cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5429: The combination of Apo2L/Trail and a death receptor 5 agonist antibody leads to enhanced antitumor activity in mouse syngeneic tumor models

Background: Death receptor-5 (DR5, TR2, TRAIL-R2) is a death domain-containing receptor that induces an apoptosis signaling cascade when engaged by Apo2L/TRAIL or a DR5 agonist antibody1. Many tumor cell lines express DR5 and are sensitive to DR5 agonists2. Despite pre-clinical efficacy, several DR5 agonists have failed to advance beyond phase II clinical trials due to poor clinical efficacy. Strong synergystic activity was observed with the combination of Apo2L/TRAIL and AMG655 (DR5 agonist antibody) pre-clinically in vitro and in vivo (manuscript submitted). Although Apo2L/TRAIL and AMG655 were well tolerated in clinical trials when delivered as single agents3, the efficacy and safety profile of combining Apo2L/TRAIL and AMG655 has not been investigated. Objective: To determine a therapeutic index for Apo2L/TRAIL + DR5 agonist antibody combination treatment in mouse syngeneic tumor cell lines and xenograft models. Results: To evaluate both efficacy and tolerability, we utilized a mouse monoclonal antibody, MD5-1, that recognizes the mouse DR5 (mDR5) receptor. In vitro, treatment with Apo2L/TRAIL + MD5-1 enhanced cell killing in multiple mouse tumor lines, which all expressed mDR5 at similar levels. In vivo, we observed marked anti-tumor activity after treatment with Apo2L/TRAIL at 5 mg/kg for 5 days per week and MD5-1 at 1ug/mouse for 2 days per week. In the Renca model, Apo2L/TRAIL + MD5-1 treatment resulted in enhanced efficacy compared to either single agent (> 92% inhibition; p Conclusion: Our preclinical findings provide evidence that a therapeutic index can be achieved for Apo2L/TRAIL in combination with a DR5 agonist antibody and may be an effective strategy for cancer therapy. Citation Format: Timothy Sullivan, Daniel Branstetter, Pamela Holland, Tammy L. Bush. The combination of Apo2L/Trail and a death receptor 5 agonist antibody leads to enhanced antitumor activity in mouse syngeneic tumor models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5429. doi:10.1158/1538-7445.AM2014-5429
Modeling hot spring chemistries with applications to martian silica formation

Abstract Many recent studies have implicated hydrothermal systems as the origin of martian minerals across a wide range of martian sites. Particular support for hydrothermal systems include silica (SiO2) deposits, in some cases >90% silica, in the Gusev Crater region, especially in the Columbia Hills and at Home Plate. We have developed a model called CHEMCHAU that can be used up to 100 °C to simulate hot springs associated with hydrothermal systems. The model was partially derived from FREZCHEM, which is a colder temperature model parameterized for broad ranges of temperature ( A theoretical simulation of silica and calcite equilibrium shows how calcite is least soluble with high pH and high temperatures, while silica behaves oppositely. Such influences imply that differences in temperature and pH on Mars could lead to very distinct mineral assemblages. Using measured solution chemistries of Yellowstone hot springs and Icelandic hot springs, we simulate salts formed during the evaporation of two low pH cases (high and low temperatures) and a high temperature, alkaline (high pH) sodic water. Simulation of an acid-sulfate case leads to precipitation of Fe and Al minerals along with silica. Consistency with martian mineral assemblages suggests that hot, acidic sulfate solutions are plausibility progenitors of minerals in the past on Mars. In the alkaline pH (8.45) simulation, formation of silica at high temperatures (355 K) led to precipitation of anhydrous minerals (CaSO4, Na2SO4) that was also the case for the high temperature (353 K) low pH case where anhydrous minerals (NaCl, CaSO4) also precipitated. Thus we predict that secondary minerals associated with massive silica deposits are plausible indicators on Mars of precipitation environments and aqueous chemistry. Theoretical model calculations are in reasonable agreement with independent experimental silica concentrations, which strengthens the validity of the new CHEMCHAU model.
Synthesis, structure and magnetic properties of an oxo-bridged dinuclear iron(III) complex [(TPyA)FFeIIIOFeIIIF(TPyA)](BF4)2 · 0.5MeOH (TPyA = tris(2-pyridylmethyl)amine) containing the FFeIIIOFeIIIF linkage

Abstract The reaction of [Fe II (H 2 O) 6 ](BF 4 ) 2 with tris(2-pyridylmethyl)amine (TPyA) and triethylamine in methanol under aerobic conditions forms [(TPyA)FFe III OFe III F(TPyA)](BF 4 ) 2 · 0.5MeOH ( 1 ), in which each Fe(III) ion is coordinated to a TPyA and an F − ion as well as an oxo ion (O 2− ) linking two Fe(III) ions. 1 has offset face-to-face π–π interactions between the dimers, and possesses a supramolecular network structure. The magnetic susceptibility of 1 can be fit with g = 2.0, J /k B = − 153 K (106 cm −1 ), and θ = − 0.3 K [ H = − 2 JS a · S b ]. These indicate that very strong antiferromagnetic interactions occur via the oxo bridge within the Fe(III) dimer and weak antiferromagnetic interactions between the dimers.
Comment on: Incidence and Risk of Hypertension with Ramucirumab in Cancer Patients: A Meta-Analysis of Published Studies

