gebhart/patrepeval huggingface dataset:
An ATP-Site On-Off Switch That Restricts Phosphatase Accessibility of Akt (2012)

The protein serine-threonine kinase Akt undergoes a substantial conformational change upon activation, which is induced by the phosphorylation of two critical regulatory residues, threonine 308 and serine 473. Paradoxically, treating cells with adenosine 5'-triphosphate (ATP)-competitive inhibitors of Akt results in increased phosphorylation of both residues. We show that binding of ATP-competitive inhibitors stabilized a conformation in which both phosphorylated sites were inaccessible to phosphatases. ATP binding also produced this protection of the phosphorylated sites, whereas interaction with its hydrolysis product adenosine 5'-diphosphate (ADP) or allosteric Akt inhibitors resulted in increased accessibility of these phosphorylated residues. ATP-competitive inhibitors mimicked ATP by targeting active Akt. Forms of Akt activated by an oncogenic mutation or myristoylation were more potently inhibited by the ATP-competitive inhibitors than was wild-type Akt. These data support a new model of kinase regulation, wherein nucleotides modulate an on-off switch in Akt through conformational changes, which is disrupted by ATP-competitive inhibitors.
Partial Acetylation of Lysine Residues Improves Intraprotein Cross-Linking (2008)

Intramolecular cross-linking coupled with mass spectrometric identification of cross-linked amino acids is a rapid method for elucidating low-resolution protein tertiary structures or fold families. However, previous cross-linking studies on model proteins, such as cytochrome c and ribonuclease A, identified a limited number of peptide cross-links that are biased toward only a few of the potentially reactive lysine residues. Here, we report an approach to improve the diversity of intramolecular protein cross-linking starting with a systematic quantitation of the reactivity of lysine residues of a model protein, bovine cytochrome c. Relative lysine reactivities among the 18 lysine residues of cytochrome c were determined by the ratio of d0 and acetyl-d3 groups at each lysine after partial acetylation with sulfosuccinimidyl acetate followed by denaturation and quantitative acetylation of remaining unmodified lysines with acetic-d6 anhydride. These lysine reactivities were then compared with theoretically derived pKa and relative solvent accessibility surface values. To ascertain if partial N-acetylation of the most reactive lysine residues prior to cross-linking can redirect and increase the observable Lys-Lys cross-links, partially acetylated bovine cytochrome c was cross-linked with the amine-specific, bis-functional reagent, bis(sulfosuccinimidyl)suberate. After proteolysis and mass spectrometry analysis, partial acetylation was shown to significantly increase the number of observable peptides containing Lys-Lys cross-links, shifting the pattern from the most reactive lysine residues to less reactive ones. More importantly, these additional cross-linked peptides contained novel Lys-Lys cross-link information not seen in the non-acetylated protein and provided additional distance constraints that were consistent with the crystal structure and facilitated the identification of the proper protein fold.
Prognostic Value of Macrophage Phenotypes in Resectable Non–Small Cell Lung Cancer Assessed by Multiplex Immunohistochemistry (2019)

