Abstract Verbal memory and reaction time of ten schizophrenia patients were compared at two different serum anticholinergic levels. Verbal recall was worse at higher drug levels, while reaction time tended to be improved by anticholinergic treatment. Implications for studies of memory in schizophrenia are considered.
Collective Algorithms for Multiported Torus Networks

Modern supercomputers with torus networks allow each node to simultaneously pass messages on all of its links. However, most collective algorithms are designed to only use one link at a time. In this work, we present novel multiported algorithms for the scatter, gather, all-gather, and reduce-scatter operations. Our algorithms can be combined to create multiported reduce, all-reduce, and broadcast algorithms. Several of these algorithms involve a new technique where we relax the MPI message-ordering constraints to achieve high performance and restore the correctordering using an additional stage of redundant communication. According to our models, on an n-dimensional torus, our algorithms should allow for nearly a 2n-fold improvement in communication performance compared to known, single-ported torus algorithms. In practice, we have achieved nearly 6x better performance on a 32k-node 3-dimensional torus.
Kinetics-Based Modeling of Bond-Metal Dissolution and IMC During Soldering

Soldering has become an indispensable joining process in the electronic packaging industry. The industry is aiming for the use of environment friendly lead-free solders. All the lead-free solders are high tin-containing alloys. During the soldering process, an intense interaction of metallization on PCB and tin from the solder occurs at the metallization/solder interface. Intermetallic compound (IMC) is formed at the interface and subsequently PCB bond-metal (substrate) is dissolved into the molten solder. In the present study the terms bond-metal and substrate will be used interchangeably and the term 'substrate' refers to the top layer of the PCB which comes in contact with the molten solder during soldering reaction. Thickness of the intermetallic phase formed at the joint interface and amount of substrate lost is critical in achieving reliable solder joints. During the wet phase of soldering process, the IMC does not grow as layered structure; rather it takes the shape of scallops. The growth of scalloped IMC during the solder/substrate interaction entails complicated physics. Understanding of the actual kinetics involved in the formation of IMC phase is important in controlling the process to achieve desired results. This paper presents theoretical analysis of the kinetics involved in the formation of the scalloped intermetallic phase. The intermetallic phase growth is experimentally investigated to support the underlying kinetics of the process. Numerical model has been suggested to translate the physics of the process. The model is based on the basic mass diffusion equations and can predict the substrate dissolution and IMC thickness as a function of soldering time.Copyright © 2006 by ASME
Fungus-Growing Ants

Fungus-growing ants (Attini) are in reality unique fungus-culturing insects.There are several hundred species in some dozen genera, of which Acromyrmex and Atta are the conspicuous leaf-cutters. The center of their activities is the fungus garden, which is also the site of the queen and brood. The garden, in most species, is made from fresh green leaves or other vegetal material. The ants forage for this, forming distinct trails to the vegetation that is being harvested. The cut leaves or other substrate are brought into the nest and prepared for the fungus. Fresh leaves and flowers are cut into pieces a millimeter or two in diameter; the ants form them into a pulpy mass by pinching them with the mandibles and adding saliva. Anal droplets are deposited on the pieces, which are then forced into place in the garden. Planting of the fungus is accomplished by an ant9s picking up tufts of the adjacent mycelium and dotting the surface of the new substrate with it. The combination of salivary and anal secretions, together with the constant care given by the ants, facilitates the growth of the ant fungus only, despite constant possibilities for contamination. When the ants are removed, alien fungi and other organisms flourish. A mature nest of Atta Sexdens may consist of 2000 chambers, some temporarily empty, some with refuse, and the remainder with fungus gardens. Thousands of kilograms of fresh leaves will have been used. A young laboratory colony of Atta cephalotes will use 1 kilogram of fresh leaves for one garden. The attines are the chief agents for introducing organic matter into the soil in tropical rain forests; this matter becomes the nucleus for a host of other organisms, including nematodes and arthropods, after it is discarded by the ants. One ant species cultures a yeast; all others grow a mycelium. In the higher species the mycelium forms clusters of inflated hyphae. Mycologists accept as valid two names for confirmed fruiting stages: Leucocoprinus ( or Leucoagaricus) gongylophora (Moeller 1893) and Lepiota n. sp.
Changes in fat cell morphology during lactation in the mouse

