gebhart/patrepeval huggingface dataset:
Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1 (2017)

A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For HIV-1 infection, during entry, the virus triggers early actin activity by hijacking chemokine coreceptor signaling, which activates a host dependency factor, cofilin, and its kinase, the LIM domain kinase (LIMK). Although knockdown of human LIM domain kinase 1 (LIMK1) with short hairpin RNA (shRNA) inhibits HIV infection, no specific small-molecule inhibitor of LIMK has been available. Here, we describe the design and discovery of novel classes of small-molecule inhibitors of LIMK for inhibiting HIV infection. We identified R10015 as a lead compound that blocks LIMK activity by binding to the ATP-binding pocket. R10015 specifically blocks viral DNA synthesis, nuclear migration, and virion release. In addition, R10015 inhibits multiple viruses, including Zaire ebolavirus (EBOV), Rift Valley fever virus (RVFV), Venezuelan equine encephalitis virus (VEEV), and herpes simplex virus 1 (HSV-1), suggesting that LIMK inhibitors could be developed as a new class of broad-spectrum antiviral drugs.<b>IMPORTANCE</b> The actin cytoskeleton is a structure that gives the cell shape and the ability to migrate. Viruses frequently rely on actin dynamics for entry and intracellular migration. In cells, actin dynamics are regulated by kinases, such as the LIM domain kinase (LIMK), which regulates actin activity through phosphorylation of cofilin, an actin-depolymerizing factor. Recent studies have found that LIMK/cofilin are targeted by viruses such as HIV-1 for propelling viral intracellular migration. Although inhibiting LIMK1 expression blocks HIV-1 infection, no highly specific LIMK inhibitor is available. This study describes the design, medicinal synthesis, and discovery of small-molecule LIMK inhibitors for blocking HIV-1 and several other viruses and emphasizes the feasibility of developing LIMK inhibitors as broad-spectrum antiviral drugs.
Systemic antibiotic therapy as an adjunct to non‐surgical peri‐implantitis treatment: A single‐blind RCT (2021)

Abstract Aim The aim of this single‐blind RCT was to evaluate the adjunctive clinical and microbiological effect of systemic amoxicillin (AMX) plus metronidazole (MTZ) to non‐surgical treatment of peri‐implantitis. Material and methods Patients ( N = 62) with peri‐implantitis were randomly assigned to receive full‐mouth mechanical debridement and decontamination and use of chlorhexidine (control group) or combined with antibiotic therapy of AMX/MTZ (test group). Primary outcome was change in bleeding score from baseline ( T 0 ) to 3‐month follow‐up ( T 3 ). Secondary parameters were plaque, suppuration, PPD, CAL, bone level, microbiology, adverse events and need for additional surgery. Data were analysed with linear multiple regression analysis. Results 57 patients with 122 implants completed 3‐month follow‐up. Both groups showed major clinical improvements at T 3 in both peri‐implant and periodontal parameters. However, no significant differences were observed between both groups for any of the primary or secondary parameters. Conclusions Systemic antibiotic therapy of AMX/MTZ does not improve clinical and microbiological outcomes of non‐surgical peri‐implantitis treatment and should not be routinely recommended. Although complete disease resolution may be difficult to achieve, meticulously performed full‐mouth non‐surgical treatment, achieving a high level of daily oral hygiene and healthy periodontal tissues, can significantly improve the starting position of the subsequent (surgical) peri‐implantitis treatment phase.
Investigating the Role of Quantum Dot Morphology and Microstructure in Resonance Energy Transfer (2013)

Semiconductive quantum dots (QDs) and quantum rods (QRs) have tailorable optical and electrical properties that are a function of; core composition, size and morphology. These quantum parameters are sensitive to the conditions in which they are prepared, and chemical synthesis can lead to a wide variety of types. In my dissertation research, I designed synthetic protocols for QDs and QRs to have tailored morphologies, aspect ratios, and microstructures for energy transfer applications. The role of QRs as energy acceptors in bioluminescence resonance energy transfer (BRET) with firefly luciferase enzymes is a particular focus. In this thesis I show how changing morphology and aspect ratio of QRs can help to optimize BRET efficiency. My work revealed that CdSe/CdS QRs with rod-in-rod morphology are the most efficient BRET acceptors. In order to gain insight into the origin of this high efficiency, systematic BRET studies were preformed using QRs of varied aspect ratios and emission wavelengths. To study the effect of bioluminescent donor energy level on BRET, I used three different combinations of modified firefly luciferase and the luciferin substrate, producing blue-green, green, and red bioluminescence. To gain insights into the binding location and mechanism of the enzyme on the QR, I monitored surface defects, by growing gold nanoparticles on the surface, which nucleate at defect sites. I extended our approach and made a near Infrared (nIR) BRET nanoconjugate, in which green bioluminescence was converted to nIR emission. Finally, I describe our latest advance that involves two-step sequential resonance energy transfer was observed in which QDs are used as an energy acceptor and donor, which was facilitated by secondary attachment of a red fluorescent protein.
Construction of a maxillary prosthesis with a hollow obturator by the balloon technique and a case report. (1989)

The authors devised a new method for making a maxillary prosthesis with a hollow obturator, which was named the Balloon Technique. This new technique has a number of advantages over the conventional method in that it not only facilitates the molding of a soft plastic hollow obturator in a single process, but also simplifies the trial fitting of the completed obturator. Furthermore, it makes possible firm adhesion of the hollow obturator and the denture base by the hot-melt method while the denture base resin is cured. Finally, the completed maxillary prosthesis is extremely light.
Flash Light Millisecond Self‐Assembly of High χ Block Copolymers for Wafer‐Scale Sub‐10 nm Nanopatterning (2017)

One of the fundamental challenges encountered in successful incorporation of directed self-assembly in sub-10 nm scale practical nanolithography is the process compatibility of block copolymers with a high Flory-Huggins interaction parameter (χ). Herein, reliable, fab-compatible, and ultrafast directed self-assembly of high-χ block copolymers is achieved with intense flash light. The instantaneous heating/quenching process over an extremely high temperature (over 600 °C) by flash light irradiation enables large grain growth of sub-10 nm scale self-assembled nanopatterns without thermal degradation or dewetting in a millisecond time scale. A rapid self-assembly mechanism for a highly ordered morphology is identified based on the kinetics and thermodynamics of the block copolymers with strong segregation. Furthermore, this novel self-assembly mechanism is combined with graphoepitaxy to demonstrate the feasibility of ultrafast directed self-assembly of sub-10 nm nanopatterns over a large area. A chemically modified graphene film is used as a flexible and conformal light-absorbing layer. Subsequently, transparent and mechanically flexible nanolithography with a millisecond photothermal process is achieved leading the way for roll-to-roll processability.
Antitumour polycyclic acridines. Part 9.1 Synthesis of 7H-pyrido[4,3,2-kl]acridines with basic side chains (2001)

[3 + 2] Cycloaddition of 3-(dialkylamino)-1-triphenylphosphoranylidenepropan-2-ones and 9-azidoacridine affords 9-[5-(dialkylaminomethyl)-1H-1,2,3-triazol-1-yl]acridines. Graebe–Ullmann thermolysis of the triazoles has been guided by differential scanning calorimetry to predict the optimum temperature for nitrogen extrusion. Boiling diphenyl ether (bp 259 °C) is a suitable solvent to convert the triazolylacridines to 2-(dialkylaminomethyl)-7H-pyrido[4,3,2-kl]acridines.
[Great number of non-recorded cases of analytical interference. Unexpected and misinterpreted laboratory levels can result in diagnostic and therapeutic errors]. (2002)

[Great number of non-recorded cases of analytical interference. Unexpectedand misinterpreted laboratory levels can result in diagnostic andtherapeutic errors]
380/400V DC powering option (2011)

Many studies have been conducted of a 380V/400V dc (HVDC) powering architecture in telecommunications and data centers. The key driving factors cited in these studies are increased reliability and energy efficiency. Discussion around a HVDC powering architecture has been recently fuelled by two issues. First the rapid increase in rack power density of server based equipment makes it less efficient and more costly to distribute dc power at traditional levels of -48V. Second, the convergence of telecommunications and IP-based internet technologies that increasingly sees server based equipment occupying floor space more traditionally reserved for "telecommunications racks". Servers are usually powered by ac equipment such as UPS. There is little debate that dc systems have traditionally out-performed ac systems on both reliability and energy efficiency. This paper will investigate the relevance of the ac versus HVDC debate on historical grounds. Is this a balanced and independent assessment of current and emerging technology options? Finally, given the traditionally more robust, engineering culture in the telecommunications space, how would a reliability comparison bear out in applying the same culture of rigor to server based technologies? This paper will present a historical comparison of the reliability and energy efficiency between the two architectures. Next, the comparison will be extended to consider present day and new developments. An independent review is presented of current and emerging factors likely to impact the question of ac versus HVDC. This will include advances in UPS systems, some global issues including the use of PDU's in North America and the question of HVDC standards. The paper will seek to present a balanced view of what has become a "hot" debate being contested amongst Telcos.
Data quality of Whole Genome Bisulfite Sequencing on Illumina platforms (2017)

Abstract The powerful HiSeq X sequencers with their patterned flowcell technology and fast turnaround times are instrumental for many large-scale genomic and epigenomic studies. However, assessment of DNA methylation by sodium bisulfite treatment results in sequencing libraries of low diversity, which may impact data quality and yield. In this report we assess the quality of WGBS data generated on the HiSeq X system in comparison with data generated on the HiSeq 2500 system and the newly released NovaSeq system. We report a systematic issue with low basecall quality scores assigned to guanines in the second read of WGBS when using certain Real Time Analysis (RTA) software versions on the HiSeq X sequencer, reminiscent of an issue that was previously reported with certain HiSeq 2500 software versions. However, with the HD.3.4.0/RTA 2.7.7 software upgrade for the HiSeq X system, we observed an overall improved quality and yield of the WGBS data generated, which in turn empowers cost-effective and high quality DNA methylation studies.
Glutamine Induces Heat Shock Protein Expression Via O‐Glycosylation and Phosphorylation of HSF‐1 and Sp1 (2008)

These results indicate that GLN induces HSF-1 and Sp1, which is known to lead to their nuclear translocation. The molecular mechanism of GLN-mediated HSP70 expression appears to be dependent on O-GlcNAc pathway activation and subsequent O-glycosylation and phosphorylation of key transcription factors required for HSP70 induction.
Synthesis of 1,1-Difluoroalkanes via Phase Transfer Catalysed Reaction of 1,1-bis-Triflates with KF in the Presence of Cocatalyst - Ph3SnF (2002)

1,1-bis-Triflates treated with KF in the presence of tri­phenyltin fluoride and tetrabutylammonium hydrogen sulfate give 1,1-difluoroalkanes
50-Gbit/s operation of lateral pin diode structure electro-absorption modulator integrated DFB laser (2014)

We developed an electro-absorption modulator integrated DFB laser using a lateral pin diode structure. Selective doping by thermal diffusion and ion implantation is essential for fabricating a monolithic integrated device. The device was modulated by 50-Gbit/s-NRZ signal with clear-eye opening.
Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies (2021)

In cystic fibrosis (CF) airways, Pseudomonas aeruginosa forms cellular aggregates called biofilms that are thought to contribute to chronic infection. To form aggregates, P. aeruginosa can use different mechanisms, each with its own pathogenic implications. However, how they form in vivo is controversial and unclear. One mechanism involves a bacterially produced extracellular matrix that holds the aggregates together. Pel and Psl exopolysaccharides are structural and protective components of this matrix. We develop an immunohistochemical method to visualize Pel and Psl in CF sputum. We demonstrate that both exopolysaccharides are expressed in the CF airways and that the morphology of aggregates is consistent with an exopolysaccharide-dependent aggregation mechanism. We reason that the cationic exopolysaccharide Pel may interact with some of the abundant anionic host polymers in sputum. We show that Pel binds extracellular DNA (eDNA) and that this interaction likely impacts current therapies by increasing antimicrobial tolerance and protecting eDNA from digestion.
Diminished Vision in Healthy Aging Is Associated with Increased Retinal L-Type Voltage Gated Calcium Channel Ion Influx (2013)

