gebhart/patrepeval huggingface dataset:
Identification of a transactivating function mapping to the putative immediate-early locus of human herpesvirus 6 (1991)

Sequencing studies have indicated that the unique component of the human herpesvirus 6 (HHV-6) genome and the unique long segment of the human cytomegalovirus genome are genetically colinear. Of particular interest is the identification of a region of local CpG dinucleotide suppression in the genome of HHV-6, a feature conserved in the genomes of human cytomegalovirus, murine cytomegalovirus, and simian cytomegalovirus, and a characteristic of the major immediate-early loci of these viruses. Adjacent to this region in HHV-6 are approximately 30 copies of a 103- to 108-bp sequence element, which contains consensus binding sites for the transcription factors AP2 and NF kappa B, in addition to a single KpnI recognition site. Together, these KpnI repeat units may compose an immediate-early enhancer, analogous to those found in the cytomegaloviruses. We present the sequence of this region of HHV-6 and demonstrate that a transactivating function is encoded by this region. We have used polymerase chain reaction to synthesize fragments containing open reading frames and 5' sequences with or without the upstream KpnI repeat units. Effector plasmids containing these HHV-6 coding and 5' sequences were able to effect activation of heterologous promoter-chloramphenicol acetyltransferase (CAT) constructs, including adenovirus E3-CAT and E4-CAT, human T-cell lymphotropic virus type I long terminal repeat (LTR)-CAT, and human immunodeficiency virus LTR-CAT, in cotransfection experiments in Vero cells and peripheral blood lymphocytes. Furthermore, we have identified the major open reading frame (RF4; 2.3 kb) as being essential for activation, and we have shown that the NF kappa B, SP1, and TATA box motifs in the human immunodeficiency virus LTR are all required for full induction of the promoter by the HHV-6-encoded transactivator.
Effect of Oxidized Spermine and Other Aldehydes on the Infectivity of Vaccinia Virus (1972)

The antiviral activity of oxidized spermine was compared with that of other aldehydes. Suspensions of vaccinia virus were incubated at 37 C with various concentrations of the aldehydes, and the infectivity of the viruses was determined by the plaque assay. Oxidized spermine at a concentration of 0.82 mM completely inactivated a suspension of vaccinia virus (1.4 x 10(8) plaque-forming units) after incubation at 37 C for 10 hr. Glutaraldehyde and formaldehyde were less active when compared on a molar basis, but acrolein resembled oxidized spermine in its antiviral activity. Because acrolein is produced from oxidized spermine at only 20 to 30% yield, it is unlikely that the biological activity of the latter is due to acrolein formed during the spontaneous degradation of oxidized spermine.
Proof-of-concept study of the Aer-O-Scope™ omnidirectional colonoscopic viewing system in ex vivo and in vivo porcine models (2007)

The OmniVision system allows for a highly sensitive inspection of the colonic mucosa without the need for tip manipulation. Clinical studies are warranted in order to validate these results in humans.
Coding Nucleotide, 5′ Regulatory, and Deduced Amino Acid Sequences of P-450BM-3, a Single Peptide Cytochrome P-450:NADPH-P-450 Reductase from Bacillus megaterium (1989)

Cytochrome P-450BM-3 (P-450BM-3) from Bacillus megaterium incorporates both a P-450 and an NADPH:P-450 reductase in proteolytically separable domains of a single, 119-kDa polypeptide and functions as a fatty acid monooxygenase independently of any other protein. A 5-kilobase DNA fragment which contains the gene encoding P-450BM-3 was sequenced. A single continuous open reading frame starting at nucleotide 1541 of the 5-kilobase fragment correctly predicted the previously determined NH2-terminal protein sequences of the trypsin-generated P-450 and reductase domains and, in toto, predicted a mature polypeptide of 1,048-amino acid residues with Mr = 117,641. The trypsin site was found at arginine residue 471. The P-450 domain is most similar (about 25%) to the fatty acid omega-hydroxylases of P-450 family IV, while the reductase domain exhibits some 33% sequence similarity with the NADPH:P-450 reductases of mammalian liver. Both the P-450 and reductase domains of P-450BM-3 define new gene families but contain highly conserved segments which display as much as 50% sequence similarity with P-450s and reductases of eukaryotic origin. The mRNA for P-450BM-3 was found by S1 mapping to be 3,339 +/- 10 nucleotides in length. In the accompanying paper, two regions in the 1.5 kilobases 5' to the P-450BM-3 coding region have been implicated in the regulation of P-450BM-3 gene expression.
<title>Integrated optic devices using micromachined metal membranes</title> (1996)