Macrophages are important inflammatory cells that regulate innate and adaptive immunity in cancer. Tumor-associated macrophages (TAMs) are thought to differentiate into two main phenotypes: proinflammatory M1 and protumorigenic M2. Currently, the prognostic impact of TAMs and their M1 and M2 phenotypes is unclear in non-small cell cancer (NSCLC). The present study was set up to evaluate an approach for identifying common M1 and M2 macrophage markers and explore their clinical significance in NSCLC. Using multiplex chromogenic immunohistochemistry, tissue microarrays of 553 primary tumors and 143 paired metastatic lymph nodes of NSCLC specimens were stained to detect various putative macrophage phenotypes: M1 (HLA-DR/CD68), M2 (CD163/CD68), M2 (CD204/CD68), and pan-macrophage (CD68/CK). Correlation analyses were performed to examine the relationship between TAMs and adaptive/innate immune infiltrates. HLA-DR<sup>+</sup>/CD68<sup>+</sup>M1 TAM level significantly decreased from pathological stage I to III. In a compartment-specific correlation analysis, moderate to strong correlations were observed between both TAM subsets (M1 and M2) with CD3-, CD8-, CD4-, and CD45RO-positive immune cells. Survival analyses, in both stromal and intratumoral compartments, revealed that high levels of HLA-DR<sup>+</sup>/CD68<sup>+</sup>M1 (stroma, hazard ratio [HR] = 0.73, P = .03; intratumor, HR = 0.7, P = .04), CD204<sup>+</sup>M2 (stroma, HR = 0.7, P = .02; intratumor, HR = 0.6, P = .004), and CD68 (stroma, HR = 0.69, P = .02; intratumor, HR = 0.73, P = .04) infiltration were independently associated with improved NSCLC-specific survival. In lymph nodes, the intratumoral level of HLA-DR<sup>+</sup>/CD68<sup>+</sup>M1 was an independent positive prognostic indicator (Cox model, HR = 0.38, P = .001). In conclusion, high levels of M1, CD204<sup>+</sup>M2, and CD68 macrophages are independent prognosticators of prolonged survival in NSCLC.
Native mass spectrometry of photosynthetic pigment–protein complexes (2013)

Native mass spectrometry (MS), or as is sometimes called "native electrospray ionization" allows proteins in their native or near-native states in solution to be introduced into the gas phase and interrogated by mass spectrometry. This approach is now a powerful tool to investigate protein complexes. This article reviews the background of native MS of protein complexes and describes its strengths, taking photosynthetic pigment-protein complexes as examples. Native MS can be utilized in combination with other MS-based approaches to obtain complementary information to that provided by tools such as X-ray crystallography and NMR spectroscopy to understand the structure-function relationships of protein complexes. When additional information beyond that provided by native MS is required, other MS-based strategies can be successfully applied to augment the results of native MS.
Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes (2013)

ABSTRACT Broadly neutralizing antibodies (bNAbs) PG9 and PG16 were isolated from an International AIDS Vaccine Initiative (IAVI) Protocol G subject infected with human immunodeficiency virus type 1 (HIV-1) clade A. Both antibodies are highly potent and neutralize greater than 70% of viruses tested. We sought to begin immunogen design based on viral sequences from this patient; however, pseudoviruses prepared with 19 envelope sequences from this subject were resistant to neutralization by PG9 and PG16. Therefore, we used a bioinformatics approach to identify closely related viruses that were potentially sensitive to PG9 and PG16. A most-recent common ancestor (MRCA) sequence for the viral envelope (Env) was determined and aligned with 99 subtype A gp160 sequences from the Los Alamos HIV database. Virus BG505.W6M.ENV.C2 (BG505) was found to have the highest degree of homology (73%) to the MRCA sequence. Pseudoviruses prepared with this Env were sensitive to neutralization with a broad panel of bNAbs, including PG9 and PG16. When expressed by 293T cells as soluble gp120, the BG505 monomer bound well to both PG9 and PG16. We further showed that a point mutation (L111A) enabled more efficient production of a stable gp120 monomer that preserves the major neutralization epitopes. Finally, we showed that an adjuvanted formulation of this gp120 protein elicited neutralizing antibodies in rabbits (following a gp120 DNA vaccine prime) and that the antisera competed with bNAbs from 3 classes of nonoverlapping epitopes. Thus, the BG505 Env protein warrants further investigation as an HIV vaccine candidate, as a stand-alone protein, or as a component of a vaccine vector.
Distributed space-time-coded protocols for exploiting cooperative diversity in wireless networks (2003)

We develop and analyze space-time coded cooperative diversity protocols for combating multipath fading across multiple protocol layers in a wireless network. The protocols exploit spatial diversity available among a collection of distributed terminals that relay messages for one another in such a manner that the destination terminal can average the fading, even though it is unknown a priori which terminals will be involved. In particular, a source initiates transmission to its destination, and many relays potentially receive the transmission. Those terminals that can fully decode the transmission utilize a space-time code to cooperatively relay to the destination. We demonstrate that these protocols achieve full spatial diversity in the number of cooperating terminals, not just the number of decoding relays, and can be used effectively for higher spectral efficiencies than repetition-based schemes. We discuss issues related to space-time code design for these protocols, emphasizing codes that readily allow for appealing distributed versions.
Transmission electron microscopy with a liquid flow cell (2011)

