gebhart/patrepeval huggingface dataset:
Pheromone gland-specific fatty-acyl reductase of the silkmoth, Bombyx mori (2003)

The C10-C18 unsaturated, acyclic, aliphatic compounds that contain an oxygenated functional group (alcohol, aldehyde, or acetate ester) are a major class of sex pheromones produced by female moths. In the biosynthesis of these pheromone components, the key enzyme required to produce the oxygenated functional groups is fatty-acyl reductase (FAR). This enzyme converts fatty-acyl pheromone precursors to their corresponding alcohols, which, depending on the moth species, can then be acetylated or oxidized to the corresponding aldehydes. Despite the significant role this enzyme has in generating the species-specific oxygenated constituents of lepidopteran sex pheromones, the enzyme has yet to be fully characterized and identified. In experiments designed to characterize a pheromone-gland-specific FAR in the silkmoth, Bombyx mori, we have isolated a cDNA clone encoding a protein homologous to a FAR from the desert shrub, Simmondsia chinensis, commonly known as jojoba. The deduced amino acid sequence of this clone predicts a 460-aa protein with a consensus NAD(P)H binding motif within the amino terminus. Northern blot analysis indicated that 2-kb transcripts of this gene were specifically expressed in the pheromone gland at 1 day before adult eclosion. Functional expression of this gene in the yeast Saccharomyces cerevisiae not only confirmed the long-chain FAR activity, but also indicated a distinct substrate specificity. Finally, the transformed yeast cells evoked typical mating behavior in male moths when cultured with the pheromone precursor fatty acid, (E,Z)-10,12-hexadecadienoic acid.
18F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging (2008)

Dual integrin alpha(v)beta(3) and GRPR recognition showed significantly improved tumor-targeting efficacy and pharmacokinetics compared with (18)F-labeled RGD and BBN analogs. The same heterodimeric ligand design may also be applicable to other receptor system combinations and other imaging modalities.
Energetics of diphtheria toxin membrane insertion and translocation: calorimetric characterization of the acid pH induced transition (1989)

The pH and temperature stabilities of diphtheria toxin and its fragments have been studied by high-sensitivity differential scanning calorimetry. These studies demonstrate that the pH-induced conformational transition associated with the mechanism of membrane insertion and translocation of the toxin involves a massive unfolding of the toxin molecule. At physiological temperatures (37 degrees C), this process is centered at pH 4.7 at low ionic strength and at pH 5.4 in the presence of 0.2 M NaCl. At pH 8, the thermal unfolding of the nucleotide-bound toxin is centered at 58.2 degrees C whereas that of the nucleotide-free toxin is centered at 51.8 degrees C, indicating that nucleotide binding (ApUp) stabilizes the native conformation of the toxin. The unfolding profile of the toxin is consistent with two transitions most likely corresponding to the A fragment (Tm = 54.5 degrees C) and the B fragment (Tm = 58.4 degrees C), as inferred from experiments using the isolated A fragment. These two transitions are not independent, judging from the fact that the isolated A fragment unfolds at much lower temperatures (Tm = 44.2 degrees C) and that the B fragment is insoluble in aqueous solutions when separated from the A fragment. Interfragment association contributes an extra -2.6 kcal/mol to the free energy of stabilization of the A fragment. Whereas the unfolding of the entire toxin is irreversible, the unfolding of the A fragment is a reversible process. These findings provide a thermodynamic basis for the refolding of the A fragment after reexposure to neutral pH immediately following translocation across the lysosomal membrane.
Characterization of vibrissa germinative cells: transition of cell types (2001)

