gebhart/patrepeval huggingface dataset:
Characterization of IgG FcR-mediated proliferation of human T cells induced by mouse and human anti-CD3 monoclonal antibodies. Identification of a functional polymorphism to human IgG2 anti-CD3 (1992)

T cell activation induced by mouse anti-CD3 mAb has shown to be dependent on the Ig isotype of these antibodies. A study of isotype dependency of human antibodies, however, seems more relevant to human effector systems, especially in view of the availability of humanized antibodies for clinical applications. We constructed a panel of mouse and mouse/human chimeric anti-CD3 mAb, which differ only in their CH region and hence have identical binding sites and affinity. By using these antibodies, we now studied their ability to induce T cell proliferation in human PBMC and analyzed the classes of IgG FcR involved in these responses. The human (h)IgG1, hIgG3, and hIgG4, as well as mouse (m)IgG2a and mIgG3 anti-CD3 mAb induced an Fc gamma RI (CD64)-dependent T cell proliferation in all donors. Activation with hIgG2 and mIgG1 anti-CD3 mAb was observed to be mediated via the low affinity Fc gamma RII (CD32). It was found that leukocytes in a normal donor population display a functional polymorphism with respect to hIgG2 anti-CD3 responsiveness. This polymorphism was found to be inversely related to the previously defined Fc gamma RII-polymorphism to mIgG1 anti-CD3 mAb. Monocytes expressing the Fc gamma RII mIgG1 low responder (LR) allele support hIgG2 anti-CD3 induced T cell proliferation efficiently, whereas cells homozygous for the Fc gamma RII mIgG1 high responder (HR) allele do not. This observation could be confirmed in T cell activation studies using hFc gamma RIIa-transfected mouse fibroblasts, expressing either the mIgG1 anti-CD3 HR or LR Fc gamma RII-encoding cDNA.
UVA sunbeds: tanning, photoprotection, acute adverse effects and immunological changes (1989)

The effects on 31 normal subjects following exposure to sunbeds containing UVA lamps with minimal UVB emission have been compared in a double-blind study with the effects on nine control subjects of a similar exposure course three times weekly for 4 weeks to sunbeds emitting visible light. On previously untanned areas, all those subjects on active treatment developed a mild tan; in tanned areas they all developed a moderate tan, while all control subjects developed a minimal to mild tan. The mean protection factor against later UVB-induced erythema was 3.2 +/- 0.3 after the active course and 1.6 +/- 0.2 among the controls. Significantly more frequent adverse cutaneous effects for active subjects were pruritus, erythema, freckling, burning sensation, dryness and polymorphic light eruption. Cutaneous Langerhans cell numbers, and blood CD3+ (pan T-cell) and CD4+ (helper T-cell) lymphocyte subsets were reduced in both active and control groups. CD8+ (cytotoxic/suppressor T-cell) counts were similarly but not significantly reduced in both groups. Pityrosporum yeast counts were significantly reduced in both groups. The changes found in both groups seem attributable to small amounts of UVB emission from both active and control lamps.
Nanogold Plasmon Resonance-Based Glucose Sensing. 2. Wavelength-Ratiometric Resonance Light Scattering (2005)

Gold colloids are well known to display strong plasmon absorption bands due to electron oscillations induced by the incident light. When the colloids are in proximity, the plasmon absorption bands are often perturbed. This has enabled us recently to successfully develop a glucose sensing platform based on the disassociation of dextran-coated gold colloids, cross-linked with Con A, by glucose. However, a much more useful and simpler property of gold colloids, which has been ill explored with regard to sensing, is their ability to efficiently scatter excitation light. We have found that our nanogold sensing aggregates are indeed efficient light scatters around the nanogold plasmon absorption band. By measuring the ratio of scattered light intensities at two different arbitrary wavelengths, 560 and 680 nm, glucose concentrations can be readily determined from a few millimolar up to approximately 60 mM, using a simple white light LED and detection system. Further, by measuring the ratio of the scattered intensities, this sensing approach is independent of the total sensing aggregate concentration and the excitation and detection instrumentation fluctuations or drifts. This simplistic and low-cost approach to glucose sensing, coupled with the sensing aggreagates' ability to scatter red light, suggests the potential use of these aggregates for use in physiological transdermal glucose monitoring, either for implantable skin sensors or glucose sensing tattoos (discussed later).
CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition (2015)

