cssi/SciSciGPT-SciSciNet huggingface dataset:
The cyclization of mouse satellite DNA.

Sheared fragments of mouse satellite DNA can form rings and other circular structures by several techniques. „Folded rings“ are formed if the sheared fragments are simply annealed, indicating that shearing produces single-chain terminals, and that the repetitious sequence is shorter than the exposed ends. The occurrence of folded rings can be sharply reduced by prior treatment with single-chain specific endonuclease, and significantly increased if the fragments are treated with exonuclease III. Denaturation of satellite DNA followed by reassociation of the single chains results in the formation of “slipped rings”. These characteristics of the DNA lead to the conclusion that the sequences of the mouse satellite DNA are arranged in a tandemly repetitious manner.-About 20% of the DNA fragments from the “main band” cyclize after partial exonuclease III degradation, but not before this treatment. This indicates that a large fraction of the main band DNA is tandemly repetitious, but that the length of the repetitious sequence is on the average longer than the single-chain terminals produced by shearing.
Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells.

1Folates have been co-administered with some antifolates to diminish host toxicity; however, the extent to which this will reduce antitumor activity is not known. To further clarify this issue, studies were undertaken to characterize and quantitate the impact of alterations in intracellular folate levels on the activities of a variety of antifolates in L1210 murine leukemia cells. Intracellular folate cofactor levels increased almost in proportion to the increase in extracellular 5-formyltetrahydrofolate (5-CHO-THF) over a concentration range that encompassed physiological levels of 5-methyltetrahydrofolate. This resulted in a spectrum of increases in the ic50 values of antifolates upon continuous exposure to drugs [Lometrexol (DDATHF) (70x) > trimetrexate (TMQ) (30x), multitargeted antifolate, LY231514 (ALIMTA) (30x) > Raltitrexed, Tomudex (ZD1694) (10x), 6R-2′,5′-thienyl-5,10-dideazatetrahydrofolic acid (LY309887) (10x) > methotrexate (MTX) (6x) > (2S)-2-{o-fluoro-p-[N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzamido}-4-(tetrazol-5-yl) butyric acid (ZD9331) (3x), Nα-(4-amino-4-deoxypteroyl)-Nδ-hemiphthaloyl-l-ornithine (PT523) (3x)]. Upon a 4-hr pulse exposure to drug, the ic50 values for DDATHF and ALIMTA were increased > 180- and 5-fold, respectively, with only a 2.5-fold increase in the extracellular 5-CHO-THF level within the physiological range. The reductions in drug sensitivities could be attributed to decreases in accumulation of polyglutamate derivatives of ALIMTA and DDATHF. Hence, in these studies, natural folates diminished the activity of agents that undergo polyglutamation by suppression of the formation of these active congeners at the level of folylpolyglutamate synthetase. For inhibitors of dihydrofolate reductase, the suppressive effect of endogenous folates appears to be due to competition between the antifolate and dihydrofolate at the level of the target enzyme. These data should be carefully considered in the design of regimens with antifolates, which incorporate co-administration of folates.
Comparison between numerical simulations and experiments for single-point diamond turning of single-crystal silicon carbide

Abstract Single-point diamond turning (SPDT) experiments conducted on single-crystal 6-H silicon carbide (SiC) have shown chip formation similar to that seen in the machining of metals. The ductile nature of SiC is believed to be the result of a high-pressure phase transformation (HPPT), which generates a plastic zone of material that behaves in a metallic manner. This metallic behavior is the basis for using AdvantEdge, a metal machining simulation software, for comparison to experimental results. Simulations (2D) were carried out by matching the SPDT experimental conditions, which were conducted at nanometer (nm) depths of cut and varying tool rake angles. The experiments were performed by machining the circumference of the single-crystal wafer, thereby conforming to a 2D orthogonal cut (plunge cuts, or an infeed, achieved the depth of cut, and no cross feed was incorporated). The cutting and thrust forces generated from the experiments under ductile cutting conditions compared favorably with the simulation. As the depth of cut is decreased (250 nm, 100 nm, and 50 nm), the experimental conditions transition from a brittle to ductile behavior, with the 50 nm cuts being dominated by the ductile regime. Thus, the forces from the experiment and the simulations are in much better agreement for the smaller depths of cut, that is, below the critical depth of cut that establishes the ductile-to-brittle transition, as ductile conditions exist in both the simulation and experiments. The differences in the results that do arise are assumed to be primarily due to a springback of the material leading to increased rubbing on the flank face.
Revisiting novice programmer errors

Although programmer errors have been investigated, only a limited range of error types typically made by novices have been scrutinized. In this paper we present an expanded classification of the types of errors considered in previous research. In particular, problems which require the use of more difficult program constructs such as nested loops, arrays, recursion and functions have been somewhat neglected. We hope this paper will encourage other researchers to further analyze the types of errors advanced novices will make and the types of misunderstandings which underlie such errors.
Irreversible oxidative inactivation of protein kinase C by photosensitive inhibitor calphostin C

Isolated protein kinase C (PKC) was irreversibly inactivated by a brief (min) incubation with calphostin C in the presence of light. This inactivation required Ca2+ either in a millimolar range in the absence of lipid activators or in a submicromolar range in the presence of lipid activators. In addition, an oxygen atmosphere was required suggesting the involvement of oxidation(s) in this inactivation process. Furthermore, PKC inactivation might involve a site-specific oxidative modification of the enzyme at the Ca2+-induced hydrophobic region. Physical quenchers of singlet oxygen such as lycopene, β-carotene, and α-tocopherol all reduced the calphostin C-induced inactivation of PKC. In intact cells treated with calphostin C, the inactivation of PKC was rapid in the membrane fraction compared to cytosol. This intracellular PKC inactivation was also found to be irreversible. Therefore, calphostin C can bring prolonged effects for several hours in cells treated for a short time. Taken together these results suggest that the calphostin C-mediated inactivation of PKC involves a site-specific and a ‘cage’ type oxidative modification of PKC.
Tessellated Structure from Motion for Midrange Perception and Tactical Planning

A typical structure from motion (SFM) technique is to construct 3-D structures from the observation of the motions of salient features tracked over time. Although the sparse feature-based SFM provides additional solutions to robotic platforms as a tool to augment navigation performance, the technique often fails to produce dense 3-D structures due to the sparseness that is introduced during the feature selection and matching processes. For midrange sensing and tactical planning, it is important to have a dense map that is able to provide not only 3-D coordinates of features, but also clustered terrain information around the features for better thematic representation of the scene. In order to overcome the shortfalls embedded in the sparse feature-based SFM, we propose an approach that uses Voronoi decomposition with an equidistance-based triangulation that is applied to each of segmented and classified regions. The set of the circumcenters of the circum-hyperspheres used in the triangulation is formed with the feature points extracted from the SFM processing. We also apply flat surface detection to find traversable surface for a robotic vehicle to be able to maneuver safely on.
Detection of piperonal emitted from polymer controlled odor mimic permeation systems utilizing Canis familiaris and solid phase microextraction–ion mobility spectrometry

Abstract Currently, in the field of odor detection, there is generally a wider variation in limit of detections (LODs) for canines than instruments. The study presented in this paper introduces an improved protocol for the creation of controlled odor mimic permeation system (COMPS) devices for use as standards in canine training and discusses the canine detection thresholds of piperonal, a starting material for the illicit drug 3,4-methylenedioxymethamphetamine (MDMA), when exposed to these devices. Additionally, this paper describes the first-ever reported direct comparison of solid phase microextraction–ion mobility spectrometry (SPME–IMS) to canine detection for the MDMA odorant, piperonal. The research presented shows the reliability of COMPS devices as low cost field calibrants providing a wide range of odorant concentrations for biological and instrumental detectors. The canine LOD of piperonal emanating from the 100 ng s −1 COMPS was found to be 1 ng as compared to the SPME–IMS LOD of piperonal in a static, closed system at 2 ng, with a linear dynamic range from 2 ng to 11 ng. The utilization of the COMPS devices would allow for training that will reduce the detection variability between canines and maintain improved consistency for training purposes. Since both SPME and IMS are field portable technologies, it is expected that this coupled method will be useful as a complement to canine detection for the field detection of MDMA.
Fifty years of operational research and emergency response

Over the past 50 years, a wealth of applications has resulted from researchers turning their attention to operations such as fire suppression, law enforcement and ambulance services. The 1970s might even be argued as the ‘golden age’ of this particular effort, producing many of the seminal works in fire station location planning, unit assignment and ambulance queuing models. Such efforts naturally continue through to the present, but with a focus shifting away from earlier contexts of established urban emergency service systems. Simultaneously, current evidence from the field suggests that far more work remains. In this paper, we review the operational research (OR) foundation in emergency response so far, highlighting the fact that most of what has been accomplished addresses the well-structured problems of emergency services. This, in turn, offers an explanation for some paradoxical challenges from the field: most of emergency response itself is semi-structured, at best. While OR has traditionally focused on the management of an organization, emergency response ultimately requires the management of disorganization, suggesting an important OR growth area for the next 50 years.
Survivor centrality among breast cancer survivors: implications for well-being.

Objective: The goal of this research was to examine the extent to which 10-year breast cancer survivors integrated cancer into their self-concept (i.e. survivor centrality), identify predictors of survivor centrality, and determine the relation of survivor centrality to well-being. Methods: Breast cancer survivors (n=240) were interviewed 10 years following the initial diagnosis. They completed measures of survivor centrality, illness valence (i.e. positive or negative views of illness), and well-being (positive and negative affect, mental and physical functioning, psychological distress, benefit finding). Results: There were few predictors of the kinds of women who were more likely to integrate breast cancer into their self-concepts, but survivor centrality was related to engaging in behaviors that suggested survivorship was relevant to women's daily lives, such as becoming involved in breast cancer activities. Survivor centrality was related to three markers of negative psychological well-being: more negative affect, poorer mental functioning, and greater psychological distress. However, in the case of negative affect and psychological distress, this relation was moderated by illness valence, such that survivor centrality was only related to negative psychological well-being when the illness was viewed in less positive terms. Conclusions: Women vary in the extent to which they define themselves in terms of the breast cancer experience. Survivor centrality in and of itself is not always indicative of adjustment to disease. When women have a more negative view of being a breast cancer survivor, survivor centrality is more likely to signify potential problems. Copyright © 2010 John Wiley & Sons, Ltd.
Local excision of rectal carcinoma: a safe alternative for more advanced tumors?

Background and Objectives: Local excision of rectal carcinoma has primarily been limited to patients with small (≤3 cm), early rectal carcinoma. We wanted to determine whether local excision (transanal or transacral), when combined with selective chemoradiation therapy, would be adequate treatment for patients with larger (>3 cm) and more advanced T3 and N1 tumors. Methods: A prospective study of 20 patients with clinical Tl-T3, N0-N 1 rectal carcinoma was initiated in 1990. Local excision (transanal or transacral) was performed on all patients. Sixteen patients were treated with postoperative 5-fluorouracil (5-FU) and leucovorin (LV) combined with radiation therapy; six high-risk patients (T3 or N1) received an additional 6 months of 5-FU and LV. All patients were followed for a minimum of 4 years. Results: Tumor size ranged from 2 to 5.5 cm (mean, 3.6 cm). Histology revealed well or moderate differentiation (19/20), gross or microscopic ulceration (14/20), and vessel invasion (5/20). Mucosal margins were 3-12 mm (mean, 8.3 mm); radial margins were clear in all patients except one (microscopically positive). Five patients had T3 tumors; two had node positive tumors (N1). With a median follow-up of 56 months (48-71), there have been no local or regional failures and two patients have died from metastatic disease. Conclusions: Local excision, when combined with selective chemoradiation therapy, can be safely applied to patients with large (>3 cm) and more advanced T3 and N1 rectal carcinomas.
Ecophysiological Characterization of Ammonia-Oxidizing Archaea and Bacteria from Freshwater

Aerobic biological ammonia oxidation is carried out by two groups of microorganisms, ammonia-oxidizing bacteria (AOB) and the recently discovered ammonia-oxidizing archaea (AOA). Here we present a study using cultivation-based methods to investigate the differences in growth of three AOA cultures and one AOB culture enriched from freshwater environments. The strain in the enriched AOA culture belong to thaumarchaeal group I.1a, with the strain in one enrichment culture having the highest identity with “Candidatus Nitrosoarchaeum koreensis” and the strains in the other two representing a new genus of AOA. The AOB strain in the enrichment culture was also obtained from freshwater and had the highest identity to AOB from the Nitrosomonas oligotropha group (Nitrosomonas cluster 6a). We investigated the influence of ammonium, oxygen, pH, and light on the growth of AOA and AOB. The growth rates of the AOB increased with increasing ammonium concentrations, while the growth rates of the AOA decreased slightly. Increasing oxygen concentrations led to an increase in the growth rate of the AOB, while the growth rates of AOA were almost oxygen insensitive. Light exposure (white and blue wavelengths) inhibited the growth of AOA completely, and the AOA did not recover when transferred to the dark. AOB were also inhibited by blue light; however, growth recovered immediately after transfer to the dark. Our results show that the tested AOB have a competitive advantage over the tested AOA under most conditions investigated. Further experiments will elucidate the niches of AOA and AOB in more detail.
Perineal reconstruction with local flaps: technique and results

Wide excision of perineal lesions, often including the entire anal canal, may be necessary for benign and malignant conditions. Closure of these large defects is challenging, especially when continence is a goal. The aim of this study was to assess our experience with local flap closure of large perineal defects. From 1994 to 2009, 20 patients underwent wide perineal and/or anal canal excisions and reconstruction using local flaps. Mean age was 45 years (range 20–65 years), 13 were male, and 8 (40 %) were immunocompromised. Primary indications included anal or perineal squamous cell carcinoma—(n = 12), Buschke-Lowenstein tumor (n = 3), and anal intraepithelial neoplasia (n = 3), hidradenitis, stenosis, ectropion, and traumatic cloaca repair (n = 1 each). Primary procedures included wide local excision of large neoplastic lesions—(n = 15) (mean size 10 cm, range 5–18 cm), abdominoperineal resection (APR) (n = 2), perineoplasty with sphincteroplasty—(n = 1), and others—(n = 2). All were reconstructed with bilateral local flaps (V–Y 18, S 2). Thirteen had complete excision of the anal canal to the anorectal ring preserving the sphincters. Six (30 %) had ostomies; 2 with APR and 4 temporary. There were no perioperative deaths. Mean hospital stay was 4.2 days. Follow-up averaged 35 months (range 3–87 months) in survivors. Five patients died during follow-up; 2 of complications of acquired immune deficiency syndrome (AIDS) and 3 of cancer (2 treated palliatively). Wound dehiscence occurred in 6 (30 %) patients: in 3 cases, this was minor dehiscence and healed quickly; in 3 cases, it was major dehiscence and occurred in the 2 radiation/APR patients and in one patient with advanced AIDS. Radiation was the only significant risk factor (P < .05). Twelve of 14 eligible patients with long-term follow-up and an intact anal canal are fully continent, and 2 are partially continent (1 traumatic cloaca; 1 the same as before surgery). Local flap reconstruction of the perineum and anal canal is an excellent method of managing large perineal defects. Most heal primarily, even in immunocompromised patients, and continence may be preserved. Local flaps should be avoided in irradiated patients.
Comparison of time to desaturation between preoxygenated and nonpreoxygenated dogs following sedation with acepromazine maleate and morphine and induction of anesthesia with propofol