Germinative cells, small cell masses attached to the stalks of dermal papillae that are able to differentiate into the hair shaft and inner root sheath, form follicular bulb-like structures when co-cultured with dermal papilla cells. We studied the growth characteristics of germinative cells to determine the cell types in the vibrissa germinative tissue. Germinative tissues, attaching to dermal papillae, were cultured on 3T3 feeder layers. The cultured keratinocytes were harvested and transferred, equally and for two passages, onto lined dermal papilla cells (LDPC) and/or 3T3 feeder layers. The resulting germinative cells were classified into three types in the present experimental condition. Type 1 cells grow very well on either feeder layer, whereas Type 3 cells scarcely grow on either feeder layer. Type 2 cells are very conspicuous and are reversible. They grow well on 3T3 but growth is suppressed on LDPC feeder layers. The Type 2 cells that grow well on 3T3 feeder layers, however, are suppressed when transferred onto LDPC and the Type 2 cells that are suppressed on LDPC begin to grow again on 3T3. The transition of one cell type to another in vitro and the cell types that these germinative cell types correspond to in vivo is discussed. It was concluded that stem cells or their close progenitors reside in the germinative tissues of the vibrissa bulb except at late anagen-early catagen.
Artificial self-assembling systems for gene delivery (1996)

Synthetic Retrotransposon Vectors and Gene Targeting A New Retroviral Vector and a New Method To Target Homologous Recombination in Mammalian Cells Development of the Hairpin Ribozyme as a Gene Therapy Approach to Human Immunodeficiency Virus Type-1 Infection Replicating Plasmid Vectors for Cancer Gene Therapy Gene Targeting Using Triple-Helix-Forming Oligonucleotides Effects of Lipololysaccahrides on Liposome-Mediated Transfection and the Consequence for DNA Preparation for Gene Therapy The Application of Electronic Pulse Delivery in Gene Therapy: Progress and Perspectives Self-Assembling DNA Photonic Nanostructures Controllable Gene Therapy Using Nonviral Systems Progress in Targeting Nucleic Acids to the Liver Advances in Receptor-Mediated Gene Transfer into Cells In Vitro and In Vivo Ligand-Polylysine Mediated Gene Transfer Efficient Transfer of Genetic Material into Mammalian Cells Using Polyamidoamine Dendrimers as Synthetic Vectors: Dendrimer-Mediated Transfection The Proton Sponge: A Trick the Viruses Did Not Exploit Biomaterials for Gene Transfer: Self-Assembling Nanostructured Aquasomes Gene Transfer by Liposome-Entrapped Polycation-Condensed DNA: LPDI and LPDII Gene Transfer into Mammalian Cells Using Synthetic Cationic Lipids
Nucleotide sequence of the ospAB operon of a Borrelia burgdorferi strain expressing OspA but not OspB (1992)

The nucleotide sequence of a 1.6-kb clone containing the gene for outer surface protein A (OspA) of a German strain (GO2) of Borrelia burgdorferi was determined. The deduced amino acid sequence showed a homology of 82% to the OspA molecules from three other B. burgdorferi strains. The best-conserved region was recognized at the 36-amino-terminal amino acids of OspA. OspB could not be identified in the strain investigated, probably because the nucleotide sequence of the ospAB operon prevented expression of the OspB gene.
Increased in vivo effector function of human IgG4 isotype antibodies through afucosylation (2016)

For some antibodies intended for use as human therapeutics, reduced effector function is desired to avoid toxicities that might be associated with depletion of target cells. Since effector function(s), including antibody-dependent cell-mediated cytotoxicity (ADCC), require the Fc portion to be glycosylated, reduced ADCC activity antibodies can be obtained through aglycosylation of the human IgG1 isotype. An alternative is to switch to an IgG4 isotype in which the glycosylated antibody is known to have reduced effector function relative to glycosylated IgG1 antibody. ADCC activity of glycosylated IgG1 antibodies is sensitive to the fucosylation status of the Fc glycan, with both in vitro and in vivo ADCC activity increased upon fucose removal ("afucosylation"). The effect of afucosylation on activity of IgG4 antibodies is less well characterized, but it has been shown to increase the in vitro ADCC activity of an anti-CD20 antibody. Here, we show that both in vitro and in vivo activity of anti-CD20 IgG4 isotype antibodies is increased via afucosylation. Using blends of material made in Chinese hamster ovary (CHO) and Fut8KO-CHO cells, we show that ADCC activity of an IgG4 version of an anti-human CD20 antibody is directly proportional to the fucose content. In mice transgenic for human FcγRIIIa, afucosylation of an IgG4 anti-mouse CD20 antibody increases the B cell depletion activity to a level approaching that of the mIgG2a antibody.
Aliskiren, a novel, orally effective renin inhibitor, lowers blood pressure in marmosets and spontaneously hypertensive rats (2005)