A meta-analysis by Wang et al. [1] assessing hypertension risk with ramucirumab use in patients with cancer was recently published in Clinical Drug Investigation. The authors concluded that ramucirumab treatment was associated with a significant increase in hypertension risk in cancer patients, and warned that treatment efficacy may be reduced due to the need to manage hypertension. We acknowledge hypertension as an adverse reaction for ramucirumab. This is highlighted in the compound’s package insert. However, the presentation by Wang et al. of the clinical severity of these events is misleading. An analysis of pooled data was performed across six Phase III trials (ramucirumab N = 2748, placebo N = 2248). In this analysis, 21.3 % (n = 585) of patients taking ramucirumab experienced hypertension of any grade during treatment, versus 7.4 % (n = 167) for patients taking placebo. This translates to an increase of 13.9 % in the number of patients developing any grade hypertension, or about 1 in 7. More severe hypertension (≥Grade 3) was seen in 9 % (n = 246) of patients taking ramucirumab, and 2.5 % (n = 57) of patients taking placebo, a 6.5 % increase, or approximately 1 in 15 patients. These percentages coincide relatively well with the data stated in the Wang et al. meta-analysis. However, of those patients experiencing hypertension, only eight cases (<2 %) led to discontinuation of any study treatment, showing that the hypertension was manageable. These additional data suggest that although hypertension is a recognized adverse event in ramucirumab clinical trials, it was manageable and resulted in low rates of discontinuation across six multinational clinical phase 3 trials. Therefore, the suggestion by Wang et al. that hypertension can have an effect on treatment efficacy is unsupported by data.
Is tubal ligation a risk factor for low bone density and increased risk of fracture

Abstract OBJECTIVE: Osteoporosis is a major women's health problem, because it is responsible for about 1.3 million fractures in the United States each year. Estrogen deficiency is a major risk factor in the pathogenesis of osteoporosis. Recent evidence has indicated that tubal ligation may cause menstrual dysfunction and estrogen deficiency. This study examined the association between tubal ligation and bone mass in a group of elderly postmenopausal women. STUDY DESIGN: Subjects were 2215 white women ≥65 years old participating in the Baltimore center of the Study of Osteoporotic Fractures. Bone mineral density of the proximal and distal radius and the calcaneus was measured by single photon absorptiometry. Multiple regression analysis was performed to determine whether tubal ligation had an independent effect on bone density. The effect of tubal ligation on the risk of hip and osteoporotic fractures was estimated by Cox proportional hazards model. RESULTS: Women who reported a tubal ligation had lower, although not statistically significant, bone density of the radius and calcaneus. The relative risk of hip (1.05, 95% confidence limit 0.84 to 1.32) and osteoporotic fractures (1.01, 0.80 to 1.29) was not significantly increased in women with tubal ligation. CONCLUSION: We conclude that elderly women who had a tubal ligation have small changes in bone density that are not of sufficient magnitude to increase their risk of osteoporotic fractures.
Global Darwin: Eastern enchantment.

People from Egypt to Japan used Darwin's ideas to reinvent and reignite their core philosophies and religions, says Marwa Elshakry in the first of four weekly pieces on how evolution was received around the world.
Mechanistic insight into the photosensory versatility of DXCF cyanobacteriochromes.

Cyanobacteriochromes (CBCRs) are photosensory proteins related to the red/far-red phytochromes. Like phytochromes, CBCRs use linear tetrapyrrole (bilin) chromophores covalently attached via a thioether linkage to a conserved Cys residue also found in plant and cyanobacterial phytochromes. Unlike almost all phytochromes, CBCRs require only an isolated GAF domain to undergo efficient, reversible photocycles that are responsible for their broad light sensing range, spanning the visible to the near ultraviolet (UV). Sensing of blue, violet, and near-UV light by CBCRs requires another Cys residue proposed to form a second linkage to the bilin precursor. Light triggers 15,16-double bond isomerization as in phytochromes. After photoisomerization, elimination of the second linkage frequently occurs, thus yielding a large red shift of the stable photoproducts. Here we examine this process for representative DXCF CBCRs, a large subfamily named for the conserved Asp-Xaa-Cys-Phe motif that contains their second Cys r...
Effects of a mandatory safety belt law on hospital admissions

Although the effectiveness of automobile safety belts in reducing risk of serious injury in traffic crashes is well documented, safety belt use in many U.S. jurisdictions remains low. Michigan's mandatory safety belt law for front-seat occupants, implemented in July 1985, is one of 34 similar laws in the United States intended to increase belt use and reduce crash-related injuries. Using time-series intervention analyses of data from 14 hospitals throughout the state, we found a 19% reduction in the rate of admitted patients for all automobile occupant injuries and a 20% reduction in the rate of admitted patients with extremity injuries following implementation of the safety belt law. The utility of hospital data for the evaluation of interventions like the safety belt law reinforce the importance of consistently recording E-codes for all injury patients.
Improved measures of quality for the atomic pair distribution function

