gebhart/patrepeval huggingface dataset:
Abstract IA07: Defining, Optimizing, and Altering the Specificities of CRISPR-Cas Nucleases (2017)

Abstract RNA-guided CRISPR-Cas nucleases are now widely used for research and are also being rapidly developed as novel therapeutics for various human diseases. In this talk, I will discuss methods developed by our group that enable unbiased, genome-wide assessment of off-target cleavage specificities of CRISPR-Cas nucleases in human cells. I will also summarize our efforts to use protein engineering to create CRISPR-Cas nuclease variants that robustly show substantially reduced off-target effects and/or altered DNA recognition specificities. Taken together, our results have yielded reagents, methods, and insights that will be important for research applications and potential clinical translation of these programmable nucleases. Citation Format: J. Keith Joung. Defining, Optimizing, and Altering the Specificities of CRISPR-Cas Nucleases [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA07.
EXTRACTION OF HEAVY METALS BY MERCAPTANS ATTACHED TO SILICA GEL BY A CORKSCREW MECHANISM (2002)

Saturated, straight chain mercaptans were attached to silica gel and used as coordinating agents for removal of cadmium(II), copper(II), lead(II), and nickel(II) ions from standard solutions. It is believed that the mercaptans become wedged in the silica pores, but are available for reaction. Four thiols were used, viz., 1-hexanethiol, 1-dodecanethiol, 1-hexadecanethiol, and 1-octadecanethiol. Standard solutions of metals (1.57 mM) were stirred with the supported mercaptans for two hours, and at 25 degrees C, and the sample supernatants were analyzed using atomic absorption spectrometry. At pH = 8, the percent removal was 99 (Cd), 91.5 (Cu), 80.8 (Pb), and 97 (Ni). It was possible to acidify the metal-containing solids, and regenerate the supported chelating agents.
Development of copper sulfide/cadmium sulfide thin-film solar cells (1982)

The most important accomplishments during this period were to demonstrate and to elucidate further the complex effects that occur during the aging of Cu/sub 2/S/CdS thin-film solar cells in flowing wet oxygen. There are two distinct effects. At constant illumination, the short-circuit current of cells aged at room temperature consistently decreases with time. The second effect, related to diode opposing current, is more involved and may result from several competing mechanisms. Over the short term (approx. 4 to 5 hours), the magnitude of diode opposing current decreases. After approx. 20 hours of aging, opposing current generally returns to the level achieved after hydrogen annealing which immediately preceded the aging sequence. Optical measurements of the spectral transmission of the Cu/sub 2/S layers in a cell content have been made using a silicon detector epoxied to the back of a CdS cell after the copper foil substrate was removed. There is no significant change in Cu/sub 2/S transmission behavior for wavelengths ranging from 525 to 1000 nm during wet-oxygen aging for periods of 2 to 36 hours. This suggests that the decrease in J/sub SC/ at constant illumination, for the aging experiments in a flowing wet-oxygen ambient, arises because of changes in minority-carrier transport properties of the Cu/sub 2/S. Before developing a method for using an epoxied silicon detector to measure optical behavior of the Cu/sub 2/S layer, we explored the possibility of using a junction-containing wafer of silicon as a substrate for deposited CdS films. Some monolithic structures were successfully fabricated. Comparisons were made of CdS grain structure details in the junction detector area and in an adjacent metallized area.
An integrated NTP-RTCP solution to audio skew detection and compensation for VoIP applications (2003)

The circuit switched POTS (plain old telephone system) preserves the timing relationship between media samples from sender to receiver through use of a common clock. For PC-based Internet multimedia, the existence of separate audio and system clocks on either end-host can introduce significant complications. Much work has taken place in recent years that addresses the issue of system clock skew and its effect on precise delay measurement. In a voice over IP (VoIP) environment, where adaptive buffering techniques are employed, system and audio clock skew can distort both delay measurement and playout control as well as lead to poor buffer performance. This paper presents a high level mechanism to measure and compensate for the skew relationships between system and audio clocks at each end of a multimedia session. The mechanism utilises both the network time protocol (NTP) and the RTP (realtime transport protocol) control protocol or RTCP. Preliminary and positive results are presented from a testbed system and plans for further work are outlined.
A Thiol–Ene Coupling Approach to Native Peptide Stapling and Macrocyclization (2015)

