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Liu F.,University of Notre Dame | Li Q.,Merck Research Labs
Computational Statistics and Data Analysis | Year: 2014

A critical step in group sequential designs is computation of the appropriate critical values for rejecting H0 at the interim look to keep the overall type I error rate at a prespecified level. When applying the sequential test in a study with an equivalence hypothesis, calculation of the critical values is complicated by the dependency between the dual test statistics at each interim look. Current methods for calculating critical values apply two primary approximations: z-statistics assuming a large sample size, and ignorance of the contribution to the overall type I error rate from rejecting one out of the two one-sided hypotheses under a null value. In the sequential testing, with smaller stagewise sample size and type I error rate, the first approximation would result in unsatisfactory inflation of the type I error rate, and the second approximation could lead to excessive conservatism. We establish a mathematical and computational framework of the exact sequential test based on bivariate non-central t statistics and propose several numerical approaches for computing the exact equivalence boundaries and futility boundaries. Examples and simulation studies are used to compare the operating characteristics between the exact test procedure and three other approximate test procedures. © 2014 Elsevier B.V. All rights reserved.


News Article | February 16, 2017
Site: www.eurekalert.org

The tenth SpaceX cargo resupply launch to the International Space Station, targeted for launch Feb. 18, will deliver investigations that study human health, Earth science and weather patterns The tenth SpaceX cargo resupply launch to the International Space Station, targeted for launch Feb. 18, will deliver investigations that study human health, Earth science and weather patterns. Here are some highlights of the research headed to the orbiting laboratory: Monoclonal antibodies are important for fighting off a wide range of human diseases, including cancers. These antibodies work with the natural immune system to bind to certain molecules to detect, purify and block their growth. The Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS PCG 5) investigation will crystallize a human monoclonal antibody, developed by Merck Research Labs, that is currently undergoing clinical trials for the treatment of immunological disease. Preserving these antibodies in crystals allows researchers a glimpse into how the biological molecules are arranged, which can provide new information about how they work in the body. Thus far, Earth-grown crystalline suspensions of monoclonal antibodies have proven to be too low-quality to fully model. With the absence of gravity and convection aboard the station, larger crystals with more pure compositions and structures can grow. The results from this investigation have the potential to improve the way monoclonal antibody treatments are administered on Earth. Crystallizing the antibodies could enable methods for large-scale delivery through injections rather than intravenously, and improve methods for long-term storage. Understanding crystal growth in space could benefit researchers on Earth Without proteins, the human body would be unable to repair, regulate or protect itself. Crystallizing proteins provides better views of their structure, which helps scientists to better understand how they function. Often times, proteins crystallized in microgravity are of higher quality than those crystallized on Earth. LMM Biophysics 1 explores that phenomena by examining the movement of single protein molecules in microgravity. Once scientists understand how these proteins function, they can be used to design new drugs that interact with the protein in specific ways and fight disease. Identifying proteins that benefit from microgravity crystal growth could maximize research efficiency Much like LMM Biophysics 1, LMM Biophysics 3 aims to use crystallography to examine molecules that are too small to be seen under a microscope, in order to best predict what types of drugs will interact best with certain kinds of proteins. LMM Biophysics 3 will look specifically into which types of crystals thrive and benefit from growth in microgravity, where Earth's gravity won't interfere with their formation. Currently, the success rate is poor for crystals grown even in the best of laboratories. High quality, space-grown crystals could improve research for a wide range of diseases, as well as microgravity-related problems such as radiation damage, bone loss and muscle atrophy. X Prize-winning device seeks insight into how deadly bacteria become drug-resistant Microgravity accelerates the growth of bacteria, making the space station an ideal environment to conduct a proof-of-concept investigation on the Gene-RADAR® device developed by Nanobiosym. This device is able to accurately detect, in real time and at the point of care, any disease that leaves a genetic fingerprint. Nanobiosym