Objective—To compare the time to desaturation in healthy dogs that breathed oxygen or room air for 3 minutes before induction of anesthesia. Animals—20 healthy dogs. Procedures—Dogs were sedated with morphine and acepromazine maleate. Dogs received a 3-minute treatment of room air or oxygen (100 mL/kg/min) via face mask. Arterial blood samples were collected before and after treatment to determine PaCO2, PaO2, pH, and SaO2; propofol (6 mg/kg, IV) was injected during a 7-second period, and the dogs were intubated. A lingual pulse oximeter probe was placed. Dogs remained disconnected from the breathing circuit until SpO2 equaled 90% (desaturation point) and then connected and ventilated until the SpO2 was ≥ 97%. Arterial blood samples were collected and SpO2 was recorded every 30 seconds for 4 minutes and then every minute until the desaturation point. Times to first breath and the desaturation point were recorded. Data were collected at 0, 5, 30, 60, 90, 120, and 150 seconds. Results—Mean ± SEM time to des...
BBC broadcasters’ unpublished views on Jung: Priestley and Freeman

This article shows the unpublished views of J. B. Priestley and John Freeman, two significant BBC broadcasters on Jung. Priestley puzzled over individuation in Jung, but his most striking comment was that H. G. Baynes’ death in 1943 had been an enormous loss to Jungians in Britain. Freeman strikingly commented on Marie-Louise von Franz as the most important person in Jung's life after Emma Jung's death, on Jung's immediate entourage regarding him as a sort of demi-God in his last years, and on India perhaps being more than he could sustain. Freeman acted as co-ordinating editor of Jung's final book, Man and his symbols.
Writing Better Software for Economics Principles Textbooks

Instructional software packages accompanying textbooks are evaluated and compared with those independently available.
A numerical integration method useful for studying ionospheric phenomena

Abstract A study of ionospheric phenomena requires a numerical integration method capable of handling large numbers of coupled, nonlinear, first order ordinary differential equations which describe the various phenomena in the ionosphere. A suitable method should be well-behaved, able to take large integration time steps, accurate, and conserve chemical and charge balance to within acceptable limits. A third-order method will be described using approximately 600 reactions and 62 interacting species. This technique is unique in that it automatically conserves chemical and charge balance to within roundoff limits of the computer, as do all classical methods.
Prediction of wave-front sensor slope measurements with artificial neural networks.

For adaptive optical systems to compensate for atmospheric turbulence effects, the wave-front perturbation must be measured with a wave-front sensor (WFS) and corrected with a deformable mirror. One limitation in this process is the time delay between the measurement of the aberrated wave front and implementation of the proper correction. Statistical techniques exist for predicting the atmospheric aberrations at the time of correction based on the present and past measured wave fronts. However, for the statistical techniques to be effective, key parameters of the atmosphere and the adaptive optical system must be known. These parameters include the Fried coherence length r0, the atmospheric wind-speed profile, and the WFS slope measurement error. Neural networks provide nonlinear solutions to adaptive optical problems while offering the possibility to function under changing seeing conditions without actual knowledge of the current state of the key parameters. We address the use of neural networks for WFS slope measurement prediction with only the noisy WFS measurements as inputs. Where appropriate, we compare with classical statistical-based methods to determine if neural networks offer true benefits in performance.
Detection of viral RNA from paraffin-embedded tissues after prolonged formalin fixation.

Background: Isolating amplifiable RNA from formalin-fixed, paraffin-embedded (FFPE) tissues is more difficult than isolating DNA because of RNases, chemical modification of the RNA, and cross-linking of nucleic acids and proteins. Tissues containing infectious disease agents that require biosafety level (BSL)-3 and -4 necessitate fixation times of 21 and 30 days, respectively. Objective: To improve procedures for extracting RNA from these FFPE tissues and detect the RNA with the more sensitive TaqMan®-based reverse transcriptase (RT)-PCR. Study design: Through a single modification of a commercially available kit, we were able to extract amplifiable RNA and detect West Nile virus (WNV), Marburg virus (MARV), and Ebola virus (EBOV)-infected tissues using TaqMan ® assays. Results: Formalin fixation results in an approximately 2 log10 reduction in detection limit when compared to fresh tissues. Increasing proteinase K digestion (24 h) improved extraction of amplifiable RNA from FFPE tissues. The TaqMan ® results were comparable to more traditional detection results such as virus isolation. Conclusion: This improved extraction procedure for obtaining RNA combined with the TaqMan ® RT-PCR assays permit retrospective and prospective studies on FFPE tissues infected with BSL-3 and -4 pathogens.
G protein–coupled receptor/arrestin3 modulation of the endocytic machinery