Abstract We report the discovery of a peptide stapling and macrocyclization method using thiol–ene reactions between two cysteine residues and an α,ω‐diene in high yields. This new approach enabled us to selectively modify cysteine residues in native, unprotected peptides with a variety of stapling modifications for helix stabilization or general macrocyclization. We synthesized stapled Axin mimetic analogues and demonstrated increased alpha helicity upon peptide stapling. We then synthesized stapled p53 mimetic analogues using pure hydrocarbon linkers and demonstrated their abilities to block the p53‐MDM2 interaction and selectively kill p53 wild‐type colorectal carcinoma HCT‐116 cells but not p53 null cells. In summary, we demonstrated a robust and versatile peptide stapling method that could be potentially applied to both synthetic and expressed peptides.
ChemInform Abstract: PREPARATION AND ANTITUMOR ACTIVITY OF A REARRANGED ESTER OF CEPHALOTAXINE (1975)

Abstract Zur Untersuchung auf Beziehungen zwischen Struktur und Aktivität werden aus Cephalotaxin (I) modifizierte Derivate hergestellt und auf Antitumor‐Aktivität untersucht.
Expanded Genome Scan in Extended Families with Age-Related Macular Degeneration (2006)

The results suggest that the use of families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q.
Estimation of the Permeabilities and Skin Factors in Layered Reservoirs With Downhole Rate and Pressure Data (1988)

Summary This paper addresses the problem of estimating horizontal and vertical permeabilities, skin factor, and average fluid pressure within the drainage area in each layer in a multilayered reservoir in the presence of formation crossflow between the layers and commingling through the wellbore. A multistep testing procedure is proposed that involves downhole measurement of the pressure and fluid flow rate. The measurements are made successively above the individual layers as transients are induced in the reservoir. A history-matching procedure is used to analyze the data from the entire multistep test simultaneously. The performance of this approach is compared with that of separate, conventional interpretation of each step in five examples with synthetic data. The simultaneous analysis benefits from the synergy between the steps and consistently yields better estimates. A linearized sensitivity analysis is developed to determine the probable errors in the parameter estimates. It indicates whether a given set of measurements with a given level of measurement noise contains sufficient information to determine the individual parameters uniquely.
Lamellar Biogels: Fluid-Membrane-Based Hydrogels Containing Polymer Lipids (1996)

A class of lamellar biological hydrogels comprised of fluid membranes of lipids and surfactants with small amounts of low molecular weight poly(ethylene glycol)-derived polymer lipids (PEG-lipids) were studied by x-ray diffraction, polarized light microscopy, and rheometry. In contrast to isotropic hydrogels of polymer networks, these membrane-based birefringent liquid crystalline biogels, labeled L-alpha,g, form the gel phase when water is added to the liquid-like lamellar L-alpha phase, which reenters a liquid-like mixed phase upon further dilution. Furthermore, gels with larger water content require less PEG-lipid to remain stable. Although concentrated (approximately 50 weight percent) mixtures of free PEG (molecular weight, 5000) and water do not gel, gelation does occur in mixtures containing as little as 0.5 weight percent PEG-lipid. A defining signature of the L-alpha,g regime as it sets in from the fluid lamellar L-alpha phase is the proliferation of layer-dislocation-type defects, which are stabilized by the segregation of PEG-lipids to the defect regions of high membrane curvature that connect the membranes.
Desalination Using Low-Grade Heat Sources (2008)