A comparison was made of changes in the morphology of fat cells in the intact mammary gland, de-epithelialized mammary fat pad, and the parametrial fat pad of female C3H mice during lactation. Mammary fat pad not in contact with actively secretory epithelium shows partial loss of fat during lactation (systemic effect) while in the presence of such epithelium there is much greater loss of fat (systemic plus local effect). In the same animal the parametrial fat pad shows greater depletion during lactation than the de-epithelialized mammary fat pad. The extent of fat depletion is dependent on the number of nursing young and the duration of lactation. In the intact mammary gland and parametrial fat pad, marked change in fat cell structure is not seen in pregnancy except possibly at the very end; after weaning, replenishment of lactation-depleted fat cells is conspicuous by 48 hours. The basic ultrastructure of mammary fat cells and the kinds of changes they undergo during depletion do not differ from those described for other mammalian adipose tissues.
Plasma diagnostics using Kα satellite emission spectroscopy in light ion beam fusion experiments

K α satellite spectroscopy can be a valuable technique for diagnosing conditions in high energy density plasmas. K α emission lines are produced in intense light ion beam plasma interaction experiments as 2p electrons fill partially open 1s shells created by the ion beam. In this paper, we present results from collisional-radiative equilibrium (CRE) calculations which show how K α emission spectroscopy can be used to determine target plasma conditions in intense lithium beam experiments on Particle Beam Fusion Accelerator-II (PBFA-II) at Sandia National Laboratories. In these experiments, 8-10 MeV lithium beams with intensities of 1-2 TW/cm 2 irradiate planar multilayer targets containing a thin Al tracer. K α emission spectra are measured using an X-ray crystal spectrometer with a resolution of λ/Δλ ≃ 1200. The spectra are analyzed using a CRE model in which multilevel (N L ∼ 10 3 ) statistical equilibrium equations are solved self-consistently with the radiation field and beam properties to determine atomic level populations. Atomic level-dependent fluorescence yields and ion-impact ionization cross sections are used in computing the emission spectra. We present results showing the sensitivity of the K α emission spectrum to temperature and density of the Al tracer. We also discuss the dependence of measured spectra on the X-ray crystal spectral resolution, and how additional diagnostic information could be obtained using multiple tracers of similar atomic number.
PCr/ATP ratio mapping of the human head by simultaneously imaging of multiple spectral peaks with interleaved excitations and flexible twisted projection imaging readout trajectories at 9.4 T.

Quantitative 31P magnetic resonance imaging of the whole human brain is often time-consuming even at low spatial resolution due to the low concentrations, long T1 relaxation times, and low detection sensitivity of phosphorus metabolites. We report herein the results of combining the increased detection sensitivity of an ultra-high field 9.4 T scanner designed for human imaging with a new pulse sequence termed simultaneously imaging of multiple spectral peaks with interleaved excitations and flexible twisted projection imaging readout trajectories to rapidly sample multiple resonances in the 31P spectrum. The phosphocreatine and γ-adenosine triphosphate images, obtained simultaneously from the entire human head, are demonstrated at 1.5 cm isotropic nominal resolution in a total acquisition time of 33 min. The phosphocreatine/γ-adenosine triphosphate ratio calculated for brain parenchyma (1–2) and the superficial temporalis muscle (3–5) are in agreement with literature values. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Simultaneous cervical diffuse idiopathic skeletal hyperostosis and ossification of the posterior longitudinal ligament resulting in dysphagia or myelopathy in two geriatric North Americans

BACKGROUND Cervical diffuse idiopathic skeletal hyperostosis (DISH) and ossification of the posterior longitudinal ligament (OPLL) rarely coexist in the North American population. Here, different surgical strategies were used to manage simultaneous DISH and OPLL resulting in dysphagia or myelopathy in two geriatric patients. METHODS A 74-year-old male with esophageal compression and dysphagia attributed to DISH, and cord compression with myelopathy due to OPLL, was treated with a cervical laminectomy followed by anterior DISH resection. On the other hand, an 80-year-old male with asymptomatic DISH but moderate myelopathy (Nurick Grade III) secondary to OPLL required only a cervical laminectomy. RESULTS In the first patient, dysphagia resolved within 3 months of surgery, while in the second individual, myelopathy improved to Nurick Grade I (mild myelopathy) within 6 months postoperatively. Improvement in both patients was maintained 1 year after surgery. CONCLUSIONS While DISH and OPLL may coexist in geriatric patients, only those with dysphagia should undergo DISH resection, while others demonstrating myelopathy should have laminectomy alone.
Influence of pig age on virus titer and bactericidal activity of porcine reproductive and respiratory syndrome virus (PRRSV)-infected pulmonary intravascular macrophages (PIMs).

