Such injection-molded parts are even suitable for mass production. Demonstration model of the experimental engine with lightweight cylinder casing to be presented at the Hannover Messe.
The researchers produce these components from granulated thermoset plastics using an injection molding process. The melted composite material
#Study finds cystic fibrosis decreases muscle strength Patients with cystic fibrosis have a muscle deficiency that gets worse with age, according to the findings of a joint study by researchers at the University of Georgia and Georgia Regents University.
and results showed cystic fibrosis patients had 15 percent less capacity than the control group -and that capacity grew worse with age.
Cystic fibrosis is a genetic disease that primarily affects the lungs and digestive system of about 30,000 Americans, producing mucus that makes it difficult to breathe
The average life span of a patient with cystic fibrosis is less than 40 years. By including children in the study,
researchers opened a door to similar tests on a range of childhood diseases. The Mito Test uses near infrared spectroscopy, a special type of light beamed through the skin
it is easier to administer than traditional methods to measure muscle capacity, such as MRIS or biopsies.#
points to this decrease of muscle strength as one reason why cystic fibrosis patients are less likely to exercise as they get older,
complicating their health problems. Mccully, who developed the Mito Test, said the excessive muscle weakness that is common in cystic fibrosis patients now can be attributed to some degree to defects in muscle mitochondria.
Mccully and other UGA researchers will continue to work with Georgia Regents University to determine what is keeping cystic fibrosis patients#muscles from properly functioning,
as well as use the Mito Test in Athens, Augusta and elsewhere to study other childhood diseases that may affect muscle mitochondria.#
#This is the start of a collaboration; we agree there is something in the muscles that accumulates,
noting the shortened life span of cystic fibrosis patients.##We#re interested in optimizing that life,
#New treatment options for colon cancer Scientists from Nanyang Technological University (NTU) and Sweden Karolinska Institutet, one of Europe largest and most prestigious medical universities, have discovered that an existing
Colorectal cancer commonly referred to as colon cancer is one of the three most common cancers worldwide and the most common in Singapore.
Almost 95 per cent of colorectal cancers are from malignant tumours. The research team found that Imatinib,
The finding is also significant as currently there is no drug available to prevent the recurrence of tumours in the intestine after the cancerous tumours have been removed by surgery.
Professor of Metabolic Disease at NTU Lee Kong Chian School of medicine and senior principal investigator with the National Cancer Centre Singapore. ur work has important clinical implications,
and cancer progression in patients predisposed to develop colorectal cancer, said Prof Pettersson, who is also a Professor of Host-Microbe Interactions at Karolinska Institutet.
which had late-stage tumours and rectal bleeding. The same effects were shown also when Imatinib was tested on colon tumour tissues taken from human patients.
where the affected section of the intestine is removed through surgery. The scientists said these findings also suggest that short term intermittent chemotherapies could be possible as a treatment model,
#Unusual Chance to Study Patient's Residual Tumor Leads to New Finding Capitalizing on a rare opportunity to thoroughly analyze a tumor from a lung cancer patient who had developed resistance to targeted drug treatment,
the researchers were able to durably wipe out cancer cells in mice implanted with cells from the drug-resistant tumor. ven in cancers that are responding to targeted therapy by conventional criteria,
the senior author of the new study, Trever Bivona, MD, Phd, assistant professor of medicine and member of the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC).
n this work we have begun to crack open the question of why residual disease persists after targeted therapy.
which drug-resistant cells that survive treatment form residual, often lethal, tumors. Understanding the biological basis of acquired resistance has proved difficult,
partly because patients with late-stage lung cancer rarely undergo surgery, leaving scientists with few drug-resistant tumors to use in research.
But as described in the online edition of Cell Reports on Thursday, April 2, 2015, a team of UCSF researchers recently had unusual access to a surgically resected tumor from an EGFR-mutant lung cancer patient who had experienced a substantial,
but incomplete, response to erlotinib. Led by first authors Collin Blakely, MD, Phd, a clinical instructor at UCSF,
and Evangelos Pazarentzos, Phd, a postdoctoral fellow, the research group analyzed cells from this tumor using next-generation genome sequencing in an effort to understand how the cells sidestepped erlotinib treatment.