Predictive Pathogen Mutation Study (Nanobiosym Genes) will analyze two strains of bacterial mutations aboard the station, providing data that may be helpful in refining models of drug resistance and support the development of better medicines to counteract the resistant strains. Microgravity may hold key to scaling up stem cell cultivation for research, treatment Stem cells are used in a variety of medical therapies, including the treatment of stroke. Currently, scientists have no way of efficiently expanding the cells, a process that may be accelerated in a microgravity environment. During the Microgravity Expanded Stem Cells investigation, crew members will observe cell growth and morphological characteristics in microgravity and analyze gene expression profiles of cells grown on the station. This information will provide insight into how human cancers start and spread, which aids in the development of prevention and treatment plans. Results from this investigation could lead to the treatment of disease and injury in space, as well as provide a way to improve stem cell production for human therapy on Earth. Lightning flashes somewhere on Earth about 45 times per second, according to space-borne lightning detection instruments. This investigation continues those observations using a similar sensor aboard the station. The Lightning Imaging Sensor (STP-H5 LIS) will measure the amount, rate and energy of lightning as it strikes around the world. Understanding the processes that cause lightning and the connections between lightning and subsequent severe weather events is a key to improving weather predictions and saving life and property. From the vantage of the station, the LIS instrument will sample lightning over a swider geographical area than any previous sensor. Future robotic spacecraft will need advanced autopilot systems to help them safely navigate and rendezvous with other objects, as they will be operating thousands of miles from Earth. The Raven (STP-H5 Raven) studies a real-time spacecraft navigation system that provides the eyes and intelligence to see a target and steer toward it safely. Raven uses a complex system to image and track the many visiting vehicles that journey to the space station each year. Equipped with three separate sensors and high-performance, reprogrammable avionics that process imagery, Raven's algorithm converts the collected images into an accurate relative navigation solution between Raven and the other vehicle. Research from Raven can be applied toward unmanned vehicles both on Earth and in space, including potential use for systems in NASA's future human deep space exploration. The Stratospheric Aerosol and Gas Experiment (SAGE) program is one of NASA's longest running Earth-observing programs, providing long-term data to help scientists better understand and care for Earth's atmosphere. SAGE was first operated in 1979 following the Stratospheric Aerosol Measurement (SAM), on the Apollo-Soyuz mission. SAGE III will measure stratospheric ozone, aerosols, and other trace gases by locking onto the sun or moon and scanning a thin profile of the atmosphere. Understanding these measurements will allow national and international leaders to make informed policy decisions regarding the protection and preservation of Earth's ozone layer. Ozone in the atmosphere protects Earth's inhabitants, including humans, plants and animals, from harmful radiation from the sun, which can cause long-term problems such as cataracts, cancer and reduced crop yield. Studying tissue regeneration in space could improve injury treatment on Earth Only a few animals, such as tadpoles and salamanders, can regrow a lost limb, but the onset of this process exists in all vertebrates. Tissue Regeneration-Bone Defect (Rodent Research-4) a U.S. National Laboratory investigation sponsored by the Center for the Advancement of Science in Space (CASIS) and the U.S. Army Medical Research and Materiel Command, studies what prevents other vertebrates such as rodents and humans from re-growing lost bone and tissue, and how microgravity conditions impact the process. Results will provide a new understanding of the biological reasons behind a human's inability to grow a lost limb at the wound site, and could lead to new treatment options for the more than 30% of the patient population who do not respond to current options for chronic non-healing wounds. Crew members in orbit often experience reduced bone density and muscle mass, a potential consequence of microgravity-induced stress. Previous research indicates that reduced gravity can promote cell growth, making microgravity a potentially viable environment for tissue regeneration research. This investigation may be able to shed more light on why bone density decreases in microgravity and whether it may be possible to counteract it. These investigations will join many others recurring around the clock aboard the station, all benefitting future spaceflight and life on Earth. For more information about the science happening on station, visit International Space Station Research and Technology.


