gebhart/patrepeval huggingface dataset:
Maspin Expression Is Transactivated by p63 and Is Critical for the Modulation of Lung Cancer Progression (2004)

Maspin inhibits metastasis of some cancer cells, and clinical studies have identified correlations between maspin loss and poor prognosis in several cancer types. Maspin was found to be significantly overexpressed in lung cancer samples as compared with matched normal lung tissues. However, the regulatory mechanism of maspin expression remains unclear. We show here that differential expression of maspin in carcinoma-derived lung cancer cells is regulated at the transcriptional level. We found that p63 is a critical factor for the transcription of maspin, which is lost in highly invasive cancer cells such as NCI-H157, NCI-322, and NCI-358. No correlation was found between maspin expression and the previously associated transcription factors, p53, Ets1, and Pdef. Instead, maspin expression was strictly dependent on the presence of p63 in lung cancer tissues (P < 0.001) and in the tested cell lines. Transient expression of p63 transactivated the maspin promoter with remarkable fold changes in cells expressing the TAp63, suggesting that TAp63 might be a novel stimulator of the maspin promoter in lung cancer. We have also demonstrated the binding of p63 protein to a previously identified p53-binding site on the maspin promoter by gel shift and chromatin immunoprecipitation assays. In tumor tissues, maspin expression was associated with lymph node involvement (P = 0.035) and tumor stage (P = 0.063) in all tested cases, except squamous carcinoma. In terms of function, ectopic expression of maspin inhibited cell invasion in squamous carcinoma as well as adenocarcinoma. Taken together, these results define maspin as a new molecular target of p63 that eventually inhibits the invasion of lung cancer.
Joining of Synthetic Ribotrinucleotides with Defined Sequences Catalyzed by T4 RNA Ligase (1977)

RNA ligase catalyzed the joining of pC-C-Ap with C-A-A in the synthesis of C-A-A-C-C-Ap, which has the sequence of the Escherichia coli tRNAfMet 3'-end. pC-C-A was also shown to be joined to C-A-A without any undesired self-polymerization. Joining of pC-C-A to various synthetic ribotriplets, such as C-C-A, A-A-A, C-C-C, U-U-U, U-A-G, C-C-G and U-U-C, was performed as well as joining to the partially substituted trimers with a photolabile o-nitrobenzyl group, C-Anbzl-A and C-C-Anbzl. The yields were C-A-A-C-C-A (69%), C-C-A-C-C-A (38%), A-A-A-C-C-A (66%), C-C-C-C-C-A (71%), U-U-U-C-C-A (50%), U-A-G-C-C-A (23%), C-C-G-C-C-A (43%) and U-U-C-C-C-A (46%). C-Anbzl-A was a slightly poorer acceptor than C-A-A and C-C-Anbzl did not serve as an acceptor. Recognition of acceptor molecules by RNA ligase is discussed in terms of affinity of oligonucleotides for the enzyme.
Stoichiometry of Complexes between Mannose-binding Protein and Its Associated Serine Proteases (2001)

Serum mannose-binding protein (MBP) initiates the lectin branch of the complement cascade by binding to sugars on the surfaces of microorganisms and activating two MBP-associated serine proteases (MASP-1 and MASP-2). Rat serum MBP consists of oligomers containing up to four copies of a subunit that is composed of three identical polypeptide chains. Biophysical analysis of intact and truncated MASPs indicates that each MASP is a homodimer that is stabilized through interactions involving an N-terminal CUB domain. The binding sites for MBP are formed from the three N-terminal MASP domains, in which two CUB modules interact with MBP. Each MASP dimer contains binding sites for two MBP subunits. Both sites must be occupied by subunits from a single MBP oligomer to form a stable complex. Thus, the smallest functional unit for complement activation consists of MBP dimers bound to MASP-1 or MASP-2 homodimers. Trimers and tetramers of MBP form complexes containing up to two MASPs. The results reveal how MASP-1 and MASP-2 can function independently to activate the complement cascade.
The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era. (2005)

