gebhart/patrepeval huggingface dataset:
In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector. (1994)

Replication-deficient adenovirus mediates transfer and expression of a foreign gene in retinal pigment epithelial and photoreceptor cells. Gene transfer to photoreceptor cells is enhanced in developing retinas or at the predegenerate stage of photoreceptors in genetically programmed retinal degeneration.
Activation of Src kinase in primary colorectal carcinoma (2002)

Src activity is an independent indicator of poor clinical prognosis in all stages of human colon carcinoma. These data suggest that Src-specific inhibitors may have a therapeutic role in inhibiting tumor progression and metastasis, and that measurement of Src activity may aid in selection of early stage patients for adjuvant therapy.
Kinetics of Initiation, Propagation, and Termination for the [rac-(C2H4(1-indenyl)2)ZrMe][MeB(C6F5)3]-Catalyzed Polymerization of 1-Hexene (2001)

Metallocene-catalyzed polymerization of 1-alkenes offers fine control of critical polymer attributes such as molecular weight, polydispersity, tacticity, and comonomer incorporation. Enormous effort has been expended on the synthesis and discovery of new catalysts and activators, but elementary aspects of the catalytic processes remain unclear. For example, it is unclear how the catalyst is distributed among active and dormant sites and how this distribution influences the order in monomer for the propagation rates, for which widely varying values are reported. Similarly, although empirical relationships between average molecular weights and monomer have been established for many systems, the underlying mechanisms of chain termination are unclear. Another area of intense interest concerns the role of ion-pairing in controlling the activity and termination mechanisms of metallocene-catalyzed polymerizations. Herein we report the application of quenched-flow kinetics, active site counting, polymer microstructure analysis, and molecular weight distribution analysis to the determination of fundamental rate laws for initiation, propagation, and termination for the polymerization of 1-hexene in toluene solution as catalyzed by the contact ion-pair, [rac-(C(2)H(4)(1-indenyl)(2))ZrMe][MeB(C(6)F(5))(3)] (1) over the temperature range of -10 to 50 degrees C. Highly isotactic (>99% mmmm) poly-1-hexene is produced with no apparent enchained regioerrors. Initiation and propagation processes are first order in the concentrations of 1-hexene and 1 but independent of excess borane or the addition of the contact ion-pair [PhNMe(3)][MeB(C(6)F(5))(3)]. Active site counting and the reaction kinetics provide no evidence of catalyst accumulation in dormant or inactive sites. Initiation is slower than propagation by a factor of 70. The principal termination process is the formation of unsaturates of two types: vinylidene end groups that arise from termination after a 1,2 insertion and vinylene end groups that follow 2,1 insertions. The rate law for the former termination process is independent of the 1-hexene concentration, whereas the latter is first order. Analysis of (13)C-labeled polymer provides support for a mechanism of vinylene end group formation that is not chain transfer to monomer. Deterministic modeling of the molecular weight distributions using the fundamental rate laws and kinetic constants demonstrates the robustness of the kinetic analysis. Comparisons of insertion frequencies with estimated limits on the rates of ion-pair symmetrization obtained by NMR suggest that ion-pair separation prior to insertion is not required, but the analysis requires assumptions that cannot be validated.
Improved accumulation and activity of ribozymes expressed from a tRNA-based RNA polymerase III promoter (1995)

RNA polymerase III (pol III) transcripts are abundant in all cells. Therefore, pol III promoters may be ideal for expressing high levels of exogenous RNAs, such as antisense RNAs, decoy RNAs and ribozymes, in many different cell types. We have improved accumulation of recombinant RNAs expressed from a human meti tRNA-derived pol III promoter > 100-fold by modifying the 3' terminus of the transcripts to hybridize to the 5' terminus. This terminal duplex includes the 8 nt leader sequence present in the primary wild-type meti tRNA transcript that is normally removed during processing to the mature tRNA. Expression of an anti-HIV ribozyme was analyzed in cells stably transduced with retroviral vectors encoding pol III transcription units containing this modification. High accumulation of recombinant pol III ribozyme transcripts was observed in all cell lines tested. Due to the enhanced transcript accumulation, ribozyme cleavage activity was readily detectable in total RNA extracted from stably transduced human T cell lines. One pol III transcription unit, termed 'TRZ', was optimized further for ribozyme cleavage activity. The improved pol III transcription units reported here may be useful for expressing a variety of functional and therapeutic RNAs.
Biocompatible SuFEx Click Chemistry: Thionyl Tetrafluoride (SOF4)‐Derived Connective Hubs for Bioconjugation to DNA and Proteins (2019)

We report here the development of a suite of biocompatible SuFEx transformations from the SOF<sub>4</sub> -derived iminosulfur oxydifluoride hub in aqueous buffer conditions. These biocompatible SuFEx reactions of iminosulfur oxydifluorides (R-N=SOF<sub>2</sub> ) with primary amines give sulfamides (8 examples, up to 98 %), while the reaction with secondary amines furnish sulfuramidimidoyl fluoride products (8 examples, up to 97 %). Likewise, under mild buffered conditions, phenols react with the iminosulfur oxydifluorides (Ar-N=SOF<sub>2</sub> ) to produce sulfurofluoridoimidates (13 examples, up to 99 %), which can themselves be further modified by nucleophiles. These transformations open the potential for asymmetric and trisubstituted linkages projecting from the sulfur(VI) center, including versatile S-N and S-O connectivity (9 examples, up to 94 %). Finally, the SuFEx bioconjugation of iminosulfur oxydifluorides to amine-tagged single-stranded DNA and to BSA protein demonstrate the potential of SOF<sub>4</sub> -derived SuFEx click chemistry in biological applications.
A Novel Linear Amphipathic β-Sheet Cationic Antimicrobial Peptide with Enhanced Selectivity for Bacterial Lipids (2001)

All known naturally occurring linear cationic peptides adopt an amphipathic alpha-helical conformation upon binding to lipids as an initial step in the induction of cell leakage. We designed an 18-residue peptide, (KIGAKI)3-NH2, that has no amphipathic character as an alpha-helix but can form a highly amphipathic beta-sheet. When bound to lipids, (KIGAKI)3-NH2 did indeed form a beta-sheet structure as evidenced by Fourier transform infrared and circular dichroism spectroscopy. The antimicrobial activity of this peptide was compared with that of (KIAGKIA)3-NH2, and it was better than that of GMASKAGAIAGKIAKVALKAL-NH2 (PGLa) and (KLAGLAK)3-NH2, all of which form amphipathic alpha-helices when bound to membranes. (KIGAKI)3-NH2 was much less effective at inducing leakage in lipid vesicles composed of mixtures of the acidic lipid, phosphatidylglycerol, and the neutral lipid, phosphatidylcholine, as compared with the other peptides. However, when phosphatidylethanolamine replaced phosphatidylcholine, the lytic potency of PGLa and the alpha-helical model peptides was reduced, whereas that of (KIGAKI)3-NH2 was improved. Fluorescence experiments using analogs containing a single tryptophan residue showed significant differences between (KIGAKI)3-NH2 and the alpha-helical peptides in their interactions with lipid vesicles. Because the data suggest enhanced selectivity between bacterial and mammalian lipids, linear amphipathic beta-sheet peptides such as (KIGAKI)3-NH2 warrant further investigation as potential antimicrobial agents.
Redox-Active Antibiotics Control Gene Expression and Community Behavior in Divergent Bacteria (2008)

It is thought that bacteria excrete redox-active pigments as antibiotics to inhibit competitors. In Pseudomonas aeruginosa, the endogenous antibiotic pyocyanin activates SoxR, a transcription factor conserved in Proteo- and Actinobacteria. In Escherichia coli, SoxR regulates the superoxide stress response. Bioinformatic analysis coupled with gene expression studies in P. aeruginosa and Streptomyces coelicolor revealed that the majority of SoxR regulons in bacteria lack the genes required for stress responses, despite the fact that many of these organisms still produce redox-active small molecules, which indicates that redox-active pigments play a role independent of oxidative stress. These compounds had profound effects on the structural organization of colony biofilms in both P. aeruginosa and S. coelicolor, which shows that "secondary metabolites" play important conserved roles in gene expression and development.
Expression of Type 2 Cystatin Genes CST1-CST5 in Adult Human Tissues and the Developing Submandibular Gland (2002)

Type 2 cystatins comprise a class of cysteine peptidase inhibitor presumed to mediate protective functions at various locations, including the oral cavity. Seven cystatin genes are clustered within a 300-kb region of human 20p11.2. "Salivary" cystatins, encoded by CST1, 2, 4, and 5, are present in saliva at significant levels but have also been reported in other secretions, such as tears, suggesting that during their evolution, these genes have acquired mechanisms directing differential tissue-specific expression. However, their patterns of expression, which might also provide additional clues to their individual functions, have not been determined. Gene-specific RNase protection assays were used to examine the qualitative and quantitative distribution of expression of these seven genes within a collection of 23 adult human tissues. The CST3 gene, encoding cystatin C, was expressed at modest levels in all tissues examined. The presumptive pseudogenes CSTP1 and CSTP2 were not expressed at detectable levels in any tissue. The CST1, 2, 4, and 5 genes were expressed in differential, tissue-specific patterns. Expression of CST2 and CST5 was restricted to the submandibular and parotid glands, while CST1 and CST4 were expressed in these tissues and in the lacrimal gland. Immunohistochemistry studies localized expression to the serous-type secretory end pieces. Coexpression of CST1 and CST4 was also observed in the epithelial lining of the gallbladder and seminal vesicle. The CST1 product was detected in the tracheal glands and CST4 in the kidney and prostate. Despite their different adult patterns of expression, analysis of CST1, 2, 4, and 5 mRNA levels in infant submandibular glands demonstrated a coordinate upregulation of expression of between 3.5 and 9 months of age. The patterns of cystatin gene expression are consistent with several proposed oral functions of the salivary cystatins but also suggest they are important in other locations and that, despite their close sequence similarity, they are individually specialized.
MitoFates: Improved Prediction of Mitochondrial Targeting Sequences and Their Cleavage Sites* (2015)

Mitochondria provide numerous essential functions for cells and their dysfunction leads to a variety of diseases. Thus, obtaining a complete mitochondrial proteome should be a crucial step toward understanding the roles of mitochondria. Many mitochondrial proteins have been identified experimentally but a complete list is not yet available. To fill this gap, methods to computationally predict mitochondrial proteins from amino acid sequence have been developed and are widely used, but unfortunately, their accuracy is far from perfect. Here we describe MitoFates, an improved prediction method for cleavable N-terminal mitochondrial targeting signals (presequences) and their cleavage sites. MitoFates introduces novel sequence features including positively charged amphiphilicity, presequence motifs, and position weight matrices modeling the presequence cleavage sites. These features are combined with classical ones such as amino acid composition and physico-chemical properties as input to a standard support vector machine classifier. On independent test data, MitoFates attains better performance than existing predictors in both detection of presequences and in predicting their cleavage sites. We used MitoFates to look for undiscovered mitochondrial proteins from 42,217 human proteins (including isoforms such as alternative splicing or translation initiation variants). MitoFates predicts 1167 genes to have at least one isoform with a presequence. Five-hundred and eighty of these genes were not annotated as mitochondrial in either UniProt or Gene Ontology. Interestingly, these include candidate regulators of parkin translocation to damaged mitochondria, and also many genes with known disease mutations, suggesting that careful investigation of MitoFates predictions may be helpful in elucidating the role of mitochondria in health and disease. MitoFates is open source with a convenient web server publicly available.
Hydroxychloroquine Serum Concentrations and Flares of Systemic Lupus Erythematosus: A Longitudinal Cohort Analysis (2016)

Noncompliance and subtherapeutic serum HCQ levels were seen frequently in these SLE patients, which was partly due to the low prescribed dose. In patients in remission, higher HCQ concentrations were associated with a trend showing fewer flares over time.
Systematic Design of Pore Size and Functionality in Isoreticular MOFs and Their Application in Methane Storage (2002)

A strategy based on reticulating metal ions and organic carboxylate links into extended networks has been advanced to a point that allowed the design of porous structures in which pore size and functionality could be varied systematically. Metal-organic framework (MOF-5), a prototype of a new class of porous materials and one that is constructed from octahedral Zn-O-C clusters and benzene links, was used to demonstrate that its three-dimensional porous system can be functionalized with the organic groups -Br, -NH2, -OC3H7, -OC5H11, -C2H4, and -C4H4 and that its pore size can be expanded with the long molecular struts biphenyl, tetrahydropyrene, pyrene, and terphenyl. We synthesized an isoreticular series (one that has the same framework topology) of 16 highly crystalline materials whose open space represented up to 91.1% of the crystal volume, as well as homogeneous periodic pores that can be incrementally varied from 3.8 to 28.8 angstroms. One member of this series exhibited a high capacity for methane storage (240 cubic centimeters at standard temperature and pressure per gram at 36 atmospheres and ambient temperature), and others the lowest densities (0.41 to 0.21 gram per cubic centimeter) for a crystalline material at room temperature.
Sesquiterpene synthases: Passive catalysts or active players? (2011)

Sesquiterpene synthases catalyse the metal dependent turnover of farnesyl diphosphate to generate a class of natural products characterised by an enormous diversity in structure, stereochemistry, biological function and application. It has been proposed that these enzymes take a passive role in the reactions they catalyse and that they serve mostly as stereochemical templates, within which the reactions take place. Here, recent research into the structure and function of sesquiterpene synthases and the mechanisms of the reactions that they catalyse will be reviewed to suggest that these fascinating enzymes play multifaceted active roles in what are arguably the most complex biosynthetic reactions.
SURVEY AND SUMMARY: The applications of universal DNA base analogues (2001)

A universal base analogue forms 'base pairs' with each of the natural DNA/RNA bases with little discrimination between them. A number of such analogues have been prepared and their applications as biochemical tools investigated. Most of these analogues are non-hydrogen bonding, hydrophobic, aromatic 'bases' which stabilise duplex DNA by stacking interactions. This review of the literature of universal bases (to 2000) details the analogues investigated, and their uses and limitations are discussed.
N,N-Dimethylsphingosine Is a Potent Competitive Inhibitor of Sphingosine Kinase but Not of Protein Kinase C:  Modulation of Cellular Levels of Sphingosine 1-Phosphate and Ceramide (1998)

Sphingosine 1-phosphate (SPP), a lipid second messenger formed by the action of sphingosine kinase, has been implicated in regulating diverse biological processes, including growth, survival, and differentiation. N,N-Dimethylsphingosine (DMS) inhibits sphingosine kinase and has been used to investigate the biological roles of SPP; however, little is known of the mechanism of inhibition of sphingosine kinase by DMS. In addition, DMS has been shown to inhibit protein kinase C in vitro. Here we report that DMS is a competitive inhibitor of sphingosine kinase from U937 monoblastic leukemia cells, Swiss 3T3 fibroblasts, and PC12 pheochromocytoma cells. DMS decreases basal levels of SPP and prevents increases in SPP in response to physiological stimuli known to activate sphingosine kinase. DMS also effectively increases cellular levels of ceramide in a variety of cell types, and resetting of the ceramide/SPP rheostat may account for the pro-apoptotic effects of DMS. Moreover, DMS, at concentrations which effectively inhibit sphingosine kinase, has no effect on protein kinase C activity or its membrane translocation. Thus, DMS acts as a specific competitive inhibitor of sphingosine kinase in diverse cell types and is a useful tool to elucidate the role of SPP as an intracellular second messenger.
Peer review report 1 on “Interannual to multidecadal climate forcings on groundwater resources of the U.S. West Coast” (2016)

DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.
An investigation of the lowest-order transverse-electric (TE_1) mode of the parallel-plate waveguide for THz pulse propagation (2009)

We experimentally and theoretically investigate the lowest-order transverse-electric (TE1) mode of the parallel-plate waveguide (PPWG) for the propagation of broadband THz pulses. We demonstrate undistorted THz pulse propagation via the single TE1 mode, solving the group-velocity-dispersion and spectral-filtering problems caused by the mode's low-frequency cutoff. We observe a remarkable counterintuitive property of the TE1 mode: its attenuation decreases with increasing frequency for all frequencies above cutoff. This phenomenon has not been observed with any other THz waveguide to date, and it can enable extremely low-loss propagation. We present a physical interpretation of this frequency-dependent behavior using a simple plane-wave description of the TE1 mode propagation. We also find that it is possible to achieve almost 100% coupling to the TE1 mode from a focused free-space Gaussian beam. In addition, using the above plane-wave analysis, we show how to mitigate the diffraction losses inherent to long path-length PPWGs via the use of transverse-concave plates.
Temporary Atrial Pacing in the Prevention of Postoperative Atrial Fibrillation (2007)

