Does femtosecond time-resolved second-harmonic generation probe electron temperatures at surfaces?

Femtosecond pump-probe second-harmonic generation (SHG) and transient linear reflectivity measurements were carried out on polycrystalline Cu, Ag and Au in air to analyze whether the electron temperature affects Fresnel factors or nonlinear susceptibilities, or both. Sensitivity to electron temperatures was attained by using photon energies near the interband transition threshold. We find that the nonlinear susceptibility carries the electron temperature dependence in case of Ag and Au, while for Cu the dependence is in the Fresnel factors. This contrasting behavior emphasizes that SHG is not a priori sensitive to electron dynamics at surfaces or interfaces, notwithstanding its cause.Comment: 11 pages, 4 figure

Resonant hyper-Raman scattering in spherical quantum dots

A theoretical model of resonant hyper-Raman scattering by an ensemble of spherical semiconductor quantum dots has been developed. The electronic intermediate states are described as Wannier-Mott excitons in the framework of the envelope function approximation. The optical polar vibrational modes of the nanocrystallites (vibrons) and their interaction with the electronic system are analized with the help of a continuum model satisfying both the mechanical and electrostatic matching conditions at the interface. An explicit expression for the hyper-Raman scattering efficiency is derived, which is valid for incident two-photon energy close to the exciton resonances. The dipole selection rules for optical transitions and Fr\"ohlich-like exciton-lattice interaction are derived: It is shown that only exciton states with total angular momentum $L=0,1$ and vibrational modes with angular momentum $l_p=1$ contribute to the hyper-Raman scattering process. The associated exciton energies, wavefunctions, and vibron frequencies have been obtained for spherical CdSe zincblende-type nanocrystals, and the corresponding hyper-Raman scattering spectrum and resonance profile are calculated. Their dependence on the dot radius and the influence of the size distribution on them are also discussed.Comment: 12 pages REVTeX (two columns), 2 tables, 8 figure

Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2

Influenza A virus’s (IAV’s) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV’s genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem–loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term ‘programmable antivirals’, with implications for antiviral prophylaxis and post-exposure therapy

Renal Cell Carcinoma with Unusual Metastasis to the Small Intestine Manifesting as Extensive Polyposis: Successful Management with Intraoperative Therapeutic Endoscopy

We present here a rare clinical case of a 53-year-old gentleman with metastasis from renal cell carcinoma (RCC) to the small intestine presenting with extensive polyposis and massive gastrointestinal bleeding which was successfully managed with intraoperative endoscopic polypectomy and segmental small bowel resection. The patient presented with melena 2 weeks after right nephrectomy for RCC. Capsule endoscopy found extensive polyposis throughout the small bowel, and the histological features confirmed the diagnosis of metastatic RCC. The patient eventually underwent laparotomy with intraoperative endoscopy of the entire small bowel. Most of the polyps were removed by snare polypectomy. Three segments of the small bowel with extensive transmural involvement had to be resected with primary anastomosis. In the 2 months following his surgery, the patient had no further evidence of gastrointestinal bleeding. The decision of meticulously removing close to 100 polyps by intraoperative endoscopy prevented the patient from requiring total small bowel resection and lifelong dependence on parenteral nutrition. In conclusion, gastrointestinal bleeding in a patient with known RCC should always trigger full gastrointestinal work-up including capsule endoscopy and, if necessary, double balloon enteroscopy

Enhanced gene repair mediated by methyl-CpG-modified single-stranded oligonucleotides

Gene editing mediated by oligonucleotides has been shown to induce stable single base alterations in genomic DNA in both prokaryotic and eukaryotic organisms. However, the low frequencies of gene repair have limited its applicability for both basic manipulation of genomic sequences and for the development of therapeutic approaches for genetic disorders. Here, we show that single-stranded oligodeoxynucleotides (ssODNs) containing a methyl-CpG modification and capable of binding to the methyl-CpG binding domain protein 4 (MBD4) are able to induce >10-fold higher levels of gene correction than ssODNs lacking the specific modification. Correction was stably inherited through cell division and was confirmed at the protein, transcript and genomic levels. Downregulation of MBD4 expression using RNAi prevented the enhancement of gene correction efficacy obtained using the methyl-CpG-modified ssODN, demonstrating the specificity of the repair mechanism being recruited. Our data demonstrate that efficient manipulation of genomic targets can be achieved and controlled by the type of ssODN used and by modulation of the repair mechanism involved in the correction process. This new generation of ssODNs represents an important technological advance that is likely to have an impact on multiple applications, especially for gene therapy where permanent correction of the genetic defect has clear advantages over viral and other nonviral approaches currently being tested

Lattice Dynamics of II-VI materials using adiabatic bond charge model

We extend the adiabatic bond charge model, originally developed for group IV semiconductors and III-V compounds, to study phonons in more ionic II-VI compounds with a zincblende structure. Phonon spectra, density of states and specific heats are calculated for six II-VI compounds and compared with both experimental data and the results of other models. We show that the 6-parameter bond charge model gives a good description of the lattice dynamics of these materials. We also discuss trends in the parameters with respect to the ionicity and metallicity of these compounds.Comment: 16 pages of RevTex with 3 figures submitted as a uuencode compressed tar fil

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Efficient Learning and Feature Selection in High Dimensional Regression

We present a novel algorithm for efficient learning and feature selection in high-dimensional regression problems. We arrive at this model through a modification of the standard regression model, enabling us to derive a probabilistic version of the well-known statistical regression technique of backfitting. Using the expectation-maximization algorithm, along with variational approximation methods to overcome intractability, we extend our algorithm to include automatic relevance detection of the input features. This variational Bayesian least squares (VBLS) approach retains its simplicity as a linear model, but offers a novel statistically robust black-box approach to generalized linear regression with high-dimensional inputs. It can be easily extended to nonlinear regression and classification problems. In particular, we derive the framework of sparse Bayesian learning, the relevance vector machine, with VBLS at its core, offering significant computational and robustness advantages for this class of methods. The iterative nature of VBLS makes it most suitable for real-time incremental learning, which is crucial especially in the application domain of robotics, brain-machine interfaces, and neural prosthetics, where real-time learning of models for control is needed. We evaluate our algorithm on synthetic and neurophysiological data sets, as well as on standard regression and classification benchmark data sets, comparing it with other competitive statistical approaches and demonstrating its suitability as a drop-in replacement for other generalized linear regression techniques