gebhart/patrepeval huggingface dataset:
Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (<i>S</i>)-4-Amino-4,5-dihydro-2-thiophenecarboxylic Acid (1999)

(S)-4-Amino-4,5-dihydro-2-thiophenecarboxylic acid ((S)-6) was previously synthesized (Adams, J. L.; Chen, T. M.; Metcalf, B. W. J. Org. Chem. 1985, 50, 2730−2736.) as a heterocyclic mimic of the natural product gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid), a mechanism-based inactivator of γ-aminobutyric acid aminotransferase (GABA-AT) (Rando, R. R. Biochemistry 1977, 16, 4604). Inactivation of GABA-AT by (S)-6 is time-dependent and protected by substrate. Two methods were utilized to demonstrate that, in addition to inactivation, about 0.7 equiv per inactivation event undergoes transamination. Inactivation results from the reaction of (S)-6 with the pyridoxal 5‘-phosphate (PLP) cofactor. The adduct was isolated and characterized by ultraviolet−visible spectroscopy, electrospray mass spectrometry, and tandem mass spectrometry. All of the results support a structure (11) that derives from the predicted aromatization inactivation mechanism (Scheme 2) originally proposed by Metcalf and co-workers for this compound. This is only the third example, besides gabaculine and l-cycloserine, of an inactivator of a PLP-dependent enzyme that acts via an aromatization mechanism.
Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants (2017)

Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established inflammation in animal models. We conducted a pilot safety and feasibility trial of autologous Treg cell therapy in three kidney transplant recipients with subclinical inflammation noted on 6-month surveillance biopsies. Tregs were purified from peripheral blood and polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received a single infusion of ~320 × 10<sup>6</sup> (319, 321, and 363.8 × 10<sup>6</sup> ) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow-up biopsies and urinary biomarkers. Nearly 1 × 10<sup>9</sup> (0.932, 0.956, 1.565 × 10<sup>9</sup> ) Tregs were successfully manufactured for each patient. There were no infusion reactions or serious therapy-related adverse events. The infused cells demonstrated patterns of persistence and stability similar to those observed in non-immunosuppressed subjects receiving the same dose of Tregs. Isolation and expansion of Tregs is feasible in kidney transplant patients on immunosuppression. Infusion of these cells was safe and well tolerated. Future trials will test the efficacy of polyclonal and donor alloantigen-reactive Tregs for the treatment of inflammation in kidney transplants.
Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by <i>Staphylococcus aureus</i> and supports fracture healing (2018)

Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat <i>Staphylococcus aureus</i> infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated <i>S. aureus</i> infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant <i>S. aureus</i> infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic <i>S. aureus</i> infections while simultaneously supporting fracture repair.
Efficient wave-equation-based diffraction imaging (2019)

ABSTRACT We have developed an efficient and practical wave-equation-based technique to image subsurface geologic features such as isolated scatterers, reflector edges, fault, fracture zones, and erosion whose information is mainly contained in diffracted waves. This technique has the ability to directly reveal and differentiate important geologic features compared with results obtained using reflected seismic waves. This new technique comprises three steps. First, the source and receiver wavefields are decomposed into left- and right-downgoing propagating waves, respectively. Second, applying the imaging condition to the right-downgoing source and receiver wavefields to generate the so-called right-right image. Similarly, a left-left image is generated. Third, the left-left and right-right images are multiplied sample-by-sample to form the final diffraction-based image. The key idea of this method is based on the fact that any dipping reflector exhibits a particular dip direction, so its subsurface image can exist either in the left-left or the right-right image, but not in both. As a result, the sample-by-sample multiplication of the two images eliminates the reflector images. Alternatively, because diffractions are generated by subsurface geologic features, which act as secondary sources and radiate in all directions, ranging from −90° to 90°, their energy can exist in both images. After multiplication of both images, only the diffractors remain, whereas the reflectors are suppressed. Our method is applicable only for diffracting objects that radiate in all directions. An exception occurs when reflectors exhibit zero dip. In such a case, zero-dip reflectors could be present in both images and leak into the final diffractor image. We mitigate this problem in several ways, such as omitting near zero-offset input data, muting vertical-propagation components, or applying an f-k filter on the final diffraction image.
816. Development of Potent DNA Vaccines by Coupling of Linear MIDGE Vectors to Peptides (2004)

The Sleeping Beauty (SB) transposon represents an important vehicle for in vivo gene delivery because it can stably integrate into the genomes of mammalian cells. Although SB is the most efficient non-viral integrating system described to date, all previous estimations of SB's integrative potential have relied on the use of antibiotic selection schemes. Previous work in other integrating systems (e.g. retroviruses) has demonstrated significant post-integrative gene silencing, leading us to investigate how genomic integration influences transposon expression in human cells. To do this we devised a new strategy to monitor SB integration that is not dependent on transgene expression. We constructed a single autonomously integrating plasmid (pT/YFP-SB) containing a YFP-marked transposon and an external plasmid-encoded transposase expression cassette, and transfected it into HeLa cells. Shortly thereafter, cells were single-cell sorted by FACS to generate a total of 183 clonal cell populations. Unexpectedly, after 6 weeks of growth (> 30 cell divisions) 28% of the cell lines continue to show stable transgene expression, as determined by fluorescence microscopy. We have begun screening these cell lines for the presence of transposon sequences by both PCR and Southern blot analyses, using various restriction enzymes to determine (i) the copy number and (ii) the molecular forms of the transposable element. Interestingly, preliminary results indicate that up to 15% of the total cell lines contain non-expressing integrated transgenes and we are currently investigating whether this may be due to post-integrative gene silencing. Surprisingly, up to 40% of the expressing cell lines contain persisting (non-dividing) episomal plasmid, as determined by DpnI/Southern blot analyses. Consequently, we are investigating whether co-delivery of SB and transposon sequences can facilitate episomal persistence in mammalian cells, possibly through transposase-mediated nuclear retention. Also of note, many individual cell lines showed heterogeneous YFP levels throughout the cell population. Currently, we are testing whether expression from an integrated transposon varies with the cell cycle, as has been seen in other integrating systems. The generation of stably silenced transposon clones provides an important new reagent to investigate the mechanism(s) by which integrating genetic elements (e.g. transposons and retroviruses) are silenced by the host cell, and should further our understanding of Sleeping Beauty biology.
STBC MIMO-OFDM peak-to-average power ratio reduction by cross-antenna rotation and inversion (2005)

Multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) has become a promising candidate for high performance 4G broadband wireless communications. However, like OFDM, one main disadvantage of MIMO-OFDM is that the signals transmitted on different antennas might exhibit a prohibitively large peak-to-average power ratio (PAPR). We will show that the PAPR reduction for MIMO-OFDM needs a more efficient solution than applying existing schemes for OFDM systems separately on each antenna. Further, we suggest a scheme of cross-antenna rotation and inversion (CARI), which utilizes additional degrees of freedom by employing multiple antennas. Two suboptimal schemes, termed successive suboptimal CARI (SS-CARI) and random suboptimal (RS-CARI) show significant performance advantages and lower computational complexity compared to the concurrent selective mapping (SLM) scheme proposed in Y. -L. Lee et al. (2003).
Current State Of The Art In InSb Infrared Staring Imaging Devices (1987)

A monolithic 128 x 128 InSb array is described for staring infrared imaging systems operating in the 3-5μm spectral region. The array is fabricated with only 4 mask levels and has almost 5 times higher responsivity and nearly 14 times greater wafer yield as compared to a previous design. The higher responsivity has resulted in demonstration of significantly improved thermal imagery.
A New Method for Nonlinear and Nonstationary Time Series Analysis and Its Application to the Earthquake and Building Response Records (1999)

A new method for analyzing nonlinear and nonstationary data has been developed. The key part of the method is the Empirical Mode Decomposition method with which any complicated data set can be decomposed into a finite and often small number of Intrinsic Mode Functions (IMF). An IMF is defined as any function having the same numbers of zero-crossing and extrema, and also having symmetric envelopes defined by the local maxima and minima respectively. The IMF also admits well-behaved Hilbert transform. This decomposition method is adaptive, and, therefore, highly efficient. Since the decomposition is based on the local characteristic time scale of the data, it is applicable to nonlinear and nonstationary processes. With the Hilbert transform, the Intrinsic Mode Functions yield instantaneous frequencies as functions of time that give sharp identifications of imbedded structures. The final presentation of the results is an energy-frequency-time distribution, designated as the Hilbert Spectrum, Example of application of this method to earthquake and building response will be given. The results indicate those low frequency components, totally missed by the Fourier analysis, are clearly identified by the new method. Comparisons with Wavelet and window Fourier analysis show the new method offers much better temporal and frequency resolutions.
Synthesis and Photoinitiated Cationic Polymerization of Epoxidized Elastomers (1994)

Abstract Low and high molecular weight cis-l,4-poly(isoprene), 1,4-poly-(butadiene), and 1,2-poly(butadiene) were epoxidized using a tungsten-based redox phase transfer catalyst and hydrogen peroxide. The epoxidation reaction was studied with respect to the influence of the structure on the rate and extent of epoxidation. A study of the photoinduced cationic crosslinking of these oligomers and polymers was carried out in the presence of UV light. Specialized photoinitiators consisting of diaryliodonium salts bearing long alkoxy chains attached to the aromatic rings were prepared and used in these studies. The effects of the structure of the epoxidized elastomer, its level of epoxidation, and the concentration and type of photoinitiator on the rate and extent of crosslinking polymerization were studied.
Sound Field Control Using a Limited Number of Loudspeakers (2009)

