gebhart/patrepeval huggingface dataset:
Targeted inhibition of tumor‐cell growth by recombinant heregulin‐toxin fusion proteins (1995)

Fusion of functional domains of proteins by in vitro recombination of gene fragments can be used to generate novel anti-tumor agents. The combination of tumor-cell-recognition functions and toxic functions results in cytotoxic molecules with a high specificity for tumor cells. Human adenocarcinomas are frequently characterized by over-expression of members of the epidermal-growth-factor (EGF) receptor family (ErbB-1, 2, 3 and 4), when compared with normal cells. These tumors are particularly suited to treatment with recombinant toxins. The human heregulins (HRG) and their rat counterparts (neu differentiation factor, NDF) have been identified as ligands for these receptors. Two chimeric heregulin-toxin fusions consisting of the EGF-like receptor recognition domain of the heregulin isoforms HRG alpha and HRG beta I, and the domains II, Ib and III of the Pseudomonas exotoxin A (ETA) were constructed. HRG beta I-ETA is highly cytotoxic for the mammary carcinoma cell lines SK-BR-3 and MDA-MB-453. HRG alpha-ETA was less active than HRG beta I-ETA. The killing activity of the recombinant toxins correlated with the expression levels of ErbB-3 and/or ErbB-4 in the cell lines studied. High expression of ErbB-2 is not sufficient to confer sensitivity towards the HRG-ETA. Treatment of mice with 0.4 mg/kg/day of HRG beta I-ETA caused growth retardation of transplanted human breast tumor cells. Higher levels of HRG beta I-ETA administration resulted in acute hemorrhagic necrosis of the liver.
Amino acid substitutions in the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase that influence catalytic activity of the holoenzyme (1992)

Four unique amino acid substitutions were introduced by site-directed mutagenesis into the third conserved region of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) from Anacystis nidulans (Synechococcus sp., PCC6301), resulting in the formation of four mutant enzymes, I87V, R88K, G91V, and F92L. Wild-type and mutant proteins were purified after synthesis in Escherichia coli. These single amino acid substitutions do not appear to perturb intersubunit interactions or induce any gross conformational changes; purified mutant proteins are stable, for the most part like the wild-type holoenzyme, and exhibit nearly identical CD spectra. Three of the four mutants, however, are severely deficient in carboxylase activity, with kcat less than or equal to 35% of the wild-type enzyme. While the substrate specificity factors were the same for the mutant and wild-type enzymes, significant alterations in some kinetic parameters were observed, particularly in the Michaelis constants for CO2, O2, and RuBP. All four mutant proteins exhibited lower KCO2 values, ranging from 37 to 88% of the wild-type enzyme. Two of the mutants, in addition, exhibited significantly lower KRuBP values, and one mutant showed a substantial decrease in KO2. The effects of the single-site mutations in rbcS of this study strengthen the hypothesis that small subunits may not contribute directly to substrate specificity; however, individual residues of the small subunit substantially influence catalysis by large subunits.
Involvement of Frizzled‐10 in Wnt‐7a signaling during chick limb development (2000)

The dorsal ectoderm of the limb bud is known to regulate anterior-posterior patterning as well as dorsal-ventral patterning during vertebrate limb morphogenesis. Wnt-7a, expressed in the dorsal ectoderm, encodes a key molecule implicated in these events. In the present study, chicken frizzled-10 (Fz-10) encoding a Wnt receptor was used to study mechanisms of Wnt-7a signaling during chick limb patterning, because its expression is restricted to the posterior-distal region of the dorsal limb bud. Fz-10 transcripts colocalize with Sonic hedgehog (Shh) in the dorsal side of stages 18-23 chick limb buds. It was demonstrated that Fz-10 interacts with Wnt-7a to induce synergistically the expression of Wnt-responsive genes, such as Siamois and Xnr3, in Xenopus animal cap assays. In the chick limb bud, Fz-10 expression is regulated by Shh and a signal from the dorsal ectoderm, presumably Wnt-7a, but not by signals from the apical ectodermal ridge. These results suggest that Fz-10 acts as a receptor for Wnt-7a and has a positive effect on Shh expression in the chick limb bud.
A Non-Randomized Multicentre Trial of Human Immune Plasma for Treatment of Hantavirus Cardiopulmonary Syndrome Caused by Andes Virus (2014)

Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.
New Approaches to Target the Androgen Receptor and STAT3 for Prostate Cancer Treatments (2009)

Prostate cancer (PCa) is a common cause of death in men and remains incurable in the androgen-refractory phase. Growing evidence has shown that the androgen receptor (AR) and signal transducers and activators of transcription 3 (STAT3) could be effective targets for androgen-refractory PCa therapy. Many strategies have been reported to inhibit the AR or STAT3 activities. In this review, we focus on the AR N-terminal domain and AR chaperones, as well as small molecule inhibitors to STAT3 with which we discuss some new approaches to target the AR and STAT3 as potential treatments for androgen-refractory PCa.
Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin (1994)

Mice rendered deficient in lymphotoxin (LT) by gene targeting in embryonic stem cells have no morphologically detectable lymph nodes or Peyer's patches, although development of the thymus appears normal. Within the white pulp of the spleen, there is failure of normal segregation of B and T cells. Spleen and peripheral blood contain CD4+CD8- and CD4-CD8+ T cells in a normal ratio, and both T cells subsets have an apparently normal lytic function. Lymphocytes positive for immunoglobulin M are present in increased numbers in both the spleen and peripheral blood. These data suggest an essential role for LT in the normal development of peripheral lymphoid organs.
Modification of HF-treated silicon (100) surfaces by scanning tunneling microscopy in air under imaging conditions (1992)

The modification of HF-etched silicon (100) surface with a scanning tunneling microscope (STM) operated in air is studied for the first time in samples subjected to the standard HF etching without the follow-up rinsing in H2O. The modifications are produced in air under normal STM imaging conditions (Vt=−1.4 V and It=2 nA). The simultaneous acquisition of topographical, current image tunneling spectroscopy and local barrier-height images clearly shows that the nature of the modification is not only topographical but also chemical. The features produced with a resolution better than 25 nm are attributed to a tip-induced oxidation enhanced by the presence of fluorine on the surface.
Transition-State Enthalpy and Entropy Effects on Reactivity and Selectivity in Hydrogenolysis ofn-Alkanes (2013)

Statistical mechanics and transition state (TS) theory describe rates and selectivities of C-C bond cleavage in C2-C10 n-alkanes on metal catalysts and provide a general description for the hydrogenolysis of hydrocarbons. Mechanistic interpretation shows the dominant role of entropy, over enthalpy, in determining the location and rate of C-C bond cleavage. Ir, Rh, and Pt clusters cleave C-C bonds at rates proportional to coverages of intermediates derived by removing 3-4 H-atoms from n-alkanes. Rate constants for C-C cleavage reflect large activation enthalpies (ΔH(‡), 217-257 kJ mol(-1)) that are independent of chain length and C-C bond location in C4+ n-alkanes. C-C bonds cleave because of large, positive activation entropies (ΔS(‡), 164-259 J mol(-1) K(-1)) provided by H2 that forms with TS. Kinetic and independent spectroscopic evidence for the composition and structure of these TS give accurate estimates of ΔS(‡) for cleavage at each C-C bond. Large differences between rate constants for ethane and n-decane (~10(8)) reflect an increase in the entropy of gaseous alkanes retained at the TS. The location of C-C bond cleavage depends solely on the rotational entropies of alkyl chains attached to the cleaved C-C bond, which depend on their chain length. Such entropy considerations account for the ubiquitous, but previously unexplained, preference for cleaving nonterminal C-C bonds in n-alkanes. This mechanistic analysis and thermodynamic treatment illustrates the continued utility of such approaches even for hydrogenolysis reactions, with complexity seemingly beyond the reach of classical treatments, and applies to catalytic clusters beyond those reported here (0.6-2.7 nm; Ir, Rh, Pt).
The complete genome sequence of the avian pathogen Mycoplasma gallisepticum strain Rlow (2003)

The complete genome of Mycoplasma gallisepticum strain R(low) has been sequenced. The genome is composed of 996,422 bp with an overall G+C content of 31 mol%. It contains 742 putative coding DNA sequences (CDSs), representing a 91 % coding density. Function has been assigned to 469 of the CDSs, while 150 encode conserved hypothetical proteins and 123 remain as unique hypothetical proteins. The genome contains two copies of the rRNA genes and 33 tRNA genes. The origin of replication has been localized based on sequence analysis in the region of the dnaA gene. The vlhA family (previously termed pMGA) contains 43 genes distributed among five loci containing 8, 2, 9, 12 and 12 genes. This family of genes constitutes 10.4% (103 kb) of the total genome. Two CDSs were identified immediately downstream of gapA and crmA encoding proteins that share homology to cytadhesins GapA and CrmA. Based on motif analysis it is predicted that 80 genes encode lipoproteins and 149 proteins contain multiple transmembrane domains. The authors have identified 75 proteins putatively involved in transport of biomolecules, 12 transposases, and a number of potential virulence factors. The completion of this sequence has spawned multiple projects directed at defining the biological basis of M. gallisepticum.
Control Message Reduction Techniques in Backward Learning Ad Hoc Routing Protocols (2008)

Most existing wireless ad hoc routing protocols rely upon the use of backward learning technique with explicit control messages to route packets. In this paper we propose a set of techniques that can be applied in a backward learning routing algorithm in order to minimize or even eliminate explicit control messages for route discovery, setup, and maintenance, while minimally using implicit data-like control messages that need no special processing. We also show that such an algorithm does not need to prevent routing loops at all costs, such as by means of extensive network-wide spanning trees in traditional LAN bridges, or destination sequence numbers in AODV, or source- routing in DSR. In fact, we prove that transient loops can be safely allowed to occur when a simple route refresh mechanism is coupled with the use of packet identification field to effectively bound the lifetime of such transient loops without negatively impacting the network performance. Results demonstrate that even a routing algorithm without explicit control messages can perform competitively in comparison to AODV and DSR protocols while significantly reducing the protocol complexity.
Activating MET kinase rearrangements in melanoma and Spitz tumours (2015)

Oncogenic gene fusions have been identified in many cancers and many serve as biomarkers or targets for therapy. Here we identify six different melanocytic tumours with genomic rearrangements of MET fusing the kinase domain of MET in-frame to six different N-terminal partners. These tumours lack activating mutations in other established melanoma oncogenes. We functionally characterize two of the identified fusion proteins (TRIM4-MET and ZKSCAN1-MET) and find that they constitutively activate the mitogen-activated protein kinase (MAPK), phosphoinositol-3 kinase (PI3K) and phospholipase C gamma 1 (PLCγ1) pathways. The MET inhibitors cabozantinib (FDA-approved for progressive medullary thyroid cancer) and PF-04217903 block their activity at nanomolar concentrations. MET fusion kinases thus provide a potential therapeutic target for a rare subset of melanoma for which currently no targeted therapeutic options currently exist.
Sonication-assisted Agrobacterium-mediated transformation of the ACC gene to interfere the production of ethylene in spring Dendrobium cv. ‘Sanya’ (2012)

In the present study, a protocol was developed to obtain stable lines of the spring Dendrobium cv. ‘Sanya’ via Sonication-Assisted Agrobacterium-mediated Transformation (SAAT) of protocorm-like bodies (PLBs). Agrobacterium tumefaciens strain LBA4404 was used with the binary vector YF9078 containing the inverted repeat (IR) of ACC gene (IRACC) for the inhibition of ethylene production, the neomycin phosphotransferase II gene (NPTII) gene as a selectable marker for kanamycin resistance, and an intron-containing β-glucuronidase gene (gus-int) as a reporter gene. PLBs were treated for 10 min with ultrasound (40 kHz) and subsequently inoculated with Agrobacterium suspension for 60 min. The addition of 100 μM acetosyringone (AS) during the preculturing, inoculation and co-cultivation resulted in the highest efficiency of gene transformation (1.04%). Following co-cultivation, PLBs were cultured on selective medium containing 200 mg/l kanamycin and 250 mg/l cefotaxime. Proliferating PLBs were repeatedly selected for kanamycin resistance, and stable transformed lines were generated. Incorporation and expression of transgenes were confirmed by GUS histochemical assay, PCR analysis, Southern blot analysis, and real-time reverse transcription-polymerase chain reaction (RT-PCR). A total of five Southern blot positive transgenic lines were obtained. The ability for ethylene suppression by small potted transgenic plants was measured. The results showed that it was significantly higher in transgenic lines than in untransformed control; different strains exhibited marked variation; and this was related to their cDNA expression.
Fungal metabolites. Part 12. Potent immunosuppressant, 14-deoxomyriocin, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyleicos-6-enoic acid and structure-activity relationships of myriocin derivatives. (1994)

In order to investigate the structure-activity relationships, fourteen derivatives of myriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyl-14-oxoeicos- 6-enoic acid) were prepared and examined for immunosuppressive activity on mouse allogeneic mixed lymphocyte reaction in vitro. Among them, 14-deoxomyriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyleicos-6-enoic acid) was the most potent. It also suppressed the generation of allo-reactive cytotoxic T lymphocytes in mice upon intraperitoneal administration, with a potency 10-fold greater than that of myriocin.
Selective binding to polymers via covalent bonds. The construction of chiral cavities as specific receptor sites (1982)

Abstract
Multi-objective convolutional learning for face labeling (2015)

This paper formulates face labeling as a conditional random field with unary and pairwise classifiers. We develop a novel multi-objective learning method that optimizes a single unified deep convolutional network with two distinct non-structured loss functions: one encoding the unary label likelihoods and the other encoding the pairwise label dependencies. Moreover, we regularize the network by using a nonparametric prior as new input channels in addition to the RGB image, and show that significant performance improvements can be achieved with a much smaller network size. Experiments on both the LFW and Helen datasets demonstrate state-of-the-art results of the proposed algorithm, and accurate labeling results on challenging images can be obtained by the proposed algorithm for real-world applications.
Kinetics of the Two Forms of Acetyl‐CoA Carboxylase from Pisum sativum (1994)

Steady‐state kinetics of the 220‐kDa form of acetyl‐CoA carboxylase (ACC220), as purified from mature pea seeds, have been investigated with respect to the substrate specificity and inhibition by quizalofop, a herbicide of the aryloxyphenoxypropionate type. The enzyme showed a dual specificity, being able to carboxylate propionyl‐CoA at a maximal rate approximately 20% that measured in the presence of the acetyl‐CoA substrate. These two reactions occur at separate sites on the enzyme. One site binds either acetyl‐CoA ( K m = 226 μM) or propionyl‐CoA ( K m = 38 μM) and is strongly inhibited by quizalofop ( K i = 25 μM and 9.3 μM for the acetyl‐CoA and propionyl‐CoA substrates, respectively). The other is specific for acetyl‐CoA ( K m = 11 μM) and is much less inhibited by quizalofop ( K i = 256 μM). Owing to the existence of these two catalytically different sites, the enzyme obeyed Michaelis‐Menten kinetics with propionyl‐CoA, but exhibited kinetic cooperativity in the presence of acetyl‐CoA. Also, kinetics of propionyl‐CoA carboxylase activity of ACC220 exhibited hyperbolic inhibition in the presence of quizalofop, but co‐operative inhibition when following the ACC activity of the enzyme. The results suggest that the higher the substrate specificity, the lower the quizalofop sensitivity of the active site. Similar kinetic behaviour was observed with ACC220 purified from pea leaves. Also, the apparent correlation between the substrate specificity and the sensitivity of ACC towards quizalofop was confirmed by kinetic analyses of the low‐molecular‐mass form of ACC present in chloroplasts of young pea leaves. This enzyme was insensitive to quizalofop inhibition and was not able to carboxylate propionyl‐CoA. No other propionyl‐CoA carboxylase activity, different from that catalysed by ACC220, could be detected from either reproductive or vegetative organs of pea plants at any stage of development.
Prokaryotic microbiota of recycled paper mills with low or zero effluent (2008)

The tendency in the paper industry is to close all water loops to save water. This leads to higher process temperatures and may increase the colloidal and dissolved material in the process circulation. Increase of nutrients in the water circuits may favor microbiological growth and fouling. In this paper the chemical and microbial compositions of water circuits and deposits were studied of two closed cycled paper/board mills, one mill totally closed (0 m(3) waste water t(-1)), and the other low discharging (about 4 m(3 )t(-1)). The zero discharge mill accumulated high amounts (>10 g C L(-1)) of organic carbon in the circulation waters, about 40% of which composed of volatile acids (lactic, acetic, propionic and butyric acid). Water contents of sulfate, chloride, sodium and calcium increased to >1 g L(-1) of each. q-PCR targeted on 16S rRNA genes indicated that the bacteria in water circuits were mainly viable cells. In both mills anaerobic growth (10(6)-10(8) CFU mL(-1)) equalled or exceeded aerobic growth, with odor problem but no actual slime problem. The major part (40%) of all identifiable bacterial sequences were closest but yet distant (<96%) to Enterococcus cecorum and in the 4 m(3 )t(-1) discharging mill also Bacillus thermoamylovorans and Bacillus coagulans. Slimes and deposits from the mills contained high amounts, > or =10(8) g(-1), of archaean, but only the genus Methanothrix was identifiable from the cloned sequences. The findings indicate that closing the water circuits strongly limited diversity of the microbiota but allowed efficient mineralization of the dissolved and suspended matter.
Structure of a shark IgNAR antibody variable domain and modeling of an early‐developmental isotype (2005)

