Budget and the National Cancer Program

The budget picture for the NCI is presented for your information and evaluation-evaluation in the sense that I need and would appreciate your comments. A major issue of course is balance, in terms of clinic versus laboratory; short-term versus long-term; academic versus commercial; targeted versus nontargeted; grants versus contracts versus intramural; national versus international, and the like. It must be recognized that within a program of this emotion, visibility, and importance scientific findings and other considerations will dictate changes on at least a monthly basis. Things other than science contribute to this balance. On any given day we live within the impact of at least three budget years (what we received and did last year, what we will receive and do this year, and what this will allow us to receive and do next year). The federal budgetary process as well as the priority-setting processes of science are such that new directions cannot be taken as qulickly as woLld be optimal. Priorities muLst be set in cancer at least in their broad sense; for in addition to other areas of biomedical research, there are other compelling demands for the limited federal dollar. There will never be enouLgh resources to do all that can be done or needs to be done in cancer research. That probably is as it should be. In this regard it is heartening that operating funds for the institutes at NIH other than NCI will increase by $264 million in 1974. It is as true that information from research in other disciplines and categorical diseases will provide leads to cancer, as well as the reverse. And certainly, virtually no one wants to see resources for cancer increased at the expense of other important tasks and opportunities. This article is not an attempt to justify or to defend the spending plan of the National Cancer Program. It is to let youL know what's going on and to seek further advice on how to do it better. Articles on other aspects of the program will be published in journals including Science, Cancer Research, and the Journal of the National Cancer Institute.     

Stromal effects on mammary gland development and breast cancer

Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.     

A perspective on cancer cell metastasis

Metastasis causes most cancer deaths, yet this process remains one of the most enigmatic aspects of the disease. Building on new mechanistic insights emerging from recent research, we offer our perspective on the metastatic process and reflect on possible paths of future exploration. We suggest that metastasis can be portrayed as a two-phase process: The first phase involves the physical translocation of a cancer cell to a distant organ, whereas the second encompasses the ability of the cancer cell to develop into a metastatic lesion at that distant site. Although much remains to be learned about the second phase, we feel that an understanding of the first phase is now within sight, due in part to a better understanding of how cancer cell behavior can be modified by a cell-biological program called the epithelial-to-mesenchymal transition.     

血清microRNA在癌症诊断中的进展

microRNA是长约19到25单位的内生性的微小RNA,它通过与靶信使RNA的3’UTR的特异性结合从而调节靶基因的表达。大量的试验证明了其在肿瘤的发生发展中microRNA发挥了重大的作用。近年来,在血清中发现了稳定存在的microRNA,而对microRNA的研究主要聚焦在血清microRNA与疾病的关系上。通过对患者和正常血清microRNA的检测和对比后,发现了一批可以用于肿瘤临床检测的microRNA。作为新的检测生物标志物,血清microRNA具有方便、快捷以及较高的准确性等优点,甚至可以区分在临床很难诊断的早期肿瘤,诸如非小细胞肺癌、胃癌以及胰腺癌。     

Molecular imaging in cancer

Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumor is located in the body, but also to visualize the expression and activity of specific molecules (e.g., proteases and protein kinases) and biological processes (e.g., apoptosis, angiogenesis, and metastasis) that influence tumor behavior and/or response to therapy. This information is expected to have a major impact on cancer detection, individualized treatment, and drug development, as well as our understanding of how cancer arises.     

Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion

Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. Here, we discuss a unifying conceptual framework called "cancer immunoediting," which integrates the immune system's dual host-protective and tumor-promoting roles.     

Modeling effects of environmental change on wolf population dynamics, trait evolution, and life history

Environmental change has been observed to generate simultaneous responses in population dynamics, life history, gene frequencies, and morphology in a number of species. But how common are such eco-evolutionary responses to environmental change likely to be? Are they inevitable, or do they require a specific type of change? Can we accurately predict eco-evolutionary responses? We address these questions using theory and data from the study of Yellowstone wolves. We show that environmental change is expected to generate eco-evolutionary change, that changes in the average environment will affect wolves to a greater extent than changes in how variable it is, and that accurate prediction of the consequences of environmental change will probably prove elusive.     

论中国古典园林设计中的曲线意识及其形成

曲线作为一种几何形态，存在于客观世界的万事万物中，尤其对以视觉感知为主的造型艺术，曲线更是一种必不可少的造型元素，其使用顺手可拈。在园林设计中，尤其相对中国古典风景园林而言，大量运用的曲线更使其意境幽远，妙趣横生。因此，从园林设计中的曲线形式开始，逐步展开对园林设计中曲线审美意识及其形成相关因素的探讨，以及进一步对中国古典造园思想与手法的深层研究，对当代园林设计有重要意义。     

Mechanism-based target identification and drug discovery in cancer research

Cancer as a disease in the human population is becoming a larger health problem, and the medicines used as treatments have clear limitations. In the past 20 years, there has been a tremendous increase in our knowledge of the molecular mechanisms and pathophysiology of human cancer. Many of these mechanisms have been exploited as new targets for drug development in the hope that they will have greater antitumor activity with less toxicity to the patient than is seen with currently used medicines. The fruition of these efforts in the clinic is just now being realized with a few encouraging results.     

