gebhart/patrepeval huggingface dataset:
A Positional Scanning Combinatorial Library of Peptoids As a Source of Biological Active Molecules:  Identification of Antimicrobials (2003)

A positional scanning library of N-alkylglycine trimers (peptoids) containing over 10 000 compounds has been synthesized on solid phase. The synthetic pathway involved the use of the submonomer strategy and a set of 22 commercially available primary amines as a chemical diversity source. The unbiased nature of the library allowed its screening against a variety of biological targets, leading to the identification of individual peptoids exhibiting remarkable biological activities (García-Martínez, C. et al. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 2374. Montoliu, et al. J. Pharm. Exp. Therap. 2002, 302, 29. Planells-Cases, R., et al. J. Pharm. Exp. Therap. 2002, 302, 163). In the present work, the screening of this library against a panel of Gram-positive and Gram-negative bacteria led to the identification of different compounds exhibiting antimicrobial activity.
Experimental model of biofilm implant‐related osteomyelitis to test combination biomaterials using biofilms as initial inocula (2012)

Currently, the majority of animal models that are used to study biofilm-related infections use planktonic bacterial cells as initial inocula to produce positive signals of infection in biomaterials studies. However, the use of planktonic cells has potentially led to inconsistent results in infection outcomes. In this study, well-established biofilms of methicillin-resistant Staphylococcus aureus were grown and used as initial inocula in an animal model of a Type IIIB open fracture. The goal of the work was to establish, for the first time, a repeatable model of biofilm implant-related osteomyelitis, wherein biofilms were used as initial inocula to test combination biomaterials. Results showed that 100% of animals that were treated with biofilms developed osteomyelitis, whereas 0% of animals not treated with biofilm developed infection. The development of this experimental model may lead to an important shift in biofilm and biomaterials research by showing that when biofilms are used as initial inocula, they may provide additional insights into how biofilm-related infections in the clinic develop and how they can be treated with combination biomaterials to eradicate and/or prevent biofilm formation.
Comparison of left atrial pressure and wedge pulmonary capillary pressure. Pressure gradients between left atrium and left ventricle. (1970)

Simultaneous records of wedged pulmonary capillary pressure and left atrial pressure have been made in I2 patients. The pressure changes in the left atrium preceded those in the pulmonary capillary bed by o-o6 to O0I4 sec.
HISTOPATHOLOGY OF THYROIDS AND LIVERS OF RATS AND MICE FED DIETS CONTAINING BRASSICA GLUCOSINOLATES (1972)

A histopathological comparison was made of thyroid and liver tissue from weanling mice and rats fed six different diets. The experimental diets contained mustard or rapeseed meal (RSM) varieties of high glucosinolate content, namely, Oriental mustard (Brassica juncea), Yellow Sarson (B. campestris), Target (B. napus) and Fe-treated Target (glucosinolate hydrolyzed by FeSO 4 ). The two control diets contained a low glucosinolate variety of rapeseed meal, Bronowski (B. napus), or casein to provide approximately 20% dietary protein. Seven mice and seven rats were fed each diet 4 and 6 weeks, respectively. Both body growth rate and the histopathology of the thyroid gland were affected by the inclusion of rapeseed meals in the diet. The effect was more marked in rats than in mice. Whereas the high glucosinolate-containing RSM (cult Target) diet produced poorest performance in rats (P &lt; 0.01) and mice (P &lt; 0.05), the low glucosinolate RSM (cult Bronowski) diet was as efficiently utilized as the casein diet. Epithelial cell heights of the thyroid follicles were increased in the mice and rats fed Target RSM, but only rats showed a high degree of papillary formation. Liver involvement at the microscopic level was slight. The measurement of epithelial cell height showed most promise as an accurate indicator of cell size.
1x11 few-mode fiber wavelength selective switch using photonic lanterns (2014)

We demonstrate an 11 port count wavelength selective switch (WSS) supporting spatial superchannels of three spatial modes, based on the combination of photonic lanterns and a high-port count single-mode WSS.
Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer (2012)

The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.
THE PREPARATION OF 4,6-O-BENZYLIDENE-D-GLUCAL AND THE REACTION OF METHYLLITHIUM WITH METHYL 2,3-ANHYDRO-4,6-O-BENZYLIDENE-α-D-ALLOPYRANOSIDE (1966)

4,6-O-Benzylidene-D-glucal has been prepared by the reaction of benzaldehyde with D-glucal. The reaction of commercial methyllithium with methyl 2,3-anhydro-4,6-O-benzylidene-α-D-allopyranoside produces the C 2 -methylated 1,2-unsaturated compound 4,6-O-benzylidene-1,2-didehydro-1,2-dideoxy-2-methyl-D-ribo-hexopyranose. Their structures have been proven by first-order analyses of their nuclear magnetic resonance spectra.
Stimulation of neurite outgrowth using an electrically conducting polymer (1997)

Damage to peripheral nerves often cannot be repaired by the juxtaposition of the severed nerve ends. Surgeons have typically used autologous nerve grafts, which have several drawbacks including the need for multiple surgical procedures and loss of function at the donor site. As an alternative, the use of nerve guidance channels to bridge the gap between severed nerve ends is being explored. In this paper, the electrically conductive polymer--oxidized polypyrrole (PP)--has been evaluated for use as a substrate to enhance nerve cell interactions in culture as a first step toward potentially using such polymers to stimulate in vivo nerve regeneration. Image analysis demonstrates that PC-12 cells and primary chicken sciatic nerve explants attached and extended neurites equally well on both PP films and tissue culture polystyrene in the absence of electrical stimulation. In contrast, PC-12 cells interacted poorly with indium tin oxide (ITO), poly(L-lactic acid) (PLA), and poly(lactic acid-co-glycolic acid) surfaces. However, PC-12 cells cultured on PP films and subjected to an electrical stimulus through the film showed a significant increase in neurite lengths compared with ones that were not subjected to electrical stimulation through the film and tissue culture polystyrene controls. The median neurite length for PC-12 cells grown on PP and subjected to an electrical stimulus was 18.14 micron (n = 5643) compared with 9.5 micron (n = 4440) for controls. Furthermore, animal implantation studies reveal that PP invokes little adverse tissue response compared with poly(lactic acid-co-glycolic acid).
Hemoglobin-Induced Binding of Candida albicans to the Cell-Binding Domain of Fibronectin Is Independent of the Arg-Gly-Asp Sequence (1998)

Hemoglobin specifically induces fibronectin (FN) binding to the pathogenic yeast Candida albicans. When grown in the complex medium Sabouraud broth, C. albicans expresses receptors that bind to several domains of FN. Growth in defined medium supplemented with 0.1% hemoglobin, however, enhanced the binding of FN to a single class of receptors, with a Kd = 4.6 x 10(-8) M. Competitive binding assays using recombinant and proteolytic fragments of FN revealed that the cell-binding domain mediated this interaction. A recombinant 40-kDa fragment of FN consisting of type III repeats 9 to 13 had an inhibitory activity similar to that of the entire 120-kDa cell-binding domain, indicating that the C-terminal portion of the cell-binding domain contains the binding site. A recombinant 33-kDa fragment of the cell-binding domain and a 33-kDa fragment with the RGD sequence deleted had the same inhibitory activities, demonstrating that the RGD sequence recognized by some mammalian integrins is not required. The addition of hemoglobin to the culture medium also enhanced Candida cell adhesion to immobilized FN and to 120- and 40-kDa fragments of FN but not to the collagen-binding or fibrin I domains. Using ligand protection, we identified a surface protein from C. albicans with an apparent molecular mass of 55 kDa that was protected by both FN and the 40-kDa fragment derived from the cell-binding domain. Therefore, hemoglobin both induces FN binding and changes the relative affinities of C. albicans for the cell- and collagen-binding domains of FN.
Early myeloid cells are high producers of nitric oxide upon CD40 plus IFN-γ stimulation through a mechanism dependent on endogenous TNF-α and IL-1α (2000)