Mazura M.T.,26 E. Lincoln Avenue | Mazura M.T.,Imclone Systems | Cardasis H.L.,26 E. Lincoln Avenue | Spellman D.S.,26 E. Lincoln Avenue | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Top-down mass spectrometry holds tremendous potential for the characterization and quantification of intact proteins, including individual protein isoforms and specific posttranslationally modified forms. This technique does not require antibody reagents and thus offers a rapid path for assay development with increased specificity based on the amino acid sequence. Top-down MS is efficient whereby intact protein mass measurement, purification by mass separation, dissociation, and measurement of product ions with ppm mass accuracy occurs on the seconds to minutes time scale. Moreover, as the analysis is based on the accurate measurement of an intact protein, top-down mass spectrometry opens a research paradigm to perform quantitative analysis of "unknown" proteins that differ in accurate mass. As a proof of concept, we have applied differential mass spectrometry (dMS) to the top-down analysis of apolipoproteins isolated from human HDL3. The protein species at 9415.45 Da demonstrates an average fold change of 4.7 (p-value 0.017) and was identified as an O-glycosylated form of apolipoprotein C-III [NANA-(2 → 3)-Gal-β(1 → 3)-GalNAc, +656.2037 Da], a protein associated with coronary artery disease. This work demonstrates the utility of top-down dMS for quantitative analysis of intact protein mixtures and holds potential for facilitating a better understanding of HDL biology and complex biological systems at the protein level.


Kreimer A.,Columbia University | Litvin O.,Columbia University | Hao K.,Merck Research Labs | Molony C.,Merck Research Labs | And 2 more authors.
Nucleic Acids Research | Year: 2012

Cataloging the association of transcripts to genetic variants in recent years holds the promise for functional dissection of regulatory structure of human transcription. Here, we present a novel approach, which aims at elucidating the joint relationships between transcripts and single-nucleotide polymorphisms (SNPs). This entails detection and analysis of modules of transcripts, each weakly associated to a single genetic variant, together exposing a high-confidence association signal between the module and this 'main' SNP. To explore how transcripts in a module are related to causative loci for that module, we represent such dependencies by a graphical model. We applied our method to the existing data on genetics of gene expression in the liver. The modules are significantly more, larger and denser than found in permuted data. Quantification of the confidence in a module as a likelihood score, allows us to detect transcripts that do not reach genome-wide significance level. Topological analysis of each module identifies novel insights regarding the flow of causality between the main SNP and transcripts. We observe similar annotations of modules from two sources of information: the enrichment of a module in gene subsets and locus annotation of the genetic variants. This and further phenotypic analysis provide a validation for our methodology. © 2012 The Author(s).


Davis H.R.,Merck Research Labs | Lowe R.S.,Sharp Corporation | Neff D.R.,Sharp Corporation
Atherosclerosis | Year: 2011

