Pushing indium phosphide quantum dot emission deeper into the near infrared

Cadmium-free near infrared (NIR) emitting quantum dots (QDs) have significant potential for multiplexed tissue-depth imaging applications in the first optical tissue window (i.e., 650 – 900 nm). Indium phosphide (InP) chemistry provides one of the more promising cadmium-free options for biomedical imaging, but the full tunability of this material has not yet been achieved. Specifically, InP QD emission has been tuned from 480 – 730 nm in previous literature reports, but examples of samples emitting from 730 nm to the InP bulk bandgap limit of 925 nm are lacking. We hypothesize that by generating inverted structures comprising ZnSe/InP/ZnS in a core/shell/shell heterostructure, optical emission from the InP shell can be tuned by changing the InP shell thickness, including pushing deeper into the NIR than current InP QDs. Colloidal synthesis methods including hot injection precipitation of the ZnSe core and a modified successive ion layer adsorption and reaction (SILAR) method for stepwise shell deposition were used to promote growth of core/shell/shell materials with varying thicknesses of the InP shell. By controlling the number of injections of indium and phosphorous precursor material, the emission peak was tuned from 515 nm to 845 nm (2.41 – 1.47 eV) with consistent full width half maximum (FWHM) values of the emission peak ~0.32 eV. To confer water solubility, the nanoparticles were encapsulated in PEGylated phospholipid micelles, and multiplexing of NIR-emitting InP QDs was demonstrated using an IVIS imaging system. These materials show potential for multiplexed imaging of targeted QD contrast agents in the first optical tissue window

piggyBac transformation of the New World screwworm, \u3ci\u3eCochliomyia hominivorax\u3c/i\u3e, produces multiple distinct mutant strains

Sterile insect technique (SIT) programs are designed to eradicate pest species by releasing mass-reared, sterile insects into an infested area. The first major implementation of SIT was the New World Screwworm Eradication Program, which successfully eliminated the New World screwworm (NWS), Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), from the Continental US, Mexico and much of Central America. Ionizing radiation is currently used for sterilization, but transgenic insect techniques could replace this method, providing a safer, more cost-effective alternative. Genetic transformation methods have been demonstrated in NWS, and verified by Southern blot hybridization, PCR and sequencing of element insertion junctions. A lethal insertional mutation and enhancer detection-like phenotypic expression variations are presented and discussed. In addition to supporting the eradication efforts, transformation methods offer potential means to identify genes and examine gene function in NWS

A Variable Metric Variant of the Karmarkar Algorithm for Linear Programming

The most time-consuming part of the Karmarkar algorithm for linear programming is the projection of a vector onto the nullspace of a matrix that changes at each iteration. We present a variant of the Karmarkar algorithm that uses standard variable-metric techniques in an innovative way to approximate this projection. In limited tests, this modification greatly reduces the number of matrix factorizations needed for the solution of linear programming problems

Mesenchymale stromale stamceltherapie voor emfyseem:Een kijkje in de toekomst

Verlies van longblaasjes bij longemfyseem is onherstelbaar. Regeneratie door stamcellen wordt als een veelbelovende toekomstige behandeling gezien voor patiënten met emfyseem. Een kenmerk van stamcellen is hun vermogen tot proliferatie en differentiatie; mesenchymale stromale stamcellen kunnen echter ook ontsteking remmen en reparatie bevorderen in hun directe omgeving. De extracellulaire matrix biedt daarbij niet alleen ruimtelijke structuur aan, maar bepaalt ook hoe mesenchymale stromale stamcellen zich gedragen en ontwikkelen. Toediening van mesenchymale stromale stamcellen aan diermodellen met emfyseem liet tekenen van weefselherstel zien, maar fundamentele vragen over de optimale dosering, herkomst, en toedieningsroute zijn tot nu toe helaas onvoldoende beantwoord. Ook het werkingsmechanisme is onduidelijk. Het fabriceren (bio-engeneering) van nieuwe longen is bij ratten gelukt door uitgenomen longen te ontdoen van cellen (decellulariseren), en de overblijvende eiwitvezelstructuur met eigen stamcellen te recellulariseren. Toediening van stamcellen aan patiënten met longemfyseem werd tot nu toe nauwelijks onderzocht. Intraveneuze toediening in kleine ‘safety studies’ bleek veilig maar klinisch niet effectief. (NED TIJDSCHR ALLERGIE & ASTMA 2017;17:12-1

Pretreatment integrase strand transfer inhibitor resistance in North Carolina from 2010-2016

