Efficient proofs of software exploitability for real-world processors

CRAhttps://eprint.iacr.org/2022/1223.pdfPublished versio

Development and Characterization of an Antimicrobial Polydopamine Coating for Conservation of Humpback Whales.

Migration patterns of humpback whales have been monitored using 316L stainless steel (SS) satellite telemetry tags. The potential for tissue infection and necrosis is increased if the bacteria, naturally a part of the diverse microbiome on the skin of humpback whales, can adhere to and colonize the surface of the tags. Polydopamine (pDA) has the potential to prevent the adhesion of one of the most prevalent bacterial strains on the surface of the skin of cetaceans

A Phase II Study of Irinotecan and Carboplatin in Advanced Non-small Cell Lung Cancer with Pharmacogenomic Analysis: Final Report

PurposeWe conducted a phase II study of carboplatin and irinotecan in patients with advanced non-small cell lung cancer (NSCLC). In addition, we studied the correlation between certain genotypes of enzymes involved in irinotecan metabolism with efficacy and toxicity.Patients and MethodsPatients with stage IIIB, IV, or recurrent NSCLC received a combination of irinotecan and carboplatin every 3 weeks at a dose of 200 mg/m2 and area under the curve of 5. Pharmacogenomic analysis was performed on several genes of interest (ABCB1, CYP3A4*1B, ERCC2, GSTP1, UGT1A1*28, and XRCC1).ResultsForty-two patients enrolled between December 2001 and January 2004. Six patients achieved partial responses (14%), and 19 (45%) had stable disease. The median progression-free survival was 6.9 months. The median overall survival was 11.7 months, with 1-year overall survival of 42%. The most common toxicities were hematologic; grade 3 or 4 neutropenia was experienced by 26 patients (62%) during treatment, and 15 patients (36%) experienced grade 3 or 4 thrombocytopenia. The homozygous UGT1A1*28 (7/7) genotype was associated with grade 4 neutropenia in three of four patients (75%), but only eight out of 30 (27%) with 6/6 or 6/7 genotypes experienced grade 4 neutropenia (p = 0.09). None of the 14 patients with the GSTP1 I105V A/A genotype had a partial response, as opposed to five out of 19 (26%) of those with the G/A or G/G genotypes (p = 0.057).ConclusionThe combination of carboplatin and irinotecan is an active combination in NSCLC, with response rates comparable with other platinum-containing doublets. Further studies with irinotecan should incorporate prospective pharmacogenomic analysis to identify markers for response and toxicity

Iterative algorithms for total variation-like reconstructions in seismic tomography

A qualitative comparison of total variation like penalties (total variation, Huber variant of total variation, total generalized variation, ...) is made in the context of global seismic tomography. Both penalized and constrained formulations of seismic recovery problems are treated. A number of simple iterative recovery algorithms applicable to these problems are described. The convergence speed of these algorithms is compared numerically in this setting. For the constrained formulation a new algorithm is proposed and its convergence is proven.Comment: 28 pages, 8 figures. Corrected sign errors in formula (25

Efficient Proofs of Software Exploitability for Real-world Processors

We consider the problem of proving in zero-knowledge the existence of vulnerabilities in executables compiled to run on real-world processors. We demonstrate that it is practical to prove knowledge of real exploits for real-world processor architectures without the need for source code and without limiting our consideration to narrow vulnerability classes. To achieve this, we devise a novel circuit compiler and a toolchain that produces highly optimized, non-interactive zero-knowledge proofs for programs executed on the MSP430, an ISA commonly used in embedded hardware. Our toolchain employs a highly optimized circuit compiler and a number of novel optimizations to construct efficient proofs for program binaries. To demonstrate the capability of our system, we test our toolchain by constructing proofs for challenges in the Microcorruption capture the flag exercises

Nonlinear regularization techniques for seismic tomography

The effects of several nonlinear regularization techniques are discussed in the framework of 3D seismic tomography. Traditional, linear, $\ell_2$ penalties are compared to so-called sparsity promoting $\ell_1$ and $\ell_0$ penalties, and a total variation penalty. Which of these algorithms is judged optimal depends on the specific requirements of the scientific experiment. If the correct reproduction of model amplitudes is important, classical damping towards a smooth model using an $\ell_2$ norm works almost as well as minimizing the total variation but is much more efficient. If gradients (edges of anomalies) should be resolved with a minimum of distortion, we prefer $\ell_1$ damping of Daubechies-4 wavelet coefficients. It has the additional advantage of yielding a noiseless reconstruction, contrary to simple $\ell_2$ minimization (`Tikhonov regularization') which should be avoided. In some of our examples, the $\ell_0$ method produced notable artifacts. In addition we show how nonlinear $\ell_1$ methods for finding sparse models can be competitive in speed with the widely used $\ell_2$ methods, certainly under noisy conditions, so that there is no need to shun $\ell_1$ penalizations.Comment: 23 pages, 7 figures. Typographical error corrected in accelerated algorithms (14) and (20

Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

<p>Abstract</p> <p>Background</p> <p>PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor^®EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.</p> <p>Methods</p> <p>In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.</p> <p>Results</p> <p>NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.</p> <p>Conclusion</p> <p>These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.</p

Molecular platforms for targeted drug delivery

The targeted delivery of bioactive molecules to the appropriate site of action, one of the critical focuses of pharmaceutical research, improves therapeutic outcomes and increases safety at the same time; a concept envisaged by Ehrlich over 100 years ago when he described the "magic bullet" model. In the following decades, a considerable amount of research effort combined with enormous investment has carried selective drug targeting into clinical practice via the advent of monoclonal antibodies (mAbs) and antibody-drug conjugates derivatives. Additionally, a deeper understanding of physiopathological conditions of disease has permitted the tailored design of targeted drug delivery platforms that carry drugs, many copies of the same drug, and different drugs in combination to the appropriate site of action least selectively or preferentially. The acquired know-how has provided the field with the design rationale to develop a successful delivery system that will provide new and improved means to treat many intractable diseases and disorders. In this review, we discuss a wide range of molecular platforms for drug delivery, and focus on those with more success in the clinic, given their potential for targeted therapies