The introduction of neutron spallation-source instruments, such as the General Materials Diffractometer (GEM) at ISIS, allows measurement of pair distribution function (PDF) data at significantly higher rates than previously possible. As a result of the increased rate, a single experiment can produce over a hundred individual runs. Manual processing of all these data using traditional methods becomes inconvenient and inefficient. This article presents quality criteria that help produce automated direct Fourier transformed PDFs of quality similar to hand-processed data, and compares optimization methods.
Tu1394 Efficacy of Endoscopic Treatment of Symptomatic Upper Gastrointestinal Leaks and Fistulas Post-Bariatric Surgery: Report of 25 Cases

Tu1394 Efficacy of Endoscopic Treatment of Symptomatic Upper Gastrointestinal Leaks and Fistulas Post-Bariatric Surgery: Report of 25 Cases Alireza Ghotb, Janak N. Shah, Kenneth F. Binmoeller, Frank Weilert, Yasser M. Bhat Interventional Endoscopy Services, California Pacific Medical Center, San Francisco, CA Background: Anastomotic leaks causing abscesses and upper gastrointestinal fistulae are a serious complication of bariatric surgery. Surgical management is challenging with significant morbidity. The aim of this study was to evaluate the efficacy of endoscopic treatment at a single center. Methods: Retrospective review of our database from March 2007 to September 2009 (42 months) was performed. Multimodality endoscopic therapy including injection (fibrin glue or cyanoacrylate), endoprosthesis (fully covered plastic or metal stents), endoclips and T-tag placement was performed at the discretion of the endoscopist. Followup included outpatient clinic visits, EGD and upper GI series to confirm resolution. Results: 31 cases of post-surgical gastrointestinal leaks and fistulae were identified. Of these, 25 cases were secondary to bariatric surgery and were included in the study. Types of surgeries were vertical sleeve gastrectomy (n 13; 52%), Roux-N-Y gastric bypass (5; 20%), duodenal switch (3, 12%), vertical sleeve gastrectomy and duodenal switch (4, 16%). The average time to diagnosis post-surgery was 56 days (range 2-221). Mean fistula size on presentation was 13.1mm (range 3-30mm). Treatment administered was: injection therapy endoprosthesis (12; 48%), injection endoprosthesis endoclips (6; 24%), injection alone (3; 12%), injection endoprosthesis T-tag (3; 12%) and endoprosthesis alone (1; 4%). Mean number of endoscopic interventions per patient was 4.48 (range: 2 13). Average duration of follow-up was 24 months (range 8 42 months). 2 patients were lost to follow-up. 5 patients required surgery for definitive treatment and were considered to have failed endotherapy. Fistulas and leaks were considered healed in 18/25 cases (72%) with endoscopic therapy. There was no difference in healing rate when stratified by type of surgery or fistula size at presentation. No complications were reported. Discussion: Endoscopic treatment of post-bariatric surgery leaks and fistulae is safe. Multimodality therapy appears to effective in the treatment of defects smaller than 30mm.
Sensor placement for surface temperature control in thin mobile form factors

Thin mobile form factors are primarily passively cooled. Because the outer case is the main heat rejection area, total dissipation capability is limited by user perception of touch temperature. The platform dissipation can only temporarily exceed this limit and may need to be controlled. Internal sensors are inexpensive proxies for surface hot spots. This paper describes best practices for locating internal sensors to represent outer surface temperature.
Enterohepatic circulation in formation of propachlor (2-chloro-N-isopropylacetanilide) metabolites in the rat.

1. Bile secreted from rats given single oral doses of 2-chloro-N-isopropylacetanilide (propachlor) contained 58% dose as metabolites from the mercapturic acid pathway (glutathione, mercapturate, cysteine conjugates, and a sulphoxide of the mercapturate).2. Bile secreted from rats given single oral doses of the cysteine conjugate of propachlor contained glucuronide conjugates of hydroxylated 2-methylsulphonyl-N-isopropylacetanilides.3. In contrast, when the intestinal microflora were bypassed by intravenous administration of the cysteine conjugate of propachlor, the bile contained only the mercapturate and the sulphoxide of the mercapturate.4. Rats fed an antibiotic-containing diet and given single oral doses of either propachlor or the cysteine conjugate of propachlor excreted only mercapturic acid pathway metabolites in the urine, bile, and faeces, and no methylsulphonyl-containing metabolites. Faecal 14C from the antibiotic-fed rats given either propachlor or the cysteine conjugate of propachlor was ext...
Comparative thermodynamic and spectroscopic properties of water interaction with human stratum corneum.