Ezetimibe (Zetia®, Ezetrol®, Merck, Whitehouse Station, NJ) is a potent inhibitor of sterol absorption, which selectively blocks the uptake of biliary and dietary cholesterol in the small intestine. Clinical trials have demonstrated the beneficial effects of ezetimibe on the reduction of atherogenic lipoproteins and the attainment of guideline-recommended lipid levels. Direct evidence that these improvements translate to a reduction in atherosclerosis or cardiovascular events is limited, although reductions in major atherosclerotic events that are consistent with the LDL-C lowering achieved have recently been presented for patients with chronic kidney disease treated with ezetimibe/simvastatin 10/20mg in the SHARP trial. Animal models of atherosclerosis have played a central role in defining the mechanisms involved in initiation and development of disease and have been used in drug development to evaluate potential therapeutic efficacy. The effect of ezetimibe on atherosclerosis has been examined in several of these animal model systems. ApoE knockout mice develop severe hypercholesterolemia and premature atherosclerosis with features similar to that seen in humans and techniques ranging from gross visualization of plaque to high-resolution MRI have demonstrated the consistent ability of ezetimibe to significantly inhibit atherosclerosis. sr-b1-/-/apoE-/- double knockout mice exhibit additional characteristics common to human coronary heart disease (CHD), and the one study of ezetimibe in sr-b1-/-/apoE-/- mice showed a significant reduction in aortic sinus plaque (57%), coronary arterial occlusion (68%), myocardial fibrosis (57%), and cardiomegaly (12%) compared with untreated controls. The effects of ezetimibe have also been evaluated in ldlr-/-/apoE-/- double knockout mice, demonstrating that functional LDL receptors were not required for ezetimibe-mediated reduction of plasma cholesterol or atherosclerosis. For the few studies that have been conducted in rabbits, ezetimibe has been shown to significantly inhibit diet and vascular-injury-induced atherosclerosis as measured by intima/media thickness, atherosclerotic lesion composition, and thrombosis. The current body of preclinical evidence consistently demonstrates that ezetimibe reduces atherosclerosis in animals, presumably due primarily to the decrease in circulating levels of atherogenic lipoproteins that the drug produces. Demonstration that ezetimibe-mediated lowering of atherogenic lipoproteins in humans has a similar effect on atherosclerosis and cardiovascular risk awaits additional results from recently completed and ongoing outcomes trials. © 2011 Elsevier Ireland Ltd.


Flach C.-F.,Gothenburg University | Ostberg A.K.,Gothenburg University | Nilsson A.-T.,Gothenburg University | Malefyt R.D.W.,Merck Research Labs | Raghavan S.,Gothenburg University
Infection and Immunity | Year: 2011

CD4 + T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection in mice. Less is known about the relative contributions of individual cell subpopulations, such as T h1 and T h17 cells, and their associated cytokines. The aim of the present study was to find immune correlates to vaccine-induced protection and further study their role in protection against H. pylori infection. Immunized and unimmunized mice were challenged with H. pylori, and immune responses were compared. Vaccine-induced protection was assessed by measuring H. pylori colonization in the stomach. Gastric gene expression of T h1- and/or T h17-associated cytokines was analyzed by quantitative PCR, and contributions of individual cytokines to protection were evaluated by antibody-mediated in vivo neutralization. By analyzing immunized and unimmunized mice, a significant inverse correlation between the levels of interleukin-12p40 (IL-12p40), tumor necrosis factor alpha (TNF), gamma interferon (IFN-γ), and IL-17 gene expression and the number of H. pylori bacteria in the stomachs of individual animals after challenge could be demonstrated. In a kinetic study, upregulation of TNF, IFN-γ, and IL-17 coincided with vaccine-induced protection at 7 days after H. pylori challenge and was sustained for at least 21 days. In vivo neutralization of these cytokines during the effector phase of the immune response revealed a significant role for IL-17, but not for IFN-γ or TNF, in vaccine-induced protection. In conclusion, although both T h1- and T h17-associated gene expression in the stomach correlate with vaccine-induced protection against H. pylori infection, our study indicates that mainly T h17 effector mechanisms are of critical importance to protection. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