Metal membranes fabricated using a surface micromachining process can be integrated with passive optical waveguides on silicon substrates to form active devices. Electrostatic actuation of a membrane into contact with a waveguide alters both the real and imaginary parts of the propagation constant of the guided mode. This effect has been used to demonstrate both on-off and routing type integrated optic switches, and has potential application to other devices such as variable attenuators and tunable Bragg filters.
Identification of carbonic anhydrase 9 as a contributor to pingyangmycin‐induced drug resistance in human tongue cancer cells (2010)

Drug resistance is the major obstacle to successful cancer treatment. To understand the mechanisms responsible for drug resistance in tongue cancer, Tca8113 cells derived from moderately differentiated human tongue squamous cell carcinoma were exposed to stepwise escalated concentrations of pingyangmycin (PYM) to develop the resistant cell line called Tca8113/PYM, which showed over 18.78-fold increased resistance to PYM as compared with Tca8113 cells, and cross-resistance to cisplatin, pirarubicin, paclitaxel, adriamycin, and mitomycin. We found that the resistance was not associated with multidrug resistance transporter 1 (p170, p-gp), multidrug resistance-associated protein 1 and breast cancer resistance protein overexpression, so we hypothesized that Tca8113/PYM cells must have some other resistance mechanism selected by PYM. To test this hypothesis, the global gene expression profiles between Tca8113 and Tca8113/PYM cells were compared by cDNA microarray. Eighty-nine genes and thirteen expressed sequence tags with differential expression levels between the two cell lines were identified. Some differential expression levels were validated with real-time PCR and western blot. Furthermore, the functional validation showed that both carbonic anhydrase (CA) inhibitor acetazolamide application and CA9 silencing with CA9 antisense oligonucleotides contribute to the medium pH increase of Tca8113/PYM cells and enhanced PYM chemosensitivity. Moreover, both acetazolamide and CA9 antisense oligonucleotides significantly increased PYM-induced caspase 3 activation in Tca8113/PYM cells. Thus, our study suggests that the resistance of Tca8113/PYM cells is probably associated with CA9 and other differential expression molecules, and that CA9 may be an important marker for prediction of PYM responsiveness in tongue cancer chemotherapy.
Treatment of Hair Loss (1999)

Hair loss is a common and distressing symptom. With the approval of two drugs that promote hair growth — finasteride and minoxidil — we can now treat patients with some types of hair loss. Both drugs influence the hair-growth cycle and increase the length and diameter of existing hair, although their mechanisms of action differ. In this article, I will focus on the treatment of two common problems, androgenetic alopecia and alopecia areata, both of which involve a reversible alteration of the hair-growth cycle.The Hair-Growth CycleHair growth is cyclic, with phases of growth (anagen), involution (catagen), and rest . . .
Danger and Beauty in the Art of Billy Atkins (2011)

The life and contribution of Yunkurra Billy Atkins to the world of country art is discussed. Some of his most outstanding works are highlighted.
Concurrent expression of recombination activating genes 1 and 2 in zebrafish olfactory sensory neurons (2001)

Each olfactory sensory neuron (OSN) expresses a single odorant receptor (OR) from a large repertoire of clustered OR genes. It has been hypothesized that OR gene regulation may involve stochastic DNA rearrangement, which in lymphocytes requires the recombination activating genes, rag1 and rag2. We have recently demonstrated that rag1 is expressed in zebrafish OSNs. Here we report that rag2, the obligate partner for rag1 function, is also expressed in OSNs and that its expression pattern mimics that of rag1. The onset of rag1 and rag2 expression preceded that of known zebrafish ORs and the number of rag1-positive OSNs corresponded with the number expressing the olfactory cyclic nucleotide-gated cation channel, an OSN marker. Zebrafish OSNs are the first example of concurrent rag expression in a nonlymphoid tissue. The expression of rag1 and rag2 in OSNs adds to the list of similarities between the olfactory and immune systems that includes monoallelic and mutually exclusive gene expression.
RNA-Dependent RNA Polymerases, Viruses, and RNA Silencing (2002)