They found that the tumor cells retained the EGFR mutation targeted by erlotinib and had acquired not additional cancer-driving mutations,
or any other mutations known to confer drug resistance. These results suggested that the cells were still potentially susceptible to erlotinib,
when cells from the tumor were implanted in mice that were treated then with erlotinib. The drug effectively inhibited EGFR activity,
and they discovered that this increase is mediated by a previously unknown biochemical complex formed within the tumor cells.
a growing body of work has tied the NF-KAPPA-B pathway to various forms of cancer. An experimental drug known as PBS-1086 directly targets the NF-KAPPA-B pathway,
the implanted tumors shrank significantly, suggesting that combining a compound like PBS-1086 with erlotinib at the outset of therapy may help to prevent acquired drug resistance in EGFR-mutant NSCLC.
Combined drug regimens designed to overcome drug resistance at the outset of therapy are now the norm in treating certain forms of melanoma,
said Bivona, and he believes PBS-1086 as a shotto play a similar role in NSCLC. he NF-KAPPA-B pathway is engaged by cells in response to EGFR inhibitors as a way to survive treatment,
we see tumors shrink. In lung cancer patients treated with these drugs, and that a substantial number of patients, this could be a very powerful companion therapy to minimize
or eliminate residual disease. i
#Engineers gain control of gene activity; new therapies may be ahead Duke researchers have developed a new method to precisely control
when genes are turned on and active. The new technology allows researchers to turn on specific gene promoters
and enhancersieces of the genome that control gene activityy chemically manipulating proteins that package DNA.
or the risk for genetic disease and it could provide a new avenue for gene therapies and guiding stem cell differentiation. he epigenome is associated everything with the genome other than the actual genetic sequence,
But the real excitement from their results is an emerging ability to probe millions of potential enhancers in a way never before possible. ome genetic diseases are straightforwardf you have a mutation within a particular gene,
then you have said the disease Isaac Hilton, postdoctoral fellow in the Gersbach Lab and first author of the study. ut many diseases, like cancer,
cardiovascular disease or neurodegenerative conditions, have a much more complex genetic component. Many different variations in the genome sequence can affect your risk of disease
and this genetic variation can occur in these enhancers that Tim has identified, where they can change the levels of gene expression.
With this technology, we can explore what exactly it is that theye doing and how it relates to disease or response to drug therapies.
Gersbach added, ot only can you start to answer those questions, but you might be able to use this technique for gene therapy to activate genes that have been silenced abnormally
#Scientists discover new treatment for dementia Pushing new frontiers in dementia research, Nanyang Technological University,
Singapore (NTU Singapore) scientists have found a new way to treat dementia by sending electrical impulses to specific areas of the brain to enhance the growth of new brain cells.
Known as deep brain stimulation, it is a therapeutic procedure that is already used in some parts of the world to treat various neurological conditions such as tremors or Dystonia,
which mitigates the harmful effects of dementia-related conditions and improves short and long-term memory. Their research has shown that new brain cells,
The increase in brain cells reduces anxiety and depression, and promotes improved learning, and boosts overall memory formation and retention.
The research findings open new opportunities for developing novel treatment solutions for patients suffering from memory loss due to dementia-related conditions such as Alzheimer and even Parkinson disease.
and reduces anxiety. emory loss in older people is not only a serious and widespread problem, but signifies a key symptom of dementia.
At least one in 10 people aged 60 and above in Singapore suffer from dementia and this breakthrough could pave the way towards improved treatments for patients.
Growing new brain cells For decades, scientists have been finding ways to generate brain cells to boost memory and learning,
but more importantly, to also treat brain trauma and injury, and age-related diseases such as dementia. As part of a natural cycle, brain cells constantly die
and get replaced by new ones. The area of the brain responsible for generating new brain cells is known as the hippocampus
#Biologists identify brain tumor weakness Biologists at MIT and the Whitehead Institute have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors.
