国际技术许可制度的战略与法律透视

国际技术许可制度是促进技术先进国家向发展中国家转让技术的极好办法。通常情况下,技术先进国一方当事人拥有对一项技术的权利,而发展中国家的一方当事人则有最为有效地使用该技术的手段。历史告诉我们,环太平洋的国家不断重复利用这种制度。例如,日本通过引进外国先进技术,只以50年的时间,就将自己置于最发达的工业化国家之林。南韩、香港、台湾及新加坡在迈向高度发达中国家进程中,都表现出同日本模式相似的特征。环太平洋国家经济上的成功,很大程度上取决于引进更发达工业化国家的技术,并且通常采用国际技术许可制度。     

Reversibility of acute B-cell leukaemia induced by BCR-ABL1

Cancer is thought to arise from multiple genetic events that establish irreversible malignancy. A different mechanism might be present in certain leukaemias initiated by a chromosomal translocation. We have taken a new approach to determine if ablation of the genetic abnormality is sufficient for reversion by generating a conditional transgenic model of BCR-ABL1 (also known as BCR-ABL)-induced leukaemia. This oncogene is the result of a reciprocal translocation and is associated with different forms of leukaemia. The most common form, p210 BCR-ABL1, is found in more than 90% of patients with chronic myelogenous leukaemia (CML) and in up to 15% of adult patients with de novoacute lymphoblastic leukaemia (ALL). Efforts to establish a useful transgenic model have been hampered by embryonic lethality when the oncogene is expressed during embryogenesis, by reduced penetrance or by extremely long latency periods. One model uses the 'knock-in' approach to induce leukaemia by p190 BCR-ABL1(ref. 10). Given the limitations of models with p210, we used a different experimental approach. Lethal leukaemia developed within an acceptable time frame in all animals, and complete remission was achieved by suppression of BCR-ABL1expression, even after multiple rounds of induction and reversion. Our results demonstrate that BCR-ABL1is required for both induction and maintenance of leukaemia.     

The gating mechanism of the large mechanosensitive channel MscL

The mechanosensitive channel of large conductance, MscL, is a ubiquitous membrane-embedded valve involved in turgor regulation in bacteria. The crystal structure of MscL from Mycobacterium tuberculosis provides a starting point for analysing molecular mechanisms of tension-dependent channel gating. Here we develop structural models in which a cytoplasmic gate is formed by a bundle of five amino-terminal helices (S1), previously unresolved in the crystal structure. When membrane tension is applied, the transmembrane barrel expands and pulls the gate apart through the S1-M1 linker. We tested these models by substituting cysteines for residues predicted to be near each other only in either the closed or open conformation. Our results demonstrate that S1 segments form the bundle when the channel is closed, and crosslinking between S1 segments prevents opening. S1 segments interact with M2 when the channel is open, and crosslinking of S1 to M2 impedes channel closing. Gating is affected by the length of the S1-M1 linker in a manner consistent with the model, revealing critical spatial relationships between the domains that transmit force from the lipid bilayer to the channel gate.     

Peripheral education of the immune system by colonic commensal microbiota

The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3(+) regulatory T (T(reg)) cells. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease. Here we show that encounter with commensal microbiota results in the peripheral generation of T(reg) cells rather than pathogenic effectors. We observed that colonic T(reg) cells used T-cell antigen receptors (TCRs) different from those used by T(reg) cells in other locations, implying an important role for local antigens in shaping the colonic T(reg)-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon T(reg) TCRs. These TCRs did not facilitate thymic T(reg)-cell development, implying that many colonic T(reg) cells arise instead by means of antigen-driven peripheral T(reg)-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic T(reg) cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo T(reg)-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of T(reg) cells in response to an individual's microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.     

X-ray illumination of the ejecta of supernova 1987A

When a massive star explodes as a supernova, substantial amounts of radioactive elements--primarily (56)Ni, (57)Ni and (44)Ti--are produced. After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements. However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium. The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.