Significance of Premature Stop Codons in \u3cem\u3eenv\u3c/em\u3e of Simian Immunodeficiency Virus

The location of the translational termination codon for the transmembrane protein (TMP) varies in three infectious molecular clones of simian immunodeficiency virus from macaques (SIVmac). The SIVmac251 and SIVmac142 infectious clones have premature stop signals that differ in location by one codon; transfection of these DNAs into human HUT-78 cells yielded virus with a truncated TMP (28 to 30 kilodaltons [kDa]). The SIVmac239 infectious clone does not have a premature stop codon in its TMP-coding region. Transfection of HUT-78 cells with this clone initially yielded virus with a full-length TMP (41 kDa). At 20 to 30 days posttransfection, SIVmac239 virus with a 41-kDa TMP gradually disappeared coincident with the emergence of a virus with a 28-kDa TMP. Virus production dramatically increased in parallel with the emergence of a virus with a 28-kDa TMP. Sequence analysis of viral DNAs from these cultures showed that premature stop codons arising by point mutation were responsible for the change in size of the TMP with time. A similar selective pressure for truncated forms of TMP was observed when the SIVmac239 clone was transfected into human peripheral blood lymphocytes (PBL). In contrast, no such selective pressure was observed in macaque PBL. When the SIVmac239 clone was transfected into macaque PBL and the resultant virus was serially passaged in macaque PBL, the virus replicated very well and maintained a 41-kDa TMP for 80 days in culture. Macaque monkeys were infected with SIVmac239 having a 28-kDa TMP; virus subsequently recovered from T4-enriched lymphocytes of peripheral blood showed only the 41-kDa form of TMP. These results indicate that the natural form of TMP in SIVmac is the full-length 41-kDa TMP, just as in human immunodeficiency virus type 1. Viruses with truncated forms of TMP appear to result from mutation and selection during propagation in unnatural human cells

Outcomes in HIV-Infected Adults With Tuberculosis at Clinics With and Without Co-Located HIV Clinics in Botswana

SETTING Gaborone, Botswana. OBJECTIVE To determine if starting anti-tuberculosis treatment at clinics in Gaborone without co-located human immunodeficiency virus (HIV) clinics would delay time to highly active antiretroviral therapy (HAART) initiation and be associated with lower survival compared to starting anti-tuberculosis treatment at clinics with on-site HIV clinics. DESIGN Retrospective cohort study. Subjects were HAART-naïve, aged ≥21 years with pulmonary tuberculosis (TB), HIV and CD4 counts ≤250 cells/mm3 initiating anti-tuberculosis treatment between 2005 and 2010. Survival at completion of anti-tuberculosis treatment or at 6 months post-treatment initiation and time to HAART after anti-tuberculosis treatment initiation were compared by clinic type. RESULTS Respectively 259 and 80 patients from clinics without and with on-site HIV facilities qualified for the study. Age, sex, CD4, baseline sputum smears and loss to follow-up rate were similar by clinic type. Mortality did not differ between clinics without or with on-site HIV clinics (20/250, 8.0% vs. 8/79, 10.1%, relative risk 0.79, 95%CI 0.36–1.72), nor did median time to HAART initiation (respectively 63 and 66 days, P = 0.53). CONCLUSION In urban areas where TB and HIV programs are separate, geographic co-location alone without further integration may not reduce mortality or time to HAART initiation among co-infected patients

State-Insensitive Trapping of Alkaline-Earth Atoms in a Nanofiber-Based Optical Dipole Trap

Neutral atoms trapped in the evanescent optical potentials of nanotapered optical fibers are a promising platform for developing quantum technologies and exploring fundamental science, such as quantum networks and quantum electrodynamics. Building on the successful advancements with trapped alkali atoms, here we demonstrate a state-insensitive optical dipole trap for strontium-88, an alkaline-earth atom, using the evanescent fields of a nanotapered optical fiber. Leveraging the low laser-cooling temperatures of $\sim\!\!1~\mu$K readily achievable with strontium, we demonstrate trapping in record low trap depths corresponding to $\sim\!\!3~\mu$K. Further, employing a double magic wavelength trapping scheme, we realize state-insensitive trapping on the kilohertz-wide 5s^{2}\;^{1}\!S_{0}-5s5p\;^{3}\!P_{1,|m|=1} cooling transition, which we verify by performing near-surface high-resolution spectroscopy of the atomic transition. This allows us to experimentally find and verify the state insensitivity of the trap nearby a theoretically predicted magic wavelength of 435.827(25) nm. Given the non-magnetic ground state and low collisional scattering length of strontium-88, this work also lays the foundation for developing versatile and robust matter-wave atomtronic circuits over nanophotonic waveguides.Comment: 14 pages, 15 figure

ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import

Heterogeneous Delays in Neural Networks

We investigate heterogeneous coupling delays in complex networks of excitable elements described by the FitzHugh-Nagumo model. The effects of discrete as well as of uni- and bimodal continuous distributions are studied with a focus on different topologies, i.e., regular, small-world, and random networks. In the case of two discrete delay times resonance effects play a major role: Depending on the ratio of the delay times, various characteristic spiking scenarios, such as coherent or asynchronous spiking, arise. For continuous delay distributions different dynamical patterns emerge depending on the width of the distribution. For small distribution widths, we find highly synchronized spiking, while for intermediate widths only spiking with low degree of synchrony persists, which is associated with traveling disruptions, partial amplitude death, or subnetwork synchronization, depending sensitively on the network topology. If the inhomogeneity of the coupling delays becomes too large, global amplitude death is induced