We treat the problem of optimizing N digital filters for a sound system consisting of N loudspeaker inputs and M measurement output positions, with the objective of creating a target sound field described by M prescribed transfer functions, one for each measurement position. We pose the problem in a control-theoretic framework, with the main interest on practical car audio systems, i.e. where N ≪M. The solution is verified in listening experiments and by objective means. It is shown that the proposed framework provides a unified solution to the problem of equalizer design, crossover design, delay and level calibration, sum-response optimization, and up-mixing (the process of routing 2-channel or 5.1-channel source material to N loudspeaker outputs).
Opioid Diketopiperazines: Synthesis and Activity of a Prototypic Class of Opioid Antagonists (1997)

Discovery of high affinity and ultraselective delta opioid dipeptide antagonists composed of 2',6'-dimethyl-L-tyrosyl (Dmt) and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic (Tic) served as the basis for the conformationally restricted diketopiperazine cyclo(Dmt-Tic) and related open chain analogues. These peptides primarily bind to delta opioid receptors: c(Dmt-Tic) displayed 30- to 50-fold higher delta affinity (Ki delta) than its diastereo-isomeric analogues and more than 4000-fold greater than its Tyr cognate; all of the c(Tyr-Tic) analogues were essentially inactive; c[(N-methyl)Dmt-Tic] lost 5-fold in Ki delta, while Ki mu increased 10-fold to yield a nonselective peptide; and the c(Dmt-Phe) series exhibited considerably reduced binding which indicated a synergism between Dmt and Tic in the binding mechanism. Whereas acetyl-Dmt-Tic linear peptides weakly interacted with opioid receptors, Ac-Dmt-Tic-NH2, exhibited better delta antagonist activity than c(Dmt-Tic) and greater delta receptor selectivity (Ki mu/Ki delta = 570). A three point attachment hypothesis for the interaction between c(Dmt-Tic) and the delta receptor was proposed: hydrophobicity imparted by the aromatic rings and the methyl groups of Dmt, hydrogen bonding through the tyramine hydroxyl group, and cation-pi interactions were suggested as contributing factors in binding the diketopiperazine in the receptor pocket. Although c(Dmt-Tic) exhibited a weak antagonist activity with mouse vas deferens, this diketopiperazine may provide a scaffolding for the formation of more potent antagonists for potential therapeutic applications.
A Progressively-trained Scale-invariant and Boundary-aware Deep Neural Network for the Automatic 3D Segmentation of Lung Lesions (2018)

Volumetric segmentation of lesions on CT scans is important for many types of analysis, including lesion growth kinetic modeling in clinical trials and machine learning of radiomic features. Manual segmentation is laborious, and impractical for large-scale use. For routine clinical use, and in clinical trials that apply the Response Evaluation Criteria In Solid Tumors (RECIST), clinicians typically outline the boundaries of a lesion on a single slice to extract diameter measurements. In this work, we have collected a large-scale database, named LesionVis, with pixel-wise manual 2D lesion delineations on the RECIST-slices. To extend the 2D segmentations to 3D, we propose a volumetric progressive lesion segmentation (PLS) algorithm to automatically segment the 3D lesion volume from 2D delineations using a scale-invariant and boundary-aware deep convolutional network (SIBA-Net). The SIBA-Net copes with the size transition of a lesion when the PLS progresses from the RECIST-slice to the edge-slices, as well as when performing longitudinal assessment of lesions whose size change over multiple time points. The proposed PLS-SiBA-Net (P-SiBA) approach is assessed on the lung lesion cases from LesionVis. Our experimental results demonstrate that the P-SiBA approach achieves mean Dice similarity coefficients (DSC) of 0.81, which significantly improves 3D segmentation accuracy compared with the approaches proposed previously (highest mean DSC at 0.78 on LesionVis). In summary, by leveraging the limited 2D delineations on the RECIST-slices, P-SiBA is an effective semi-supervised approach to produce accurate lesion segmentations in 3D.
Test structures and test methodology for developing high voltage ESD protection (2003)

In this work, test structures and a test methodology is developed to evaluate proposed silicon controlled rectifier based ESD clamps in all modes of operation. TCAD analysis is used to identify possible ESD clamp structures. Standard ESD testing on the stand-alone test structures is used to screen the ESD capability of the candidate clamps. The transmission line pulse technique, with variation in pulse rise time, is used to evaluate the dynamic triggering characteristics of a snapback based clamp and select an appropriate clamp for fast switching applications. Finally, a very efficient local ESD clamp based on a bipolar-silicon controlled rectifier in a 24 V complementary power BiCMOS smart power process is presented.
Prevention of PCR Cross-Contamination by UNG Treatment of Bisulfite-Treated DNA (2008)

