gebhart/patrepeval huggingface dataset:
Diphtheria Pathogenesis in Guinea Pig Tracheal Organ Culture (1974)

The effect of diphtheria toxin on guinea pig trachea in organ culture was examined to measure the susceptibility of respiratory epithelial cells to toxin action. Exposure of individual tracheal rings to toxin resulted in cessation of protein synthesis as well as the development of cytopathology within a few hours. Continued incubation led to further inhibition of protein synthesis and extensive disorganization of the epithelial layer. Other inhibitors of protein synthesis were monitored for their effect on the structural integrity of tracheal cells but were found incapable of eliciting similar histopathology. Early after its addition, toxin at minute concentrations possessed cytotoxic properties as well as the ability to inhibit protein synthesis. Interpretation of these data is correlated with current information on the structure and activity of diphtheria toxin.
Enhanced mobilization of hepatic cadmium in mice upon coadministration of an N, N-disubstituted dithiocarbamate and an alkyl monoester of dimercaptosuccinate. (1992)

Oral (po) administration of mono-iso-amyl (2,3-dimercapto) succinate (Mi-ADMS), 0.5 mmol/kg for three consecutive days, to mice previously injected with cadmium (Cd) chloride reduced the whole body Cd burden 34%. Intraperitoneal (ip) administration of N-iso-amyl-N-glucaminedithiocarbamate (i-AmGDTC) by the same regimen reduced total body Cd 41%. Coadministration of the two compounds reduced the whole body Cd burden 60% (p less than 0.05). The liver Cd concentration was reduced 56% and 50%, respectively, by Mi-ADMS given po and i-AmGDTC given ip, each at 0.5 mmol/kg for three consecutive days. Coadministration of the two chelators reduced the liver Cd concentration 90% (p less than 0.05). The kidney Cd concentration was reduced 10% by Mi-ADMS alone, and 60% by i-AmGDTC alone, but there was only a 47% reduction when the two chelators were coadministered, probably as a result of redistribution of mobilized hepatic Cd to the kidneys. As 50-55% of the administered Cd is sequestered in the liver in this mouse model, it is concluded that coadministration of the two chemical classes of Cd complexing agents may offer a therapeutic advantage over administration of either agent alone.
Oxidoreductases and Hydroxynitrilase Lyases: Complementary Enzymatic Technologies for Chiral Alcohols (2006)

Abstract Biocatalytic processes are useful methods for the production of chiral intermediates. As an example, alcohol dehydrogenases are applied for the production of chiral alcohols by asymmetric reduction of prochiral ketones. From this class of enzymes alcohol dehydrogenase from Lactobacillus brevis will be described with respect to its industrial application. The process for the production of methyl ( R )‐3‐hydroxybutyrate using this enzyme is discussed in more detail. The application of alcohol dehydrogenases can be limited by the commercial availability of the starting material as, for instance, in the case of the synthesis of chiral α‐hydroxy acids. For these products asymmetric addition of hydrocyanic acid to aldehydes catalyzed by hydroxynitrile lyases such as ( S )‐oxynitrilase from Manihot esculenta is a complementary approach. Also, this enzyme will be characterized in more detail with respect to its industrial production and application.
Multiple Choice Learning: Learning to Produce Multiple Structured Outputs (2012)

We address the problem of generating multiple hypotheses for structured prediction tasks that involve interaction with users or successive components in a cascaded architecture. Given a set of multiple hypotheses, such components/users typically have the ability to retrieve the best (or approximately the best) solution in this set. The standard approach for handling such a scenario is to first learn a single-output model and then produce M-Best Maximum a Posteriori (MAP) hypotheses from this model. In contrast, we learn to produce multiple outputs by formulating this task as a multiple-output structured-output prediction problem with a loss-function that effectively captures the setup of the problem. We present a max-margin formulation that minimizes an upper-bound on this lossfunction. Experimental results on image segmentation and protein side-chain prediction show that our method outperforms conventional approaches used for this type of scenario and leads to substantial improvements in prediction accuracy.
Oligonucleotide directed mutagenesis of the human β-globin gene: a general method for producing specific point mutations in cloned DNA (1981)

A nonadecanucleotide has been used both as a site specific mutagen to introduce a T leads to A transversion mutation in the human beta-globin gene cloned in pBR322 as well as a probe to screen transformed colonies for the desired mutant. The specificity of the oligonucleotide as a mutagen and as a hybridization probe provide a general method for producing site specific mutations in DNA cloned in plasmid vectors such as pBR322.
NOVAS PERSPECTIVAS DE CRIAÇÃO FICCIONAL: UM DIÁLOGO SOBRE ESTÉTICA E LITERATURA EM WILDE E KIERKEGAARD (2013)

