142 research outputs found
Phase I Clinical Trials in Acute Myeloid Leukemia: 23-Year Experience From Cancer Therapy Evaluation Program of the National Cancer Institute
Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time
ŠŃŠæŠ¾Š»ŃŠ·Š¾Š²Š°Š½ŠøŠµ Š±Š°ŃŠøŠ¹-ŃŃŃŠ¾Š½ŃŠøŠµŠ²Š¾Š³Š¾ ŠŗŠ°ŃŠ±Š¾Š½Š°ŃŠøŃŠ° ŠæŃŠø ŠøŠ·Š³Š¾ŃŠ¾Š²Š»ŠµŠ½ŠøŠø ŃŠ²Š°ŃŠ¾ŃŠ½ŃŃ ŃŠ»ŃŃŠ¾Š² Š½Š° Š¾ŃŠ½Š¾Š²Šµ ŃŠµŃ Š½Š¾Š³ŠµŠ½Š½ŃŃ Š¾ŃŃ Š¾Š“Š¾Š² Š¼ŠµŃŠ°Š»Š»ŃŃŠ³ŠøŃŠµŃŠŗŠ¾Š³Š¾ ŠæŃŠ¾ŠøŠ·Š²Š¾Š“ŃŃŠ²Š°
Š Š“Š°Š½Š½Š¾Š¹ ŃŠ°Š±Š¾ŃŠµ ŃŠ°ŃŃŠ¼Š¾ŃŃŠµŠ½Š° Š²Š¾Š·Š¼Š¾Š¶Š½Š¾ŃŃŃ ŠøŃŠæŠ¾Š»ŃŠ·Š¾Š²Š°Š½ŠøŃ Š±Š°ŃŠøŠ¹-ŃŃŃŠ¾Š½ŃŠøŠµŠ²Š¾Š³Š¾ ŠŗŠ°ŃŠ±Š¾Š½Š°ŃŠøŃŠ° ŠæŃŠø ŠøŠ·Š³Š¾ŃŠ¾Š²Š»ŠµŠ½ŠøŠø ŃŠ²Š°ŃŠ¾ŃŠ½ŃŃ
ŃŠ»ŃŃŠ¾Š² Š½Š° Š¾ŃŠ½Š¾Š²Šµ ŃŠ»Š°ŠŗŠ° ŠæŃŠ¾ŠøŠ·Š²Š¾Š“ŃŃŠ²Š° ŃŠøŠ»ŠøŠŗŠ¾Š¼Š°ŃŠ³Š°Š½ŃŠ°, Š° ŃŠ°Šŗ Š¶Šµ Š½Š° Š¾ŃŠ½Š¾Š²Šµ ŠŗŠ¾Š²ŃŠµŠ²ŃŃ
ŃŠ»ŠµŠŗŃŃŠ¾ŃŃŠ°Š»ŠµŠæŠ»Š°Š²ŠøŠ»ŃŠ½ŃŃ
ŃŠ»Š°ŠŗŠ¾Š², Š¾Š±ŃŠ°Š·Š¾Š²Š°Š½Š½ŃŃ
ŠæŃŠø ŠæŃŠ¾ŠøŠ·Š²Š¾Š“ŃŃŠ²Šµ ŃŠµŠ»ŃŃŠ¾Š²ŃŃ
Š¼Š°ŃŠ¾Šŗ ŃŃŠ°Š»Šø. Š ŃŠµŃŠøŠø Š¾ŠæŃŃŠ¾Š² Š² Š»Š°Š±Š¾ŃŠ°ŃŠ¾ŃŠ½ŃŃ
ŃŃŠ»Š¾Š²ŠøŃŃ
ŠøŠ·Š³Š¾ŃŠ°Š²Š»ŠøŠ²Š°Š»Šø Šø ŠøŃŃŠ»ŠµŠ“Š¾Š²Š°Š»Šø ŃŠ°Š·Š»ŠøŃŠ½ŃŠµ ŃŠ¾ŃŃŠ°Š²Ń ŃŠ²Š°ŃŠ¾ŃŠ½ŃŃ
ŃŠ»ŃŃŠ¾Š², Š±ŃŠ»Šø Š¾ŠæŃŠµŠ“ŠµŠ»ŠµŠ½Ń Ń
ŠøŠ¼ŠøŃŠµŃŠŗŠøŠµ ŃŠ¾ŃŃŠ°Š²Ń Š½Š°ŠæŠ»Š°Š²Š»ŠµŠ½Š½Š¾Š³Š¾ Š¼ŠµŃŠ°Š»Š»Š°, ŠæŃŠ¾Š²ŠµŠ“ŠµŠ½ Š¼ŠµŃŠ°Š»Š»Š¾Š³ŃŠ°ŃŠøŃŠµŃŠŗŠøŠ¹ Š°Š½Š°Š»ŠøŠ·.In this paper the possibility of using barium-strontium carbonatite in the manufacture of welding fluxes on the basis of slag from the production of silicomanganese, and based on ladle steelmaking slags formed in the production of rail steel grades. In a series of experiments in the laboratory have produced and investigated different compositions of welding fluxes, were determined the chemical compositions of the weld metal metallographic analysis
Prevalence of sexual dimorphism in mammalian phenotypic traits.
The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans
Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.
Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes
The Structural Biology Knowledgebase: a portal to protein structures, sequences, functions, and methods
The Protein Structure Initiativeās Structural Biology Knowledgebase (SBKB, URL: http://sbkb.org) is an open web resource designed to turn the products of the structural genomics and structural biology efforts into knowledge that can be used by the biological community to understand living systems and disease. Here we will present examples on how to use the SBKB to enable biological research. For example, a protein sequence or Protein Data Bank (PDB) structure ID search will provide a list of related protein structures in the PDB, associated biological descriptions (annotations), homology models, structural genomics protein target status, experimental protocols, and the ability to order available DNA clones from the PSI:Biology-Materials Repository. A text search will find publication and technology reports resulting from the PSIās high-throughput research efforts. Web tools that aid in research, including a system that accepts protein structure requests from the community, will also be described. Created in collaboration with the Nature Publishing Group, the Structural Biology Knowledgebase monthly update also provides a research library, editorials about new research advances, news, and an events calendar to present a broader view of structural genomics and structural biology
Transancestral mapping and genetic load in systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), reļ¬ned association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identiļ¬es both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL
IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1
Macrophages (M Phi s) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident M Phi s during a Th2-biased tissue nematode infection. We now show that proliferation of M Phi s during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires M Phi-intrinsic IL-4R signaling. However, both IL-4R alpha-dependent and -independent mechanisms contributed to M Phi proliferation during nematode infections. IL-4R-independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4R alpha expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4R alpha(+) compared with IL-4R alpha(-) cells. Mechanistically, this occurred by conversion of IL-4R alpha(+) M Phi s from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4 increases the relative density of tissue M Phi s by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4R alpha signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident M Phi numbers without coincident monocyte recruitment
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