gebhart/patrepeval huggingface dataset:
Multiple Site‐Selective Insertions of Noncanonical Amino Acids into Sequence‐Repetitive Polypeptides (2013)

A simple and efficient method is described for the introduction of noncanonical amino acids at multiple, defined sites within recombinant polypeptide sequences. Escherichia coli MRA30, a bacterial host strain with attenuated activity of release factor 1 (RF1), was assessed for its ability to support incorporation of a diverse range of noncanonical amino acids in response to multiple encoded amber (TAG) codons within genes derived from superfolder GFP and an elastin-mimetic protein polymer. Suppression efficiency and protein yield depended on the identity of the orthogonal aminoacyl-tRNA synthetase/tRNA(CUA) pair and the noncanonical amino acid. Elastin-mimetic protein polymers were prepared in which noncanonical amino acid derivatives were incorporated at up to 22 specific sites within the polypeptide sequence with high substitution efficiency. The identities and positions of the variant residues were confirmed by mass spectrometric analysis of the full-length polypeptides and proteolytic cleavage fragments from thermolysin digestion. The data suggest that this multisite suppression approach permits the preparation of protein-based materials in which novel chemical functionalities can be introduced at precisely defined positions within the polypeptide sequence.
The Complete Atomic Structure of the Large Ribosomal Subunit at 2.4 Å Resolution (2000)

The large ribosomal subunit catalyzes peptide bond formation and binds initiation, termination, and elongation factors. We have determined the crystal structure of the large ribosomal subunit from Haloarcula marismortui at 2.4 angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of its 31 proteins. The domains of its RNAs all have irregular shapes and fit together in the ribosome like the pieces of a three-dimensional jigsaw puzzle to form a large, monolithic structure. Proteins are abundant everywhere on its surface except in the active site where peptide bond formation occurs and where it contacts the small subunit. Most of the proteins stabilize the structure by interacting with several RNA domains, often using idiosyncratically folded extensions that reach into the subunit's interior.
The Influence of J.G. Goodchild (1988)

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Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease (2011)

Chronic kidney disease (CKD) and several other catabolic conditions are characterized by increased circulating inflammatory cytokines, defects in IGF-1 signaling, abnormal muscle protein metabolism, and progressive muscle atrophy. In these conditions, no reliable treatments successfully block the development of muscle atrophy. In mice with CKD, we found a 2- to 3-fold increase in myostatin expression in muscle. Its pharmacological inhibition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC(50) ∼1.2 nM) reversed the loss of body weight (≈5-7% increase in body mass) and muscle mass (∼10% increase in muscle mass) and suppressed circulating inflammatory cytokines vs. results from CKD mice injected with PBS. Pharmacological myostatin inhibition also decreased the rate of protein degradation (16.38 ± 1.29%; P<0.05), increased protein synthesis in extensor digitorum longus muscles (13.21 ± 1.09%; P<0.05), markedly enhanced satellite cell function, and improved IGF-1 intracellular signaling. In cultured muscle cells, TNF-α increased myostatin expression via a NF-κB-dependent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and MEK1 pathways. Because IL-6 stimulates muscle protein breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading to muscle atrophy. Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics.
Membrane remodeling during reticulocyte maturation (2009)

The transition of reticulocytes into erythrocytes is accompanied by extensive changes in the structure and properties of the plasma membrane. These changes include an increase in shear resistance, loss of surface area, and acquisition of a biconcave shape. The processes by which these changes are effected have remained largely undefined. Here we examine how the expression of 30 distinct membrane proteins and their interactions change during murine reticulocyte maturation. We show that tubulin and cytosolic actin are lost, whereas the membrane content of myosin, tropomyosin, intercellular adhesion molecule-4, glucose transporter-4, Na-K-ATPase, sodium/hydrogen exchanger 1, glycophorin A, CD47, Duffy, and Kell is reduced. The degradation of tubulin and actin is, at least in part, through the ubiquitin-proteasome degradation pathway. In regard to the protein-protein interactions, the formation of membrane-associated spectrin tetramers from dimers is unperturbed, whereas the interactions responsible for the formation of the membrane-skeletal junctions are weaker in reticulocytes, as is the attachment of transmembrane proteins to these structures. This weakness, in part, results from the elevated phosphorylation of 4.1R in reticulocytes, which leads to a decrease in shear resistance by reducing its interaction with spectrin and actin. These observations begin to unravel the mechanistic basis of crucial changes accompanying reticulocyte maturation.
Time-resolved fluorometer for lanthanide chelates--a new generation of nonisotopic immunoassays. (1983)

