Lipid-hydrogel films for sustained drug release

We report a hybrid system, fabricated from nanostructured lipid particles and polysaccharide based hydrogel, for sustained release applications. Lipid particles were prepared by kinetically stabilizing self-assembled lipid nanostructures whereas the hydrogel was obtained by dissolving kappa-carrageenan (KC) in water. The drug was incorporated in native as well as lipid particles loaded hydrogels, which upon dehydration formed thin films. The kinetics of drug release from these films was monitored by UV–vis spectroscopy while the films were characterized by Fourier transform infra-red (FTIR) spectroscopy and small angle X-ray scattering techniques. Pre-encapsulation of a drug into lipid particles is demonstrably advantageous in certain ways; for instance, direct interactions between KC and drug molecules are prohibited due to the mediation of hydrophobic forces generated by lipid tails. Rapid diffusion of small drug molecules from porous hydrogel network is interrupted by their encapsulation into rather large sized lipid particles. The drug release from the lipid-hydrogel matrix was sustained by an order of magnitude timescale with respect to the release from native hydrogel films. These studies form a strong platform for the development of combined carrier systems for controlled therapeutic applications

Individual Privacy Accounting for Differentially Private Stochastic Gradient Descent

Differentially private stochastic gradient descent (DP-SGD) is the workhorse algorithm for recent advances in private deep learning. It provides a single privacy guarantee to all datapoints in the dataset. We propose output-specific $(\varepsilon,\delta)$-DP to characterize privacy guarantees for individual examples when releasing models trained by DP-SGD. We also design an efficient algorithm to investigate individual privacy across a number of datasets. We find that most examples enjoy stronger privacy guarantees than the worst-case bound. We further discover that the training loss and the privacy parameter of an example are well-correlated. This implies groups that are underserved in terms of model utility simultaneously experience weaker privacy guarantees. For example, on CIFAR-10, the average $\varepsilon$ of the class with the lowest test accuracy is 44.2\% higher than that of the class with the highest accuracy.Comment: Published in Transactions on Machine Learning Research (TMLR

A discontinuous Galerkin formulation for solution of parabolic equations on nonconforming meshes

Non-conforming meshes are frequently employed in multi-component simulations and adaptive refinement. In this work we develop a discontinuous Galerkin framework capable of accommodating non-conforming meshes and apply our approach to analyzing the transient heat conduction problem

The sub-energetic GRB 031203 as a cosmic analogue to GRB 980425

Over the six years since the discovery of the gamma-ray burst GRB 980425, associated with the nearby (distance, ~40 Mpc) supernova 1998bw, astronomers have fiercely debated the nature of this event. Relative to bursts located at cosmological distances, (redshift, z~1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed the explosion was sub-energetic by a factor of 10. Here, we report observations of the radio and X-ray afterglow of the recent z=0.105 GRB 031203 and demonstrate that it too is sub-energetic. Our result, when taken together with the low gamma-ray luminosity, suggest that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. Intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRBs 031203 and 980425) may enable us to reveal their expected large population.Comment: To Appear in Nature, August 5, 200

Selective Pre-training for Private Fine-tuning

Suppose we want to train text prediction models in email clients or word processors. The models must preserve the privacy of user data and adhere to a specific fixed size to meet memory and inference time requirements. We introduce a generic framework to solve this problem. Specifically, we are given a public dataset $D_\text{pub}$ and a private dataset $D_\text{priv}$ corresponding to a downstream task $T$. How should we pre-train a fixed-size model $M$ on $D_\text{pub}$ and fine-tune it on $D_\text{priv}$ such that performance of $M$ with respect to $T$ is maximized and $M$ satisfies differential privacy with respect to $D_\text{priv}$? We show that pre-training on a {\em subset} of dataset $D_\text{pub}$ that brings the public distribution closer to the private distribution is a crucial ingredient to maximize the transfer learning abilities of $M$ after pre-training, especially in the regimes where model sizes are relatively small. Besides performance improvements, our framework also shows that with careful pre-training and private fine-tuning, {\em smaller models} can match the performance of much larger models, highlighting the promise of differentially private training as a tool for model compression and efficiency

Regulation of Calcium-Permeable TRPV2 Channel by Insulin in Pancreatic β-Cells

OBJECTIVE—Calcium-permeable cation channel TRPV2 is expressed in pancreatic β-cells. We investigated regulation and function of TRPV2 in β-cells

