gebhart/patrepeval huggingface dataset:
The Growing Impact of Bioorthogonal Click Chemistry on the Development of Radiopharmaceuticals (2013)

Click chemistry has become a ubiquitous chemical tool with applications in nearly all areas of modern chemistry, including drug discovery, bioconjugation, and nanoscience. Radiochemistry is no exception, as the canonical Cu(I)-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, inverse electron demand Diels-Alder reaction, and other types of bioorthogonal click ligations have had a significant impact on the synthesis and development of radiopharmaceuticals. This review will focus on recent applications of click chemistry ligations in the preparation of imaging agents for SPECT and PET, including small molecules, peptides, and proteins labeled with radionuclides such as (18)F, (64)Cu, (111)In, and (99m)Tc.
Passive recruitment of circulating leukocytes into capillary sprouts from existing capillaries in a microfluidic system (2011)

Recent evidence implicating leukocytes in angiogenesis raises the question of whether leukocytes and other cells circulating with the blood in microvascular networks can home to capillary sprouts intraluminally. This study describes an investigation of leukocyte trafficking in sprouting capillaries fabricated using soft lithography. The leukocytes passing with whole blood through existing capillaries were able to enter microfabricated capillary sprouts of variable length and sprouting angle due to the mechanical interaction with red blood cells (RBCs) at the sprouting bifurcation, in spite of the complete absence of blood flow through the blind-ended sprouts or any chemoattractants. The RBCs formed "comet tails" (the densely packed cellular trains forming behind leukocytes as they move through narrow capillaries) and effectively pushed leukocytes into the microfabricated sprouts while bypassing them at the sprouting bifurcation. Individual sprouts filled with several leukocytes, as wells as RBCs and platelets, were observed. The results of this study suggest that (i) blood cells are likely present in capillary sprouts throughout their development, (ii) leukocytes and other circulating cells may use this mechanism to home to capillary sprouts intraluminally for direct engraftment, and (iii) tissues may use this phenomenon as another mechanism for local recruitment of leukocytes from the blood stream.
Reversible Inhibition of the Fusion Activity of Measles Virus F Protein by an Engineered Intersubunit Disulfide Bridge (2007)

In search of target sites for the development of paramyxovirus inhibitors, we have engineered disulfide bridges to introduce covalent links into the prefusion F protein trimer of measles virus. F-Edm-452C/460C, predicted to bridge head and stalk domains of different F monomers, shows a high degree of proteolytic maturation and surface expression, predominantly as stable, dithiothreitol-sensitive trimers, but no fusion activity. Reduction of disulfide bridges partially restores activity. These findings underscore the importance of reversible intersubunit interactions between the stalk and head domains for F activity. Noncovalent small molecules mimicking this behavior may constitute a potent strategy for preventing paramyxovirus entry.
Reaction of 2′‐Deoxyguanosine with Glyceraldehyde (1994)

Abstract Reaction of 2′‐deoxyguanosine with glyceraldehyde under physiological conditions leads to the formation of ammonium 2‐[9‐(2‐deoxy‐β‐ D ‐ribofuranosyl)‐6,9‐dihydro‐6‐oxo‐1 H ‐purin‐2‐ylamino]propionate ( 8 ). The same substance can be detected in 2′‐deoxyguanosine/glucose reaction mixtures as minor product. magnified image
Using Biomarkers to “Guide” Heart Failure Management (2012)

Over the last several years, cardiac biomarkers have proven to be increasingly useful for disease screening, diagnosis, and prognostication. The most widely used biomarkers in heart failure (HF) are natriuretic peptides (NPs), which can aid in diagnosing HF, while also identifying those who are at higher risk of adverse outcomes. Multiple clinical trials have investigated the role of NPs as therapeutic targets for HF management, but results have been conflicting. Collectively, however, the data suggest that NP levels may be useful in guiding HF management and improving HF-related morbidity and mortality. In this review, we summarize existing data investigating the use of NPs as targets for outpatient HF therapy, focusing on differences in study designs and lessons learned from the results. Although the results for this approach are promising overall, we propose that additional well-designed prospective randomized controlled trials-specifically incorporating the relevant lessons learned from previous studies-are necessary to pivotally establish the role of NP-guided outpatient HF management.
Improve reliability of hearing instruments using nano technology (2015)

Historically, hearing aids have been prone to damages by foreign materials. Manufacturers have applied various techniques to address this issue, most recently by using hydrophobic nano coating. However, these methods have shown to be inadequate, especially in dealing with oily substances such as earwax. HydraShield2 nanotechnology has been developed to mitigate the ingress of both water and oily substances for hearing aids. This was accomplished by significantly modifying the surface's interaction with foreign materials. Through both lab tests and human subjec tstudies, this technology has been found to be very effective in mitigating the ingress of foreign materials. As a result, the reliability of hearing instruments has been enhanced and the customers' satisfaction has been improved.
Dictyoquinazols A, B, and C, New Neuroprotective Compounds from the Mushroom<i>Dictyophora indusiata</i> (2002)

In an effort to identify neuroprotective compounds against excitatory neurotoxins from edible and medicinal mushrooms, dictyoquinazols A (1), B (2), and C (3) have been isolated from the methanolic extract of the mushroom Dictyophora indusiata. On the basis of NMR studies, their structures have been assigned as unique quinazoline compounds, which are very rare in nature. 2 and 3 existed as mixtures of rotamers (2a, 2b and 3a, 3b) inseparable by HPLC because of fast interconversion. The E/Z isomers of these compounds were assigned by comparison of (1)H NMR, (13)C NMR, and NOESY spectra and by (3)J(C,H) coupling constants. Dictyoquinazols protected primary cultured mouse cortical neurons from glutamate- and NMDA-induced excitotoxicities in a dose-dependent manner.
Quantitative microbiome profiling in lumenal and tissue samples with broad coverage and dynamic range via a single-step 16S rRNA gene DNA copy quantification and amplicon barcoding (2020)

ABSTRACT Current methods for detecting, accurately quantifying, and profiling complex microbial communities based on the microbial 16S rRNA marker genes are limited by a number of factors, including inconsistent extraction of microbial nucleic acids, amplification interference from contaminants and host DNA, different coverage of PCR primers utilized for quantification and sequencing, and potentially biases in PCR amplification rates among microbial taxa during amplicon barcoding. Here, we describe a single-step method that enables the quantification of microbial 16S rRNA gene DNA copies with wide dynamic range and broad microbial diversity, and simultaneous amplicon barcoding for quantitative 16S rRNA gene amplicon profiling of microbiota. The method is suitable for a variety of sample types and is robust in samples with low microbial abundance, including samples containing high levels of host mammalian DNA, as is common in human clinical samples. We demonstrate that our modification to the Earth Microbiome Project (EMP) V4 16S rRNA gene primers expands their microbial coverage while dramatically reducing non-specific mammalian mitochondrial DNA amplification, thus achieving wide dynamic range in microbial quantification and broad coverage for capturing high microbial diversity in samples with or without high host DNA background. The approach relies only on broadly available hardware (real-time PCR instruments) and standard reagents utilized for conventional 16S rRNA gene amplicon library preparation both of which make it amenable for immediate and widespread adoption. Simultaneous 16S rRNA gene DNA copy quantification and amplicon barcoding for multiplexed next-generation sequencing from the same analyzed sample, performed in a combined workflow, reduces the amount of sample needed and reduces time and reagent costs. Additionally, we demonstrate that using our modified 16S rRNA gene primers in a digital PCR (dPCR) format enables precise and exact microbial quantification in samples with very high host DNA background levels without the need for quantification standards. Potential future applications of this approach include: (1) quantitative microbiome profiling in human and animal microbiome research; (2) detection of monoinfections and profiling of polymicrobial infections in tissues, stool, and bodily fluids in human and veterinary medicine; (3) environmental sample analyses (e.g., soil and water); and (4) broad-coverage detection of microbial food contamination in products high in mammalian DNA, such as meat products. We predict that utilization of this approach primarily for quantitative microbiome profiling will be invaluable to microbiome studies, which have historically been limited to analysis of relative abundances of microbes.
An antibody derivative expressed from viral vectors passively immunizes pigs against transmissible gastroenteritis virus infection when supplied orally in crude plant extracts (2006)

To investigate the potential of antibody derivatives to provide passive protection against enteric infections when supplied orally in crude plant extracts, we have expressed a small immune protein (SIP) in plants using two different plant virus vectors based on potato virus X (PVX) and cowpea mosaic virus (CPMV). The epsilonSIP molecule consisted of a single-chain antibody (scFv) specific for the porcine coronavirus transmissible gastroenteritis virus (TGEV) linked to the epsilon-CH4 domain from human immunoglobulin E (IgE). In some constructs, the sequence encoding the epsilonSIP molecule was flanked by the leader peptide from the original murine antibody at its N-terminus and an endoplasmic reticulum retention signal (HDEL) at its C-terminus to allow the expressed protein to be directed to, and retained within, the endoplasmic reticulum. Western blot analysis of samples from Nicotiana clevelandii or cowpea tissue infected with constructs revealed the presence of SIP molecules which retained their ability to dimerize. The analysis of crude plant extracts revealed that the plant-expressed epsilonSIP molecules could bind to and neutralize TGEV in tissue culture, the levels of binding and neutralization reflecting the level of expression. Oral administration of crude extracts from SIP-expressing plant tissue to 2-day-old piglets demonstrated that the extracts which showed the highest levels of in vitro neutralization could also provide in vivo protection against challenge with TGEV.
Susceptibility of <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i> biofilms towards ciprofloxacin: effect of specific growth rate (1991)

Methods of cell culture which enable the control of specific growth rate and expression of iron-regulated membrane proteins within Gram-negative biofilms were employed for various clinical isolates of Pseudomonas aeruginosa taken from the sputum of cystic fibrosis patients and of a laboratory strain of Escherichia coli. Susceptibility towards ciprofloxacin was assessed as a function of growth-rate for intact biofilms, cells resuspended from the biofilms and also for newly formed daughter cells shed from the biofilm during its growth and development. Patterns of susceptibility with growth rate were compared to those of suspended cultures grown in a chemostat. In all instances the susceptibility of chemostat cultures was directly related to growth rate. Whilst little difference was observed in the susceptibility pattern for P. aeruginosa strains with different observed levels of mucoidness, such populations were generally more susceptible towards ciprofloxacin than those of E. coli. At fast rates of growth P. aeruginosa cells resuspended from biofilms were significantly more resistant than chemostat grown cells. Intact P. aeruginosa biofilms were significantly more resistant than cells resuspended from them. This is in contrast to E. coli, where cells resuspended from biofilm and intact biofilms were, at the slower rates of growth, equivalent and significantly more susceptible than chemostat-grown cells. At high growth rates all methods of E. coli culture produced cells of equivalent susceptibility. For all strains, daughter cells dislodged from the biofilms demonstrated a high level of susceptibility towards ciprofloxacin which was unaffected by growth rate. This sensitivity corresponded to that of the fastest grown cells in the chemostat.
Una proposta per a comprendre millor l'Apocalipsi (1996)

Transition metal oxides (TMOs) hold great potential for lithium-ion batteries (LIBs) on account of the high theoretical capacity. Unfortunately, the unfavorable volume expansion and low intrinsic electronic conductivity of TMOs lead to irreversible structural degradation, disordered particle agglomeration, and sluggish electrochemical reaction kinetics, which result in perishing rate capability and long-term stability. This work reports an Fe<sub>2</sub>O<sub>3</sub>/MoO<sub>3</sub>@NG heterostructure composite for LIBs through the uniform growth of Fe<sub>2</sub>O<sub>3</sub>/MoO<sub>3</sub> heterostructure quantum dots (HQDs) on the N-doped rGO (NG). Due to the synergistic effects of the "couple tree"-type heterostructures constructed by Fe<sub>2</sub>O<sub>3</sub> and MoO<sub>3</sub> with NG, Fe<sub>2</sub>O<sub>3</sub>/MoO<sub>3</sub>@NG delivers a prominent rate performance (322 mA h g<sup>-1</sup> at 20 A g<sup>-1</sup>, 5.0 times higher than that of Fe<sub>2</sub>O<sub>3</sub>@NG) and long-term cycle stability (433.5 mA h g<sup>-1</sup> after 1700 cycles at 10 A g<sup>-1</sup>). Theoretical calculations elucidate that the strong covalent Fe-O-Mo, Mo-N, and Fe-N bonds weaken the diffusion energy barrier and promote the Li<sup>+</sup>-ion reaction to Fe<sub>2</sub>O<sub>3</sub>/MoO<sub>3</sub>@NG, thereby facilitating the structural stability, pseudocapacitance contribution, and electrochemical reaction kinetics. This work may provide a feasible strategy to promote the practical application of TMO-based LIBs.
Phenotypic Profiling of Antibiotic Response Signatures in Escherichia coli Using Raman Spectroscopy (2013)

Identifying the mechanism of action of new potential antibiotics is a necessary but time-consuming and costly process. Phenotypic profiling has been utilized effectively to facilitate the discovery of the mechanism of action and molecular targets of uncharacterized drugs. In this research, Raman spectroscopy was used to profile the phenotypic response of Escherichia coli to applied antibiotics. The use of Raman spectroscopy is advantageous because it is noninvasive, label free, and prone to automation, and its results can be obtained in real time. In this research, E. coli cultures were subjected to three times the MICs of 15 different antibiotics (representing five functional antibiotic classes) with known mechanisms of action for 30 min before being analyzed by Raman spectroscopy (using a 532-nm excitation wavelength). The resulting Raman spectra contained sufficient biochemical information to distinguish between profiles induced by individual antibiotics belonging to the same class. The collected spectral data were used to build a discriminant analysis model that identified the effects of unknown antibiotic compounds on the phenotype of E. coli cultures. Chemometric analysis showed the ability of Raman spectroscopy to predict the functional class of an unknown antibiotic and to identify individual antibiotics that elicit similar phenotypic responses. Results of this research demonstrate the power of Raman spectroscopy as a cellular phenotypic profiling methodology and its potential impact on antibiotic drug development research.
An optimised sample preparation method for NMR-based faecal metabonomic analysis (2010)

Faecal metabonomic NMR analysis plays an essential role in investigating the interactions between mammalian metabolism and symbiotic gut microbiota. However, the faecal metabolite extraction method remains to be optimised and standardised to take into consideration signal-to-noise ratios, pH and chemical shift consistency. In the current investigation, we compared extraction consistency of three homogenisation methods including manual ultrasonication, automatic homogenization with tissuelyser and their combination, and systematically optimised faecal metabolite extraction parameters, including the faeces-to-buffer ratio (W(f) : V(b)), extraction repetition times and duration. We found that automatic homogenisation with tissuelyser was the choice of extraction method owning to its good metabolite extraction consistency and high throughput. We also recommend W(f) : V(b) of 1 : 10 (mg microl(-1)) and use of the combined first two extracts as the resultant samples to represent faecal metabolite composition. Such recommendation is based on considerations of maximisation of the spectral signal-to-noise ratio, pH and chemical shift consistency, completeness of metabolite extraction and sample preparation throughput so that the method is suitable for analysing a large number of samples especially in human population studies.
<title>Virtual rounds: simulation-based education in procedural medicine</title> (1999)

Computer-based simulation is a goal for training physicians in specialties where traditional training puts patients at risk. Intuitively, interactive simulation of anatomy, pathology, and therapeutic actions should lead to shortening of the learning curve for novice or inexperienced physicians. Effective transfer of knowledge acquired in simulators must be shown for such devices to be widely accepted in the medical community. We have developed an Interventional Cardiology Training Simulator which incorporates real-time graphic interactivity coupled with haptic response, and an embedded curriculum permitting rehearsal, hypertext links, personal archiving and instructor review and testing capabilities. This linking of purely technical simulation with educational content creates a more robust educational purpose for procedural simulators.
Discovery and Characterization of Alamandine (2013)

The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.
Transcriptional Activation of the Human Rod cGMP-Phosphodiesterase  -Subunit Gene Is Mediated by an Upstream AP-1 Element (1997)

During photoactivation retinal cGMP-phosphodiesterase (PDE) mediates signal transduction in the photoreceptor outer segments. Mutations in the beta-subunit gene of rod-specific PDE (beta-PDE) have been associated with inherited retinal degeneration in a number of species, including human. Here we have investigated the proximal upstream sequences that participate in transcriptional activation of this gene. Transient transfections demonstrated that the sequence from -72 to +53 bp contained sufficient information to direct high levels of gene expression in cells of retinal origin. Deletion or mutagenesis of an AP-1 motif present in this region caused 90-95% reduction in reporter gene expression. By gel mobility shift assay we demonstrated specific interactions between putative nuclear transcription factors and this AP-1 element. These findings indicate that the proximal AP-1 site in the human beta-PDE promoter is functionally relevant and necessary for transcriptional activation of this gene.
Optimal self-referenced sensing using long- and short- range surface plasmons (2007)

Dual-mode surface-plasmon resonance (SPR) sensors use both long- and short- range surface plasmon waves to differentiate surface binding interactions from interfering bulk effects. We have optimized the design of these sensors for minimum surface limit of detection (LOD) using a Cramer-Rao lower bound for spectral shift estimation. Despite trade-offs between resonance width, minimum reflectivity, and sensitivity for the two modes, a range of reasonable design parameters provides nearly optimal performance. Experimental verification using biotin-streptavidin binding as a model system reveals that sensitivity and LOD for dual-mode sensors remains competitive with single-mode sensors while compensating for bulk effects.
Uniform 8×8 array InGaAs/InP multiquantum well asymmetric Fabry–Perot modulators for flipchip solder bond hybrid optical interconnect (1992)

The first 8×8 arrays of multiquantum well asymmetric Fabry–Perot modulators in the InGaAs/InP material system are reproted. These arrays have optical access through the substrate and are flipchip solder bond assembled for direct connection to silicon integrated circuits for optical interconnect applications. A high degree of uniformity of response is obtained across the array with a mean contrast ratio of 35 dB, with a standard deviation of 0.25 dB. Over a 4×4 mm2 chip the standard deviation of peak operating wavelength of the cavity resonance is 3.3 nm.
Preconception Vaccination with a Glycoprotein B (gB) DNA Vaccine Protects against Cytomegalovirus (CMV) Transmission in the Guinea Pig Model of Congenital CMV Infection (2003)

DNA vaccines expressing the guinea pig cytomegalovirus (GPCMV) homologs of the glycoprotein B (gB) and UL83 proteins were evaluated for protection against congenital GPCMV infection. After 4 doses of DNA administered by epidermal (gene gun) route, all guinea pigs developed enzyme-linked immunosorbent assay (ELISA) antibody and, for gB-vaccine recipients, neutralizing antibody. Dams were challenged with 1 x 10(4) plaque-forming units of GPCMV in the third trimester. Preconception vaccination with gB did not decrease overall pup mortality, although, within the gB-vaccine group, pup mortality was lower among dams with high ELISA responses. Preconception maternal vaccination with gB vaccine significantly reduced congenital transmission in liveborn pups. In contrast, UL83 vaccine had no significant effect on pup mortality or vertical transmission of GPCMV. Virus load was significantly lower in infected pups born to gB- and UL83-vaccinated dams than in infected pups born to control dams. These data support the concept that subunit gB vaccination may be useful in protecting against CMV-induced disease.
Design, Synthesis, and Biological Evaluation of 3,4-Diarylmaleimides as Angiogenesis Inhibitors (2006)

The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 microM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely related to this lead, no other compound was found to be active in the tubulin polymerization assay. However, by screening in the in vivo chick embryo assay 10 was identified as a potent angiogenesis inhibitor indicating an alternative target. Indeed, molecular modeling studies suggest a reasonable binding mode of 10 at the ATP-binding site of the model kinase CDK2. Motivated by these results, analogues of 10 were screened for inhibitory activity in a panel of 12 selected protein kinases and a high affinity of 10 to VEGF-R2 was found showing an IC50 of 2.5 nM. Structure-activity relationships (SAR) for this compound series with the isolated enzyme and equivalent antiangiogenic activity in the chick embryo assay are presented herein.