gebhart/patrepeval huggingface dataset:
The composition, structure and stability of a group II chaperonin are temperature regulated in a hyperthermophilic archaeon (2003)

The hyperthermoacidophilic archaeon Sulfolobus shibatae contains group II chaperonins, known as rosettasomes, which are two nine-membered rings composed of three different 60 kDa subunits (TF55 alpha, beta and gamma). We sequenced the gene for the gamma subunit and studied the temperature-dependent changes in alpha, beta and gamma expression, their association into rosettasomes and their phylogenetic relationships. Alpha and beta gene expression was increased by heat shock (30 min, 86 degrees C) and decreased by cold shock (30 min, 60 degrees C). Gamma expression was undetectable at heat shock temperatures and low at normal temperatures (75-79 degrees C), but induced by cold shock. Polyacrylamide gel electrophoresis indicated that in vitro alpha and beta subunits form homo-oligomeric rosettasomes, and mixtures of alpha, beta and gamma form hetero-oligomeric rosettasomes. Transmission electron microscopy revealed that beta homo-oligomeric rosettasomes and all hetero-oligomeric rosettasomes associate into filaments. In vivo rosettasomes were hetero-oligomeric with an average subunit ratio of 1alpha:1beta:0.1gamma in cultures grown at 75 degrees C, a ratio of 1alpha:3beta:1gamma in cultures grown at 60 degrees C and a ratio of 2alpha:3beta:0gamma after 86 degrees C heat shock. Using differential scanning calorimetry, we determined denaturation temperatures (Tm) for alpha, beta and gamma subunits of 95.7 degrees C, 96.7 degrees C and 80.5 degrees C, respectively, and observed that rosettasomes containing gamma were relatively less stable than those with alpha and/or beta only. We propose that, in vivo, the rosettasome structure is determined by the relative abundance of subunits and not by a fixed geometry. Furthermore, phylogenetic analyses indicate that archaeal chaperonin subunits underwent multiple duplication events within species (paralogy). The independent evolution of these paralogues raises the possibility that chaperonins have functionally diversified between species.
Distantly sampled soils carry few species in common (2008)

The bacterial phylogenetic structure of soils from four distinctly different sites in South and North America was analyzed. One hundred and thirty-nine thousand sequences of the V9 region of the small subunit of the bacterial ribosomal RNA gene generated for a previous study were used for this work. Whereas the previous work estimated levels of species richness, this study details the degree of bacterial community overlap between the four soils. Sequences from the four soils were classified and grouped into different phyla and then assigned to operational taxonomic units (OTUs) as defined by 97 or 100% sequence similarity. Pairwise Jaccard and theta similarity indices averaged over all phyla equalled 6 and 12% respectively at the 97% similarity level, and 15% for both at the 100% similarity level. At 100 and 97% sequence similarity, 1.5 and 4.1% of OTUs were found in all four soils respectively, and 87.9 and 74.4%, respectively were a unique particular soil. These analyses, based on the largest soil bacterial sequence retrieval to date, establish the high degree of community structure difference for randomly sampled dissimilar soils and support the idea that wide sampling is important for bioprospecting. The 10 most abundant cultured genera were determined in each soil. These 10 genera comprised a significant proportion of the reads obtained from each soil (31.3-37.4%). Chitinophaga was the most abundant or the second most abundant genus in all four soils with 7.5-13.8% of the total bacterial sequences in these soils. The striking result is that several culturable genera, whose roles in soil are virtually unknown, were found among these dominant sequences.
Femtomolar Transition State Analogue Inhibitors of 5′-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Escherichia coli (2005)

Escherichia coli 5'-methylthioadenosine/S-adenosyl-homocysteine nucleosidase (MTAN) hydrolyzes its substrates to form adenine and 5-methylthioribose (MTR) or S-ribosylhomocysteine (SRH). 5'-Methylthioadenosine (MTA) is a by-product of polyamine synthesis and SRH is a precursor to the biosynthesis of one or more quorum sensing autoinducer molecules. MTAN is therefore involved in quorum sensing, recycling MTA from the polyamine pathway via adenine phosphoribosyltransferase and recycling MTR to methionine. Hydrolysis of MTA by E. coli MTAN involves a highly dissociative transition state with ribooxacarbenium ion character. Iminoribitol mimics of MTA at the transition state of MTAN were synthesized and tested as inhibitors. 5'-Methylthio-Immucillin-A (MT-ImmA) is a slow-onset tight-binding inhibitor giving a dissociation constant (K(i)(*)) of 77 pm. Substitution of the methylthio group with a p-Cl-phenylthio group gives a more powerful inhibitor with a dissociation constant of 2 pm. DADMe-Immucillins are better inhibitors of E. coli MTAN, since they are more closely related to the highly dissociative nature of the transition state. MT-DADMe-Immucillin-A binds with a K(i)(*) value of 2 pm. Replacing the 5'-methyl group with other hydrophobic groups gave 17 transition state analogue inhibitors with dissociation constants from 10(-12) to 10(-14) m. The most powerful inhibitor was 5'-p-Cl-phenylthio-DADMe-Immucillin-A (pClPhT-DADMe-ImmA) with a K(i)(*) value of 47 fm (47 x 10(-15) m). These are among the most powerful non-covalent inhibitors reported for any enzyme, binding 9-91 million times tighter than the MTA and SAH substrates, respectively. The inhibitory potential of these transition state analogue inhibitors supports a transition state structure closely resembling a fully dissociated ribooxacarbenium ion. Powerful inhibitors of MTAN are candidates to disrupt key bacterial pathways including methylation, polyamine synthesis, methionine salvage, and quorum sensing. The accompanying article reports crystal structures of MTAN with these analogues.
Effect of linker variation on the stability, potency, and efficacy of carcinoma-reactive BR64-doxorubicin immunoconjugates. (1997)

The internalizing anti-Le(y) monoclonal antibody (MAb) BR64 was conjugated to the anticancer drug doxorubicin (DOX) using an acid-labile hydrazone bond to the DOX and either a disulfide or thioether bond to the MAb. The resulting disulfide (BR64-SS-DOX) and thioether (BR64-S-DOX) conjugates were evaluated for stability, potency, and antigen-specific activity in both in vitro and in vivo model systems. The BR64-SS-DOX conjugates demonstrated antigen-specific activity both in vitro and when evaluated against antigen-expressing, DOX-sensitive human carcinoma xenografts. However, the stability and potency of disulfide conjugates were poor, and in vivo activity superior to unconjugated DOX was seen only at doses approaching the maximum tolerated dose. Furthermore, BR64-SS-DOX conjugates were not active against antigen-expressing, DOX-insensitive colon tumor xenografts. In contrast, the BR64-S-DOX conjugates demonstrated good stability both in vitro and in vivo. The increased stability of the BR64-S-DOX conjugates resulted in the delivery of more biologically active DOX to tumors with a concomitant increase in potency and efficacy over that which could be achieved with either unconjugated DOX or BR64-SS-DOX conjugates. Delivery of DOX by BR64-SS-DOX conjugates resulted in complete regressions and cures of both DOX-sensitive lung xenografts and DOX-intensitive colon tumor xenografts. These results demonstrate the importance of linker stability when delivering drugs such as DOX to carcinomas via internalizing antibodies and are likely to have direct relevance to the clinical utility of MAb-directed delivery.
Correction: A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells (2013)

Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.
Coal Oxidation. Comparative Studies on Phenols1 (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCoal Oxidation. Comparative Studies on Phenols1G. R. Yohe, D. R. Hill, J. E. Dunbar, and F. M. ScheidtCite this: J. Am. Chem. Soc. 1953, 75, 11, 2688–2693Publication Date (Print):June 1, 1953Publication History Published online1 May 2002Published inissue 1 June 1953https://pubs.acs.org/doi/10.1021/ja01107a041https://doi.org/10.1021/ja01107a041research-articleACS PublicationsRequest reuse permissionsArticle Views160Altmetric-Citations26LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Inflammatory Response in the Hippocampus of PS1M146L/APP751SLMouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic (2008)

Although the microglial activation is concomitant to the Alzheimer's disease, its precise role (neuroprotection vs neurodegeneration) has not yet been resolved. Here, we show the existence of an age-dependent phenotypic change of microglial activation in the hippocampus of PS1xAPP model, from an alternative activation state with Abeta phagocytic capabilities (at 6 months) to a classic cytotoxic phenotype (expressing TNF-alpha and related factors) at 18 months of age. This switch was coincident with high levels of soluble Abeta oligomers and a significant pyramidal neurodegeneration. In vitro assays, using astromicroglial cultures, demonstrated that oligomeric Abeta42 and soluble extracts from 18-month-old PS1xAPP hippocampus produced a potent TNF-alpha induction whereas monomeric Abeta42 and soluble extract from 6- or 18-month-old control and 6-month-old PS1xAPP hippocampi produced no stimulation. This stimulatory effect was avoided by immunodepletion using 6E10 or A11. In conclusion, our results show evidence of a switch in the activated microglia phenotype from alternative, at the beginning of Abeta pathology, to a classical at advanced stage of the disease in this model. This change was induced, at least in part, by the age-dependent accumulation of extracellular soluble Abeta oligomers. Finally, these cytotoxic activated microglial cells could participate in the neuronal lost observed in AD.
Treatment of human malignant meningiomas by G207, a replication-competent multimutated herpes simplex virus 1. (1995)