The study, led by researchers from the Whitehead Institute and MIT Koch Institute for Integrative Cancer Research, found that a subset of glioblastoma tumor cells is dependent on a particular enzyme that breaks down the amino acid glycine.
Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. GLDC caught the researchersattention as they investigated diseases known as nborn errors of metabolism
which occur when cells are missing certain metabolic enzymes. Many of these disorders specifically affect brain development;
the most common of these is marked phenylketonuria by an inability to break down the amino acid phenylalanine.
Such patients must avoid eating phenylalanine to prevent problems such as intellectual disability and seizures. Loss of GLDC produces a disorder called nonketotic hyperglycinemia,
which causes glycine to build up in the brain and can lead to severe mental retardation. GLDC is also often overactive in certain cells of glioblastoma,
the most common and most aggressive type of brain tumor found in humans. The researchers found that GLDC,
These regions are often found at the center of tumors, which are inaccessible to blood vessels.
which makes them better suited to survive in the ischemic tumor microenvironment, Kim says. However, this highly active SHMT2 also produces a glut of glycine,
Without GLDC, glycine enters a different metabolic pathway that generates toxic products that accumulate and kill the cell. n interesting aspect of the current study is uncovered that they why glycine accumulation is toxic,
says Navdeep Chandel, a professor of medicine and cellular biology at Northwestern University who was not part of the research team.
LDC loss accumulates glycine, causing nonketotic hyperglycinaemia, a disorder that severely affects the developing brain.
resulting in funneling of glycine into metabolic pathways that generate toxic molecules, such as aminoacetone and methylglyoxal.
#In first human study, new antibody therapy shows promise in suppressing HIV infection In the first results to emerge from HIV patient trials of a new generation of so-called broadly neutralizing antibodies,
Rockefeller University researchers have found the experimental therapy can dramatically reduce the amount of virus present in a patient blood.
or even preventing HIV infection. hiv antibodies In a person infected with HIV, there is an ongoing arms race between the virus and the body immune system.
Even as the body produces new antibodies that target the virus the virus is constantly mutating to escape,
The new study, conducted in Michel Nussenzweig Laboratory of Molecular Immunology, finds that administration of a potent antibody,
called 3bnc117, can catch HIV off guard and reduce viral loads. HIV antibodies previously tested in humans had shown disappointing results. 3bnc117 belongs to a new generation of broadly neutralizing antibodies that potently fight a wide range of HIV strains. hat special about these antibodies is that they have activity against over 80 percent
of HIV strains and they are extremely potent, says Marina Caskey, assistant professor of clinical investigation in the Nussenzweig lab and co-first author of the study. 3bn117,
Broadly neutralizing antibodies are produced naturally in some 10 to 30 percent of people with HIV,
but only after several years of infection. By that time the virus in their bodies has evolved typically to escape even these powerful antibodies.
However by isolating and then cloning these antibodies, researchers are able to harness them as therapeutic agents against HIV infections that have had less time to prepare.
Earlier work in the Nussenzweig lab had demonstrated that these potent antibodies could prevent or suppress infection in mouse and nonhuman primate models of HIV.
But these animal models are very rough approximations of human infections, explains Caskey. The mice must be engineered genetically to be susceptible to HIV
and therefore lack an intact immune system, and the primates used in HIV studies can only be infected with a simian version of the virus. The proof of principle awaited human trials.
In the new study uninfected and HIV-infected individuals were given intravenously a single dose of the antibody
and monitored for 56 days. At the highest dosage level tested in the study, 30 milligrams per kilogram of weight,
all eight infected individuals treated showed up to 300-fold decreases in the amount of virus measured in their blood,
The drop in viral load depended on the individual starting viral load and also the sensitivity of their particular strains of HIV to the antibody.
This is the first time that the new generation of HIV antibodies has been tested in humans. Not only was a single dose of 3bn117 well tolerated and effective in temporarily reducing viral loads,
Researchers also believe that antibodies may be able to enhance the patient immune responses against HIV, which can in turn lead to better control of the infection.