Extensive evidence implicates an increase in hippocampal L-type voltage-gated calcium channel (L-VGCC) expression, and ion influx through these channels, in age-related cognitive declines. Here, we ask if this "calcium hypothesis" applies to the neuroretina: Is increased influx via L-VGCCs related to the well-documented but poorly-understood vision declines in healthy aging? In Long-Evans rats we find a significant age-related increase in ion flux through retinal L-VGCCs in vivo (manganese-enhanced MRI (MEMRI)) that are longitudinally linked with progressive vision declines (optokinetic tracking). Importantly, the degree of retinal Mn(2+) uptake early in adulthood significantly predicted later visual contrast sensitivity declines. Furthermore, as in the aging hippocampus, retinal expression of a drug-insensitive L-VGCC isoform (α1D) increased - a pattern confirmed in vivo by an age-related decline in sensitivity to L-VGCC blockade. These data highlight mechanistic similarities between retinal and hippocampal aging, and raise the possibility of new treatment targets for minimizing vision loss during healthy aging.
Quantitative Protein Corona Composition and Dynamics on Carbon Nanotubes in Biological Environments (2020)

Abstract When nanoparticles enter biological environments, proteins adsorb to form the “protein corona” which alters nanoparticle biodistribution and toxicity. Herein, we measure protein corona formation on DNA‐functionalized single‐walled carbon nanotubes (ssDNA‐SWCNTs), a nanoparticle used widely for sensing and delivery, in blood plasma and cerebrospinal fluid. We characterize corona composition by mass spectrometry, revealing high‐abundance corona proteins involved in lipid binding, complement activation, and coagulation. We investigate roles of electrostatic and entropic interactions driving selective corona formation. Lastly, we study real‐time protein binding on ssDNA‐SWCNTs, obtaining agreement between enriched proteins binding strongly and depleted proteins binding marginally, while highlighting cooperative adsorption mechanisms. Knowledge of protein corona composition, formation mechanisms, and dynamics informs nanoparticle translation from in vitro design to in vivo application.
Atherosclerosis Inflammation Imaging with 18F-FDG PET: Carotid, Iliac, and Femoral Uptake Reproducibility, Quantification Methods, and Recommendations (2008)

We found that both mean and maximum TBR in the carotid, iliac, and femoral arteries were highly reproducible. We suggest the mean TBR be used for tracking systemic arterial therapies, whereas the maximum TBR is optimal for detecting and monitoring local, plaque-based therapy.
In Silico Evaluation Platform for Artificial Pancreatic β -Cell Development—A Dynamic Simulator for Closed-Loop Control with Hardware-in-the-Loop (2009)

A complete artificial beta-cell evaluation platform was realized with the flexibility to interface various algorithms and patient models, allowing for the systematic analysis of monitoring and control algorithms. The system facilitates a variety of tests and challenges to the software and the component devices, streamlining preclinical validation trials.
Certificateless public key encryption with keyword search (2014)

Public Key Encryption with Keyword Search (PEKS), an indispensable part of searchable encryption, is stock-in-trade for both protecting data and providing operability of encrypted data. So far most of PEKS schemes have been established on Identity-Based Cryptography (IBC) with key escrow problem inherently. Such problem severely restricts the promotion of IBC-based Public Key Infrastructure including PEKS component. Hence, Certifcateless Public Key Cryptography (CLPKC) is efficient to remove such problem. CLPKC is introduced into PEKS, and a general model of Certifcateless PEKS (CLPEKS) is formalized. In addition, a practical CLPEKS scheme is constructed with security and efficiency analyses. The proposal is secure channel free, and semantically secure against adaptive chosen keyword attack and keyword guessing attack. To illustrate the superiority, massive experiments are conducted on Enron Email dataset which is famous in information retrieval field. Compared with existed constructions, CLPEKS improves the efficiency in theory and removes the key escrow problem.
Novel structures by microlayer coextrusion—talc‐filled PP, PC/SAN, and HDPE/LLDPE (1997)