Background/purpose: The water content of skin has a significant impact on skin properties; sufficient hydration is necessary to keep the skin supple, flexible, and smooth. To understand more completely the water retention properties of the human skin barrier, physical macroscopic properties must be related to the structural organization of the stratum corneum (SC). Water, lipids, and natural moisturizing factor (NMF) influence the molecular structures that affect the properties of SC, including water sorption and binding enthalpy. In the research reported here, isothermal microcalorimetry was used to study the interaction of water vapor with isolated human SC in intact, delipidized, and water-washed delipidized forms to identify the influences of the principal components of SC on water sorption. The calorimetric data are interpreted in conjunction with spectroscopic results to identify the conformational changes in keratins induced by lipid and NMF removal and to assess the influence of these changes on water binding in SC. Methods: Isothermal calorimetry was used to measure the integral heat of water vapor sorption on intact, delipidized, and water-washed delipidized human SC at 32 °C as a function of relative humidity using back and thigh skin from three donors. Calorimetric measurements were combined with water vapor sorption measurements to determine the differential thermodynamic properties of these systems. Attenuated total reflection–Fourier transform infrared spectroscopy was used to investigate effects of extraction on protein secondary structure. Results: The magnitudes of the differential enthalpy, entropy, and free energy were greatest for intact SC and least for water-washed delipidized SC. Water sorption followed a similar trend. Delipidization led to a significantly reduced binding enthalpy at low water content; water washing the delipidized SC had only a small additional effect on binding enthalpy. Delipidization converts a fraction of keratin α-helixes to turns and random coils, while water sorption converts a fraction of keratin α-helixes to β-sheets, turns, and random coils. Conclusions: The results of this study are consistent with a water sorption model in which keratin–keratin hydrogen bonds are replaced by keratin–water hydrogen bonds. Delipidization reduces the fraction of dry keratin that is in the α-helix conformation, suggesting that lipids hold the keratins in a conformation conducive to optimal hydration.
Operational Experience with the CMS Pixel Detector

The CMS pixel detector consists of 15840 readout chips, containing a total of almost 66 million pixels. In this paper, I describe the preparation for the first data-taking with LHC beams, in which the performance of the readout chips was optimized using a suite of calibrations. The detector thresholds have been adjusted to be less than 3000 electrons, and the effect of timing on the thresholds has been studied. After the arrival of LHC beam in December of 2009, the timing of the detector was optimized to achieve maximum efficiency, using both online and offline analysis. I will also discuss the challenges presented by beam backgrounds.
Mission concept for the remote sensing of the cryosphere using autonomous aerial observation systems

Improving the understanding of the Cryosphere and its impact on global hydrology is an important element of NASA’s Earth Science Enterprise (ESE). A Cold Land Processes Working Group (CLPWG) was formed by the NASA Terrestrial Hydrology Program to identify important science objectives necessary to address ESE priorities. These measurement objectives included Snow Water Equivalent (SWE), snow wetness, and freeze/thaw status of underlying soil. The spatial resolution requirement identified by the CLPWG was 100 m to 5000 m. Microwave sensors are well suited to measure these and other properties of interests to the study of the terrestrial cryosphere. It is well known that the EM properties of snow and soil at microwave frequencies are a strong function of the phase of water, i.e. ice/water. Further, both active and passive microwave sensors have demonstrated sensitivity to important properties of snowpack including, depth, density, wetness, crystal size, ice crust layer structure, and surface roughness. These sensors are also sensitive to the underlying soil state (frozen or thawed). Multiple microwave measurements including both active and passive sensors will likely be required to invert the effects of various snowpack characteristics, vegetation, and underlying soil properties to provide the desired characterization of the surface and meet the science needs required by the ESE. A major technology driver with respect to fully meeting these measurement needs is the 100 to 5000 m spatial resolution requirement. Meeting the threshold requirement of 5000 m at microwave frequencies from Low Earth Orbit is a technology challenge. The emerging capabilities of unmanned aircraft and particularly the system perspective of the Autonomous Aerial Observation Systems (AAOS) may provide high-fidelity/high-resolution measurements on regional scales or larger that could greatly improve our measurement capability. This paper explores a vehicle/sensor concept that could augment satellite measurements to enhance our understanding of the Cryosphere. The measurement performance and technology issues related to the sensor and aircraft will be assessed. Finally, specific technology needs and research necessary to enable this AAOS concept will be discussed.
Traitement endovasculaire d'un anévrysme rompu de l'aorte thoracique descendante chez un malade ayant un anévrysme de l'aorte ascendante : reconstruction hybride par chirurgie conventionnelle de la crosse aortique avec trompe d'éléphant distale et endoprothèse thoracique simultanées

Le traitement endovasculaire des lesions de l'aorte thoracique est maintenant largement pratique. L'extension de cette technique aux situations urgentes en est a ses debuts. Les lesions de l'aorte ascendante et de la crosse aortique peuvent empecher la mise en place d'une endoprothese de l'aorte thoracique en raison de l'absence de zone d'ancrage fixation proximale. Plusieurs approches hybrides, associant chirurgie conventionnelle et endovasculaire ont ete decrites. Nous avons recemment ete confrontes au probleme difficile d'une rupture contenue d'un anevrysme de l'aorte thoracique descendante de 6,8 cm de diametre chez un malade de 60 ans ayant un anevrysme degeneratif de l'aorte ascendante et de la crosse aortique. Ce malade a ete traite par une approche hybride associant une chirurgie conventionnelle de l'aorte ascendante et de la crosse aortique a un traitement simultane par endoprothese de l'aorte thoracique descendante. L'approche chirurgicale conventionnelle a permis d'etablir une excellente zone d'implantation proximale grâce a l'utilisation de la technique de la trompe d'elephant. Cette technique a egalement permis la suture de l'endoprothese a la prothese de la crosse aortique pour prevenir une migration de l'endoprothese. Cette approche chirurgicale hybride a ete couronnee de succes et a evite la morbidite supplementaire qu'aurait ajoute a la sternotomie un abord thoraco-abdominal gauche. L'utilisation future de ces nouvelles techniques hybrides aura sans aucun doute un role plus important dans le traitement des pathologies de l'aorte thoracique.
The terminal amino acid residues of ovine interstitial cell-stimulating hormone and its subunits