Cancer stem cells (CSCs, also called cancer stem-like cells, CSLCs) can function as "seed cells" for tumor recurrence and metastasis. Here, we report that, in the presence of CD133+ ovarian CSLCs, CD133- non-CSLCs can undergo an epithelial-mesenchymal transition (EMT)-like process and display enhanced metastatic capacity in vitro and in vivo. Highly elevated expression of chemokine (C-C motif) ligand 5 (CCL5) and its receptors chemokine (C-C motif) receptor (CCR) 1/3/5 are observed in clinical and murine metastatic tumor tissues from epithelial ovarian carcinomas. Mechanistically, paracrine CCL5 from ovarian CSLCs activates the NF-κB signaling pathway in ovarian non-CSLCs via binding CCR1/3/5, thereby inducing EMT and tumor invasion. Taken together, our results redefine the metastatic potential of non-stem cancer cells and provide evidence that targeting the CCL5:CCR1/3/5-NF-κB pathway could be an effective strategy to prevent ovarian cancer metastasis.
291. Carbonyl halides of manganese and some related compounds (1959)

E. W. Abel and G. Wilkinson, J. Chem. Soc., 1959, 1501 DOI: 10.1039/JR9590001501
Direct Time-Domain Measurements of the Pulse Amplitude Statistics of a Fiber Supercontinuum Source (2007)

We demonstrate a simple high-brightness all-fiber supercontinuum source that controllably produces amplitude-stable or unstable pulse trains. We present the first direct time-domain measurements of the amplitude statistics of a supercontinuum source in these distinct regimes.
Acalabrutinib and its Use in Treatment of Chronic Lymphocytic Leukemia (2018)

Acalabrutinib received an accelerated US FDA approval for patients with relapsed/refractory mantle cell lymphoma in 2017 and is currently being evaluated in chronic lymphocytic leukemia (CLL). To date, ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that's approved for treatment of CLL. Acalabrutinib is a second generation BTK inhibitor that binds covalently to the Cys481 residue on BTK and has half maximal inhibitory concentration (IC<sub>50</sub>) of 3 nM. In preclinical mouse models, acalabrutinib significantly reduced proliferation of CLL cells. Results of Phase I/II trials revealed overall response rates (ORR) of 96% in treatment-naive, 93% in relapsed/refractory and 76% in ibrutinib intolerant patients with CLL. The most common adverse effects (>20%) were grade 1-2 comprising constitutional symptoms, GI toxicity, rash and myelosuppression. There were limited grade 3 or 4 toxicities, involving syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia.
Fibroblast Growth Factor-2 Suppression of Tumor Necrosis Factor α-Mediated Apoptosis Requires Ras and the Activation of Mitogen-activated Protein Kinase (1996)

Treatment of L929 cells with tumor necrosis factor alpha (TNFalpha) activates a programmed cell death pathway resulting in apoptosis. We investigated the intracellular signaling pathways activated in L929 cells by TNFalpha. TNFalpha robustly activates Jun kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family. In addition, p42(MAPK) is activated, but a 10-fold greater concentration of TNFalpha was required for substantial MAPK activation than was needed for maximal JNK stimulation. Simultaneous treatment of L929 cells with fibroblast growth factor (FGF-2) significantly reduced the apoptotic response to TNFalpha. FGF-2 substantially activated the Raf/MEK/MAPK (where MEK is mitogen-activated protein kinase kinase) pathway but did not affect TNFalpha activation of JNK. These results indicate that although JNK may play an important role in transmitting the TNFalpha signal from the cell surface to the nucleus, activation of the JNK pathway is not sufficient to induce apoptosis. Expression of dominant-negative Asn-17 Ras in L929 cells diminished the FGF-2 stimulation of p42(MAPK) and eliminated the protective effect of FGF-2. Asn-17 Ras expression did not affect JNK activity and had no effect on TNFalpha activation of JNK. Pharmacological inhibition of MEK-1 activity by incubation of cells with the compound PD 098059 blocked p42(MAPK) activation and FGF-2 protection against apoptosis. Interestingly, activated Val-12 Ras expression substantially enhanced TNFalpha-mediated apoptosis in L929 cells, but Val-12 Ras did not constitutively activate MAPK in L929 cells and FGF-2 partially protected Val-12 Ras-expressing cells from TNFalpha-mediated apoptosis. Our data indicate that activation of the MAPK pathway mediates an FGF-2 protective effect against apoptosis and highlights the important role that integration of multiple intracellular signaling pathways plays in the regulation of cell growth and death.
CC Chemokine Receptor 2 Deficiency Aggravates Cognitive Impairments and Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease (2011)

