2,315 research outputs found
A regularization projection algorithm for various problems with nonlinear mappings in Hilbert spaces
Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations
There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes
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Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates.
Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments
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Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice.
Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases
Characteristics of Sediment Bacterial Community in Response to Environmental Impacts in a Sewage Polluted River
The Jiaolai River is the main source of industrial and irrigation water for its catchment of 3900 km(2). Anthropogenic activities have caused heavy pollution of this river, but their impacts on biota have never been evaluated. In this study, molecular techniques were applied to investigate the impacts of environmental pollution on the river. Quantitative PCR revealed that total bacterial abundance ranged from 2.90x10(7) to 2.12x10(8) copies/g, with no significant differences among sampling sites or seasons. Bacterial abundance and pore water ammonium concentration were negatively correlated. Cluster analysis revealed that bacterial communities were mainly distributed into groups corresponding to nitrate concentration. Two clone libraries were constructed to compare the bacterial composition of samples with high (J308) and moderate (J304) nitrate impact. Sample J308 was characterized by more members in Clostridia and disappearance of Betaproteobacteria members, which are the primary contributors to nitrogen biogeochemical cycling. Bacterial communities in the sediment were clearly differentiated by environmental nitrogen pollution, suggesting that nitrogen eutrophication was the main environmental problem influencing the Jiaolai River
Characterization of a potent non-cytotoxic shRNA directed to the HIV-1 co-receptor CCR5
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
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