The imaging of microscopic structures at nanometre-scale spatial resolution in a liquid environment is of interest for a wide range of studies. Recently, a liquid flow transmission electron microscopy (TEM) holder equipped with a microfluidic cell has been developed and shown to exhibit flow of nanoparticles through an electron transparent viewing window. Here we demonstrate the application of the flow cell system for both scanning and conventional transmission electron microscopy imaging of immobilized nanoparticles with a resolution of a few nanometres in liquid water of micrometre thickness. The spatial resolution of conventional TEM bright field imaging is shown to be limited by chromatic aberration due to multiple inelastic scattering in the water, and we demonstrate that the liquid in the cell can be displaced by a gas phase that forms under intense electron irradiation. Our data suggest that under appropriate conditions, TEM imaging with a liquid flow cell is a promising method for understanding the in situ behaviour of nanoscale structures in a prescribed and dynamically changing chemical environment.
Revival: A Variation-Tolerant Architecture Using Voltage Interpolation and Variable Latency (2009)

Process variations will significantly degrade the performance benefits of future microprocessors as they move toward nanoscale technology. Device parameter fluctuations can introduce large variations in peak operation among chips, cores on a single chip, and microarchitectural blocks within one core. The revival technique combines the post-fabrication tuning techniques voltage interpolation (VI) and variable latency (VL) to reduce such frequency variations.
New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations (2001)

No abstract.
Code compression for VLIW processors using variable-to-fixed coding (2002)

Memory has been one of the most restricted resources in the embedded computing system domain. Code compression has been proposed as a solution to this problem. Previous work used fixed-to variable coding algorithms that translate fixed-length bit sequences into variable-length bit sequences. In this paper, we propose code compression schemes that use variable-to-fixed (V2F) length coding. We also propose an instruction bus encoding scheme, which can effectively reduce the bus power consumption. Though the code compression algorithm can be applied to any embedded processor, it favors VLIW architectures because VLIW architectures require a high-bandwidth instruction pre-fetch mechanism to supply multiple operations per cycle. Experiments show that the compression ratios using memoryless V2F coding for IA-64 and TMS320C6x are around 72.7% and 82.5% respectively. Markov V2F coding can achieve better compression ratio up to 56% and 70% for IA-64 and TMS320C6x respectively. A greedy algorithm for codeword assignment can reduce the bus power consumption and the reduction depends on the probability model used.
The effect of powder particle fusion on the mechanical properties of ultra‐high molecular weight polyethylene (1985)

Abstract Rheo‐optical and mechanical property studies with compression molded ultra‐high molecular weight polyethylene specimens at different temperatures indicate that their mechanical performance is dependent on the degree of fusion of the powder particles during compression and can be enhanced by heating the polymer powder at temperatures above 220°C. Although the mechanical performance of the compression molded specimens can be improved further by solid‐state drawing at a draw ratio 5, the anisotropic morphologies from molded specimen above 220°C have higher initial slope of stress to elongation, strength to break, and an outstanding elastic recovery in compreision to the compression molded specimens at 180°C.
Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines (2008)

Epigenetic changes have been implicated in silencing several B-cell genes in Hodgkin and Reed-Sternberg cells (HRS) of Hodgkin lymphoma (HL), and this mechanism has been proposed to promote HRS survival and escape from immunosurveillance. However, the molecular and functional consequences of histone deacetylase (HDAC) inhibition in HL have not been previously described. In this study, we report that the HDAC inhibitor vorinostat induced p21 expression and decreased Bcl-xL levels causing cell-cycle arrest and apoptosis. Furthermore, vorinostat inhibited STAT6 phosphorylation and decreased its mRNA levels in a dose- and time-dependent manner, which was associated with a decrease in the expression and secretion of Thymus and Activation-Regulated Chemokine (TARC/CCL17) and interleukin (IL)-5 and an increase in IP-10 levels. Moreover, vorino-stat inhibited TARC secretion by dendritic cells that were activated by the thymic stromal lymphopoietin (TSLP). Collectively, these data suggest that pharmacologic HDAC inhibition in HL may induce favorable antitumor activity by a direct antiproliferative effect on HRS cells, and possibly by an immune mediated effect by altering cytokine and chemokines secretion in the microenvironment.
Cyberlindnera xylosilytica sp. nov., a xylitol-producing yeast species isolated from lignocellulosic materials (2015)

