gebhart/patrepeval huggingface dataset:
Chimeric RNA:DNA Donorguide Improves HDR <i>in vitro</i> and <i>in vivo</i> (2021)

Abstract Introducing small genetic changes to study specific mutations or reverting clinical mutations to wild type has been an area of interest in precision genomics for several years. In fact, it has been found that nearly 90% of all human pathogenic mutations are caused by small genetic variations, and the methods to efficiently and precisely correct these errors are critically important. One common way to make these small DNA changes is to provide a single stranded DNA (ssDNA) donor containing the desired alteration together with a targeted double-strand break (DSB) at the genomic target. The donor is typically flanked by regions of homology that are often ~30-100bp in length to leverage the homology directed repair (HDR) pathway. Coupling a ssDNA donor with a CRISPR-Cas9 to produce a targeted DSB is one of the most streamlined approaches to introduce small changes. However, in many cell types this approach results in a low rate of incorporation of the desired alteration and has undesired imprecise repair at the 5’ or 3’ junction due to artifacts of the DNA repair process. We herein report a technology that couples the spatial temporal localization of an ssDNA repair template and leverages the nucleic acid components of the CRISPR-Cas9 system. We show that by direct fusion of an ssDNA template to the trans activating RNA (tracrRNA) to generate an RNA-DNA chimera, termed Donorguide, we recover precise integration of genetic alterations, with both increased integration rates and decreased imprecision at the 5’ or 3’ junctions relative to an ssODN donor in vitro in HEK293T cells as well as in vivo in zebrafish. Further, we show that this technology can be used to enhance gene conversion with other gene editing tools such as TALENs.
Nonlinear modeling of adaptive magnetorheological landing gear dampers under impact conditions (2016)

Adaptive landing gear dampers that can continuously adjust their stroking load in response to various operating conditions have been investigated for improving the landing performance of a lightweight helicopter. In prior work, adaptive magnetorheological (MR) landing gear dampers that maintained a constant peak stroking force of 4000 lbf across sink rates ranging from 6 to 12 ft s−1 were designed, fabricated and successfully tested. In this follow-on effort, it is desired to expand the high end of the sink rate range to hold the peak stroking load constant for sink rates ranging from 6 to 26 ft s−1, thus extending the high end of the speed range from 12 (in the first study) to 26 ft s−1. To achieve this increase, a spring-based relief valve MR landing gear damper was developed. In order to better understand the MR landing gear damper behavior, a modified nonlinear Bingham Plastic model was formulated, and it incorporates Darcy friction, viscous forces across the MR and relief valves to better account for the damper force behavior at higher speeds. In addition, gas pressure inside the MR damper piston is considered so the total damper force includes a gas force. The MR landing gear damper performance is characterized using drop tests, and the experiments are used to validate model predictions data at low and high nominal impact speeds up to 26 ft s−1 (shaft velocity of 9.6 ft s−1).
ChemInform Abstract: Structure‐Based Design and Synthesis of a Series of Hydroxamic Acids with a Quaternary‐Hydroxy Group in P1 as Inhibitors of Matrix Metalloproteinases. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A female sterile screen of the Drosophila melanogaster X chromosome using hybrid dysgenesis: identification and characterization of egg morphology mutants. (1989)

We have conducted a hybrid dysgenic screen of the X chromosome for mutations affecting female fertility, with particular attention to those causing abnormal egg and eggshell morphology. In a screen of 4017 dysgenic strains, 398 mutants derived from 168 different germ lines were isolated and assigned to eight classes according to their diverse phenotypes. One interesting class consists of mutants that block oogenesis at specific stages. Our analysis has focused on mutations affecting eggshell formation, including mutants that lay morphologically abnormal sterile eggs as well as those that lay no eggs but exhibit blocks in the late stages of oogenesis. A subset of 48 mutants was assorted into 30 allelic groups by inter se complementation and genetically localized by interval mapping. Two multiallele complementation groups, de1 (7 alleles) and ne1 (8 alleles), were identified as well as five two-allele complementation groups. A search for alleles among mutants generated in other female sterile screens was unsuccessful, pointing to the distinctive nature of the dysgenic mutant collection. The single case of allelism determined in this study was one with a lethal allele of the Broad-Complex, l(1)npr, suggesting a possible involvement of ecdysone in choriogenesis. A subset of 18 dysgenic strains was analyzed for P element hybridization and 16 of these were found to have hybridization signals in the appropriate cytogenetic interval. By examining these signals in two or more alleles of the same complementation group, we have been able to tentatively localize two mutations. Light and electron microscopy of the eggshell in 43 different strains has revealed a variety of effects. The respiratory appendages were defective in 27 of these mutants. Effects on the ultrastructure of the main body of the endochorion were not strongly correlated with the appendage defects, and could be classified as minor (14 mutants) or major (16 mutants). Although 13 mutants showed no ultrastructural chorion defects, six of these had defective respiratory appendages.
Surface texture limits transfer of <i>S. aureus</i> , T4 Bacteriophage, Influenza B virus and Human coronavirus (2020)

