Lenin and the Iskra faction of the RSDLP: 1899-1903

Using primary material, much of which has been overlooked up to now, this thesis argues that the Iskra newspaper and its organisational appendages were conceived by Lenin and his closest collaborators in a pragmatic attempt to strike a balance between the theoretically authoritative and revolutionary, yet inactive Osvobozhdenie Truda and the more active, but reformist and theoretically unclear Rabochee Delo grouping. As such, Iskra does not appear to have been the product of a detailed plan conceived in Siberian exile, as is often thought. Nor did it represent the extreme left wing of the Russian social-democratic movement of the time, a place occupied by Osvobozhdenie Truda. Iskra and its supporting organisations formed a faction of a broader party, the RSDLP, whose institutions it aimed to rebuild and to which it aimed to give ideological leadership broadly in sympathy with the basic views of Plekhanov, though differing with him in terms of tactics. Starting from a position of weakness both in the emigration and inside Russia, Lenin at first sought an alliance with the 'Economists' of Rabochee Delo rather than a policy of open factional struggle, which was at this stage (1900-01) advocated by Plekhanov. Only when serious vacillations in the Rabochee Delo line started to emerge in the spring of 1901 did Lenin break with this tactic, in despair of any useful co-operation with the politically unstable followers of the economist journal. From the end of 1901an open struggle for the support of the RSDLP local committees inside Russia began, in which the Economists were unable to martial support, whilst Iskra, owing to its network of full-time 'agents' and their assistance, eventually won a dominant position. On this basis, plans were laid for a Second Congress of the RSDLP that reveal a distinctly democratic and pluralist conception of party organisation on the part of Lenin, A conception which does not square with his dictatorial reputation. Accordingly, this thesis argues that the Second Congress was a credible, if not perfect representation of rank and file opinion within the RSDLP at the time and that the split within the Iskra faction that took place at this meeting owes more to pre-existing tensions with the Russian Iskra organisation rather than any unreasonable behaviour on the part of Lenin. Specifically, individual agents showed signs of weariness in relation to Lenin‘s policy of factional struggle prior to the Second Congress. For this reason they sought, but failed to find compromise at the congress with the Bund and the economists, and as such provoked a split with the supporters of Lenin within Iskra. As such, it was actually an inopportune search for compromise which appears to have provoked the split within Iskra, rather than dictatorial or intolerant practices on the part of Lenin. The supporters of Martov assumed that the Bund and the supporters of economism could be appeased, but this was not in fact the case

Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis.

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lowe

Exploring the failing right ventricle in pulmonary hypertension by cardiac magnetic resonance: an in vivo study utilizing Macitentan

Cardiac magnetic resonance (CMR) imaging is used to assess the right ventricle (RV) of pulmonary hypertensive (PH) patients and more recently to track changes in response to therapy. We wished to investigate if repeat CMRs could be used to assess ventricular changes in the Sugen 5416 hypoxic (Su/Hx) rat model of PH treated with the dual endothelin receptor antagonist Macitentan. Male Sprague Dawley Su/Hx rats were dosed for 3 weeks with either vehicle or Macitentan (30 mg/kg) daily, control rats received only vehicle. All rats underwent three CMR scans; before treatment, 2 weeks into treatment, and end of the study. A separate group of Su/Hx and control rats, treated as above, underwent terminal hemodynamic measurements. Using terminal and CMR measurements, Macitentan was found to lower RV systolic pressure pulmonary artery remodeling and increase RV ejection fraction but not change RV hypertrophy (RVH). Repeat CMRs determined that Su/Hx rats treated with Macitentan had significantly reversed RVH via reducing RV mass as well as reducing elevated left ventricular eccentricity index; reductions in RV mass were also observed in Su/Hx vehicle rats exposed to normoxic conditions. We have demonstrated that repeat CMRs can be used to assess the volume and structural changes in the ventricles of the Su/Hx rat model. Using repeat CMRs has allowed us to build a more complete picture of the response of the RV and the left ventricle to treatment. It is unknown if these effects are a consequence of direct action on the RV or secondary to improvements in the lung vasculature

Advanced power sources for space missions

Approaches to satisfying the power requirements of space-based Strategic Defense Initiative (SDI) missions are studied. The power requirements for non-SDI military space missions and for civil space missions of the National Aeronautics and Space Administration (NASA) are also considered. The more demanding SDI power requirements appear to encompass many, if not all, of the power requirements for those missions. Study results indicate that practical fulfillment of SDI requirements will necessitate substantial advances in the state of the art of power technology. SDI goals include the capability to operate space-based beam weapons, sometimes referred to as directed-energy weapons. Such weapons pose unprecedented power requirements, both during preparation for battle and during battle conditions. The power regimes for these two sets of applications are referred to as alert mode and burst mode, respectively. Alert-mode power requirements are presently stated to range from about 100 kW to a few megawatts for cumulative durations of about a year or more. Burst-mode power requirements are roughly estimated to range from tens to hundreds of megawatts for durations of a few hundred to a few thousand seconds. There are two likely energy sources, chemical and nuclear, for powering SDI directed-energy weapons during the alert and burst modes. The choice between chemical and nuclear space power systems depends in large part on the total duration during which power must be provided. Complete study findings, conclusions, and eight recommendations are reported

Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

Background: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast‐enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. Purpose: To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Study Type: Animal model. Subjects: Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line. Field Strength/Sequences: 7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient). Assessment: Immunohistochemistry sections were stained for human leukocyte antigen (probing human‐derived tumor cells). To achieve quantitative MRI‐tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a “ground truth.” Statistical Tests: Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis. Results: High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). Data Conclusion: These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy