cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4207: JAK inhibition reverses IL10-mediated resistance to B cell receptor (BCR) pathway inhibition in DLBCL

Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin9s lymphoma, and can be classified into activated B-cell like (ABC) and germinal center B-cell like (GCB) DLBCL according to gene expression profiling. In both subtypes, dysregulation of the B cell receptor (BCR) signaling pathway plays a critical role in tumorigenesis and survival. BCR activation induces phosphorylation of CD79A/B by Src family tyrosine kinases, which leads to the activation of the BTK and PI3Kδ/Akt pathways. Oncogenic mutations have been identified in DLBCL impacting CD79A/B (BCR complex), PTEN (negative regulator of PI3K), CARD11 and MYD88 (NF-kB activating factors) function. The influence of these mutations on the DLBCL phenotype appears to be further modified by aberrant cytokine signaling and JAK/Stat pathway activation. High levels of JAK/Stat-activating cytokines such as IL6 and IL10 are present in DLBCL, and patients with high serum IL10 have been shown to have shorter event-free survival and a higher international Prognostic Index score. Therefore, concurrent inhibition of both the BCR and JAK/Stat pathways may provide an attractive therapeutic approach in DLBCL. We have developed and characterized a potent and selective PI3Kδ inhibitor INCB040093 and have established that DLBCL cells are sensitive to INCB040093 treatment. We demonstrate that IL10 activates the JAK/Stat signaling pathway in DLBCL cells, which renders the cells resistant to INCB040093 in cell proliferation assays. This resistance can be reversed by co-treatment with a JAK1/JAK2 inhibitor. Although INCB040093 induces apoptosis in DLBCL cells, concurrent activation of the JAK/Stat pathway by IL10 prevents INCB040093-induced apoptosis, an effect that can be abrogated by a JAK1/JAK2 inhibitor. Similar resistance to IL-10 is observed with the BTK inhibitor, ibrutinib, which can also be reversed by a JAK1/JAK2 inhibitor. Interestingly, a JAK1 selective inhibitor is as effective as a JAK1/JAK2 inhibitor in reversing the IL10-mediated resistance to PI3Kδ and BTK inhibition. Combination treatment blocks both PI3K/Akt and JAK/Stat signaling pathways and results in the down-regulation of pro-survival proteins, including Pim2 and c-myc. These data illustrate the functional cross-talk that exists in DLBCL between the BCR and JAK/Stat signaling pathways, and support the clinical evaluation of combined BCR and JAK inhibition as a novel approach to targeted therapy. Citation Format: Xuesong (Mike) Liu, Margaret Favata, Jun Li, Niu Shin, Kathy He Wang, Qian Wang, Yun-Long Li, Andrew Combs, Chu-Biao Xue, Robert Newton, Kris Vaddi, Peggy Scherle. JAK inhibition reverses IL10-mediated resistance to B cell receptor (BCR) pathway inhibition in DLBCL. [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 4207. doi:10.1158/1538-7445.AM2014-4207
Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony-stimulating factor.

We administered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM-CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM-CSF added to chemotherapy in patients with newly diagnosed AML.
Adapting to Student Uncertainty Improves Tutoring Dialogues

This study shows that affect-adaptive computer tutoring can significantly improve performance on learning efficiency and user satisfaction. We compare two different student uncertainty adaptations which were designed, implemented and evaluated in a controlled experiment using four versions of a wizarded spoken dialogue tutoring system: two adaptive systems used in two experimental conditions (basic and empirical), and two non-adaptive systems used in two control conditions (normal and random). In prior work we compared learning gains across the four systems; here we compare two other important performance metrics: learning efficiency and user satisfaction. We show that the basic adaptive system outperforms the normal (non-adaptive) and empirical (adaptive) systems in terms of learning efficiency. We also show that the empirical (adaptive) and random (non-adaptive) systems outperform the basic adaptive system in terms of user perception of tutor response quality. However, only the basic adaptive system shows a positive correlation between learning and user perception of decreased uncertainty.
An optimization model for sequential fast pyrolysis facility location-allocation under renewable fuel standard

Abstract In this paper, an MILP (mixed integer linear programming) model is formulated to perform a sequential expansion planning of biofuel production system with fast pyrolysis, hydroprocessing and refining technology. Liquid transportation fuels are the major products of this renewable conversion process. The planning objective is to maximize the net present profit of the entire biofuel production system over the planning horizon. The planning horizon selected is from 2014 to 2022, the target year of the RFS2 (revised renewable fuel standard). A case study in Iowa is implemented, analyzing the sequential spatial construction decisions under a variety of processing goals. The potential of drop-in fuels production from corn stover in Iowa is examined, showing an around 40 cents per gallon profit under the optimal location-allocation planning.
Regulation of Alveolar Procoagulant Activity and Permeability in Direct Acute Lung Injury by Lung Epithelial Tissue Factor

Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury, leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) after intratracheal LPS administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with intratracheal LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type (WT) levels at baseline and to 29% of WT levels after intratracheal LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF did not differ from WT mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after intratracheal LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung, contributing 60-70% of total lung TF, and that lung epithelial, but not myeloid, TF may be protective in direct ALI.
The Interactions of Climate and Biotic Factors on Life History Characteristics and Vital Rates of Yellowstone Cutthroat Trout in Spread Creek, WY

Habitat degradation and introduction of non-native salmonids have caused substantial declines in abundance and distribution of Yellowstone cutthroat trout. Additionally, global climate change is expected to exacerbate current threats through changes to thermal regimes, hydrology, stream productivity, and distributions of non-native species. Understanding how factors such as climate and local stressors (e.g., non-native species) interact to affect Yellowstone cutthroat trout is critical for developing management strategies to enhance future persistence. However, research investigating relationships among these factors and life history characteristics and vital rates of Yellowstone cutthroat trout is lacking. To address this need, we examined the influences of temperature, streamflow, food availability, and presence of brook trout on life history characteristics of Yellowstone cutthroat trout in Spread Creek, Wyoming. We used passive integrated transponder (PIT) tags and a combination of stationary and mobile PIT tag antennae within a capture-recapture framework to monitor growth, movement, and survival of Yellowstone cutthroat trout and brook trout throughout the Spread Creek drainage. Considerable differences existed in frequencies of movements between species and among tributaries. Significant differences existed among growth rates of trout in three tributary streams. Preliminary results suggest the observed differences were driven by the complex interactions of streamflows, fish densities, and prey abundances, rather than stream temperatures. We discuss our results in the context of maintaining diversity of life-history patterns within watersheds as a means to increase metapopulation resiliency. Our findings provide critical information needed to refine climate risk assessments and to better direct limited resources to ensure the long term persistence of the subspecies.
Severity of pelvic organ prolapse associated with measurements of pelvic floor function

This study tested the hypothesis that clinical measurements of the superficial perineum and of pelvic floor muscle (PFM) function correlate with the severity of pelvic organ prolapse. This retrospective cross-sectional study assessed 1037 women in an academic urogynecologic practice. Greatest descent of prolapse, by the Pelvic Organ Prolapse Quantification system, was correlated with two assessments of levator function—the Oxford grading scale and levator hiatus (LH) size measured by digital examination. Correlations were calculated using Pearson’s correlation for continuous variables and Kendall’s tau-b. Severity of prolapse correlated moderately with genital hiatus (GH) (r=0.5, p<0.0001) and with LH (transverse r=0.4, p<0.0001; longitudinal r=0.5, p<0.0001), but weakly with the Oxford grading scale (r=−0.16, p<0.0001). LH correlated with GH (r=0.5, p<0.0001) but not with perineal body (r=0.06, p=0.06). Both GH and LH size are associated with the severity of prolapse. LH size correlates more strongly to prolapse severity than assessment of PFM function by the Oxford grading scale.
The Diagnostic Dilemma: A Clinician's Viewpoint

The prevalence of renovascular hypertension appears to be increasing, particularly in older patients with generalized arteriosclerosis, hypertension and impaired renal function. While clinical clues remain extremely useful in identifying patients at increased risk, older screening tests have been largely abandoned in favor of angiographic methods that provide visual identification of renal artery lesions. Renal scintigraphic techniques, with or without angiotensin-converting enzyme (ACE) inhibition, offer the potential for providing accurate measurements of renal function, and may be particularly useful in identifying critical renal arterial stenosis. In assessing the future role of scintigraphy, careful clinical validation of these correlations will be necessary, as will determinations of their usefulness in patients with renal insufficiency and those with bilateral renal artery stenosis. The role of adrenal scintigraphy in the localization of adrenal tumors is also reviewed. Their cost-effectiveness, limitations in sensitivity and specificity compared to current diagnostic technologies, and potential applications are discussed.
Increase in spontaneous motor activity following infusion of neurotensin into the ventral tegmental area

Microinjection of neurotensin (NT) into the ventral tegmental area (VTA) of the rat produced a dose-dependent increase in spontaneous motor activity. The NT-induced hyperactivity consisted of an increase in exploratory behaviors, such as locomotion, rearing and sniffing, and a decrease in sleep or resting. The structural specificity of this response was demonstrated by microinjecting NT analogues endogeneous neuropeptides into the VTA. The fact that high levels of immunoreactive NT have been demonstrated in the VTA indicates that the observed behavioral effects may reflect an underlying physiological action by endogenous NT.
Vibration Frequencies of Tapered Bars With End Mass