Aliskiren is an orally effective, long-lasting renin inhibitor that shows antihypertensive efficacy in animals superior to previous renin inhibitors and at least equivalent to angiotensin-converting enzyme inhibitors and AT1-receptor blockers. Aliskiren may therefore represent an effective, novel approach to the treatment of hypertension and related disorders, alone or in combination with other antihypertensive agents.
Some Considerations for Implementing the SMART Information Retrieval System Under UNIX (1983)

Since the early 1960's the SMART project has tested out new ideas in information science aimed at fully automatic document retrieval. Beginning in 1980 development of an enhanced and generalized version of SMART has progresses at Cornell. The current implementation is in the C language and runs under the UNIX operating system on a VAX 11/780 computer. The history of SMART is outlined. Considerations that led to the current design are described. Since SMART now allows multiple concept types to be manipulated in connection with an extended vector representation, storage and processing issues are discussed, including use of INGRES relations. Clustering algorithms are presented and run parameters are given for document clustering and subsequent clustered searching. SMART experiments (e.g. with p-norm queries, or probabilistic methods) can be compared using the evaluation package. The S statistical package can be applied to performing other special analysis and descriptive tasks. Finally, to illustrate the usefulness of these facilities, an outline is given of current SMART activities and of future plans.
Individual Variation in the Activation and Inactivation of Metabolic Pathways of Cyclophosphamide (1992)

These data confirm an earlier observation of a phenotypic deficiency of carboxyphosphamide excretion in British patients treated with cyclophosphamide. This deficiency may arise from a polymorphism in the enzyme aldehyde dehydrogenase. Carboxylation phenotype may have important implications for both the therapeutic effect and toxicity of cyclophosphamide.
Characterization of the Binding of Serum Amyloid P to Type IV Collagen (1996)

Serum amyloid P (SAP), a member of the evolutionarily conserved pentraxin family, is a normal component of a number of basement membranes, including glomerular and alveolar. In vitro SAP binds to a variety of proteins including fibronectin, proteoglycans, and the collagen-like region of the complement component C1q. In these studies, binding of SAP to type IV collagen, a major component of basement membrane, was examined. Purified SAP binds to human and mouse type IV collagen but not type I, II, or III collagens. Binding of SAP to type IV collagen is dependent on the presence of Ca2+. This binding is saturable with a Kd approximately 1.2 x 10(-7) M based on solid phase binding and 4 x 10(-8) M based on the IC50 value from fluid phase binding data. Binding of SAP to type IV collagen was inhibited by both SAP and C-reactive protein (CRP). However, a 5-fold molar excess of CRP as compared with SAP was required to inhibit the SAP binding by 50%. Binding of SAP to type IV collagen was inhibited by both collagen IV and C1q but not by phosphatidylethanolamine or bovine serum albumin. The inhibition data indicate that SAP may bind to the triple helical region of type IV collagen via a site distinct from its galactan binding site. The most likely site of SAP involved in its interaction with type IV collagen may be the region spanning amino acid residues 108-120, which shows a great deal of sequence homology (60% strict identity) with the CRP region implicated in its binding to the collagen-like region of the C1q molecule.
Synthesis and Structure of Chemically Stable Metal−Organic Polyhedra (2009)

Two imidazolate-metal based rhombic dodecahedra (termed MOP-100 and MOP-101) were designed and prepared from [(NH(3))(4)Pd(NO(3))(2)] and hydrogen tetrakis(1-imidazolyl)borate or hydrogen tetrakis(4-methyl-1-imidazolyl)borate in a concentrated ammonium hydroxide solution at 85 degrees C. Both rhombic dodecahedra show unusual chemical stability in acidic and basic solutions as well as common organic solvents. Permanent porosity was examined by gas adsorption studies. From the N(2) isotherm for MOP-101, the Langmuir and BET surface areas of MOP-101 were calculated to be 350 and 280 m(2) g(-1), respectively. Anion exchange experiments confirmed the internal cavities of such polyhedra are accessible.
Increased Responsivity of Suspended Graphene Photodetectors (2013)