Most viruses have RNA genomes that are replicated and transcribed into messenger RNA by viral RNA-dependent RNA polymerases (RdRps), usually in concert with other viral and host factors. Many, if not most, eukaryotes also encode putative RdRps that have been implicated in sequence-specific, RNA-triggered gene silencing. Although the viral and cellular RdRps have no sequence homology, they share functional similarities such as copying messenger RNA templates and intercellular spread of the amplified sequences. Better understanding of viral and host RdRps will improve our ability to control viruses and to use RNA silencing and viruses as tools for research, biotechnology, and medicine.
Solid-Phase Synthesis of Tris-Benzamides as α-Helix Mimetics (2010)

Small molecules mimicking α-helices are of great interest since numerous protein-protein interactions use helical structures at the interface. With a goal of generating libraries of α-helix mimetics, an efficient solid-phase synthetic method was developed to produce tris-benzamides. The tris-benzamide scaffold was designed to place three side-chain functional groups found at the i, i + 4, and i + 7 positions of an α-helix, emulating one helical face. The synthetic strategy involves simple and iterative reactions of removal of an allyl ester, formation of an amide bond via an O → N acyl migration, and an O-alkylation. A small library of twenty tris-benzamides containing a variety of functional groups was prepared in high purity (83-99%) to demonstrate the versatility of the synthetic approach. This methodology allowed the facile and rapid construction of α-helix mimetics that would facilitate the identification of small molecules for target proteins.
Phagocytosis of rod outer segments by retinal pigment epithelial cells requires αvβ5 integrin for binding but not for internalization (1997)

Phagocytosis of shed photoreceptor rod outer segments (ROS) by the retinal pigment epithelium (RPE) is essential for retinal function. Here, we demonstrate that this process requires alpha(v)beta5 integrin, rather than alpha(v)beta3 integrin utilized by systemic macrophages. Although adult rat RPE expressed both alpha(v)beta3 and alpha(v)beta5 integrins, only alpha(v)beta3 was expressed at birth, when the retina is immature and phagocytosis is absent. Expression of alpha(v)beta5 was first detected in RPE at PN7 and reached adult levels at PN11, just before onset of phagocytic activity. Interestingly, alpha(v)beta5 localized in vivo to the apical plasma membrane, facing the photoreceptors, and to intracellular vesicles, whereas alpha(v)beta3 was expressed basolaterally. Using quantitative fluorimaging to assess in vitro uptake of fluorescent particles by human (ARPE-19) and rat (RPE-J) cell lines, alpha(v)beta5 function-blocking antibodies were shown to reduce phagocytosis by drastically decreasing (85%) binding of ROS but not of latex beads. In agreement with a role for alpha(v)beta5 in phagocytosis, immunofluorescence experiments demonstrated codistribution of alpha(v)beta5 integrin with internalized ROS. Control experiments showed that blocking alpha(v)beta3 function with antibodies did not inhibit ROS phagocytosis and that alpha(v)beta3 did not colocalize with phagocytosed ROS. Taken together, our results indicate that the RPE requires the integrin receptor alpha(v)beta5 specifically for the binding of ROS and that phagocytosis involves internalization of a ROS-alpha(v)beta5 complex. Alpha(v)beta5 integrin does not participate in phagocytosis by other phagocytic cells and is the first of the RPE receptors involved in ROS phagocytosis that may be specific for this process.
On the efficiency limit of triplet–triplet annihilation for photochemical upconversion (2009)

