gebhart/patrepeval huggingface dataset:
Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. (1989)

T-cell lymphomas induced in rats by Moloney murine leukemia virus acquire increasing numbers of proviruses in their genome during tumor progression in vivo and passage of tumor cells in vitro. To determine whether the proviruses progressively acquired during tumor progression play a causal role in this process, we cloned one of them from a cell line derived from the primary tumor 2772. A probe from the cellular DNA flanking the provirus was used to analyze 79 DNA samples from primary tumor tissues of 28 tumor-bearing rats and 80 DNA samples from 30 independent tumor cell lines. This analysis revealed a rearrangement in this region in the primary tumor derived from the thymus of one animal but not in a clone of the same tumor segregating in the spleen. Of the cell line DNA samples, three carried a provirus in this region. Two of these integration events had occurred independently in two clonally related sublines derived from tumor 2772, and they were followed by rapid selection in culture. On the basis of these findings this locus was named Tpl-1 (tumor progression locus 1). The Tpl-1 locus was mapped to rat chromosome 8 and to mouse chromosome 9 at a genetic distance of 1.2 +/- 0.9 centimorgans from the Ets-1 protooncogene. Although the genetic distance between Tpl-1 and Ets-1 indicates that they are different genes, analysis of Tpl-1 cDNA clones revealed that the two are closely related.
In-vivostudies on dexamethasone sodium phosphate liposomes (1996)

Dexamethasone Sodium Phosphate (DSP) is a water soluble anti-inflammatory steroid commonly used in the therapy of serious types of ophthalmic inflammation. It has been demonstrated that unless the corneal epithelium is damaged, DSP is poorly absorbed by the cornea (Kupferman et al. 1974). Thus, it is doubtful whether such a drug would cure inflammation of the anterior segments. For this purpose, several liposomal DSP formulations containing phospholipid: charge inducer: cholesterol in molar ratios of 10:1:4 were investigated. Both gel state (PL 90H: SA: Cho1) and liquid state (PL 100: SA: Cho1) liposomes were prepared. For the preparation of liposomes, the film method followed by bath sonication was used. Liposomes were labelled with (99m)-Tc and administered intra-ocularly to New Zealand white rabbits weighing 2.5-3 kg for in vivo experiments. The biodistribution of the labelled liposomes were determined. For this purpose, eye segments (such as cornea, lens, iris, ciliar body, vitreous, aqueous humor, conjuctiva and sclera) and RES organs (such as liver, pancreas, spleen) were removed at fixed time intervals. In the present study, the efficiency of liposomes for the delivery of water-soluble drugs was evaluated in rabbit eyes using DSP as a model drug in different liposomal formulations.
Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly (2008)

The extent to which polypeptide conformation depends on side-chain composition and sequence has been widely studied, but less is known about the importance of maintaining an alpha-amino acid backbone. Here, we examine a series of peptides with backbones that feature different repeating patterns of alpha- and beta-amino acid residues but an invariant side-chain sequence. In the pure alpha-backbone, this sequence corresponds to the previously studied peptide GCN4-pLI, which forms a very stable four-helix bundle quaternary structure. Physical characterization in solution and crystallographic structure determination show that a variety of alpha/beta-peptide backbones can adopt sequence-encoded quaternary structures similar to that of the alpha prototype. There is a loss in helix bundle stability upon beta-residue incorporation; however, stability of the quaternary structure is not a simple function of beta-residue content. We find that cyclically constrained beta-amino acid residues can stabilize the folds of alpha/beta-peptide GCN4-pLI analogues and restore quaternary structure formation to backbones that are predominantly unfolded in the absence of cyclic residues. Our results show a surprising degree of plasticity in terms of the backbone compositions that can manifest the structural information encoded in a sequence of amino acid side chains. These findings offer a framework for the design of nonnatural oligomers that mimic the structural and functional properties of proteins.
Targeted Therapy for Early and Locally Advanced Breast Cancer (2010)