Nonvisual arrestins (arr) modulate G protein–coupled receptor (GPCR) desensitization and internalization and bind to both clathrin (CL) and AP-2 components of the endocytic coated pit (CP). This raises the possibility that endocytosis of some GPCRs may be a consequence of arr-induced de novo CP formation. To directly test this hypothesis, we examined the behavior of green fluorescent protein (GFP)-arr3 in live cells expressing β2-adrenergic receptors and fluorescent CL. After agonist stimulation, the diffuse GFP-arr3 signal rapidly became punctate and colocalized virtually completely with preexisting CP spots, demonstrating that activated complexes accumulate in previously formed CPs rather than nucleating new CP formation. After arr3 recruitment, CP appeared larger: electron microscopy analysis revealed an increase in both CP number and in the occurrence of clustered CPs. Mutant arr3 proteins with impaired binding to CL or AP-2 displayed reduced recruitment to CPs, but were still capable of inducing CP clustering. In contrast, though constitutively present in CPs, the COOH-terminal moiety of arr3, which contains CP binding sites but lacks receptor binding, did not induce CP clustering. Together, these results indicate that recruitment of functional arr3–GPCR complexes to CP is necessary to induce clustering. Latrunculin B or 16°C blocked CP rearrangements without affecting arr3 recruitment to CP. These results and earlier studies suggest that discrete CP zones exist on cell surfaces, each capable of supporting adjacent CPs, and that the cortical actin membrane skeleton is intimately involved with both the maintenance of existing CPs and the generation of new structures.
Eigenmode resonance in a two-layer stratification

In this paper, we study the velocity field at the density interface of a two-layer stratification system when the flow is forced at the mid-depth of the lower layer by the source–sink forcing method. It is known that, in a sufficiently strong linear stratification, the source–sink forcing in certain configurations produces a single-vortex pattern which corresponds to the lowest eigenmode of the Helmholtz equation (Kanda & Linden 2001). Two types of forcing configuration are used for the two-layer experiments: one that leads to a steady single-vortex pattern in a linear stratification, and one that results in an unsteady irregular state. Strong single-vortex patterns appear intermittently for the former configurations despite the absence of stratification at the forcing height. When the single-vortex pattern occurs at the density interface, a similar flow field extends down to the forcing height. The behaviour is explained as the coupling of the resonant eigenmode at the interface with the horizontal component of the forcing jets. The results show that stratification can organise a flow, even though it is forced by an apparently random three-dimensional forcing.
Simulation-based optimization for material dispatching in a retailer network

This paper presents preliminary work done on simulation-based optimization of a stochastic material-dispatching system in a retailer network. The problem we consider is one of determining the optimal number of trucks and quantities to be dispatched in such a system. Theoretical solution models for versions of this problem can be found in the literature. Unlike most theoretical models, we can accommodate many real-life considerations, such as arbitrary distributions of the governing random variables, and all important cost elements, such as inventory-holding costs, stock-out costs, and transportation costs. We have used two techniques, namely, neuro-response surfaces and simulated annealing, for optimizing our system. We have also used a problem-specific heuristic, known as the mean demand heuristic, to provide us with a good starting point for simulated annealing and a benchmark for our other methods. Some computational results are also provided.
Sequential Metastatic Breast Cancer Chemotherapy: Should the Median be the Message?

Background: Counseling and anticipatory guidance of the expected course of treatment for women newly diagnosed with metastatic breast cancer (MBC) are difficult due to multiple factors influencing survival following metastatic breast cancer therapy. In order to better tailor counseling at the onset and through the duration of metastatic breast cancer we used non-clinical trial data to better characterize real life experience of sequential metastatic breast cancer treatment. We examined the following aims: 1. What demographic and tumor characteristics are predictive of survival in metastatic breast cancer? 2. What is the median duration of each sequential chemotherapy regimen and subsequent survival of women following each sequence of chemotherapy regimen in metastatic breast cancer? Methods: Retrospective study included 792 women diagnosed from January 1999 through December 2009 at the University of Pittsburgh Cancer Institute Breast Cancer Program. Results: Median duration of sequential chemotherapy regimen and median survival from completion of sequence of chemotherapy regimens were relatively short with a wide range of treatment duration and survival. Characteristics for poor survival included hormone status, human epidermal growth factor receptor-2 (HER 2/neu) status, and increased number and type of metastatic sites. Women who took more than the second sequential chemotherapy regimens had no more than median 3 months of treatment duration and 6 months survival from treatment termination. Discussion: Median clinical response and survival shorten with sequential chemotherapy regimen but with wide ranges. The rare clinical response of the minority should not set the standard for treatment expectations. All cancer clinicians, including oncology nurses, must ensure that patients are receiving tailored counseling regarding their specific risks and benefits for sequential metastatic breast cancer chemotherapy.
Ambiguous Commodities, Unstable Frontiers: The Case of Burma, Siam, and Imperial Britain, 1800-1900