We have demonstrated that replication-competent attenuated mutants of herpes simplex virus type 1 (HSV-1) have therapeutic potential for malignant gliomas. Moreover, a recently described multiple mutant HSV (termed G207) has properties which may allow human clinical trials. G207 is able to replicate within and kill cells from three human malignant meningiomas in cell culture. In nude mice harboring s.c. human malignant meningioma (F5), G207 can inhibit growth in a dose-dependent fashion. In nude mice harboring intracranial subdural human malignant meningioma (F5), one injection of G207 caused significantly decreased tumor growth and one apparent cure with neither neurological dysfunction nor pathological changes in the surrounding brain. These results suggest that G207 should be considered for therapeutic trials in the treatment of malignant meningioma refractory to currently available therapies.
Estimating the class prior and posterior from noisy positives and unlabeled data (2016)

We develop a classification algorithm for estimating posterior distributions from positive-unlabeled data, that is robust to noise in the positive labels and effective for high-dimensional data. In recent years, several algorithms have been proposed to learn from positive-unlabeled data; however, many of these contributions remain theoretical, performing poorly on real high-dimensional data that is typically contaminated with noise. We build on this previous work to develop two practical classification algorithms that explicitly model the noise in the positive labels and utilize univariate transforms built on discriminative classifiers. We prove that these univariate transforms preserve the class prior, enabling estimation in the univariate space and avoiding kernel density estimation for high-dimensional data. The theoretical development and both parametric and nonparametric algorithms proposed here constitutes an important step towards wide-spread use of robust classification algorithms for positive-unlabeled data.
Mechanisms for Oxidative Stress in Diabetic Cardiovascular Disease (2007)

Obesity, metabolic syndrome, and diabetes are increasingly prevalent in Western society, and they markedly increase the risk for atherosclerotic vascular disease, the major cause of death in diabetics. Although recent evidence suggests a causal role for oxidative stress in insulin resistance, diabetes, and atherosclerosis, there is considerable controversy regarding its nature, magnitude, and underlying mechanisms. Glucose promotes glycoxidation reactions in vitro, and products of glycoxidation and lipoxidation are elevated in plasma and tissue from humans suffering from diabetes, but the exact relationships between hyperglycemia and oxidative stress are poorly understood. This review focuses on molecular mechanisms of increased oxidative stress in diabetes, the relationship of oxidant production to hyperglycemia, and the potential interaction of reactive carbonyls and lipids in oxidant generation. Using highly sensitive and specific gas chromatography-mass spectrometry, molecular signatures of specific oxidation pathways were identified in tissues of diabetic humans and animals. These studies support the hypothesis that unique reactive intermediates generated in localized microenvironments of vulnerable tissues promote diabetic damage. Therapies interrupting these reactive pathways in vascular tissue might help prevent cardiovascular disease in this high-risk population.
Robust Self-Localization in Industrial Environments based on 3D Ceiling Structures (2006)

This paper introduces a new perceptual model for Monte Carlo localization (MCL). In our approach a 3D laser scanner is used to observe the ceiling. The MCL matches ceiling structures like beams, columns, air condition and lightning installation against a world model containing line and point features. Thus the localization is not effected by clutter or any kind of dynamic obstacles on the ground level. Different experiments show that our system can be used to localize robustly in factory buildings and halls. Experimental results include a 5 day run of an autonomous fork lift truck on a logistics fair in Hannover
Neutrophil Mediated Microvascular Injury in Acute, Experimental Compartment Syndrome (1997)

The purpose of this study was to determine the contribution of neutrophils and tissue xanthine oxidase to the skeletal muscle microvascular dysfunction in an ex vivo model of acute compartment syndrome. Adult dogs were rendered neutropenic or depleted of tissue xanthine oxidase before gracilis muscle isolation. Compared with continuously perfused, nonischemic muscles, acute, experimental compartment syndrome resulted in a dramatic increase in microvascular permeability, muscle neutrophil content, and muscle vascular resistance. Neutropenia prevented, whereas xanthine oxidase depletion had no effect on, the microvascular dysfunction and muscle neutrophil infiltration elicited by experimental compartment syndrome. These results suggest that neutrophils contribute to the microvascular dysfunction and blood flow distribution abnormalities elicited by acute, experimental compartment syndrome.
Protection and polymerization of functional monomers, 23. Synthesis of well‐defined poly(2‐hydroxyethyl methacrylate) by means of anionic living polymerization of protected monomers (1994)