News Article | February 16, 2017
Site: www.24-7pressrelease.com

HOUSTON, TX, February 16, 2017 /24-7PressRelease/ -- The tenth SpaceX cargo resupply launch to the International Space Station, targeted for launch Feb. 18, will deliver investigations that study human health, Earth science and weather patterns. Here are some highlights of the research headed to the orbiting laboratory: Crystal growth investigation could improve drug delivery, manufacturing Monoclonal antibodies are important for fighting off a wide range of human diseases, including cancers. These antibodies work with the natural immune system to bind to certain molecules to detect, purify and block their growth. The Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS PCG 5) investigation will crystallize a human monoclonal antibody, developed by Merck Research Labs, that is currently undergoing clinical trials for the treatment of immunological disease. Preserving these antibodies in crystals allows researchers a glimpse into how the biological molecules are arranged, which can provide new information about how they work in the body. Thus far, Earth-grown crystalline suspensions of monoclonal antibodies have proven to be too low-quality to fully model. With the absence of gravity and convection aboard the station, larger crystals with more pure compositions and structures can grow. The results from this investigation have the potential to improve the way monoclonal antibody treatments are administered on Earth. Crystallizing the antibodies could enable methods for large-scale delivery through injections rather than intravenously, and improve methods for long-term storage. Understanding crystal growth in space could benefit researchers on Earth Without proteins, the human body would be unable to repair, regulate or protect itself. Crystallizing proteins provides better views of their structure, which helps scientists to better understand how they function. Often times, proteins crystallized in microgravity are of higher quality than those crystallized on Earth. LMM Biophysics 1 explores that phenomena by examining the movement of single protein molecules in microgravity. Once scientists understand how these proteins function, they can be used to design new drugs that interact with the protein in specific ways and fight disease. Identifying proteins that benefit from microgravity crystal growth could maximize research efficiency Much like LMM Biophysics 1, LMM Biophysics 3 aims to use crystallography to examine molecules that are too small to be seen under a microscope, in order to best predict what types of drugs will interact best with certain kinds of proteins. LMM Biophysics 3 will look specifically into which types of crystals thrive and benefit from growth in microgravity, where Earth's gravity won't interfere with their formation. Currently, the success rate is poor for crystals grown even in the best of laboratories. High quality, space-grown crystals could improve research for a wide range of diseases, as well as microgravity-related problems such as radiation damage, bone loss and muscle atrophy. X Prize-winning device seeks insight into how deadly bacteria become drug-resistant Microgravity accelerates the growth of bacteria, making the space station an ideal environment to conduct a proof-of-concept investigation on the Gene-RADAR device developed by Nanobiosym. This device is able to accurately detect, in real time and at the point of care, any disease that leaves a genetic fingerprint. Nanobiosym Predictive Pathogen Mutation Study (Nanobiosym Genes) will analyze two strains of bacterial mutations aboard the station, providing data that may be helpful in refining models of drug resistance and support the development of better medicines to counteract the resistant strains. Microgravity may hold key to scaling up stem cell cultivation for research, treatment Stem cells are used in a variety of medical therapies, including the treatment of stroke. Currently, scientists have no way of efficiently expanding the cells, a process that may be accelerated in a microgravity environment. During the Microgravity Expanded Stem Cells investigation, crew members will observe cell growth and morphological characteristics in microgravity and analyze gene expression profiles of cells grown on the station. This information will provide insight into how human cancers start and spread, which aids in the development of prevention and treatment plans. Results from this investigation could lead to the treatment of disease and injury in space, as well as provide a way to improve stem cell production for human therapy on Earth. Space-based lightning sensor could improve climate monitoring Lightning flashes somewhere on Earth about 45 times per second, according to space-borne lightning detection instruments. This investigation continues those observations using a similar sensor aboard the station. The Lightning Imaging Sensor (STP-H5 LIS) will measure the amount, rate and energy of lightning as it strikes around the world. Understanding the processes that cause lightning and the connections between lightning and subsequent severe weather events is a key to improving weather predictions and saving life and property. From the vantage of the station, the LIS instrument will sample lightning over a swider geographical area than any previous sensor. Raven seeks to save resources with versatile autonomous technologies Future robotic spacecraft will need advanced autopilot systems to help them safely navigate and rendezvous with other objects, as they will be operating thousands of miles from Earth. The Raven (STP-H5 Raven) studies a real-time spacecraft navigation system that provides the eyes and intelligence to see a target and steer toward it safely. Raven uses a complex system to image and track the many visiting vehicles that journey to the space station each year. Equipped with three separate sensors and high-performance, reprogrammable avionics that process imagery, Raven's algorithm converts the collected images into an accurate relative navigation solution between Raven and the other vehicle. Research from Raven can be applied toward unmanned vehicles both on Earth and in space, including potential use for systems in NASA's future human deep space exploration. Understanding Earth's atmosphere health could inform policy, protection The Stratospheric Aerosol and Gas Experiment (SAGE) program is one of NASA's longest running Earth-observing programs, providing long-term data to help scientists better understand and care for Earth's atmosphere. SAGE was first operated in 1979 following the Stratospheric Aerosol Measurement (SAM), on the Apollo-Soyuz mission. SAGE III will measure stratospheric ozone, aerosols, and other trace gases by locking onto the sun or moon and scanning a thin profile of the atmosphere. Understanding these measurements will allow national and international leaders to make informed policy decisions regarding the protection and preservation of Earth's ozone layer. Ozone in the atmosphere protects Earth's inhabitants, including humans, plants and animals, from harmful radiation from the sun, which can cause long-term problems such as cataracts, cancer and reduced crop yield. Studying tissue regeneration in space could improve injury treatment on Earth Only a few animals, such as tadpoles and salamanders, can regrow a lost limb, but the onset of this process exists in all vertebrates. Tissue Regeneration-Bone Defect (Rodent Research-4) a U.S. National Laboratory investigation sponsored by the Center for the Advancement of Science in Space (CASIS) and the U.S. Army Medical Research and Materiel Command, studies what prevents other vertebrates such as rodents and humans from re-growing lost bone and tissue, and how microgravity conditions impact the process. Results will provide a new understanding of the biological reasons behind a human's inability to grow a lost limb at the wound site, and could lead to new treatment options for the more than 30% of the patient population who do not respond to current options for chronic non-healing wounds. Crew members in orbit often experience reduced bone density and muscle mass, a potential consequence of microgravity-induced stress. Previous research indicates that reduced gravity can promote cell growth, making microgravity a potentially viable environment for tissue regeneration research. This investigation may be able to shed more light on why bone density decreases in microgravity and whether it may be possible to counteract it. These investigations will join many others recurring around the clock aboard the station, all benefitting future spaceflight and life on Earth. For more information about the science happening on station, visit International Space Station Research and Technology.


News Article | February 23, 2017
Site: www.npr.org

SpaceX Cargo Craft Is Now In Space Station's Grip, One Day After Aborted Docking With a nudge of a robotic arm, astronauts aboard the International Space Station captured a space capsule carrying 5,500 pounds of cargo early Thursday. "Capture confirmed," NASA TV's announcer stated at 5:44 a.m. ET. The capture took place as the space station and the SpaceX capsule flew in orbit 250 miles over Australia's northwest coast. The safe rendezvous should help soothe the nerves of NASA and SpaceX teams that have seen this mission encounter delays at crucial moments. In NASA's timetable that was released last week, the agency had planned for the Dragon craft to reach the space station three days ago. On Saturday, the craft's launch was aborted just seconds ahead of rocket ignition, due to an anomaly in its steering system. The actual launch one day later went perfectly, but when the Dragon craft was less than a mile from its space station dock early Wednesday, its computer automatically aborted the maneuver due to an error in its GPS software. That set up today's meeting, which comes just a day before a Russian resupply rocket is slated to arrive early Friday. It will take the ISS crew about a month to unload the spacecraft, NASA says. In late March, it will splash down in the Pacific Ocean, off the coast of Baja California. NASA describes some of the experiments Dragon is carrying along with crew supplies: "Science investigations launching on Dragon include commercial and academic research investigations that will enable researchers to advance their knowledge of the medical, psychological and biomedical challenges astronauts face during long-duration spaceflight. "One experiment will use the microgravity environment to grow stem cells that are of sufficient quality and quantity to use in the treatment of patients who have suffered a stroke. A Merck Research Labs investigation will test growth in microgravity of antibodies important for fighting a wide range of human diseases, including cancer."


