San Francisco Giants run into issue typically reserved for winning teams

first_imgLOS ANGELES — The San Francisco Giants have won five of their last six games and must now confront a dilemma typically reserved for the most successful teams in baseball.When should they rest their closer?Will Smith has earned saves in all five of the team’s wins over the last week and has seen his workload increase dramatically during the club’s best stretch of the season.After Smith saved Monday’s 3-2 victory over the Dodgers, manager Bruce Bochy said he would prefer to rest Smith on …last_img read more

Molecular Machines on Parade

first_imgThe fact that protein machines use energy to undergo conformational rearrangements, and that these “moving parts” perform functional work, places them squarely in the realm of machinery – except on a scale so tiny, their operations are only now coming to light.1.  Valeria V�squez and Eduardo Perozo, “Structural Biology: A channel with a twist,” Nature 461, 47-49 (3 September 2009) | doi:10.1038/461047a.2.  Liu, Gandhi and Rees, “Structure of a tetrameric MscL in an expanded intermediate state,” Nature 461, 120-124 (3 September 2009) | doi:10.1038/nature08277.3.  Cook, Fukuhara, Jinek and Conti, “Structures of the tRNA export factor in the nuclear and cytosolic states,” Nature 461, 60-65 (3 September 2009) | doi:10.1038/nature08394.4.  Guydosh and Block, “Direct observation of the binding state of the kinesin head to the microtubule,” Nature 461, 125-128 (3 September 2009) | doi:10.1038/nature08259.Molecular machines – the very concept is only a couple of decades old.  This is phenomenal.  It is marvelous and wonderful beyond description.  You can almost sense the astonishment and excitement of these biophysicists uncovering these tiny wonders in the cell.  Who could have imagined this is how life works?  Think of the centuries, the millennia, of people going about their business, oblivious to the fact that at scales too tiny to imagine a whole factory of automated molecular machines was keeping them alive.  The few thinkers after the discovery of cells by Robert Hooke envisioned little people (homunculi) doing some of it, but our instruments were too coarse to elucidate the workings inside till recently – till our generation.  Next to the discovery of DNA and the genetic code this must be considered one of the most important discoveries in the history of science.  If Antony van Leeuwenhoek was astonished at what he saw with his primitive hand lens, how much more should we be flabbergasted at what is coming into focus, now that we can discern the activity of individual molecules?    The Darwinists are strangely silent about all this.  In our 9 years of reporting, very few papers on molecular machines have even mentioned evolution (e.g., 10/02/2001, 01/09/2002), and those that did usually just assumed it rather than tried to seriously explain how the most primitive life-forms could have became endowed with factories of mechanical filters, scribes, taxicabs and walking robots by chance (e.g., 09/16/2000, 08/24/2009 08/26/2005).  Search on “molecular machines” in the search bar above and check.  There are lots of examples.  It’s time to cast off that antiquated 19th-century mindset that tried to imagine all this from the bottom up.  Let us regard as silly the tales of miracles of “emergence” occurring mindlessly in “a chance Motion of I don’t know what little Particles,” as Christiaan Huygens, our Scientist of the Month, quipped.  Paley is back with a vengeance.  The contrivances of nature are more wonderful than he or any other philosopher or scientist could have imagined.  It’s a Designed world after all.  Rejoice, give thanks and sing!(Visited 10 times, 1 visits today)FacebookTwitterPinterestSave分享0 Scientific papers continue to exhibit the exquisite mechanisms in the cell for handling all kinds of situations, through the operation of molecular machines.  Here are a few recent examples from this week’s issue of Nature (Sept 3, 2009).Molecular sieve:  What happens when a cell gets bloated?  Too much water entering a cell can increase the pressure against the membrane, “potentially compromising the integrity of the cell,” said Valeria V�squez and Eduardo Perozo in Nature this week.1  They described findings about a molecular sieve named MscL by Liu et al in the same issue of Nature.2  MscL in bacteria is made up of multiple protein parts that form a pore in the cell membrane.  The research team from Caltech and Howard Hughes Medical Institute found that the components flatten out and pivot, opening up the pore like an iris when sufficient pressure is applied.  This is called “mechanosensation” because it operates automatically via mechanical pressure.  “These channels act as ‘emergency relief valves,’ protecting bacteria from lysis [disruption] upon acute osmotic down-shock,” the authors said.  “MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative non-conductive expanded state and at least three sub-conducting states.”  The team’s contribution was to image one of the intermediate states.    The research paper did not mention evolution.  V�squez and Perozo, however, said, “free-living cells have evolved a variety of mechanisms to deal with sudden variations in the physicochemical properties of their surroundings,” and later said, “Most prokaryotes (bacteria and archaea) have therefore evolved a ‘pressure-release valve’ mechanism in which changes in membrane tension open up channels to form large, aqueous pores in the membrane,” but they did not explain how evolution could have accomplished this.  They made it sound like the bacteria purposely employed evolution (whatever they meant by the term) to solve a real problem.  They did not explain how bacteria got through osmotic down-shock without the pressure release valves.Molecular taxicab:  Transfer RNAs (tRNA) are made in the nucleus but need to commute to work outside, in the cytoplasm, where the ribosomes are.  They are small enough to barely squeeze through the nuclear pore complex (NPC) – the complicated gates in the nuclear membrane that control traffic in and out – but they don’t avail themselves of that freedom, lest their exposed parts interact with the authentication mechanisms of the NPC.  Instead, they hale a taxicab to escort them through.  That taxicab, or “tRNA export factor,” is called Xpot.    Xpot is a complex molecule that fits around the exposed parts of the tRNA.  It literally “wraps around” the tRNA, undergoing conformational changes as it clamps on.  Imagine a taxicab wrapping around you, and you get the picture.  Xpot is general enough to fit all 20 kinds of tRNAs, but specific enough to protect their delicate active sites.  It is also able to recognize and reject tRNAs that are immature.  Only tRNAs that have passed a processing exam are allowed in the taxi.  The authors of a paper in Nature who studied Xpot said, “Xpot undergoes a large conformational change on binding cargo, wrapping around the tRNA and, in particular, binding to the tRNA 5′ and 3′ ends.  The binding mode explains how Xpot can recognize all mature tRNAs in the cell and yet distinguish them from those that have not been properly processed, thus coupling tRNA export to quality control.”3  As an additional control, Xpot does not interact with tRNA except in the presence of another factor in the nucleus called RanGTP.  After safe transport through the nuclear pore complex, another factor in the cytoplasm unlocks the RanGTP, allowing the Xpot taxicab to unwrap from the tRNA.  The tRNA then heads off to the ribosome to fulfill its work shift as a scribe, translating the genetic code into the protein code.  “Transfer RNAs are among the most ubiquitous molecules in cells,” they said, “central to decoding information from messenger RNAs on translating ribosomes.”    The authors of the paper did not discuss how Xpot originated, but six times they said that parts of Xpot are either “conserved,” “evolutionarily conserved” or “highly conserved” (i.e., unevolved) throughout the living world.Molecular sherpa:  Kinesin is among the most fascinating molecular machines in the cell, because it literally “walks” hand-over-hand on microtubule trails, carrying cargo.  In doing this, it converts chemical energy from ATP into mechanical work.  Writing in this week’s Nature,4 Guydosh and Block of Stanford described direct observation of the binding state of the hands (called heads) of kinesin to the microtubule.  They found that it walks tiptoe on the tightrope: “Here we report the development of a single-molecule assay that can directly report head binding in a walking kinesin molecule, and show that only a single head is bound to the microtubule between steps at low ATP concentrations.”  The rear head has to unbind before the forward head can bind.  This keeps the kinesin from getting stuck with both feet (heads) on the tightrope.  If you can stand some jargon, here is what they said about the complexities of how this works:The inability of one head to bind the microtubule offers a natural explanation for the observation that the microtubule-stimulated release of ADP is inhibited until the microtubule-attached head binds ATP and docks its neck linker (Fig. 4, state 2).  Strain produced by an unfavourable neck-linker conformation also explains the observation that ATP does not bind prematurely to the front, nucleotide-free head of a 2-HB kinesin molecule (Fig. 4, state 3).  Any tight binding of ATP is disfavoured because it is coupled to neck-linker docking and, therefore, to the generation of a strained configuration in which both neck linkers are docked (Fig. 4, S3).  We anticipate that the single-molecule techniques presented here will be applicable to the study of dynamic properties of other motors and macromolecules that undergo analogous conformational rearrangements.last_img read more