Abstract Spread of pathogens on contaminated surfaces plays a key role in disease transmission. Surface technologies that control pathogen transfer can help control fomite transmission and are of great interest to public health. Here, we report a novel bead transfer method for evaluating fomite transmission in common laboratory settings. We show that this method meets several important criteria for quantitative test methods, including reasonableness, relevancy, resemblance, responsiveness, and repeatability, and therefore may be adaptable for standardization. In addition, this method can be applied to a wide variety of pathogens including bacteria, phage, and human viruses. Using the bead transfer method, we demonstrate that an engineered micropattern limits transfer of Staphylococcus aureus by 97.8% and T4 bacteriophage by 93.0% on silicone surfaces. Furthermore, the micropattern significantly reduces transfer of influenza B virus and human coronavirus on silicone and polypropylene surfaces. Our results highlight the potential of using surface texture as a valuable new strategy in combating infectious diseases. Importance Disease transmission often occurs through contact with contaminated surfaces, called fomites. Efforts to reduce this method of fomite transmission include surface cleaning, personal hygiene, alteration of habits, and novel technologies to reduce pathogen spread. This manuscript presents a novel method for the consistent contamination of surfaces to mimic the transmission of pathogens via fomites. Using this method, we present a surface texture modeled on shark skin that significantly reduces the transfer of a variety of pathogens, including Staphylococcus aureus , influenza B virus, and human coronavirus 229E. Utilization of novel technologies to limit pathogen spread can enhance existing methods of disease mitigation.
Maintaining Hard Disk Integrity With Digital Legal Professional Privilege (LPP) Data (2013)

The concept of legal professional privilege (LPP) in the Common Law is to enable a client to make full disclosure to his legal advisor for seeking advice without worrying that anything so disclosed will be used against him. Thus, some of the communications and documents between a legal advisor and his client can be excluded as evidence for prosecution. Protection of LPP information in the physical world is well addressed and proper procedures for handling LPP documents have been established. However, there does not exist a forensically sound procedure for protecting digital LPP information. In this correspondence, motivated by a real case of a commercial crime investigation, we introduce the LPP data integrity problem. While finding an ideal solution to solve the problem is difficult, we propose a practical solution that was adopted to solve the real case investigation. We also analyze the performance of our solution based on simulated data.
Wireless sensor network for real-time air pollution monitoring (2013)

This paper presents an ambient real-time air quality monitoring system. The system consists of several distributed monitoring stations that communicate wirelessly with a backend server using machine-to-machine communication. Each station is equipped with gaseous and meteorological sensors as well as data logging and wireless communication capabilities. The backend server collects real time data from the stations and converts it into information delivered to users through web portals and mobile applications. The system is implemented in pilot phase and four solar-powered stations are deployed over an area of 1 km <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Data over four months has been collected and performance analysis and assessment are performed. As the historical data bank becomes richer, more sophisticated operations can be performed.
Supplementary Table 2 from MiR-122/Cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells (2023)

Supplementary Table 2 from MiR-122/Cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells
Towards virtual clay (2006)

Providing the user with an intuitive sculpting system similar to real clay is one of the most challenging goals of interactive shape modeling. A user should ideally be able to deform, add and remove material freely in real time, without any geometric or topological constrains on the modeled shape.This chapter reviews and compares three techniques that bring virtual shape modeling closer to this objective. The two first ones rely on a specific representation of the sculpted shape, namely the iso-surface of a scalar field stored in a grid. Because this representation conveniently captures topological changes, adding and removing material is straightforward. Based on this representation, we compare a geometric versus a physically-based method for handling local and global shape deformations that make the model closer to virtual clay. We also discuss solutions for providing users with an intuitive interface with haptic feedback. A third and very different approach is to define the deformations of the sculpted model as spatial deformations, such that the operation is applicable to a wide range of shape representations. We show that the extension of sweepers (presented in the space deformation chapter of this tutorial) to constant volume "swirling-sweepers" produces an intuitive clay-like behavior of the modeled shape. This technique provides a very good alternative to physically-based virtual clay when preserving the shape's topology is desirable.
Short-Term Deterioration of Polymer-Coated 55% Al-Zn: Part 3 — Protective Mechanism of Inhibitor-Modified Coatings (1999)