Twelve pigs (six 4-week-old and six 4-month-old cross-bred, specific pathogen free pigs) were used as donors for both pulmonary intravascular macrophages (PIMs) and pulmonary alveolar macrophages (PAMs). The PIMs and PAMs were infected in vitro with low (ISU-55) or high (VR-2385) virulence strains of PRRSV at 1 multiplicity of infection (m.o.i.) for comparisons of virus titers at 48 h post infection (PI). PIMs were as permissive as PAMs to infection with both PRRSV isolates yielding similar progeny titers (10(4.81) vs. 10(5.22) TCID50/ml, respectively). Both ISU-55 and VR-2385 were able to infect PIMs and no significant difference in virus replication as measured by virus titers between isolates was found (10(5.33) vs. 10(4.69) TCID50/ml, respectively). PIMs from 4-weak-old pigs yielded a higher virus titer following PRRSV infection than PIMs from 4-month-old pigs (10(5.43) vs. 10(4.59) TCID50/ml, respectively; p < 0.02). VR-2385-infected PIMs had significantly decreased bactericidal (Staphylococcus aureus) activity compared with uninfected PIMS at 48 h PI (p < 0.05). There was no difference in bactericidal activity between ISU-55 (low virulence)-infected PIMs and VR-2385 (high virulence)-infected PIMs. Both ISU-55 and VR-2385 infection significantly decreased the production of superoxide anion (SOA) at 24 and 48 h PI (p < 0.01). In conclusion, (1) PRRSV had a detrimental effect on bactericidal activity and SOA production of PIMs, (2) PIMs from younger pigs were more permissive to PRRSV infection, and (3) the selected PRRSV strains, which differ in their abilities to induce pneumonia in vivo were not different when tested in vitro by measuring virus titer and bactericidal functions.
Searching for Planets by Differential Astrometry with Large Telescopes

Traditional astrometric methods are limited in accuracy by the atmosphere in a way that does not show much improvement with increased telescope aperture. However, there is the potential for very high accuracy with large telescopes if advantage can be taken of these factors: First, the differential atmospheric distortion of images of closely adjacent stars is less with larger aperture; second, the diffraction limit is sharper, and third, photon statistics are improved. In this paper we analyze and give experimental tests of techniques that could be applied to the detection of planets with the mass of Jupiter or Uranus, if they are present in nearby binary star systems.
Comparison of four bifunctional chelates for radiolabeling monoclonal antibodies with copper radioisotopes: biodistribution and metabolism.

The bifunctional chelating agents (BFCs), 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-1,4 ,8, 11-tetraacetic acid (BAT), 6-[p-(isothiocyanato)benzyl]-1,4,8, 11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (SCN-TETA), 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid (CPTA), and 1-[(1,4, 7,10,13-pentaazacyclopentadec-1-yl)methyl]benzoic acid (PCBA), were synthesized and conjugated to the anti-colorectal monoclonal antibody (mAB), 1A3, and antibody fragments, 1A3-F(ab')2, for radiolabeling with 64,67CU and comparison in animal models. In vivo metabolism studies were carried out in liver and kidneys in order to correlate the nature of the metabolites formed to the uptake and retention of the radiolabel in each organ. Animal biodistribution studies were performed in Golden Syrian hamsters bearing the GW39 human colon cancer tumors and in normal Sprague-Dawley rats. All conjugates showed good tumor uptake in hamsters. Biodistribution in rats showed that 64CU-BAT-2IT-1A3 had the lowest liver and kidney uptake of the intact 1A3 conjugates (p 85% degraded in the kidneys to small molecular weight metabolites by 1 day post-injection. In contrast, in the liver at 1 day post-injection, greater than 70% of the 67Cu-labeled 1A3 conjugates were unmetabolized. By day 5, a 35 kDa peak appeared in the liver of rats injected with the 67 Cu-labeled 1A3 conjugates, possibly due to transchelation of the 67Cu to proteins. Superoxide dismutase chromatographically elutes at the same retention time as this 67Cu-labeled metabolite. The TLC data indicate that the low molecular weight metabolite (< 5 kDa) of both 67Cu-CPTA-1A3 and 67Cu-CPTA-1A3-F(ab')2 conjugates co-chromatographed with a 67Cu-CPTA-epsilon-lysine standard. Our data suggest that chelate charge and lipophilicity play a large role in kidney retention of 64/67Cu-labeled BFC-1A3-F(ab')2 conjugates, while transchelation of the copper label appears to be the major factor for liver accumulation of 64/67Cu-labeled BFC-1A3 conjugates.
Recent Observations of Variability in the Path and Vertical Structure of the Alaskan Stream