Abstract Ovine ICSH and its subunits, C I and C II, have been analyzed for their NH 2 - and COOH-terminal groups. The phenylisothiocyanate reaction has shown proline to be at the N-terminus of ICSH, C I, and C II, a fact not previously known. Studies with carboxypeptidase A show that the native ICSH has two C-terminal amino acids; namely, serine and leucine. Subunit C I has serine at its COOH-terminus with the sequence ..... Tyr.Tyr.Ser.OH; subunit C II terminates with a leucine residue with the sequence ..... Cys.Ile.Leu.OH.
A Probabilistic Cascade of Detectors for Individual Object Recognition

A probabilistic system for recognition of individual objects is presented. The objects to recognize are composed of constellations of features, and features from a same object share the common reference frame of the image in which they are detected. Features appearance and pose are modeled by probabilistic distributions, the parameters of which are shared across features in order to allow training from few examples. In order to avoid an expensive combinatorial search, our recognition system is organized as a cascade of well-established, simple and inexpensive detectors. The candidate hypotheses output by our algorithm are evaluated by a generative probabilistic model that takes into account each stage of the matching process. We apply our ideas to the problem of individual object recognition and test our method on several data-sets. We compare with Lowe's algorithm [7] and demonstrate significantly better performance.
Monte Carlo refinement of rigid‐body protein docking structures with backbone displacement and side‐chain optimization

Structures of hitherto unknown protein complexes can be predicted by docking the solved protein monomers. Here, we present a method to refine initial docking estimates of protein complex structures by a Monte Carlo approach including rigid-body moves and side-chain optimization. The energy function used is comprised of van der Waals, Coulomb, and atomic contact energy terms. During the simulation, we gradually shift from a novel smoothed van der Waals potential, which prevents trapping in local energy minima, to the standard Lennard-Jones potential. Following the simulation, the conformations are clustered to obtain the final predictions. Using only the first 100 decoys generated by a fast Fourier transform (FFT)-based rigid-body docking method, our refinement procedure is able to generate near-native structures (interface RMSD <2.5 A) as first model in 14 of 59 cases in a benchmark set. In most cases, clear binding funnels around the native structure can be observed. The results show the potential of Monte Carlo refinement methods and emphasize their applicability for protein–protein docking.
Obstacles to the Development of Media Education in the United States

This article examines the political, economic, historic, and cultural explanations for why the United States lags behind other major English-speaking countries in the formal delivery of media education. The research relies on formal documents and newsletters, interviews with leading media education researchers and teachers from numerous nations, and site visits to five countries. Among the many factors explored are the sheer physical size of the U.S., its highly heterogeneous population, resistance to the federal government’s making central educational or broadcasting policy, the fact that the U.S. exports far more media products than it imports, and a long-standing reluctance to take the popular arts seriously. * * * The United States finds itself in the ironic position of being the world’s leading exporter of media products while lagging behind every other major Eng1ish-speaking country in the world in the formal delivery of media education in its schools. Are there specific reasons that explain the less developed state of U.S. media education? If so, what obstacles lie ahead? The formal research for this study began in 1993 when I began collecting material from around the world, including formal documents, brochures, newsletters, and educational plans; interviewing leading media education scholars and researchers, as well as experienced media education master teachers and inexperienced teachers from around the world; and directly observing in five countries, spending the greatest periods in England, Scotland, and the United States. A worldwide movement in media literacy education has been growing for roughly 30 years. Since the mid-1990s, Australia has mandated media education from kindergarten through 12th grade. Ontario has mandated it for grades 7-12 since 1987. In Britain in 1996, approximately 25,000 students took their GCSE exams (for 16-year-olds) and some 8,000 university-bound 18-year-o1ds took their A Level (advanced level) exams in media studies. Even before the fall of apartheid, South Africa was already ahead of the United States in formal media education (Criticos, 1997). Numerous non-English-speaking regions and countries have also developed media education initiatives at a rapid rate. Substantive developments have occurred in Scandinavia, South America, Europe, Asia, Russia, and Israel (see Brown, 1991; Piette & Giroux, 1997). In the United States, significant statewide initiatives are now in place in New Mexico and North Carolina, with noteworthy developments having occurred in Wisconsin, Minnesota, and other states. Most states are home to one or more organized groups working to advance the cause of media education, locally, statewide, or nationally. In 1992, the first National Leadership Conference on
The fluid mechanics of dissolution trapping in geologic storage of CO2

Sequestration of carbon dioxide by injecting it into the deep subsurface is critical to successful mitigation of climate change by reducing anthropogenic emissions of greenhouse gases into the atmosphere. To achieve this we must understand how CO2 moves in the subsurface. Many interesting fluid mechanics problems emerge. Szulczewski, Hesse & Juanes (J. Fluid Mech., vol. 736, 2013, pp. 287–315) focus on one critical aspect, namely the dissolution of CO2 into the fluid resident in the subsurface and the flow dynamics that ensue. Even for this single problem, an elegant analysis identifies seven behavioural regimes that control the amount and timing of dissolution.
REM sleep and cortisol responses to scopolamine during depression and remission in women