The treatment of patients with breast cancer continues to evolve, with cytotoxic chemotherapy, endocrine therapy, and molecular targeted therapies representing the backbones of modern systemic breast cancer treatment. As we learn better to understand the biology of breast cancer cells, therapies to target specific pathways continue to be developed with the goal of expanding available effective therapy in specific populations. Several targeted drugs with different molecular pathways have achieved approval for metastatic breast cancer, but for early breast cancer trastuzumab is the only one that is currently approved in combination with chemotherapy for adjuvant or neoadjuvant treatment in women with HER2-positive breast cancer. Lapatinib and bevacizumab are both approved for the treatment of metastatic breast cancer and are now investigated in phase III clinical trials testing their effectiveness in the treatment of early breast cancer. In this publication, we review the current status in the treatment of early and locally advanced breast cancer with molecular targeted therapies that are currently approved or in advanced clinical development.
A Nonlinear Method for Stochastic Spectrum Estimation in the Modeling of Musical Sounds (2007)

We propose an original technique for separating the spectrum of the noisy component from that of the sinusoidal, quasi-deterministic one, for the sinusoids + transients + noise modeling of musical sounds. It also enables estimation of the time-domain noise envelope and detection of transients with standard techniques. The algorithm for spectrum separation relies on nonlinear transformations of the amplitude spectrum of the sampled signal obtained via fast Fourier transform, which allow to eliminate the dominant partials without the need for precisely tuned notch filters. The envelope estimation is performed by calculating the energy of the signal in the frequency domain, over a sliding time window. Several transformations (such as pitch shifting, time stretching, etc.) can be performed on the so-obtained stochastic spectrum prior to resynthesis. The synthesized sound is built via inverse fast Fourier transform with overlap-add method. The performance of the proposed algorithm is assessed on synthetic, instrumental, and natural sounds in terms of different quality measures
Bone Resorption Restored in Osteopetrotic Mice by Transplants of Normal Bone Marrow and Spleen Cells (1975)

Capacity to resorb bone and calcified cartilage was restored permanently in mice with inherited osteopetrosis by the intravenous administration of cell suspensions prepared from spleen and bone marrow of normal littermates. Beginning near active growth plates as early as 2 weeks after transplantation, replacement of the abnormal spongiosa continued until medullary cavitites were fully expanded.
Transport Mechanisms of Alkanethiols during Microcontact Printing on Gold (1998)

Microcontact printing (μCP) with elastomeric stamps is a versatile method to modify the chemistry of surfaces. We explore this patterning process here, examining the origin and character of its limits and demonstrating how best to use μCP and alkanethiols for lithography on gold at submicron scales. We find that, ultimately, this type of lithography is constrained by the need to carry the monolayer-forming reaction to completion, with significant degradation of the accuracy of prints at sub-500-nm scales due to molecular diffusion. Printing monolayers of eicosanethiol on gold proved to be the best practical compromise between self-assembly of the resist and its transport along the stamp and substrate interfaces as well as through the gas phase. Results for this system were particularly sensitive to the geometry of the stamp and how eicosanethiol was placed on, and transferred from, its surface to the gold. Our experiments, and simulations that corroborate them, show the relative importance of the various paths in controlling the chemical contrast on the substrate. We demonstrate the fabrication of high-density arrays of ≈90-nm gold dots using these criteria.
Development of a single tube 640-plex genotyping method for detection of nucleic acid variations on microarrays (2008)

Detection of DNA sequence variation is critical to biomedical applications, including disease genetic identification, diagnosis and treatment, drug discovery and forensic analysis. Here, we describe an arrayed primer extension-based genotyping method (APEX-2) that allows multiplex (640-plex) DNA amplification and detection of single nucleotide polymorphisms (SNPs) and mutations on microarrays via four-color single-base primer extension. The founding principle of APEX-2 multiplex PCR requires two oligonucleotides per SNP/mutation to generate amplicons containing the position of interest. The same oligonucleotides are then subsequently used as immobilized single-base extension primers on a microarray. The method described here is ideal for SNP or mutation detection analysis, molecular diagnostics and forensic analysis. This robust genetic test has minimal requirements: two primers, two spots on the microarray and a low cost four-color detection system for the targeted site; and provides an advantageous alternative to high-density platforms and low-density detection systems.
Early determinants of cardiovascular risk factors in adults. A. Plasma lipids (1993)

The aim of the study was to examine the effect of birth weight, infant nutrition, body mass and social status from early childhood and adulthood on plasma lipid levels in 192 adult subjects examined in the first three years of life (mean age 1.4 years in males and 1.3 years in females) and again as adults (mean age 19.9 years in males and 19.6 in females). According to the results obtained, total cholesterol was significantly higher in adult male subjects breast fed for the shortest period of time (p < 0.05). Those males who were leanest in the first three years of life and fattest as adults had the highest levels of total cholesterol (p = 0.03) and LDL cholesterol (p = 0.02). Birth weight had no significant influence on plasma lipid levels in adults subjects. When data on nutrition, anthropometry and social status from both age periods were included in multivariate regression analyses, the most significant predictors of higher levels of total cholesterol and LDL cholesterol in males were lower adult height and poor social status in early childhood, while in females they were a shorter duration of breast feeding and earlier introduction of solids.
NhaR, a protein homologous to a family of bacterial regulatory proteins (LysR), regulates nhaA, the sodium proton antiporter gene in Escherichia coli. (1992)

On the basis of protein homology, nhaR has previously been shown to belong to a large family of regulatory proteins, the LysR family (Henikoff, S., Haughn, G.W., Calvo, J.M., and Wallace, J.C. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 6602-6606). In this work we show that nhaR is a regulator of nhaA, a gene encoding a Na+/H+ antiporter in Escherichia coli. Multicopy plasmid bearing nhaR enhances the Na(+)-dependent induction of a chromosomal nhaA'-'lacZ fusion. Extracts derived from cells overexpressing nhaR exhibit specific DNA binding capacity to the upstream sequences of nhaA. Construction of an nhaR deletion mutant (OR100) shows that nhaR is required in addition to nhaA to tolerate the extreme conditions under which nhaA is indispensable. Whereas OR100 grows like the wild type at neutral pH even at high Na+ concentrations (700 mM), it becomes much more sensitive to Na+ (greater than 300 mM) at pH 8.5; furthermore, OR100 is more sensitive to Li+ (100 mM) than the wild type. Nevertheless, the phenotype of OR100, which is more resistant to Na+, Li+, and alkaline pH than a delta nhaA strain (NM81), implies that the regulation exerted by nhaR is not complete and that some expression of nhaA exists in OR100. Accordingly, the effect of nhaR in cells is dependent on the level of nhaA. OR200, a nhaA and nhaR deletion mutant, has the same phenotype as NM81. Multicopy plasmid bearing nhaR does not change the phenotype of either OR200 or NM81. On the other hand, multicopy nhaA renders the cells Li(+)- and and Na(+)-resistant even without nhaR.
Long-Term Follow-Up of Patients Immunized with AN1792: Reduced Functional Decline in Antibody Responders (2009)

Approximately 4.6 years after immunization with AN1792, patients defined as responders in the phase 2a study maintained low but detectable, sustained anti-AN1792 antibody titers and demonstrated significantly reduced functional decline compared with placebo-treated patients. Brain volume loss in antibody responders was not significantly different from placebo-treated patients approximately 3.6 years from the end of the original study. No further cases of encephalitis were noted. These data support the hypothesis that Abeta immunotherapy may have long-term functional benefits.
A Non‐Intercalating Proflavine Derivative (1973)

A proflavine derivative with bulky substituents, 2,7‐di‐ t ‐butyl‐proflavine, binds to DNA but apparently not by intercalation. The methods used to study this problem include equilibrium dialysis, relaxation kinetics and hydroxdynamic studies on low‐molecular‐weight and closed‐circular DNA. These show that binding produces no detectable lengthening or unwinding of the double helix, and that the binding reaction is much faster than is the case with unsubstituted proflavine. We conclude that an outside‐bound complex is formed. We also measured equilibrium binding isotherms for DNA samples of varying G · C content, and for several synthetic polynucleotides. These results are consistent with a model in which a bound 2,7‐di‐ t ‐butyl‐proflavine molecule occupies three base pairs, and strong binding requires that two of these three be A · T pairs. Comparison of poly(dA) · poly(dT) with poly(A) · poly(U) shows a preference of at least 100‐fold for binding to the former over the latter. Also, we found that the thymine methyl groups are probably not responsible for the A · T specificity. The optical properties of the outside complex include a red shift of the absorbance maximum, with an increase in maximum absorbance instead of the more common decrease. The fluorescence of the dye is enhanced on binding, especially to an A · T‐rich‐DNA. The kinetic results show that two complex forms are present, differing in intrinsic affinity by about an order of magnitude. Both are formed with second‐order rate constants in excess of 10 8 M −1 s −1 and it is therefore very unlikely that either is an intercalated form. The absorbance spectrum of the bound dye changes as the degree of binding increases, due, at least in part, to the changing contribution of the two binding mechanisms. The conclusions concerning binding specificity refer to the dominant complex form; we have no firm information about the specificity of the weaker complex.
Turismo: instigar o gosto pela sua pesquisa (2014)

Editorial do Vol. 2, N. 2 (jul./dez.) de 2012 da Revista Iberoamericana de Turismo - RITUR.
A multispectral fluorescence imaging system: Design and initial clinical tests in intra‐operative Photofrin‐photodynamic therapy of brain tumors (2003)

The system performed to specification under realistic operating conditions and could reveal unresected residual tumor tissue. It may be used for either PDT dosimetry/monitoring and/or for surgical guidance.
HMGB1: The jack‐of‐all‐trades protein is a master DNA repair mechanic (2009)

The high mobility group protein B1 (HMGB1) is a highly abundant protein with roles in several cellular processes, including chromatin structure and transcriptional regulation, as well as an extracellular role in inflammation. HMGB1's most thoroughly defined function is as a protein capable of binding specifically to distorted and damaged DNA, and its ability to induce further bending in the DNA once it is bound. This characteristic in part mediates its function in chromatin structure (binding to the linker region of nucleosomal DNA and increasing the instability of the nucleosome structure) as well as transcription (bending promoter DNA to enhance the interaction of transcription factors), but the functional consequences of HMGB1's binding to damaged DNA is still an area of active investigation. In this review we describe HMGB1's actions in the nucleotide excision repair (NER) pathway, and we discuss aspects of both the "repair shielding" and "repair enhancing" hypotheses that have been suggested. We also report information regarding HMGB1's roles in the mismatch repair (MMR), nonhomologous end-joining (NHEJ), and V(D)J recombination pathways, as well as its newly-discovered involvement in the base excision repair (BER) pathway. We further explore the potential of HMGB1 in DNA repair in the context of chromatin. The elucidation of HMGB1's role in DNA repair is critical for the complete understanding of HMGB1's intracellular functions, which is particularly relevant in the context of anti-HMGB1 therapies that are being developed to treat inflammatory diseases.
DNA Binding by 4-Methoxypyrrolic Natural Products. Preference for Intercalation at AT Sites by Tambjamine E and Prodigiosin (1999)

The 4-methoxypyrrolic natural products contain a common 4-methoxy-2,2'-bipyrrole chromophore and exhibit promising anticancer, antimicrobial, and immunosuppressive activities. Herein, the ability of two representative members, tambjamine E (1) and prodigiosin (2), to bind calf thymus DNA (CT-DNA), polyd[G-C](2), and polyd[A-T](2) has been characterized using absorption and fluorescence spectroscopy. Scatchard plots showed that 1 occupies a site size (n) of ca. three base pairs and possesses affinity constants (K) ranging from 1 to 0.1 x 10(5) M(-)(1). Prodigiosin (2) binds DNA by mixed modes, as isobestic points were not evident in titration experiments. The neutral aldehyde precursor 4 was found to possess no measurable DNA binding affinity, indicating that the enamine structure of 1 and the pyrromethene of 2 are essential elements for DNA binding affinity. The enamine of 1 was found to undergo hydrolysis to 4 with a half-life (t(1/2)) of 14.5 h at pH 7.4 and 37.5 degrees C. For the B-ring nitrogen atom of 1, a pK(a) value of 10.06 was also established. From fluorescence spectroscopy it was found that 1, 2, and 4 possess weak emission spectra in water that is increased in nonaqueous solvents. For 1 and 2, DNA binding also increased the emission yield. Energy-transfer measurements suggested an intercalative binding mode, with preference for AT sites. The ability of distamycin to displace 1 and 2 from the helix also suggested that they intercalate from the minor-groove. This specificity differs from other unfused aromatic cations that bind by a minor-groove mode at AT sequences and intercalate at GC sites. Reasons for the specificity displayed by 1 and 2, as well as the implications of our findings to their biological properties are discussed.
The role of 5-HT(1A) receptors in the locomotor-suppressant effects of LSD: WAY-100635 studies of 8-OH-DPAT, DOI and LSD in rats. (1996)

The selective 5-HT(1A) antagonist WAY-100635 was employed to further clarify the respective contributions of 5-HT(1A) receptors to the effects of the 5-HT(1A) agonist 8-OH-DPAT, the 5-HT(2) agonist DOI, and the mixed 5-HT(1A/2) agonist LSD on exploratory locomotion in rats. In nocturnal studies of well-handled rats during their first exposure to the Behavioral Pattern Monitor, which enables analyses of quantitative and qualitative changes in locomotor activity, locomotor and investigatory responses were reduced by treatment with either 8-OH-DPAT, DOI, or LSD. The hypoactivity produced by 8-OH-DPAT, but not that produced by DOI, was antagonized by pretreatment with WAY-100635. These results substantiate the effectiveness and functional specificity of WAY-100635 as a 5-HT(1A) antagonist. Furthermore, these results are inconsistent with a functional interaction between 5-HT(1A) and 5-HT(2) receptors in the control of locomotor behavior. The decreases in locomotion produced by LSD were attenuated by pretreatment with WAY-100635, indicating that the effects of LSD in this paradigm are due partly to agonist actions at 5-HT(1A) receptors. Therefore, 5-HT(1A) receptors appear to play a direct role in mediating the effects of LSD on rodent locomotion.
IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice (2000)

We investigated the effects of interleukin (IL)-10 administration on allergen-induced Th2 cytokine production, eosinophilic inflammation, and airway reactivity. Mice were sensitized by intraperitoneal injection of ragweed (RW) adsorbed to Alum and challenged by intratracheal instillation of the allergen. Sensitization and challenge with RW increased concentrations of IL-10 in bronchoalveolar lavage (BAL) fluid from undetectable levels to 60 pg/ml over 72 h. Intratracheal instillation of 25 ng of recombinant murine IL-10 at the time of RW challenge further elevated BAL fluid IL-10 concentration to 440 pg/ml but decreased BAL fluid IL-4, IL-5, and interferon-gamma levels by 40-85% and eosinophil numbers by 70% (P < 0.0001). Unexpectedly, the same IL-10 treatment increased airway reactivity to methacholine in spontaneously breathing mice that had been sensitized and challenged with RW (P < 0.001). IL-10 treatment in naive animals or RW-sensitized mice challenged with PBS failed to increase airway reactivity, demonstrating that IL-10 induces an increase in airway reactivity only when it is administered in conjunction with allergic sensitization and challenge. The results demonstrate that IL-10 reduces Th2 cytokine levels and eosinophilic inflammation but augments airway hyperreactivity. Thus, despite its potent anti-inflammatory activity, IL-10 could contribute to the decline in pulmonary function observed in asthma.
Ecdysone agonist inducible transcription in transgenic tobacco plants (1999)

A novel chemical-induced gene regulatory system for plants consisting of two molecular components is described. The first, or regulatory, cassette comprises a chimeric receptor composed of the hinge and ligand binding domains of the Heliothis virescens ecdysone receptor and the transactivation domain of the Herpes simplex VP16 protein fused to the DNA binding domain and transactivation of a mammalian glucocorticoid receptor. The second component, a reporter cassette, contains six copies of the glucocorticoid response element (GRE) fused to the minimal 35SCaMV promoter and beta-glucuronidase. The system uses a commercially available non-steroidal ecdysone agonist, RH5992 (tebufenozide), as an inducer. Activation of gene expression is shown in both tobacco transient protoplasts and transgenic plants. The response is ligand dependent and is modulated by the change in minimal promoter context. The system is capable of inducing transgene activity up to 420-fold corresponding to 150% of the activity observed with positive controls (35SCaMV:GUS).
Pseudomonas exotoxin coupled to a monoclonal antibody against ovarian cancer inhibits the growth of human ovarian cancer cells in a mouse model. (1987)

In an effort to devise an alternative treatment for human ovarian cancer, we have isolated a monoclonal antibody (OVB-3) that reacts with all ovarian cancers tested (10/10) but few normal tissues. An immunotoxin produced by coupling OVB-3 to Pseudomonas exotoxin kills ovarian cancer cells in tissue culture and prolongs the life of animals bearing human ovarian cancers. These data suggest that this immunotoxin should be evaluated as a treatment for ovarian cancer in women.