This study evaluated the feasibility of utilizing low-grade heat sources such as solar energy or waste heat from industrial processes for desalination. The premise of the approach is that saline waters can be desalinated by evaporation and condensation of fresh water at near-ambient temperatures at low pressures. Low pressures can be achieved naturally in the head space of water columns of height equal to the local barometric head. By connecting the head space of such a saline water column to that of a distilled water column, and by maintaining the temperature of the former about 15–20°C above that of the latter, fresh water can be evaporated from the saline column and condensed in the distilled water column. In this study, it is proposed to use a sensible heat thermal energy storage (TES) system to heat the head space of the saline water column. The TES can be maintained at the desired temperature using solar energy and/or waste heat from thermal power plants, refrigeration plants, or air conditioning units. This paper presents the feasibility of the proposed approach, where the TES is maintained at the design temperature by a solar-powered absorption refrigeration system (ARS) augmented by an electric heater. Results of this feasibility study show that the heat rejected by an ARS of cooling capacity of 3.25kW (0.975 tons of refrigeration) along with an additional energy input of 208kJ∕kg of desalinated water is adequate to produce desalinated water at an average rate of 4.5kg∕h . The solar panel area required for this application was 25m2 . An integrated process model and performance curves of the proposed approach are presented.
Polymerization and processing of polymers in magnetic fields (1997)

Liquid crystalline thermosets (LCT`s) have become recognized over the past few years as an important class of materials. Numerous reports from the authors laboratory and others have described their synthesis and phase behavior. In particular, the authors have described important effects due to the orientation of the rodlike molecules in a liquid crystalline phase. They have found that curing rates are enhanced compared to reaction in an isotropic phase, and that the glass transition of the fully cured material can be significantly higher than the final cure temperature. For structural applications, orientation of LCT`s will allow maximum improvement in mechanical properties. A few studies have described use of magnetic fields to orient LCT`s. However, no measurements were made of the tensile properties of materials processed in magnetic fields. The authors have conducted experiments which describe the tensile modulus dependence of an LCT over the complete range of magnetic field strengths from 0 to 18 Tesla. Their work has focused on the system composed of the diglycidyl ether of dihydroxy-{alpha}-methylstilbene (DGE-DHAMS) cured with sulfanilamide (SAA).
Using fourier velocity encoded MRI data to guide CFD simulations (2015)

Fourier velocity encoding (FVE) is a promising magnetic resonance imaging (MRI) method for assessment of cardiovascular blood flow. FVE provides considerably higher signal-to-noise ratio than phase contrast (PC) imaging, is robust to partial-volume effects and can be acquired rapidly using spiral readouts. On the other hand, FVE data do not directly provide a velocity map. These maps are useful for calculating the actual blood flow through a vessel, or for guiding computational fluid dynamics simulations (CFD). In this paper, FVE data were simulated from PC velocity maps from a pulsatile carotid flow phantom; velocity maps were then reconstructed from these FVE data, and used to guide CFD simulations. FVE-guided CFD velocity fields were qualitatively and quantitatively compared with the PC-measured velocity field, with the pure CFD solution, and with PC-guided CFD. The results show that FVE-guided CFD achieves better agreement with the PC-measured velocity field than pure CFD. Compared with PC-guided CFD, FVE provides considerably better results than PC with similar scan time, and equivalent results when compared with PC with 9 times longer scan time.
Ultra-high-resolution optical coherence tomography gets adaptive-optic 'glasses' (2008)

Ultra-high-resolution (UHR) optical coherence tomography (OCT) imaging technique is using adaptive optics, to perform better better treatment and monitoring of retinal diseases. Researchers have developed a new generation of adaptive optics (AO) UHR OCT (AO-UHR-OCT) instrument that combines an ultrabroadband spectral light source and an achromatizing element, to increase measured axial resolution to around 3.5 Î¼m. The measured axial resolution is increased without reducing lateral resolution and image quality. The new instrument uses an AO system in the spectral/Fourier domain OCT sample arm, to facilitate correction of a patient's ocular aberrations. The detection channel of the OCT spectrometer acquires spectral fringes of light, back-scattered from the retina, along with light from the reference arm.
Observation of magnetic interaction between the soft magnetic and the recording layers in double-layer perpendicular media (2001)