Objective: We sought to define the prevalence of pretreatment integrase strand transfer inhibitor (INSTI) resistance and assess the transmission networks of those with pretreatment INSTI resistance. Design: A retrospective cohort study of HIV-positive patients with genotypic resistance testing sent to a single referral laboratory in North Carolina between 2010 and 2016. Methods: We linked genotype and public health data for in-care HIV-positive individuals to determine the prevalence of INSTI resistance among treatment-naive (defined as those with a first genotype ≤3 months after diagnosis) and treatment-experienced (defined as those with a first genotype >3 months after diagnosis) patients. We performed molecular and phylogenetic analyses to assess whether pretreatment INSTI resistance mutations represented clustered HIV transmission. Results: Of 8825 individuals who contributed sequences for protease, reverse transcriptase, or INSTI genotypic resistance testing during the study period, 2784 (31%) contributed at least one sequence for INSTI resistance testing. Of these, 840 were treatment-naive individuals and 20 [2.4%, 95% confidence interval (CI): 1.5, 3.6%] had INSTI mutations; only two (0.2%, 95% CI: 0.02, 0.9%) had major mutations. Of 1944 treatment-experienced individuals, 9.6% (95% CI: 8.3, 11.0%) had any INSTI mutation and 7.0% (95% CI: 5.9, 8.3%) had major mutations; the prevalence of INSTI mutations among treatment-experienced patients decreased overtime (P<0.001). In total 12 of 20 individuals with pretreatment INSTI mutations were part of 10 molecular transmission clusters; only one cluster shared identical minor mutations. Conclusion: The prevalence of major pretreatment INSTI resistance is very low. Pretreatment INSTI mutations do not appear to represent clustered HIV transmission

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations

OBJECTIVE: To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance. DESIGN: Prospective clinical cohort of HIV-infected patients at the University of North Carolina. METHODS: Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016. RESULTS: A total of 3682 patients contributed 23 169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes. CONCLUSION: Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently

High-energy physics with particles carrying non-zero orbital angular momentum

Thanks to progress in optics in the past two decades, it is possible to create photons carrying well-defined non-zero orbital angular momentum (OAM). Boosting these photons into high-energy range preserving their OAM seems feasible. Intermediate energy electrons with OAM have also been produced recently. One can, therefore, view OAM as a new degree of freedom in high-energy collisions and ask what novel insights into particles' structure and interactions it can bring. Here we discuss generic features of scattering processes involving particles with OAM in the initial state. We show that they make it possible to perform a Fourier analysis of a plane wave cross section with respect to the azimuthal angles of the initial particles, and to probe the autocorrelation function of the amplitude, a quantity inaccessible in plane wave collisions.Comment: 7 pages, 1 figure, talk given at the workshop "30 years of strong interactions", Spa, Belgium, 6-8 April 201

Clinical and Molecular Profiling to Develop a Potential Prediction Model for the Response to Alemtuzumab Therapy for Acute Kidney Transplant Rejection

Alemtuzumab, a monoclonal antibody that depletes CD52‐bearing immune cells, is an effective drug for the treatment of severe or glucocorticoid‐resistant acute kidney transplant rejection (AR). Patient‐specific predictions on treatment response are, however, urgently needed, given the severe side effects of alemtuzumab. This study developed a multidimensional prediction model with the aim of generating clinically useful prognostic scores for the response to alemtuzumab. Clinical and histological characteristics were collected retrospectively from patients who were treated with alemtuzumab for AR. In addition, targeted gene expression profiling of AR biopsy tissues was performed. Least absolute shrinkage and selection operator (LASSO) logistic regression modeling was used to construct the ALEMtuzumab for Acute Rejection (ALEMAR) prognostic score. Response to alemtuzumab was defined as patient and allograft survival and at least once an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m(2) during the first 6 months after treatment. One hundred fifteen patients were included, of which 84 (73%) had a response to alemtuzumab. The ALEMAR‐score accurately predicted the chance of response. Gene expression analysis identified 13 differentially expressed genes between responders and nonresponders. The combination of the ALEMAR‐score and selected genes resulted in improved predictions of treatment response. The present preliminary prediction model is potentially helpful for the development of stratified alemtuzumab treatment for acute kidney transplant rejection but requires validation

Human Immunodeficiency Virus Type 1 Phylodynamics to Detect and Characterize Active Transmission Clusters in North Carolina

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) phylodynamics can be used to monitor epidemic trends and help target prevention through identification and characterization of transmission clusters. METHODS: We analyzed HIV-1 pol sequences sampled in North Carolina from 1997 to 2014. Putative clusters were identified using maximum-likelihood trees and dated using Bayesian Markov Chain Monte Carlo inference. Active clusters were defined as clusters including internal nodes from 2009 to 2014. Effective reproductive numbers (Re) were estimated using birth-death models for large clusters that expanded ≥2-fold from 2009 to 2014. RESULTS: Of 14 921 persons, 7508 (50%) sequences were identified in 2264 clusters. Only 288 (13%) clusters were active from 2009 to 2014; 37 were large (10-36 members). Compared to smaller clusters, large clusters were increasingly populated by men and younger persons; however, nearly 60% included ≥1 women. Clusters with ≥3 members demonstrated assortative mixing by sex, age, and sample region. Of 15 large clusters with ≥2-fold expansion, nearly all had Re approximately 1 by 2014. CONCLUSIONS: Phylodynamics revealed transmission cluster expansion in this densely sampled region and allowed estimates of Re to monitor active clusters, showing the propensity for steady, onward propagation. Associations with clustering and cluster characteristics vary by cluster size. Harnessing sequence-derived epidemiologic parameters within routine surveillance could allow refined monitoring of local subepidemics