Temporary right atrial or biatrial pacing after CABG significantly decreased the postoperative incidence of AF. Multivariable analysis identified older age and no pacing as predictors of AF occurrence.
TH17 Cells Mediate Steroid-Resistant Airway Inflammation and Airway Hyperresponsiveness in Mice (2008)

Steroid-resistant asthma comprises an important source of morbidity in patient populations. T(H)17 cells represent a distinct population of CD4(+) Th cells that mediate neutrophilic inflammation and are characterized by the production of IL-17, IL-22, and IL-6. To investigate the function of T(H)17 cells in the context of Ag-induced airway inflammation, we polarized naive CD4(+) T cells from DO11.10 OVA-specific TCR-transgenic mice to a T(H)2 or T(H)17 phenotype by culturing in conditioned medium. In addition, we also tested the steroid responsiveness of T(H)2 and T(H)17 cells. In vitro, T(H)17 cytokine responses were not sensitive to dexamethasone (DEX) treatment despite immunocytochemistry confirming glucocorticoid receptor translocation to the nucleus following treatment. Transfer of T(H)2 cells to mice challenged with OVA protein resulted in lymphocyte and eosinophil emigration into the lung that was markedly reduced by DEX treatment, whereas T(H)17 transfer resulted in increased CXC chemokine secretion and neutrophil influx that was not attenuated by DEX. Transfer of T(H)17 or T(H)2 cells was sufficient to induce airway hyperresponsiveness (AHR) to methacholine. Interestingly, AHR was not attenuated by DEX in the T(H)17 group. These data demonstrate that polarized Ag-specific T cells result in specific lung pathologies. Both T(H)2 and T(H)17 cells are able to induce AHR, whereas T(H)17 cell-mediated airway inflammation and AHR are steroid resistant, indicating a potential role for T(H)17 cells in steroid-resistant asthma.
Atomic layer deposition of metal and nitride thin films: Current research efforts and applications for semiconductor device processing (2003)

Atomic layer deposition (ALD) has been studied for several decades now, but the interest in ALD of metal and nitride thin films has increased only recently, driven by the need for highly conformal nanoscale thin films in modern semiconductor device manufacturing technology. ALD is a very promising deposition technique with the ability to produce thin films with excellent conformality and compositional control with atomic scale dimensions. However, the applications of metals and nitrides ALD in semiconductor device processes require a deeper understanding about the underlying deposition process as well as the physical and electrical properties of the deposited films. This article reviews the current research efforts in ALD for metal and nitride films as well as their applications in modern semiconductor device fabrication.
The human adult cardiomyocyte phenotype (2003)

Characterization of the redifferentiation capabilities of cultured adult cardiac myocytes in culture, provides an important system for comparing cardiomyocytes differentiating from human stem cells and provides the basis for an in vitro transplantation model to study interaction and communication between primary adult and stem cell-derived cardiomyocytes.
Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs (2004)

We delivered controlled radio frequency energy to the airways of anesthetized, ventilated dogs to examine the effect of this treatment on reducing airway narrowing caused by a known airway constrictor. The airways of 11 dogs were treated with a specially designed bronchial catheter in three of four lung regions. Treatments in each of the three treated lung regions were controlled to a different temperature (55, 65, and 75 degrees C); the untreated lung region served as a control. We measured airway responsiveness to local methacholine chloride (MCh) challenge before and after treatment and examined posttreatment histology to 3 yr. Treatments controlled to 65 degrees C as well as 75 degrees C persistently and significantly reduced airway responsiveness to local MCh challenge (P < or = 0.022). Airway responsiveness (mean percent decrease in airway diameter after MCh challenge) averaged from 6 mo to 3 yr posttreatment was 79 +/- 2.2% in control airways vs. 39 +/- 2.6% (P < or = 0.001) for airways treated at 65 degrees C, and 26 +/- 2.7% (P < or = 0.001) for airways treated at 75 degrees C. Treatment effects were confined to the airway wall and the immediate peribronchial region on histological examination. Airway responsiveness to local MCh challenge was inversely correlated to the extent of altered airway smooth muscle observed in histology (r = -0.54, P < 0.001). We conclude that the temperature-controlled application of radio frequency energy to the airways can reduce airway responsiveness to MCh for at least 3 yr in dogs by reducing airway smooth muscle contractility.