Dynamic Structure Factor of Liquid and Amorphous Ge From Ab Initio Simulations

We calculate the dynamic structure factor S(k,omega) of liquid Ge (l-Ge) at temperature T = 1250 K, and of amorphous Ge (a-Ge) at T = 300 K, using ab initio molecular dynamics. The electronic energy is computed using density-functional theory, primarily in the generalized gradient approximation, together with a plane wave representation of the wave functions and ultra-soft pseudopotentials. We use a 64-atom cell with periodic boundary conditions, and calculate averages over runs of up to 16 ps. The calculated liquid S(k,omega) agrees qualitatively with that obtained by Hosokawa et al, using inelastic X-ray scattering. In a-Ge, we find that the calculated S(k,omega) is in qualitative agreement with that obtained experimentally by Maley et al. Our results suggest that the ab initio approach is sufficient to allow approximate calculations of S(k,omega) in both liquid and amorphous materials.Comment: 31 pages and 8 figures. Accepted for Phys. Rev.

The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003

Many past studies of cosmological gamma-ray bursts (GRBs) have been limited because of the large distance to typical GRBs, resulting in faint afterglows. There has long been a recognition that a nearby GRB would shed light on the origin of these mysterious cosmic explosions, as well as the physics of their fireballs. However, GRBs nearer than z=0.2 are extremely rare, with an estimated rate of localisation of one every decade. Here, we report the discovery of bright optical afterglow emission from GRB 030329. Our prompt dissemination and the brilliance of the afterglow resulted in extensive followup (more than 65 telescopes) from radio through X-ray bands, as well as measurement of the redshift, z=0.169. The gamma-ray and afterglow properties of GRB 030329 are similar to those of cosmological GRBs (after accounting for the small distance), making this the nearest known cosmological GRB. Observations have already securely identified the progenitor as a massive star that exploded as a supernova, and we anticipate futher revelations of the GRB phenomenon from studies of this source.Comment: 13 pages, 4 figures. Original tex

Evidence for Cold Accretion: Primitive Gas Flowing onto a Galaxy at z~0.274

We present UV and optical observations from the Cosmic Origins Spectrograph on the Hubble Space Telescope and Keck of a z= 0.27395 Lyman limit system (LLS) seen in absorption against the QSO PG1630+377. We detect H I absorption with log N(HI)=17.06\pm0.05 as well as Mg II, C III, Si III, and O VI in this system. The column densities are readily explained if this is a multi-phase system, with the intermediate and low ions arising in a very low metallicity ([Mg/ H] =-1.71 \pm 0.06) photoionized gas. We identify via Keck spectroscopy and Large Binocular Telescope imaging a 0.3 L_* star-forming galaxy projected 37 kpc from the QSO at nearly identical redshift (z=0.27406, \Delta v = -26 \kms) with near solar metallicity ([O/ H]=-0.20 \pm 0.15). The presence of very low metallicity gas in the proximity of a near-solar metallicity, sub-L_* galaxy strongly suggests that the LLS probes gas infalling onto the galaxy. A search of the literature reveals that such low metallicity LLSs are not uncommon. We found that 50% (4/8) of the well-studied z < 1 LLSs have metallicities similar to the present system and show sub-L_* galaxies with rho < 100 kpc in those fields where redshifts have been surveyed. We argue that the properties of these primitive LLSs and their host galaxies are consistent with those of cold mode accretion streams seen in galaxy simulations.Comment: Accepted for publication in the Astrophysical Journa

An HST Study of the Supernovae Accompanying GRB 040924 and GRB 041006

We present the results from a {\it Hubble Space Telescope/ACS} study of the supernovae associated with gamma-ray bursts 040924 ($z=0.86$) and 041006 ($z=0.71$). We find evidence that both GRBs were associated with a SN 1998bw-like supernova dimmed by $\sim 1.5$ and $\sim 0.3$ magnitudes, respectively, making GRB 040924 the faintest GRB-associated SN ever detected. We study the luminosity dispersion in GRB/XRF-associated SNe and compare to local Type Ibc supernovae from the literature. We find significant overlap between the two samples, suggesting that GRB/XRF-associated SNe are not necessarily more luminous nor produce more $^{56}$Ni than local SNe. Based on the current (limited) datasets, we find that the two samples may share a similar $^{56}$Ni production mechanism.Comment: ApJ accepted (in press). Revised version. High-resolution figures available at http://www.astro.caltech.edu/~ams/GRB-SNe.htm