Cystic fibrosis (CF) is the most common inherited disorder of childhood. The diagnosis of CF has traditionally been based on clinical features with confirmatory evidence by sweat electrolyte analysis. Since 1989 it has been possible to also use gene mutation analysis to aid the diagnosis. Cloning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has advanced our understanding of CF, in particular the molecular basis of an expanded CF phenotype. However, because there are over 1000 mutations and 200 polymorphisms, many without recognised effects on CFTR, the molecular diagnosis can be troublesome. This has necessitated measurement of CFTR function with renewed interest in the sweat test. This review provides an overview of the clinical features of CF, the diagnosis and complex genetics. We provide a detailed discussion of the structure and function of CFTR and the classification of CFTR mutations. Sweat electrolyte analysis is discussed, from the physiology of sweating to the rigours of a properly performed sweat test and its interpretation. With this information it is possible to understand the relevance of the sweat test in the genomic era.
Osmotic Pressure of Aqueous Polyethylene Glycols (1989)

Osmotic pressures (II) of aqueous solutions of polyethylene glycols (PEGs) of average relative molecular weight (M(r)) between 200 and 10,000 were measured using vapor pressure deficit osmometry. The relationships between molarity and II were described with high precision by second order polynomials for each of the PEGs studied. In contrast to previous reports, equivalent weights of different polymers in solution did not generate the same II; low M(r) PEGs generated a higher II than the higher M(r) PEGs. The effect of PEGs upon II represents an interaction between concentration and M(r).
A phase II trial of weekly paclitaxel and carboplatin for elderly patients with advanced non-small cell lung cancer (NSCLC) (2005)

7248 Background: Paclitaxel combined with carboplatin (PC) is a commonly used regimen in advanced NSCLC. Although some studies suggested that PC is also effective for elderly patients, weekly paclitaxel combined with carboplatin for those patients has not been reported. We conducted this phase II trial to evaluate the safety and the efficacy of weekly paclitaxel and carboplatin for elderly patients with advanced NSCLC. Methods: Patients with stage IIIB, IV or postoperative recurrent NSCLC, PS ≤ 1, ≥ 70 years old received weekly paclitaxel (70mg/m2/wk) on d1, 8, 15, and carboplatin (AUC 6) on d1. Treatment was repeated every 4 weeks. Results: From May 2002 to Aug 2004, 42 patients were enrolled: median age (range), 75 (70–81); male/female, 32/10; stage IIIB/IV/postoperative recurrence, 13/25/4. Two patients never received study drug and 40 patients were evaluable for the safety and the efficacy. ≥Grade 3 toxicities included neutropenia (70%); thrombocytopenia (15%); anemia (13%); infection (10%); fatigue and febrile neutropenia (5%). No ≥grade 3 neurotoxicity was observed. One treatment related death (infection) was observed. Overall response rate was 45%; CR=0, PR=18, SD=11, PD=7, NE=4. To date, median survival time was 13 months and the 1-year survival rate was 58%. Conclusion: These results suggest that weekly paclitaxel and carboplatin is comparable to standard PC in efficacy and seems to be safer than standard PC. We are now conducting a randomized trial that compare weekly paclitaxel and carboplatin to standard PC. No significant financial relationships to disclose.
Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice (2008)

Vectors derived from adeno-associated virus (AAV) are promising for human gene therapy, including treatment for retinal blindness. One major limitation of AAVs as vectors is that AAV cargo capacity has been considered to be restricted to 4.7 kb. Here we demonstrate that vectors with an AAV5 capsid (i.e., rAAV2/5) incorporated up to 8.9 kb of genome more efficiently than 6 other serotypes tested, independent of the efficiency of the rAAV2/5 production process. Efficient packaging of the large murine Abca4 and human MYO7A and CEP290 genes, which are mutated in common blinding diseases, was obtained, suggesting that this packaging efficiency is independent of the specific sequence packaged. Expression of proteins of the appropriate size and function was observed following transduction with rAAV2/5 carrying large genes. Intraocular administration of rAAV2/5 encoding ABCA4 resulted in protein localization to rod outer segments and significant and stable morphological and functional improvement of the retina in Abca4(-/-) mice. This use of rAAV2/5 may be a promising therapeutic strategy for recessive Stargardt disease, the most common form of inherited macular degeneration. The possibility of packaging large genes in AAV greatly expands the therapeutic potential of this vector system.
Macrophages and Brucella. (1994)

The studies reviewed here indicate that during the course of infection with B. abortus protective immune responses occur and that macrophages are activated for antimicrobial activity in both susceptible and resistant animals. Yet in susceptible animals chronic infections with B. abortus become established. There is circumstantial evidence from experiments in vitro that the outcome of infection is related to macrophage/Brucella interactions. This includes the following: 1) the virulence of strains of B. abortus is proportional to their ability to inhibit host phagocyte functions and to survive in murine, bovine, and guinea pig macrophages; and 2) the ability of guinea pig and bovine macrophages to inhibit intracellular growth of brucellae is directly proportional to the innate resistance of the host from which the macrophages were derived. In the murine model, the relative resistance of C57Bl/10 mice to infection with virulent B. abortus strain 2308 correlated with more efficient clearance during the first week following infection, compared with the susceptible BALB/c strain. It is not known whether this was due to innate differences in the recruitment or bactericidal activities of macrophage populations in the two mouse strains, as demonstrated with L. monocytogenes, or to other nonimmune factors such as natural killer cells secreting IFN-gamma and lysing infected macrophages following direct interaction with the brucellae, as shown with other intracellular bacteria. It is also of interest that clearance of strain 2308 following the plateau phase was slower in BALB/c than in C57Bl/10 mice. Since at this time protective T cells are known to be present in the spleens of BALB/c mice, this difference may have been due either to more efficient clearance of brucellae by C57Bl/10 macrophages following activation with T cell cytokines, or to the inability of immune T cells to interact with Brucella-infected macrophages in the susceptible BALB/c strain. CD8 T cells have been shown to have an important role in clearance of brucellae following the peak of infection and may act by lysing chronically infected macrophages. Although protective T cells have been demonstrated in susceptible strains of mice, chronically infected macrophages in these animals may fail to act as targets or may down-regulate T cell functions. As a result, infected macrophages could persist in the presence of Brucella-specific T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparative study of the topical effectiveness of the andiroba oil (Carapa guianensis) and DEET 50% as repellent for Aedes sp (2004)

DEET (N,N-diethyl-3-methylbenzamide) is nowadays the most effective mosquito repellent available, however, its use can present some topical and systemic side effects. Some botanical compositions, as Andiroba (Carapa guianensis), have been proved repellent properties at low cost and toxicity. An experimental study was driven involving four volunteers submitting their forearms covered with Andiroba oil at 100%, DEET 50%, refined soy oil, Andiroba oil 15% and in the absence of products, directly to healthy females of Aedes sp. The times of first and third bites were checked. The results showed that the median of the first bite without any product was 17.5s and the third bite, 40.0s. In the soy oil, the bites happened in 60.0s and 101.5s, in the presence of Andiroba oil 100%, in 56.0s and 142.5s and in Andiroba oil 15%, in 63.0s and 97.5s. The volunteers using DEET 50% had not received bites after 3600s in most of the experiments (p < 0.001 Wilcoxon). Pure Andiroba oil compared to the soy oil, forearm without product and Andiroba oil 15%, showed discreet superiority (p < 0.001 Wilcoxon). Our conclusion is that this study demonstrated that the pure Andiroba oil presents discreet repellent effect against bite of Aedes sp., being significantly inferior to DEET 50%.
G Protein Activation without Subunit Dissociation Depends on a Gαi-specific Region (2005)