Baseline electroencephalographic (EEG) sleep and the EEG sleep response to scopolamine were studied in 10 adult female patients with unipolar major depressive disorder. Subjects were studied twice for two consecutive nights while depressed and, again, during remission. On the second night of each two-night session, normal saline or scopolamine (1.5 microg/kg, i.m.) was administered in a randomized, double-blind, cross-over fashion. Nocturnal urinary free cortisol (NUFC) measures also were collected. Compared to the depressed state, NUFC was significantly lower during remission. In contrast, baseline EEG sleep measures did not differ from episode to remission. Scopolamine suppressed rapid eye movement (REM) sleep to a comparable extent during the depressive episode and in remission. Scopolamine also reduced NUFC secretion during both clinical states, but to a lesser extent than REM sleep suppression. The findings suggest that the dysregulation in cholinergic systems associated with depressive illness may be persistent during remission, at least for some cholinergic systems. The results also suggest that the central cholinergic system(s) that regulate(s) REM sleep may be more sensitive to dysregulation than the cholinergic system(s) that control(s) nocturnal cortisol secretion.
Tissue and Species Differences in the Application of Quantum Dots as Probes for Biomolecular Targets in the Inner Ear and Kidney

Quantum dots (QDs) are useful biological probes because of the increased photostability and quantum efficiency they offer over organic fluorophores. However, toxicity concerns arise because the QD core is composed of cadmium and selenium, metals known to be unsafe for humans and animals. We investigated the feasibility of quantum dots as biological labels for imaging studies of inner ear and kidney, tissues that share a polarized epithelial arrangement and drug susceptibility. We found that methods for labeling the actin cytoskeleton of monolayers of cultured amphibian kidney cells (Xenopus A6) with 565 nm QD conjugates were not feasible with large Xenopus inner ear organs. We then compared the uptake of 565 nm cationic peptide-targeted and nontargeted QDs in live kidney cell lines (amphibian, A6 and XLK-WG; human, HEK-293). Results showed that targeted QDs are internalized by all three kidney cell lines, and that nontargeted CdSe nanocrystals are sequestered only by human kidney cells. CellTracker Red CMTPX confirmed the membrane integrity and viability of HEK-293 cells that internalized QDs. Our results demonstrate species and tissue differences in QD uptake and labeling, and underscore the need for long-term studies of QD toxicity and fate in cells
Effects of Simultaneous Dietary Exposure to 2,2′,4,4′,5,5′-Hexabromobiphenyl and 3,3′,4,4′,5,5′-Hexachlorobiphenyl on Hepatic Tumor Promotion in Rats

Female Sprague-Dawley rats were partially hepatectomized, initiated with diethylnitrosamine (DEN), and fed diets containing 2,2′,4,4′,5,5′-hexabromobiphenyl (245-HBB), 3,3′,4,4′,5,5′-hexachlorobiphenyl (345-HCB), or combinations of 245-HBB and 345-HCB to determine the tumor-promoting ability of these compounds in a two-stage (initiation/promotion) hepatocar-cinogenesis system. Tumor-promoting ability was assessed by measuring hepatic foci positive for gamma glutamyl transpeptidase (GGT) activity. Concentrations of 10 or 100 mg 245-HBB/kg of diet caused significantly increased numbers of GGT-positive hepatic foci. When 245-HBB and 345-HCB were fed simultaneously, an additive effect on tumor-promoting ability was observed at dietary concentrations of 10 mg/kg 245-HBB and 0.1 mg/kg 345-HCB. However, an inhibitory effect on tumor promotion occurred when dietary concentrations of 100 mg/kg 245-HBB and 1.0 mg/kg 345-HCB were fed simultaneously. These results suggest that the tumor-promoting ability of simultane...
Fighting Organized Crime: Politics, Justice, and the Legacy of Thomas E. Dewey

A thoughtful and colorful account of the 'law and order' issue in Franklin Roosevelt's own New York State, showing how a young Republican, Thomas Dewey, captured the nation's attention and almost succeeded FDR in the White House by waging war on big time crime and Empire State politics. -- Calvin Woodard, University of Virginia
Sub-THz high gain wide-band low noise amplifiers in 90nm RF CMOS technology

In the future, CMOS technology is expected to enable low-cost sub-THz applications such as high data-rate communication links, passive and active imaging and sensor systems, and instrumentation and measurements equipment. This paper presents key design techniques for different CMOS LNA topologies with over 20GHz bandwidth ranging from 90GHz to 110GHz. The proposed LNA topologies are, the three-stage cascode RF NMOS configuration and four-stage Common Gate followed by Common Source configuration. Simulation results show that the first topology can achieve a peak gain of 23.5 dB at 92.1 GHz with a 3-dB bandwidth of 25 GHz, and a noise figure less than 5.5 dB over the entire bandwidth. The achieved peak gain from the second topology is 23.2 dB at 105 GHz with a 3-dB bandwidth of 15 GHz and a noise figure less than 6.1 dB over the entire bandwidth. The LNAs are designed in 90nm RF CMOS and consume 27mW/40mW for topology I/topology II respectively.
Adjacent-2 disjunction of a maternal t(9;22) leading to duplication 9pter----q22 and deficiency of 22pter----q11.2.