Abstract Anionic polymerizations of 2‐[(trimethylsilyl)oxy]ethyl methacrylate ( 1 ), 2‐[( tert ‐butyldimethylsilyl)oxy]ethyl methacrylate ( 2 ), and 2‐[(methoxymethyl)oxy]ethyl methacrylate ( 3 ), the protected forms of 2‐hydroxyethyl methacrylate (HEMA), were carried out in THF at −78°C with 1,1‐diphenylhexyllithium or 1,1‐diphenyl‐3‐methylpentyllithium in the presence of LiCl. The resulting poly( 1–3 )s were found to possess predictable molecular weights and very narrow molecular weight distributions. The sequential polymerizations of tert ‐butyl methacrylate with the anionic propagating ends of poly( 1–3 ) gave block copolymers in quantitative efficiency. Thus, the anionic polymerizations of 1–3 proceeded without transfer and termination reactions to afford stable living polymers. Complete hydrolysis of the protective groups of poly( 1–3 )s produced linear poly(HEMA) quantitatively. Novel well‐defined di‐ and triblock copolymers containing hydrophobic [polystyrene, poly(4‐octylstyrene), polyisoprene] and hydrophilic segments [poly(HEMA)] were also prepared by sequential polymerization of the corresponding hydrophobic comonomers with 1 , followed by deprotection.
Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer (2009)

Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.
Full-duplex wireless communications using off-the-shelf radios: Feasibility and first results (2010)

We study full-duplex wireless communication systems where same band simultaneous bidirectional communication is achieved via cancellation of the self-interfering signal. Using off-the-shelf MIMO radios, we present experimental results that characterize the suppression performance of three self-interference cancellation mechanisms, which combine a different mix of analog and digital cancellation. Our experimental results show that while the amount of self-interference increases linearly with the transmitted power, the self-interference can be sufficiently cancelled to make full-duplex wireless communication feasible in many cases. Our experimental results further show that if the self-interference is cancelled in the analog domain before the interfering signal reaches the receiver front end, then the resulting full-duplex system can achieve rates higher than the rates achieved by a half-duplex system with identical analog resources.
A library of gene expression signatures to illuminate normal and pathological lymphoid biology (2006)

Genomics has provided a lever to pry open lymphoid cells and examine their regulatory biology. The large body of available gene expression data has also allowed us to define the of coordinately expressed genes, termed gene expression signatures, which characterize the states of cellular physiology that reflect cellular differentiation, activation of signaling pathways, and the action of transcription factors. Gene expression signatures that reflect the action of individual transcription factors can be defined by perturbing transcription factor function using RNA interference (RNAi), small-molecule inhibition, and dominant-negative approaches. We have used this methodology to define gene expression signatures of various transcription factors controlling B-cell differentiation and activation, including BCL-6, B lymphocyte-induced maturation protein-1 (Blimp-1), X-box binding protein-1 (XBP1), nuclear factor-kappaB (NF-kappaB), and c-myc. We have also curated a wide variety of gene expression signatures from the literature and assembled these into a signature database. Statistical methods can define whether any signature in this database is differentially expressed in independent biological samples, an approach we have used to gain mechanistic insights into the origin and clinical behavior of B-cell lymphomas. We also discuss the use of genomic-scale RNAi libraries to identify genes and pathways that may serve as therapeutic targets in B-cell malignancies.
Contamination-Free Continuous Flow Microfluidic Polymerase Chain Reaction for Quantitative and Clinical Applications (2005)

We present a method for performing polymerase chain reaction (PCR) using isolated droplets flowing in an immiscible fluorinated solvent system. Thanks to an optimized control of interfacial properties, we could achieve in this capillary-based system reproducible amplification factors, without any detectable contamination between neighboring droplets. The system is readily amenable to further miniaturization and automation and serves as the first step toward a clinically viable, high-throughput, quantitative continuous flow PCR apparatus.
Pirh2 and tumor (2012)

Pirh2 (p53-induced protein with a Ring-H2 domain),one of the ubiquitin-protein E3 ligases,can promote p53 degradation via ubiquitin-proteasome pathway,and repress the biological functions of p53.Researchers have found that the Pirh2 is overexpressed in many cancers,which suggests Pirh2 is probably correlated with tumorigenesis and cancer development,and it may become a promising cancer therapeutic target.

Key words: 
Neoplasms ;  Ubiquitin-protein ligases ;  Pirh2 ;