The responsivity of graphene photodetectors depends critically on the elevated temperature of the electronic subsystem upon photoexcitation. We investigate the role of the substrate in providing cooling pathways for photoexcited carriers under ambient conditions by partially suspending few-layer graphene over a trench. Through photocurrent microscopy, we observe p-n junctions near the supported/suspended interfaces that produce photothermoelectric currents. Most importantly, we find the photocurrent in suspended p-n junctions to be an order of magnitude larger than in supported structures. This enhancement is attributed to the elimination of a dominant electronic cooling channel via the surface phonons of the polar substrate. Our work documents this mechanism of energy exchange between graphene and its environment, and it points to the importance of dielectric engineering for future improved graphene photodetectors.
Enzyme-Catalyzed Acylation of Homoserine:  Mechanistic Characterization of the Haemophilus influenzae met2-Encoded Homoserine Transacetylase (2000)

The first unique step in bacterial and plant methionine biosynthesis involves the acylation of the gamma-hydroxyl of homoserine. In Haemophilus influenzae, acylation is accomplished via an acetyl-CoA-dependent acetylation catalyzed by homoserine transacetylase. The activity of this enzyme regulates flux of homoserine into multiple biosynthetic pathways and, therefore, represents a critical control point for cell growth and viability. We have cloned homoserine transacetylase from H. influenzae and present the first detailed enzymatic study of this enzyme. Steady-state kinetic experiments demonstrate that the enzyme utilizes a ping-pong kinetic mechanism in which the acetyl group of acetyl-CoA is initially transferred to an enzyme nucleophile before subsequent transfer to homoserine to form the final product, O-acetylhomoserine. The maximal velocity and V/K(homoserine) were independent of pH over the range of values tested, while V/K(acetyl)(-)(CoA) was dependent upon the ionization state of a single group exhibiting a pK value of 8.6, which was required to be protonated. Solvent kinetic isotope effect studies yielded inverse effects of 0.75 on V and 0.74 on V/K(CoA) on the reverse reaction and effects of 1.2 on V and 1.7 on V/K(homoserine) on the forward reaction. Direct evidence for the formation of an acetyl-enzyme intermediate was obtained using rapid-quench labeling studies. On the basis of these observations, we propose a chemical mechanism for this important member of the acyltransferase family and contrast its mechanism with that of homoserine transsuccinylase.
Multi-faceted substrate specificity of heparanase (2013)

Heparan sulfate is a highly sulfated polysaccharide abundantly present in the extracellular matrix. Heparan sulfate consists of a disaccharide repeating unit of glucosamine and glucuronic and iduronic acid residues. The functions of heparan sulfate are largely dictated by its size as well as the sulfation patterns. Heparanase is an enzyme that cleaves heparan sulfate polysaccharide into smaller fragments, regulating the functions of heparan sulfate. Understanding the substrate specificity plays a critical role in dissecting the biological functions of heparanase and heparan sulfate. The prevailing view is that heparanase recognizes specific sulfation patterns in heparan sulfate. However, emerging evidence suggests that heparanase is capable of varying its substrate specificities depending on the saccharide structures around the cleavage site. The plastic substrate specificity suggests a complex role of heparanase in regulating the structures of heparan sulfate in matrix biology.
Structure and function of the bacteriophage T4 DNA polymerase holoenzyme (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and function of the bacteriophage T4 DNA polymerase holoenzymeMark C. Young, Michael K. Reddy, and Peter H. Von HippelCite this: Biochemistry 1992, 31, 37, 8675–8690Publication Date (Print):September 22, 1992Publication History Published online1 May 2002Published inissue 22 September 1992https://doi.org/10.1021/bi00152a001RIGHTS & PERMISSIONSArticle Views307Altmetric-Citations76LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (4 MB) Get e-Alerts Get e-Alerts
Genetic Variants of Anaplasma phagocytophilum Infecting Dogs in Western Washington State (2005)