Bone marrow contains nonadherent low-density wheat germ agglutinin-positive (Fr3-WGA(+)) cells that release large amounts of NO and show natural suppressor activity if stimulated with activated T cells. We have assessed the involvement of CD40-derived signals in NO production and their cytokine requirements. Production of NO by Fr3-WGA(+) cells in co-culture with activated T cells is inhibited by a competing CD40 soluble fusion protein. Fr3-WGA(+) cells express the inducible NO synthase (iNOS) and release NO following CD40 plus IFN-gamma activation. Production of NO through CD40 is strictly dependent on endogenous TNF-alpha and / or IL-1alpha, since it is inhibited by neutralizing these cytokines or blocking the TNF receptor (p55). Both cytokines are transcribed when Fr3-WGA(+) cells are stimulated by CD40 signaling plus IFN-gamma, although TNF-alpha remains below detection limits in stimulated Fr3-WGA(+) cell cultures. Phenotypic studies combined with data on intracellular iNOS expression and cell sorting indicate that NO-producing cells are CD40, CD31 (ER-MP12), CD11b (Mac-1)low, ER-MP20 (Ly-6C) and Gr-1 (Ly-6G) positive, consistent with myeloid progenitors. The results point to early myeloid cells as an important cell source of NO once triggered by activated T cells through CD40 and IFN-gamma-derived signals, in a mechanism involving the production of TNF-alpha and / or IL-1alpha.
UAV aided intelligent routing for ad-hoc wireless network in single-area theater (2002)

Large homogeneous ad hoc wireless networks have a problem: the bandwidth available to a mobile user decreases as the number of nodes in the network increases. Using the embedded ad-hoc networking mechanism, nodes are able to transport packets across the network in a multihop fashion. An embedded mobile backbone is dynamically constructed to form a 2-level physical heterogeneous multihop wireless network. These backbone nodes provide two critical functions: (1) direct communication between neighboring cluster heads; and (2) efficient route discovery in HSR. With the broadcast feature of unmanned aerial vehicle (UAV), the link state can be broadcast to backbone nodes instead of "flooding" on the level 2. Thus, the routing overhead can be tremendously reduced, and the throughput will be improved. We modified hierarchical state routing (HSR) to have an intelligent selection algorithm to reduce the system latency caused by the long propagation delay of the UAV channel. The performance of the system is evaluated through simulation experiments.
Mild and Efficient Modular Synthesis of Poly(acrylonitrile-co-butadiene) Block and Miktoarm Star Copolymer Architectures (2012)

An efficient approach for the synthesis of block copolymers of poly(acrylonitrile-co-butadiene) (NBR) and poly(styrene-co-acrylonitrile) (SAN) is described. Conjugation of preformed polymer building blocks is achieved via a hetero-Diels-Alder (HDA) mechanism employing cyclopentadiene-capped NBRs with dienophile SAN copolymers, both synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization. The protocol is further extended toward the synthesis of 4-miktoarm star polymers, consisting of two NBR and two SAN arms. Molar masses of the obtained complex macromolecular architectures range from below 10 000 g·mol–1 up to 110 000 g·mol–1 with dispersities below 1.5. Molecular verification of the coupling moieties is provided via NMR spectroscopy as well as ESI mass spectrometry. Size exclusion chromatography (SEC) traces of the obtained block copolymers and miktoarm star polymers were analyzed via deconvolution techniques, revealing the presence of 9.9–12.6 wt % (block copolymers) and 20 wt % (stars) of polymer chains not participating in the HDA conjugation, respectively. The residual polymers were analyzed toward their origin from either the loss of functionality during RAFT polymerization or incomplete conversion during the conjugation process. The comprehensive analysis of the macromolecular material was underpinned by kinetic simulations to estimate the fractions of nonfunctional polymer chains generated during the NBR and SAN polymerizations. The simulations evidenced that NBR-b-SAN samples cannot contain more than 94.4 wt % (Mn 13 000 g·mol–1), 93.6 wt % (Mn 57 000 g·mol–1), or 93.9 wt % (Mn 110 000 g·mol–1) of polymer chains actually possessing the targeted block copolymer structures when assuming an ideal RAFT process. These results unambiguously reveal that nonfunctionalized polymer chains formed during RAFT polymerization cause the incomplete conjugation of polymer building blocks, evidencing the limitations of end-group control in controlled/living radical polymerizations.
Localized Density Measurements on ASDEX Using Microwave Reflectometry (1990)

Reflectometry is based on the propagation and reflection of probing waves in the inhomogeneous fusion plasma.
Coherent coupling of laser gain media using phase conjugation (1986)

We have experimentally demonstrated a laser energy-scaling technique, based on a phase-conjugate oscillator/amplifier scheme that permits the coupling of several parallel amplifiers to form a single coherent output beam. This, is achieved despite dramatic differences in the individual amplifier energies and optical path lengths. When many amplifiers are coupled together, energy can be scaled significantly beyond the limit imposed by the maximum available volume of a single active medium. Although the present demonstration utilized Nd:YAG, this technique is quite general and can be applied to a variety of laser media.
Micromarkers: miRNAs in cancer diagnosis and prognosis (2010)