The proposita presented at birth with multiple congenital anomalies including craniofacial anomalies, bilateral cleft lip and palate, abnormalities of the urogenital system, talipes equinovarus, and the DiGeorge sequence. Cytogenetic investigation showed a 46,XX,- 22,+der(9)t(9;22)(q22;q11.2) karyotype. The mother, maternal uncle, and maternal grandmother of the infant are carriers of a reciprocal balanced translocation involving chromosomes 9 and 22 at regions q22 and q11.2, respectively. The unbalanced karyotype seen in the proposita arose due to an adjacent-2 disjunction of the quadrivalent in the mother. Prenatal diagnosis of the second pregnancy of this woman showed a similar karyotype. Review of the literature shows that adjacent-2 disjunction may occur preferentially when certain chromosomes are involved in translocations.
Choice Feminism and the Fear of Politics

Choice feminism is motivated by a fear of politics. It arises in response to three common criticisms of feminism: that feminism is too radical, too exclusionary, and too judgmental. In response, choice feminism offers a worldview that does not challenge the status quo, that promises to include all women regardless of their choices, and that abstains from judgment altogether. Moreover, it enables feminists to sidestep the difficulties of making the personal political: making judgments and demanding change of friends, family, and lovers. Yet judgment, exclusion, and calls for change are unavoidable parts of politics. If feminists are not to withdraw from political life altogether, we have to acknowledge the difficulty of engaging in politics. Political claims are partial; we will inevitably exclude, offend, or alienate some of those whom we should wish to have as allies. The political concerns and dilemmas to which choice feminism responds are very real. However, we can take seriously the political motivations behind choice feminism without withdrawing from politics. Instead, we need to complement an acknowledgment of the political dilemmas facing feminists with a celebration of the pleasures of engaging in politics with those who differ from and disagree with us.
Introduction: “The Genius of Alice Munro”

Do you have a hopeful feeling about the woman at the end of the story [?]Why, or why not?I don’t know.Why, or why not?Alice Munro, Draft of “Bardon Bus” (1981–82; (38.8.9. f 22 [verso]))On July 13,...
Optical Probing of Metabotropic Glutamate Receptors

G protein-coupled receptors (GPCRs), the largest family of membrane proteins, enable cells to respond to a wide array of extracellular stimuli and control a diverse array of intracellular signaling pathways. The Class C GPCRs, which contain the metabotropic glutamate receptors (mGluRs) and GABAB receptors, are expressed throughout the nervous system where they control excitability and synaptic strength and serve as drug targets for many neurological disorders. Despite the presence of high resolution crystal structures of isolated domains, many questions remain about the dynamic processes of receptor activation and G protein coupling in full length receptors. Furthermore, the limitations of pharmacology and classical assays have made it difficult to control and measure individual receptors with high spatiotemporal precision and subtype specificity. In this study we have developed and refined methods for attaching photoswitchable tethered ligands (PTLs) for the in vivo photocontrol of mGluRs, with a focus on mGluR2. Optical control of mGluR2 via tethering of photoswitches to SNAP-tags allowed for efficient, orthogonal labeling of mGluR2 without the complications of maleimide chemistry. This new approach to PTL tethering allowed for dual optical control of multiple receptors within the same cell. We also used PTLs to selectively ligand one or both memebers of linked mGluR2 homodimers to reveal substantial cooperativity. Strikingly, in mGluR2/3 heterodimers this cooperativity is asymmetric. These experiments were complemented with intersubunit ensemble and single molecule fluorescence resonance energy transfer (FRET) experiments that revealed the role of the dimer interface in the conformational dynamics underling receptor activation. Together this work contributes a number of new tools for optical probing of GPCRs and leads to a model for subunit-dependent activation of mGluRs.
The Uses of Echinacea angustifolia and Other Echinacea Species by Native Americans

Echinacea was the most widely used medicinal plant of the Plains Indians. It was used for a variety of ailments, including toothache, coughs, colds, sore throats, snakebite, and as a painkiller. Lewis and Clark learned about it during their Expedition and in 1805 shipped the roots and seeds back to President Jefferson as one of their more important finds. A total of 19 tribes have been documented using Echinacea species, with Echinacea angustifolia being the best documented, primarily because little ethnobotany was reported from eastern and southern tribes in the USA. Echinacea is still being used by Native Americans across the Great Plains for a variety of treatments.
Higher-order collision enhanced wave mixing; theory and experiment

Collision enhanced resonances represent an interesting class of nonlinear-optical processes. They occur because collisional dephasing can rephase quantum mechanical amplitudes that ordinarily cancel out exactly, thereby allowing otherwise unobservable wave-mixing resonances to be seen. This is an especially interesting phenomenon because these resonances are coherent effects that are induced by an incoherent process (collisional dephasing). First predicted1 in the late 1970s and eventually observed2 in 1981, these novel effects have now been seen in a wide variety of four-wave-mixing experiments, ranging from self-focusing to coherent anti-Stokes Raman spectroscopy.
Gottfried Weber, Das Nibelungenlied: Problem und Idee

(1966). Gottfried Weber, Das Nibelungenlied: Problem und Idee. The Germanic Review: Literature, Culture, Theory: Vol. 41, No. 1, pp. 72-75.
Negative externalities of GPS-enabled routing applications: A game theoretical approach