Abstract Current records were recently obtained from two sites on the Continental slope southwest of Kodiak Island. At the inshore site (10-month record), flow mainly resembled the weak shelf-break flow typical of the Gulf of Alaska. Except for two periods, each of ∼3 months duration, the offshore site (31-mouth record) was in the path of the Alaskan Stream. During the Alaskan Stream segments, flow Characteristics (low eddy energy, high vertical coherence, and high stability) were similar to those in the stream at other locations. When the stream was absent from the offshore site, it made a seaward excursion of ∼50 km as evidences by satellite-tracked drifters. The cause of this migration is unclear. During a period of ∼6 months, a subsurface velocity maximum was measured at 165 m. Flow near 1000 m was very weak for almost two years; geostrophic flow estimates, however, suggest this is a rare situation.
Abstract 1081: Rapamycin is a chemopreventive and chemotherapeutic agent for ras-driven epidermal squamous cell carcinoma: evidence from mouse models.

Braf inhibitors are clinically important agents for the treatment of advanced melanoma however secondary cutaneous tumors are a common side effect; non-melanoma skin cancers (NMSCs) arise in 15-30% of patients on Braf inhibitor therapy and 60% of these harbor ras mutations. NMSC also occurs in 40% of organ transplant patients receiving immunosuppressive therapy, and switching from a calcineurin inhibitor-containing regimen to rapamycin reduces the incidence. To examine the effect of rapamycin on ras-driven epidermal squamous cell tumors, we treated mutant K-RasLA2 mice with rapamycin or vehicle by intraperitoneal injection and found that rapamycin prevented the development of squamous skin tumors (0/21 vs 6/24; p=0.04), and also rapidly reduced the tumor size. To explore this effect we employed a syngeneic orthotopic grafting model using H-Ras mutant primary murine keratinocytes to determine if rapamycin could hamper the ability of a Braf inhibitor to enhance squamous skin tumor growth. Similar to results in the K-RasLA2 model, rapamycin alone diminished the growth of tumors (size difference; 334.5 vs 22.3mm3; p=0.03), and decreased the volume even more in the presence of a Braf inhibitor (size difference; 699.6 vs 17.6 mm3; p=0.02). Treatment of established tumors with rapamycin resulted in significant tumor shrinkage even in the continuous presence of a Braf inhibitor. Size reduction was 78.7% and 66.7% in Braf inhibitor untreated and treated groups respectively. In vitro, Braf inhibition enhanced mutant H-Ras-induced activation of the Raf-ERK and mTOR pathways in keratinocytes, while rapamycin addition blocked the activation of signaling pathways and decreased cell proliferation. Taken together, rapamycin prevents murine skin tumor development arising from oncogenic mutations in two distinct types of ras gene alleles, and reduced the tumor size by inhibiting downstream oncogenic pathways. Rapamycin may have clinical application as a chemopreventive and therapeutic agent for patients at high risk to develop ras-driven NMSC, including those receiving Braf inhibitors. Citation Format: Hiroshi Kitagawa, Christophe Cataisson, Alessandra Handisurya, Patricia M. Day, Stuart H. Yuspa, Phillip A. Dennis. Rapamycin is a chemopreventive and chemotherapeutic agent for ras-driven epidermal squamous cell carcinoma: evidence from mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1081. doi:10.1158/1538-7445.AM2013-1081
Durability choice with differentiated products

Abstract In a two-period setting we explore the impact of a related non-durable good or service on a monopolists’ choice of product durability. We show that a renting firm will provide the social efficient cost-minimizing durability independent of the related non-durable product. Thus Swan’s [Swan, P., 1970. Durability of consumption goods. American Economic Review 60, 884–894; Swan, P., 1971. The durability of goods and the regulation of monopoly. Bell Journal of Economics and Management Science 2, 347–357] market independence result can be extended to include durable goods renters that manufacture related non-durables. This finding, however, does not extend to sales markets. With sales, the monopolist will practice planned obsolescence (manufacture goods with uneconomically short lives). We find that planned obsolescence is maximized when the related output is highly complementary with the durable good. This indicates that in durable products markets, such as the electronics industry, public policies that encourage the adoption of complements for the durable may well lead to a less efficient durability choice.
Micromachined free-space integrated optics