复合肥大企业如何建立竞争优势

面对小企业长年开展“游击战”或“地道战”的复合肥市场,人们深感市场上制订规则者不是大企业而是在后院加工的小作坊,它们似乎才是价格制订者。面对如此竞争环境,大企业自身的竞争优势究竟何在?     

p53 regulates mitochondrial respiration

The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism.     

圆榫数量对刨花板构件抗弯强度的影响

文章对刨花板部件角部接合抗弯强度与圆榫数量之间关系进行初步探讨,对实验中所获得的数据进行回归分析,找出了圆榫数量与抗弯强度之间关系为三次曲线关系,在一定圆榫数量范围内,随着圆榫数量增多,抗弯强度增大。这在制品设计中确定圆榫数量和进行结构强度设计均有实用性。实验中还发现刨花板内部结合强度,板材断裂模量和弹性模量均对构件抗弯强度有一定影响。可以着出,圆榫数量少时,试件破坏形式是板件A的边部劈裂,而圆榫数量多时,破坏形式是板件A折断。如果圆榫之间距离过小,或者是最外边圆榫端部过近,当装入圆榫时,板件就被胀裂,这不仅影响制品外观,而且也使结合强度降低。     

胴体性状同胞选择的最佳设计

 本文从以下5个方面探讨了胴体性状同胞选择的最佳设计问题:1.当测定规模一定时,怎样安排同胞测定使遗传进展最大;2.当测定的总成本一定时,怎样使遗传进展最大;3.当删定规摸一定时,怎样使单位成本的遗传进展最大;4.当遗传进展一定时,怎样使测定规模最小;5.当遗传进展一定时,怎样使测定的总成本最低。     

Recombinant origin of the retrovirus XMRV

The retrovirus XMRV (xenotropic murine leukemia virus-related virus) has been detected in human prostate tumors and in blood samples from patients with chronic fatigue syndrome, but these findings have not been replicated. We hypothesized that an understanding of when and how XMRV first arose might help explain the discrepant results. We studied human prostate cancer cell lines CWR22Rv1 and CWR-R1, which produce XMRV virtually identical to the viruses recently found in patient samples, as well as their progenitor human prostate tumor xenograft (CWR22) that had been passaged in mice. We detected XMRV infection in the two cell lines and in the later passage xenografts, but not in the early passages. In particular, we found that the host mice contained two proviruses, PreXMRV-1 and PreXMRV-2, which share 99.92% identity with XMRV over >3.2-kilobase stretches of their genomes. We conclude that XMRV was not present in the original CWR22 tumor but was generated by recombination of two proviruses during tumor passaging in mice. The probability that an identical recombinant was generated independently is negligible (~10(-12)); our results suggest that the association of XMRV with human disease is due to contamination of human samples with virus originating from this recombination event.     

Extinction and ecosystem function in the marine benthos

Rapid changes in biodiversity are occurring globally, yet the ecological impacts of diversity loss are poorly understood. Here we use data from marine invertebrate communities to parameterize models that predict how extinctions will affect sediment bioturbation, a process vital to the persistence of aquatic communities. We show that species extinction is generally expected to reduce bioturbation, but the magnitude of reduction depends on how the functional traits of individual species covary with their risk of extinction. As a result, the particular cause of extinction and the order in which species are lost ultimately govern the ecosystem-level consequences of biodiversity loss.     

The shifting ground of swidden agriculture on Palawan Island,the Philippines

Recent literature describing the process and pathways of the agrarian transition in Southeast Asia suggests that the rise of agricultural intensification and the growth of commodity markets will lead to the demise of swidden agriculture. This paper offers a longitudinal overview of the conditions that drive the agrarian transition amongst indigenous swidden cultivators and migrant paddy farmers in central Palawan Island, the Philippines. In line with regional agrarian change, we describe how a history of conservation policies has criminalized and pressured swidden farmers to adopt more intensive “modern” agricultural practices. We examine how indigenous swidden cultivators adjust their practice in response to recent changes in policies, security of harvests, and socio-cultural values vis-à-vis intensification. Rather than suggest that this transition will lead to the demise of swidden, results reveal that farmers instead negotiate a shifting ground in which they lean on and value swidden as a means of negotiating agrarian change.     

Maintenance of genome stability in Saccharomyces cerevisiae

Most human cancer cells show signs of genome instability, ranging from elevated mutation rates to gross chromosomal rearrangements and alterations in chromosome number. Little is known about the molecular mechanisms that generate this instability or how it is suppressed in normal cells. Recent studies of the yeast Saccharomyces cerevisiae have begun to uncover the extensive and redundant pathways that keep the rate of genome rearrangements at very low levels. These studies, which we review here, have implicated more than 50 genes in the suppression of genome instability, including genes that function in S-phase checkpoints, recombination pathways, and telomere maintenance. Human homologs of several of these genes have well-established roles as tumor suppressors, consistent with the hypothesis that the mechanisms preserving genome stability in yeast are the same mechanisms that go awry in cancer.     

“平等”的内涵

"平等"在近代宪法上有重要地位,它既是一项法律权利又是一项法律原则;宪法规定中的平等与法律适用中的平等并不等同。平等分为法律平等与事实平等,形式平等与实质平等。现实生活中,存在诸多不平等现象,究其原因,既有法律本身的欠缺,也有执法的不力。