Institution
Novartis
Company•Basel, Switzerland•
About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.
Topics: Alkyl, Population, Alkoxy group, Tolerability, Receptor
Papers published on a yearly basis
Papers
More filters
••
TL;DR: mTor, acting mainly via mTORC1, controls dystrophin transcription in a raptor- and rictor-independent mechanism.
Abstract: Mammalian target of rapamycin (mTOR) is a key regulator of cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) and mTORC2, respectively. Raptor is required for oxidative muscle integrity, whereas rictor is dispensable. In this study, we show that muscle-specific inactivation of mTOR leads to severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar to those observed in muscles lacking raptor, including impaired oxidative metabolism, altered mitochondrial regulation, and glycogen accumulation associated with protein kinase B/Akt hyperactivation. In addition, mTOR-deficient muscles exhibit increased basal glucose uptake, whereas whole body glucose homeostasis is essentially maintained. Importantly, loss of mTOR exacerbates the myopathic features in both slow oxidative and fast glycolytic muscles. Moreover, mTOR but not raptor and rictor deficiency leads to reduced muscle dystrophin content. We provide evidence that mTOR controls dystrophin transcription in a cell-autonomous, rapamycin-resistant, and kinase-independent manner. Collectively, our results demonstrate that mTOR acts mainly via mTORC1, whereas regulation of dystrophin is raptor and rictor independent.
334 citations
••
TL;DR: The ability of AFM to continuously monitor growth, directionality, and changes in morphology for individual fibrils, provides a significant advantage over spectroscopy-based bulk methods which average the growth of many fibrili and typically require 100 to 1000-fold more protein.
334 citations
••
TL;DR: Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial.
Abstract: BACKGROUND
Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial.
METHODS
Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3–4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone.
RESULTS
Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]).
CONCLUSIONS
The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36–43. © 2003 American Cancer Society.
333 citations
••
TL;DR: This manuscript reviews several methods for historical borrowing, illustrating how key parameters in each method affect borrowing behavior, and then, compares these methods on the basis of mean square error, power and type I error.
Abstract: Clinical trials rarely, if ever, occur in a vacuum. Generally, large amounts of clinical data are available prior to the start of a study, particularly on the current study's control arm. There is obvious appeal in using (i.e., 'borrowing') this information. With historical data providing information on the control arm, more trial resources can be devoted to the novel treatment while retaining accurate estimates of the current control arm parameters. This can result in more accurate point estimates, increased power, and reduced type I error in clinical trials, provided the historical information is sufficiently similar to the current control data. If this assumption of similarity is not satisfied, however, one can acquire increased mean square error of point estimates due to bias and either reduced power or increased type I error depending on the direction of the bias. In this manuscript, we review several methods for historical borrowing, illustrating how key parameters in each method affect borrowing behavior, and then, we compare these methods on the basis of mean square error, power and type I error. We emphasize two main themes. First, we discuss the idea of 'dynamic' (versus 'static') borrowing. Second, we emphasize the decision process involved in determining whether or not to include historical borrowing in terms of the perceived likelihood that the current control arm is sufficiently similar to the historical data. Our goal is to provide a clear review of the key issues involved in historical borrowing and provide a comparison of several methods useful for practitioners.
333 citations
••
TL;DR: Crosstalk between lymphoid tissue–inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence.
Abstract: The generation of lymphoid microenvironments in early life depends on the interaction of lymphoid tissue-inducer cells with stromal lymphoid tissue-organizer cells. Whether this cellular interface stays operational in adult secondary lymphoid organs has remained elusive. We show here that during acute infection with lymphocytic choriomeningitis virus, antiviral cytotoxic T cells destroyed infected T cell zone stromal cells, which led to profound disruption of secondary lymphoid organ integrity. Furthermore, the ability of the host to respond to secondary antigens was lost. Restoration of the lymphoid microanatomy was dependent on the proliferative accumulation of lymphoid tissue-inducer cells in secondary lymphoid organs during the acute phase of infection and lymphotoxin alpha(1)beta(2) signaling. Thus, crosstalk between lymphoid tissue-inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence.
333 citations
Authors
Showing all 41972 results
Name | H-index | Papers | Citations |
---|---|---|---|
Irving L. Weissman | 201 | 1141 | 172504 |
Peter J. Barnes | 194 | 1530 | 166618 |
Paul G. Richardson | 183 | 1533 | 155912 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Jie Zhang | 178 | 4857 | 221720 |
Lei Jiang | 170 | 2244 | 135205 |
Marc A. Pfeffer | 166 | 765 | 133043 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Bruce D. Walker | 155 | 779 | 86020 |
Timothy P. Hughes | 145 | 831 | 91357 |
Kurt Wüthrich | 143 | 739 | 103253 |
Leonard Guarente | 143 | 352 | 80169 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |