gebhart/patrepeval huggingface dataset:
Sumoylation of Peroxisome Proliferator-Activated Receptor γ by Apoptotic Cells Prevents Lipopolysaccharide-Induced NCoR Removal from κB Binding Sites Mediating Transrepression of Proinflammatory Cytokines (2008)

Efficient clearance of apoptotic cells (AC) by professional phagocytes is crucial for tissue homeostasis and resolution of inflammation. Macrophages respond to AC with an increase in antiinflammatory cytokine production but a diminished release of proinflammatory mediators. Mechanisms to explain attenuated proinflammatory cytokine formation remain elusive. We provide evidence that peroxisome proliferator-activated receptor gamma (PPARgamma) coordinates antiinflammatory responses following its activation by AC. Exposing murine RAW264.7 macrophages to AC before LPS stimulation reduced NF-kappaB transactivation and lowered target gene expression of, that is, TNF-alpha and IL-6 compared with controls. In macrophages overexpressing a dominant negative mutant of PPARgamma, NF-kappaB transactivation in response to LPS was restored, while macrophages from myeloid lineage-specific conditional PPARgamma knockout mice proved that PPARgamma transmitted an antiinflammatory response, which was delivered by AC. Expressing a PPARgamma-Delta aa32-250 deletion mutant, we observed no inhibition of NF-kappaB. Analyzing the PPARgamma domain structures within aa 32-250, we anticipated PPARgamma sumoylation in mediating the antiinflammatory effect in response to AC. Interfering with sumoylation of PPARgamma by mutating the predicted sumoylation site (K77R), or knockdown of the small ubiquitin-like modifier (SUMO) E3 ligase PIAS1 (protein inhibitor of activated STAT1), eliminated the ability of AC to suppress NF-kappaB. Chromatin immunoprecipitation analysis demonstrated that AC prevented the LPS-induced removal of nuclear receptor corepressor (NCoR) from the kappaB site within the TNF-alpha promoter. We conclude that AC induce PPARgamma sumoylation to attenuate the removal of NCoR, thereby blocking transactivation of NF-kappaB. This contributes to an antiinflammatory phenotype shift in macrophages responding to AC by lowering proinflammatory cytokine production.
Sentiment analysis of blogs by combining lexical knowledge with text classification (2009)

The explosion of user-generated content on the Web has led to new opportunities and significant challenges for companies, that are increasingly concerned about monitoring the discussion around their products. Tracking such discussion on weblogs, provides useful insight on how to improve products or market them more effectively. An important component of such analysis is to characterize the sentiment expressed in blogs about specific brands and products. Sentiment Analysis focuses on this task of automatically identifying whether a piece of text expresses a positive or negative opinion about the subject matter. Most previous work in this area uses prior lexical knowledge in terms of the sentiment-polarity of words. In contrast, some recent approaches treat the task as a text classification problem, where they learn to classify sentiment based only on labeled training data. In this paper, we present a unified framework in which one can use background lexical information in terms of word-class associations, and refine this information for specific domains using any available training examples. Empirical results on diverse domains show that our approach performs better than using background knowledge or training data in isolation, as well as alternative approaches to using lexical knowledge with text classification.
AAA ATPase p97/Valosin-containing Protein Interacts with gp78, a Ubiquitin Ligase for Endoplasmic Reticulum-associated Degradation (2004)

Endoplasmic reticulum-associated degradation (ERAD) is a protein quality control mechanism that eliminates unwanted proteins from the endoplasmic reticulum (ER) through a ubiquitin-dependent proteasomal degradation pathway. gp78 is a previously described ER membrane-anchored ubiquitin ligase (E3) involved in ubiquitination of ER proteins. AAA ATPase (ATPase associated with various cellular activities) p97/valosin-containing protein (VCP) subsequently dislodges the ubiquitinated proteins from the ER and chaperones them to the cytosol, where they undergo proteasomal degradation. We now report that gp78 physically interacts with p97/VCP and enhances p97/VCP-polyubiquitin association. The enhanced association correlates with decreases in ER stress-induced accumulation of polyubiquitinated proteins. This effect is abolished when the p97/VCP-interacting domain of gp78 is removed. Further, using ERAD substrate CD3delta, gp78 consistently enhances p97/VCP-CD3delta binding and facilitates CD3delta degradation. Moreover, inhibition of endogenous gp78 expression by RNA interference markedly increases the levels of total polyubiquitinated proteins, including CD3delta, and abrogates VCP-CD3delta interactions. The gp78 mutant with deletion of its p97/VCP-interacting domain fails to increase CD3delta degradation and leads to accumulation of polyubiquitinated CD3delta, suggesting a failure in delivering ubiquitinated CD3delta for degradation. These data suggest that gp78-p97/VCP interaction may represent one way of coupling ubiquitination with retrotranslocation and degradation of ERAD substrates.
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs (2002)

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
Parity check codes for partial response channels (2003)

The use of turbo coding and decoding techniques in digital magnetic recording is now being given serious consideration. Major technical concerns are implementation complexity and decoding delay. In this paper, we present and analyze the performance of a simple, serial concatenation scheme comprising an outer parity check code, interleaver, and a precoded partial response channel. We apply an iterative decoding procedure incorporating separate a posteriori probability (APP) detectors for the code and precoded channel. Simulation results for a dicode channel show a bit-error-rate (BER) of 10/sup -5/ at rate-normalized signal-to-noise ratio SNR=6.7 dB for a rate 8/9 code, representing a gain of about 3.5 dB over the uncoded channel. We also present simulation results for higher-rate codes and other partial response channels, confirming the performance benefits of the new scheme.
American Journal of Reproductive Immunology (2010)

Graphical Abstract This study reveals the association between thyroid autoimmunity and TSH level, the prevalence of RM. And LT4 supplementation may effectively increase live birth rate.
The Java class libraries (1998)

PACKAGE OVERVIEWS. java.io. java.lang. java.lang.ref. java.lang.reflect. java.math. java.net. java.text. java.util. java.util.jar. java.util.zip. ALPHABETICAL REFERENCE OF CLASSES. AbstractCollection. AbstractList. AbstractMap. AbstractSequentialList. AbstractSet. AccessibleObject. Adler32. Annotation. Array. ArrayList. Arrays. AttributedCharacterIterator. AttributedString. Attributes. Atrributes.Name. Authenticator. BigDecimal. BigInteger. BitSet. BreakIterator. BufferedInputStream. Byte. ByteArrayInputStream. ByteArrayOutputStream. Calendar. Character. ChoiceFormat. Class. ClassLoader. ClassNotFoundException. Cloneable. Collection. Collections. Comparable. Comparator. ConcurrentModificationException. DatagramPacket. DatagramSocket. DatagramSocketImpl. Date. DecimalFormatSymbols. Double. ExceptionInInitializerError. FieldPosition. File. FileFilter. FilePermission. Float. GregorianCalendar. HashMap. HashSet. Hashtable. HttpURLConnection. InflaterInputStream. InheritableThreadLocal. Integer. InvocationTargetException. Iterator. JarEntry. JarFile. JarInputStream. JarOutputStream. JarURLConnection. LinkedList. List. ListIterator. Locale. Long. Manifest. Map. Math. Modifier. MulticastSocket. NetPermission. ObjectInputStream. ObjectInputStream.getField. ObjectOutputStream. ObjectOutputStream.putField. ObjectStreamClass. ObjectStreamConstants. ObjectStreamField. Package. ParsePosition. PasswordAuthentication. PhantomRef. PipedReader. PipedWriter. PrintStream. PrintWriter. Properties. PropertyPermission. PushbackInputStream. PushbackReader. Random. RandomAccessFile. Reference. ReferenceQueue. ResourceBundle. RuleBasedCollator. RuntimePermission. SecurityManager. Serializable. SerializablePermission. Set. Short. SimpleDateFormat. SimpleTimeZone. Socket. SocketOptions. SocketPermission. SoftReference. SortedMap. SortedSet. String. StringBuffer. StringCharacterIterator. System. Thread. ThreadLocal. ThreadGroup. TimeZone. TreeMap. TreeSet. UnsupportedOperationException. URL. URLClassLoader. URLConnection. URLDecoder. Vector. WeakHashMap. WeakReference. ZipEntry. ZipFile. ZipInputStream. 0201485524T04062001
Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation. (1996)

To further understand the biology of rhinovirus (RV), we determined whether IL-6 was produced during RV infections and characterized the mechanism by which RV stimulates lung cell IL-6 production. In contrast to normals and minimally symptomatic volunteers, IL-6 was detected in the nasal washings from patients who developed colds after RV challenge. RV14 and RV1A, major and minor receptor group RVs, respectively, were potent stimulators of IL-6 protein production in vitro. These effects were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promoter-driven luciferase activity. This stimulation was modestly decreased by mutation of the nuclear factor (NF)-IL-6 site and abrogated by mutation of the NF-kappa B site in this promoter. An NF-kappa B-DNA binding activity, mediated by p65, p50, and p52 NF-kappa B moieties, was rapidly induced in RV-infected cells. Activator protein 1-DNA binding was not similarly altered. These studies demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation IL-6 production is mediated by an NF-kappa B-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, and NF-kappa B activation is likely to be an important event in RV-induced pathologies.
Reduction of alkynes into 1,2-dideuterioalkenes with hexamethyldisilane and deuterium oxide in the presence of a palladium catalyst (2005)

