gebhart/patrepeval huggingface dataset:
An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo (1993)

Most Borrelia burgdorferi strains have two major surface proteins, OspA and OspB. In the present study, we selected from a clonal population of infectious B. burgdorferi an OspB escape mutant, identified the genetic basis for this phenotype, and evaluated its functional activities. Selection with the anti-OspB antibody H614 was performed in vitro in medium and extended in vivo in scid mice. Mutants with a truncated OspB protein were selected at a frequency of 1 x 10(-5) to 3 x 10(-5). After no major rearrangements in DNA were detected, sequence analysis of the mutant's ospAB locus revealed a single base change in the consensus ribosomal binding sequence for ospB and a single nucleotide deletion in the ospB gene itself. The effect of these mutations was reduced expression of a truncated OspB protein. When functional abilities of the wild type and mutant were compared, the mutant had a threefold-lower capacity to penetrate a human endothelium umbilical vein cell monolayer. Infectivity of wild-type and mutant cells for scid mice was evaluated by culturing different organs, and the median infectious dose was calculated. The inoculum of mutant cells for infecting the mice was 30- to 300-fold higher than that of wild-type cells. This study shows that reduced size and expression of OspB are associated with lowered virulence of B. burgdorferi. Selection of mutants that to some degree remain infectious is one approach to defining the role of different surface proteins in the pathogenesis of Lyme disease.
Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver (2014)

Background: Colorectal cancer is the third most frequently diagnosed cancer and the third cause of cancer deaths in the United States. Despite the fact that tumor cell-intrinsic mechanisms controlling colorectal carcinogenesis have been identified, novel prognostic and diagnostic tools as well as novel therapeutic strategies are still needed to monitor and target colon cancer progression. We and others have previously shown, using mouse models, that the extracellular matrix (ECM), a major component of the tumor microenvironment, is an important contributor to tumor progression. In order to identify candidate biomarkers, we sought to define ECM signatures of metastatic colorectal cancers and their metastases to the liver. Methods: We have used enrichment of extracellular matrix (ECM) from human patient samples and proteomics to define the ECM composition of primary colon carcinomas and their metastases to liver in comparison with normal colon and liver samples. Results: We show that robust signatures of ECM proteins characteristic of each tissue, normal and malignant, can be defined using relatively small samples from small numbers of patients. Comparisons with gene expression data from larger cohorts of patients confirm the association of subsets of the proteins identified by proteomic analysis with tumor progression and metastasis. Conclusions: The ECM protein signatures of metastatic primary colon carcinomas and metastases to liver defined in this study, offer promise for development of diagnostic and prognostic signatures of metastatic potential of colon tumors. The ECM proteins defined here represent candidate serological or tissue biomarkers and potential targets for imaging of occult metastases and residual or recurrent tumors and conceivably for therapies. Furthermore, the methods described here can be applied to other tumor types and can be used to investigate other questions such as the role of ECM in resistance to therapy.
Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus (2011)

Influenza A and B viruses are major human respiratory pathogens that contribute to the burden of seasonal influenza. They are both members of the family Orthomyxoviridae but do not interact genetically and are classified in different genera. Defective interfering (DI) influenza viruses have a major deletion of one or more of their eight genome segments, which renders them both non-infectious and able to interfere in cell culture with the production of infectious progeny by a genetically compatible, homologous virus. It has been shown previously that intranasal administration of a cloned DI influenza A virus, 244/PR8, protects mice from various homologous influenza A virus subtypes and that it also protects mice from respiratory disease caused by a heterologous virus belonging to the family Paramyxoviridae. The mechanisms of action in vivo differ, with homologous and heterologous protection being mediated by probable genome competition and type I interferon (IFN), respectively. In the current study, it was shown that 244/PR8 also protects against disease caused by a heterologous influenza B virus (B/Lee/40). Protection from B/Lee/40 challenge was partially eliminated in mice that did not express a functional type I IFN receptor, suggesting that innate immunity, and type I IFN in particular, are important in mediating protection against this virus. It was concluded that 244/PR8 has the ability to protect in vivo against heterologous IFN-sensitive respiratory viruses, in addition to homologous influenza A viruses, and that it acts by fundamentally different mechanisms.
Design and biological evaluation of synthetic retinoids: probing length <i>vs.</i> stability <i>vs.</i> activity (2013)