Photochemical upconversion is performed, whereby emitter triplet states are produced through triplet energy transfer from sensitizer molecules excited with low energy photons. The triplet emitter molecules undergo triplet-triplet annihilation to yield excited singlet states which emit upconverted fluorescence. Experiments comparing the 560 nm prompt fluorescence when rubrene emitter molecules are excited directly, using 525 nm laser pulses, to the delayed, upconverted fluorescence when the porphyrin sensitizer molecules are excited with 670 nm laser pulses reveal annihilation efficiencies to produce excited singlet emitters in excess of 20%. Conservative measurements reveal a 25% annihilation efficiency, while a direct comparison between the prompt and delayed fluorescence yield suggests a value as high as 33%. Due to fluorescence quenching, the photon upconversion efficiencies are lower, at 16%.
Localization of vascular endothelial growth factor-D in malignant melanoma suggests a role in tumour angiogenesis (2001)

Expression of angiogenic and lymphangiogenic factors by tumours may influence the route of metastatic spread. Vascular endothelial growth factor (VEGF) is a regulator of tumour angiogenesis, but studies of the inhibition of solid tumour growth by neutralizing anti-VEGF antibodies indicated that other angiogenic factors may be involved. VEGF-D may be an alternative regulator because like VEGF it is angiogenic and it activates VEGF receptor-2 (VEGFR-2), an endothelial cell receptor which is a key signalling molecule in tumour angiogenesis. This study reports the generation of monoclonal antibodies to the receptor-binding domain of VEGF-D and the use of these antibodies to localize VEGF-D in malignant melanoma. VEGF-D was detected in tumour cells and in vessels adjacent to immunopositive tumour cells, but not in vessels distant from the tumours. These findings are consistent with a model in which VEGF-D, secreted by tumour cells, activates endothelial cell receptors and thereby contributes to the regulation of tumour angiogenesis and possibly lymphangiogenesis. In addition, VEGF-D was detected in the vascular smooth muscle, but not the endothelium, of vessels in adult colon. The endothelium of these vessels was negative for VEGFR-2 and VEGFR-3. As VEGF receptors can be up-regulated on endothelium in response to vessel damage and ischaemia, these findings of a specific localization of VEGF-D in smooth muscle of the blood vessels suggest that VEGF-D produced by vascular smooth muscle could play a role in vascular repair by stimulating the proliferation of endothelial cells.
New Water-Soluble Duocarmycin Derivatives: Synthesis and Antitumor Activity of A-Ring Pyrrole Compounds Bearing β-Heteroarylacryloyl Groups (1999)

A series of A-ring pyrrole compounds of duocarmycin bearing 4'-methoxy-beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the 4'-methoxy-beta-heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4'-methoxycinnamates. Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates, compound 15b having a (4-methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates had high aqueous solubility.
Rapid protein structure classification using one-dimensional structure profiles on the BioSCAN parallel computer (1995)

Rapid growth of protein structures database in recent years requires an effective approach for objective comparison and classification of deposited protein structures. We describe a novel method for structure comparison and classification based on the alignment of one-dimensional structure profiles. These profiles are obtained by calculating the OCCO pseudodihedral angles (formed by O-C-C-O atoms of carbonyl groups of consecutive amino acid residues) from protein three-dimensional coordinates. These angle measurements are then converted into a 24 letter alphabet, and the protein structures are represented by sequences of letter from this alphabet. The BioSCAN parallel computer, designed for primary sequence alignment, is used to rapidly align and classify these one-dimensional structure profiles. We have developed and implemented weighted scoring matrix to identify structural classes based on commonly found structural motifs. The results of our experiments are in good agreement with the traditional protein structure classification schemes. One-dimensional structure profiles significantly improve efficiency of structure comparison and classification.
Dynamic control of TGF‐β signaling and its links to the cytoskeleton (2008)

Transforming growth factor beta (TGF-beta) regulates cellular behavior in embryonic and adult tissues. TGF-beta binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that coordinately regulate gene expression or cytoplasmic processes such as cytoskeletal dynamics. In turn, the activity and duration of the Smad pathway seems to be regulated by cytoskeletal components, which facilitate the shuttling process that segregates Smad proteins in the cytoplasm and nucleus. We discuss mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of the TGF-beta signal.
Effect of codon optimization on the expression of Trichoderma reesei endoglucanase 1 in Pichia pastoris (2011)

