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Zeitschriftenartikel zum Thema "Proteins, programmed instruction"

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Yin, Changhong, Tae-Hoon Chung, Janet Ayello, Tae-Hyun Park, Carmella van de Ven, Mitchell S. Cairo und Sanghoon Lee. „Overexpression Of Deleted In Lymphocytic Leukemia 1 (DLEU1) Significantly Induces Programmed Cell Death and Inhibits Cell Proliferation In Primary Mediastinal B-Cell Lymphoma (PMBL): DLEU1 May Be a Tumor Suppressor Gene In a Subset Of Patients With PMBL“. Blood 122, Nr. 21 (15.11.2013): 3852. http://dx.doi.org/10.1182/blood.v122.21.3852.3852.

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Abstract Background Primary Mediastinal large B-cell lymphoma (PMBL) is a rare form of Non Hodgkin Lymphoma (NHL) representing 2% of mature B-cell non-Hodgkin lymphoma in patients less than 18 years of age (Lones/Cairo et al., JCO, 2000; Burkhardt et al., BJH, 2005). PMBL has similar histo-pathological features along the biologic spectrum between Diffuse Large B-Cell Lymphoma (DLBCL) and classical HL (cHL) (Abramson et al., Blood, 2005). We have recently reported that a significantly decrease in EFS among children and adolescent PMBL patients compared with other stage III non-PMBL pediatric DLBCL patients following FAB/LMB96 therapy, suggesting that children and adolescent PMBL may be an inherently different B-NHL (Gerrard/Cairo et al., Blood, 2013). Nevertheless, the genetic mechanisms underlying the pathogenesis of PMBL remain unknown. Using high-resolution, microarray-based genomic techniques chromosomal losses at 13q14 was identified in 5 of the 37 (13%) PMBL tumor samples indicating localization of potential tumor suppressor genes at 13q that may be involved in the etiology of PMBL (Wessondorf, et al, Leuk., 2007). DLEU1 (Deleted in lymphocytic Leukemia 1) is a Burkitt lymphoma (BL) classifier gene (Dave et al., NEJM, 2006) and is located in the chromosome 13q14.3 region. DLEU1 interacts with 19 proteins including of c-Myc, RASSF1, TUBB2C and UBR1. DLEU1 has been implicated as a tumor suppressor in BL (Lee/Yin/Cairo et al., ASH, 2012) and in chronic lymphocytic leukemia (Garding et al., Plos Genet., 2013). Objectives We hypothesize that DLEU1 may act as a tumor suppressor gene through induction of caspase-3/7 activity thereby inhibiting cell proliferation and down-regulation of constitutively activated signaling pathways in PMBL. Methods The full length of cDNA encoding DLEU1 was fused into pEGFP-N3 vector and pEGFP-DLEU1fusion construct (Lee/Yin/Cairo et al., ASH, 2012) was transfected into Karpas-1106P cells using Amaxa Nucleofector kit, followed by the manufacturer’s instruction. Forty-eight hours post transient transfection, total RNA was extracted and 1ug of total RNA was used for cDNA synthesized as above. For comparison of mRNA expression of network genes, quantitative RT-PCR was performed by CFX96 Real-time (Bio-rad). The expression of DLEU1 protein in DLEU1 transient transfected Karpas-1106P cells was confirmed both by western blotting analysis and under fluorescent microscope. In brief, the total lysates was prepared from DELU1 transfected cells at 48hours post-transfection, and membrane was hybridized with Rabbit polyclonal DLEU1 antibody (ProteinTech) on immune blotting. MTS (Promega) and Caspase 3/7 assay (Promega) were employed to examine the effects on cell proliferation and apoptosis. Statistical significance was determined by one tailed paired Student t-test. Results The expression of DLEU1 mRNA in DLEU1 transiently transfected Karpas-1106P (DLEU1-Karpas) cells was significantly higher than empty vector alone transfected cell as mock control (78-fold increase, p<0.01). Comparing mRNA expression of DLEU1 network genes in DLEU1-Karpas cells to mock control cells, we observed a significant decrease in mRNA expression of the anti-apoptotic gene, Bcl-xL (73% reduction, p<0.01) and suppressors of cell signaling genes, SOCS1 and SOCS3 (52% reduction, p<0.05 and 44% reduction, p<0.01, respectively). There was a significant reduction in the mRNA expression of oncogenes, Pim-1 and c-Myc (72% reduction, p<0.04 and 54% reduction, p<0.03) respectively, in DLEU1-Karpas cells compared to mock control cells. Cell proliferation was significantly inhibited 18% (p<0.03) whereas Caspase 3/7 activity was significantly increased 1.5-fold (p<0.03) in DLEU1-Karpas cells at 48hours post transfection. Lastly, we found significant decreases of protein expression in phoshpho-Akt (67% reduction, p<0.01), phoshpho-ikBa (48% reduction, p<0.02), phoshpho-STAT3 (15% reduction, p<0.02) and c-Myc (25% reduction, p<0.01), respectively in DLEU1-Karpas cells. Conclusions We demonstrated that transient overexpression of DLEU1 1) significantly inhibits cell proliferation and induces programmed cell death, and 2) downregulates constitutively activated signaling pathways in PMBL, and therefore, DLEU1 may in part act as a tumor suppressor gene in a subset of patients with PMBL. Disclosures: No relevant conflicts of interest to declare.
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Giaveri, Simone, Nitin Bohra, Christoph Diehl, Hao Yuan Yang, Martine Ballinger, Nicole Paczia, Timo Glatter und Tobias J. Erb. „Integrated translation and metabolism in a partially self-synthesizing biochemical network“. Science 385, Nr. 6705 (12.07.2024): 174–78. http://dx.doi.org/10.1126/science.adn3856.

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One of the hallmarks of living organisms is their capacity for self-organization and regeneration, which requires a tight integration of metabolic and genetic networks. We sought to construct a linked metabolic and genetic network in vitro that shows such lifelike behavior outside of a cellular context and generates its own building blocks from nonliving matter. We integrated the metabolism of the crotonyl-CoA/ethyl-malonyl-CoA/hydroxybutyryl-CoA cycle with cell-free protein synthesis using recombinant elements. Our network produces the amino acid glycine from CO 2 and incorporates it into target proteins following DNA-encoded instructions. By orchestrating ~50 enzymes we established a basic cell-free operating system in which genetically encoded inputs into a metabolic network are programmed to activate feedback loops allowing for self-integration and (partial) self-regeneration of the complete system.
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Jassinskaja, Maria, Kristýna Pimková, Emil Johansson, Ewa Sitnicka Quinn und Jenny Hansson. „In-Depth Proteomic Characterization of Lineage-Biased Hematopoietic Progenitor Cells in the Fetus and Adult“. Blood 134, Supplement_1 (13.11.2019): 3703. http://dx.doi.org/10.1182/blood-2019-121799.

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The process of hematopoiesis is subject to extensive ontogenic remodeling that is accompanied by alterations in cellular fate both during normal development and upon malignant transformation. Although the functional differences between fetal and adult hematopoiesis are well established, the responsible molecular mechanisms have long remained largely unexplored at the proteomic level. We hypothesize that an intrinsically programmed proteomic switch in hematopoietic stem and progenitor cells (HSPCs) during ontogeny regulates the outcome of hematopoiesis both during normal development and upon leukemia initiation, and that the proteomic makeup of the leukemia-initiating cell has an instructive role in determining the outcome of the resulting cancer. In our latest work, we utilized quantitative mass spectrometry-based proteomics to characterize and compare the proteomic makeup of fetal and adult Lin- Sca-1+ cKit+ (LSK) HSPCs (Jassinskaja et al., 2017, Cell Reports), representing all of the earliest stem and progenitors in fetal and adult hematopoiesis. We identified differences in several important cellular processes not previously described to play a role in hematopoiesis, highlighting the need for applying proteomic-centric approaches in the field. In order to further increase our understanding of normal and malignant hematopoiesis during ontogeny, we are now continuing this work by focusing on more stringently defined populations of lineage-biased hematopoietic progenitor cells (HPCs). Here, we have utilized encapsulated methods for preparation of microscale samples in combination with state-of-the-art mass spectrometry to gain deep coverage of the proteome of 100,000 fetal (E14.5) and adult lymphoid-primed multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs) and granulocyte-macrophage progenitors (GMPs). Our analysis resulted in the identification and quantification of 4189 proteins, with over 200 proteins per cell type displaying differential expression between the fetus and the adult. Importantly, the differentially expressed proteins were enriched for a broad variety of biological processes. Similar to our previous findings in HSPCs, for all three cell types, proteins higher expressed in the fetus showed a strong enrichment for cell cycle- and translation-related processes, whereas those higher expressed in the adult were enriched for processes related to immune response and redox homeostasis. Our preliminary analysis of hematopoietic cell subset signatures associated with the differentially expressed proteins suggests a stronger lymphoid bias in fetal compared to adult LMPPs as well as CLPs. Surprisingly, the proteomic signature of fetal GMPs suggests a retained megakaryocyte-erythroid potential, which is corroborated by a significantly higher expression of megakaryocyte progenitor marker CD41 on the fetal cells. Upon analyzing expression of transcription factors (TFs) in fetal and adult HPCs, we could confirm differential expression of TFs known to have ontogeny-specific roles in hematopoiesis (e.g. Arid3a and Etv6). Importantly, we also identified several differentially expressed TFs that could represent novel regulators of fetal- and adult-specific features of hematopoiesis, such as Irf8, Btf3, Mndal and Pura. Furthermore, the difference in expression of Irf8 observed here could indicate a previously unknown ontogenic switch in the balance between neutrophil and monocyte production from myeloid-competent progenitors. Lastly, our data shows strong indications of a differential sensitivity towards Rho kinase inhibition between the fetal and the adult HPCs. Collectively, our work represents a significant advancement in the understanding of the molecular programs that govern ontogenic differences in hematopoiesis and provides a solid foundation for future investigation of which factors are responsible for the difference in susceptibility and outcome of different leukemias in infants and in adults. Disclosures No relevant conflicts of interest to declare.
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Mortensen, Julie Bondgaard, Vladimirova Yoanna, Ida Monrad Hansen, Mette Bjerre und Francesco d'Amore. „Characterization of Soluble Immune Checkpoint Protein PD-1, PD-L1 and PD-L2 Levels in Different Types of Lymphoid Malignancies“. Blood 132, Supplement 1 (29.11.2018): 5306. http://dx.doi.org/10.1182/blood-2018-99-114509.

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Abstract Background Checkpoint proteins regulate the immune system and their down-regulation of effector mechanisms is exploited by malignant cells to evade antitumor immune response. Membrane bound programmed death 1 protein (PD-1) and its ligands 1 and 2 (PD-L1 and PD-L2) are pivotal members of the immune checkpoint family. The significance of the PD-1 pathway have been demonstrated in a variety of malignant diseases and suppressing the pathway with targeting antibodies can re-establish antitumor immunity. Soluble forms of the proteins (sPD-1, sPD-L1 and sPD-L2) are detectable in the peripheral blood, but their biological and clinical significance are still largely unknown. To our knowledge, this is the first study to simultaneously characterize sPD-1, sPD-L1 and sPD-L2 in different types of lymphoma. Aims The aim of the present study was to measure the pre-therapeutic sPD-1, sPD-L1 and sPD-L2 levels in different lymphoid malignancies and correlate them with clinico-pathological features and outcome. Methods We established and validated a Time Resolved Immunoflourometric assay (TRIFMA) to determine levels of sPD-1 and sPD-L2. Soluble PD-L1 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) applied according to manufacturer's instructions. In total, archival serum samples from 102 patients were analysed in duplicate for each protein. This single-institution study population consisted of patients with chronic lymphocytic leukemia (CLL; n=42), diffuse large B cell lymphoma (DLBCL; n=33), follicular lymphoma (FL; 15) and Hodgkin lymphoma (HL; n=12). In addition, 22 and 17 healthy controls were included for analysis of sPD-1/sPD-L1 and sPD-L2, respectively. Information on clinical parameters, response to treatment and outcome was obtained from medical records. Measured levels were compared between patient subgroups and controls using a non-parametric test (Mann-Whitney). P-values below 0.05 were considered statistically significant. Results Soluble PD-1 levels were higher in patients, taken as one group, compared to controls (p=0.0002). When analyzed according to lymphoma type, patients with DLBCL, CLL and FL still had significantly elevated sPD-1 levels as compared to controls (p=0.0089, p=0.0008 and p<0.0001, respectively). Highest sPD-1 levels were observed in FL and these were also significantly higher than in any of the other lymphoma subtypes analyzed. Soluble PD-L1 levels were similar in patients, taken as one group, and controls. Interestingly, patients with FL had lower sPD-L1 levels than patients from all the other lymphoma subtypes and it was the only histology whose sPD-L1 levels differed significantly (lower values) from healthy controls (p=0.0017, see table 1). Moreover, we identified a reverse expression pattern of sPD-1/sPD-L1 in FL as compared to other lymphoma subtypes, as FL had significantly higher sPD-1 and lower sPD-L1 than all other remaining patients (see table 1). Soluble PD-L2 levels were generally higher than those of sPD-1 and sPD-L1, and the highest values were found in healthy controls. When analyzed according to histological subtype, patients with CLL, DLBCL and FL had all significantly lower sPD-L2 levels than healthy controls (see table 1). Interestingly, the sPD-1, sPD-L1 and sPD-L2 levels measured in HL patients did not differ significantly from controls, however, this may be due to limited sample size. Conclusion We simultaneously characterized sPD-1, sPD-L1 and sPD-L2 in selected lymphomas subtypes and found varying levels across the investigated lymphoma entities. In particular, we identified a reverse expression pattern of sPD-1 and sPD-L1 in FL compared to other lymphoid malignancies. We were the first to also characterize sPD-L2 levels in the same patients and found its levels to be generally high throughout lymphoma entities, but highest in healthy controls. A correlation analysis with outcome-related parameters is ongoing. Disclosures No relevant conflicts of interest to declare.
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Brien, Donna Lee. „Unplanned Educational Obsolescence: Is the ‘Traditional’ PhD Becoming Obsolete?“ M/C Journal 12, Nr. 3 (15.07.2009). http://dx.doi.org/10.5204/mcj.160.

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Discussions of the economic theory of planned obsolescence—the purposeful embedding of redundancy into the functionality or other aspect of a product—in the 1980s and 1990s often focused on the impact of such a design strategy on manufacturers, consumers, the market, and, ultimately, profits (see, for example, Bulow; Lee and Lee; Waldman). More recently, assessments of such shortened product life cycles have included calculations of the environmental and other costs of such waste (Claudio; Kondoh; Unruh). Commonly utilised examples are consumer products such as cars, whitegoods and small appliances, fashion clothing and accessories, and, more recently, new technologies and their constituent components. This discourse has been adopted by those who configure workers as human resources, and who speak both of skills (Janßen and Backes-Gellner) and human capital itself (Chauhan and Chauhan) being made obsolete by market forces in both predictable and unplanned ways. This includes debate over whether formal education can assist in developing the skills that make their possessors less liable to become obsolete in the workforce (Dubin; Holtmann; Borghans and de Grip; Gould, Moav and Weinberg). However, aside from periodic expressions of disciplinary angst (as in questions such as whether the Liberal Arts and other disciplines are becoming obsolete) are rarely found in discussions regarding higher education. Yet, higher education has been subsumed into a culture of commercial service provision as driven by markets and profit as the industries that design and deliver consumer goods. McKelvey and Holmén characterise this as a shift “from social institution to knowledge business” in the subtitle of their 2009 volume on European universities, and the recent decade has seen many higher educational institutions openly striving to be entrepreneurial. Despite some debate over the functioning of market or market-like mechanisms in higher education (see, for instance, Texeira et al), the corporatisation of higher education has led inevitably to market segmentation in the products the sector delivers. Such market segmentation results in what are called over-differentiated products, seemingly endless variations in the same product to attempt to increase consumption and attendant sales. Milk is a commonly cited example, with supermarkets today stocking full cream, semi-skimmed, skimmed, lactose-free, soy, rice, goat, GM-free and ‘smart’ (enriched with various vitamins, minerals and proteins) varieties; and many of these available in fresh, UHT, dehydrated and/or organic versions. In the education market, this practice has resulted in a large number of often minutely differentiated, but differently named, degrees and other programs. Where there were once a small number of undergraduate degrees with discipline variety within them (including the Bachelor of Arts and Bachelor of Science awards), students can now graduate with a named qualification in a myriad of discipline and professional areas. The attempt to secure a larger percentage of the potential client pool (who are themselves often seeking to update their own skills and knowledges to avoid workforce obsolescence) has also resulted in a significant increase in the number of postgraduate coursework certificates, diplomas and other qualifications across the sector. The Masters degree has fractured from a research program into a range of coursework, coursework plus research, and research only programs. Such proliferation has also affected one of the foundations of the quality and integrity of the higher education system, and one of the last bastions of conventional practice, the doctoral degree. The PhD as ‘Gold-Standard’ Market Leader? The Doctor of Philosophy (PhD) is usually understood as a largely independent discipline-based research project that results in a substantial piece of reporting, the thesis, that makes a “substantial original contribution to knowledge in the form of new knowledge or significant and original adaptation, application and interpretation of existing knowledge” (AQF). As the highest level of degree conferred by most universities, the PhD is commonly understood as indicating the height of formal educational attainment, and has, until relatively recently, been above reproach and alteration. Yet, whereas universities internationally once offered a single doctorate named the PhD, many now offer a number of doctoral level degrees. In Australia, for example, candidates can also complete PhDs by Publication and by Project, as well as practice-led doctorates in, and named Doctorates of/in, Creative Arts, Creative Industries, Laws, Performance and other ‘new’ discipline areas. The Professional Doctorate, introduced into Australia in the early 1990s, has achieved such longevity that it now has it’s own “first generation” incarnations in (and about) disciplines such as Education, Business, Psychology and Journalism, as well as a contemporary “second generation” version which features professionally-practice-led Mode 2 knowledge production (Maxwell; also discussed in Lee, Brennan and Green 281). The uniquely Australian PhD by Project in the disciplines of architecture, design, business, engineering and education also includes coursework, and is practice and particularly workplace (or community) focused, but unlike the above, does not have to include a research element—although this is not precluded (Usher). A significant number of Australian universities also currently offer a PhD by Publication, known also as the PhD by Published Papers and PhD by Published Works. Introduced in the 1960s in the UK, the PhD by Publication there is today almost exclusively undertaken by academic staff at their own institutions, and usually consists of published work(s), a critical appraisal of that work within the research context, and an oral examination. The named degree is rare in the USA, although the practice of granting PhDs on the basis of prior publications is not unknown. In Australia, an examination of a number of universities that offer the degree reveals no consistency in terms of the framing policies except for the generic Australian Qualifications Framework accreditation statement (AQF), entry requirements and conditions of candidature, or resulting form and examination guidelines. Some Australian universities, for instance, require all externally peer-refereed publications, while others will count works that are self-published. Some require actual publications or works in press, but others count works that are still at submission stage. The UK PhD by Publication shows similar variation, with no consensus on purpose, length or format of this degree (Draper). Across Australia and the UK, some institutions accept previously published work and require little or no campus participation, while others have a significant minimum enrolment period and count only work generated during candidature (see Brien for more detail). Despite the plethora of named degrees at doctoral level, many academics continue to support the PhD’s claim to rigor and intellectual attainment. Most often, however, these arguments cite tradition rather than any real assessment of quality. The archaic trappings of conferral—the caps, gowns and various other instruments of distinction—emphasise a narrative in which it is often noted that doctorates were first conferred by the University of Paris in the 12th century and then elsewhere in medieval Europe. However, challenges to this account note that today’s largely independently researched thesis is a relatively recent arrival to educational history, being only introduced into Germany in the early nineteenth century (Bourner, Bowden and Laing; Park 4), the USA in a modified form in the mid-nineteenth century and the UK in 1917 (Jolley 227). The Australian PhD is even more recent, with the first only awarded in 1948 and still relatively rare until the 1970s (Nelson 3; Valadkhani and Ville). Additionally, PhDs in the USA, Canada and Denmark today almost always incorporate a significant taught coursework element (Noble). This is unlike the ‘traditional’ PhD in the UK and Australia, although the UK also currently offers a number of what are known there as ‘taught doctorates’. Somewhat confusingly, while these do incorporate coursework, they still include a significant research component (UKCGE). However, the UK is also adopting what has been identified as an American-inflected model which consists mostly, or largely, of coursework, and which is becoming known as the ‘New Route British PhD’ (Jolley 228). It could be posited that, within such a competitive market environment, which appears to be driven by both a drive for novelty and a desire to meet consumer demand, obsolescence therefore, and necessarily, threatens the very existence of the ‘traditional’ PhD. This obsolescence could be seen as especially likely as, alongside the existence of the above mentioned ‘new’ degrees, the ‘traditional’ research-based PhD at some universities in Australia and the UK in particular is, itself, also in the process of becoming ‘professionalised’, with some (still traditionally-framed) programs nevertheless incorporating workplace-oriented frameworks and/or experiences (Jolley 229; Kroll and Brien) to meet professionally-focused objectives that it is acknowledged cannot be met by producing a research thesis alone. While this emphasis can be seen as operating at the expense of specific disciplinary knowledge (Pole 107; Ball; Laing and Brabazon 265), and criticised for that, this workplace focus has arisen, internationally, as an institutional response to requests from both governments and industry for training in generic skills in university programs at all levels (Manathunga and Wissler). At the same time, the acknowledged unpredictability of the future workplace is driving a cognate move from discipline specific knowledge to what have been described as “problem solving and knowledge management approaches” across all disciplines (Gilbert; Valadkhani and Ville 2). While few query a link between university-level learning and the needs of the workplace, or the motivating belief that the overarching role of higher education is the provision of professional training for its client-students (see Laing and Brabazon for an exception), it also should be noted that a lack of relevance is one of the contributors to dysfunction, and thence to obsolescence. The PhD as Dysfunctional Degree? Perhaps, however, it is not competition that threatens the traditional PhD but, rather, its own design flaws. A report in The New York Times in 2007 alerted readers to what many supervisors, candidates, and researchers internationally have recognised for some time: that the PhD may be dysfunctional (Berger). In Australia and elsewhere, attention has focused on the uneven quality of doctoral-level degrees across institutions, especially in relation to their content, rigor, entry and assessment standards, and this has not precluded questions regarding the PhD (AVCC; Carey, Webb, Brien; Neumann; Jolley; McWilliam et al., "Silly"). It should be noted that this important examination of standards has, however, been accompanied by an increase in the awarding of Honorary Doctorates. This practice ranges from the most reputable universities’ recognising individuals’ significant contributions to knowledge, culture and/or society, to wholly disreputable institutions offering such qualifications in return for payment (Starrs). While generally contested in terms of their status, Honorary Doctorates granted to sports, show business and political figures are the most controversial and include an award conferred on puppet Kermit the Frog in 1996 (Jeffries), and some leading institutions including MIT, Cornell University and the London School of Economics and Political Science are distinctive in not awarding Honorary Doctorates. However, while distracting, the Honorary Doctorate itself does not answer all the questions regarding the quality of doctoral programs in general, or the Doctor of Philosophy in particular. The PhD also has high attrition rates: 50 per cent or more across Australia, the USA and Canada (Halse 322; Lovitts and Nelson). For those who remain in the programs, lengthy completion times (known internationally as ‘time-to-degree’) are common in many countries, with averages of 10.5 years to completion in Canada, and from 8.2 to more than 13 years (depending on discipline) in the USA (Berger). The current government performance-based funding model for Australian research higher degrees focuses attention on timely completion, and there is no doubt that, under this system—where universities only receive funding for a minimum period of candidature when those candidates have completed their degrees—more candidates are completing within the required time periods (Cuthbert). Yet, such a focus has distracted from assessment of the quality and outcomes of such programs of study. A detailed survey, based on the theses lodged in Australian libraries, has estimated that at least 51,000 PhD theses were completed in Australia to 2003 (Evans et al. 7). However, little attention has been paid to the consequences of this work, that is, the effects that the generation of these theses has had on either candidates or the nation. There has been no assessment, for instance, of the impact on candidates of undertaking and completing a doctorate on such facets of their lives as their employment opportunities, professional choices and salary levels, nor any effect on their personal happiness or levels of creativity. Nor has there been any real evaluation of the effect of these degrees on GDP, rates of the commercialisation of research, the generation of intellectual property, meeting national agendas in areas such as innovation, productivity or creativity, and/or the quality of the Australian creative and performing arts. Government-funded and other Australian studies have, however, noted for at least a decade both that the high numbers of graduates are mismatched to a lack of market demand for doctoral qualifications outside of academia (Kemp), and that an oversupply of doctorally qualified job seekers is driving wages down in some sectors (Jones 26). Even academia is demanding more than a PhD. Within the USA, doctoral graduates of some disciplines (English is an often-cited example) are undertaking second PhDs in their quest to secure an academic position. In Australia, entry-level academic positions increasingly require a scholarly publishing history alongside a doctoral-level qualification and, in common with other quantitative exercises in the UK and in New Zealand, the current Excellence in Research for Australia research evaluation exercise values scholarly publications more than higher degree qualifications. Concluding Remarks: The PhD as Obsolete or Retro-Chic? Disciplines and fields are reacting to this situation in various ways, but the trend appears to be towards increased market segmentation. Despite these charges of PhD dysfunction, there are also dangers in the over-differentiation of higher degrees as a practice. If universities do not adequately resource the professional development and other support for supervisors and all those involved in the delivery of all these degrees, those institutions may find that they have spread the existing skills, knowledge and other institutional assets too thinly to sustain some or even any of these degrees. This could lead to the diminishing quality (and an attendant diminishing perception of the value) of all the higher degrees available in those institutions as well as the reputation of the hosting country’s entire higher education system. As works in progress, the various ‘new’ doctoral degrees can also promote a sense of working on unstable ground for both candidates and supervisors (McWilliam et al., Research Training), and higher degree examiners will necessarily be unfamiliar with expected standards. Candidates are attempting to discern the advantages and disadvantages of each form in order to choose the degree that they believe is right for them (see, for example, Robins and Kanowski), but such assessment is difficult without the benefit of hindsight. Furthermore, not every form may fit the unpredictable future aspirations of candidates or the volatile future needs of the workplace. The rate with which everything once new descends from stylish popularity through stages of unfashionableness to become outdated and, eventually, discarded is increasing. This escalation may result in the discipline-based research PhD becoming seen as archaic and, eventually, obsolete. Perhaps, alternatively, it will lead to newer and more fashionable forms of doctoral study being discarded instead. Laing and Brabazon go further to find that all doctoral level study’s inability to “contribute in a measurable and quantifiable way to social, economic or political change” problematises the very existence of all these degrees (265). Yet, we all know that some objects, styles, practices and technologies that become obsolete are later recovered and reassessed as once again interesting. They rise once again to be judged as fashionable and valuable. Perhaps even if made obsolete, this will be the fate of the PhD or other doctoral degrees?References Australian Qualifications Framework (AQF). “Doctoral Degree”. AQF Qualifications. 4 May 2009 ‹http://www.aqf.edu.au/doctor.htm›. Australian Vice-Chancellors’ Committee (AVCC). Universities and Their Students: Principles for the Provision of Education by Australian Universities. Canberra: AVCC, 2002. 4 May 2009 ‹http://www.universitiesaustralia.edu.au/documents/publications/Principles_final_Dec02.pdf›. Ball, L. “Preparing Graduates in Art and Design to Meet the Challenges of Working in the Creative Industries: A New Model For Work.” Art, Design and Communication in Higher Education 1.1 (2002): 10–24. Berger, Joseph. “Exploring Ways to Shorten the Ascent to a Ph.D.” Education. The New York Times, 3 Oct. 2008. 4 May 2009 ‹http://nytimes.com/2007/10/03/education/03education.html›. Borghans, Lex, and Andries de Grip. Eds. The Overeducated Worker?: The Economics of Skill Utilization. Cheltenham, UK: Edward Elgar, 2000. Bourner, T., R. Bowden and S. Laing. “Professional Doctorates in England”. Studies in Higher Education 26 (2001) 65–83. Brien, Donna Lee. “Publish or Perish?: Investigating the Doctorate by Publication in Writing”. The Creativity and Uncertainty Papers: the Refereed Proceedings of the 13th Conference of the Australian Association of Writing Programs. AAWP, 2008. 4 May 2009 ‹http://www.aawp.org.au/creativity-and-uncertainty-papers›. Bulow, Jeremy. “An Economic Theory of Planned Obsolescence.” The Quarterly Journal of Economics 101.4 (Nov. 1986): 729–50. Carey, Janene, Jen Webb, and Donna Lee Brien. “Examining Uncertainty: Australian Creative Research Higher Degrees”. The Creativity and Uncertainty Papers: the Refereed Proceedings of the 13th Conference of the Australian Association of Writing Programs. AAWP, 2008. 4 May 2009 ‹http://www.aawp.org.au/creativity-and-uncertainty-papers›. Chauhan, S. P., and Daisy Chauhan. “Human Obsolescence: A Wake–up Call to Avert a Crisis.” Global Business Review 9.1 (2008): 85–100. Claudio, Luz. "Environmental Impact of the Clothing Industry." Environmental Health Perspectives 115.9 (Set. 2007): A449–54. Cuthbert, Denise. “HASS PhD Completions Rates: Beyond the Doom and Gloom”. Council for the Humanities, Arts and Social Sciences, 3 March 2008. 4 May 2009 ‹http://www.chass.org.au/articles/ART20080303DC.php›. Draper, S. W. PhDs by Publication. 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Bücher zum Thema "Proteins, programmed instruction"

1

Project, BIOTOL, Open Universiteit (Heerlen Netherlands) und Thames Polytechnic, Hrsg. Analysis of amino acids, proteins, and nucleic acids. Oxford: Butterworth-Heinemann, 1992.

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2

Srinivas, Iyer. Applications of Proteomics to Cell Signaling. CRC Press LLC, 2015.

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Buchteile zum Thema "Proteins, programmed instruction"

1

Palmer, Rex A. „X-ray crystallographic studies of protein-ligand interactions“. In Protein-Ligand Interactions: structure and spectroscopy, 1–98. Oxford University PressOxford, 2001. http://dx.doi.org/10.1093/oso/9780199637508.003.0001.

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Abstract This chapter is concerned with current methods employed for the X-ray analysis of protein structures complexed with ligands. It deals with the methods used for growing crystals, the background to the use of X-ray intensity data, collection and measurement of the X-ray data, methods for analysing and interpretation of the structures. Whilst emphasis is given to the practical aspect of this type of work, in view of the highly specialized nature of X-ray crystallography it has been felt necessary to provide the reader with a background to the underlying theory. X-ray crystallography is highly computational and a great variety of software is available for performing the various stages of the calculations and graphics display. Some of the software used is specific to local research groups whilst other programmes are widely available and employed world-wide. Those programmes mentioned in the text are readily available and prospective users should have no difficulties obtaining copies complete with instructions. Important Internet addresses are included and major suppliers of specialised equipment are listed. The flow chart in Figure 1 indicates the various stages covered in the chapter.
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Schwob, Etienne, und Kim Nasmyth. „Cell cycle control of DNA replication in Saccharomyces cerevisiae“. In Eukaryotic DNA Replication, 165–96. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635863.003.0007.

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Abstract Living organisms grow and divide to produce genetically identical progeny. To divide continuously, a eukaryotic cell must duplicate all of its constituents including DNA, proteins, ribosomes, organelles, etc., and segregate them more or less equally to daughter cells. To perpetuate its genetic information, a cell must, how-ever, duplicate and segregate its chromosomes with high fidelity 10-6 mutation/bp and 10-5 chromosome loss/ cell division in yeast). An important question in cell biology is therefore how cells manage to replicate and segregate faithfully their chromo-somes? Furthermore, how is cell division regulated by cell growth and external conditions? This formidable task is achieved following the instructions of a programme, the cell cycle, which integrates the many biochemical events needed for chromosome duplication, transmission, and cell separation over time and space. For example, this programme ensures that DNA is replicated before sister chromatids begin to separate, or that sisters move to opposite poles.
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