A proposta investigativa deste texto centra-se na leitura da obra de Oscar Wilde, O retrato de Dorian Gray, por meio da concepção estética defendida pelo filósofo dinamarquês Søren Kierkegaard. Contudo, a preocupação maior da análise em foco é não estagnar o aspecto literário do personagem da obra de Wilde, Dorian Gray, sob o alicerce de teorias fechadas e conclusivas e, muito menos, aproximá-lo da história da estética tradicional. Dessa forma, procura-se dar ênfase à articulação de novos parâmetros de leitura e crítica ao cruzar discurso filosófico e literário, aproximando-se o conceito de estética em Kierkegaard do universo literário de Wilde, autores relevantes no contexto filosófico-literário do século XIX e da contemporaneidade.
Immunological and Inflammatory Functions of the Interleukin-1 Family (2009)

More than any other cytokine family, the interleukin (IL)-1 family is closely linked to the innate immune response. This linkage became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I is highly homologous to the cytoplasmic domains of all Toll-like receptors (TLRs). Thus, fundamental inflammatory responses such as the induction of cyclooxygenase type 2, increased expression of adhesion molecules, or synthesis of nitric oxide are indistinguishable responses of both IL-1 and TLR ligands. Both families nonspecifically affect antigen recognition and lymphocyte function. IL-1beta is the most studied member of the IL-1 family because of its role in mediating autoinflammatory diseases. Although the TLR and IL-1 families evolved to assist in host defense against infection, unlike the TLR family, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also nonspecifically for TLR ligands and the innate immune response.
Deregressing estimated breeding values and weighting information for genomic regression analyses (2009)

Genomic prediction of breeding values involves a so-called training analysis that predicts the influence of small genomic regions by regression of observed information on marker genotypes for a given population of individuals. Available observations may take the form of individual phenotypes, repeated observations, records on close family members such as progeny, estimated breeding values (EBV) or their deregressed counterparts from genetic evaluations. The literature indicates that researchers are inconsistent in their approach to using EBV or deregressed data, and as to using the appropriate methods for weighting some data sources to account for heterogeneous variance. A logical approach to using information for genomic prediction is introduced, which demonstrates the appropriate weights for analyzing observations with heterogeneous variance and explains the need for and the manner in which EBV should have parent average effects removed, be deregressed and weighted. An appropriate deregression for genomic regression analyses is EBV/r2 where EBV excludes parent information and r2 is the reliability of that EBV. The appropriate weights for deregressed breeding values are neither the reliability nor the prediction error variance, two alternatives that have been used in published studies, but the ratio (1 - h2)/[(c + (1 - r2)/r2)h2] where c > 0 is the fraction of genetic variance not explained by markers. Phenotypic information on some individuals and deregressed data on others can be combined in genomic analyses using appropriate weighting.
Performance characteristics of a transcription‐mediated nucleic acid amplification assay for qualitative detection of hepatitis C virus RNA (2001)

The detection of hepatitis C virus (HCV) RNA by nucleic acid amplification techniques is the method of choice to differentiate between ongoing and past infection, and can be used to monitor the course of HCV infection. In this study, we evaluated the performance characteristics of a newly developed transcription-mediated amplification (TMA)-based assay, the VERSANT HCV RNA qualitative assay, which was designed to qualitatively detect HCV RNA. Samples tested by the TMA assay included 100 HCV antibody negative sera; serial dilutions of an HCV genotype 1a panel; the WHO HCV RNA standard 76/790; an HCV genotyping panel; and 150 clinical specimens, including sera from patients who had received alpha interferon (IFN) treatment or liver transplants. TMA test results were compared with the Cobas Amplicor HCV polymerase chain reaction (PCR) assay. The analytical specificity of the HCV TMA assay was > 98%. No carry-over contaminations were observed. The assay demonstrated an analytical sensitivity of 100% at 41 HCV RNA copies/mL (genotype 1a panel) and 5 IU/mL (WHO standard), respectively. HCV genotypes and subtypes did not affect the results. Qualitative RNA detection by diagnostic Amplicor PCR and TMA was in agreement in > 97% of all 150 clinical samples tested. In our study, the TMA-based assay proved to be a specific and sensitive method for qualitative HCV RNA detection. The test may turn out to be an attractive alternative to already established techniques for HCV RNA amplification in routine clinical laboratories.
Active oxygen acts as a promoter of transformation in mouse embryo C3H/10T1/2/C18 fibroblasts. (1984)