Pulsed-light time-resolved fluorometry of lanthanide chelates has proved to be very sensitive for use with nonisotopic immunoassays. We describe a manually operated fluorometer with a conventional xenon flashtube. Sensitivity for 1-s determinations is similar to that of radioisotopic methods.
Pulmonary Surfactant Protein B (SP-B): Structure-Function Relationships (1991)

SP-B is a protein in pulmonary surfactant that is, in greatest part, responsible for resistance to surface tension and prevention of collapse of pulmonary alveoli. Peptides of 21 residues, synthesized following the sequence of SP-B or resembling the hydrophobic and hydrophilic domains of SP-B (such as RLLLLRLLLLRLLLLRLLLLR, R, Arg, and L, Leu), enhanced the abilities of phospholipids to reduce surface tension both in vitro and in vivo. Intermittent positively charged residues were essential for this activity. The SP-B-like peptides were found by tryptophan fluorescence to partition within the phospholipid layer in contact with both polar head groups and acyl side chains. These data, together with findings that the SP-B-related peptides increase inter- and intramolecular order of the phospholipid layer, suggest that SP-B resists surface tension by increasing lateral stability of the phospholipid layer.
Recognition and Accommodation at the Androgen Receptor Coactivator Binding Interface (2004)

Prostate cancer is a leading killer of men in the industrialized world. Underlying this disease is the aberrant action of the androgen receptor (AR). AR is distinguished from other nuclear receptors in that after hormone binding, it preferentially responds to a specialized set of coactivators bearing aromatic-rich motifs, while responding poorly to coactivators bearing the leucine-rich "NR box" motifs favored by other nuclear receptors. Under normal conditions, interactions with these AR-specific coactivators through aromatic-rich motifs underlie targeted gene transcription. However, during prostate cancer, abnormal association with such coactivators, as well as with coactivators containing canonical leucine-rich motifs, promotes disease progression. To understand the paradox of this unusual selectivity, we have derived a complete set of peptide motifs that interact with AR using phage display. Binding affinities were measured for a selected set of these peptides and their interactions with AR determined by X-ray crystallography. Structures of AR in complex with FxxLF, LxxLL, FxxLW, WxxLF, WxxVW, FxxFF, and FxxYF motifs reveal a changing surface of the AR coactivator binding interface that permits accommodation of both AR-specific aromatic-rich motifs and canonical leucine-rich motifs. Induced fit provides perfect mating of the motifs representing the known family of AR coactivators and suggests a framework for the design of AR coactivator antagonists.
Calreticulin Functions as a Molecular Chaperone in the Biosynthesis of Myeloperoxidase (1995)