The new antigen receptor (IgNAR) antibodies from sharks are disulphide bonded dimers of two protein chains, each containing one variable and five constant domains. Three types of IgNAR variable domains have been discovered, with Type 3 appearing early in shark development and being overtaken by the antigen-driven affinity-matured Type 1 and 2 response. Here, we have determined the first structure of a naturally occurring Type 2 IgNAR variable domain, and identified the disulphide bond that links and stabilizes the CDR1 and CDR3 loops. This disulphide bridge locks the CDR3 loop in an "upright" conformation in contrast to other shark antibody structures, where a more lateral configuration is observed. Further, we sought to model the Type 3 isotype based on the crystallographic structure reported here. This modeling indicates (1) that internal Type 3-specific residues combine to pack into a compact immunoglobulin core that supports the CDR loop regions, and (2) that despite apparent low-sequence variability, there is sufficient plasticity in the CDR3 loop to form a conformationally diverse antigen-binding surface.
Studies in the Way of Words (1989)

This volume, Grice's first hook, includes the long-delayed publication of his enormously influential 1967 William James Lectures. But there is much, much more in this work. Paul Grice himself has carefully arranged and framed the sequence of essays to emphasize not a certain set of ideas but a habit of mind, a style of philosophizing. Grice has, to be sure, provided philosophy with crucial ideas. His account of speaker-meaning is the standard that others use to define their own minor divergences or future elaborations. His discussion of conversational implicatures has given philosophers an important tool for the investigation of all sorts of problems; it has also laid the foundation for a great deal of work by other philosophers and linguists about presupposition. His metaphysical defense of absolute values is starting to be considered the beginning of a new phase in philosophy. This is a vital book for all who are interested in Anglo-American philosophy.
Educação ambiental e inclusão social: participação de crianças com deficiência visual em atividades de educação ambiental (2014)

Este trabalho teve o objetivo de avaliar e ampliar o conhecimento e a percepcao de criancas com deficiencia visual em relacao aos animais e suas interacoes com o meio ambiente, utilizando-se de experiencias de aprendizado ludicas, que fizeram o uso dos sentidos tateis, auditivos e olfativos. Foram realizadas entrevistas e atividades, onde os deficientes visuais tocaram animais vivos e empalhados, sentiram seus cheiros e sons, que possibilitaram novas experiencias de conhecimentos e sensacoes.  A experiencia sensitiva e a melhor maneira para a captacao de conhecimento do deficiente visual, portanto e por meio do desenvolvimento e estimulacao constante dos sentidos, que assimilacoes de objetos e de espacos irao ocorrer. Essa proposta de educacao ambiental observou que atividades sensitivas sao muito importantes para a construcao de imagens mentais, as aproximando da realidade, ja que muitas vezes, sao construidas por meio de descricoes verbais, nem sempre muito claras para os deficientes visuais. Palavras-chave: educacao ambiental; inclusao social; deficiencia visual; crianca; ludico; sentidos. ABSTRACT This work had the objective to evaluate and enlarge the knowledge and perception of visual impaired children regarding animals and interactions with the environment by using ludic learning experiences, which encompassed tactile, hearing and olfactory senses. Interviews and activities were carried out in which the visually impaired children could touch living and stuffed animals, smell and hear them, enabling new experiences of knowledge and senses. The sensitive experience is the best way of knowledge capture by visually impaired people, so it is through development and constant sense stimulation that assimilation of objects and spaces will take place. This environmental education proposal has shown that sensory activities are very important to mental image construction, approaching them to reality, since they are built through verbal description, not often too evident for the visually impaired. Keywords: environmental education; social inclusion; visually impaired; child; ludic; senses.