There is much evidence from in vivo and in vitro carcinogenesis studies that active oxygen species play a role in tumor promotion. We tested directly whether superoxide produced extracellularly by xanthine-xanthine oxidase (X-XO) has the capacity to promote initiated mouse embryo C3H/10T1/2 fibroblasts. Cell cultures initiated with either 137Cs gamma-rays or benzo[a]pyrene diol epoxide I were found to transform 3-30 times more effectively when subsequently treated daily for 3 weeks with nontoxic doses of X-XO. Scavengers of active oxygen radicals such as superoxide dismutase or superoxide dismutase in combination with catalase reduced the frequency of appearance of transformed foci by 3-25 times when compared to cultures receiving X-XO alone. These results show that active oxygen species such as superoxide and H2O2 can act in a promotional manner that mimics the effects of the mouse skin promoter phorbol 12-myristate 13-acetate in this system. X-XO also acted as a weak complete carcinogen.
Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. (1996)

Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity. In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1). Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7. In the current study, we tested these recombinant vaccinia for in vivo protection against an E7+ tumor, TC-1, which was derived from primary epithelial cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes. All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection. Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden. These findings point out the therapeutic limitations of recombinant vaccinia expressing unmodified tumor antigens. Further, they demonstrate that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.
Imaging Drug Delivery to Skin with Stimulated Raman Scattering Microscopy (2011)

Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a recently developed, label-free chemical imaging tool, is used to acquire high resolution images of multiple chemical components of a topical formulation as it penetrates into mammalian skin. This technique uniquely provides label-free, nondestructive, three-dimensional images with high spatiotemporal resolution. It reveals novel features of (trans)dermal drug delivery in the tissue environment: different rates of drug penetration via hair follicles as compared to the intercellular pathway across the stratum corneum are directly observed, and the precipitation of drug crystals on the skin surface is visualized after the percutaneous penetration of the cosolvent excipient in the formulation. The high speed three-dimensional imaging capability of SRS thus reveals features that cannot be seen with other techniques, providing both kinetic information and mechanistic insight into the (trans)dermal drug delivery process.
Secretory Leukocyte Protease Inhibitor Inhibits Infection of Monocytes and Lymphocytes with Human Immunodeficiency Virus Type 1 but Does Not Interfere with Transcytosis of Cell-Associated Virus across Tight Epithelial Barriers (2000)

In the present study, we demonstrate that recombinant human secretory leukocyte protease inhibitor (rhSLPI) inhibits infection of lymphocyte- and monocyte-derived tumor cell lines and peripheral blood lymphocytes with laboratory-adapted isolates and with the primary isolate, NDK, of free human immunodeficiency virus type 1 (HIV-1). In contrast, rhSLPI did not exhibit inhibitory activity toward transcytosis of cell-associated HIV-1 through a tight monolayer of endometrial epithelial cells. These observations indicate that the inhibitory effect of SLPI is restricted to free HIV-1 in corporal fluids.
A Pilot Symbol Pattern Enabling Data Recovery Without Side Information in PTS-Based OFDM Systems (2011)

Partial transmit sequence (PTS) scheme is one of the most popular peak-to-average power ratio (PAPR) reduction schemes for orthogonal frequency division multiplexing (OFDM) systems. In the PTS scheme, one OFDM symbol is partitioned into disjointed sub-blocks, and each sub-block is multiplied by a phase factor to generate signals with low PAPR. For data recovery, receivers must have side information (SI), e.g., phase factors, from transmitters. In this letter, a novel data recovery scheme in PTS-based OFDM systems without SI is proposed. In the proposed scheme, an additional pilot symbol is intentionally inserted at the end of each sub-block, so that efficient data decoding based on channel estimation can be executed with known pilot symbols. Simulation results show that the BER performance of the proposed scheme without SI is approximately the same as those of the PTS scheme with perfect SI and a maximum likelihood decoding scheme. Considering the cost for SI encoding and decoding, the proposed scheme is practically more advantageous over the PTS scheme.
Sociotechnical Considerations for Accessible Visualization Design (2019)