At the turn of the nineteenth century in Southeast Asia, the Kingdoms of Burma and Siam were largely stable, independent polities: powerful in relation to their neighbors, self-sufficient in terms of food, and possessing little reason to believe that these parameters would be changing within the clearly foreseeable future.' A century later, Burma as an independent entity had disappeared off the map, and Siam-at least in terms of its official foreign trade-was an economic satellite of the British Empire. Burmese teak now floated downstream to British Rangoon, while Siamese rice was carried to the world in the hulls of British ships. The Burmese monarchy had been disbanded; 93 percent of all official Siamese imports and exports were in the hands of London's merchants.2 How did these transformations occur, and why? Were the processes of domination geared toward the economies, politics, or "geobodies" of these two countries, or toward an integrated combination of all three? What role did material objects of trade themselves play in this process, objects that were often deemed illegal as they passed through unstable, liminal spaces along the frontier? This paper approaches these questions through the intertwined threads of boundary-formation, political maneuvering, and quasi-legal commodities. I show how an initial British priority of protection for India and the sea-routes to China gradually evolved into a demand for open markets, and finally, into territorial dominion. Burma's geography, in one sense, put her at a disadvantage Acknowledgments: I wish to thank the SSRC for inviting me to their "Beyond Borders" workshop in Paris, where an earlier version of this paper was initially presented. Special thanks to Itty Abraham and Willem van Schendel, David Atwill, and Sun Laichen for their comments at that gathering. Thanks also to CSSH's three anonymous referees, and Michael Charney, Robert Kubicek, and Tamara Loos, historians of Burma, Imperial Britain, and Siam, respectively, for reading and commenting on this article.
Genetic perturbation of the putative cytoplasmic membrane-proximal salt bridge aberrantly activates α4 integrins

α4 integrins play a pivotal role in leukocyte migration and tissue-specific homing. The ability of integrins to bind ligand is dynamically regulated by activation-dependent conformational changes triggered in the cytoplasmic domain. An NMR solution structure defined a putative membrane-proximal salt bridge between the αIIbβ3 integrin cytoplasmic tails, which restrains integrins in their low-affinity state. However, the physiological importance of this salt bridge in α4 integrin regulation remains to be elucidated. To address this question, we disrupted the salt bridge in murine germ line by mutating the conserved cytoplasmic arginine RGFFKR in α4 integrins. In lymphocytes from knock-in mice (α4-R/AGFFKR), α4β1 and α4β7 integrins exhibited constitutively up-regulated ligand binding. However, transmigration of these cells across VCAM-1 and MAdCAM-1 substrates, or across endothelial monolayers, was reduced. Perturbed detachment of the tail appeared to cause the reduced cell migration of α4-R/AGFFKR lymphocytes. In vivo, α4-R/AGFFKR cells exhibited increased firm adhesion to Peyer patch venules but reduced homing to the gut. Our results demonstrate that the membrane-proximal salt bridge plays a critical role in supporting proper α4 integrin adhesive dynamics. Loss of this interaction destabilizes the nonadhesive conformation, and thereby perturbs the properly balanced cycles of adhesion and deadhesion required for efficient cell migration.
Upregulation of Kupffer cell beta-adrenoceptors and cAMP levels during the late stage of sepsis.

Although a burst of immunoresponsiveness may occur during the early stage of sepsis, late sepsis is characterized by severe immunodepression. In addition, although studies have shown that stimulation of macrophage beta-adrenoceptors results in an increase in cAMP and an associated reduction in macrophage phagocytic activity, it remains unknown whether Kupffer cell beta-adrenoceptor characteristics and cAMP levels are altered during polymicrobial sepsis. To study this, Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h (i.e., the early stage of sepsis) or 20 h (late sepsis) after CLP or sham operation, the liver was perfused with collagenase solution and Kupffer cells were isolated. beta-Adrenoceptor characteristics of the isolated Kupffer cells were determined using [125I]iodopindolol, and basal levels of cAMP were measured by radioimmunoassay. The results indicate that while maximum binding capacity (Bmax) of Kupffer cell beta-adrenoceptors was not altered at 5 h, it increased significantly at 20 h after CLP. Similarly, basal levels of cAMP in Kupffer cells did not change at 5 h but increased markedly at 20 h after the onset of sepsis. In contrast, the dissociation constant (Kd, 1/affinity) of Kupffer cell beta-adrenoceptors was not significantly affected by sepsis at both 5 h and 20 h after CLP. Thus, upregulation of beta-adrenoceptors and increase in cAMP levels in Kupffer cells occur during the late stage of polymicrobial sepsis, and this may contribute to the depression of macrophage phagocytic function under such conditions.
Dendritic tiling through TOR signalling.

In many sensory systems, dendrites of sensory neurons cover an entire sensory field in a complete and non‐redundant manner, a phenomenon called dendritic tiling. Previous studies have identified the Tricornered (Trc) kinase as an important regulator of this process. In this issue of The EMBO Journal , Koike‐Kumagai et al (2009) found that the target of rapamycin (TOR) complex 2 (TORC2) is essential for dendritic tiling by way of regulating Trc kinase activity in Drosophila class IV dendritic arborization (da) neurons. This study provides the first in vivo evidence for a function of TORC2 activity in nervous system development.
Psychological effects of snacks and altered meal frequency