Small-Size Resonant Photoacoustic Cell of Inclined Geometry for Gas Detection

A photoacoustic cell intended for laser detection of trace gases is represented. The cell is adapted so as to enhance the gas-detection performance and, simultaneously, to reduce the cell size. The cell design provides an efficient cancellation of the window background (a parasite response due to absorption of laser beam in the cell windows) and acoustic isolation from the environment for an acoustic resonance of the cell. The useful photoacoustic response from a detected gas, window background and noise are analyzed in demonstration experiments as functions of the modulation frequency for a prototype cell with the internal volume ~ 0.5 cm^3. The minimal detectable absorption for the prototype is estimated to be ~ 1.2 10^{-8} cm^{-1} W Hz^{-1/2}.Comment: 11 pages, 5 figure

VennPlex--a novel Venn diagram program for comparing and visualizing datasets with differentially regulated datapoints.

With the development of increasingly large and complex genomic and proteomic data sets, an enhancement in the complexity of available Venn diagram analytical programs is becoming increasingly important. Current freely available Venn diagram programs often fail to represent extra complexity among datasets, such as regulation pattern differences between different groups. Here we describe the development of VennPlex, a program that illustrates the often diverse numerical interactions among multiple, high-complexity datasets, using up to four data sets. VennPlex includes versatile output features, where grouped data points in specific regions can be easily exported into a spreadsheet. This program is able to facilitate the analysis of two to four gene sets and their corresponding expression values in a user-friendly manner. To demonstrate its unique experimental utility we applied VennPlex to a complex paradigm, i.e. a comparison of the effect of multiple oxygen tension environments (1–20% ambient oxygen) upon gene transcription of primary rat astrocytes. VennPlex accurately dissects complex data sets reliably into easily identifiable groups for straightforward analysis and data output. This program, which is an improvement over currently available Venn diagram programs, is able to rapidly extract important datasets that represent the variety of expression patterns available within the data sets, showing potential applications in fields like genomics, proteomics, and bioinformatics

A highly efficient multi-core algorithm for clustering extremely large datasets

<p>Abstract</p> <p>Background</p> <p>In recent years, the demand for computational power in computational biology has increased due to rapidly growing data sets from microarray and other high-throughput technologies. This demand is likely to increase. Standard algorithms for analyzing data, such as cluster algorithms, need to be parallelized for fast processing. Unfortunately, most approaches for parallelizing algorithms largely rely on network communication protocols connecting and requiring multiple computers. One answer to this problem is to utilize the intrinsic capabilities in current multi-core hardware to distribute the tasks among the different cores of one computer.</p> <p>Results</p> <p>We introduce a multi-core parallelization of the k-means and k-modes cluster algorithms based on the design principles of transactional memory for clustering gene expression microarray type data and categorial SNP data. Our new shared memory parallel algorithms show to be highly efficient. We demonstrate their computational power and show their utility in cluster stability and sensitivity analysis employing repeated runs with slightly changed parameters. Computation speed of our Java based algorithm was increased by a factor of 10 for large data sets while preserving computational accuracy compared to single-core implementations and a recently published network based parallelization.</p> <p>Conclusions</p> <p>Most desktop computers and even notebooks provide at least dual-core processors. Our multi-core algorithms show that using modern algorithmic concepts, parallelization makes it possible to perform even such laborious tasks as cluster sensitivity and cluster number estimation on the laboratory computer.</p

Training Hospital Providers in Basic CPR Skills in Botswana: Acquisition, Retention and Impact of Novel Training Techniques

Objective Globally, one third of deaths each year are from cardiovascular diseases, yet no strong evidence supports any specific method of CPR instruction in a resource-limited setting. We hypothesized that both existing and novel CPR training programs significantly impact skills of hospital-based healthcare providers (HCP) in Botswana. Methods HCP were prospectively randomized to 3 training groups: instructor led, limited instructor with manikin feedback, or self-directed learning. Data was collected prior to training, immediately after and at 3 and 6 months. Excellent CPR was prospectively defined as having at least 4 of 5 characteristics: depth, rate, release, no flow fraction, and no excessive ventilation. GEE was performed to account for within subject correlation. Results Of 214 HCP trained, 40% resuscitate ≥1/month, 28% had previous formal CPR training, and 65% required additional skills remediation to pass using AHA criteria. Excellent CPR skill acquisition was significant (infant: 32% vs. 71%, p \u3c 0.01; adult 28% vs. 48%, p \u3c 0.01). Infant CPR skill retention was significant at 3 (39% vs. 70%, p \u3c 0.01) and 6 months (38% vs. 67%, p \u3c 0.01), and adult CPR skills were retained to 3 months (34% vs. 51%, p = 0.02). On multivariable analysis, low cognitive score and need for skill remediation, but not instruction method, impacted CPR skill performance. Conclusions HCP in resource-limited settings resuscitate frequently, with little CPR training. Using existing training, HCP acquire and retain skills, yet often require remediation. Novel techniques with increased student: instructor ratio and feedback manikins were not different compared to traditional instruction

Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks

<p>Abstract</p> <p>Background</p> <p>The identification of genomic signatures of colorectal cancer for risk stratification requires the study of large series of cancer patients with an extensive clinical follow-up. Multicentric clinical studies represent an ideal source of well documented archived material for this type of analyses.</p> <p>Methods</p> <p>To verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.</p> <p>Results</p> <p>The majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.</p> <p>Conclusion</p> <p>Archival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.</p