Molecular diagnostics in cancer should provide the highest specificity and sensitivity in classification, prognostic stratification and early detection. miRNAs could contribute to hitting the mark, or at least to come nearer, by virtue of their cancer-specific expression and stability. Indeed, different to other RNA classes, miRNAs can be detected and quantified not only in frozen tissues, but also in formalin-fixed paraffin-embedded tissues, as well as serum/plasma samples. Thus, miRNA studies have quickly moved from research on the molecular basis of cancer to areas of clinical application. This review summarizes the potential role of miRNAs as molecular markers for cancer classification, prognostic stratification and drug-response prediction. It also summarizes their potential as circulating markers and cancer-predisposing genes. If we consider that studies on miRNAs in cancer therapy have already given important contributions, miRNAs have an impact in all cancer areas. Whether this will translate into clinical applications is still too early to say. However, in the diagnostic field, miRNAs may already represent an improvement over presently available approaches; for example, their expression profile is effective in the identification of tissue of origin of metastasis. In addition, circulating miRNAs are expected to provide improved specificity and/or sensitivity over presently available markers.
M-CSF neutralization and Egr-1 deficiency prevent ovariectomy-induced bone loss (2000)

Increased stromal cell production of M-CSF, an event caused by enhanced phosphorylation of the nuclear protein Egr-1, is central to the mechanism by which estrogen (E2) deficiency upregulates osteoclast (OC) formation. However, the contribution of enhanced M-CSF production to the bone loss induced by E2 deficiency remains to be determined. We found that treatment with an Ab that neutralizes M-CSF in vivo completely prevents the rise in OC number, the increase in bone resorption, and the resulting bone loss induced by ovariectomy (ovx). We also found that adult, intact Egr-1-deficient mice, a strain characterized by maximally stimulated stromal cell production of M-CSF, exhibit increased bone resorption and decreased bone mass. In these mice, treatment with anti-M-CSF Ab restored normal levels of bone resorption, thus confirming that increased M-CSF production accounts for the remodeling abnormalities of Egr-1-deficient mice. Consistent with the failure of ovx to further increase M-CSF production in Egr-1-deficient mice, ovx neither increased bone resorption further, nor caused bone loss in these animals. In summary, the data demonstrate that E2 deficiency induces M-CSF production via an Egr-1-dependent mechanism that is central to the pathogenesis of ovx-induced bone loss. Thus, Egr-1 and M-CSF are critical mediators of the bone sparing effects of E2 in vivo.
Critical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles (2002)

Virus-like particles (VLPs) are known to induce strong Ab responses in the absence of adjuvants. In addition, VLPs are able to prime CTL responses in vivo. To study the efficiency of this latter process, we fused peptide p33 derived from lymphocytic choriomeningitis virus to the hepatitis B core Ag, which spontaneously assembles into VLPs (p33-VLPs). These p33-VLPs were efficiently processed in vitro and in vivo for MHC class I presentation. Nevertheless, p33-VLPs induced weak CTL responses that failed to mediate effective protection from viral challenge. However, if APCs were activated concomitantly in vivo using either anti-CD40 Abs or CpG oligonucleotides, the CTL responses induced were fully protective against infection with lymphocytic choriomeningitis virus or recombinant vaccinia virus. Moreover, these CTL responses were comparable to responses generally induced by live vaccines, because they could be measured in primary ex vivo (51)Cr release assays. Thus, while VLPs alone are inefficient at inducing CTL responses, they become very powerful vaccines if applied together with substances that activate APCs.
Extracellular high-mobility group 1 protein is essential for murine erythroleukaemia cell differentiation (1996)

A high-mobility group 1 (HMG1) protein type isolated from murine erythroleukaemia (MEL) cells promotes acceleration of the differentiation process when added to a MEL cell culture together with the inducer hexamethylene bisacetamide. We now provide direct evidence that the presence of HMG1 protein in the extracellular medium is essential for terminal erythroid differentiation. An extracellular function for HMG1 protein in MEL cell is further supported by a demonstration that this protein is released from MEL cells exposed to the chemical inducer and that the addition of an anti-(HMG1 protein) monoclonal antibody to the cell culture inhibits the differentiation process almost completely. The release of HMG1 protein from MEL cells is modulated by compounds affecting cell calcium homoeostasis, such as a calcium ionophore or verapamil. In fact, in the presence of the ionophore an increased rate of differentiation is accompanied by an enhanced extracellular release of HMG1 protein, whereas in the presence of verapamil both phenomena are significantly decreased.
BMP‐3 promotes mesenchymal stem cell proliferation through the TGF‐β/activin signaling pathway (2010)