Over the past two decades, substantial research has been conducted to investigate the idea that alterations in short-term nutritional intake play a role in influencing cognitive behaviour and mood. A portion of this research has examined specifically the effect of meal intake on the performance of mental tasks and subjective feelings of mood. Results of this research indicate that a number of variables including the timing and nutritional composition of the meal, nutritional status, habitual patterns of feeding behaviour, beliefs about food, and the nature of the mental tasks, can influence the effects of meals on cognitive behaviour. For example, studies have demonstrated that breakfast intake generally is associated with an improvement in cognitive performance later in the morning, while lunch intake is associated with an impairment in mid-afternoon performance on mental tasks and more negative reports of mood. Intake of nutrients late in the afternoon appears to have a positive effect on subsequent performance on tasks involving sustained attention or memory. Although research has provided insights into the role of meal intake on cognitive behaviour and mood, there are a number of factors which remain to be studied. These include the interaction of age, gender, activity level, meal composition, personality factors, stress with the effects of meals on cognitive behaviour. Additionally, more work is needed on the time-course of short-term nutrient effects, and the effects of chronic changes in meal intake on behaviour.
Arthroscopic and magnetic resonance arthrogram features of Kim's lesion in posterior shoulder instability.

Purpose The purpose of this study was to describe the anatomic features of the glenoid and labrum for shoulders with and without Kim's lesions, as well as define the sensitivity, specificity, and reliability of magnetic resonance arthrogram for the detection of these lesions and determine the interobserver reliability of Kim's classification for posterior labral tears. Methods A retrospective, blinded analysis of 41 shoulders was performed. Twenty-one shoulders composed the Kim's lesion group. Three observers measured glenoid and chondrolabral retroversion and anterior and posterior labral height. The shoulders were classified as 1 of 3 types according to Kim's classification. Results There were no differences in glenoid version, chondrolabral version, glenoid depth, and labral height between the groups. The sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing Kim's lesions were 85.7%, 75%, 78.3%, and 83.3%, respectively. The κ values for interobserver reliability for detecting and classifying Kim's lesions were 0.739 (substantial) and 0.329 (fair), respectively. Conclusions Patients with incomplete posteroinferior labral tears have similar retroversion (bony and soft tissue) and labral height to patients without posterior shoulder instability. The sensitivity, specificity, and reliability of magnetic resonance arthrogram for detecting these lesions are substantial. The interobserver reliability of Kim's classification is fair. Level of Evidence Level IV, retrospective case-control study.
The synthesis of coliphage T1 DNA: Requirement for host dna genes involved in elongation

Abstract Available Escherichia coli mutants with temperature-sensitive mutations in genes essential for DNA replication have been used to investigate the host protein involvement in the DNA synthesis of bacteriophage T1. This study has shown that T1 is independent of the E. coli initiation gene products dna A, dna C, dna I, dna P, and dna T. The gene products of the pol C, dna G, and dna Z loci, know to be involved in the elongation events of replication, are required for a productive T1 infection. T1 was found to be independent of the functioning of the dna B gene product in the four dna B mutants tested.
Recent historically low global tropical cyclone activity

[1] Tropical cyclone accumulated cyclone energy (ACE) has exhibited strikingly large global interannual variability during the past 40-years. In the pentad since 2006, Northern Hemisphere and global tropical cyclone ACE has decreased dramatically to the lowest levels since the late 1970s. Additionally, the global frequency of tropical cyclones has reached a historical low. Here evidence is presented demonstrating that considerable variability in tropical cyclone ACE is associated with the evolution of the character of observed large-scale climate mechanisms including the El Nino Southern Oscillation and Pacific Decadal Oscillation. In contrast to record quiet North Pacific tropical cyclone activity in 2010, the North Atlantic basin remained very active by contributing almost one-third of the overall calendar year global ACE.
Results of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis.

This randomized, double-blind, phase II study evaluated the pharmacodynamics, safety and tolerability of ISIS 329993 (ISIS-CRPRx), an antisense oligonucleotide, in patients with active rheumatoid arthritis (RA). Patients with active RA of at least six months duration were randomized into three cohorts to receive ISIS-CRPRx (100 mg, 200 mg or 400 mg) or placebo (3 active:1 placebo within each cohort) via subcutaneous (SC) injection on Days 1, 3, 5 and 8 and then once weekly for the next 11 weeks. The effects of study treatment on high-sensitivity C-reactive protein (hs-CRP) level were evaluated. An exploratory analysis on disease activity was assessed via the American College of Rheumatology 20% improvement criteria (ACR20). Safety was evaluated via adverse events and laboratory measures. Fifty-one patients received one of the following treatments: ISIS-CRPRx 100 mg, n = 12; 200 mg, n = 13, 400 mg, n = 14; placebo n = 12. In the ISIS-CRPRx treatment groups there were dose-dependent reductions in hs-CRP. At Day 36 the mean percent change from baseline was: placebo: −14.4%; ISIS-CRPRx 100 mg: −19.5%; 200 mg: −56.6% and 400 mg: −76.7%, (P = 0.0015 placebo compared to 400 mg). There were no differences between treatment groups and placebo in the ACR20 at Day 36 or Day 92. There were no serious infections and no elevations in liver function tests, lipids, creatinine or other lab abnormalities related to ISIS-CRPRx. In this study, ISIS-CRPRx selectively reduced hs-CRP in a dose-dependent manner, and was well-tolerated in patients with RA. Its utility as a therapy in RA remains unclear. Clinicaltrials.gov NCT01414101 . Registered 21 July 2011.
Upregulation of Arterial Serotonin 1B and 2B Receptors in Deoxycorticosterone Acetate-Salt Hypertension

