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Modern human children take about twice as long as their closest biological relative, the chimpanzee, to mature. One standard explanation for the evolution of “delayed maturation” at an early stage of human evolution is that it provided the time necessary for immature individuals to learn complex skills, most notably those relating to tool-making abilities. However, after comparing dental maturational profiles of early hominids from South Africa (who apparently did make and use stone tools) (Susman [1994] Science 265:1570–1573) to those of extant humans and chimpanzees, we find no evidence to document an association between “delayed maturation” and tool-making abilities in the early stages of human evolution. This also suggests that the assumed association between prolonged childhood dependency and other behaviors often associated with the advent of tool-making such as cooperative hunting, food sharing, home bases, sexual division of labor, etc., is also suspect. Instead, we must look for other, or additional, selective pressures for the evolution of “delayed maturation,” which may postdate the australopithecine radiation. © 1995 Wiley-Liss, Inc. 相似文献
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Conflicts resolution is one of the key issues in maintaining consistency and in supporting smooth human–human interaction for real-time collaborative systems. This paper presents a novel approach of meta-operation conflict resolution for feature-based collaborative CAD system. Although commutative replicated data type (CRDT) is an emerging technique for conflict resolution, it is not capable of resolving conflicts among meta operations for 3D CAD systems. By defining 3 types of meta operations, this work extends CRDT capability to meta operation conflict resolution from 1D to 3D applications. The paper defines the dependency, casuality, conflict and compatible relations specific for 3D collaborative CAD systems. The conflicts of feature-based operations are automatically detected by tracking topological entity changes with the assistance of a persistent data structure, topological entity structure tree (\(TES\_Tree\)). An efficient commutativity-based confliction combination method is proposed to preserve the design intention of each user in a transparent way and maintains the eventual consistent state of the system. The proposed methods are tested in a prototype system with case studies, time complexity analysis and correctness proof. 相似文献
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Mikkelsen TS 《Genome biology》2004,5(8):238
The sequence of chimpanzee chromosome 22 is starting to help us to define the set of genetic attributes that are unique to humans, but interpreting the biological consequences of these remains a major challenge. 相似文献
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Glycopeptides have been isolated from tryptic digests of kappa-type light chains separated from human myeloma proteins obtained from the serum of two patients, Car and Rai. The glycopeptides are derived from the variable region of the chain in both cases, but from different sections. On the basis of homology it is deduced that glycopeptide from Car, kappaI type, is derived from position 25-31 whereas that from Rai, kappaII type, is from position 62-77, their sequences being respectively Ala-Ser-Gln-Asn-Ile-Ser and Phe-Ser-Gly-Ser-Gly-Ser-Gly(Thr,Asp)Phe-Thr-Leu-Asx-Ile-Ser-Arg. The significance of the results is discussed in connexion with the nature of the attachment site of carbohydrate to protein. 相似文献
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R.E. Fenna 《Journal of molecular biology》1982,161(1):211-215
Crystals of human milk α-lactalbumin have been grown from ammonium sulfate solutions in the presence of calcium ions at 35 °C. They belong to space group P21212, with unit cell dimensions: and have a single molecule in the asymmetric unit. The crystals diffract X-rays strongly to Bragg spacings of 2 Å and appear suitable for X-ray structural analysis. 相似文献
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《Journal of steroid biochemistry》1976,7(9):665-672
Progesterone binding activity has been detected in cytosols prepared from human cervical tissue. Cytosols showed high affinity (Ka, 0.2–1 nM−1) for progesterone and synthetic progestogens but not for corticosteroids or other steroids (norethindrone, medroxyprogesterone acetate > chlormadinone acetate, progesterone > 5α-pregnane-3,20-dione > norethisterone acetate > 17α-hydroxyprogesterone > cortisol, estradiol). Addition of 49 nM cortisol to the assay buffer permitted measurement of high affinity progesterone binding sites in those cytosols with high concentrations of CBG-like contaminants. The hormone dissociated from the complex with a dissociation rate constant of 6.9 × 10−5s−1 (0°C, 18% glycerol).Binding sites exhibited similar Ka values throughout the cervix and were found in highest concentration in the region encompassing the columnar epithelium when expressed per mg protein and per g. The concentrations of sites per mg DNA were similar in the columnar epithelium and in the stroma but higher than in the region of the squamous epithelium.Endometrial tissue exhibited higher concentrations of progesterone binding sites than did the corresponding cervix. In both the endometrium and cervix, the mean concentrations expressed per mg protein were significantly higher for proliferative phase than for secretory phase tissues. The corresponding differences in concentration per mg DNA were significant only for cervical cytosols. 相似文献
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Su Ho Han Jeong-A Park Yong-Sun Kim Ihn-Geun Choi 《Biochemical and biophysical research communications》2009,389(3):443-448
Defensins have a broad range of antimicrobial activity against bacteria, fungi, and viruses. The expression of human β-defensin-2 (hBD-2) is prevalently observed in epithelial cells and is induced by bacterial infection. Here, we have shown that the expression of the hBD-2 gene and release of hBD-2 protein into the medium is up-regulated in response to CpG-DNA in human B cell line RPMI 8226. The induction of hBD-2 was dependent on CG sequence and phosphorothioate backbone-modification. This was also confirmed in primary human lymphocytes. To shed light on the molecular mechanism involved in hBD-2 induction by CpG-DNA, we examined the contribution of the NF-κB signaling pathway in RPMI 8226 cells. Suppression of MyD88 function and inhibition of NF-κB nuclear localization blocked hBD-2 induction. The NF-κB pathway inhibitors also abolished hBD-2 induction. These results may contribute to a better understanding on the therapeutic effects of CpG-DNA against infectious diseases. 相似文献
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Mauro S Sandrin Hilary A Vaughan Pei-Xiang Xing Ian F.C McKenzie 《Glycoconjugate journal》1997,14(1):97-105
We have recently demonstrated that both antibodies to Gal(1,3)Gal, and the Gal(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal(1,3)Gal antibodies and IB4 lectin with a Gal(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal(1,3)Gal expressed after transfection of COS cells (Gal(1,3)Gal-, Muc1-) with cDNA encoding the pig ,3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal(1,3)Gal antibodies react with mucin peptides. Abbreviations: HPLC, high performance liquid phase chromatography; HRP, horse radish peroxidase; mAb, monoclonal antibody; NHS, normal human serum; PBS, phosphate buffered saline; VNTR, variable number of tandem repeats 相似文献
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The activity of purified human Waldenstr?m's IgM protein to fix complement of human and guinea pig origins was compared at different temperatures using the polystyrene latex particle-adsorption method. It was shown that the interaction of the IgM proteins with complement differed depending on the source of complement and that a pronounced heterogeneity in complement-fixing activity was observed among the IgM proteins when tested with guinea pig complement. Thus, by the use of guinea pig complement, six human IgM proteins examined were classified roughly into two groups, one having a high and the other a low activity at 3 C as well as at 37 degrees C. With human complement, five proteins showed a rather uniform activity at 37 degrees C. However, there was one protein with no detectable activity, suggesting the presence of non-complement-fixing protein in the IgM class. All the six proteins showed no significant activity with human complement at 3 C. No antigenic difference has been found as yet in the Fc or Cmu2 region among these IgM proteins examined. 相似文献
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Characterization of golimumab,a human monoclonal antibody specific for human tumor necrosis factor α
《MABS-AUSTIN》2013,5(4):428-439
We prepared and characterized golimumab (CNTO148), a human IgG1 tumor necrosis factor alpha (TNFα) antagonist monoclonal antibody chosen for clinical development based on its molecular properties. Golimumab was compared with infliximab, adalimumab and etanercept for affinity and in vitro TNFα neutralization. The affinity of golimumab for soluble human TNFα, as determined by surface plasmon resonance, was similar to that of etanercept (18 pM versus 11 pM), greater than that of infliximab (44 pM) and significantly greater than that of adalimumab (127 pM, p=0.018). The concentration of golimumab necessary to neutralize TNFα-induced E-selectin expression on human endothelial cells by 50% was significantly less than those for infliximab (3.2 fold; p=0.017) and adalimumab (3.3-fold; p=0.008) and comparable to that for etanercept. The conformational stability of golimumab was greater than that of infliximab (primary melting temperature [Tm] 74.8 °C vs. 69.5 °C) as assessed by differential scanning calorimetry. In addition, golimumab showed minimal aggregation over the intended shelf life when formulated as a high concentration liquid product (100 mg/mL) for subcutaneous administration. In vivo, golimumab at doses of 1 and 10 mg/kg significantly delayed disease progression in a mouse model of human TNFα-induced arthritis when compared with untreated mice, while infliximab was effective only at 10 mg/kg. Golimumab also significantly reduced histological scores for arthritis severity and cartilage damage, as well as serum levels of pro-inflammatory cytokines and chemokines associated with arthritis. Thus, we have demonstrated that golimumab is a highly stable human monoclonal antibody with high affinity and capacity to neutralize human TNFα in vitro and in vivo. 相似文献
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《MABS-AUSTIN》2013,5(2):163-171
Natural IgM antibodies play an important role in the body’s defense mechanisms against transformed cells in the human body and are currently being exploited both in prognoses of malignant lesions and in the therapy of cancer patients. However, despite growing interest and clinical promise, thus far the IgM class of antibodies has failed to gain widespread commercial interest as these are considered to be difficult to produce recombinantly. IgMs are polymeric and have a relatively large mass. In addition, IgM molecules are heavily glycosylated and, when produced in non-human cell lines, they may contain non-human glycan structures which may be potentially immunogenic. Clearly, production systems capable of expressing human recombinant IgM antibodies are needed. We have successfully used PER.C6® cells – a human cell line - to generate three separate human recombinant monoclonal IgMs in suspension cultures in protein-free medium. All three of the IgMs were constructed with joining (J) chain and were expressed in the pentameric form. One of the IgMs was also expressed as a hexamer without J chain. Clones with cell specific productivities greater than 20 pg/cell/day were generated, which led to yields of 0.5 g/L to 2g/L in fed-batch production. All the IgMs expressed were biologically active as shown in binding and cytotoxicity assays. These studies demonstrate the potential of PER.C6® cells for the production of high levels of functional recombinant IgM and other polymeric molecules, using a straightforward and rapid stable cell line generation method. 相似文献
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Anna Tchoudakova Frank Hensel Alec Murillo Bernie Eng Marketa Foley Lakee Smith Frank Schoenen Antonia Hildebrand Arndt-René Kelter Leodevico L Ilag H Peter Vollmers Stephanie Brandlein Jane McIninch John Chon Gene Lee Marco Cacciuttolo 《MABS-AUSTIN》2009,1(2):163-171
Natural IgM antibodies play an important role in the body''s defense mechanisms against transformed cells in the human body and are currently being exploited both in prognoses of malignant lesions and in the therapy of cancer patients. However, despite growing interest and clinical promise, thus far the IgM class of antibodies has failed to gain widespread commercial interest as these are considered to be difficult to produce recombinantly. IgMs are polymeric and have a relatively large mass. In addition, IgM molecules are heavily glycosylated and, when produced in non-human cell lines, they may contain non-human glycan structures which may be potentially immunogenic. Clearly, production systems capable of expressing human recombinant IgM antibodies are needed. We have successfully used PER.C6® cells—a human cell line—to generate three separate human recombinant monoclonal IgMs in suspension cultures in protein-free medium. All three of the IgMs were constructed with joining (J) chain and were expressed in the pentameric form. One of the IgMs was also expressed as a hexamer without J chain. Clones with cell specific productivities greater than 20 pg/cell/day were generated, which led to yields of 0.5 g/L to 2g/L in fed-batch production. All the IgMs expressed were biologically active as shown in binding and cytotoxicity assays. These studies demonstrate the potential of PER.C6® cells for the production of high levels of functional recombinant IgM and other polymeric molecules, using a straightforward and rapid stable cell line generation method.Key words: PER.C6®, IgM, expression, hexamer, pentamer, J chain 相似文献
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Wiuf C 《Genetics》2001,159(2):749-756
The possibility of recombination in human mitochondrial DNA (mtDNA) has been hotly debated over the last few years. In this study, a general model of recombination in circular molecules is developed and applied to a recently published African sample (n = 21) of complete mtDNA sequences. It is shown that the power of correlation measures to detect recombination in circular molecules can be vanishingly small and that the data are consistent with the given model and no recombination only if the overall heterogeneity in mutation rate is <0.09. 相似文献
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Michael Eisenbach Ilan Tur-Kaspa 《BioEssays : news and reviews in molecular, cellular and developmental biology》1999,21(3):203-210
A key process in human fertilization is bringing the two gametes together, so that the complex molecular events involved in sperm and egg interaction can begin. Does nature allow fertilization to occur only as a consequence of a chance collision, or is there a precontact sperm-egg communication? This review summarizes the bioassays used in testing human spermatozoa for chemotaxis, emphasizing the necessity to distinguish between chemotaxis and other accumulation-causing processes, and the results obtained. It demonstrates that human sperm chemotaxis to a follicular factor(s) does occur, at least in vitro, and that only capacitated spermatozoa are chemotactically responsive. Substances that have been proposed as attractants for human spermatozoa are reassessed. The potential role of sperm chemotaxis in vivo is discussed. Faulty precontact sperm-egg communication may be one of the causes of male infertility, female infertility, or both. On the other hand, interfering with human sperm chemotaxis may represent an exciting new approach to contraception. BioEssays 21:203–210, 1999. © 1999 John Wiley & Sons, Inc. 相似文献
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De Los Angeles A Loh YH Tesar PJ Daley GQ 《Current opinion in genetics & development》2012,22(3):272-282
Pluripotency manifests during mammalian development through formation of the epiblast, founder tissue of the embryo proper. Rodent pluripotent stem cells can be considered as two distinct states: na?ve and primed. Na?ve pluripotent stem cell lines are distinguished from primed cells by self-renewal in response to LIF signaling and MEK/GSK3 inhibition (LIF/2i conditions) and two active X chromosomes in female cells. In rodent cells, the na?ve pluripotent state may be accessed through at least three routes: explantation of the inner cell mass, somatic cell reprogramming by ectopic Oct4, Sox2, Klf4, and C-myc, and direct reversion of primed post-implantation-associated epiblast stem cells (EpiSCs). In contrast to their rodent counterparts, human embryonic stem cells and induced pluripotent stem cells more closely resemble rodent primed EpiSCs. A critical question is whether na?ve human pluripotent stem cells with bona fide features of both a pluripotent state and na?ve-specific features can be obtained. In this review, we outline current understanding of the differences between these pluripotent states in mice, new perspectives on the origins of na?ve pluripotency in rodents, and recent attempts to apply the rodent paradigm to capture na?ve pluripotency in human cells. Unraveling how to stably induce na?ve pluripotency in human cells will influence the full realization of human pluripotent stem cell biology and medicine. 相似文献
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