Abstract Numerous examples in the literature illustrate how the coextrusion of film with three or more polymeric layers is economically used to achieve a desirable mix of end‐use characteristics. More recently, layer‐multiplying devices permit two polymers of widely dissimilar solid‐state properties to be combined into unique microlayer and nanolayer structures with hundreds or thousands of alternating layers. If the layers are thin enough, the key properties of the constituents can combine synergistically. The microlayer structure is also an effective research tool. Because the microlayer and nanolayer structures contain large specific interfacial areas, they are ideal for fundamental studies of phenomena such as interdiffusion and adhesion. Three examples of microlayered materials with up to 1024 layers illustrate the versatility of this coextrusion process: talc‐filled PP, PC/SAN, and HDPE/LLDPE.
2392 (2017)

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to use the baboon as a novel animal model for breath research and to identify and characterize baboon breath metabolites that reflect cardiometabolic function to inform us in the development of a noninvasive, cost-effective, and repeatable point-of-care diagnostic breath test. METHODS/STUDY POPULATION: Blood and urine was collected from control and IUGR at the approximate age of 3.5 years. Both groups were then placed on a high fat, high sugar, high salt diet for 7 weeks, after which blood, urine, and breath were collected. The breath samples were then subjected to comprehensive, 2-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Using ChromaTOF software, breath VOCs were identified with at least an 80% spectral match against the National Institute of Standards and Technology (NIST) chemical reference library. The raw data were then statistically analyzed using MetaboAnalyst. We then interrogated multiple online databases to characterize and identify the role of VOCs that were present in both control and IUGR groups. RESULTS/ANTICIPATED RESULTS: Preliminary analyses of the breath VOCs indicate differences in expression between sexes and in control Versus IUGR groups. These results indicate unique “breath signatures.” Further analysis of the breath VOCs reveals the presence of metabolites that are involved in β-oxidation and oxidative stress pathways. DISCUSSION/SIGNIFICANCE OF IMPACT: This breath study, a first of its kind, will develop the baboon as a superior animal model for breath biomarker research. Our observed unique “breath signatures” indicate changes in lipid metabolism and oxidative stress pathways, which we hypothesize are the early metabolic changes at the cellular level that are not yet reflected in clinical lab measures. Future directions include analyzing breath VOCs that did not meet 80% spectral match, validation using SPME technology and commercial standards, and initiating a human pilot study in clinically obese, at-risk children in collaboration with physicians at the Children’s Hospital of San Antonio to develop a noninvasive, cost-effective, rapid, and repeatable point-of-care diagnostic breath test.
Arthroscopically Repaired Bucket-Handle Meniscus Tears: Patient Demographics, Postoperative Outcomes, and a Comparison of Success and Failure Cases (2018)

With the exception of the absence of other knee pathology (including ligament tear, contralateral compartment meniscal tear, or cartilage lesions) noted intraoperatively, no other variables were significantly associated with re-tear. The results are relatively durable with 84.6% survival at 1 year. Surgeons should attempt meniscal repair when presented with a bucket-handle tear.
Exploring the Gender Gap in Engineering: A Re‐Specification and Test of the Hypothesis of Cumulative Advantages and Disadvantages (2001)

Abstract Researchers using the hypothesis of cumulative advantages and disadvantages argue that the accumulation of small advantages for men and small disadvantages for women contributes to the gender gap in engineering. This paper uses data from a 1998 survey of engineering undergraduates to test a re‐specification of this hypothesis that treats the gender distribution of advantages and disadvantages as an empirical question. We considered four sets of factors that have been shown to promote choice of an engineering major, persistence in engineering, and progress in engineering: family background, high school participation in mathematics and science, university participation in engineering, and integration into engineering. We found gender differences for each set of factors. We also found that men and women accumulate different advantages and disadvantages as they move through the education pipeline. By demonstrating that the accumulation of advantages and disadvantages is gendered, these results highlight the importance of examining the impact of micro‐inequities on the persistence and progress of men and women in engineering.