Accessibility-the process of designing for people with disabilities (PWD)-is an important but under-explored challenge in the visualization research community. Without careful attention, and if PWD are not included as equal participants throughout the process, there is a danger of perpetuating a vision-first approach to accessible design that marginalizes the lived experience of disability (e.g., by creating overly simplistic "sensory translations" that map visual to non-visual modalities in a one-to-one fashion). In this paper, we present a set of sociotechnical considerations for research in accessible visualization design, drawing on literature in disability studies, tactile information systems, and participatory methods. We identify that using state-of-the-art technologies may introduce more barriers to access than they remove, and that expectations of research novelty may not produce outcomes well-aligned with the needs of disability communities. Instead, to promote a more inclusive design process, we emphasize the importance of clearly communicating goals, following existing accessibility guidelines, and treating PWD as equal participants who are compensated for their specialized skills. To illustrate how these considerations can be applied in practice, we discuss a case study of an inclusive design workshop held in collaboration with the Perkins School for the Blind.
Thyrocytes from Autoimmune Thyroid Disorders Produce the Chemokines IP-10 And Mig and Attract CXCR3+ Lymphocytes (2001)

To better understand the selective migration of lymphocytes in autoimmune thyroid disorders (AITDs), we analyzed thyroid samples and demonstrated an enhanced expression of the chemokines interferon (IFN)-inducible protein (Ip)-10 and regulated on activation normal T lymphocyte expressed and secreted (RANTES) in thyroids from AITD patients. Ip-10 and monokine induced by IFN-gamma (Mig) were expressed in vivo in thyroid follicular cells (TFCs) from AITD thyroids. Interestingly, Ip-10 mRNA, although not basally detected in cultured TFCs, was strongly induced by IFN-gamma and synergistically increased by TNF-alpha addition. Furthermore, high levels of Ip-10 protein were detected in the supernatants of IFN-gamma-stimulated TFCs. Likewise, Mig protein was strongly induced in TFCs by the same stimuli as Ip-10. Unlike Ip-10 and Mig, the expression of RANTES was induced mainly by TNF-alpha. In addition, intrathyroidal lymphocytes from AITD patients showed higher expression of CXCR3, CCR2, and CCR5 chemokine receptors than autologous peripheral blood lymphocytes. T lymphoblasts expressing CXCR3 showed an increased migration to supernatants from stimulated TFCs, which was abolished by specific antibodies to the chemokines Ip-10 and Mig, as well as to their receptor CXCR3. Taken together, these data suggest a potential role of TFCs, through the production of the chemokines Ip-10, Mig and RANTES, in regulating the recruitment of specific subsets of activated lymphocytes in AITDs.
Neuroprosthetic-enabled control of graded arm muscle contraction in a paralyzed human (2017)

Neuroprosthetics that combine a brain computer interface (BCI) with functional electrical stimulation (FES) can restore voluntary control of a patients' own paralyzed limbs. To date, human studies have demonstrated an "all-or-none" type of control for a fixed number of pre-determined states, like hand-open and hand-closed. To be practical for everyday use, a BCI-FES system should enable smooth control of limb movements through a continuum of states and generate situationally appropriate, graded muscle contractions. Crucially, this functionality will allow users of BCI-FES neuroprosthetics to manipulate objects of different sizes and weights without dropping or crushing them. In this study, we present the first evidence that using a BCI-FES system, a human with tetraplegia can regain volitional, graded control of muscle contraction in his paralyzed limb. In addition, we show the critical ability of the system to generalize beyond training states and accurately generate wrist flexion states that are intermediate to training levels. These innovations provide the groundwork for enabling enhanced and more natural fine motor control of paralyzed limbs by BCI-FES neuroprosthetics.
A 3D structure model of the melibiose permease of Escherichia coli represents a distinctive fold for Na + symporters (2009)

The melibiose permease of Escherichia coli (MelB) catalyzes the coupled stoichiometric symport of a galactoside with a cation (either Na(+), Li(+), or H(+)), using free energy from the downhill translocation of one cosubstrate to catalyze the accumulation of the other. Here, we present a 3D structure model of MelB threaded through a crystal structure of the lactose permease of E. coli (LacY), manually adjusted, and energetically minimized. The model contains 442 consecutive residues ( approximately 94% of the polypeptide), including all 12 transmembrane helices and connecting loops, with no steric clashes and superimposes well with the template structure. The electrostatic surface potential calculated from the model is typical for a membrane protein and exhibits a characteristic ring of positive charges around the periphery of the cytoplasmic side. The 3D model indicates that MelB consists of two pseudosymmetrical 6-helix bundles lining an internal hydrophilic cavity, which faces the cytoplasmic side of the membrane. Both sugar and cation binding sites are proposed to lie within the internal cavity. The model is consistent with numerous previous mutational, biochemical/biophysical characterizations as well as low-resolution structural data. Thus, an alternating access mechanism with sequential binding is discussed. The proposed overall fold of MelB is different from the available crystal structures of other Na(+)-coupled transporters, suggesting a distinctive fold for Na(+) symporters.
Frequency of regulatory T cells in peripheral blood and in tumour‐infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma (2010)

• Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.