Abstract All trans-retinoic acid (ATRA) is widely used to direct the differentiation of cultured stem cells. When exposed to the pluripotent human embryonal carcinoma (EC) stem cell line, TERA2.cl.SP12, ATRA induces ectoderm differentiation and the formation of neuronal cell types. We report in this study that novel polyene chain length analogues of ATRA require a specific chain length to elicit a biological responses of the EC cells TERA2.cl.SP12, with synthetic retinoid AH61 being particularly active, and indeed more so than ATRA. The impacts of both the synthetic retinoid AH61 and natural ATRA on the TERA2.cl.SP12 cells were directly compared using both RT-PCR and Fourier Transform Infrared Micro-Spectroscopy (FT-IRMS) coupled with multivariate analysis. Analytical results produced from this study also confirmed that the synthetic retinoid AH61 had biological activity comparable or greater than that of ATRA. In addition to this, AH61 has the added advantage of greater compound stability than ATRA, therefore, avoiding issues of oxidation or decomposition during use with embryonic stem cells.
Effect of Ti substitution on the thermoelectric properties of the pentatelluride materials M1−xTixTe5 (M=Hf, Zr) (1998)

The thermoelectric properties (resistivity and thermopower) of single crystals of the low dimensional pentatelluride materials, HfTe5 and ZrTe5, have been measured as a function of temperature from 10 K&lt;T&lt;320 K. The effect of small amounts of Ti substitutional doping (M1−xTixTe5, where M=Hf, Zr) on the thermoelectric properties is reported here. A resistive transition occurs in the pentatellurides, as evidenced by a peak in the resistivity, TP≈80 K for HfTe5 and TP≈145 K for ZrTe5. Both parent materials exhibit a large positive (p-type) thermopower near room temperature which undergoes a change to negative (n-type) below the peak temperature. The thermal conductivity is relatively low (≈5 W/m K) for the MTe5 materials. The Ti substitution affects the electronic properties strongly, producing a substantial shift in the peak temperature while the large values of thermopower remain essentially unaffected. These results warrant further investigation of these materials as candidates for low temperature thermoelectric applications.
Improving Paclitaxel Delivery:<i>In Vitro</i>and<i>In Vivo</i>Characterization of PEGylated Polyphosphoester-Based Nanocarriers (2015)

Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to <2.0 μg/mL for the aqueous solubility of the drug alone. Drug release studies indicated that PTX released from these nanostructures was defined through a structure-function relationship, whereby the half-life of sustained PTX release was doubled through cross-linking of the micellar structure to form SCKs. In vitro, physically loaded micellar and SCK nanotherapeutics demonstrated IC50 values against osteosarcoma cell lines, known to metastasize to the lungs (CCH-OS-O and SJSA), similar to the pharmaceutical Taxol formulation. Evaluation of these materials in vivo has provided an understanding of the effects of nanoparticle structure-function relationships on intratracheal delivery and related biodistribution and pharmacokinetics. Overall, we have demonstrated the potential of these novel nanotherapeutics toward future sustained release treatments via administration directly to the sites of lung metastases of osteosarcoma.
Development of a novel method for synthesis of a polymeric ultrasound contrast agent (2003)

Medical ultrasound is a highly valuable diagnostic tool, especially when compared with other imaging modalities. It is a noninvasive, real-time, portable, extremely safe method compared with X-ray and inexpensive relative to magnetic resonance imaging. However, ultrasound is limited in its ability to distinguish between diseased and normal tissue. This limitation has led to the development of contrast agents. We have produced novel poly (lactic-co-glycolic) acid air-filled microcapsules that work well as ultrasound contrast agents, giving up to 24 and 25 dB enhancement when insonated in the medical imaging range at 5 and 7.5 MHz, respectively. The capsules were fabricated by modifying a double emulsion method to encapsulate camphor in the oil phase and ammonium carbonate in the aqueous phase, and later sublime the encapsulated material, leaving voids capable of being filled with a gas in their place. The role of the surfactant, poly vinyl alcohol, solution temperature, was studied and found to play an important role in the morphology of the capsules, altering their acoustic response.
Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype (2014)

Polycystic ovary syndrome (PCOS), characterized by increased ovarian androgen biosynthesis, anovulation, and infertility, affects 5-7% of reproductive-age women. Genome-wide association studies identified PCOS candidate loci that were replicated in subsequent reports, including DENND1A, which encodes a protein associated with clathrin-coated pits where cell-surface receptors reside. However, these studies provided no information about functional roles for DENND1A in the pathogenesis of PCOS. DENND1A protein was located in the cytoplasm as well as nuclei of theca cells, suggesting a possible role in gene regulation. DENND1A immunostaining was more intense in the theca of PCOS ovaries. Using theca cells isolated and propagated from normal cycling and PCOS women, we found that DENND1A variant 2 (DENND1A.V2) protein and mRNA levels are increased in PCOS theca cells. Exosomal DENND1A.V2 RNA was significantly elevated in urine from PCOS women compared with normal cycling women. Forced overexpression of DENND1A.V2 in normal theca cells resulted in a PCOS phenotype of augmented CYP17A1 and CYP11A1 gene transcription, mRNA abundance, and androgen biosynthesis. Knock-down of DENND1A.V2 in PCOS theca cells reduced androgen biosynthesis and CYP17A1 and CYP11A1 gene transcription. An IgG specific to DENND1A.V2 also reduced androgen biosynthesis and CYP17 and CYP11A1 mRNA when added to the medium of cultured PCOS theca cells. We conclude that the PCOS candidate gene, DENND1A, plays a key role in the hyperandrogenemia associated with PCOS. These observations have both diagnostic and therapeutic implications for this common disorder.
Design and Synthesis of 6‐Substituted Amino‐4‐oxa‐1‐azabicyclo[3,2,0]heptan‐7‐one Derivatives as Cysteine Proteases Inhibitors. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Improved glycaemic control in obese diabetic ob/ob mice using N-terminally modified gastric inhibitory polypeptide (2000)

Gastric inhibitory polypeptide (GIP) is an important insulin-releasing hormone of the enteroinsular axis which is rapidly inactivated by the exopeptidase dipeptidyl peptidase (DPP) IV. The present study has examined the ability of Tyr(1)-glucitol GIP to be protected from plasma degradation and to enhance insulin-releasing and antihyperglycaemic activity in 20- to 25-week-old obese diabetic ob/ob mice. Degradation of GIP by incubation at 37 degrees C with obese mouse plasma was clearly evident after 3 h (35% degraded). After 6 h, more than 61% of GIP was converted to GIP(3-42) whereas N-terminally modified Tyr(1)-glucitol GIP was resistant to degradation in plasma (>99% intact after 6 h). The formation of GIP(3-42) was almost completely abolished by inhibition of plasma DPP IV with diprotin A. Effects of GIP and Tyr(1)-glucitol GIP were examined in overnight-fasted obese mice following i.p. injection of either peptide (20 nmol/kg) together with glucose (18 mmol/kg) or in association with feeding. Most prominent effects were observed in the former group where plasma glucose values at 60 min together with the area under the curve (AUC) for glucose were significantly lower following GIP (AUC, 874+/-72 mmol/l.min; P<0.01) or Tyr(1)-glucitol GIP (770+/-134 mmol/l.min; P<0.001) as compared with administration of glucose alone (1344+/-136 mmol/l.min). This was associated with a significantly greater and more protracted insulin response following Tyr(1)-glucitol GIP than GIP (AUC, 491+/-118 vs 180+/-33 ng/ml.min; P<0.05). Administration of Tyr(1)-glucitol GIP also enhanced the glucose-lowering ability of 50 units/kg insulin (218.4+/-30.2 vs insulin alone 133.9+/-16.2 mmol/l.min; P<0.05). These data demonstrate that Tyr(1)-glucitol GIP displays resistance to plasma DPP IV degradation in a commonly used animal model of type 2 diabetes, resulting in enhanced antihyperglycaemic activity and insulin-releasing action in vivo.
Dynamics of Mycotoxin and <i>Aspergillus flavus</i> Levels in Aging Bt and Non-Bt Corn Residues under Mississippi No-Till Conditions (2008)

Mycotoxin and Aspergillus flavus levels in soil-surface corn debris left by no-till agriculture methods (stover, cobs, and cobs with grain) were determined during the December-March fallow period for near-isogenic Bt and non-Bt hybrid corn. By December, average mycotoxin levels in non-Bt corn were many times higher in cobs with grain than in grain harvested in September (total aflatoxins, 774 vs 211 ng/g; total fumonisins, 216 vs 3.5 microg/g; cyclopiazonic acid, 4102 vs 72.2 microg/g; zearalenone, 0.2 vs < 0.1 microg/g). No trichothecenes were detected. Levels of mycotoxins and A. flavus propagules were approximately 10- to 50-fold lower in cobs without grain and stover, respectively, for all mycotoxins except zearalenone. Mycotoxin levels in corn debris fractions decreased during winter but began to rise in March. Levels of all mycotoxins and A. flavus propagules were lower in harvested grain and debris from Bt than non-Bt corn, but differences were significant (p < 0.05) only for aflatoxins.
Efficient remote transmission line probe tuning (1990)

An approach is described which allows remote tuning of a probe via a length of transmission line, while retaining nearly ideal efficiency relative to the equivalent locally tuned coil. This preservation of efficiency is accomplished through the principle of "partial local matching." In comparison to common methods of remote tuning which involve half-wavelength cables, or in which a length of transmission line is itself utilized as a tuning element, the partial matching method results in a substantial increase in the efficiency of power transfer to the coil, and therefore increased B1 field intensity and signal-to-noise ratio. Applications in which the use of local variable tuning capacitors is made difficult by either space, accessibility, or environmental considerations should benefit from this method.
Co‐polarized monostatic antenna with high Tx–Rx isolation for 2.4 GHz single channel full duplex applications (2018)

Abstract This article presents a linear co‐polarized (same polarization for transmit and receive modes), proximity coupled monostatic patch antenna with high port to port RF isolation for 2.4 GHz single channel full duplex (SCFD) wireless applications. The presented proximity coupled monostatic patch antenna deploys differential feeding for receive (R x ) mode to significantly suppress RF leakage from transmit (T x ) port and external single‐tap self‐interference cancellation (SIC) circuit provides additional interport isolation. The measurements for implemented prototype of antenna in lab environment provide around 50 dB T x –R x isolation for 50 MHz bandwidth in addition to better than 75 dB peak isolation. Moreover, the deployed single‐tap RF SIC circuit can be used to suppress SI resulted from environmental reflections and 50 MHz SIC bandwidth with 50 dB isolation can be tuned within antenna's 10 dB return loss impedance bandwidth of 150 MHz.
On synopses for distinct-value estimation under multiset operations (2007)

The task of estimating the number of distinct values (DVs) in a large dataset arises in a wide variety of settings in computer science and elsewhere. We provide DV estimation techniques that are designed for use within a flexible and scalable "synopsis warehouse" architecture. In this setting, incoming data is split into partitions and a synopsis is created for each partition; each synopsis can then be used to quickly estimate the number of DVs in its corresponding partition. By combining and extending a number of results in the literature, we obtain both appropriate synopses and novel DV estimators to use in conjunction with these synopses. Our synopses can be created in parallel, and can then be easily combined to yield synopses and DV estimates for arbitrary unions, intersections or differences of partitions. Our synopses can also handle deletions of individual partition elements. We use the theory of order statistics to show that our DV estimators are unbiased, and to establish moment formulas and sharp error bounds. Based on a novel limit theorem, we can exploit results due to Cohen in order to select synopsis sizes when initially designing the warehouse. Experiments and theory indicate that our synopses and estimators lead to lower computational costs and more accurate DV estimates than previous approaches.
Homonuclear J‐Coupling Spectroscopy at Low Magnetic Fields using Spin‐Lock Induced Crossing** (2021)

Nuclear magnetic resonance (NMR) spectroscopy usually requires high magnetic fields to create spectral resolution among different proton species. Although proton signals can also be detected at low fields the spectrum exhibits a single line if J-coupling is stronger than chemical shift dispersion. In this work, we demonstrate that the spectra can nevertheless be acquired in this strong-coupling regime using a novel pulse sequence called spin-lock induced crossing (SLIC). This techniques probes energy level crossings induced by a weak spin-locking pulse and produces a unique J-coupling spectrum for most organic molecules. Unlike other forms of low-field J-coupling spectroscopy, our technique does not require the presence of heteronuclei and can be used for most compounds in their native state. We performed SLIC spectroscopy on a number of small molecules at 276 kHz and 20.8 MHZ and show that the simulated SLIC spectra agree well with measurements.
RAM-Based frame synchronizer (1980)

Frame synchronizer for serial telemetry is rapidly reconfigured for changing formats. Synchronizer generates signals marking data-word boundaries, beginning of each frame, and beginning of each paragraph. Also derived are search, check, and lock status signals. Existing unit is assembled from standard random-access memory elements and MOS and low-power-Schottky logic.
Optimal Grid Coarsening: A Fast Proxy for Large Reservoir Optimization (2007)

Abstract Reservoir simulation models often require grids sufficiently resolved to capture the complexities of the geological structures present so that pressure and saturation profiles are deemed reasonable enough for decisions to be made with confidence. However, high resolution often implies long simulation run times, which is compounded in optimization problems. Reservoir optimization problems usually involve localized decisions, e.g., production control for a specific time-dependent objective function. With this tighter focus on optimization objectives, the reservoir simulator can often be replaced by an approximate proxy function, e.g., decline curves, neural networks and polynomial response surfaces. This accelerates the run time, allowing the optimizer to make more calls to the simulator, but at the cost of simplified physics and some consequent loss of accuracy. Recent work in numerical solutions of partial differential equations (PDE) by Druskin and Knizhnerman (2000) introduced a finite-volume optimal grid approach to improve solution accuracy of linear PDEs at targeted points of a computational domain. This approach was applied to the solution of electromagnetic and acoustic forward and inverse problems arising in oil exploration and medical imaging. We extend this work to non-linear PDEs by introducing a reservoir simulator that is used as its own proxy. We distinguish our optimal grid from an optimal upscaling in that it may not preserve local features of the model, but will preserve some aggregate objective value used in production optimization. This narrow focus allows greater coarseness than a properly upscaled grid by replacing the fine-grid model with a coarser grid whose coarsening is determined by an optimizer that preserves the accuracy of a predefined aggregate objective value. In this work we optimize injection and production rates to maximize the field oil production total (FOPT) over a fixed period of time. The proxy optimizer will seek the best coarsening that preserves this objective value over a range of injection/production rates for each well. The resulting coarse-grid model has a similar physical behavior in these output values to that of the fine-grid model. The grid coarsening problem is a non-linear discrete optimization problem, where the optimizer adjusts the grid coarsening while preserving the fine-grid response of interest. Although we focus on FOPT here, other reservoir objectives can also be handled.
Resonance Raman detection of carotenoid antioxidants in living human tissues (2001)

We have used resonance Raman scattering as a novel noninvasive optical technology to measure carotenoid antioxidants in living human tissues of healthy volunteers. By use of blue-green laser excitation, clearly distinguishable carotenoid Raman spectra superimposed on a fluorescence background are obtained. The Raman spectra are obtained within less than a minute, and the required laser light exposure levels are well within safety standards. Our technique can be used for rapid screening of carotenoid levels in large populations and may have applications for assessing antioxidant status and the risk for diseases related to oxidative stress.