What the Real-Time Web Can Deliver

first_imgA Web Developer’s New Best Friend is the AI Wai… Related Posts I certainly wasn’t watching for the change. A robot was doing that for me and let me know about the change in near real time. It was pretty awesome, but it wasn’t real time and the services I patched together to do it are all marginal enough that they often don’t work or are very late. Put real time at the center of the web and we’ll be able to automate all kinds of information monitoring. At first it will be a competitive advantage for those who use it strategically; then it will just change the game, become standard practice and require competitive knowledge workers to come up with something else that’s new.Read the last section of this post and the comments readers left here: 3 Models of Value in the Real-Time Web Top Reasons to Go With Managed WordPress Hosting In the above image you can see a custom search engine we use here at ReadWriteWeb, with Mark Carey’s Twitter on Google greasemonkey script running on top of it. If you want to know about streaming video, Forrester’s, Jeremiah Owyang, has a running list of vendors in the space (1) and that’s where you want to start – but wouldn’t you like to know about the very freshest (2) live streaming vendors on the market as well? That’s what people are talking about, in real time, on Twitter.In our experience these Twitter augmented search results are valuable because they are up to the minute – but sometimes they are also just better.Someday you’ll be able to discover Owyang’s list and be prompted to view the most recent, the most authoritative and the most “socially relevant to you” conversations about the same concept going on all around the web. People are working on all of that and as research-lovers we hope they succeed.The point is that no matter what you’re doing on the web, there are valuable related activities going on elsewhere – probably simultaneously. Exposing those is exciting.AutomationWe probably should have started out with this, but what’s the most obviously valuable example of clear value in real-time information delivery in recent internet history? Blackberry and the push email! We tend to assume that the real time web is something we’ll be looking at constantly, because it’s constantly bringing up new information. That doesn’t have to be the case, though. The real time web could very well just do its thing and notify us, in real time, of important events. Thresholds crossed. Simple changes made.For example, when the already controversial Google Chrome Terms of Service were changed again last December, I got an SMS sent to my phone notifying me that it had been changed. I was able to jump online, grab a screenshot of the changes from the application that was monitoring the document and report on the change before anyone else. Why Tech Companies Need Simpler Terms of Servic…center_img marshall kirkpatrick Google launched its version of integrated real-time search, one of a number of impressive product demos given, at a press event this morning. It’s much better than what Bing and Yahoo! have done, but it’s still just the beginning of a full-scale engagement with the real-time web. To provide further context to this discussion, we’re rerunning a post we wrote in seven months ago, titled “3 Models of Value in the Real-Time Web.” We hope you find it useful and interesting.Hey web DJ. Reach into your magic bag of search tools and pull out a big result – dripping with related ephemera born just moments ago. Those could hold the grain of information you’re really looking for, or they could sparkle with data that changes your course of action in unexpected ways.Alert! Another factor has emerged, elsewhere on another site. You said you wanted to be told, right away, about any online artifacts that crossed a threshold of popularity within a certain group of people in your field. That has just occurred, so it’s time to watch the replay of how it got so hot, evaluate its usefulness and decide whether to bring this emergent phenomenon into the work you were doing before you were interrupted, drop the former for the latter or return to your original focus. How would you like this to be your job description? It could well be – if the red hot Real Time Web keeps showing up on sites all around the internet.The Real Time Web is coming so fast we’ve hardly had any time to think about it yet. So let’s do that, shall we? The two hottest technologies online, Twitter and Facebook, are fast integrating real-time delivery of activity streams to their users. Paul Buchheit, the man who built the first versions of both Gmail and Adsense, says the real time web is going to be the next big thing. Buchheit’s FriendFeed is a key point of innovation in real time. Social media ping server Gnip promised to turn everything online into Instant Messaging-style XMPP feeds, and though that’s been put on hold in favor of more immediately clear value – we’ve still got our fingers crossed. Our investigation of companies like Bit.ly and OneRiot this morning turned up even more big news that’s right around the corner for the Real Time Web.But what’s the point? What’s in it for us, as users? We offer below three models of value that we suspect will be found in the Real Time Web. They are the concepts that underly the vision described above at the top of this post. Those concepts are Ambiance, Automation and Emergence. This is just an initial exploration of ideas, reality will undoubtedly be more complicated shortly. We welcome your participation in thinking about this part of the fast-approaching future of the web.AmbianceThe web is made up of web pages linked together, but hovering around many of those pages are now social media signals like blog posts, bookmarks, tweets and other URLs that refer to a page but aren’t visible when you’re looking at it. The same is true for concepts. Most of us use Google to find pages about things we’re looking for, but Google prioritizes historical inbound links and the text on pages. Tags:#Real-Time Web#web 8 Best WordPress Hosting Solutions on the Marketlast_img read more