Abstract Electrochemical impedance spectroscopy (EIS) was used to investigate 55% Al-Zn coated with different thin polymer coatings (≈ 1 μm) containing a passivating inhibitor (Cr[VI]) after exposu...
Generation of Oxamic Acid Libraries:  Antimalarials and Inhibitors of <i>Plasmodium falciparum</i> Lactate Dehydrogenase (2007)

Lactate dehydrogenase (LDH) is a key enzyme in the glycolytic pathway of Plasmodium falciparum (pf) and has several unique amino acids, related to other LDHs, at the active site, making it an attractive target for antimalarial agents. Oxamate, a competitive inhibitor, shows high substrate affinity for pfLDH. This class of compounds has been viewed as potential antimalarial agents. Thus, we have developed an effective automated synthetic strategy for the rapid synthesis of oxamic acid and ester libraries to screen for potential lead inhibitors. One hundred sixty-seven oxamic acids were synthesized using a "catch and release" method with overall yields of 20-70%. Most of the compounds synthesized had some inhibitory effects, but compounds 5 and 6 were the most active against both chloroquine- and mefloquine-resistant strains with IC50 values of 15.4 and 9.41 microM and 20.4 and 8.40 microM, respectively. Some oxamic acids showed activities against pfLDH and mammalian LDH (mLDH) at the micromolar range. These oxamic acids selectively inhibited pfLDH 2-5 fold over mLDH. Oxamic acid 21 was the most active against pfLDH at IC50 = 14 and mLDH at IC50 = 25 microM, suggesting that oxamic acid derivatives are potential inhibitors of pfLDH and that further study is required to develop selective inhibitors of pfLDH over mLDH.
Renal extracapsular hypoechoic rim and kidney cortical thickness (2017)

It is our opinion that in case of unilateral finding of an hypoechoic rim, the association between the hypoechoic rim and the cortical thinning is consistent and therefore more accurate than the correlation between the presence of the hypoechoic rim and the reduction of the glomerular filtration rate.
Endocannabinoids in Synaptic Plasticity and Neuroprotection (2014)

Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of physiological, pharmacological, and pathological processes. While activation of the eCB system primarily induces inhibitory effects on both GABAergic and glutamatergic synaptic transmission and plasticity through acting on presynaptically expressed CB1 receptors in the brain, accumulated information suggests that eCB signaling is also capable of facilitating or potentiating excitatory synaptic transmission in the hippocampus. Recent studies show that a long-lasting potentiation of excitatory synaptic transmission at Schaffer collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs, accompanying with a long-term depression of inhibitory synaptic transmission (I-LTD) in hippocampal CA1 pyramidal neurons. This input timing-dependent long-lasting synaptic potentiation at SC-CA1 synapses is mediated by 2-arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic N-methyl-D-aspartate receptors, group I metabotropic glutamate receptors (mGluRs), and a concurrent rise in intracellular Ca(2+). Emerging evidence now also indicates that 2-AG is an important signaling mediator keeping brain homeostasis by exerting its anti-inflammatory and neuroprotective effects in response to harmful insults through CB1/2 receptor-dependent and/or -independent mechanisms. Activation of the nuclear receptor protein peroxisome proliferator-activated receptor-γ apparently is one of the important mechanisms in resolving neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the information summarized in this review suggests that the role of eCB signaling in maintaining integrity of brain function is greater than what we thought previously.
ChemInform Abstract: Production of 4‐Hydroxyphenyl‐trichloromethylcarbinol. (1986)

Abstract The reaction of phenol (I) with chloral hydrate (II) in the presence of basic agents has been investigated and an effective method for the synthesis of the title compound (III) is described.
SPRINT: Phase II study of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN). (2018)