Myeloperoxidase (MPO), a lysosomal heme protein found exclusively in neutrophils and monocytes, is necessary for efficient oxygen-dependent microbicidal activity. Acquisition of heme by the heme-free MPO precursor apopro-MPO appears to be a prerequisite for its subsequent proteolytic processing and advancement along the biosynthetic pathway to mature MPO. We present data indicating that calreticulin (CRT), a high capacity calcium-binding protein residing in the lumen of the endoplasmic reticulum of a wide variety of cells, interacts specifically with fully glycosylated apopro-MPO. Biosynthetically radiolabeled CRT (60 kDa) and apopro-MPO (90 kDa) were coprecipitated from PLB 985 cells by monospecific antiserum against CRT when the immunoprecipitations were performed either under nondenaturing conditions or following reversible crosslinking. Nonglycosylated MPO precursors synthesized in the presence of tunicamycin did not interact with CRT. The CRT-apopro-MPO interaction was restricted to an early phase of MPO biosynthesis, and CRT did not interact with the later appearing, heme-containing species of MPO, i.e. pro-MPO or the heavy subunit of mature MPO. These data show that CRT participates in the post-translational processing of MPO, perhaps by maintaining apopro-MPO in a conformation competent to accommodate insertion of the heme group. In this general way, CRT shares certain functional properties with the structurally homologous transmembrane calcium-binding endoplasmic reticulum protein calnexin. Both interact with glycosylated biosynthetic precursors of proteins selectively expressed in specialized cells.
Total current collapse in high-voltage GaN MIS-HEMTs induced by Zener trapping (2013)

We investigate current collapse in GaN MIS-HEMTs for >600 V operation. Extreme trapping leading to total current collapse has been observed after OFF-state stress at high voltage. We attribute this to high-field tunneling-induced electron trapping (“Zener trapping”) inside the AlGaN barrier or the GaN channel layers. The trapping takes place in a narrow region right under the edge of the outermost field plate in the drain portion of the device. The trapping characteristics are consistent with those responsible for the yellow luminescence band in GaN or AlGaN. This finding gives urgency to defect control during epitaxial-growth and the design of appropriate field plate structures for the reliable high-voltage operation of MIS-HEMTs.
Specific interaction of HeLa cell proteins with coxsackievirus B3 3'UTR: La autoantigen binds the 3' and 5'UTR independently of the poly(A) tail (2007)

Coxsackievirus B3 (CVB3) is a positive, single-stranded RNA virus. The secondary structure of the 3' untranslated region (3'UTR) of CVB3 RNA consists of three stem-loops and is followed by a poly(A) tail sequence. These stem-loop structures have been suggested to participate in the regulation of viral replication through interaction with cellular proteins that are yet to be identified. In this study, by competitive UV cross-linking using mutated 3'UTR probes we have demonstrated that the poly(A) tail is essential for promoting HeLa cell protein interactions with the 3'UTR because deletion of this sequence abolished most of the protein interactions. Unexpectedly, mutations that disrupted the tertiary loop-loop interactions without affecting the stem-loops did not apparently affect these protein interactions, indicating that secondary structure rather than the high-order structure may play a major role in recruiting these RNA binding proteins. Among the observed 3'UTR RNA binding proteins, we have confirmed a 52 kDa protein as the human La autoantigen by using purified recombinant protein and a polyclonal La antibody. This protein can interact with both the 3' and 5'UTRs independently of the poly(A) tail. Further analysis by two-stage UV cross-linking, we found that the 3' and 5'UTR sequences may share the same binding site on the La protein.
Body Mass Index, Weight Change, and Risk of Mobility Disability in Middle-aged and Older Women (1994)

These prospective data suggest that high BMI is a strong predictor of long-term risk for mobility disability in older women and that this risk persists even to very old age. However, the paradoxical increase in risk associated with weight loss in the old-old women requires further study. Programs to prevent overweight may have potential for decreasing disability in women.
A New Start (2012)

This chapter deals with Joseph's transfer to Austin to investigate corruption in the administration of then–Texas governor Dolph Briscoe. Joseph spent his first three months in Austin in a motel at the government's expense. When he was officially transferred in early 1978, he got a small furnished apartment. He built relationship with Judy Gregor in Austin. His time with the FBI in Austin was largely a waste for two reasons. First, by the time he landed in Texas, he had a bad attitude about the Bureau, even though he should not have. Second, he had 13 years to go before he would even be eligible to retire and he knew his chances of spending it all in Austin were small. After spending nearly three years in Austin, he was sent to the division headquarters in San Antonio. The chapter also discusses his interaction with his ex-wife Dawn and his resignation from FBI office.
Hockey Violence: A Test of the Violent Subculture Hypothesis (1979)

The fundamental tenet of the violent subculture hypothesis, in its generic form, is that violent behavior results from a set of proviolence values and attitudes. The present research was to test this hypothesis as an explanation of violence in Canadian amateur ice-hockey. Interviews with over 700 players and nonplayers yielded data on values and attitudes; self-reports of fighting and official records of major hockey penalties were used as measures of violent behavior. The results support the violent subculture hypothesis. Individuals who professed values and attitudes supportive of violence were significantly more violent than those who did not. The data do not support the societal version of the hypothesis, described by Wolfgang and Ferracuti and other theorists in the criminological tradition; values and attitudes were poor predictors of off-ice fighting and bore no relationship to social class. What the findings do point to is an occupational subculture, composed mainly of older players in highly competitive select and junior leagues, where professional criteria regarding the use of violence prevail. Compared to younger, house-league boys and to nonplayers, these performers endorsed values and attitudes of violence.
Antigenic and Molecular Conservation of the Gonococcal NspA Protein (1999)

A low-molecular-weight protein named NspA (neisserial surface protein A) was recently identified in the outer membrane of all Neisseria meningitidis strains tested. Antibodies directed against this protein were shown to protect mice against an experimental meningococcal infection. Hybridization experiments clearly demonstrated that the nspA gene was also present in the genomes of the 15 Neisseria gonorrhoeae strains tested. Cloning and sequencing of the nspA gene of N. gonorrhoeae B2 revealed an open reading frame of 525 nucleotides coding for a polypeptide of 174 amino acid residues, with a calculated molecular weight of 18,316 and a pI of 10.21. Comparison of the predicted amino acid sequence of the NspA polypeptides from the gonococcal strains B2 and FA1090, together with that of the meningococcal strain 608B, revealed an identity of 93%, suggesting that the NspA protein is highly conserved among pathogenic Neisseria strains. The level of identity rose to 98% when only the two gonococcal predicted NspA polypeptides were compared. To evaluate the level of antigenic conservation of the gonococcal NspA protein, monoclonal antibodies (MAbs) were generated. Four of the seven NspA-specific MAbs described in this report recognized their corresponding epitope in 100% of the 51 N. gonorrhoeae strains tested. Radioimmunobinding assays clearly indicated that the gonococcal NspA protein is exposed at the surface of intact cells.
Isolation and characterization of bacteria associated with two sand dune plant species, Calystegia soldanella and Elymus mollis. (2005)

Little is known about the bacterial communities associated with the plants inhabiting sand dune ecosystems. In this study, the bacterial populations associated with two major sand dune plant species, Calystegia soldanella (beach morning glory) and Elymus mollis (wild rye), growing along the costal areas in Tae-An, Chungnam Province, were analyzed using a culture-dependent approach. A total of 212 bacteria were isolated from the root and rhizosphere samples of the two plants, and subjected to further analysis. Based on the analysis of the 16S rDNA sequences, all the bacterial isolates were classified into six major phyla of the domain Bacteria. Significant differences were observed between the two plant species, and also between the rhizospheric and root endophytic communities. The isolates from the rhizosphere of the two plant species were assigned to 27 different established genera, and the root endophytic bacteria were assigned to 21. Members of the phylum Gammaproteobacteria, notably the Pseudomonas species, comprised the majority of both the rhizospheric and endophytic bacteria, followed by members of Bacteroidetes and Firmicutes in the rhizosphere and Alphaproteobacteria and Bacteroidetes in the root. A number of isolates were recognized as potentially novel bacterial taxa. Fifteen out of 27 bacterial genera were commonly found in the rhizosphere of both plants, which was comparable to 3 out of 21 common genera in the root, implying the host specificity for endophytic populations. This study of the diversity of culturable rhizospheric and endophytic bacteria has provided the basis for further investigation aimed at the selection of microbes for the facilitation of plant growth.
The Wisconsin Hα Mapper (WHAM): A Brief Review of Performance Characteristics and Early Scientific Results (1998)