Magnetic force microscopy was used to study the magnetic interaction in double-layer perpendicular media between the CoCrPt recording layer and the CoTaZr soft magnetic layer by observing the magnetization structure from the soft magnetic layer side. A strong magnetic interaction between the two layers was observed when the layers were in direct contact. Introducing a thin nonmagnetic layer between the two magnetic layers reduced the magnetic interaction and resulted in the reduction of the media noise of double-layer perpendicular media.
Wideband Acoustic Positioning With Precision Calibration and Joint Parameter Estimation (2017)

This paper presents an instrument for finding the location of an object in 3-D space. The location is determined using estimates of the object's distance from static anchor points with known coordinates. This process involves three main challenges: 1) a way of measuring the Euclidean distance between two points; 2) estimating system parameters such as the position of the anchor points, the speed of sound, and data acquisition delay; and 3) computing the position of the object from its distance to the anchor points. This paper addresses each of these challenges. A wideband acoustic signal is used for distance estimation. Nonlinear regression techniques are used to estimate the positions of the anchors and jointly optimize other system parameters. After calibration, a similar method is also used, this time using the optimized parameter set, to estimate the position of the target object. The design and performance of a prototype system, based on the proposed method, are discussed. The prototype, using five anchors and 13 reference locations, achieved a mean positioning accuracy of 0.86 mm over a test volume spanning 0.5 m × 0.5 m × 0.25 m.
Microstructure and Thermoelectric Properties of Mechanically Robust PbTe-Si Eutectic Composites (2009)

The microstructure and thermoelectric properties of the PbTe-Si eutectic system are presented in detail. When rapidly quenched from the melt this system yields materials with thermoelectric properties similar to PbTe itself but with improved mechanical properties. Doping optimization was performed using PbI2 as an n-type dopant giving precise control of the thermoelectric properties. Electron microscopy indicates that the PbTe-Si system is both a nanocomposite and microcomposite. Despite the added Si, the thermal conductivity of this composite follows closely that of PbTe. The temperature dependence of the Lorenz number was estimated, and it shows a significant departure from the value of metals (L0) reaching only 45% of L0 at 650 K. The optimized ZT for the PbTe-Si(8%) eutectic was 0.9 at 675 K. The improved mechanical robustness of these composites makes them attractive for use in large scale thermoelectric device fabrication.
Absorption-reduced waveguide structure for efficient terahertz generation (2015)

An absorption-reduced planar waveguide structure is proposed for increasing the efficiency of terahertz (THz) pulse generation by optical rectification of femtosecond laser pulses with tilted-pulse-front in highly nonlinear materials with large absorption coefficient. The structure functions as waveguide both for the optical pump and the generated THz radiation. Most of the THz power propagates inside the cladding with low THz absorption, thereby reducing losses and leading to the enhancement of the THz generation efficiency by up to more than one order of magnitude, as compared with a bulk medium. Such a source can be suitable for highly efficient THz pulse generation pumped by low-energy (nJ-μJ) pulses at high (MHz) repetition rates delivered by compact fiber lasers.
Development of an Automated Malaria Discriminant Factor Using VCS Technology (2006)

Malaria diagnosis presents a challenge to all laboratories. There is a need for rapid, sensitive, and cost-effective screening on all samples, particularly in areas where malaria is endemic. Response to malaria infection involves an increased monocyte count and production of large activated monocytes. These changes can be detected by volume, conductivity, and scatter (VCS) technology on certain automated blood cell counters (Beckman Coulter, Miami, FL). The SD of the volume of lymphocytes and monocytes demonstrates a significant difference from normal when malaria is present. By using a calculation derived from the SD volume of the lymphocytes and monocytes, herein termed the malaria factor, sensitivity of 98% and specificity of 94% were demonstrated for the detection of malaria. Based on this derived discriminant, VCS technology should become a useful tool in the detection of malaria. A flag to indicate the potential presence of malaria could then be generated by the instrument if the user or manufacturer chose to do so.
Taxol and Taxane Production by <i>Taxomyces andreanae</i> , an Endophytic Fungus of Pacific Yew (1993)

