gebhart/patrepeval huggingface dataset:
Mesenchymal cells isolation from Wharton’s jelly, in perspective to clinical applications (2011)

Recent years have seen progress in isolation and expansion of mesenchymal cells (MSCs) from human umbilical cord tissue, namely the Wharton’s jelly. Situated between the subamnion and the perivascular zone that surrounds the blood vessels (Troyer & Weiss, 2008), Wharton’s jelly is a matrix of mucous connective tissue, composed of fibroblast-like stromal cells, collagen fibers and proteoglycans, mainly hyaluronic acid (Can & Karahuseyinoglou, 2007). Several studies have demonstrated the proliferative capacity and multipotentiality of these stromal cells; they were shown to differentiate into a neural phenotype in vitro (Mitchell et al., 2003; Ma et al., 2005; Yang et al., 2005; Lu et al., 2006; Ma et al., 2006; Karahuseyinoglou et al., 2007) and into chondrocytes (Wang et al., 2004; Karahuseyinoglou et al., 2007), osteocytes (Wang et al., 2004; Sarugaser et al., 2005; Conconi et al., 2006; Karahuseyinoglou et al., 2007), cardiomyocytes (Wang et al., 2004), skeletal myocytes (Conconi et al., 2006), adipocytes (Conconi et al., 2006; Lu et al., 2006; Mesenchymal cells isolation from Wharton’s jelly, in perspective to clinical applications
Proteolysis of smooth muscle myosin light chain kinase. Formation of inactive and calmodulin-independent fragments. (1987)

Proteolysis by trypsin of gizzard myosin light chain kinase in the absence of Ca2+-calmodulin causes a biphasic effect on kinase activity. During the initial phase of proteolysis, Ca2+-calmodulin-dependent kinase activity is reduced over a thousand-fold. Further proteolysis, in the second phase, causes an increase in activity that is independent of Ca2+-calmodulin. Loss of activity is associated with the formation of a 64,000-dalton fragment. Calmodulin-independent activity is associated with the formation of a 61,000-dalton fragment. Procedures for the isolation of each fragment are outlined. Tryptic hydrolysis of the isolated 64,000-dalton peptide generates the 61,000-dalton peptide and increases calmodulin-independent activity. Km values for ATP and light chains for the native kinase and two fragments are the same, i.e. approximately 100 and 5 microM, respectively. Neither fragment binds to F-actin. Amino acid analyses of both fragments are given. Synthetic peptides corresponding to the calmodulin-binding regions of the smooth and skeletal muscle kinases are potent inhibitors of the 61,000-dalton fragment. These data demonstrate the existence of an inhibitory region that is suggested to be located between the active site and the calmodulin-binding site. Whether it is distinct from or at the N-terminal end of the calmodulin-binding site cannot be determined from these data.
Mice Lacking Bioactive IL-12 Can Generate Protective, Antigen-Specific Cellular Responses to Mycobacterial Infection Only if the IL-12 p40 Subunit Is Present (2002)

Recent evidence suggests that absence of the IL-12p40 subunit is more detrimental to the generation of protective responses than is the absence of the p35 subunit. To determine whether this is the case in tuberculosis, both p35 and p40 knockout mice were infected with Mycobacterium tuberculosis. Mice lacking the p40 subunit were highly susceptible to increased bacterial growth, exhibited reduced production of IFN-gamma, and had increased mortality. In contrast, mice lacking the p35 subunit exhibited a moderate ability to control bacterial growth, were able to generate Ag-specific IFN-gamma responses, and survived infection longer. The superior Ag-specific responses of the p35 gene-disrupted mice, when compared with the p40 gene-disrupted mice, suggest that the p40 subunit may act other than as a component of IL-12. A candidate molecule capable of driving the protective responses in the p35 gene-disrupted mice is the novel cytokine IL-23. This cytokine is composed of the IL-12 p40 subunit and a p19 subunit. In support of a role for this cytokine in protective responses to M. tuberculosis, we determined that the p19 subunit is induced in the lungs of infected mice.
Chemoprotectants for cancer chemotherapy. (1991)

Maximal dosing of cytotoxic chemotherapy drugs is often limited by the development of severe nonmyelosuppressive toxicities. Numerous studies have demonstrated that sulfur-containing nucleophiles can antagonize the dose-limiting effects of alkylating agents on the genitourinary tract. Examples include the use of sodium thiosulfate to prevent cisplatin-induced renal tubular necrosis and the use of sulfhydryl-containing compounds like N-acetylcysteine and 2-mercaptoethanesulfonate (mesna) to block oxazophosphorine-induced bladder toxicity. Mesna does not block the antitumor action of oxazophosphorines due to its rapid formation of the inactive dimer dimesna in the bloodstream. The active monomer is selectively reduced from dimesna in renal tubule cells, thereby limiting the inactivation of toxins like acrolein to the genitourinary tract. Recent clinical trials suggest that oral mesna has adequate bioavailability (roughly 50% by urinary thiol measurements) to prevent urotoxicity in high-dose ifosfamide regimens. In addition, mesna is stable in aqueous oral formulations. This may facilitate more convenient oral mesna dosing in protocols using high-dose cyclophosphamide or ifosfamide. Whereas agents like mesna and sodium thiosulfate complex directly with activated (electrophilic) alkylator species, chemoprotectants for the anthracyclines appear to complex with metal cofactors like iron, which are required for the production of cardiotoxicity. Several ethylenediaminetetraacetic-like agents have been evaluated, and a water-soluble piperazinyl derivative, ICRF-187, is currently undergoing clinical evaluation in patients receiving large cumulative doxorubicin doses. An initial clinical trial suggests that ICRF-187 can prevent doxorubicin-induced cardiomyopathy. As with mesna, ICRF-187 does not block the myelosuppressive or the antitumor effects of doxorubicin. Overall, these studies show that site-selective chemoprotection is now feasible for at least two major classes of anticancer agents.
Disruption of an Internal Membrane-Spanning Region in Shiga Toxin 1 Reduces Cytotoxicity (1998)

Shiga toxin type 1 (Stx1) belongs to the Shiga family of bipartite AB toxins that inactivate eukaryotic 60S ribosomes. The A subunit of Stxs are N-glycosidases that share structural and functional features in their catalytic center and in an internal hydrophobic region that shows strong transmembrane propensity. Both features are conserved in ricin and other ribosomal inactivating proteins. During eukaryotic cell intoxication, holotoxin likely moves retrograde from the Golgi apparatus to the endoplasmic reticulum. The hydrophobic region, spanning residues I224 through N241 in the Stx1 A subunit (Stx1A), was hypothesized to participate in toxin translocation across internal target cell membranes. The TMpred computer program was used to design a series of site-specific mutations in this hydrophobic region that disrupt transmembrane propensity to various degrees. Mutations were synthesized by PCR overlap extension and confirmed by DNA sequencing. Mutants StxAF226Y, A231D, G234E, and A231D-G234E and wild-type Stx1A were expressed in Escherichia coli SY327 and purified by dye-ligand affinity chromatography. All of the mutant toxins were similar to wild-type Stx1A in enzymatic activity, as determined by inhibition of cell-free protein synthesis, and in susceptibility to trypsin digestion. Purified mutant or wild-type Stx1A combined with Stx1B subunits in vitro to form a holotoxin, as determined by native polyacrylamide gel electrophoresis immunoblotting. StxA mutant A231D-G234E, predicted to abolish transmembrane propensity, was 225-fold less cytotoxic to cultured Vero cells than were the wild-type toxin and the other mutant toxins which retained some transmembrane potential. Furthermore, compared to wild-type Stx1A, A231D-G234E Stx1A was less able to interact with synthetic lipid vesicles, as determined by analysis of tryptophan fluorescence for each toxin in the presence of increasing concentrations of lipid membrane vesicles. These results provide evidence that this conserved internal hydrophobic motif contributes to Stx1 translocation in eukaryotic cells.
Fieldwork (2018)

Abstract Fieldwork involves long‐term research in which the investigator spends an intensive amount of time inquiring into the way of life of a specific human population. Used properly, it can result in extremely useful portraits of little‐known, misunderstood, or fully unknown ways of life. The main goal is to learn an inside point of view, or what it is like to live as a member of a specific sociocultural formation. Instead of relying on the statistical methods of quantitative research, fieldworkers gather information through a wide variety of ethnographic or qualitative methods. The reliability issue is dealt with through comparing information gathered through more than one research method and by analyzing information in relation to the broader context (e.g., economic, political, religious, institutional). Reliability may also be checked more formally through the use of simple counting schedules. Key methods include participant observation, several kinds of interviewing techniques, and self‐reporting methods. The researcher is always the first and primary research instrument of fieldwork. The key to fieldwork lies in the relationship of mutual trust established between the researcher and those with whom s/he is working. Without such a relationship, productive fieldwork is not possible.
Immunotherapeutics of multiple sclerosis. (1991)

Immunosuppressive therapy may act specifically by inhibiting a certain stage of the immune response, or, by contrast, by inducing an overall inhibition of the immune system. Low dosage, a specific immunosuppressive therapeutic protocols with corticosteroids or azathioprine are used routinely, although there is no evidence of their effects. There are, however, unquestionable data on the numerous (and serious) side effects. High dosage, a specific immunosuppression appears to be better tolerated (probably due to the brevity of the treatment) and to have certain immunodepressant effects within the CNS. ACTH and methylprednisolone are recommended for short-term relapse therapy. Specific immunosuppressive treatment will no doubt be part of future autoimmune disease therapy, but for the time being is no more than theoretically stimulating experimentation (anti-idiotypic monoclonal antibodies, specific T cell suppressor factor, T cell "vaccination"). Important multicentric studies on cyclosporin-A and copolymer 1 are almost complete on the numerous side effects as regard to cyclosporin-A. Clinical trials with alpha or beta-interferons are still in progress and, so far at least, these drugs appear to be characterized by the absence of important side effects.
Inhibition of epidermal Langerhans cell function by low dose ultraviolet B radiation. Ultraviolet B radiation selectively modulates ICAM-1 (CD54) expression by murine Langerhans cells (1991)

Immunosuppressive effects of low levels of ultraviolet B (UVB) radiation on cutaneous immune responses have been attributed to deleterious effects of UVB radiation on epidermal Langerhans cells (LC). To determine how UVB radiation modulates LC function we examined the effect of in vitro UVB exposure on LC accessory cell activity and surface phenotype. Exposure of BALB/c murine epidermal cells to low dose (less than or equal to 200 J/m2) UVB radiation in vitro inhibited their ability to support the mitogenic response of unstimulated, accessory cell-depleted splenic T cells to anti-CD3 mAb. LC accessory cell activity was also inhibited when LC were exposed to UVB radiation in situ, although several-fold higher doses of UVB radiation were required to achieve complete inhibition of LC function. This dose-dependent inhibition was mediated through a direct effect on LC that could not be reversed by IL-1 or IL-6 alone or in combination, or granulocyte-macrophage-CSF. TNF-alpha did not inhibit LC accessory cell function in this assay and anti-TNF-alpha neutralizing antibodies did not reverse the inhibitory effects of UVB radiation. UVB irradiated LC failed to participate in the anti-CD3-dependent clustering that normally occurs between T cells and LC during the proliferative response of murine T cells to anti-CD3 mAb, suggesting that UV radiation may interfere with accessory cell function by preventing intercellular adhesion. Two-color flow cytometric studies revealed low levels of the ICAM-1 on freshly isolated LC and some keratinocytes. ICAM-1 expression on LC increased 15 to 20-fold within the first 24 h in vitro and continued to increase during a 72-h culture period. The integrin LFA-1 was not identified on freshly isolated or cultured LC but was detected on responding T cells. Prior exposure of LC to UVB radiation (50 or 100 J/m2) inhibited the increase in ICAM-1 expression that normally occurs in vitro by up to 70% whereas surface levels of class II MHC Ag, CD45 and Fc-gamma receptors were not affected. Blocking studies revealed that anti-CD3 induced T cell proliferation and T cell-LC cluster formation was inhibited by both anti-LFA-1 and anti-ICAM-1 mAb suggesting that ICAM-1 expressed on LC must bind to LFA-1 on T cells to facilitate proliferative responses of T cells to anti-CD3 mAb. We conclude that the in vitro inhibitory effects of low dose UVB radiation on LC accessory function may result because UVB radiation prevents upregulation of ICAM-1 expression by LC in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Thermal properties of the optically transparent pore-free nanostructured yttria-stabilized zirconia (2009)

The authors report results of investigation of thermal conductivity of nanocrystalline yttria-stabilized zirconia. The optically transparent pore-free bulk samples were prepared via the spark plasma sintering process to ensure homogeneity. Thermal conductivity K was measured by two different techniques. It was found that the pore-free nanostructured bulk zirconia is an excellent thermal insulator with the room-temperature K∼1.7–2.0 W/m K. It was also shown that the “phonon-hopping” model can accurately describe specifics of K dependence on temperature and the grain size. The obtained results are important for optimization of zirconia properties for specific applications in advanced electronics and coatings.
A mixture model-based approach to the clustering of microarray expression data (2002)

EMMIX-GENE is available at http://www.maths.uq.edu.au/~gjm/emmix-gene/
Western Areas looks to the drill bit (2017)

Western Areas Ltd is set for a bumper second half of FY2017 after returning to profit for the first half.
La particule mais est-elle une conjonction ? (2010)

On se propose de montrer que l’emploi argumentatif de « mais » ne relie pas deux énoncés, ou plutôt deux jugements – entendant par « jugement » le contenu sémantique propre des énoncés. Bien sûr, c’est là une de ses caractéristiques grammaticales, l’emploi argumentatif de « mais » a une portée double mais les deux éléments reliés n’ont pas, selon nous, le même rôle et la particule ne relie pas un jugement à un autre jugement. Après une première partie consacrée à cette thèse négative, on montre, de manière cette fois positive, que « mais » a pour fonction fondamentale de construire une négation partielle : tout emploi argumentatif de « mais » fait en quelque sorte le tri à l’intérieur de la signification d’un des segments qu’il relie, en marquant que le locuteur exclut telle partie de son sens et affirme telle autre.
Joint Learning of Facial Expression and Head Pose from Speech (2018)

Natural movement plays a significant role in realistic speech animation, and numerous studies have demonstrated the contribution visual cues make to the degree human observers find an animation acceptable.Natural, expressive, emotive, and prosodic speech exhibits motion patterns that are difficult to predict with considerable variation in visual modalities.Recently, there have been some impressive demonstrations of face animation derived in some way from the speech signal.Each of these methods have taken unique approaches, but none have included rigid head pose in their predicted output.We observe a high degree of correspondence with facial activity and rigid head pose during speech, and exploit this observation to jointly learn full face animation and head pose rotation and translation combined.From our own corpus, we train Deep Bi-Directional LSTMs (BLSTM) capable of learning long-term structure in language to model the relationship that speech has with the complex activity of the face.We define a model architecture to encourage learning of rigid head motion via the latent space of the speaker's facial activity.The result is a model that can predict lip sync and other facial motion along with rigid head motion directly from audible speech.
Abstract P4-15-14: Preclinical data of SYD985 support the clinical investigation of this novel anti-HER2 antibody-drug conjugate in breast cancer patients with low levels of HER2 expression (2015)

Abstract SYD985 is a novel anti-HER2 antibody-drug conjugate (ADC) in development for breast cancer. The ADC consists of three parts: i) the monoclonal antibody trastuzumab, ii) a linker that can be cleaved by tumor-resident proteases at the dipeptide valine-citrulline (vc) motif, and iii) the prodrug seco-DUocarmycin-hydroxyBenzamide-Azaindole. The average ‘drug to antibody ratio’ (DAR) of this ADC, also named trastuzumab vc-seco-DUBA, is ∼2.8. After antibody-mediated binding of SYD985 to its molecular target HER2 on the surface of tumor cells, the ADC is internalized. Subsequently, the active duocarmycin is released and binds to DNA in the minor groove, followed by alkylation of the DNA and killing of the tumor cells. In vitro and in vivo experiments were performed to (directly) compare various pharmacodynamic and pharmacokinetic properties of SYD985 with those of the most progressed (marketing-approved) HER2-targeting ADC, i.e. ado-trastuzumab emtansine (T-DM1). T-DM1 is currently indicated for second line treatment of breast cancer patients overexpressing HER2 tumor tissue. In in vitro experiments, SYD985 shows potencies similar to T-DM1 in cell lines expressing HER2 at high levels (IHC HER2 3+), whereas SYD985 is significantly more potent compared to T-DM1 in cell lines expressing low HER2 levels (IHC HER2 2+ or 1+). In line with these results, SYD985 has superior efficacy compared to T-DM1 in xenograft models in which patient-derived breast cancer tumor tissue with low HER2 levels (IHC HER2 2+ or 1+/FISH-) have been used. Pharmacokinetic experiments (in vitro and in vivo) have revealed that whereas in mice SYD985 has limited stability, in cynomolgus monkey SYD985 is very stable. Excellent stability in vitro is also observed in human plasma. Moreover, after i.v. administration of SYD985 in the cynomolgus monkey the amount of free toxin (DUBA) detected in the monkey plasma is many-fold lower than levels reported for the toxin (DM1) released from T-DM1. Resuming, the preclinical data of SYD985 support clinical studies to investigate whether SYD985 has benefit in cancer patients with moderate or even low HER2 levels of the tumor tissue. Citation Format: Gijs Verheijden, Patrick Beusker, Ruud Ubink, Miranda van der Lee, Patrick Groothuis, Peter Goedings, David Egging, Marco Timmers, Wim Dokter. Preclinical data of SYD985 support the clinical investigation of this novel anti-HER2 antibody-drug conjugate in breast cancer patients with low levels of HER2 expression [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-14.
A Comparative Study between RTL and HLS for Image Processing Applications with FPGAs (2016)