10503 Background: PN in NF1 can cause substantial morbidity, and there are no approved medical therapies. In a phase I trial of selumetinib, 17/24 (71%) patients (pts) had a partial response (PR)(Dombi, et al. N Engl J Med 2016; 375:2550-2560). This open-label phase II study (NCT01362803) determines the PR rate of PN treated with selumetinib and changes in PN related morbidities. Methods: Patients 2-18 years old with NF1, inoperable PN and ≥ 1 PN related morbidity received selumetinib at the recommended phase II dose (25 mg/m2 PO BID) with continuous dosing (1 cycle = 28 days). Response was evaluated with volumetric MRI analysis (PR = target PN volume decrease ≥20%) and PN related morbidities (pain, disfigurement, functional morbidities) assessed with standardized evaluations after every 4 cycles. Results: Fifty children (30 male, median age 10.2 years, range 3.5, 17.4) enrolled. Disfigurement (n=44), motor dysfunction (n=33) and pain (n=28) were the most frequent PN related morbidities. As of November 5, 2017: median cycle number 19.5 (range 0, 29) with 38 pts remaining on treatment; median change in PN volume from baseline -27.7% (range -50.6%, 2.2%); best response PR (36 pts, 72%), stable disease (12 pts, 24%); 2 subjects (4%) had no re-staging. Of the 36 total PR, 32 were confirmed on ≥ two consecutive restaging scans and 22 continue to have a PR ≥ 1 year after it was first achieved. Between baseline and end of year 1 evaluations, parent and child-reported pain intensity and pain interference scores significantly improved (p <0.01), as did strength (0-5 scale) and range of motion (degrees) of affected muscle groups/joints (p < 0.01). The most frequent toxicities were nausea/vomiting, diarrhea, asymptomatic creatine kinase increase, acneiform rash and paronychia. Selumetinib dose was reduced in 12 pts, of which 5 were removed from treatment. Conclusions: The response rate from this study (72%) confirms our previously observed response rate (71%). Most responses were sustained ≥6 months. Improvements in PN related pain and motor impairment demonstrate that selumetinib can provide clinical benefit. Data validation and further analyses are ongoing. Clinical trial information: NCT01362803.
Multimodal evaluation of tissue engineered cartilage maturation in a pre-clinical implantation model (Conference Presentation) (2019)

Tissue engineers rely on expensive, time-consuming, and destructive techniques to monitor the composition and function of engineered tissue equivalents. A non-destructive solution to monitor tissue quality and maturation would greatly reduce costs and accelerate the development of tissue-engineered products. A label-free multimodal system combining fluorescence lifetime imaging (FLIm) and optical coherence tomography (OCT) via a single fiber-optic interface was used for evaluation of biochemical and structural properties of tissue-engineered articular cartilage in a murine model of cartilage maturation. Nude mice (n=5) received 2 dorsal subcutaneous tissue-engineered cartilage implants each consisting of: 1) latent transforming growth factor-beta1 (LAP) treated; and 2) untreated control (CTL) constructs. At 6 weeks post-implantation, mice were sacrificed and multimodal imaging was performed in situ. FLIm showed clear delineation of the implant in all spectral bands (SB). Quantification of the cartilage construct fluorescence lifetime (LT) showed a lower LT in SB-1 (375-410 nm) and higher SB-3 LT (515-565 nm) as compared to the surrounding muscle tissue. Comparison between treatment groups showed a significant increase in FLIm SB-3 LT in LAP-treated constructs over CTL (p < 0.01). Quantification of OCT images allowed implant morphology and 3D volume comparisons between treatment groups. These results suggest that FLIm-OCT based tools are a potential non-destructive method for quantitatively monitoring the growth and quality of tissue engineered articular cartilage. The use of optical techniques to monitor maturation could represent a significant element in reducing costs in research, meeting the FDA regulatory requirements for manufacturing, and providing novel diagnostic tools in the clinic.
Measurement of the Branching Fraction, and Bounds on the CP-Violating Asymmetries, of Neutral<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>B</mml:mi></mml:math>Decays to<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:msup><mml:mi>D</mml:mi><mml:mrow><mml:mo>*</mml:mo><mml:mo>±</mml:mo></mml:mrow></mml:msup><mml:msup><mml:mi>D</mml:mi><mml:mo>∓</mml:mo></mml:msup></mml:math> (2003)

We present measurements of the branching fraction and CP-violating asymmetries for neutral B decays to D(*+/-)D-/+. The measurement uses a data sample of approximately 88x10(6) Upsilon(4S)-->BBmacr; decays collected with the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)-e(-) collider. By fully reconstructing the D(*+/-)D-/+ decay products, we measure the branching fraction to be (8.8+/-1.0+/-1.3)x10(-4) and the time-integrated CP-violating asymmetry between the rates to D(*-)D+ and D(*+)D- to be A=-0.03+/-0.11+/-0.05. We also measure the time-dependent CP-violating asymmetry parameters to be S(-+)=-0.24+/-0.69+/-0.12, C(-+)=-0.22+/-0.37+/-0.10 for B-->D(*-)D+ and S(+-)=-0.82+/-0.75+/-0.14, C(+-)=-0.47+/-0.40+/-0.12 for B-->D(*+)D-. In each case, the first error is statistical and the second error is systematic.
ChemInform Abstract: Spirocyclic Amino Alcohol Building Blocks Prepared via a Prins‐Type Cyclization in Aqueous Sulfuric Acid. (2016)

Abstract The Prins cyclization of azacycloalkanones with homoallylic alcohols is achieved in aqueous sulfuric acid providing a wide range of spirocyclic amino alcohols.