Extension des resultats pour une poutre cantilever aux effets d'une masse concentree a l'extremite libre d'une poutre conique
System For Phase Shifting Interferometry In The Presence Of Vibration

Very accurate and detailed testing of small and moderate size optical surfaces can be realized by phase shifting interferometry. However, for the very large primaries needed for the next generation of telescopes, it is difficult and expensive to keep vibrations low enough for this method to work. A modification to the usual phase shifting interferometry reduction algorithm permits measurements to be taken fast enough to essentially freeze out vibrations. Only two interferograms are needed with an exact phase relationship; and these can be recorded very rapidly on either side of the interline transfer of a standard CCD video camera, prior to charge transfer readout. The third required interferogram is a null. In the developed implementation, two frequencies, dv/v.10-8, are generated with orthogonal polarizations. A Pockels cell rapidly switches the frequency entering the interferometer, resulting in a phase shift over the long path difference of the interferometer. The two time critical interferograms are acquired with a lms separation resulting in a reduction in sensitivity to vibration of one to two orders of magnitude. Laboratory tests were performed to compare this "2 + 1" system with a commercial phase shifting package. Similar phase determination accuracies were found when vibrations were low. However, the "2 + 1" system also succeeded when vibrations were large enough to wash out video rate fringes.© (1989) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
'Insulin-like' effects of lithium ion on isolated rat adipocytes. I. Stimulation of glycogenesis beyond glucose transport.

Both insulin and lithium ion stimulated cytochalasin B-sensitive glucose transport in isolated rat adipocytes. As a result of enhanced glucose transport, the incorporation of [14C]glucose into CO2, glycogen and lipid were increased by both agents. However, the action of these two agents was distinguished. Cytochalasin B decreased insulin-stimulated glucose oxidation, glycogenesis and lipogenesis. In contrast, lithium-stimulated glycogenesis was decreased but lithium-stimulated glucose oxidation and lipogenesis were completely blocked. These results indicate that lithium ion in rat adipocytes has a specific insulin-like effect on glycogenesis without affecting glucose oxidation and lipogenesis.
Pupil size and quality of vision after LASIK.

Abstract Purpose To evaluate factors related to the quality of vision after LASIK. Design Survey study. Participants One hundred consecutive patients. Intervention LASIK with a 6.0-mm elliptical ablation pattern without transition zone to treat mild to moderate myopia or astigmatism (preoperative manifest spherical equivalent [MSE], −4.79 ± 1.33 diopters [D]; range, −2.88 to −9.25 D). The second eye was treated 1 month after the first. Main outcome measures Completed questionnaires assessing night vision problems (glare, haze, and halo symptoms) before surgery and at 1, 3, and 6 months after surgery in 97, 75, 81, and 66 subjects, respectively. Mesopic pupil size and preoperative and postoperative variables were analyzed with questionnaire data using an analysis of variance (ANOVA) and multivariate regression analysis. Results Patients with large mesopic pupils had significantly more reports of glare, haze, and halo than did those with smaller pupils in the treated eye at 1 month after surgery ( P =0.02, P =0.03, and P =0.02, respectively ANOVA) and of glare at 3 months ( P =0.05). Significant predictors of symptoms at 6 months, identified through multivariate regression analysis, included preoperative MSE (for glare and haze), preoperative contrast acuity (glare), postoperative uncorrected visual acuity (UCVA; haze), and residual cylinder (haze). Together, these factors accounted for only 19% of the overall variability in glare and 37% of the variability in haze responses. No relationship between pupils and symptoms was noted at 6 months after surgery in either the ANOVA or regression analysis group. Conclusions Patients with large pupils had more quality of vision symptoms in the early postoperative period, but no correlation was observed 6 months after surgery. Factors related to long-term symptoms include the level of treatment (preoperative myopia), preoperative contrast acuity, postoperative UCVA, and residual cylinder. Most of the variability in visual quality could not be explained by preoperative or clinical outcome measures, including pupil size.
Cartilage damaging activities of fibronectin fragments derived from cartilage and synovial fluid.