Previous studies have established a role for 5-hydroxytryptamine (5-HT) 2B and 5-HT 1B receptors in mediating enhanced contraction to serotonin (5-HT) in arteries from hypertensive deoxycorticosterone acetate (DOCA)-salt rats. To determine whether the observed increase in responsiveness was due to upregulation of 5-HT receptors, we used Western analysis to measure 5-HT 1B and 5-HT 2B receptor protein density. In endothelium-denuded aortas from hypertensive DOCA-salt rats (mean systolic blood pressure 192±6 mm Hg), 5-HT 1B and 5-HT 2B receptor proteins were upregulated ≈2-fold compared with the response in the aortas of sham-operated control rats (mean systolic blood pressure 119±2 mm Hg). Contraction to 5-HT 2B receptor agonists was also enhanced in arteries from Wistar-Furth rats given DOCA and salt. This strain is relatively resistant to the hypertensive effects of DOCA and salt treatment. A common factor between the model of DOCA-salt hypertension and the DOCA-salt–treated Wistar-Furth rats is the presence of mineralocorticoids. Therefore, we tested the hypothesis that mineralocorticoids can upregulate 5-HT 1B and 5-HT 2B receptors. Aortas from normal Sprague-Dawley rats were incubated with aldosterone (100 nmol/L) for 8, 12, 24, and 48 hours. The expression of 5-HT 2B and 5-HT 1B receptor proteins was significantly increased (≈2- fold over vehicle treatment) by 8 hours. 5-HT 2B and 5-HT 1B receptors were upregulated by aldosterone in a concentration-dependent manner, and incubation with spironolactone (10 μmol/L) blocked this upregulation. These data support the conclusion that the increased expression of 5-HT 1B and 5-HT 2B receptors observed in arteries from DOCA-salt rats may be partially due to mineralocorticoids acting via the mineralocorticoid receptor to modulate gene expression.
The influence of grain‐selection on the meaning of quartz‐diagrams

The most important factor which would reduce confusion in fabric analyses is the expanded use of partial diagrams. The purpose of this paper is to stress the significance of partial diagrams in a consideration of some confusing aspects of petrofabrics. Any statistical study results in the accumulation of a mass of detail. In quartz-fabric analyses the detail consists of the measuring and plotting of thousands of quartz-axes; in an analysis of joints it consists of the measuring and plotting of thousands of joint-attitudes. In each case limiting factors are required to give meaning to the accumulated data. The study of joints, to be significant, must be confined to an area with well-integrated structural features. In quartz-fabric studies discrimination between grain-types is essential to the development of interpretable diagrams.
Finding the Evidence in Tamper-Evident Logs

Secure logs are powerful tools for building systems that must resist forgery, prove temporal relationships, and stand up to forensic scrutiny. The proofs of order and integrity encoded in these tamper-evident chronological records, typically built using hash chaining, may be used by applications to enforce operating constraints or sound alarms at suspicious activity. However, existing research stops short of discussing how one might go about automatically determining whether a given secure log satisfies a given set of constraints on its records. In this paper, we discuss our work on Querifier, a tool that accomplishes this. It can be used offline as an analyzer for static logs, or online during the runtime of a logging application. Querifier rules are written in a flexible pattern-matching language that adapts to arbitrary log structures; given a set of rules and available log data, Querifier presents evidence of correctness and offers counterexamples if desired. We describe Querfier's implementation and offer early performance results.
SMALL SONG REPERTOIRES AND HIGH RATE OF SONG-TYPE SHARING AMONG CANYON WRENS

Abstract. The song of the Canyon Wren (Catherpes mexicanus) is widely recognized but poorly studied. Here we present the first comprehensive description of Canyon Wren song, including data from a focused study in northern Colorado and data from songs recorded across the species' geographic range. Both male and female Canyon Wrens produce a stereotyped contact call and sex-specific song. Females sing infrequently, using a single song type. Males typically sing five song types, all consisting of a descending cascade of notes to which they variably append up to seven broadband notes. Songs are delivered with eventual variety in bouts that include an average of 4.6 repetitions of one song type, with temporal breaks between bouts. In the population we studied most song types were widely shared and males' repertoires overlapped by 94%. Some song types are apparently geographically restricted, while others are sung across large areas of the species' range. Overall, our results suggest that the Canyon Wren's song...
Scalable arbitration of partitioned bus interconnection networks in 3D-IC systems

In this paper, we describe a scalable interconnection network architecture intended for very large multicore processors implemented on stacked chip 3D integrated circuits (3D-IC). These networks provide fully interconnected, low latency, single hop performance with wiring complexity that scales linearly with the size of the network. The enabling technology for these networks is a novel, fully distributed arbitration and control algorithm that operates solely at the edges of the network without the need for any routers within the network core. This paper is focused on a description of that algorithm. We present simulation results for average, worst-case, and per-node latencies showing that our arbitration algorithm performs efficiently, scales for a wide range of partition sizes, and effectively manages highly non-uniform traffic patterns.