Adipogenesis plays a key role in the pathogenesis of obesity. It begins with the commitment of mesenchymal stem cells (MSCs) to the adipocyte lineage, followed by terminal differentiation of preadipocytes to mature adipocytes. A critical, but poorly understood, component of adipogenesis involves proliferation of MSCs and preadipocytes. The present study was undertaken to examine the hypothesis that bone morphogenetic protein-3 (BMP-3) promotes adipogenesis using C3H10T1/2 MSCs and 3T3-L1 preadipocytes as in vitro model systems. We demonstrated that although it did not promote the commitment of MSCs to the adipocyte lineage or the differentiation of preadipocytes to adipocytes, BMP-3-stimulated proliferation by threefold in both cell types. Owing to a lack of information on MSC proliferation, we then delineated the molecular mechanisms underlying BMP-3-stimulated MSC proliferation. We showed that BMP-3 activated the transforming growth factor-beta (TGF-beta)/activin but not ERK1/2, p38 MAPK, or JNK signaling pathways in C3H10T1/2 cells. Furthermore, the TGF-beta/activin receptor kinase inhibitor SB-431542 blocked BMP-3-stimulated proliferation. Importantly, siRNA-mediated knockdown of the key TGF-beta/activin signaling pathway components, ActRIIB, ALK4, or Smad2, abrogated the mitogenic effects of BMP-3 on MSCs. Together, these results demonstrate that BMP-3 stimulates MSC proliferation via the TGF-beta/activin signaling pathway, thus revealing a novel role for this divergent and poorly understood member of the TGF-beta superfamily in regulating MSC proliferation.
Orexin Receptors: Pharmacology and Therapeutic Opportunities (2011)

Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides produced in the lateral hypothalamus that promote many aspects of arousal through the OX1 and OX2 receptors. In fact, they are necessary for normal wakefulness, as loss of the orexin-producing neurons causes narcolepsy in humans and rodents. This has generated considerable interest in developing small-molecule orexin receptor antagonists as a novel therapy for the treatment of insomnia. Orexin antagonists, especially those that block OX2 or both OX1 and OX2 receptors, clearly promote sleep in animals, and clinical results are encouraging: Several compounds are in Phase III trials. As the orexin system mainly promotes arousal, these new compounds will likely improve insomnia without incurring many of the side effects encountered with current medications.
Induction of Hepatitis C Virus E1 Envelope Protein-Specific Immune Response Can Be Enhanced by Mutation of N-Glycosylation Sites (2001)

Deglycosylation of viral glycoproteins has been shown to influence the number of available epitopes and to modulate immune recognition of antigens. We investigated the role played by N-glycans in the immunogenicity of hepatitis C virus (HCV) E1 envelope glycoprotein, a naturally poor immunogen. Eight plasmids were engineered, encoding E1 protein mutants in which the four N-linked glycosylation sites of the protein were mutated separately or in combination. In vitro expression studies showed an influence of N-linked glycosylation on expression efficiency, instability, and/or secretion of the mutated proteins. Immunogenicity of the E1 mutants was studied in BALB/c mice following intramuscular and intraepidermal injection of the plasmids. Whereas some mutations had no or only minor effects on the antibody titers induced, mutation of the fourth glycosylation site (N4) significantly enhanced the anti-E1 humoral response in terms of both seroconversion rates and antibody titers. Moreover, antibody induced by the N4 mutant was able to recognize HCV-like particles with higher titers than those induced by the wild-type construct. Epitope mapping indicated that the E1 mutant antigens induced antibody directed at two major domains: one, located at amino acids (aa) 313 to 332, which is known to be reactive with sera from HCV patients, and a second one, located in the N-terminal domain of E1 (aa 192 to 226). Analysis of the induced immune cellular response confirmed the induction of gamma interferon-producing cells by all mutants, albeit to different levels. These results show that N-linked glycosylation can limit the antibody response to the HCV E1 protein and reveal a potential vaccine candidate with enhanced immunogenicity.