Taxomyces andreanae, a fungal endophyte, was isolated from the phloem (inner bark) of the Pacific yew, Taxus brevifolia. The fungus is hyphomyceteous and, when grown in a semi-synthetic liquid medium, produced taxol and related compounds. Taxol was identified by mass spectrometry, chromatography, and reactivity with monoclonal antibodies specific for taxol. Both [1-14C]acetic acid and L-[U-14C]phenylalanine served as precursors of [14C]taxol in fungal cultures. No taxol was detected in zero-time cultures or in the small agar plugs used to inoculate the culture flasks.
Hello, Is It Me You're Looking For? (2018)

Voice interfaces are increasingly becoming integrated into a variety of Internet of Things (IoT) devices. Such systems can dramatically simplify interactions between users and devices with limited displays. Unfortunately voice interfaces also create new opportunities for exploitation. Specifically any sound-emitting device within range of the system implementing the voice interface (e.g., a smart television, an Internet-connected appliance, etc) can potentially cause these systems to perform operations against the desires of their owners (e.g., unlock doors, make unauthorized purchases, etc). We address this problem by developing a technique to recognize fundamental differences in audio created by humans and electronic speakers. We identify sub-bass over-excitation, or the presence of significant low frequency signals that are outside of the range of human voices but inherent to the design of modern speakers, as a strong differentiator between these two sources. After identifying this phenomenon, we demonstrate its use in preventing adversarial requests, replayed audio, and hidden commands with a 100%/1.72% TPR/FPR in quiet environments. In so doing, we demonstrate that commands injected via nearby audio devices can be effectively removed by voice interfaces.
Incremental motion estimation through modified bundle adjustment (2004)

An incremental motion estimation scheme for long image sequence analysis is introduced. It applies to a sliding window of triplet images and maintains local motion consistency without resort to post-concatenation. This is possible thanks to our newly developed local process called three-view partial bundle adjustment. Unlike previous approaches that rely only on point matches across three or more views, our local process also takes into account all available two-view matches, leading to more accurate motion estimation. For sparse image sequences, two-view matches are very reliable and it becomes even more important to use them since the number of matches across more views decreases quickly. In this case, our incremental method can produce results very close to those obtained with a global bundle adjustment but in a fraction of time. Experiments with both synthetic and real data have been conducted to compare the proposed technique with other techniques, and have shown our technique to be clearly superior.
Outsourcing Multi-Party Computation. (2011)

We initiate the study of secure multi-party computation (MPC) in a server-aided setting, where the parties have access to a single server that (1) does not have any input to the computation; (2) does not receive any output from the computation; but (3) has a vast (but bounded) amount of computational resources. In this setting, we are concerned with designing protocols that minimize the computation of the parties at the expense of the server. We develop new definitions of security for this server-aided setting that generalize the standard simulation-based definitions for MPC and allow us to formally capture the existence of dishonest but non-colluding participants. This requires us to introduce a formal characterization of non-colluding adversaries that may be of independent interest. We then design general and special-purpose server-aided MPC protocols that are more efficient (in terms of computation and communication) for the parties than the alternative of running a standard MPC protocol (i.e., without the server). Our main general-purpose protocol provides security when there is at least one honest party with input. We also construct a new and efficient server-aided protocol for private set intersection and give a general transformation from any secure delegated computation scheme to a server-aided two-party protocol. ∗Microsoft Research. senyk@microsoft.com. †University of Calgary. pmohassel@cspc.ucalgary.ca. Work done while visiting Microsoft Research. ‡Columbia University. mariana@cs.columbia.edu. Work done as an intern at Microsoft Research.