Amplification of sodium bisulfite-treated DNA is widely used to study DNA methylation. The proportion of methylated sequences of a specific DNA region in a sample can be determined by the analysis of PCR products or directly calculated from real-time PCR amplification of bisulfite-treated DNA. At the same time, PCR based methods always involve the risk of false positive or incorrect quantitative results due to the unintended reamplification of contaminating PCR products. The incubation of PCR reactions with Uracil-DNA Glycosylase (UNG) prior to the thermal cycling in combination with the use of dUTP in the PCR amplification is a commonly used technology to prevent such cross-contamination. Since sodium bisulfite treatment converts unmethylated cytosine bases into uracil residues, not only contaminating PCR products but also the converted template DNAs would be degraded as well. This chapter describes a modified bisulfite treatment procedure to generate sulfonated DNA enabling the application of UNG-based carryover prevention to DNA methylation analysis. The high efficiency of the decontamination procedure as well as the universal applicability of this simple method is shown.
A Human Thermoregulation Simulator for Calibrating Water-Perfused Cooling Pad Systems for Therapeutic Hypothermia (2017)

The induction of a mild reduction in body core temperature has been demonstrated to provide neuroprotection for patients who have suffered a medical event resulting in ischemia to the brain or vital organs. Temperatures in the range of 32–34 °C provide the required level of protection and can be produced and maintained by diverse means for periods of days. Rewarming from hypothermia must be conducted slowly to avoid serious adverse consequences and usually is performed under control of the thermal therapeutic device based on a closed-loop feedback strategy based on the patient's core temperature. Given the sensitivity and criticality of this process, it is important that the device control system be able to interact with the human thermoregulation system, which itself is highly nonlinear. The therapeutic hypothermia device must be calibrated periodically to ensure that its performance is accurate and safe for the patient. In general, calibration processes are conducted with the hypothermia device operating on a passive thermal mass that behaves much differently than a living human. This project has developed and demonstrated an active human thermoregulation simulator (HTRS) that embodies major governing thermal functions such as central metabolism, tissue conduction, and convective transport between the core and the skin surface via the flow of blood and that replicates primary dimensions of the torso. When operated at physiological values for metabolism and cardiac output, the temperature gradients created across the body layers and the heat exchange with both an air environment and a clinical water-circulating cooling pad system match that which would occur in a living body. Approximately two-thirds of the heat flow between the core and surface is via convection rather than conduction, highlighting the importance of including the contribution of blood circulation to human thermoregulation in a device designed to calibrate the functioning of a therapeutic hypothermia system. The thermoregulation simulator functions as anticipated for a typical living patient during both body cooling and warming processes. This human thermoregulatory surrogate can be used to calibrate the thermal function of water-perfused cooling pads for a hypothermic temperature management system during both static and transient operation.
Engineering the Substrate Transport and Cofactor Regeneration Systems for Enhancing 2′-Fucosyllactose Synthesis in <i>Bacillus subtilis</i> (2019)

Human milk oligosaccharides (HMOs) have been proven to be beneficial to infants' intestinal health and immune systems. 2'-Fucosyllactose (2'-FL) is the most abundant and thoroughly studied HMO and has been approved to be an additive of infant formula. How to construct efficient and safe microbial cell factories for the production of 2'-FL attracts increasing attention. In this work, we engineered the <i>Bacillus subtilis</i> as an efficient 2'-FL producer by engineering the substrate transport and cofactor guanosine 5'-triphosphate (GTP) regeneration systems. First, we constructed a synthesis pathway for the 2'-FL precursor guanosine 5'-diphosphate-l-fucose (GDP-l-fucose) by introducing the <i>salvage</i> pathway gene <i>fkp</i> from <i>Bacteriodes fragilis</i> and improved the fucose importation by overexpressing the transporters. Then, the complete synthesis pathway of 2'-FL was constructed by introducing the heterologous fucosyltransferases from different sources, and it was found that the gene from <i>Helicobacter pylori</i> was the best one for 2'-FL synthesis. We also improved the substrate lactose importation by introducing heterologous lactose permeases and eliminated endogenous β-galactosidase (<i>yesZ</i>) to block the lactose degradation. Next, the production of 2'-FL and GDP-l-fucose was improved by fine-tuning the expression of cofactor guanosine 5'-triphosphate regeneration module genes <i>gmd</i>, <i>ndk</i>, <i>guaA</i>, <i>guaC</i>, <i>ykfN</i>, <i>deoD</i>, and <i>xpt</i>. Finally, a 3 L fed-batch fermentation was performed, and the highest 2'-FL titer reached 5.01 g/L with a yield up to 0.85 mol/mol fucose. We optimized the synthesis modules of 2'-FL in <i>B. subtilis</i>, and this provides a good starting point for metabolic engineering to further improve 2'-FL production in the future.