TOTEM: Forward Physics at the LHC

The TOTEM experiment with its detectors in the forward region of CMS and the Roman Pots along the beam line will determine the total pp cross-section via the optical theorem by measuring both the elastic cross-section and the total inelastic rate. TOTEM will have dedicated runs with special high-beta* beam optics and a reduced number of proton bunches resulting in a low effective luminosity between 1.6 x 10^{28} cm^{-2} s^{-1} and 2.4 x 10^{29} cm^{-2} s^{-1}. In these special conditions also an absolute luminosity measurement will be made, allowing the calibration of the CMS luminosity monitors needed at higher luminosities. The acceptance of more than 90 % of all leading protons in the Roman Pot system, together with CMS's central and TOTEM's forward detectors extending to a maximum rapidity of 6.5, makes the combined CMS+TOTEM experiment a unique instrument for exploring diffractive processes. Scenarios for running at higher luminosities necessary for hard diffractive phenomena with low cross-sections are under study.Comment: 6 pages, 4 figures (6 eps files),latex class file dis04.cls included, to be published in the proceedings of the DIS2004, Strbske Pleso, Slovaki

Pileup Probabilities and Events per Bunch-Crossing

This note collects some formulas and numbers for dealing with pileup at the LHC

Algebraic Determination of Roman Pot Acceptance and Resolution for the beta* = 1540 m Optics

This note describes algebraic methods for calculating Roman Pot acceptance and reconstruction resolution in the kinematic variables of diffractively scattered protons. This approach being based on a parameterisation of the optical functions for beta* = 1540 m}, results are obtained rather fast without tracking individual protons through the LHC ring. Evidently, the precision of the results relies on the accuracy of the parameterisation. Slight differences between the results in this note and the ones given in the (older) CMS/TOTEM physics TDR are due to the correction of some suboptimal program features

Renal Involvement in Preeclampsia: Similarities to VEGF Ablation Therapy

Glomerular VEGF expression is critical for the maintenance and function of an intact filtration barrier. Alterations in glomerular VEGF bioavailability result in endothelial as well as in podocyte damage. Renal involvement in preeclampsia includes proteinuria, podocyturia, elevated blood pressure, edema, glomerular capillary endotheliosis, and thrombotic microangiopathy. At least the renal signs, symptoms, and other evidence can sufficiently be explained by reduced VEGF levels. The aim of this paper was to summarize our pathophysiological understanding of the renal involvement of preeclampsia and point out similarities to the renal side effects of VEGF-ablation therapy

The Podocyte Power-Plant Disaster and Its Contribution to Glomerulopathy

Proper podocyte function within the glomerulus demands a high and continuous energy supply that is mainly derived from the respiratory chain of the inner mitochondrial membrane. Dysregulations in the metabolic homoeostasis of podocytes may result in podocyte damage and glomerular disease. This article highlights the current knowledge about podocyte energy supply by the respiratory chain. We review the regulation of mitochondrial oxidative metabolism with regard to podocytopathy and discuss the latest understanding of different mitochondrial dysfunctions of the podocyte in diabetic nephropathy and focal segmental glomerulosclerosis (FSGS). We discuss genetic forms of mitochondriopathy of the podocyte and end with recent knowledge about crosstalk between NADH and NADPH and potential therapeutic options for podocyte mitochondriopathy. We aim to raise awareness for the complex and interesting mechanisms of podocyte damage by impaired energy supply that, despite of novel findings in recent years, is poorly understood so far

Beam Coupling Impedance Measurement and Mitigation for a TOTEM Roman Pot

The longitudinal and transverse beam coupling impedance of the first final TOTEM Roman Pot unit has been measured in the laboratory with the wire method. For the evaluation of transverse impedance the wire position has been kept constant, and the insertions of the RP were moved asymmetrically. With the original configuration of the RP, resonances with fairly high Q values were observed. In order to mitigate this problem, RF-absorbing ferrite plates were mounted in appropriate locations. As a result, all resonances were sufficiently damped to meet the stringent LHC beam coupling impedance requirements.Comment: 3 pages, 8 figures, proceedings of the 11th European Particle Accelerator Conference (EPAC08), Genova, Italy, June 200

Characterizing Intraindividual Podocyte Morphology In Vitro with Different Innovative Microscopic and Spectroscopic Techniques

Podocytes are critical components of the glomerular filtration barrier, sitting on the outside of the glomerular basement membrane. Primary and secondary foot processes are characteristic for podocytes, but cell processes that develop in culture were not studied much in the past. Moreover, protocols for diverse visualization methods mostly can only be used for one technique, due to differences in fixation, drying and handling. However, we detected by single-cell RNA sequencing (scRNAseq) analysis that cells reveal high variability in genes involved in cell type-specific morphology, even within one cell culture dish, highlighting the need for a compatible protocol that allows measuring the same cell with different methods. Here, we developed a new serial and correlative approach by using a combination of a wide variety of microscopic and spectroscopic techniques in the same cell for a better understanding of podocyte morphology. In detail, the protocol allowed for the sequential analysis of identical cells with light microscopy (LM), Raman spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Skipping the fixation and drying process, the protocol was also compatible with scanning ion-conductance microscopy (SICM), allowing the determination of podocyte surface topography of nanometer-range in living cells. With the help of nanoGPS Oxyo®, tracking concordant regions of interest of untreated podocytes and podocytes stressed with TGF-β were analyzed with LM, SEM, Raman spectroscopy, AFM and SICM, and revealed significant morphological alterations, including retraction of podocyte process, changes in cell surface morphology and loss of cell-cell contacts, as well as variations in lipid and protein content in TGF-β treated cells. The combination of these consecutive techniques on the same cells provides a comprehensive understanding of podocyte morphology. Additionally, the results can also be used to train automated intelligence networks to predict various outcomes related to podocyte injury in the future

Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease

Author Correction: Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease