gebhart/patrepeval huggingface dataset:
Stimulation of renal tubular transport by ethacrynic acid in rats of different ages. (1979)

The transport system for organic acids in the kidney is not fully developed in the neonatal period. The effect of repeated administrations of ethacrynic acid on the renal excretion of p-aminohippurate (PAH) was studied in rats of different ages. Pretreatment with ethacrynic acid was followed by an increase in the renal excretion of PAH in 33-, 55-, 105- and 240-day-old rats but not in newborn rats. In 55-day-old rats the increase in renal excretion of PAH after pretreatment with ethacrynic acid was not associated with any consistent change of the glomerular filtration rate. It is concluded from these results that the stimulation of transport processes in the kidney by ethacrynic acid and some other drugs is linked with their affinity to tissue proteins.
In Silico Analysis of Differential Gene Expression in Three Common Rat Models of Diastolic Dysfunction (2018)

Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences. The top differentially expressed genes in the left ventricle of Dahl salt sensitive (Dahl/SS), spontaneous hypertensive heart failure (SHHF), and diabetes 1 induced HFpEF models were derived from published data in Gene Expression Omnibus and used for a comprehensive interpretation of the underlying pathophysiological context of each model. The diversity of the underlying transcriptomic of the heart of each model is clearly observed by the different panel of top regulated genes: the diabetic model has 20 genes in common with the Dahl/SS and 15 with the SHHF models. Advanced analytics performed in Ingenuity Pathway Analysis (IPA<sup>®</sup>) revealed that Dahl/SS heart tissue transcripts triggered by upstream regulators lead to dilated cardiomyopathy, hypertrophy of heart, arrhythmia, and failure of heart. In the heart of SHHF, a total of 26 genes were closely linked to cardiovascular disease including cardiotoxicity, pericarditis, ST-elevated myocardial infarction, and dilated cardiomyopathy. IPA Upstream Regulator analyses revealed that protection of cardiomyocytes is hampered by inhibition of the ERBB2 plasma membrane-bound receptor tyrosine kinases. Cardioprotective markers such as natriuretic peptide A (<i>NPPA</i>), heat shock 27 kDa protein 1 (<i>HSPB1</i>), and angiogenin (<i>ANG</i>) were upregulated in the diabetes 1 induced model; however, the model showed a different underlying mechanism with a majority of the regulated genes involved in metabolic disorders. In conclusion, our findings suggest that multiple mechanisms may contribute to diastolic dysfunction and HFpEF, and thus drug therapies may need to be guided more by phenotypic characteristics of the cardiac remodeling events than by the underlying molecular processes.
Soluble and membrane levels of molecules involved in the interaction between clonal plasma cells and the immunological microenvironment in multiple myeloma and their association with the characteristics of the disease (2008)

Clonal plasma cells (PC) from different types of monoclonal gammopathies (MG) display distinct phenotypes consistent with an increased antigen-presentation and T-cell costimulation in MG of undetermined significance that deteriorates in malignant conditions. Expression of other cell surface and soluble molecules (e.g. adhesion/proliferation molecules) involved in the interaction between clonal PC and the bone marrow (BM) microenvironment has also been related to malignant PC, although the exact clinical significance of their expression remains largely unknown. Analysis of cell surface levels of several of these molecules in multiple myeloma (MM) patients shows an association between lower expression on BMPC of the HLA-I and beta2-microglobulin antigen-presenting molecules, the CD126 and CD130 IL6 receptor (IL6R) chains, and CD38, and adverse prognostic features of the disease. Likewise, patients showing higher soluble levels of antigen-presenting molecules (HLA-I and beta2-microglobulin), IL6R and CD95 tended to be associated with more aggressive disease behavior. In contrast, CD40, CD86, CD56, CD19, and CD45 were not associated with patients' outcome. Interestingly, upon considering the ratio between the soluble and PC membrane expression of each molecule, an increased adverse prognostic impact was observed for both HLA-I and beta2-microglobulin, but not for the other molecules. Multivariate analysis confirmed the independent prognostic value of cell surface expression of CD126 on BMPC together with serum beta2-microglobulin and LDH. In summary, our results show an abnormal distribution of the cellular and soluble compartments of the HLA-I, IL6R, and to a lower extent, CD95 molecules, in MM, associated with the clinical characteristics and behavior of the disease.
3D Microstructure Characterization and Analysis of Al-Si Foundry Alloys at Different Length Scales (2014)

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Colloidal crystal engineering with metal–organic framework nanoparticles and DNA (2020)

Colloidal crystal engineering with nucleic acid-modified nanoparticles is a powerful way for preparing 3D superlattices, which may be useful in many areas, including catalysis, sensing, and photonics. To date, the building blocks studied have been primarily based upon metals, metal oxides, chalcogenide semiconductors, and proteins. Here, we show that metal-organic framework nanoparticles (MOF NPs) densely functionalized with oligonucleotides can be programmed to crystallize into a diverse set of superlattices with well-defined crystal symmetries and compositions. Electron microscopy and small-angle X-ray scattering characterization confirm the formation of single-component MOF superlattices, binary MOF-Au single crystals, and two-dimensional MOF nanorod assemblies. Importantly, DNA-modified porphyrinic MOF nanorods (PCN-222) were assembled into 2D superlattices and found to be catalytically active for the photooxidation of 2-chloroethyl ethyl sulfide (CEES, a chemical warfare simulant of mustard gas). Taken together, these new materials and methods provide access to colloidal crystals that incorporate particles with the well-established designer properties of MOFs and, therefore, increase the scope of possibilities for colloidal crystal engineering with DNA.
Studies of relativistic backward-wave oscillator operation in the cross-excitation regime (2000)

We first reported the operation of a relativistic backward-wave oscillator (BWO) in the so-called cross-excitation regime in 1998. This instability, whose general properties were predicted earlier through numerical studies, resulted from the use of a particularly shallow rippled-wall waveguide [slow wave structure (SWS)] that was installed in an experiment to diagnose pulse shortening in a long-pulse electron beam-driven high-power microwave (HPM) source. This SWS was necessary to accommodate laser interferometry measurements along the SWS during the course of microwave generation. Since those early experiments, we have studied this regime in greater detail using two different SWS lengths. We have invoked time-frequency analysis, the smoothed-pseudo Wigner-Ville distribution in particular, to interpret the heterodyned signals of the radiated power measurements. These recent results are consistent with earlier theoretical predictions for the onset and voltage scaling for this instability. This paper presents data for a relativistic BWO operating in the single-frequency regime for two axial modes, operating in the cross-excitation regime, and discusses the interpretation of the data, as well as the methodology used for its analysis. Although operation in the cross-excitation regime is typically avoided due to its poorer efficiency, it may prove useful for future HPM effects studies.
The RhoA‐ and CDC42‐specific exchange factor Dbs promotes expansion of immature thymocytes and deletion of double‐positive and single‐positive thymocytes (2004)

Specific members of the Rho family of GTPases exert unique influences on thymocyte proliferation, differentiation and deletion. Dbs is a guanine nucleotide exchange factor which is expressed throughout thymocyte development and is able to activate the Rho family GTPases CDC42, RhoA and RhoG. Transgenic mice expressing an activated form of Dbs had increased numbers of double-negative thymocytes. The Dbs transgene promoted expansion of double-negative thymocytes in the absence of pre-TCR, but had no effect on pre-TCR-dependent differentiation of double-negative thymocytes into double-positive thymocytes. Transgenic double-positive thymocytes were proliferative in vivo, but were also susceptible to apoptosis in vivo and in vitro. The transgenic single-positive thymocytes had attenuated proliferative responses following TCR ligation, and were depleted rather than expanded during culture in the presence of anti-CD3. When expressing a positively selectable TCR, transgenic double-positive thymocytes were increased in number and activated, but the output of single-positive thymocytes was reduced. Transgenic double-positive thymocytes were acutely sensitive to deletion by TCR ligation in vivo. These results indicate that activation of Dbs has the potential to promote proliferation throughout thymocyte development, but also sensitizes double-positive and single-positive thymocytes to deletion.
Evaluation of semiautomated procedure for lymphocyte subset analysis. (1990)

The findings of recent surveys indicate a need for standardisation in lymphocyte subset analysis by flow cytometry. Major areas of concern are the methods used for labelling subsets and the choice of appropriate monoclonal antibodies. A standard dual colour manual whole blood lysis technique for flow cytometry was compared with the recently available Coulter Q-Prep EPICS technique. Overall, there was no significant difference (Student's t test) between the use of anticoagulated blood treated with heparin or EDTA. When normal subjects were examined there was a decrease in the absolute number of CD3+ and Leu-7+/CD8- cells and an increase in CD19+ and CD20+ cells. When human immunodeficiency virus (HIV) antibody positive subjects were examined there was a significant decrease in the absolute number of CD2+, CD3+, CD4+ and Leu 7+/CD8- cells and an absolute increase in CD19+ and CD20+ cells. CD8+ cells were decreased only with the Cyto-Stat reagents. Occasionally, the Q-Prep did not lyse the red cells efficiently. While the Q-Prep EPICS system has the potential to standardise and automate the labelling procedures used in lymphocyte subset analysis, further refinement, such as the choice of monoclonal antibodies or alternative preparative reagents, may be required to resolve the cause of the discordant findings between the two approaches.
Steric and electronic interactions controlling the cis/trans isomer equilibrium at X‐pro tertiary amide motifs in solution (2013)

A systematic understanding of the noncovalent interactions that influence the structures of the cis conformers and the equilibrium between the cis and the trans conformers, of the X-Pro tertiary amide motifs, is presented based on analyses of (1)H-, (13)C-NMR and FTIR absorption spectra of two sets of homologous peptides, X-Pro-Aib-OMe and X-Pro-NH-Me (where X is acetyl, propionyl, isobutyryl and pivaloyl), in solvents of varying polarities. First, this work shows that the cis conformers of any X-Pro tertiary amide motif, including Piv-Pro, are accessible in the new motifs X-Pro-Aib-OMe, in solution. These conformers are uniquely observable by FTIR spectroscopy at ambient temperatures and by NMR spectroscopy from temperatures as high as 273 K. This is made possible by the persistent presence of n(i-1) →π(i)* interactions at Aib, which also influence the disappearance of steric effects at these cis X-Pro rotamers. Second, contrary to conventional understanding, the energy contribution of steric effects to the cis/trans equilibrium at the X-Pro motifs is found to be nonvariant (0.54 ± 0.02 kcal/mol) with increase in steric bulk on the X group. Third, the current studies provide direct evidence for the weak intramolecular interactions namely the n(i-1) →π(i)*, the N(Pro) •••H(i+1) (C5a), and the C7 hydrogen bond that operate and influence the structures, stabilities, and dynamics between different conformational states of X-Pro tertiary amide motifs. NMR and IR spectral data suggest that the cis conformers of X-Pro motifs are ensembles of short-lived rotamers about the C'(X)-N(Pro) bond.
Defect modes in photonic crystals studied using terahertz time-domain spectroscopy (2004)

Two-dimensional photonic crystal band gaps have been studied using terahertz time-domain spectroscopy. We observe the effects of defect modes in both the amplitude and phase spectra. These results are in reasonable agreement with calculations.
SLE‐associated risk factors affect DC function (2015)

Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non-activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity.
Fabrication of Stretchable Copper Coated Carbon Nanotube Conductor for Non-Enzymatic Glucose Detection Electrode with Low Detection Limit and Selectivity (2018)

The increasing demand for wearable glucose sensing has stimulated growing interest in stretchable electrodes. The development of the electrode materials having large stretchability, low detection limit, and good selectivity is the key component for constructing high performance wearable glucose sensors. In this work, we presented fabrication of stretchable conductor based on the copper coated carbon nanotube sheath-core fiber, and its application as non-enzymatic electrode for glucose detection with high stretchability, low detection limit, and selectivity. The sheath-core fiber was fabricated by coating copper coated carbon nanotube on a pre-stretched rubber fiber core followed by release of pre-stretch, which had a hierarchically buckled structure. It showed a small resistance change as low as 27% as strain increasing from 0% to 500% strain, and a low resistance of 0.4 Ω·cm<sup>-1</sup> at strain of 500%. This electrode showed linear glucose concentration detection in the range between 0.05 mM and 5 mM and good selectivity against sucrose, lactic acid, uric acid, acrylic acid in phosphate buffer saline solution, and showed stable signal in high salt concentration. The limit of detection (LOD) was 0.05 mM, for the range of 0.05⁻5 mM, the sensitivity is 46 mA·M<sup>-1</sup>. This electrode can withstand large strain of up to 60% with negligible influence on its performance.
Intramodal cortical plastic changes after moderate visual impairment in human amblyopia (2022)

Early blindness results in alterations in the neural responses to auditory stimuli. Here we show that even moderately reduced vision in one eye early in life is sufficient to induce neural plastic changes in voice processing. We asked individuals with reduced visual acuity in one eye due to amblyopia to attend to vocal cues during electroencephalogram recording. We found enhanced frontal auditory responses at 125 ms-225 ms, which were correlated with reduced vision in the amblyopic eye, but not the fellow eye. Our results indicate intramodal reorganization, typically observed after congenital profound visual deprivation.
Electric Field Directed Fabrication of Biosensor Devices From Biomolecule Derivatized Nanoparticles (2007)

An electronic microarray has been used to carry out directed self-assembly of higher order 3D structures from Biotin/Streptavidin and DNA derivatized nanoparticles. Structures with more than forty layers of alternating biotin and streptavidin and DNA nanoparticles were fabricated using a 400 site CMOS microarray system. In this process, reconfigurable electric fields produced by the microarray device have been used to rapidly transport, concentrate and accelerate the binding of 40 and 200 nanometer biotin, streptavidin, DNA and peroxidase derivatized nanoparticles to selected sites on the microarray. The nanoparticle layering process takes less than one minute per layer (10–20 seconds for addressing and binding nanoparticles, 40 seconds for washing). The nanoparticle addressing/binding process can be monitored by changes in fluorescence intensity as each nanoparticle layer is deposited. The final multilayered 3-D structures are about two microns in thickness and 50 microns in diameter. Work is now focused on assembling “micron size” biosensor devices from bio-molecule derivatized luminescent and fluorescent nanoparticles. The proposed structure for a nanolayered glucose sensor device includes a base layer of biotin/streptavidin nanoparticles, a layer of glucose oxidase derivatized nanoparticles, a layer of peroxidase derivatized nanoparticles, a layer of quantum dots, and a final layer of biotin/streptavidin nanoparticles. Such a device will serve as a prototype for a wide variety of applications which includes other biosensor devices, lab-on a-chip devices, in-vivo drug delivery systems and “micron size” dispersible bio/chem sensors for environmental, military and homeland security applications.
Recent Advances in BACE1 Biology and Inhibitors in Clinical Development (2017)

Medicinal Chemistry Reviewsis an outstanding 600 page volume providing timely and critical reviews of important topics in medicinal chemistry. It is provided free of charge to MEDI members in electronic format. Members can also order a print copy, for the cost of printing, shipping and handling
Cavity Solitons in a Vertical Cavity Semiconductor Optical Amplifier: From Single to Cluster States (2009)

We present experimental results on the formation and control of single and cluster states of cavity solitons in a vertical cavity semiconductor optical amplifier. A parameter region where cluster states are inhibited is demonstrated.
Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge (2023)

Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly circulating strain and vaccine are mismatched. The novel influenza vaccine platform M2- or BM2-deficient single replication (M2SR and BM2SR) has been shown to safely induce strong systemic and mucosal antibody responses and provide protection against significantly drifted influenza strains. In this study, we demonstrate that both monovalent and quadrivalent (Quad) formulations of M2SR are non-pathogenic in mouse and ferret models, eliciting robust neutralizing and non-neutralizing serum antibody responses to all strains within the formulation. Following challenge with wildtype influenza strains, vaccinated mice and ferrets demonstrated reduced weight loss, decreased viral replication in the upper and lower airways, and enhanced survival as compared to mock control groups. Mice vaccinated with H1N1 M2SR were completely protected from heterosubtypic H3N2 challenge, and BM2SR vaccines provided sterilizing immunity to mice challenged with a cross-lineage influenza B virus. Heterosubtypic cross-protection was also seen in the ferret model, with M2SR vaccinated animals exhibiting decreased viral titers in nasal washes and lungs following the challenge. BM2SR-vaccinated ferrets elicited robust neutralizing antibodies toward significantly drifted past and future influenza B strains. Mice and ferrets that received quadrivalent M2SR were able to mount immune responses equivalent to those seen with each of the four monovalent vaccines, demonstrating the absence of strain interference in the commercially relevant quadrivalent formulation.
Three-dimensional evaluation of postoperative swelling in treatment of zygomatic bone fractures using two different cooling therapy methods: a randomized, observer-blind, prospective study (2013)

German Clinical Trials Register ID: DRKS00004846.
NI-65 * DIFFERENTIATING RADIATION EFFECT AND NECROSIS FROM GLIOBLASTOMA WITH DYNAMIC SUSCEPTIBILITY CONTRAST (DSC) MRI (2014)

BACKGROUND: In glioblastoma (GBM), pseudoprogression (PsP) appears as increased enhancement on T1-weighted imaging following concurrent chemoradiotherapy (CRT), making it difficult to distinguish from true progression. This increased enhancement, due to radiation and necrotic induced changes, is associated with effective treatment response. The goal of this study was to determine the ability of measures derived from dynamic susceptibility contrast (DSC) MRI to distinguish radiation effect (RE) and necrosis from GBM. METHODS: All patients gave informed written consent according to IRB policy. Thirty-three tissue samples from 11 previously treated patients were spatially correlated to MRI with a median = 13 days between surgery and MRI. Preload and leakage-corrected metrics of DSC-MRI were co-registered with the pre-surgical Stealth exam, and positive, median values of standardized (sRCBV) or normalized (nRCBV) relative cerebral blood volume, and normalized relative cerebral blood flow (nRCBF) were obtained within 3-mm regions precisely matched to the surgically recorded biopsy locations. Statistical analysis included generalized estimating equations (to account for multiple samples from the same subject) with receiver operator characteristic curves. RESULTS: Gender and median age were similar between tissue groups. Pathologic diagnosis confirmed 11 samples with pure RE/Necrosis and 22 samples with pure GBM. All metrics showed significant differences between RE/Necrosis and GBM (p < 0.001). Interestingly, both sRCBV and nRCBV showed equally higher sensitivity and specificity (81.8%/90.9%, thresholds = 4287 and 1.32, respectively) than nRCBF (72.7%/81.8%, threshold = 1.13) for differentiating RE/Necrosis and GBM. CONCLUSIONS: Accurate assessment of treatment response using measures of DSC-MRI is promising, as these measures show high sensitivity and specificity for differentiating RE/Necrosis and GBM. Both nRCBV and sRCBV provide equally greater accuracy than nRCBF. Visualizing these differentiated regions on imaging could help clinicians better assess treatment response following CRT, with potential to impact treatment management decisions.