Independent surveys of yeasts associated with lignocellulosic-related materials led to the discovery of a novel yeast species belonging to the Cyberlindnera clade (Saccharomycotina, Ascomycota). Analysis of the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domains of the large subunit rRNA gene showed that this species is related to C. japonica, C. maesa and C. easanensis. Six isolates were obtained from different sources, including rotting wood, tree bark and sugar cane filter cake in Brazil, frass from white oak in the USA and decayed leaf in Taiwan. A novel species is suggested to accommodate these isolates, for which the name C. xylosilytica sp. nov. is proposed. The type strain of C. xylosilytica sp. nov. is NRRL YB-2097(T) ( = CBS 13984(T) = UFMG-CM-Y347(T)) and the allotype is UFMG-CM-Y409 ( = CBS 14083). The novel species is heterothallic and complementary mating types are represented by the type and allotype strains. The MycoBank number is MB 811428.
Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs (2010)

siRNAs confer sequence specific and robust silencing of mRNA. By virtue of these properties, siRNAs have become therapeutic candidates for disease intervention. However, their use as therapeutic agents can be hampered by unintended off-target effects by either or both strands of the siRNA duplex. We report here that unlocked nucleobase analogs (UNAs) confer desirable properties to siRNAs. Addition of a single UNA at the 5'-terminus of the passenger strand blocks participation of the passenger strand in RISC-mediated target down-regulation with a concomitant increase in guide strand activity. Placement of a UNA in the seed region of the guide strand prevents miRNA-like off-target silencing without compromising siRNA activity. Most significantly, combined substitution of UNA at the 3'-termini of both strands, the addition of a UNA at the 5'-terminus of the passenger strand, and a single UNA in the seed region of the guide strand, reduced the global off-target events by more than 10-fold compared to unmodified siRNA. The reduction in off-target events was specific to UNA placement in the siRNA, with no apparent new off-target events. Taken together, these results indicate that when strategically placed, UNA substitutions have important implications for the design of safe and effective siRNA-based therapeutics.
A Review for Conductive Polymer Piezoresistive Composites and a Development of a Compliant Pressure Transducer (2012)

This paper presents the development process for a new kind of compliant piezoresistive transducer based on carbon-nanotube-filled silicone rubber composite. The methods for the composite fabrication and the sensor probe encapsulation are specified. The piezoresistive mechanism of the composite is researched based on the tunneling effect theory. The calibration and transforming method is designed based on the piezoresistivity of the composite. The signal processing system is developed to realize the data conversion, acquisition, processing, and pressure displaying. The transducer system is tested within the measurement range from 0 to 2 MPa at room temperature. The measuring error is 4% full scale. The transducer system can be used to measure the interlaminar pressure of the industrial equipment. Its key technologies can also be used to fabricate an electronic skin and a robotic haptic sensing system.
Biochemical and Structural Basis for Feedback Inhibition of Mevalonate Kinase and Isoprenoid Metabolism, (2008)