Objective: to investigate whether fibronectin fragments (Fn-fs), shown to damage cultured cartilage, can be found in cartilage from patients with osteoarthritis (OA) or rheumatoid arthritis, or can be generated from fibronectin (Fn) within synovial fluids or from Fn in the matrix of cultured cartilage. To also determine whether cartilage or synovial fluid Fn-fs are active and, thus, could contribute to cartilage damagein vivo. Methods Fn-fs were immunochemically identified in cartilage extracts from patients with OA or rheumatoid arthritis or in bovine cartilage cultured with IL-1α or in bovine synovial fluids treated with stromelysin-1 (MMP-3). The effect of removal of Fn-fs from OA synovial fluids was tested by passing fluids over an anti-Fn column and adding the resultant fluids to bovine cartilage cultures to measure proteoglycan (PG) degradation. Gelatin–Sepharose purified Fns from bovine plasma, synovial fluid or cartilage were digested with MMP-3 and the Fn-fs tested for degradation of PG in cultured cartilage. Results: Extracts of cartilage from patients with rheumatoid arthritis or with OA contained a range of Fn-fs. Removal of Fn-fs from OA synovial fluids significantly reduced the resultant damage when the fluids were added to cultured cartilage. Addition of IL-1α to cultured cartilage or of MMP-3 to synovial fluids enhanced generation of Fn-fs. Fn-fs, whether derived from bovine plasma or synovial fluid or cartilage Fns, damaged cartilage. Conclusions: These data demonstrate that although Fn-fs could be generatedin vivo, Fn-fs could also be generated within cartilage and amplify cartilage damage. Thus, Fn-fs may be both autocrine and paracrine regulators of cartilage metabolism.
Workshop — HigherEd 2.0: Engineering education using web 2.0 technologies

Web 2.0 technologies and social media have become pervasive elements of modern life, especially for the college-age population. Recent substantial advances in media authoring tools provide powerful platforms for academic content creation-by faculty and students alike. Leveraging these technologies in the service of education presents great promise, but also many challenges. In this workshop, we present hands-on training in the tools and strategies we have developed through the HigherEd 2.0 initiative. A four-university collaboration, HigherEd 2.0 encompasses digital content creation, digital library management, course deployment, and intervention evaluation. This workshop will address each of these elements, and include specific, hand-on training in multimedia development, course blog creation and management, and student creation of sharable digital course content.
Providing location anonymity in a multi-base station wireless sensor network

Wireless Sensor Networks (WSNs) often operate in inhospitable environments to serve mission-critical and security-sensitive applications that involve hostile adversaries. These adversaries are eager to disrupt the WSN operation. Given the important role that the base-station (BS) plays in a WSN, the adversary opts to identify the BS and determine its location in order to damage the BS or launch a targeted denial of service attack. Therefore, maintaining the BS anonymity is of utmost importance in WSNs. Even if the adversary cannot decode packets, correlating the intercepted transmission through traffic analysis can reveal the position of the BS. This paper considers setups in which the network has multiple base-stations and proposes a novel approach in which these base-stations collaborate on confusing the adversary and averting attacks. The proposed Multi-player Anonymity optimization Game theoretic (MAG) approach calls for the introduction of inter-BS deceptive traffic and use game theory to determine the volume and destination of such traffic so that the variance in the location anonymity over all BSs is reduced. The simulation results demonstrate the effectiveness of MAG.
Juice Quality of Valencia Oranges as Affected by Petroleum Oils Applied During the Postbloom and Summer Periods

Changes in juice quality occurred most frequently in samples from trees receiving double applications of oils during the sampling period in January 1965-67. Only 2 instances of changes in juice quality were found between tree samples treated with 448 and 410 oil when applied in June or August or in double applications. Reduced soluble solids were found on 3 of 4 sampling dates in fruit from trees sprayed twice with either oil in comparison with fruit from trees sprayed in June with the same oil or non-oil treatment. Fruit from trees sprayed twice with 448 oil had consistently smaller percentages of soluble solids than fruit from trees receiving 448 oil in August, while fruit from trees sprayed twice with 410 oil had smaller percentages of soluble solids than fruit from trees sprayed in August with 410 oil on only I sampling date. Reductions in percentage acid were found most frequently in samples from trees receiving double oil applications than in samples from trees receiving oil only in June or August. Ratios of soluble solids to acid differed in only a few instances. Ratios of samples from trees sprayed with 448 oil in June tended to be small be cause of the tendency of these samples to have a larger percentage acid. Minimum maturity requirements were met in 3 of 4 years in practically all the samples taken in early January.
Abundance, Adventure, Bearing Witness, and Joy Reflections on MPH Students’ Commitments Upon Graduation

The moment of graduation offers a unique opportunity for commitment to core principles of the public health profession and leadership for what lies ahead. Inspired by Noreen Clark’s 1992 speech and 1994 article “Health Educators and the Future: Lead, Follow, or Get Out of the Way,” our master of public health program has implemented a three-part learning activity with 20 graduating cohorts since 2000. The result of the activity is a set of “commitments upon graduation” that the master of public health program students affirm together during their graduation ceremony. This article describes the three components of the learning activity, with details on implementation that can be applied to settings beyond higher education. Results of content analysis of the commitments from the more than 450 students graduating between 2000 and 2014 are then presented. Six enduring themes are discussed: health, social justice, promoting and advancing the profession, holding a dream, relationships, and lifelong learning. In...
The alkaloidal content of blue lupine ( Lupinus angustifolius L.) and its toxicity on small laboratory animals

1. A method of extraction and isolation of the alkaloid of blue lupine was adopted for small samples of the various plant parts: seeds, leaves and pods.2. From the evidence presented, it is shown that the seeds of blue lupine contain a higher percentage of crude alkaloid, than do the pods and leaves. On the basis of the extractions and isolation, seeds contained as much as 2·25%, leaves were found to contain 0·69%, and pods contained 1·46%.3. The alkaloid isolated was identified as D-lupanine by its characteristic physical and chemical properties. The anhydrous monohydrochloride salt was prepared in pure form and from it were obtained samples of the pure free base, d-lupanine.4. Toxicity determinations, involving the injection of water solutions of the crude free base, hydrochloride salt and the pure free base, administered intraperitoneally in guinea-pigs, rats and mice were carried out. Mice were found to be most susceptible, rats less susceptible, and guineapigs least susceptible to the effect of the various solutions injected. The minimal lethal dose (m.l.d.) is given for all three species of animals, and in addition the 50% lethal doses l.d. 50 are given for mice. The purest samples were the most toxic.5. The symptoms shown by guinea-pigs, rats and mice poisoned by the alkaloid are similar. Gross pathology of the animals killed indicated death by asphyxiation.
The electronic ground state and coordination environment of iron (II) in ferrous bleomycin

Abstract Zero field iron-57 Mossbauer spectra are used to demonstrate that the ferrous complex of the anti-tumor agent bleomycin contains Fe(II) as a high-spin species that is six coordinate in the solid state.
Postnatal experiences influence how the brain integrates information from different senses.

Sensory Processing Disorder (SPD) is characterized by anomalous reactions to, and integration of, sensory cues. Although the underlying etiology of SPD is unknown, one brain region likely to reflect these sensory and behavioral anomalies is the Superior Colliculus (SC); a structure involved in the synthesis of information from multiple sensory modalities and the control of overt orientation responses. In this review we describe normal functional properties of this structure, the manner in which its individual neurons integrate cues from different senses, and the overt SC-mediated behaviors that are believed to manifest this “multisensory integration.” Of particular interest here is how SC neurons develop their capacity to engage in multisensory integration during early postnatal life as a consequence of early sensory experience, and that it is the intimate communication between cortex and the midbrain makes this developmental process possible.
Interpersonal Impairment and the Prediction of Depressive Symptoms in Adolescent Children of Depressed and Nondepressed Mothers

ABSTRACT Objective Different pathways to youth depression should be explored. Based on an interpersonal impairment perspective on depression, the currently depressed children of depressed mothers were hypothesized to differ in predictors of their depression compared with depressed children of nondepressed mothers. Chronic social difficulties were expected to be more predictive of depressive symptoms in offspring of depressed women, while recent stressful life events were expected to predict depression in offspring of never‐depressed women. Method A community sample of 812 fifteen‐year‐old children of depressed and nondepressed women was studied in Queensland, Australia, between 1996 and 1999; chronic and episodic stress in the past 6 to 12 months were examined in relation to current depressive disorders. Results Depressive states in children of depressed mothers were more associated with chronic interpersonal difficulties than were the depressions of children of nondepressed women, and the latter group had greater increases in depression level associated with episodic stressors than did children of depressed women. Conclusions The results may reflect greater depression reactivity to chronic social difficulties among offspring of depressed mothers. Depressive experiences may have different predictors in subgroups of depressed youths and imply potentially different courses and needs for treatment. J. Am. Acad. Child Adolesc. Psychiatry , 2003, 42(5):571‐577.
Synthesis of Vicinal Dimethyl Chirons by Asymmetric Hydrogenation of Trisubstituted Alkenes

Roche ester derivatives were converted to trisubstituted alkenes with allylic chiral centers. Hydrogenation of these substrates with chiral analogues of Crabtree’s catalyst, specifically, an optically active carbene oxazoline derivative, were found to be mostly catalyst controlled. However, the peripheral functionalities and protecting groups had significant effects and could be adjusted to give high stereoselectivities. The upshot of this work is that α,ω-functionalized chirons to introduce 1,2-dimethyl functionalities into acyclic chains have been developed.
Streaming Potential Generated by a Pressure-Driven Flow Over Superhydrophobic Stripes