Abstract. The Wisconsin H α Mapper (WHAM) is a recently completed facility for the detection and study of faint optical emission lines from diffuse ionised gas in the disk and halo of the Galaxy. WHAM consists of a 15 cm diameter Fabry–Perot spectrometer coupled to a 0·6 m ‘telescope’, which provide a 1° diameter beam on the sky and produce a 12 km s −1 resolution spectrum within a 200 km s −1 spectral window. This facility is now located at Kitt Peak in Arizona and operated remotely from Madison, Wisconsin, 2400 km distant. Early results include a velocity-resolved H α map of a 70° × 100° region of the sky near the Galactic anticentre, the first detections of H α emission from the M I and A high velocity clouds, and the first detections of [O I] λ6300 and other faint ‘diagnostic’ lines from the warm ionised medium. Through the summer of 1998, WHAM will be devoted almost exclusively to a survey of the northern sky, which will provide maps of the distribution and kinematics of the diffuse HII through the optical H α line in a manner that is analogous to earlier sky surveys of the HI made through the 21 cm line.
Framework for security and privacy in automotive telematics (2002)

Automotive telematics may be defined as the information-intensive applications that are being enabled for vehicles by a combination of telecommunications and computing technology. Telematics by its nature requires the capture of sensor data, storage and exchange of data to obtain remote services. In order for automotive telematics to grow to its full potential, telematics data must be protected. Data protection must include privacy and security for end-users, service providers and application providers. In this paper, we propose a new framework for data protection that is built on the foundation of privacy and security technologies. The privacy technology enables users and service providers to define flexible data model and policy models. The security technology provides traditional capabilities such as encryption, authentication, non-repudiation. In addition, it provides secure environments for protected execution, which is essential to limiting data access to specific purposes.
When Translation Meets Metabolism: Multiple Links to Diabetes (2003)

Type 2 diabetes is a polygenic disorder characterized by multiple biochemical defects including transcriptional, translational, and posttranslational abnormalities. Although major progress has been made in elucidation of factors at the transcriptional and posttranslational levels, defects at the translational level remain elusive. Mutation of a kinase that regulates translation initiation has been implicated in the etiology of a monogenic form of diabetes known as Wolcott-Rallison syndrome. Characterization of mice rendered deficient in eukaryotic initiation factors has provided model systems to study the involvement of translation in regulating insulin synthesis and secretion, hepatic function, peripheral insulin resistance, and diabetic complications. Recent progress in the understanding of endoplasmic reticulum overload by unfolded proteins has begun to uncover mechanisms leading to pancreatic beta-cell exhaustion. Future advances in this area may lead to identification of the missing links in the pathogenesis of beta-cell failures due to conditions such as hyperinsulinemia, hyperglycemia, and long-term treatment with sulfonylureas, and thus may identify novel therapeutic targets for diabetes.
Beyond post-synthesis modification: evolution of metal–organic frameworks via building block replacement (2014)

Metal-organic frameworks (MOFs) are hybrid porous materials with many potential applications, which intimately depend on the presence of chemical functionality either at the organic linkers and/or at the metal nodes. Functionality that cannot be introduced into MOFs directly via de novo syntheses can be accessed through post-synthesis modification (PSM) on the reactive moieties of the linkers and/or nodes without disrupting the metal-linker bonds. Even more intriguing methods that go beyond PSM are herein termed building block replacement (BBR) which encompasses (i) solvent-assisted linker exchange (SALE), (ii) non-bridging ligand replacement, and (iii) transmetalation. These one-step or tandem BBR processes involve exchanging key structural components of the MOF, which in turn should allow for the evolution of protoMOF structures (i.e., the utilization of a parent MOF as a template) to design MOFs composed of completely new components, presumably via single crystal to single crystal transformations. The influence of building block replacement on the stability and properties of MOFs will be discussed, and some insights into their mechanistic aspects are provided. Future perspectives providing a glimpse into how these techniques can lead to various unexplored areas of MOF chemistry are also presented.