475 research outputs found
Revisiting the Use of Customer Information for CRM
For the past decade, customer relationship management (CRM) has been one of the priorities in marketing research and practice. However, many of the CRM systems did not perform as the companies expected. As such shortcoming could be due to inappropriate data input, this study provides a comprehensive overview of the empirical CRM literature. Along the phases of the CRM process, the authors show which kind of data has successfully proven to achieve the CRM objectives. The study provides researchers with a review of the empirical research on CRM and allows practitioners insights on the usability of customer data for CRM. --Customer Relationship Management (CRM),Customer Data
Urocortin and corticotropin-releasing factor receptor 2 in human renal cell carcinoma: disruption of an endogenous inhibitor of angiogenesis and proliferation
Podocytic PKC-Alpha Is Regulated in Murine and Human Diabetes and Mediates Nephrin Endocytosis
Background: Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss of high molecular weight proteins in the urine is usually associated with decreased expression of slit diaphragm proteins. Nephrin, is the major component of the glomerular slit diaphragm and loss of nephrin has been well described in rodent models of experimental diabetes as well as in human diabetic nephropathy. Methodology/Principal Findings: In this manuscript we analyzed the role of PKC-alpha (PKCa) on endocytosis of nephrin in podocytes. We found that treatment of diabetic mice with a PKCa-inhibitor (GÖ6976) leads to preserved nephrin expression and reduced proteinuria. In vitro, we found that high glucose stimulation would induce PKCa protein expression in murine and human podocytes. We can demonstrate that PKCa mediates nephrin endocytosis in podocytes and that overexpression of PKCa leads to an augmented endocytosis response. After PKC-activation, we demonstrate an inducible association of PKCa, PICK1 and nephrin in podocytes. Moreover, we can demonstrate a strong induction of PKCa in podocytes of patients with diabetic nephropathy. Conclusions/Significance: We therefore conclude that activation of PKCa is a pathomechanistic key event during the development of diabetic nephropathy. PKCa is involved in reduction of nephrin surface expression and therefore PKC
Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer
<p>Abstract</p> <p>Background</p> <p>Fibronectin 1 (<it>FN1</it>) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of <it>FN1 </it>in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.</p> <p>Methods</p> <p>212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of <it>FN1 </it>mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.</p> <p>Results</p> <p>Mean tissue specific <it>FN1 </it>mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean <it>FN1 </it>expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10<sup>-5</sup>; Wilcoxon rank sum test). Patients with advanced disease had higher <it>FN1 </it>expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher <it>FN1 </it>mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).</p> <p>Conclusions</p> <p>To our knowledge, this is the first study to show that <it>FN1 </it>mRNA expression is higher in RCC compared to normal renal tissue. <it>FN1 </it>mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.</p
Data mining methods for the prediction of different forms of asthma
The article examines the diagnosis of bronchial asthma, cites the classification of the disease, proves the relevance of this research, and represents the result of primary data analysis by using a powerful tool for data analysis - Rapid Miner
"What's (the) Matter?", A Show on Elementary Particle Physics with 28 Demonstration Experiments
We present the screenplay of a physics show on particle physics, by the
Physikshow of Bonn University. The show is addressed at non-physicists aged 14+
and communicates basic concepts of elementary particle physics including the
discovery of the Higgs boson in an entertaining fashion. It is also
demonstrates a successful outreach activity heavily relying on the university
physics students. This paper is addressed at anybody interested in particle
physics and/or show physics. This paper is also addressed at fellow physicists
working in outreach, maybe the experiments and our choice of simple
explanations will be helpful. Furthermore, we are very interested in related
activities elsewhere, in particular also demonstration experiments relevant to
particle physics, as often little of this work is published.
Our show involves 28 live demonstration experiments. These are presented in
an extensive appendix, including photos and technical details. The show is set
up as a quest, where 2 students from Bonn with the aid of a caretaker travel
back in time to understand the fundamental nature of matter. They visit
Rutherford and Geiger in Manchester around 1911, who recount their famous
experiment on the nucleus and show how particle detectors work. They travel
forward in time to meet Lawrence at Berkeley around 1950, teaching them about
the how and why of accelerators. Next, they visit Wu at DESY, Hamburg, around
1980, who explains the strong force. They end up in the LHC tunnel at CERN,
Geneva, Switzerland in 2012. Two experimentalists tell them about colliders and
our heroes watch live as the Higgs boson is produced and decays. The show was
presented in English at Oxford University and University College London, as
well as Padua University and ICTP Trieste. It was 1st performed in German at
the Deutsche Museum, Bonn (5/'14). The show has eleven speaking parts and
involves in total 20 people.Comment: 113 pages, 88 figures. An up to date version of the paper with high
resolution pictures can be found at
http://www.th.physik.uni-bonn.de/People/dreiner/Downloads/. In v2 the
acknowledgements and a citation are correcte
High-dose Vitamin D Supplementation in Multiple Sclerosis - Results From the Randomized EVIDIMS (Efficacy of Vitamin D Supplementation in Multiple Sclerosis) Trial
Background:
Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity.
Objectives:
The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing-remitting MS or clinically isolated syndrome.
Methods:
The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-β1b.
Results:
Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disability progression) and radiographical (T2-weighted lesion development, contrast-enhancing lesion development, brain atrophy) did not differ between both treatment arms. Post-study power calculations suggested that the sample size was too low to prove the hypothesis.
Conclusions:
The results neither support nor disprove a therapeutic benefit of high-dose VD supplementation but provide a basis for sound sample size estimations in future confirmatory studies. www.clinicaltrials.gov/NCT01440062
Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial
BACKGROUND: Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. METHODS/DESIGN: The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. DISCUSSION: It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. TRIAL REGISTRATION: Clinical trials gov. number: NCT0111766
Gasdermin D-deficient mice are hypersensitive to acute kidney injury
Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD-protein expression in whole kidney lysates increased during the first 84 h following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD-protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea, and serum creatinine. This hypersensitivity was reversed by a combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI
D3-instantons, Mock Theta Series and Twistors
The D-instanton corrected hypermultiplet moduli space of type II string
theory compactified on a Calabi-Yau threefold is known in the type IIA picture
to be determined in terms of the generalized Donaldson-Thomas invariants,
through a twistorial construction. At the same time, in the mirror type IIB
picture, and in the limit where only D3-D1-D(-1)-instanton corrections are
retained, it should carry an isometric action of the S-duality group SL(2,Z).
We prove that this is the case in the one-instanton approximation, by
constructing a holomorphic action of SL(2,Z) on the linearized twistor space.
Using the modular invariance of the D4-D2-D0 black hole partition function, we
show that the standard Darboux coordinates in twistor space have modular
anomalies controlled by period integrals of a Siegel-Narain theta series, which
can be canceled by a contact transformation generated by a holomorphic mock
theta series.Comment: 42 pages; discussion of isometries is amended; misprints correcte
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