The streaming potential generated by a pressure-driven flow over a weakly charged slip-stick surface [the zeta potential of the surface is smaller than the thermal potential (25 mV)] with an arbitrary double layer thickness is theoretically studied by solving the Debye–Huckel equation and Stokes equation. A series solution of the streaming potential is derived. Approximate expressions for the streaming potential in the limits of thin double layers and thick double layers are also given in excellent agreement with the full solution. To understand the impact of the slip, the streaming potential is compared against that over a homogeneously charged smooth surface. Our results indicate that the streaming potential over a superhydrophobic surface can only be enhanced under certain conditions. Moreover, as the double layer thickness increases, the advantage of the superhydrophobic surface diminishes. In addition, the Onsager relation which directly relates the magnitude of electro-osmotic effect to that of the ...
GeoJournal: a new focus on spatially integrated social sciences and humanities

Since Professor Wolf Tietze founded the journal in 1977, GeoJournal has served the international geographical community with distinction. As of Janunary 1, 2010, GeoJournal has published more than 215 issues in 74 volumes. When I took over the editor-inchief for GeoJournal back in 2007, I had indicated back then that gradual changes will be made to better serve the international community. About a year ago, I met with the Springer management team and we discussed what should be the new focus of GeoJournal during the 2nd decade of 21st century and beyond. Based upon new trends across the disciplines, detailed market analysis, consultation of key editorial board members, we've decided to relaunch GeoJournal in 2010 to focus primarily on human geography with six issues per year. We also decided to open up GeoJournal to social scientists and humanity scholars who take a geographical or spatial approach in their work. With this change of focus, we hope GeoJournal can become the hub of cutting edge research by social scientists and humanity scholars in the coming decade. This issue consists of nine papers four are invited contributions specifically for the relaunching of GeoJournal, five are regular submissions. All these nine papers are closely related to the broad themes of spatial integrated social sciences and humanities. The first paper by two geographersMike Goodchild and
The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1 ,5-a]-pyrimidine: a corticotropin-releasing factor (hCRF1) antagonist.

Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
Discovery of a Novel Dopamine Transporter Inhibitor, 4-Hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-Methylphenyl Ketone, as a Potential Cocaine Antagonist through 3D-Database Pharmacophore Searching. Molecular Modeling, Structure−Activity Relationships, and Behavioral Pharmacological Studies

A novel, fairly potent dopamine transporter (DAT) inhibitor, 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone (3, K(i) values of 492 and 360 nM in binding affinity and inhibition of dopamine reuptake, respectively), with significant functional antagonism against cocaine and a different in vitro pharmacological profile from cocaine at the three transporter sites (dopamine, serotonin, and norepinephrine) was discovered through 3D-database pharmacophore searching. Through structure-activity relationships and molecular modeling studies, we found that hydrophobicity and conformational preference are two additional important parameters that determine affinity at the DAT site. Chemical modifications of the lead compound (3) led to a high affinity analogue (6, K(i) values of 11 and 55 nM in binding affinity and inhibition of dopamine reuptake, respectively). In behavioral pharmacological testing, 6 mimics partially the effect of cocaine in increasing locomotor activity in mice but lacks cocaine-like discriminative stimulus effect in rats. Taken together, these data suggest that 6 represents a promising lead for further evaluations as potential therapy for the treatment of cocaine abuse.
BAC contig from a 3-cM region of mouse chromosome 11 surrounding Brca1.

Even with the completion of a draft version of the human genome sequence only a fraction of the genes identified from this sequence have known functions. Chromosomal engineering in mouse cells, in concert with gene replacement assays to prove the functional significance of a given genomic region or gene, represents a rapid and productive means for understanding the role of a given set of genes. Both techniques rely heavily on detailed maps of chromosomal regions, initially to understand the scope of the regions being modified and finally to provide the cloned resources necessary to allow both finished sequencing and large insert complementation. This report describes the creation of a BAC clone contig on mouse chromosome 11 in a region showing conservation of synteny with sequences on human chromosome 17. We have created a detailed map of an approximately 3-cM region containing at least 33 genes through the use of multiple BAC mapping strategies, including chromosome walking and multiplex oligonucleotide hybridization and gap filling. The region described is one of the targets of a large effort to create a series of mice with regional deletions on mouse chromosome 11 (33-80 cM) that can subsequently be subjected to further mutagenesis.
On a pair of axisymmetric forces inside a sphere

In this paper, the stresses in a sphere under a pair of concentrated forces acting axisymmetrically inside the sphere are solved by using a Love's stress function. The method of solution is also applied to solve the problem of a pair of ring forces acting axisymmetrically inside the sphere. In either problem, the solution covers the limiting case in which the pair of forces or ring forces is acting on the sphere.
Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.

Abstract Background and Objectives: Central nervous system and cardiac toxicity following the administration of local anesthetics is a recognized complication of regional anesthesia. Levobupivacaine, the pure S(-) enantiomer of bupivacaine, was developed to improve the cardiac safety profile of bupivacaine. We describe 2 cases of grand mal seizures following accidental intravascular injection of levobupivacaine. Case Report: Two patients presenting for elective orthopedic surgery of the lower limb underwent blockade of the lumbar plexus via the posterior approach. Immediately after the administration of levobupivacaine 0.5% with epinephrine 2.5 μg/mL, the patients developed grand mal seizures, despite negative aspiration for blood and no clinical signs of intravenous epinephrine administration. The seizures were successfully treated with sodium thiopental in addition to succinylcholine in 1 patient. Neither patient developed signs of cardiovascular toxicity. Both patients were treated preoperatively with β-adrenergic antagonist medications, which may have masked the cardiovascular signs of the unintentional intravascular administration of levobupivacaine with epinephrine. Conclusions: Although levobupivacaine may have a safer cardiac toxicity profile than racemic bupivacaine, if adequate amounts of levobupivacaine reach the circulation, it will result in convulsions. Plasma concentrations sufficient to result in central nervous system toxicity did not produce manifestations of cardiac toxicity in these 2 patients. Reg Anesth Pain Med 2003;28:144-147.
The atmospheric chemistry of organic nitrates

Abstract The chemistry of organic compounds containing the covalently-bound nitrate group is reviewed with the purpose of summarizing the state of knowledge concerning their importance in atmospheric chemistry. Information pertinent to the conduct of research is contained in sections titled Nomenclature; Preparation, Properties and Spectroscopic Data; and Measurement Techniques. Information specific to atmospheric chemistry is contained in sections titled Atmospheric Formation Processes, Atmospheric Removal Processes, Atmospheric Observations, and Modeling Studies. Areas of potential importance and areas of major uncertainty are identified throughout to provide focus for future research activities.
Chiral interconnects based on topological insulators

Topological insulators are new states of quantum matter with novel electronic properties. Inside two dimensional magnetic topological insulators, electrical currents are confined at the edge of the sample, and counter propagating directions are spatially separated like automobiles on a highway. Local electrical resistivity is completely eliminated in such topological insulators, and only terminal or contact resistances remain. We show that this principle can be used to construct chiral interconnects on computing devices where the total resistance is independent of the length, thus eliminating a major obstacle of the electronics technology.
Alpha emission at the Fermi energy

Alpha particles have been measured in coincidence with both projectile-like fragments (Z = 5--8) and light fragments (Z = 3--4) in the reactions of 35 MeV/nucleon /sup 16/O with /sup 58/Ni. These results provide an extension of previous systematics studying the evolution of nonequilibrium emission of ..cap alpha.. particles from reactions at 6 to 20 MeV/nucleon. Two nonequilibrium components can be identified: one consists of beam velocity ..cap alpha.. particles and the other consists of intermediate velocity ..cap alpha.. particles. Compared to lower bombarding energies, no drastic change in the reaction mechanism has been observed at the Fermi energy.
Magnetic resonance angiography in the management of lower extremity arterial occlusive disease: a prospective study.