News Article | February 23, 2017
Site: www.npr.org

SpaceX Cargo Craft Is Now In Space Station's Grip, One Day After Aborted Docking With a nudge of a robotic arm, astronauts aboard the International Space Station captured a space capsule carrying 5,500 pounds of cargo early Thursday. "Capture confirmed," NASA TV's announcer stated at 5:44 a.m. ET. The capture took place as the space station and the SpaceX capsule flew in orbit 250 miles over Australia's northwest coast. The safe rendezvous should help soothe the nerves of NASA and SpaceX teams that have seen this mission encounter delays at crucial moments. In NASA's timetable that was released last week, the agency had planned for the Dragon craft to reach the space station three days ago. On Saturday, the craft's launch was aborted just seconds ahead of rocket ignition, due to an anomaly in its steering system. The actual launch one day later went perfectly, but when the Dragon craft was less than a mile from its space station dock early Wednesday, its computer automatically aborted the maneuver due to an error in its GPS software. That set up today's meeting, which comes just a day before a Russian resupply rocket is slated to arrive early Friday. It will take the ISS crew about a month to unload the spacecraft, NASA says. In late March, it will splash down in the Pacific Ocean, off the coast of Baja California. NASA describes some of the experiments Dragon is carrying along with crew supplies: "Science investigations launching on Dragon include commercial and academic research investigations that will enable researchers to advance their knowledge of the medical, psychological and biomedical challenges astronauts face during long-duration spaceflight. "One experiment will use the microgravity environment to grow stem cells that are of sufficient quality and quantity to use in the treatment of patients who have suffered a stroke. A Merck Research Labs investigation will test growth in microgravity of antibodies important for fighting a wide range of human diseases, including cancer."