High-level synthesis (HLS) and register transfer level (RTL) are two popular methods to design FPGAs. Both of methods have advantages and disadvantages: HLS provides ease of development, and is less prone to error. Thus, it reduces the development time significantly when designing a hardware system. On the other hand, RTL development enables the developer to make lower level design decisions which can increase the performance and efficiency of the system. Although there have been several studies on comparing HLS and RTL in terms of cost, performance, and area for higher level applications, these studies do not make a one-on-one comparison on the micro-architectural details of a given application. In this thesis, we take further steps to compare HLS and RTL by analyzing the lower level micro-architectural details in HLS and RTL designs for the same applications. We also provide guidelines on how to create these architectures efficiently in both methods. We investigate several image processing algorithms and their designs in RTL and HLS. The algorithms were selected based on their ubiquitous nature and widespread use in image processing applications. We show that if HLS is used to its full potential, it can achieve comparable level of performance as the systems designed using RTL.
Polymeric coatings that inactivate both influenza virus and pathogenic bacteria (2006)

Painting a glass slide with branched or linear N,N-dodecyl methyl-polyethylenimines (PEIs) and certain other hydrophobic PEI derivatives enables it to kill influenza virus with essentially a 100% efficiency (at least a 4-log reduction in the viral titer) within minutes, as well as the airborne human pathogenic bacteria Escherichia coli and Staphylococcus aureus. For most of the coating polyions, this virucidal action is shown to be on contact, i.e., solely by the polymeric chains anchored to the slide surface; for others, a contribution of the polyion leaching from the painted surface cannot be ruled out. A relationship between the structure of the derivatized PEI and the resultant virucidal activity of the painted surface has been elucidated.
Topological analysis of the major protein in isolated intact rat liver gap junctions and gap junction-derived single membrane structures. (1987)

The topological organization of the major rat liver gap junction protein has been examined in intact gap junctions and gap junction-derived single membrane structures. Two methods, low pH and urea at alkaline pH, were used to "transform" or "split" double membrane gap junctions into single membrane structures. Low pH treatment "transforms" rat liver gap junctions into small single membrane vesicles which have an altered sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile after digestion with L-1-to-sylamido-2-phenylethylchloromethyl ketone-trypsin. Alkaline pH treatment in the presence of 8 M urea can split isolated rat liver gap junctions into single membrane sheets which have no detectable structural alteration or altered sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile after proteolytic digestion, suggesting that these single membrane sheets may be useful for topological studies of the gap junction protein. Proteolytic digestion studies have been used to localize the carboxyl terminus of the molecule on the cytoplasmic surface of the intact gap junction. However, the amino terminus does not appear to be accessible to proteases or to interaction with an antibody that is specific for the amino-terminal region of the molecule in intact or split gap junctions. Binding of antibodies, that block junctional channel conductance, can be eliminated by proteolytic digestion of intact gap junctions, suggesting that all antigenic sites for these antibodies are located on the cytoplasmic surface of the intact gap junction. In addition, calmodulin gel overlays indicate that at least two calmodulin binding sites exist on the cytoplasmic surface of the junctional protein. The information generated from these studies has been used to develop a low resolution two-dimensional model for the organization of the major rat liver gap junctional protein in the junctional membrane.