Fwd: Bioinformatics

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Escape analysis and lock coarsening in JAVA 6.0 Posted: 16 Oct 2010 12:37 AM PDT The popularity of the Java programming language has made escape analysis a target of interest. Java's combination of heap-only object allocation, built-in threading, and the Sun HotSpot dynamic compiler creates a candidate platform for escape analysis related optimizations. Escape analysis is implemented in Java Standard Edition 6. Example (Java) class A { final int finalValue; public A( B b ) { super(); b.doSomething( this ); // this escapes! finalValue = 23; } int getTheValue() { return finalValue; } } class B { void doSomething( A a ) { System.out.println( a.getTheValue() ); } } In this example, the constructor for class A passes the new instance of A to B.doSomething. As a result, the instance of A—and all of its fields—escapes the scope of the constructor. Java is able to manage multithreading at the language level. Multithreading is a technique that allows programs to operate faster on computer system that have multiple CPUs. Also, a multithreaded application has the ability to remain responsive to input, even when it is performing long running tasks. However, programs that use multithreading need to take extra care of objects shared between threads, locking access to shared methods or blocks when they are used by one of the threads. Locking a block or an object is a time-consuming operation due to the nature of the underlying operating system-level operation involved . As the Java library does not know which methods will be used by more than one thread, the standard library always locks blocks when necessary in a multithreaded environment. Prior to Java 6, the virtual machine always locked objects and blocks when asked to by the program even if there was no risk of an object being modified by two different threads at the same time. For example, in this case, a local Vector was locked before each of the add operations to ensure that it would not be modified by other threads (Vector is synchronized), but because it is strictly local to the method this is not necessary: public String getNames() { Vector v = new Vector(); v.add("Me"); v.add("You"); v.add("Her"); return v.toString(); } Starting with Java 6, code blocks and objects are locked only when necessary , so in the above case, the virtual machine would not lock the Vector object at all

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Cockroach brains, coming to a pharmacy near you -Insect tissue extracts show antibacterial activity

Cockroaches may be nasty bugs, but they could help fight even nastier ones. New research finds that the rudimentary brains of cockroaches and locusts teem with antimicrobial compounds that slay harmful E. coli and MRSA, the antibiotic-resistant staph bacterium. The work could lead to new compounds for fighting infectious diseases in humans.

Extracts of ground-up brain and other nerve tissue from the American cockroach, Periplaneta americana, and desert locust, Schistocerca gregaria, killed more than 90 percent of a type of E. coli that causes meningitis, and also killed methicillin-resistant staph, microbiologist Simon Lee reported September 7 at the Society for General Microbiology meeting at the University of Nottingham in England.

"Some of these insects live in the filthiest places ever known to man," says Naveed Khan, coauthor of the new study. "These insects crawl on dead tissue, in sewage, in drainage areas. We thought, 'How do they cope with all the bacteria and parasites?'"

Khan and his colleagues became intrigued by insect antimicrobials when they noticed that many soldiers were returning from the Middle East with unusual infections, yet locusts living in the same areas were unperturbed. So the researchers, all from the University of Nottingham, began investigating how the insects ward off disease.

The team ground up various body parts from both cockroaches and locusts that had been reared in the lab and incubated them for two hours with different bacteria. Leaving these mixtures overnight on petri dishes revealed that the extracts from brains and from locust thorax nerve tissue killed nearly 100 percent of the bacteria.

Yet the insect brain extracts didn't seem to bother human kidney or epithelial cells when grown with them in a lab dish.

Curiously, extracts of insect fat, muscle and blood didn't bother the bacteria at all. Cockroaches and locusts often eat stuff loaded with microbes, says parasitologist Carl Lowenberger of Simon Fraser University in Burnaby, Canada, so you would think insect guts and blood, which bathes the organs, would have similar antimicrobial activity.

Nine molecules appear to be responsible for the antimicrobial activity in locust tissue, although they have yet to be identified. The team is also still working out the details of the cockroach compounds.

The compounds may work together as a cocktail, Lowenberger says. Insects make hundreds of antimicrobial compounds, and it may be that very high concentrations of those molecules would be required for fighting an infection in humans. But the research "is pretty neat stuff," he says. And perhaps down the road, the yet-unidentified molecules will prove useful in fighting infections in people.

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Doggy Genes: Newly Sequenced Genome Could Shed Light on Human Diseases

Molecular biologists have completely sequenced the first dog genome. Understanding how genetics plays a role in canine diseases could lead to new treatments for diseases shared by humans, such as diabetes, epilepsy and cancer. Breeders could also soon be able to check the purity of pedigrees by sending dogs' cheek swabs to the lab.

We may be more like dogs than we think. Now, a complete map of dog genes not only helps explain what gives dogs their unique set of traits, behaviors, and diseases -- it could help identify human diseases, too. Why are some dogs excellent ball chasers and others perfect for your lap? The answer to dog differences is hidden in specific sequences of DNA called genes. A standard poodle, named Shadow, was the first dog to have its genes mapped, but it was only about 80-percent complete. For the first time, molecular biologists have completely mapped out the genes of a boxer.

