Generation of Lamprey Monoclonal Antibodies (Lampribodies) Using the Phage Display System.

The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent VLRB antibodies were isolated from sea lamprey larvae after immunization with model antigens. Further, the cloned VLR cDNAs from activated lamprey leukocytes were transfected into human cell lines or yeast to select best binders. Here, we expand on the overall utility of the VLRB technology by introducing it into a filamentous phage display system. We first tested the efficacy of isolating phage into which known VLRB molecules were cloned after a series of dilutions. These experiments showed that targeted VLRB clones could easily be recovered even after extensive dilutions (1 to 109). We further utilized the system to isolate target-specific "lampribodies" from phage display libraries from immunized animals and observed an amplification of binders with relative high affinities by competitive binding. The lampribodies can be individually purified and ostensibly utilized for applications for which conventional monoclonal antibodies are employed

Atmospheric neutron measurements with the SONTRAC science model

–The SOlar Neutron TRACking (SONTRAC) telescope was originally developed to measure the energy spectrum and incident direction of neutrons produced in solar flares, in the energy range 20 - 250 MeV. While developed primarily for solar physics, the SONTRAC detector may be employed in virtually any application requiring both energy measurement and imaging capabilities. The SONTRAC Science Model (SM) is presently being operated at the University of New Hampshire (UNH) as a ground-based instrument to investigate the energy spectrum, zenith and azimuth angle dependence of the cosmic-ray induced sea-level atmospheric neutron flux. SONTRAC measurements are based on the non-relativistic double scatter of neutrons off ambient protons within a block of scintillating fibers. Using the n-p elastic double-scatter technique, it is possible to uniquely determine the neutron’s energy and direction on an event-by-event basis. The 3D SM consists of a cube of orthogonal plastic scintillating fiber layers with 5 cm sides, read out by two CCD cameras. Two orthogonal imaging chains allow full 3D reconstruction of scattered proton tracks

Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD.

Purpose3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD.MethodsWe performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases.ResultsWe determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD.ConclusionOur study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.Genet Med 17 8, 660-667

Optimal Guidance of a Relay Aircraft to Extend Small Unmanned Aircraft Range

This paper developed guidance laws to optimally and autonomously position a relay Micro Aerial Vehicle (MAV) to provide an operator with real-time Intelligence, Surveillance, and Reconnaissance (ISR) by relaying communication and video signals from a rover MAV to the base, thus extending the rover\u27s reach. The ISR system is comprised of two MAVs, the Relay and the Rover, and a Base. The Relay strives to position itself so as to minimize the radio frequency (RF) power required for maintaining communications between the Rover and the Base, while the Rover performs the ISR mission, which may maximize the required RF power. The optimal control of the Relay MAV then entails the solution of a differential game. Applying Pontryagin\u27s Maximum Principle yields a standard, albeit nonlinear, Two-Point Boundary Value Problem (TPBVP). Suboptimal solutions are first obtained as an aid in solving the TPBVP which yields the solution of the differential game. One suboptimal approach is based upon the geometry of the ISR system: The midpoint between the Rover and the Base is the ideal location which minimizes the RF power required, so the Relay heads toward that point—assuming that the Rover is stationary. At the same time, to maximize the rate of required RF power, the Rover moves in the opposite direction of the Relay—assuming the Relay is stationary. These are optimal strategies in the end-game, but it is suboptimal to use them throughout the game. Another suboptimal approach investigated envisions the Rover to remain stationary and solves for the optimal path for the Relay to minimize the RF power requirement. This one-sided optimization problem is analyzed using a Matlab-based optimization program, GPOCS, which uses the Gauss pseudospectral method of discretization. The results from GPOCS corroborated with the geometry-based suboptimal Relay strategy of heading straight toward the midpoint between the Rover and the Base. The suboptimal solutions are readily implementable for real-time operation and are used to facilitate the solutions of the TPBVP

Immune factors preceding diagnosis of glioma: a Prostate Lung Colorectal Ovarian Cancer Screening Trial nested case-control study.

BackgroundEpidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.MethodsWe conducted a nested case-control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.ResultsA family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend <.0001).ConclusionThe results from this prospective prediagnostic study suggest that several immune-related factors are associated with glioma risk. The association observed for TGF-β1 when sampling closer to the time of diagnosis may reflect the nascent brain tumor's feedback on immune function

A genomic view of the NOD-like receptor family in teleost fish: identification of a novel NLR subfamily in zebrafish

<p>Abstract</p> <p>Background</p> <p>A large multigene family of NOD-like receptor (NLR) molecules have been described in mammals and implicated in immunity and apoptosis. Little information, however, exists concerning this gene family in non-mammalian taxa. This current study, therefore, provides an in-depth investigation of this gene family in lower vertebrates including extensive phylogenetic comparison of zebrafish NLRs with orthologs in tetrapods, and analysis of their tissue-specific expression.</p> <p>Results</p> <p>Three distinct NLR subfamilies were identified by mining genome databases of various non-mammalian vertebrates; the first subfamily (NLR-A) resembles mammalian NODs, the second (NLR-B) resembles mammalian NALPs, while the third (NLR-C) appears to be unique to teleost fish. In zebrafish, NLR-A and NLR-B subfamilies contain five and six genes respectively. The third subfamily is large, containing several hundred NLR-C genes, many of which are predicted to encode a C-terminal B30.2 domain. This subfamily most likely evolved from a NOD3-like molecule. Gene predictions for zebrafish NLRs were verified using sequence derived from ESTs or direct sequencing of cDNA. Reverse-transcriptase (RT)-PCR analysis confirmed expression of representative genes from each subfamily in selected tissues.</p> <p>Conclusion</p> <p>Our findings confirm the presence of multiple NLR gene orthologs, which form a large multigene family in teleostei. Although the functional significance of the three major NLR subfamilies is unclear, we speculate that conservation and abundance of NLR molecules in all teleostei genomes, reflects an essential role in cellular control, apoptosis or immunity throughout bony fish.</p

Orbital-free Bond Breaking via Machine Learning

Machine learning is used to approximate the kinetic energy of one dimensional diatomics as a functional of the electron density. The functional can accurately dissociate a diatomic, and can be systematically improved with training. Highly accurate self-consistent densities and molecular forces are found, indicating the possibility for ab-initio molecular dynamics simulations