In addition, antibodies like 3bnc117 may be able to kill viruses hidden in infected cells, which serve as viral reservoirs inaccessible to current antiretroviral drugs.
Most likely 3bnc117, like other anti-retrovirals, will need to be used in combination with other antibodies
or antiretroviral drugs to keep infections under control. ne antibody alone, like one drug alone, will not be sufficient to suppress viral load for a long time
because resistance will arise, says Caskey. One important benefit is the dosing schedule: an antibody therapy for HIV might require treatment just once every few months,
compared to daily regimens of antiretroviral drugs that are now the front-line treatment for HIV. n contrast to conventional antiretroviral therapy,
antibody-mediated therapy can also engage the patient immune cells, which can help to better neutralize the virus,
says co-first author Florian Klein, also assistant professor of clinical investigation in the Nussenzweig laboratory.
Besides the possibility of treatment, the study also raises hopes for an HIV vaccine. If researchers can induce an uninfected person immune system to generate potent antibodies such as 3bnc117
it might be enough to block the HIV infection before it can be established. Ongoing clinical research in Nussenzweig lab and The Rockefeller University Hospital aims to address the impact of additional broadly neutralizing antibodies, alone or in combination, on viral load in HIV-infected patients.
Source: Rockefeller Universit l
#Wearable device Slows Deadly Brain tumors, Clinical Trial Finds A wearable device that emits low-level electrical fields can slow the progression of glioblastoma, the deadliest form of brain cancer,
and extend patientslifespans, a major clinical trial at the University of Virginia School of medicine and more than 80 other institutions has found.
Dr. David Schiff of the U. Va. Department of Neurology said the results of the trial have come as a eal shocker to the field,
noting that glioblastoma is notoriously difficult to treat. his is a tumor type that it been very hard to make real progress against.
From the 1960s to the present we haven improved the average survival by more than a few months less than a handful of months.
So anybody who been in the field for a while has seen a lot of bright ideas fail, he said. ut this trial in newly diagnosed disease is a different kettle of fish.
Because this trial clearly shows an improvement both in time until the tumor starts growing but more importantly in overall survival.
And if you can make a difference in overall survival, youe really doing something. Prolonged Survival Median survival among the 210 newly diagnosed patients who wore the device was 19.6 months
including surgery and chemotherapy.)Forty-three percent of device wearers survived two years; only 29 percent of those who didn wear the device lived that long.
A major challenge of ASD diagnosis and treatment is that the neurological condition which affects 1 in 68 children in the United states,
in part because the underlying causes for different subtypes of autism are diverse and not well-understood. here is no better example than early language development,
professor of neurosciences and co-director of the Autism Center of Excellence at UC San diego. ome individuals are minimally verbal throughout life.
more individualized treatments, said co-author Karen Pierce, Phd, associate professor of neurosciences and co-director of the Autism Center of Excellence.
The researchers combined prospective fmri measurements of neural systemsresponse to speech in children at the earliest ages at which risk of ASD can be detected clinically in a general pediatric population (at approximately ages 1-2 years
They found that pre-diagnosis fmri response to speech in ASD toddlers with relatively good language outcomes was highly similar to non-ASD comparison groups with robust responses to language in superior temporal cortices,
and underlie later good versus poor language outcome in autism. These findings said researchers, will open new avenues of progress towards identifying the causes and best treatment for these two very different types of autism. or the first time,
our study shows a strong relationship between irregularities in speech-activation in the language-critical superior temporal cortex and actual,
but not all, on the autism spectrum. t
#Graphics in reverse Most recent advances in artificial intelligence such as mobile apps that convert speech to text are the result of machine learning, in
#New Way to Fight Cancer Targeted cancer therapies work by blocking a single oncogenic pathway to halt tumor growth.
But because cancerous tumors have the unique ability to activate alternative pathways, they are often able to evade these therapies and regrow.
Moreover, tumors contain a small portion of cancer stem cells that are believed to be responsible for tumor initiation, metastasis and drug resistance.
Thus, eradicating cancer stem cells may be critical for achieving long-lasting remission, but there are no drugs available that specifically attack cancer stem cells.