A combination of hexamethyldisilane and deuterium oxide was found to work as a deuterium transfer reagent for alkynes in the presence of a catalytic amount of a palladium complex to give (E)-1,2-dideuterioalkenes selectively through the corresponding (Z)-isomer.
The decision systems group: creating a framework for decision making. (1999)

The Decision Systems Group is pursuing a vision in which every available medical resource can be brought together at the point of need. The DSG focuses on the components and tools in specific areas as well as on the models, approaches, and infrastructure that make this type of integration possible. Its academic mission is to train individuals with dual expertise: those who understand and appreciate the issues involved in developing and validating a method or technique, plus the issues of deployment, operation, and interaction in practical environments. Ultimately, the application of this vision can only serve to enhance the current level of healthcare.
Experiments on the synthesis of tetracycline. Part 16. Improved photocyclic preparation of 12-keto-derivatives and their deprotection using benzeneseleninic anhydride (1981)

Improved methods for the photocyclisation of 4-[2-(1,3-dithiolan-2-yl)benzyl]-2-phenylnaphtho[1,8-bc]furan-5-one (6; X = Y = S) and 4-[2-(1,3-dithiolan-2-yl)-3,5-dihydroxy-4-methoxycarbonylbenzyl]-2-phenylnaphtho[1,8-bc]furan-5-one (1; X = Y = S) to their tetracyclic analogues are described. Deprotection of the C-12 thioacetal unit in the cyclised products was achieved using benzeneseleninic anhydride. Introduction of a 6α-methyl substituent and an amide grouping into C-2 of certain tetracyclic substrates provides compounds which have potential use for tetracycline synthesis.
Catalytic Asymmetric Synthesis ofSyn-Aldol Products from Intermolecular C−H Insertions between Allyl Silyl Ethers and Methyl Aryldiazoacetates (1999)

Rh2(R-DOSP)4-catalyzed decomposition of methyl aryldiazoacetate in the presence of allyl silyl ethers results in a regioselective C−H insertion. The resulting β-siloxy esters are formed with high enantioselectivity (74−92% ee) and diastereoselectivity (96−98% de) when trans-disubstituted allyl silyl ethers are used as substrates.
The turnover of medium‐chain‐length polyhydroxyalkanoates in Pseudomonas putida KT2442 and the fundamental role of PhaZ depolymerase for the metabolic balance (2009)

Polyhydroxyalkanoates (PHAs) are biodegradable polymers produced by a wide range of bacteria, including Pseudomonads. These polymers are accumulated in the cytoplasm as carbon and energy storage materials when culture conditions are unbalanced and hence, they have been classically considered to act as sinks for carbon and reducing equivalents when nutrients are limited. Bacteria facing carbon excess and nutrient limitation store the extra carbon as PHAs through the PHA polymerase (PhaC). Thereafter, under starvation conditions, PHA depolymerase (PhaZ) degrades PHA and releases R-hydroxyalkanoic acids, which can be used as carbon and energy sources. To study the influence of a deficient PHA metabolism in the growth of Pseudomonas putida KT2442 we have constructed two mutant strains defective in PHA polymerase (phaC1)- and PHA depolymerase (phaZ)-coding genes respectively. By using these mutants we have demonstrated that PHAs play a fundamental role in balancing the stored carbon/biomass/number of cells as function of carbon availability, suggesting that PHA metabolism allows P. putida to adapt the carbon flux of hydroxyacyl-CoAs to cellular demand. Furthermore, we have established that the coordination of PHA synthesis and mobilization pathways configures a functional PHA turnover cycle in P. putida KT2442. Finally, a new strain able to secrete enantiomerically pure R-hydroxyalkanoic acids to the culture medium during cell growth has been engineering by redirecting the PHA cycle to biopolymer hydrolysis.
Size‐exclusion reaction chromatography (SERC): A new technique for protein PEGylation (2003)

A new, widely applicable process that combines reaction and separation in a single unit operation is described. The process, size-exclusion reaction chromatography (SERC), simultaneously allows control of the extent of reactions in which molecular size is altered and the separation of products and reactants. In SERC, a moving reaction zone is formed by injection of reactants onto a size-exclusion chromatography column. Reactants and products are partitioned differently within the mobile phase, resulting in different linear flow rates through the column. The products are therefore removed selectively from the reaction zone, minimizing their residence time in the reaction zone and allowing their separation in the downstream section of the column. For reactions such as protein PEGylation, in which successive addition of PEG groups to the protein results in significant molecular size increases, SERC potentially offers a method by which a dominant final PEGylated protein size can be produced at high yield. The SERC PEGylation of two model proteins, alpha-lactalbumin and beta-lactoglobulin, is demonstrated and results show that simultaneous reaction and separation was obtained.
Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster ovary cells (1997)

Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to and are efficiently internalized by cultured epithelial cells such as the Chang conjunctiva cell line. Both adherence and uptake require interactions between OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese hamster ovary (CHO) cells also support adherence of gonococci through interactions of OpaA with cell surface heparan sulfate proteoglycans. However, despite this similarity in the requirements for adherence, CHO cells are not capable of internalizing gonococci. In this report, we characterized this apparent deficiency and identified a factor in fetal calf serum (FCS) which is capable of mediating uptake of gonococci by CHO cells. In the absence of FCS, OpaA+ gonococci adhered to but were not internalized by CHO cells, whereas in the presence of up to 15% FCS, the bacteria were efficiently internalized by the cells. Preincubation of bacteria, but not cells, with FCS also stimulated internalization, suggesting that a factor present in FCS was binding to the surface of gonococci and subsequently stimulating entry. Using a combination of chromatographic purification procedures, we identified the adhesive glycoprotein vitronectin as the serum factor which mediates the internalization of gonococci by CHO cells. Vitronectin-depleted serum did not support gonococcal entry, and this deficiency was restored by the addition of purified vitronectin. Further experiments using a set of gonococcal recombinants, each expressing a single member of the family of Opa outer membrane proteins, demonstrated that vitronectin bound to the surface of OpaA-producing gonococci only and that the vitronectin-mediated uptake by the CHO cells was limited to this bacterial phenotype. To our knowledge, our data are the first example that vitronectin can serve as a molecule that drives bacterial entry into epithelial cells.
Chemical Diversity of Locked Nucleic Acid-Modified Antisense Oligonucleotides Allows Optimization of Pharmaceutical Properties (2019)

The identification of molecules that can modulate RNA or protein function and the subsequent chemical and structural optimization to refine such molecules into drugs is a key activity in drug discovery. Here, we explored the extent to which chemical and structural differences in antisense oligonucleotides, designed as gapmers and capable of recruiting RNase H for target RNA cleavage, can affect their functional properties. To facilitate structure-activity learning, we analyzed two sets of iso-sequential locked nucleic acid (LNA)-modified gapmers, where we systematically varied the number and positions of LNA modifications in the flanks. In total, we evaluated 768 different and architecturally diverse gapmers in HeLa cells for target knockdown activity and cytotoxic potential and found widespread differences in both of these properties. Binding affinity between gapmer and RNA target, as well as the presence of certain short sequence motifs in the gap region, can explain these differences, and we propose statistical and machine-learning models that can be used to predict region-specific, optimal LNA-modification architectures. Once accessible regions in the target of interest have been identified, our results show how to refine and optimize LNA gapmers with improved pharmacological profiles targeting such regions.
CCL18/PARC stimulates hematopoiesis in long-term bone marrow cultures indirectly through its effect on monocytes (2006)

Chemokines play a role in regulating hematopoietic stem cell function, including migration, proliferation, and retention. We investigated the involvement of CCL18 in the regulation of bone marrow hematopoiesis. Treatment of human long-term bone marrow cultures (LTBMCs) with CCL18 resulted in significant stimulation of hematopoiesis, as measured by the total number of hematopoietic cells and their committed progenitors produced in culture. Monocytes/macrophages, whose survival was almost doubled in the presence of CCL18 compared with controls, were the primary cells mediating this effect. Conditioned media from CCL18-treated mature monocytes fostered colony-promoting activity that increased the number of colonies formed by hematopoietic progenitor cells. Gene expression profiling of CCL18-stimulated monocytes demonstrated more than 200 differentially expressed genes, including those regulating apoptosis (caspase-8) and proliferation (IL-6, IL-15, stem cell factor [SCF]). Up-regulation of these cytokines was confirmed on the protein expression level. The contribution of SCF and IL-6 in CCL18-mediated stimulatory activity for hematopoiesis was confirmed by SCF- and IL-6-blocking antibodies that significantly inhibited the colony-promoting activity of CCL18-stimulated conditioned medium. In addition to the effect on monocytes, CCL18 facilitated the formation of the adherent layer in LTBMCs and increased the proliferation of stromal fibroblast-like cells.
CBL Exon 8/9 Mutants Activate the FLT3 Pathway and Cluster in Core Binding Factor/11q Deletion Acute Myeloid Leukemia/Myelodysplastic Syndrome Subtypes (2009)

CBL exon8/9 mutants occur in genetically defined AML/MDS subtypes and transform hematopoietic cells by constitutively activating the FLT3 pathway. This phenotype resembles the one of mutated RTKs and suggests that CBL mutant AML patients might benefit from treatment with FLT3 PTK inhibitors.