Eight dogs from western Washington State suspected of being infected with Anaplasma phagocytophilum because of the finding of morulae in peripheral blood neutrophils were studied for determination of the etiologic agent of disease. All cases were diagnosed between April 2003 and April 2004. Six of the eight dogs had no travel history during the 6 months prior to presentation. Two dogs had traveled within the Northwest United States and Canada. Fever, lethargy, and anorexia were the most common clinical signs in the dogs. Lymphopenia, thrombocytopenia, and an elevated activity of alkaline phosphatase in the serum were the most common laboratory findings. All dogs tested during the acute phase of clinical signs were seropositive for A. phagocytophilum antibodies but negative for Ehrlichia canis antibodies. PCR amplification and direct sequencing of portions of the 16S rRNA gene from the whole blood of all seven dogs that were tested yielded A. phagocytophilum after a comparison to bacterial sequences available in the GenBank database. Five genetic variants were identified based on one or two nucleotide differences in the 16S rRNA gene sequences at nucleotide positions 54, 84, 86, and 120. Individual dogs were infected with more than one variant. Treatment with doxycycline or tetracycline resulted in a rapid resolution of clinical signs. The occurrence of canine granulocytic anaplasmosis in western Washington State suggests that A. phagocytophilum infection should be considered in differential diagnoses of dogs presenting with lethargy, anorexia, fever, and lameness, particularly in the context of lymphopenia, thrombocytopenia, and increased serum alkaline phosphatase. The zoonotic importance of A. phagocytophilum should support an increase in surveillance for horses and people residing in this area.
Protein Sequencing Protocols (1996)

Bryan Smith draws together in Protein Sequencing Protocols a timely collection of current and state-of-the-art techniques for protein and peptide preparation and sequencing-all described by hands-on masters of the procedures. These well-tested methods convey valuable lessons and insights into using automated sequencers and/or mass spectrometers, preparing proteins and peptides on a microgram and submicrogram scale, mapping peptides, analyzing amino acid by pre- and post-column derivatization methods, and sequencing N- and C-terminal peptides by classical and newly developed techniques. They also deal with such troublesome problems as identifying sites of modification and handling very small samples. Protein Sequencing Protocols offers self-contained, step-by-step recipes that ensure easily reproducible results for those already doing sequencing, and for those who are still learning the methods, as well as for those already in one area but wishing to learn associated techniques. Its multiplicity of proven protocols will guide the challenged experimenter to successful results
On computing correlated aggregates over continual data streams (2001)

In many applications from telephone fraud detection to network management, data arrives in a stream, and there is a need to maintain a variety of statistical summary information about a large number of customers in an online fashion. At present, such applications maintain basic aggregates such as running extrema values (MIN, MAX), averages, standard deviations, etc., that can be computed over data streams with limited space in a straightforward way. However, many applications require knowledge of more complex aggregates relating different attributes, so-called correlated aggregates. As an example, one might be interested in computing the percentage of international phone calls that are longer than the average duration of a domestic phone call. Exact computation of this aggregate requires multiple passes over the data stream, which is infeasible.
A Disintegrin and Metalloproteinase-10 (ADAM-10) Mediates DN30 Antibody-induced Shedding of the Met Surface Receptor (2010)

Met, the tyrosine kinase receptor for the hepatocyte growth factor is a prominent regulator of cancer cell invasiveness and has emerged as a promising therapeutic target. Binding of the anti-Met monoclonal antibody DN30 to its epitope induces the proteolytic cleavage of Met, thereby impairing the invasive growth of tumors. The molecular mechanism controlling this therapeutic shedding process has so far been unknown. Here, we report that A Disintegrin And Metalloproteinase (ADAM)-10, but not ADAM-17, is required for DN30-induced Met shedding. Knockdown of ADAM-10 in different tumor cell lines or abrogation of its proteolytic activity by natural or synthetic inhibitors abolished Met down-regulation on the cell surface as well as reduction of Met activation. Moreover, hepatocyte growth factor-induced tumor cell migration and invasion were impaired upon ADAM-10 knockdown. Thus, the therapeutic effect of DN30 involves ADAM-10-dependent Met shedding, linking for the first time a specific metalloprotease to target therapy against a receptor tyrosine kinase.