We report a novel surface-micromachined micro-optical bench (MOB) technology which enables us to monolithically integrate 'flipped-up' free-space optical elements with micro-positioners and micro- actuators. This technology allows complete optical systems be implemented on a single Si chip using IC-like microfabrication processes. We have, for the first time, successfully fabricated micro-Fresnel lenses, mirrors, beam-splitters, gratings, and precision optical mounts, as well as rotational stages and other micro- positioners. Self-aligned hybrid integration with edge-emitting lasers and vertical cavity surface-emitting lasers (VCSEL) are also demonstrated for the first time. The MOB technology could significantly reduce the size, weight, and cost of most optical systems, and has a significant impact on optical switching, optical data storage, optoelectronic packaging.
A comparison of combination of botox (botulinum toxin) and nitroglycerin in the treatment of chronic anal fissures

A comparison of combination of botox (botulinum toxin) and nitroglycerin in the treatment of chronic anal fissures
Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase.

A recent crystallographic study of recombinant human O6-alkylguanine−DNA alkyltransferase (hAGT) revealed a previously unknown zinc atom [Daniels et al., (2000) EMBO J. 19, 1719−1730]. The effects of zinc on the properties of hAGT are reported here. In bacterial expression systems, recombinant hAGT was produced in increasingly larger quantities when growth media are supplemented with up to 0.1 mM ZnCl2. Metal-enriched hAGT samples had a 5-fold increase in repair rate constant over conventionally purified protein samples and a 60-fold increase over metal-stripped hAGT. In addition, mutants of the zinc-binding residues had decreases in zinc occupancy that correlated with reductions in repair rate. Zinc modulation did not abolish the repair capacity of a fraction of the hAGT population, as evidenced by the stoichiometric reaction with an oligodeoxyribonucleotide substrate. Zinc occupancy had a similar effect on the rate of reaction with O6-benzylguanine, a free base substrate, as on the repair of methylated ...
Uric acid in CHF: Marker or player in a metabolic disease?

Cardiovascular medicine is a story of success in many aspects, especially with regard to improved outcome in acute cardiovascular events. An immediate consequence is of course a growing prevalence of cardiovascular diseased patients. A wealth of epidemiological data from recent decades highlights the fact that we are confronted with an epidemic development in CHF. Indeed, the prevalence of CHF has been estimated at 4.8 million in the United States alone. To meet this challenge, much research has focused on understanding the complex pathophysiology of CHF. This has led to deduce that CHF is much more than mere pump failure. Neuroendocrine activation, for example, has been recognised as a cornerstone in CHF pathophysiology and has become a major target in the treatment of CHF patients. On the other hand, immune activation [1] and, more recently, hormonal and metabolic derangement [2], have emerged as significant contributors to CHF morbidity and mortality. Importantly, hyperuricaemia has been established as a characteristic feature in CHF with both symptomatic and prognostic significance. In this issue of International Journal of Cardiology, Jankowska et al. report the significance of hyperuricaemia to predict survival in patients with CHF [3]. This study is in line with earlier reports showing uric acid (UA) as a strong and independent prognostic marker in moderate to severe CHF [4]. Jankowska et al. expand the previous data on prognostic value of UA to a broader patient population such as patients with mild to moderate CHF (mean NYHA class 2.3, 63% in NYHA class I and II, mean LVEF 32%). The investigators observed that more consistent adherence to beta blocker
PHYSIOLOGIC AND STRUCTURAL CHANGES ASSOCIATED WITH AGING SKIN

The spectrum of photoaging in human skin shows a recognizable progression from subtle to profound, reflecting the various anatomic and structural changes that appear with aging skin. Qualification and quantification of these changes on both the macroscopic and microscopic levels enable the physician to select and evaluate appropriate therapeutic approaches to the problem of chronic solar damage. Comparative studies remain to be done that will further refine our abilities to match the right solutions to the recognized problems.
A Low-Cost Smartphone-Based Electrochemical Biosensor for Point-of-Care Diagnostics.

This paper describes the development of a smartphone-based electrochemical biosensor module. The module contains a low power potentiostat that interfaces and harvests power from a smartphone through the phone’s audio jack. A prototype with two different potentiostat designs was constructed and used to conduct proof of concept cyclic voltammetry experiments with potassium ferro-/ferricyanide (K4[Fe(CN)6] / K3[Fe(CN)6]) in a side-by-side comparison with a laboratory grade instrument. Results show that the module functions within the available power budget and that the recovered voltammogram data matches well with the data from an expensive bench top tool. Excluding the loses from supply rectification and regulation, the module consumes either 5.7 mW or 4.3 mW peak power, depending on which of the two discussed potentiostat designs is used. At single quantity pricing, the hardware for the prototype device costs less than $30.
Production of hypertension in adrenalectomized rats given hypertonic salt solution to drink.