"The boxer genome will help us get at the genes responsible for diseases and traits in dogs," says Ewen Kirkness, a molecular biologist at The Institute for Genomic Research in Rockville, Md. Dogs and humans share many of the same diseases, like diabetes, epilepsy and cancer. Mapping dog genes could be the chief tool in finding disease-causing genes in people, because Kirkness says the same genes will be responsible for similar diseases in humans. Genes that cause disease in dogs are easier to find than in people. Mutations in a dozen different genes can cause human disease, almost impossible to find. In dogs, only one gene mutation can cause a disease, and that same mutated gene causes an identical disease in humans. "Then we have a better handle on what is causing the disease in humans, also," Kirkness says.

Studying dog families also helps get a better handle on their own health and help eliminate dog diseases.

"Testing can be done by breeders to limit the passage of these mutations into future generations." Having a genetic map may also mean owners of pure-bred dogs and mutts may soon be able to document which breeds their dogs come from by simply sending a cheek swab or blood sample to a genetics lab. BACKGROUND: For the first time ever, scientists have successfully sequenced the entire genomic structures of two dog breeds: the boxer and the poodle. This is a major step forward for research in such fields as veterinary medicine. Extending this work to the human genome could help doctors better understand and fight human diseases and illnesses, including cancer research. THE

STUDY: In a new study, scientists at the Institute for Genomic Research found distinct genetic differences between boxer and poodle dog breeds, and went on to compare those variations in the genomes from nine other breeds, as well as the genomes from four types of wolves and a coyote. They did this by tracking short stretches of DNA that occur randomly, called short interspersed elements (SINEs), which often turn the expression of those genes up, down or even off. Ultimately they found that the overall dog population contains at least 20,000 differences. THE

IMPLICATIONS: For genomics researchers, variable SINEs can act as signposts for specific genes linked to a disease or traits. Identifying those genes is easier to do in dogs because they have been selectively bred for so long, creating the highest degree of physical and behavioral differences seen within a species. A dog genome is estimated to include 19,300 genes, and nearly all of them correspond to similar human genes. Specific breeds are predisposed, for instance, to heart disease, cancer, blindness, deafness, and other common disorders. A second study documented many of those disease-related differences.

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Better Marker for Breast Cancer May Reduce Need for Second Surgeries

A new material could help surgeons more accurately locate breast cancers, reduce the need for second surgeries and minimize pre-surgical discomfort for patients. Microscopic gas-filled spheres of silica, a porous glass, can mark the location of early-stage tumors to show their position using ultrasound imaging in the operating room.

A team of chemists, radiologists and surgeons at the University of California, San Diego, created the new material, which they describe in a forthcoming issue of the journal MedChemComm.
The X-rays used to make mammograms reveal calcium deposits associated with breast cancer even in tumors too small to be felt. But surgeons can't use X-rays while operating. Instead, radiologists place guide wires into tumors hours or even the day before surgery. The wires don't mark depth well and can shift. Patients find them both uncomfortable and unsettling.

As an alternative, the researchers created spheres of silica and filled them with perfluoropentane, a gas that has been used before in short-lived contrast materials for medical imaging. The rigid silica shells help the new material last longer.

"These little gas-filled microbubbles stick to human breast tissue for days and can be seen with ultrasound," said William Trogler, professor chemistry. "If doctors placed them in early stage breast cancer, which is difficult to see during surgery, they could help surgeons remove all of it in the first operation."

In the past few years, radiologists have tried implanting radioactive "seeds" instead of wires to mark tumors, but the seeds last only a few hours and must be inserted with a large-bore needle, which is painful. In addition, only one abnormal region can be marked, but patients with a form of breast cancer called ductal in situ carcinoma often have several. The seeds also expose both patient and staff to radiation, can't been imaged in three dimensions and create radioactive medical waste.

At just two micrometers in diameter - half the width of a strand of spider silk - small silica microbubbles can be precisely injected into clusters of abnormal cells using a thin needle. Radiologists would be able to inject the durable material days before surgery. And ultrasound scans reveal the position of the bubble in three dimensions on the operating table.

"Instead of just using a Geiger-counterlike device to say you're getting closer to the radioactive seed, you could actually see where to carve," said Andrew Kummel, professor of chemistry. The increased precision should help surgeons avoid the need for second surgeries.

"By outlining the tumor more completely in multiple directions, the particles could potentially help surgeons remove non-palpable tumors in a single operation," said Sarah Blair, a surgeon at Moores UCSD Cancer Center. "They will definitely make the operation more comfortable for patients."

The researchers think the ultrasound pressure waves burst the microbubbles. "They're thin, fragile balls of porous glass, like Christmas tree ornaments," Kummel said. "The shell is just one two-hundredth of the diameter of the ball. When it breaks, the gas squirts out. Doppler ultrasound detects that movement."
Nano-scale silica microbubbles, which the team reports in this paper as well, are too small to remain in place, but might drain from a cancerous site to help identify which lymph nodes are most likely to contain stray cells that could help the cancer spread.
The current study demonstrates the feasibility of the technology in tissue samples. Tests in animal models are underway, and toxicology studies must also be completed before clinical trials in humans could begin.

Chemists Bill Trogler, and Andy Kummel, of UCSD's Division of Physical Sciences, and radiologist Robert Mattrey and surgeon Sarah Blair of the Moores UCSD Cancer Center led the project. Additional co-authors include radiologist Yuko Kono, and Sergio Sandoval, Moores UCSD Cancer Center; Paul Martinez of the Department of Chemistry and Biochemistry; and Jessica Wang-Rodriguez of the Department of Pathology.

The National Cancer Institute provided financial support for this study.

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