This work studies the impact of the increasing penetration of routing apps on road usage. Its conclusions apply both to manned vehicles in which human drivers follow app directions, and unmanned vehicles following shortest path algorithms. To address the problem caused by the increased usage of routing apps, we model two distinct classes of users, one having limited knowledge of low-capacity road links. This approach is in sharp contrast with some previous studies assuming that each user has full knowledge of the network and optimizes his/her own travel time. We show that the increased usage of GPS routing provides a lot of benefits on the road network of Los Angeles, such as decrease in average travel times and total vehicle miles traveled. However, this global increased efficiency in urban mobility has negative impacts as well, which are not addressed by the scientific community: increase in traffic in cities bordering highway from users taking local routes to avoid congestion.
Evidence That BRCA1 - or BRCA2 -Associated Cancers Are Not Inevitable

Inheriting a BRCA1 or BRCA2 gene mutation can cause a deficiency in repairing complex DNA damage. This step leads to genomic instability and probably contributes to an inherited predisposition to breast and ovarian cancer. Complex DNA damage has been viewed as an integral part of DNA replication before cell division. It causes temporary replication blocks, replication fork collapse, chromosome breaks and sister chromatid exchanges (SCEs). Chemical modification of DNA may also occur spontaneously as a byproduct of normal processes. Pathways containing BRCA1 and BRCA2 gene products are essential to repair spontaneous complex DNA damage or to carry out SCEs if repair is not possible. This scenario creates a theoretical limit that effectively means there are spontaneous BRCA1/2-associated cancers that cannot be prevented or delayed. However, much evidence for high rates of spontaneous DNA mutation is based on measuring SCEs by using bromodeoxyuridine (BrdU). Here we find that the routine use of BrdU has probably led to overestimating spontaneous DNA damage and SCEs because BrdU is itself a mutagen. Evidence based on spontaneous chromosome abnormalities and epidemiologic data indicates strong effects from exogenous mutagens and does not support the inevitability of cancer in all BRCA1/2 mutation carriers. We therefore remove a theoretical argument that has limited efforts to develop chemoprevention strategies to delay or prevent cancers in BRCA1/2 mutation carriers.
FabSquare: Fabricating Photopolymer Objects by Mold 3D Printing and UV Curing

The FabSquare system is a personal fabrication method that lets users fabricate objects by molding photopolymers inside a 3D printed mold. The molds are printed with UV-transparent materials that allow for UV curing--the polymerization and solidification of the fluid content. The molds can be repeatedly reused to fabricate identical objects or create new objects with identical geometry, but different components. Because the necessary equipment is easily obtainable and affordable, the FabSquare approach is suitable for ordinary users in nonspecialized labs, allowing them to rapidly fabricate a range of objects. https://extras.computer.org/extra/mcg2017030034s1.mp4https://extras.computer.org/extra/mcg2017030034s2.pdf
Homology modeling inspired synthesis of 5-HT2A receptor inhibitors: A diazepine analogue of the atypical antipsychotic JL13

The benzoxazepine JL13 is an analogue of the clozapine family which targets the 5-HT2A receptor, and has showed promise as an atypical antipsychotic agent. Following structure function analysis with a series of synthetic analogues, homology modeling was performed to determine key interaction sites with the receptor. An aza analogue was synthesized for evaluation, and demonstrated seventeen times greater affinity for the receptor. An improved synthetic route was developed to allow rapid modifications of the core and synthesis of related libraries.
Pressure ulcer risk detection from complexity of activity

Activity levels in nursing home residents were measured with accelerometers over one week as part of a multicenter randomized controlled trial, and complexity of the resulting activity patterns were characterized. Among 813 study participants on whom activity data had been collected, 16 participants developed pressure ulcers by the end of the study. The fractal dimension D 0 of the activity series was lower (p=0.039) in residents who developed pressure ulcers than in controls matched on the basis of race, randomization group, score on the Braden scale, and diagnoses of cardiovascular disease and dementia. Hurst exponents indicated that the scaling of the power spectrum was close to 1/ƒ in pressure ulcer cases. At timescales exceeding 30 minutes, approximate entropy tended to be higher in the controls than in the pressure ulcer cases. The fractal structure of the activity time series and its information content offer the ability to predict higher risk of development of pressure ulcers in nursing home residents.
A multi-carrier protocol for in-band control of tactical data network systems

Network management requires both awareness of the status of the network and the ability to manage key systems to maintain full network efficiency. OrderNet is an application layer protocol which rides within existing message sets to manage heterogeneous networks. This paper summarizes the analysis of alternatives performed that selected OrderNet as a promising technology for the monitoring, management, and control of tactical data networks. This paper also describes selection of the OrderNet message carriers, the OrderNet protocol design and preliminary performance analysis.
IBD: Step-up vs top-down therapy for Crohn's disease: medicine vs surgery.

Ileocaecal resection has traditionally been reserved for the treatment of biologic-refractory inflammatory, fibrostenotic or fistulizing Crohn's disease of the terminal ileum. Now, for the first time, this surgical approach has been investigated as an initial treatment for steroid or immunomodulator-refractory Crohn's ileitis, in comparison with anti-TNF therapy.