PS2消防游戏《厄运》登场

最近一段时间,消防员游戏似乎一下子受到了游戏厂商们的关注.自<18号消防员>和<樱坂消防队>后,知名游戏公司Spike在不久前又公布了一款以消防员为题材的PS2动作冒险游戏<厄运:英雄归来(HardLuck:Return of the Heroes)>,在这款游戏中,三位消防英雄将会奋不顾身的冲入火场,拯救火灾中的无数遇害者.     

监测环境十管齐下

2000年2月28日晚,欧洲最大的环境监测卫星“恩维萨特号”(Envisat)将被发射升空——这颗肩负监测地球环境一系列重要“信号”的卫星,可能首次在太空完成对大气中二氧化碳最为肆虐的温室气体的测量。     

A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol

Elimination of misfolded proteins from the endoplasmic reticulum (ER) by retro-translocation is an important physiological adaptation to ER stress. This process requires recognition of a substrate in the ER lumen and its subsequent movement through the membrane by the cytosolic p97 ATPase. Here we identify a p97-interacting membrane protein complex in the mammalian ER that links these two events. The central component of the complex, Derlin-1, is a homologue of Der1, a yeast protein whose inactivation prevents the elimination of misfolded luminal ER proteins. Derlin-1 associates with different substrates as they move through the membrane, and inactivation of Derlin-1 in C. elegans causes ER stress. Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor.     

A turbulent wake as a tracer of 30,000 years of Mira's mass loss history

Mira is one of the first variable stars ever discovered and it is the prototype (and also the nearest example) of a class of low-to-intermediate-mass stars in the late stages of stellar evolution. These stars are relatively common and they return a large fraction of their original mass to the interstellar medium (ISM) (ref. 2) through a processed, dusty, molecular wind. Thus stars in Mira's stage of evolution have a direct impact on subsequent star and planet formation in their host galaxy. Previously, the only direct observation of the interaction between Mira-type stellar winds and the ISM was in the infrared. Here we report the discovery of an ultraviolet-emitting bow shock and turbulent wake extending over 2 degrees on the sky, arising from Mira's large space velocity and the interaction between its wind and the ISM. The wake is visible only in the far ultraviolet and is consistent with an unusual emission mechanism whereby molecular hydrogen is excited by turbulent mixing of cool molecular gas and shock-heated gas. This wind wake is a tracer of the past 30,000 years of Mira's mass-loss history and provides an excellent laboratory for studying turbulent stellar wind-ISM interactions.     

Early human use of marine resources and pigment in South Africa during the Middle Pleistocene

Genetic and anatomical evidence suggests that Homo sapiens arose in Africa between 200 and 100 thousand years (kyr) ago, and recent evidence indicates symbolic behaviour may have appeared approximately 135-75 kyr ago. From 195-130 kyr ago, the world was in a fluctuating but predominantly glacial stage (marine isotope stage MIS6); much of Africa was cooler and drier, and dated archaeological sites are rare. Here we show that by approximately 164 kyr ago (+/-12 kyr) at Pinnacle Point (on the south coast of South Africa) humans expanded their diet to include marine resources, perhaps as a response to these harsh environmental conditions. The earliest previous evidence for human use of marine resources and coastal habitats was dated to approximately 125 kyr ago. Coincident with this diet and habitat expansion is an early use and modification of pigment, probably for symbolic behaviour, as well as the production of bladelet stone tool technology, previously dated to post-70 kyr ago. Shellfish may have been crucial to the survival of these early humans as they expanded their home ranges to include coastlines and followed the shifting position of the coast when sea level fluctuated over the length of MIS6.     

The Abductive Loop: Tracking Irrational Sets

We argue from the Church-Turing thesis (Kleene Mathematical logic. New York: Wiley 1967) that a program can be considered as equivalent to a formal language similar to predicate calculus where predicates can be taken as functions. We can relate such a calculus to Wittgenstein’s first major work, the Tractatus, and use the Tractatus and its theses as a model of the formal classical definition of a computer program. However, Wittgenstein found flaws in his initial great work and he explored these flaws in a new thesis described in his second great work; the Philosophical Investigations. The question we address is “can computer science make the same leap?” We are proposing, because of the flaws identified by Wittgenstein, that computers will never have the possibility of natural communication with people unless they become active participants of human society. The essential difference between formal models used in computing and human communication is that formal models are based upon rational sets whereas people are not so restricted. We introduce irrational sets as a concept that requires the use of an abductive inference system. However, formal models are still considered central to our means of using hypotheses through deduction to make predictions about the world. These formal models are required to continually be updated in response to peoples’ changes in their way of seeing the world. We propose that one mechanism used to keep track of these changes is the Peircian abductive loop.     

Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome

Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing.     

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size.     

Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress.     

Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks

The mechanisms by which eukaryotic cells sense DNA double-strand breaks (DSBs) in order to initiate checkpoint responses are poorly understood. 53BP1 is a conserved checkpoint protein with properties of a DNA DSB sensor. Here, we solved the structure of the domain of 53BP1 that recruits it to sites of DSBs. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues. In vitro, the 53BP1 tandem tudor domain bound histone H3 methylated on Lys 79 using residues that form the walls of the pocket; these residues were also required for recruitment of 53BP1 to DSBs. Suppression of DOT1L, the enzyme that methylates Lys 79 of histone H3, also inhibited recruitment of 53BP1 to DSBs. Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site.