Monoclonal antibodies are important for fighting off a wide range of human diseases, including cancers. These antibodies work with the natural immune system to bind to certain molecules to detect, purify and block their growth. The Microgravity Growth of Crystalline Monoclonal Antibodies for Pharmaceutical Applications (CASIS PCG 5) investigation will crystallize a human monoclonal antibody, developed by Merck Research Labs, that is currently undergoing clinical trials for the treatment of immunological disease. Preserving these antibodies in crystals allows researchers a glimpse into how the biological molecules are arranged, which can provide new information about how they work in the body. Thus far, Earth-grown crystalline suspensions of monoclonal antibodies have proven to be too low-quality to fully model. With the absence of gravity and convection aboard the station, larger crystals with more pure compositions and structures can grow. The results from this investigation have the potential to improve the way monoclonal antibody treatments are administered on Earth. Crystallizing the antibodies could enable methods for large-scale delivery through injections rather than intravenously, and improve methods for long-term storage. Understanding crystal growth in space could benefit researchers on Earth Without proteins, the human body would be unable to repair, regulate or protect itself. Crystallizing proteins provides better views of their structure, which helps scientists to better understand how they function. Often times, proteins crystallized in microgravity are of higher quality than those crystallized on Earth. LMM Biophysics 1 explores that phenomena by examining the movement of single protein molecules in microgravity. Once scientists understand how these proteins function, they can be used to design new drugs that interact with the protein in specific ways and fight disease. Identifying proteins that benefit from microgravity crystal growth could maximize research efficiency Much like LMM Biophysics 1, LMM Biophysics 3 aims to use crystallography to examine molecules that are too small to be seen under a microscope, in order to best predict what types of drugs will interact best with certain kinds of proteins. LMM Biophysics 3 will look specifically into which types of crystals thrive and benefit from growth in microgravity, where Earth's gravity won't interfere with their formation. Currently, the success rate is poor for crystals grown even in the best of laboratories. High quality, space-grown crystals could improve research for a wide range of diseases, as well as microgravity-related problems such as radiation damage, bone loss and muscle atrophy. X Prize-winning device seeks insight into how deadly bacteria become drug-resistant Microgravity accelerates the growth of bacteria, making the space station an ideal environment to conduct a proof-of-concept investigation on the Gene-RADAR® device developed by Nanobiosym. This device is able to accurately detect, in real time and at the point of care, any disease that leaves a genetic fingerprint. Nanobiosym Predictive Pathogen Mutation Study (Nanobiosym Genes) will analyze two strains of bacterial mutations aboard the station, providing data that may be helpful in refining models of drug resistance and support the development of better medicines to counteract the resistant strains. Microgravity may hold key to scaling up stem cell cultivation for research, treatment Stem cells are used in a variety of medical therapies, including the treatment of stroke. Currently, scientists have no way of efficiently expanding the cells, a process that may be accelerated in a microgravity environment. During the Microgravity Expanded Stem Cells investigation, crew members will observe cell growth and morphological characteristics in microgravity and analyze gene expression profiles of cells grown on the station. This information will provide insight into how human cancers start and spread, which aids in the development of prevention and treatment plans. Results from this investigation could lead to the treatment of disease and injury in space, as well as provide a way to improve stem cell production for human therapy on Earth. Lightning flashes somewhere on Earth about 45 times per second, according to space-borne lightning detection instruments. This investigation continues those observations using a similar sensor aboard the station. The Lightning Imaging Sensor (STP-H5 LIS) will measure the amount, rate and energy of lightning as it strikes around the world. Understanding the processes that cause lightning and the connections between lightning and subsequent severe weather events is a key to improving weather predictions and saving life and property. From the vantage of the station, the LIS instrument will sample lightning over a swider geographical area than any previous sensor. Future robotic spacecraft will need advanced autopilot systems to help them safely navigate and rendezvous with other objects, as they will be operating thousands of miles from Earth. The Raven (STP-H5 Raven) studies a real-time spacecraft navigation system that provides the eyes and intelligence to see a target and steer toward it safely. Raven uses a complex system to image and track the many visiting vehicles that journey to the space station each year. Equipped with three separate sensors and high-performance, reprogrammable avionics that process imagery, Raven's algorithm converts the collected images into an accurate relative navigation solution between Raven and the other vehicle. Research from Raven can be applied toward unmanned vehicles both on Earth and in space, including potential use for systems in NASA's future human deep space exploration. The Stratospheric Aerosol and Gas Experiment (SAGE) program is one of NASA's longest running Earth-observing programs, providing long-term data to help scientists better understand and care for Earth's atmosphere. SAGE was first operated in 1979 following the Stratospheric Aerosol Measurement (SAM), on the Apollo-Soyuz mission. SAGE III will measure stratospheric ozone, aerosols, and other trace gases by locking onto the sun or moon and scanning a thin profile of the atmosphere. Understanding these measurements will allow national and international leaders to make informed policy decisions regarding the protection and preservation of Earth's ozone layer. Ozone in the atmosphere protects Earth's inhabitants, including humans, plants and animals, from harmful radiation from the sun, which can cause long-term problems such as cataracts, cancer and reduced crop yield. Studying tissue regeneration in space could improve injury treatment on Earth Only a few animals, such as tadpoles and salamanders, can regrow a lost limb, but the onset of this process exists in all vertebrates. Tissue Regeneration-Bone Defect (Rodent Research-4) a U.S. National Laboratory investigation sponsored by the Center for the Advancement of Science in Space (CASIS) and the U.S. Army Medical Research and Materiel Command, studies what prevents other vertebrates such as rodents and humans from re-growing lost bone and tissue, and how microgravity conditions impact the process. Results will provide a new understanding of the biological reasons behind a human's inability to grow a lost limb at the wound site, and could lead to new treatment options for the more than 30% of the patient population who do not respond to current options for chronic non-healing wounds. Crew members in orbit often experience reduced bone density and muscle mass, a potential consequence of microgravity-induced stress. Previous research indicates that reduced gravity can promote cell growth, making microgravity a potentially viable environment for tissue regeneration research. This investigation may be able to shed more light on why bone density decreases in microgravity and whether it may be possible to counteract it.

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