G proteins transmit a variety of extracellular signals into intracellular responses. The Galpha and Gbetagamma subunits are both known to regulate effectors. Interestingly, the Galpha subunit also determines subtype specificity of Gbetagamma effector interactions. However, in light of the common paradigm that Galpha and Gbetagamma subunits dissociate during activation, a plausible mechanism of how this subtype specificity is generated was lacking. Using a fluorescence resonance energy transfer (FRET)-based assay developed to directly measure mammalian G protein activation in intact cells, we demonstrate that fluorescent Galpha(i1,2,3), Galpha(z), and Gbeta(1)gamma(2) subunits do not dissociate during activation but rather undergo subunit rearrangement as indicated by an activation-induced increase in FRET. In contrast, fluorescent Galpha(o) subunits exhibited an activation-induced decrease in FRET, reflecting subunit dissociation or, alternatively, a distinct subunit rearrangement. The alpha(B/C)-region within the alpha-helical domain, which is much more conserved within Galpha(i1,2,3) and Galpha(z) as compared with that in Galpha(o), was found to be required for exhibition of an activation-induced increase in FRET between fluorescent Galpha and Gbetagamma subunits. However, the alpha(B/C)-region of Galpha(il) alone was not sufficient to transfer the activation pattern of Galpha(i) to the Galpha(o) subunit. Either residues in the first 91 amino acids or in the C-terminal remainder (amino acids 93-354) of Galpha(il) together with the alpha(B/C)-helical region of Galpha(i1) were needed to transform the Galpha(o)-activation pattern into a Galpha(i1)-type of activation. The discovery of subtype-selective mechanisms of G protein activation illustrates that G protein subfamilies have specific mechanisms of activation that may provide a previously unknown basis for G protein signaling specificity.
Overview of the ARPA human language technology workshop (1993)

For five years, 1988-1992, the Defense Advanced Projects Agency sponsored a series of meetings called the DARPA Speech and Natural Language Workshops. These workshops provided a forum where researchers in speech and natural language, particularly as relating to the DARPA programs in spoken and written language understanding, could exchange information about recent research and technical progress.
Achieving Human Parity in Conversational Speech Recognition (2016)

Conversational speech recognition has served as a flagship speech recognition task since the release of the Switchboard corpus in the 1990s. In this paper, we measure the human error rate on the widely used NIST 2000 test set, and find that our latest automated system has reached human parity. The error rate of professional transcribers is 5.9% for the Switchboard portion of the data, in which newly acquainted pairs of people discuss an assigned topic, and 11.3% for the CallHome portion where friends and family members have open-ended conversations. In both cases, our automated system establishes a new state of the art, and edges past the human benchmark, achieving error rates of 5.8% and 11.0%, respectively. The key to our system's performance is the use of various convolutional and LSTM acoustic model architectures, combined with a novel spatial smoothing method and lattice-free MMI acoustic training, multiple recurrent neural network language modeling approaches, and a systematic use of system combination.
CD44 and EpCAM: Cancer-Initiating Cell Markers (2008)

Embryonic stem cells are immortal, can self renew, and differentiate into all cells of the body. The adult organism maintains adult stem cells in regenerative organs that can differentiate into all cells of the respective organ. Virchow's hypothesis that cancer may arise from embryonic-like cells has received strong support, as it was demonstrated that tumors contain few cells, known as cancer stem or cancer-initiating cells (CIC), that account for primary and metastatic tumor growth. CIC are mostly defined by expression of CIC-markers that are associated and correlated with the potential of CIC to grow in xenogeneic mice. CIC marker profiles have been elaborated for many tumors, with several markers as CD24, CD44, CD133, CD166, EpCAM, and some integrins, being expressed by tumors of different histological type. Their function in promoting CIC maintenance and activity is largely unknown. The fate of stem cells, determined by their position, is minutely regulated by few adjacent cells creating a niche. CIC also require a niche, mostly for settlement and growth in distant organs. This so called pre-metastatic niche is initiated by the primary tumor before metastasizing cell arrival. How do CIC prepare the pre-metastatic niche? Cancer cells secrete a matrix that serves a cross-talk with surrounding tissues. Additionally, cancer cells can abundantly deliver exosomes, which function as long-distance intercellular communicators. Studies on a rat pancreatic adenocarcinoma support our hypothesis that tumor-derived matrix and exosomes are the main actors in forming the pre-metastatic niche with CIC markers being engaged in matrix preparation and/or exosome delivery.
Structured prediction models for RNN based sequence labeling in clinical text (2016)

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.
Data parallel volume rendering as line drawing (1992)

In this paper we describe an algorithm for volume raytracing in a data parallel framework.
The Primary Structure of the Coat Protein of the Broad‐Host‐Range RNA Bacteriophage PRR1 (1979)

The complete amino acid sequence of the coat protein of RNA bacteriophage PRR1 is presented. After thermolysin digestion, 26 peptides were isolated, covering the complete coat protein chain. Their alignment was established in part using automated Edman degradation on the intact protein, in part with overlapping peptides obtained by enzymic hydrolysis with trypsin, pepsin, subtilisin and Staphylococcus aureus protease, and by chemical cleavage with cyanogen bromide and N-bromosuccinimide. To obtain the final overlaps, a highly hydrophobic, insoluble tryptic peptide was sequenced for seven steps by the currently used manual dansyl-Edman degradation procedure, which was slightly modified for application on insoluble peptides. PRR1 coat protein contains 131 amino acids, corresponding to a molecular weight of 14534. It is highly hydrophobic, and the residues with ionizable side chains are distributed unevenly: acidic residues are absent in the middle third of the sequence, whereas a clustering of basic residues occurs between positions 44 and 62. PRR1 coat protein was compared with the coat proteins of RNA coliphages MS2 and Q beta, and the minimum mutation distance was calculated for both comparisons. It is highly probable that PRR1. Q beta and MS2 share a common ancestor. The basic region present in the three coat proteins is recognized as an essential structural feature of RNA phage coat proteins.
Hydrogen Sulfide (2010)

Hydrogen sulfide is a relatively common, frequently lethal, and unique occupational hazard for which research since 1990 has uncovered many anomalies and subtleties and a previously unsuspected physiological role for the endogenous agent. The result has been uncertainty and misunderstanding, particularly for persons new to the literature. This review addresses evidence that settles past controversies, guides practical issues in evaluating human toxicity, addresses unresolved issues involving chronic exposure, and points the way to a deeper understanding of the agent and its effects.
Studies on bone formation by cartilage reconstructed by isolated epiphyseal chondrocytes, transplanted syngeneically or across known histocompatibility barriers in mice. (1983)

Calcified cartilage transplants induce bone formation. This process may be inhibited if the recipient is immunized by the transplant. To study the relation between the degree of antigen incompatibility between the donor and recipient and bone formation in more detail, chondrocytes isolated from cartilaginous epiphyses of five-day-old mice were transplanted within a fully compatible syngeneic system and across weak (H-Y, non-H-2) and strong (H-2) histocompatibility barriers. Reconstruction of cartilage occurred in all cases. In these transplants, which did not evoke immunologic reaction (fully compatible system, transplants across H-Y barrier in nonrejector strain), reconstructed cartilage hypertrophied, calcified, yielded to resorption by mesenchyme, and finally, was replaced by bone. When (independently of the degree of antigenic difference) cartilage was surrounded by mononuclear infiltration, bone formation did not occur or was delayed. The presence of infiltrations around transplants led to the degeneration of chondrocytes as well as of matrix in peripheral regions of cartilage. Immunologic infiltration may prevent endochondral osteogenesis by inhibiting cartilage invasion by vascularized mesenchyme, and/or interfering with matrix mineralization. The function of the chondrocyte is not yet defined, but in endochondral ossification, it plays more than a passive role.