gebhart/patrepeval huggingface dataset:
Long Functionalized Poly(ethylene glycol)s of Defined Molecular Weight: Synthesis and Application in Solid-Phase Synthesis of Conjugates (2008)

A concise synthesis of long-chain poly(ethylene glycol) (PEG) of defined molecular weight up to 29 ethyleneoxy units is described. These PEG diols were converted in a two-step synthesis into Fmoc-protected PEG amino acids, suitable as long linkers and compatible with solid-phase peptide synthesis. Long PEG chains (MW > 1000) can be readily synthesized with this method, which has the advantage of defined single molecular weight products over the comparable commercial polymers. The application of these PEG linkers to the synthesis of peptide-PEG-folate conjugates on a solid support was investigated. A method for the solid support synthesis of the targeting component of the conjugate, folic acid-cysteine, was developed, resulting in improved yields with respect to literature methods. The assembly of the peptide, PEG linker, and targeting group on solid support resulted in the synthesis of a conjugate of defined molecular weight and structure.
MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation (2020)

Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) constitute a mammalian STE20-like serine/threonine kinase subfamily. Recent studies provide substantial evidence for MAP4K family kinases in the Hippo pathway regulation, suggesting a broad role of MAP4Ks in human physiology and diseases. However, a comprehensive analysis of the regulators and effectors for this key kinase family has not been fully achieved. Using a proteomic approach, we define the protein-protein interaction network for human MAP4K family kinases and reveal diverse cellular signaling events involving this important kinase family. Through it, we identify a STRIPAK complex component, STRN4, as a generic binding partner for MAP4Ks and a key regulator of the Hippo pathway in endometrial cancer development. Taken together, the results of our study not only generate a rich resource for further characterizing human MAP4K family kinases in numerous biological processes but also dissect the STRIPAK-mediated regulation of MAP4Ks in the Hippo pathway.
Toward the Discovery of Vaccine Adjuvants: Coupling In Silico Screening and In Vitro Analysis of Antagonist Binding to Human and Mouse CCR4 Receptors (2009)

Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice.
Transcription Factors Recognizing Overlapping C1-A2 Binding Sites Positively Regulate Insulin Gene Expression (2001)

Transcription factors binding the insulin enhancer region, RIPE3b, mediate beta-cell type-specific and glucose-responsive expression of the insulin gene. Earlier studies demonstrate that activator present in the beta-cell-specific RIPE3b1-binding complex is critical for these actions. The DNA binding activity of the RIPE3b1 activator is induced in response to glucose stimulation and is inhibited under glucotoxic conditions. The C1 element within the RIPE3b region has been implicated as the binding site for RIPE3b1 activator. The RIPE3b region also contains an additional element, A2, which shares homology with the A elements in the insulin enhancer. Transcription factors (PDX-1 and HNF-1 alpha) binding to A elements are critical regulators of insulin gene expression and/or pancreatic development. Hence, to understand the roles of C1 and A2 elements in regulating insulin gene expression, we have systematically mutated the RIPE3b region and analyzed the effect of these mutations on gene expression. Our results demonstrate that both C1 and A2 elements together constitute the binding site for the RIPE3b1 activator. In addition to C1-A2 (RIPE3b) binding complexes, three binding complexes that specifically recognize A2 elements are found in nuclear extracts from insulinoma cell lines; the A2.2 complex is detected only in insulin-producing cell lines. Furthermore, two base pairs in the A2 element were critical for binding of both RIPE3b1 and A2.2 activators. Transient transfection results indicate that both C1-A2 and A2-specific binding activators cooperatively activate insulin gene expression. In addition, RIPE3b1- and A2-specific activators respond differently to glucose, suggesting that their overlapping binding specificity and functional cooperation may play an important role in regulating insulin gene expression.
A Hheuristic for Non-bifurcated Routing in Communication Networks (1986)

This paper considers the routing problem in session-based communication network, particularly where the pattern of message transmission is characterized by non-bifurcated traffic flows. Due to the discreteness property of its solution space, the problem is formulated as normalized mlticommodity network flows with integer restrictions and an effective penalty system is suggested to solve it. To show its effectiveness, a simple example and a preliminary computational experience are provided. Finally, numerous application areas of the algorithm are suggested.
VASCULAR BIOLOGY OF ENDOTHELIN SIGNAL TRANSDUCTION (1999)

1. Endothelins regulate cell function by interacting with two classes of cell surface receptors, ETA and ETB receptors. Both receptor types are members of the heptahelical transmembrane-spanning receptor superfamily and couple via G-proteins to multiple intracellular effectors. 2. Many of the cellular responses induced by endothelins are mediated by changes in cytoplasmic Ca2+ concentration. Stimulation of inositol 1,4,5-trisphosphate (IP3) formation promotes release of Ca2+ from intracellular stores via IP3-sensitive Ca2+ channels. This mechanism accounts for the initial transient peak of the Ca2+ elevation. The entry of Ca2+ across the plasma membrane through multiple types of Ca2+ channels is responsible for the sustained phase of Ca2+ elevation and, together, both mechanisms regulate cell function. 3. Endothelin-mediated Ca2+ signals vary markedly in duration, spatial organization and temporal pattern. The elevations in Ca2+ are sustained, transient or oscillatory and occur either globally or are localized to discrete spatial domains. These different Ca2+ signals, which are dependent on the availability of specific ion channels, control distinct cellular functions. Ryanodine-sensitive Ca2+ release channels may be important in determining the organization of the Ca2+ signal. 4. Endothelin-induced Ca2+ elevations near the plasma membrane stimulate the opening of Ca(2+)-dependent K+ and Cl- channels. These channels are key regulators of membrane potential and, consequently, regulate the activity of voltage-dependent Ca2+ influx pathways. 5. Endothelin regulates the growth and differentiation of cells. It markedly potentiates the mitogenic response of other growth factors, an effect that involves activation of the mitogen-activated protein kinase cascade and induction of early response genes. 6. Finally, the vascular actions of endothelin are influenced by the relative expression of specific ion channels, the spatial and temporal pattern of the Ca2+ signal and the cellular composition of the vascular wall.
RTX proteins: a highly diverse family secreted by a common mechanism (2010)

Repeats-in-toxin (RTX) exoproteins of Gram-negative bacteria form a steadily growing family of proteins with diverse biological functions. Their common feature is the unique mode of export across the bacterial envelope via the type I secretion system and the characteristic, typically nonapeptide, glycine- and aspartate-rich repeats binding Ca(2+) ions. In this review, we summarize the current state of knowledge on the organization of rtx loci and on the biological and biochemical activities of therein encoded proteins. Applying several types of bioinformatic screens on the steadily growing set of sequenced bacterial genomes, over 1000 RTX family members were detected, with the biological functions of most of them remaining to be characterized. Activities of the so far characterized RTX family members are then discussed and classified according to functional categories, ranging from the historically first characterized pore-forming RTX leukotoxins, through the large multifunctional enzymatic toxins, bacteriocins, nodulation proteins, surface layer proteins, up to secreted hydrolytic enzymes exhibiting metalloprotease or lipase activities of industrial interest.
Genetic immunization of mice with human tyrosinase-related protein 2: Implications for the immunotherapy of melanoma (2000)

The melanosomal protein TRP2 expressed by melanocytes and most melanoma cells is an attractive, clinically relevant model antigen for the experimental development of melanoma immunotherapy in mice. A peptide shared by murine and human TRP2 can be recognized by melanoma-reactive CTL in C57BL/6 mice, as well as in human melanoma patients. Previous experiments demonstrated that gene gun immunization of mice with plasmid DNA encoding autologous murine TRP2 was unable to induce protective immunity against B16 melanoma cells naturally expressing TRP2. In the present study, we investigated whether the use of cDNA encoding xenogeneic human TRP2, which is highly homologous to murine TRP2, would be more effective. Genetic immunization of mice with human TRP2 resulted in coat depigmentation as a sign of autoimmune-mediated destruction of melanocytes and provided significant protection against metastatic growth of B16 melanoma Induction of protective immunity was associated with TRP2-reactive antibodies and CD8+ T cells. Furthermore, immunization with recombinant adenovirus was more effective than immunization with plasmid DNA using the gene gun. Our results provide new insights for the development of antigen-specific immunotherapy of melanoma.
ChemInform Abstract: Asymmetric Synthesis of Fluorinated L‐Tyrosine and meta‐L‐Tyrosines. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Olvidados discursos formalistas (2015)

Un documentado artículo de Javier Monedero (La forma como molde. La forma como proceso) recorría, primeramente y bajo un principio evolutivo, la historia del pensamiento hasta la Gestalt, para luego detenerse en aquellas teorías contemporáneas que fundamentan un carácter procesual –y en cierto modo espontáneo– tanto en el arte como en la arquitectura de las últimas décadas. Ahora, en Olvidados discursos formalistas se contempla la relevancia filosófica de otras reflexiones en torno a la naturaleza, además de las focalizadas en la disciplina de la estética. De hecho, la línea argumental que vamos a explorar está organizada a partir de dos grandes relatos: uno conectado a la biología, que tendría su origen en el concepto de morfología de Goethe; mientras el otro estaría relacionado con la escuela de la pura visualidad, cuyas raíces se sitúan en las ideas de Kant, llegando a constituir una de las vertientes más importantes del formalismo.
Detection wavelength of very long wavelength quantum-well infrared photodetector (2003)

Based on a detailed discussion of the energy band structure and optical transitions in very long wavelength () GaAs/AlGaAs quantum well infrared photodetectors (QWIPs), we have built a practical QWIP model. We have studied various key factors that determine the photogenerated carriers and detection wavelength of very long wavelength QWIPs. Consequently, we have found and confirmed a distinctive difference between the photocurrent of QWIPs with only one confined state in the quantum well (QW) and those binding two confined states, which resulted in a different dependence of the detection wavelength on the QW width. Also, we have discussed the dependence of the response wavelength on several other parameters for very long wavelength QWIPs, such as barrier width and Al mole fraction. Afterwards, a series of very long wavelength QWIP devices have been fabricated and measured, whose photocurrents are well reproduced by our calculation. Based on the theoretical model and experimental data, a simple and convenient polynomial equation has been deduced, using structure parameters of very long wavelength QWIPs to calculate the detection wavelength and offering convenience in device designing.
Basic fibroblast growth factor accumulates in the nuclei of various bFGF‐producing cell types (1990)

The intracellular localization of basic fibroblast growth factor (bFGF) was studied in BHK-21 cells transfected with an expression vector containing the complementary DNA (cDNA) of the human bFGF gene (pbFGF). The intracellular location of bFGF was determined using indirect immunofluorescence. The antibodies used were polyclonal antibodies directed against either recombinant human bFGF or recombinant Xenopus bFGF. The nuclei of transfected cells that produce bFGF, but not the nuclei of untransfected cells, were labeled strongly by the antibodies. The nuclear staining was totally abolished when anti-bFGF antibodies preadsorbed with bFGF were used. Several types of endothelial cells known to produce bFGF were also stained in their nuclei by the antibodies. Nuclear extracts prepared from transfected cells were found to contain bFGF as determined using heparin-sepharose affinity chromatography, followed by Western blot analysis of fractions, which stimulated the proliferation BHK-21 cells. The mitogenic activity associated with the nuclei was not destroyed when isolated cell nuclei were digested by trypsin. It is therefore likely that the nucleus associated bFGF is intranuclear. These findings suggest that some biological activities of bFGF may be mediated by nuclear bFGF binding proteins or by the direct binding of bFGF to DNA.
Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy (2001)

Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play an important role in angiogenesis associated with tumor growth and metastasis. VEGF exerts its biologic activities through 2 transmembrane tyrosine kinase receptors: the fms-like tyrosine kinase receptor (Flt-1, or VEGFR1) and kinase insert domain-containing receptor (KDR or VEGFR2). We have previously produced a panel of antibodies directed against KDR from mice immunized with the recombinant form receptor. These antibodies efficiently neutralized VEGF-induced KDR activation and mitogenesis of human umbilical vascular endothelial cells (HUVEC). Murine antibodies, however, may not be suitable candidates for human therapy because of their propensity to elicit human anti-mouse antibody response. Here we isolated several high-affinity human Fab antibody fragments directed against KDR from an antibody phage display library constructed from the pooled B lymphocytes of nonimmunized healthy human donors. These human Fab fragments bind specifically to KDR with nanomolar affinity and block KDR/VEGF interaction with IC(50) of approximately 2-20 nM. Further, they effectively inhibit VEGF-stimulated mitogenesis of HUVEC and migration of human leukemia cells. Epitope mapping studies demonstrated that all neutralizing human antibodies bound the epitope(s) located within the first 3 N-terminal immunoglobulin-like domains of KDR, the same region that encompasses the binding site of VEGF. Our results suggest that these human anti-KDR antibodies may have potential application in the treatment of cancer and other diseases in which pathologic angiogenesis occurs.
Metal-free Inorganic Ligands for Colloidal Nanocrystals: S2–, HS–, Se2–, HSe–, Te2–, HTe–, TeS32–, OH–, and NH2– as Surface Ligands (2011)

All-inorganic colloidal nanocrystals were synthesized by replacing organic capping ligands on chemically synthesized nanocrystals with metal-free inorganic ions such as S(2-), HS(-), Se(2-), HSe(-), Te(2-), HTe(-), TeS(3)(2-), OH(-) and NH(2)(-). These simple ligands adhered to the NC surface and provided colloidal stability in polar solvents. The versatility of such ligand exchange has been demonstrated for various semiconductor and metal nanocrystals of different size and shape. We showed that the key aspects of Pearson's hard and soft acids and bases (HSAB) principle, originally developed for metal coordination compounds, can be applied to the bonding of molecular species to the nanocrystal surface. The use of small inorganic ligands instead of traditional ligands with long hydrocarbon tails facilitated the charge transport between individual nanocrystals and opened up interesting opportunities for device integration of colloidal nanostructures.
Dichotomous roles for externalized cardiolipin in extracellular signaling: Promotion of phagocytosis and attenuation of innate immunity (2015)

Among the distinct molecular signatures present in the mitochondrion is the tetra-acylated anionic phospholipid cardiolipin, a lipid also present in primordial, single-cell bacterial ancestors of mitochondria and multiple bacterial species today. Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy. Given the immunogenicity of mitochondrial and bacterial membranes that are released during sterile and pathogen-induced trauma, we hypothesized that cardiolipins might function as "eat me" signals for professional phagocytes. In experiments with macrophage cell lines and primary macrophages, we found that membranes with mitochondrial or bacterial cardiolipins on their surface were engulfed through phagocytosis, which depended on the scavenger receptor CD36. Distinct from this process, the copresentation of cardiolipin with the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide dampened TLR4-stimulated production of cytokines. These data suggest that externalized, extracellular cardiolipins play a dual role in host-host and host-pathogen interactions by promoting phagocytosis and attenuating inflammatory immune responses.
A critical evaluation of loss of heterozygosity detected in tumor tissues, blood serum and bone marrow plasma from patients with breast cancer (2007)

Our study demonstrates heterogeneous profiles and low rates of LOH, particularly on free DNA in BM and blood samples. However, the significant associations of LOH with some risk factors and the demonstrated possibility of monitoring free DNA in patients undergoing systemic therapy suggest that LOH analysis may be developed into a useful diagnostic tool.
Technical solutions for the 3G long-term evolution (2006)

Work has started in the 3GPP to define a long-term evolution for 3G, sometimes referred to as super-3G, which will stretch the performance of 3G technology, thereby meeting user expectations in a 10-year perspective and beyond. The fundamental targets of this evolution - to further reduce user and operator costs and to improve service provisioning - will be met through improved coverage and system capacity as well as increased data rates and reduced latency. This article presents promising technologies to fulfil these targets, including OFDM, multi-antenna solutions, evolved QoS and link layer concepts, and an evolved architecture. Furthermore, the results of a performance evaluation are presented, indicating that the requirements can indeed be reached using the proposed technologies.
An economical and preparative orthogonal solid phase synthesis of fluorescein and rhodamine derivatized peptides: FRET substrates for the Staphylococcus aureus sortase SrtA transpeptidase reactionElectronic supplementary information (ESI) available: HPLC and analytical data. See http://www.rsc.org/suppdata/cc/b2/b206303d/ (2002)

An economical and preparative-scale orthogonal solid-phase method of incorporating carboxyrhodamine and carboxyfluorescein fluorescence resonance energy transfer (FRET) probes site-specifically into synthetic peptide substrates for the S. aureus Sortase transpeptidase SrtA has been developed.
CHAPTER 6. Bicontinuous Emulsions Stabilized by Colloidal Particles (2014)

The liquid–liquid phase separation of binary fluids, induced by a temperature quench, can be arrested by colloidal particles trapped at the interface. The arrested structure, a novel soft solid known as a bicontinuous interfacially jammed emulsion gel (bijel), was first predicted by computer simulations and subsequently realized in the lab. Initially the mechanical properties are controlled by the interfacial tension between the two fluid domains (e.g. a deeper quench yields a stronger bijel) and the volume fraction of particles. Reversing the temperature quench results in the two fluids becoming miscible again. Whether or not this leaves a colloidal gel in place which is stable without a liquid–liquid interface (a ‘monogel’) depends on the age of the gel and the choice of liquids. In this chapter we describe the current state of bijel research using experimental, theoretical and computational approaches. We discuss possible areas of application and, finally, we contrast the physical route with which the bijel is prepared with a related material that is prepared via direct particle–particle interactions.
Possibilities and constraints in the regeneration of trees from cotyledonary needles of Picea abies in vitro (1983)

Although use of embryonic or seedling tissues for mass clonal micropropagation in vitro in conifer reforestation programmes is questionable, there is a potential application in the regeneration of plants from scarce and costly seed derived from controlled pollination. In addition, in vitro culture shortens considerably the lag phase in numbers during the initial stages of vegetative propagation via rooted cuttings. Successive steps of the present technique are described whereby cotyledonary needles (secondary explants) were subcultured on a hormone‐free medium after administration of cytokinin or auxin to 14‐day‐old seedling (primary) explants of Picea abies . For bud induction, N 6 ‐benzyladenine (BA) was applied either as a short‐duration (3 h), high‐concentration (125 μ M ) pulse or by vacuum infiltration and incubation in a BA‐containmg (5 μ M ) infusion medium. Induced adventitious shoots were elongated with the aid of far‐red light and rooted in vivo after a long‐duration (12 h), high‐concentration (625 μ M ) application of indolebutyric acid. Pulse and infusion treatments resulted in the induction of greater numbers of adventitious buds (average of 12 per needle) over a three to four week shorter culture period than was the case with the conventional inclusion of growth regulators in the agarified medium. No exogenous auxin was required in the bud‐induction programme; its inclusion even at nanomolar levels promoted histo‐ rather than morphogenesis. In cotyledonary needles, to the primary explants of which BA was applied as a pulse or by infusion, the cell divisions which gave rise to the meristemoids from which adventitious buds were produced, appeared to commence mainly in undifferentiated hypodermal layer cells but also in the mesophyll immediately below. By contrast, where BA was incorporated in the agarified medium the first divisions occurred mainly in cells of the epidermal layer. A number of factors affected plantlet regeneration, for instance seed variability, age of seedlings, and mode of application of growth substances. It should also be accepted that the xeromorphic nature of the conifer leaf might impose physiological and morphological constraints on its culture in vitro that could militate against easy morphogenic manipulation. It is deemed essential that the current mean ratio of regenerated plants to cotyledonary needles of 1:1 be increased 10 to 20 fold in order to approach commercial feasibility.