The adrenal glands of the rat do not appear to be necessary for development of hypertension induced by administration of hypertonic NaCl solution as drinking fluid. Systolic blood pressures of these rats became elevated within 3 to S weeks after treatment began. The lowest concentration of salt solution which significantly elevated blood pressure was 1.75‰. Renal hypertrophy ac-companied the elevated blood pressure in most cases and cardiac hypertrophy in some cases. The life span of the adrenalectomized rats receiving hypertonic salt solution to drink was less than that of untreated adrenalectomized rats.
Coherent photodissociation-recombination dynamics of I2 isolated in matrix Ar and Kr

Time-resolved studies of photodissociation-recombination dynamics of I2 isolated in Ar and Kr matrices, are reported.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Membership-concealing overlay networks

We introduce the concept of membership-concealing overlay networks (MCONs), which hide the real-world identities of participants. We argue that while membership concealment is orthogonal to anonymity and censorship resistance, pseudonymous communication and censorship resistance become much easier if done over a membership-concealing network. We formalize the concept of membership concealment, discuss a number of attacks against existing systems and present real-world attack results. We then propose three proof-of-concept MCON designs that resist those attacks: one that is more efficient, another that is more robust to membership churn, and a third that balances efficiency and robustness. We show theoretical and simulation results demonstrating the feasibility and performance of our schemes.
Effect of combined thyroxin-cortisone-growth hormone therapy on hematopoiesis in hypophysectomized rats.

SummaryPrevious work has shown that a combined thyroxin-cortisone therapy in hypophysectomized rats will eliminate the anemia and induce a marked decrease in peripheral white cells; this was accompanied by severe hypoplasia of the bone marrow. It has also been shown that growth hormone increases peripheral white cell count in hypophysectomized rats but has no effect on peripheral anemia; the bone marrow was hyperplastic. Adding growth hormone to the thyroxin-cortisone therapy resulted in repair of post-hypophysectomy anemia, in normal histological appearance of bone marrow, in normal total number of cells/mm3 of marrow tissue, and in values for myeloid elements/mm3 of marrow and peripheral white cells slightly above normal. The values for erythroid elements/mm3 of marrow averaged 82% of normal. These hematological findings were accompanied by a normal oxygen consumption.
Postnatal Changes in Cathepsin D in Rat Neural Tissue

: Cathepsin D, an aspartyl endopeptidase, was analyzed in cortex from forebrain and cerebellum, spinal cord, and optic and sciatic nerves, and in the liver of rats from 1 to 120 days of age. Cathepsin D was quantitated in tissue extracts by measurement of enzyme specific activity on a substrate of [methyl-14C]-methylated hemoglobin and by radioimmunoassay. Immunocytochemistry was used to ascertain the identity of the mixed cell types that contributed to the cathepsin D detected. As quantitated by radioimmunoassay, immunoreactive cathepsin D varied between 0.2 and 1 ng/μg of total protein. Maximum activity occurred at approximately the 15th postnatal day; the least amount of immunoreactive cathepsin D was found at 30 or 60 days of age. A subsequent increase of varying magnitude occurred at postnatal day 120. There was good correspondence between immunoreactive enzyme and enzyme specific activity, which ranged from 1 to 4 ng/μg of total protein, and the activities determined by the two methods provided similar, but not identical, developmental profiles. Cathepsin D was demonstrated by immunocytochemistry to be present in most neurons, in all choroid plexus epithelium, and in certain oligodendrocytes from the first postnatal day. Cathepsin D was present in oligodendrocytes in cord lateral funiculi and optic nerve by the first postnatal day, and by the sixth postnatal day many oligodendrocytes were abundantly stained. In contrast, oligodendrocytes in the corpus callosum and in the cerebellar white matter did not contain demonstrable cathepsin D until postnatal days 10 and 15, respectively. These results indicate a role for cathepsin D during the postnatal development of rat CNS and suggest that this proteinase may be involved in the steps of myelination.
A Novel Function for BRCA1 In Crosslink Repair

In this issue of Molecular Cell, Bunting et al. (2012) provide new evidence that BRCA1 plays an important role in DNA interstrand crosslink repair that is distinct from its established function in promoting DNA end resection during homologous recombination.