Trichoderma reesei cellulases are important biocatalysts for a wide range of industrial applications that include the paper, feed, and textile industries. T. reesei endoglucanase 1 (egl1) was successfully expressed as an active and stable catalyst in Pichia pastoris for the first time. Codon optimization was applied to egl1 of T. reesei to enhance its expression levels in P. pastoris. When compared with the originally cloned egl1 gene of T. reesei, the synthetic codon optimized egl1 gene (egl1s) was expressed at a higher level in P. pastoris. Batch fermentations of both clones with the same copy number under controlled conditions indicated that codon optimized EGI enzyme activity increased to 1.24 fold after 72 h of methanol induction. Our research indicated that P. pastoris is a suitable host for cellulase production.
Duration of Neuroprotective Treatment for Ischemic Stroke (1998)

Important considerations influencing drug administration should include the pharmacology of the compound (pharmacokinetics, mechanism of action, preclinical toxicity, and pharmaceutical properties), its safety and tolerability in patients, and the likelihood of continuing or recurrent cerebral ischemia, along with practical issues such as ease of administration and interactions with early rehabilitation and other therapies. Optimization of treatment will be possible only when neuroprotection is confirmed to be effective.
Support vector machine classification and validation of cancer tissue samples using microarray expression data (2000)

The SVM software is available at http://www.cs. columbia.edu/ approximately bgrundy/svm.
Linoleic acid derivative DCP-LA improves learning impairment in SAMP8 (2005)

In the water-maze test, the linoleic acid derivative, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) (1 mg/kg, intraperitoneally), significantly shortened the prolonged latency for accelerated-senescence-prone mice 8 (SAMP8), reaching a level similar to the latency for accelerated-senescence-resistant mice 1 (SAMR1) as control. In the open-field test to assess motor activity, it was confirmed that the DCP-LA effect is not due to increased motor activity. In the passive avoidance test to assess fear memory, DCP-LA had no effect on the latency of acquisition and retention for SAMP8. The results of the present study, thus, suggest that DCP-LA could improve age-related learning impairment by enhancing cognitive functions.
Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo (2009)

CNM of gene expression data from mice treated with SRT501 or SRT1720 in combination with supporting in vitro and in vivo data demonstrates that SRT501 and SRT1720 produce a signaling profile that mirrors CR, improves glucose and insulin homeostasis, and acts via SIRT1 activation in vivo. Taken together these results are encouraging regarding the use of small molecule activators of SIRT1 for therapeutic intervention into type 2 diabetes, a strategy which is currently being investigated in multiple clinical trials.
Comparison of aggregating agents for the surface-enhanced Raman analysis of benzodiazepines (2013)

Benzodiazepines are among the most prescribed compounds and are commonly present in many toxicological screens. They are also of concern forensically in cases of drug facilitated sexual assault. Currently these compounds are predominantly analyzed using immunoassay techniques; however more specific screening methods are needed. This paper demonstrates the applicability of surface enhanced Raman spectroscopy as a method for the analysis and detection of benzodiazepines. The procedure involves mixing urine extracts with gold nanoparticles and appropriate aggregating agents for trace detection of these compounds and their metabolites. In this paper we will discuss the optimization of various parameters of this technique as well as its application to screening urine samples. Eleven different benzodiazepines and metabolites were examined, including 1,2-triazolo-benzodiazepines and 1,4-benzodiazpines. Experiments were performed using four different chloride salts, MgCl2, CaCl2, KCl, and NaCl, as aggregating agents for the colloidal gold nanoparticles. Overall it was found that each aggregating agent produced different levels of signal enhancement for each drug. MgCl2 provided the lowest limit of detection at 2.5 ng mL(-1), and linearity over a wide range of concentrations for a variety of drugs chosen. It was also determined that the optimum MgCl2 concentration was 1.67 M. This method has shown the applicability of SERS for the detection of trace quantities of benzodiazepines in aqueous solutions as well as the optimization of the technique over a wide range of compounds. This technique can be utilized in the detection of trace benzodiazepines in toxicological samples following extraction of the analyte.