A Surprising Discovery Now a research team led by investigators at Harvard Medical school and the Cancer Center at Beth Israel Deaconess Medical center
has identified an inhibitor of the Pin1 enzyme that can address both these challenges in acute promyelocytic leukemia (APL) and triple-negative breast cancer.
Their surprising discovery demonstrates that the Vitamin a derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy,
can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme.
Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancerarticularly cancers that are aggressive
or drug resistant. in1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease,
explained co-senior author Kun Ping Lu, HMS professor of medicine and director of translational therapeutics in the Cancer Research Institute at Beth Israel Deaconess. in1 is a common key regulator in many types of cancer
and as a result can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells.
Lu also co-discovered the enzyme in 1996. A Different Approach Until now, agents that inhibit Pin1 have been developed mainly through rational drug design.
Although these inhibitors have proven active against Pin1 in the test tube when they are tested in vitro in a cell model
or in vivo in a living animal they are unable to efficiently enter cells to successfully inhibit Pin1 function.
In this new work, co-senior author Xiao Zhen Zhou, HMS assistant professor of medicine and an investigator in the Division of Translational Therapeutics at Beth Israel Deaconess, decided to take a different
approach to identify Pin1 inhibitors: She developed a mechanism-based high-throughput screen to identify compounds that were targeting active Pin1. e had identified previously Pin1 substrate-mimicking peptide inhibitors,
explained Zhou. e therefore used these as a probe in a competition binding assay and screened approximately 8,
in order to bind Pin1. hile it has been shown previously that ATRA ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL,
when two tumor suppressors fuse together to become an oncogene, added co-author Pier Paolo Pandolfi, the HMS George C. Reisman Professor of Medicine and director of the Cancer Genetics Program at Beth Israel Deaconess,
whose own pioneering work revealed the molecular underpinnings of APL and led to its cure. hese new findings demonstrate that by inhibiting Pin1,
you can degrade this fusion oncogene, thereby stopping cancer stem cells from replicating. This is a critically important discovery that will impact the treatment of other forms of cancer
since Pin1 inhibition is also affecting other key oncogenes. To that end, the authors also tested ATRA in triple-negative breast cancer, one of the most aggressive types of breast cancer.
They discovered that ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer growth in human cells and in animal models by simultaneously turning off many oncogenes and turning on many tumor suppressors.
Aiming at ream Targets These new results, say the authors, provide a rationale for developing longer half-life ATRA
or more potent and specific Pin1-targeted ATRA variants for cancer treatment. he current ATRA drug has a very short half life of only 45 minutes in humans,
and offers a promising new approach for targeting a Pin1-dependent common oncogenic mechanism in numerous cancer-driving pathways in cancer
and cancer stem cells. This is especially critical for treating aggressive or drug-resistant cancers. a
#Computer-Designed Rocker Protein Worlds First To Biomimic Ion Transport For the first time, scientists recreated the biological function of substrate transportation across the cell membranes by computationally designing a transporter protein.
such as targeting medicines more specifically into cancer cells and driving charge separation potentially for harvesting energy for batteries.
said Jean Chin of the National institutes of health National Institute of General Medical sciences, which funded the work through grants to several of the paper co-authors. he highly collaborative team used its deep knowledge of the structures,
and medicine. e envision that this protein can create an electrochemical gradient using things like ph,
But if you could transport something into the cell such as a toxic ion or small molecule that could be quite interesting,
According to the American Heart Association, African americans are at a higher risk than whites to die of heart disease.
Research over the last decade has demonstrated that discrimination against African americans may be a direct cause of many of these health problems
as well as information about stress and perceived discrimination through interviews. Goosby found a strong correlation between perceived discrimination and levels of C reactive-protein protein,
and blood pressure. didn expect that discrimination would have such a strong relationship with these particular markers of cardiovascular disease risk in kids this young,
#New transitional stem cells discovered Preeclampsia is a disease that affects 5 to 8 percent of pregnancies in America.
Complications from this disease can lead to emergency cesarean sections early in pregnancies to save the lives of the infants and mothers.