Four held in Odisha’s Berhampur on charges of torture of students

first_imgFour personnel of a residential higher secondary institution, including a lecturer and three hostel staff, were arrested in Odisha’s Berhampur on charges of torture of students. According to Santosini Oram, Inspector in-charge of the Berhampur Sadar police station, the misdeeds of the arrested persons came to light on Saturday. As part of an investigation into a case related to disappearance of a plus 2 student of the same institution, a police team had reached its hostel. According to police sources, the student went missing from the hostel on September 26. The institution is located in the Bhabinipur area of Berhampur and around 200 students reside in its hostel..Deep wounds During interrogation of hostel inmates, four students complained that they had been ruthlessly beaten up by a lecturer and three staff of the hostel. The students also had deep wounds. The lecturer and the hostel staff had resorted to physical torture of the students alleging that they had information about their missing classmate.Later, parents of one of the injured students filed an FIR that led to arrest of the lecturer and the three hostel staff of the institution.last_img read more

Nehru Cup 2012: India hold edge over Maldives

first_imgA victory to start a tournament is always welcome, and if it comes against a higher-ranked opponent, the confidence will only be high. India began their title defence of Nehru Cup with a 2-1 win over Syria and the hosts would be looking to continue the good run against Maldives on Saturday.A familiar foe for the hosts and former SAFF champions, Maldives, too, began their campaign on a bright note, beating Nepal 2-1 in their opener at the Jawaharlal Nehru Stadium on Thursday.India, however, will hold the edge as they were impressive against the Syrians. Captain Sunil Chhetri has already put up his name on the goal scorers list and the midfield generals looked in good touch.Clifford Miranda, Lenny Rodrigues and Francis Fenandes fed Chhetri well with precise passes and pierced the Syrian defence line time and again.The newly propounded possession football was on display and the players tried hard to string along six-seven short passes, until rain forced them to tweak their style and rely on aerial shots.However, defence remains a concern for the defending champions.Raju Gaikewad will have to raise his level on the right. His under-performance against Syria put more load on the other three Gouramangi Singh, Nirmal Chhetri and Syed Rahim Nabi.With talented striker like Ali Ashfaq on the rivals ranks, the defenders need to tighten up.Against Nepal, the Maldives captain had tormented the defenders with his ability to single-handedly create openings in the front.Two rookies Abdulla Asadhulla and Umair Mohamed impressed on the flanks, and Koeverman’s need to keep a plan ready for the trio. Like India, Maldives also need to shore up its defence. The central defence manned by Abdul Ghani Akram and Mohamed Sifan had some jittery moments against Nepal.Maldives coach Istvan Urbanyi did not want to read too much into Indias win against Syria.Its impossible to comment on India at the moment. Rain played a major role in Indias match against Syria. I just cant draw any comparison between this Indian side and former ones,” he said.In their last meeting at the SAFF Championships here in December, last year, India had defeated Maldives 3-1 but even that record isnt giving Koevermans an absolute confidence.”We got three yellow cards in the first match and that remains a matter of concern. Maldives has some quality players who can create a difference,” he said.Ashfaq has already caught Koevermans attention, but the Indian coach was tight-lipped about whether he was going to mark the striker. He also refrained to comment on any change in India’s starting line-up.He might draw solace from the fact that the Maldives coach is concerned about his teams fitness.”Most of my players have just come after observing a month of Ramadan. Also we had little practice before coming here,” he said.But I am happy with the way the youngsters have played in the first match.advertisementlast_img read more