Abstract Purpose: We conducted a prospective study to clarify the clinical utility of magnetic resonance angiography (MRA) in the treatment of patients with lower extremity arterial occlusive disease. Methods: During the interval of September 1993 through March 1995, 79 patients (43% claudicants, 57% limb-threatening ischemia) were studied with both MRA and contrast arteriography (ANGIO) and underwent intervention with either balloon angioplasty (9%), surgical inflow (28%), or outflow (63%) procedures. MRA and ANGIO were interpreted by separate blinded vascular radiologists, and arterial segments from the pelvis to the foot were graded as normal or with increasing degrees of mild (25% to 50%), moderate (51% to 75%), or severe (75% to 99%) stenosis or occlusion. Treatment plans were formulated by the attending surgeon and were based initially on hemodynamic, clinical, and MRA data and thereafter with ANGIO. Additional study surgeons formulated independent and specific treatment plans based on MRA or ANGIO alone. Indexes of agreement (beyond chance) for arterial segments depicted by MRA and ANGIO were assessed (kappa value), and treatment plans formulated were compared (χ-square). Results: Precise agreement (%) and the percent of major discrepancies (segment classified as normal/mild stenosis on one study and severe stenosis/occlusion on the other) between MRA and ANGIO for respective arterial segments was as follows: common and external iliacs (n = 256) 77/3.5; superficial femoral and above-knee popliteal (n = 255) 73/6.7; below-knee popliteal (n = 131) 84/3.8; infrapopliteal runoff vessels (n = 864) 74/12.4; pedal vessels (n = 111) 69/19.8 Kappa values indicated moderate agreement (between MRA and ANGIO) beyond chance for all arterial segments. Treatment plans formulated by the attending surgeon, the MRA surgeon, and the ANGIO surgeon agreed in more than 85% of cases. Inability of MRA to assess the significance of inflow disease and inadequate detail of tibial/pedal vessels were the principal deficiencies of MRA in those cases where it was considered an inadequate examination. Conclusion: These findings suggest MRA and ANGIO are nearly equivalent examinations in the demonstration of infrainguinal vascular anatomy. MRA is an adequate preoperative imaging study (and may replace ANGIO), particularly in those circumstances when the risk of ANGIO is increased or when clinical and hemodynamic evaluation predict the likelihood of straightforward aortofemoral or femoral-popliteal reconstruction. (J Vasc Surg 1997;25:380-9.)
Stratification of bile in the normal gallbladder during intravenous cholangiography

Stratification in the gallbladder with a radiolucent zone of nonopacified bile may be a physiologic phenomenon during intravenous cholangiography, and should not be confused with floating cholesterol gravel or sludge. A post-fatty-meal and/or delayed films may aid in the differentiation of these two conditions. If a fatty stimulus is given at least 1 hr. prior to the X-ray study, the stratification phenomenon may be avoided.
The Development of Identity as a Privileged Relation in Classification: When Very Similar is Just Not Similar Enough

Young children classify by overall similarity the same stimuli that older children and adults classify by part identity. This developmental trend is typically discussed in terms of a shift from comparing wholes to comparing parts. The present study investigates if the trend reflects more than one developing ability. The results of Experiment 1 showed that, in the absence of a part identity relation, older children classify by wholes, not parts. Experiment 2 demonstrated a developmental trend from classifying by similarity to classifying by identity and showed that absolute identity classifications are made more readily than overall similarity classifications by older but not by younger children. Experiment 3 investigated adults' use of absolute identity and showed that identity classifications reflect a strategically imposed and thus shiftable criterion by which stimuli may be classified. In conclusion, the results of the present study suggest that the developmental trend from overall similarity to part identity classifications involves a shift from comparing wholes to comparing parts, and also involves a shift from classifying by similarity to classifying by identity. The revised description of the developmental trend may be related to the trend from conceptual representations based on characteristic features to representations based on defining features.
Targeted therapy in metastatic renal carcinoma

Abstract Background Advanced renal cell carcinoma is one of the most treatment-resistant malignancies to conventional cytotoxic chemotherapy. The development of new targeted therapy was result of understanding biological pathways underlying renal cell carcinoma. Our objective is to provide an overview of current therapies in metastatic renal cell carcinoma. Methods MEDLINE/PUBMED was queried in December 2012 to identify abstracts, original and review articles. The research was conducted using the following words: “metastatic renal cell carcinoma” and “target therapy”. Phase II and Phase III clinical trials were included followed FDA approval. Total of 40 studies were eligible for review. Conclusion The result of this review shows benefit of these target drugs in tumor burden, increase progression-free and overall survival and improvement the quality of life compared with previous toxic immunotherapy, although complete response remains rare.
Genetics of resistance to kernel infection by Aspergillus flavus in maize

Although kernel infection by Aspergillus flavus Link ex Fries and subsequent pre-harvest aflatoxin contamination of maize (Zea mays L.) grain are major production problems in the south-eastern United States and elsewhere in the world, limited progress has been made in developing and identifying sources for resistance. Genetics of kernel infection by A. flavus remains poorly understood. A 10-parent diallel experiment was conducted in 1992 and 1994 to study the genetic nature of percentage kernel infection (PKI) by A. flavus. General combining ability (GCA), specific combining ability (SCA), and reciprocal mean squares for PKI were significant. The GCA and SCA sums of squares were about equal. The GCA, SCA, and reciprocal effects varied across years, which implied that percentage kernel infection was greatly influenced by environments. The percentage kernel infection was always greater when Mo 17 was the male parent in a cross than when it was the female parent. The percentage kernel infection mean for female Mo 17 was 38.5% lower than that for male Mol7. Similarly, percentage kernel infection mean for female L668 was 23.7% lower than that for male L668. The use of inbred lines L729 and B73 as female parents should be avoided, as they showed significant, positive maternal reciprocal effects.