Scientists believe preeclampsia is caused by a number of factors, including shallow placentas that are associated insufficiently with maternal blood vessels.
Now, researchers from the University of Missouri, in an effort to grow placenta cells to better study the causes of preeclampsia,
and his colleagues, says these new stem cells can help advance research on preeclampsia and a number of other areas of the human reproductive process. hese new cells,
what causes diseases like preeclampsia and other prenatal problems. Embryonic stem cells are pluripotent, meaning they can develop into a number of different types of cells such as muscle cells, bone cells, skin cells, etc.
Says Study Angiogenesis inhibitors widely used class of cancer drugs designed to shrink tumors by preventing them from forming new blood vesselsften work in the short term,
and prevent cancer relapse. Working with laboratory models of pancreatic and breast cancer, the scientists found that myeloid cells,
and are part of the body first-line of defensehe so-called nnateimmune systemt first work in concert with the therapy
2015 online issue of Cell Reports, the researchers, under the direction of senior investigator Gabriele Bergers, Phd, UCSF professor of neurological surgery,
and first author Lee B. Rivera, Phd, a UCSF postdoctoral scholar in the Bergers laboratory, also identified a potential way to stop myeloid cells from sabotaging the therapy
In one state, myeloid cells are immunity-enhancing and angiostatic that is, they prevent the formation of new blood vessels. his is important in the early stages of wound healing,
she explained, hen they need to be immune-stimulatory and attack when bacteria, for example, are invading.
During anti-angiogenic therapy, said Bergers, the Neill H. and Linda S. Brownstein Endowed Chair in Brain tumor Research and a member of the UCSF Helen Diller Family Comprehensive Cancer Center,
he tumor hijacks the second stage of the natural process we see in wound healing for its own advantage.
But we have learned that we can also manipulate this process to make therapy more effective.
which prevents the tumor from forming new blood vessels, thereby shrinking it. The researchers found that during the initial phase of therapy,
VEGF inhibition stimulates myeloid cells within the tumor to release the signaling protein CXCL14, which is angiostatic
and stimulates immunity. During this phase, myeloid cells complement the therapy to prevent the creation of new blood vessels,
and the tumor shrinks. But thenrobably in response to reduced oxygen flow within the tumoryeloid cells switch to their opposite state nd become real bad guys
said Bergers. At this stage the cells activate the PI3-kinase (PI3K) signaling pathway, which neutralizes CXCL14
and promotes angiogenesis and tumor growth. nce the PI3K pathway is activated, therapy becomes ineffective, and you have said relapse,
she. In breast cancer, Bergers noted, anti-VEGF therapy is not very effective to begin with. his tells us why,
she said. n a laboratory model of breast cancer, about 45 percent of myeloid cells are activated already,
so the cancer just ignores the therapy. The researchers found that targeting specific innate immune cells within the tumor did not reverse the negative effects of PI3K activation.
Eliminating macrophages one type of white blood cell resulted in an increase in neutrophils another type of white blood cell.
But eliminating neutrophils brought on an increase in macrophages. This so-called myeloid-cell oscillation maintained the tumor resistance to the therapy.
Instead, said Bergers, e found that what you need to do is target the central signaling node,
Ultimately, the researchers demonstrated that combining a PI3K inhibitor with anti-VEGF therapy prevented relapse
and significantly increased survival in a mouse model of pancreatic neuroendocrine tumor. Bergers noted that the discovery potentially gives physicians a way to determine how effective anti-VEGF therapy might be in individual patients
as well as to monitor the course of therapy. n some new patients, we could test to determine how many myeloid cells in the tumor were activated already,
which could tell us to what extent the tumor would still be responsive to anti-VEGF therapy,
she said. In patients undergoing therapy, e could take advantage of the fact that myeloid cells occur not only in the tumor,
but also in the blood, said Bergers. simple blood test would give us a noninvasive biomarker to check on the state of myeloid activation.
Right now, one of the major issues in anti-VEGF therapy is that there are no biomarkers for response and relapse. t
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011