Mevalonate kinase (MK), which catalyzes a key reaction in polyisoprenoid and sterol metabolism in many organisms, is subject to feedback regulation by farnesyl diphosphate and related compounds. The structures of human mevalonate kinase and a binary complex of the rat enzyme incubated with farnesyl thiodiphosphate (FSPP) are reported. Significant FSPP hydrolysis occurs under crystallization conditions; this results in detection of farnesyl thiophosphate (FSP) in the structure of the binary complex. Farnesyl thiodiphosphate competes with substrate ATP to produce feedback inhibition of mevalonate kinase. The binding sites for these metabolites overlap, with the phosphate of FSP nearly superimposed on ATP's beta-phosphate and FSP's polyisoprenoid chain overlapping ATP's adenosine moiety. Several hydrophobic amino acid side chains are positioned near the polyisoprenoid chain of FSP and their functional significance has been evaluated in mutagenesis experiments with human MK, which exhibits the highest reported sensitivity to feedback inhibition. Results suggest that single and double mutations at T104 and I196 produce a significant inflation of the K(i) for FSPP (approximately 40-fold for T104A/I196A). Such an effect persists when K(i) values are normalized for effects on the K(m) for ATP, suggesting that it may be possible to engineer MK proteins with altered sensitivity to feedback inhibition. Comparison of animal MK protein alignments and structures with those of a MK protein from Streptococcus pneumoniae indicates that sequence differences between N- and C-terminal domains correlate with differences in interdomain angles. Bacterial MK proteins exhibit more solvent exposure of feedback inhibitor binding sites and, consequently, weaker binding of these inhibitors.
Synthesis and Characterization of Technetium-99m-Labeled Tropanes as Dopamine Transporter-Imaging Agents (1997)

In the development of novel Tc-99m-labeled tropane derivatives as dopamine transporter (reuptake site)-imaging agents, a series of neutral and lipophilic complexes containing bis-(aminoethanethiol) as a neutral complexing moiety for a [99mTc]TcO3+ center core was successfully prepared. Biological evaluation of the Tc-99m-labeled complexes 13-16 as central nervous system (CNS) dopamine transporter-imaging agents was reported. Synthesis of the tropane derivatives was achieved by stepwise reactions adding two aminoethanethiol units. The final free thiol ligands were obtained by deblocking the 4-methoxybenzyl protecting group with Hg(OAc)2 to obtain trifluoroacetate salts. All of the Tc-99m complexes, with the exception of 16, displayed good initial brain uptake and selective uptake in the striatal area, where dopamine transporters are concentrated. One of the compounds, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethy] amino]ethanethiolato-(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)]- [99mTc]technetium,[99mTc]TRODAT-1 (13), displayed the highest initial uptake in rat brain (0.4% at 2 min post iv injection); the striatal/cerebellar (ST/ CB) ratio reached 2.8 at 60 min after an iv injection. The specific uptake in rat brain can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; iv, 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal uptake was not affected by pretreating rats with a noncompeting ligand, haldol (iv, 1 mg/kg). After an iv injection of 9 mCi of [99mTc]TRODAT-1 (13), in vivo images of baboon brain using single-photon emission-computed tomography exhibited excellent localization in striatum (basal ganglia), where dopamine neurons are known to be concentrated. This series of compounds may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS diseases (i.e., Parkinson's disease) in which changes in the dopamine transporter concentration are implicated.
Associating figures with descriptions for patent documents (2010)

Patent document images maintained by the U.S. patent database have a specific format, in which figures and text descriptions are separated into different sections. This makes it difficult for users to refer to a figure while reading the description or vice versa. This paper introduces a method to associate figures with corresponding description paragraphs, and thus help to make patent documents more friendly for users to browse. In this method, after extracting individual figures out of the drawing section, figures and relevant descriptions are associated by evaluating the similarity between the text content of figures and description paragraphs using vector space model.
Improving nanoimprint lithography stamps for the 10 nm features (2002)

Nanoimprint lithography has been demonstrated to produce structures down to a size range of approximately 10 nm. However, such resolution has only been obtained when printing small areas. A prerequisite for producing such structures repeatedly over a large area is a good stamp, of which the quality does not deteriorate with usage. The smaller the features on the stamp the more important are the interactions between stamp and polymer layer. A stamp rich in small structures will effectively show a surface area enlargement, which a generally leads to an adhesion of the polymer to the stamp. This makes a subsequent imprint impossible without troublesome and time-consuming cleaning. The anti-adhesion properties of Si- or SiO/sub 2/-based stamps can be improved by binding fluorinated silanes covalently to the surface. In this paper we demonstrate that the deposition procedure as well as the environment during deposition are important with respect to the quality of the molecular layer.