Circulating monocytoid cells have the ability to infiltrate nervous tissue, differentiate into microglia, and clear amyloid-β (Aβ) from the brain of mouse models of Alzheimer's disease. Interaction between the chemokine CCL2 and its CC chemokine receptor 2 (CCR2) plays a critical role in the recruitment of inflammatory monocytes into the injured/diseased brain. Here, we show that CCR2 deficiency aggravates mnesic deficits and amyloid pathology in transgenic mice expressing the chimeric mouse/human β-amyloid precursor protein and presenilin 1 (APP(Swe)/PS1). Indeed, memory impairment was accelerated and enhanced in APP(Swe)/PS1/CCR2(-/-) mice. Apparition of cognitive decline occurred earlier (i.e., at 3 months of age before plaque formation) and correlated with intracellular accumulation of soluble oligomeric forms of Aβ. Memory deficits worsened with age and were aggravated in APP(Swe)/PS1/CCR2(-/-) mice compared with their respective control groups. Soluble Aβ assemblies increased significantly in APP(Swe)/PS1 mice in a context of CCR2 deficiency, whereas the plaque load remained relatively similar in the brain of aging APP(Swe)/PS1 and APP(Swe)/PS1/CCR2(-/-) mice. However, CCR2 deficiency stimulated the expression of TGF-β1, TGF-β receptors, and CX(3)CR1 transcripts in plaque-associated microglia, a pattern that is characteristic of an antiinflammatory subset of myeloid cells. A decreased expression of CCR2 could play a potential role in the etiology of Alzheimer's disease, a neurodegenerative pathology that could be treated by a genetic upregulation of the transgene in monocytoid cells.
Model-based phase shifting interferometry (2014)

A general method of surface profiling with phase-shifting interferometry techniques uses iterative linear regression to fit the sequence of interferograms to a physical model of the cavity. The physical model incorporates all important cavity influences, including environmentally induced rigid-body motion, phase shifter miscalibrations, multiple interference, geometry-induced spatial phase-shift variations, and their cross-couplings. By incorporating an initial estimate of the surface profile and iteratively solving for space- and time-dependent variables separately, convergence is robust and rapid. The technique has no restriction on surface shape or departure.
Roles for c-Myc in Self-renewal of Hematopoietic Stem Cells (2004)

Notch and HOXB4 have been reported to expand hematopoietic stem cells (HSCs) in vitro. However, their critical effector molecules remain undetermined. We found that the expression of c-myc, cyclin D2, cyclin D3, cyclin E, and E2F1 was induced or enhanced during Notch1- or HOXB4-induced self-renewal of murine HSCs. Since c-Myc can act as a primary regulator of G(1)/S transition, we examined whether c-Myc alone can induce self-renewal of HSCs. In culture with stem cell factor, FLT3 ligand, and IL-6, a 4-hydroxytamoxifen-inducible form of c-Myc (Myc/ERT) enabled murine Lin(-)Sca-1(+) HSCs to proliferate with the surface phenotype compatible with HSCs for more than 28 days. c-Myc activated by 4-hydroxytamoxifen augmented telomerase activities and increased the number of CFU-Mix about 2-fold in colony assays. Also, in reconstitution assays, HSCs expanded by c-Myc could reconstitute hematopoiesis for more than 6 months. As for the mechanism of c-myc induction by Notch1, we found that activated forms of Notch1 (NotchIC) and its downstream effector recombination signal-binding protein-J kappa (RBP-VP16) can activate the c-myc promoter through the element between -195 bp and -161 bp by inducing the DNA-binding complex. Together, these results suggest that c-Myc can support self-renewal of HSCs as a downstream mediator of Notch and HOXB4.
Characterization of the Surface to Thiol Bonding in Self-Assembled Monolayer Films of C12H25SH on InP(100) by Angle-Resolved X-ray Photoelectron Spectroscopy (1999)

Angle-resolved X-ray photoelectron spectroscopy (ARXPS) was used to characterize the bonding of alkanethiols to n-InP surfaces and to measure the monolayer thickness. A careful comparison of the angle-dependent spectra for three different sample preparations (oxidized InP(100), HF-etched InP(100), and HF-etched InP(100) with a self-assembled monolayer of C12H25SH) shows that the sulfur binds to In atoms on the surface. Comparison of the angle-dependence of the intensity ratios for the In 3d5/2 core level of InP with the self-assembled monolayer (SAM) to that of sputtered InP provides a thickness for the SAM of 14 ± 4 Å, corresponding to alkane chains at a tilt angle of 44 ± 16° from the surface normal.
A Novel Human STE20-related Protein Kinase, HGK, That Specifically Activates the c-Jun N-terminal Kinase Signaling Pathway (1999)

The yeast serine/threonine kinase STE20 activates a signaling cascade that includes STE11 (mitogen-activated protein kinase kinase kinase), STE7 (mitogen-activated protein kinase kinase), and FUS3/KSS1 (mitogen-activated protein kinase) in response to signals from both Cdc42 and the heterotrimeric G proteins associated with transmembrane pheromone receptors. Using degenerate polymerase chain reaction, we have isolated a human cDNA encoding a protein kinase homologous to STE20. This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that encode an open reading frame of 1165 amino acids with 11 kinase subdomains. HGK was a serine/threonine protein kinase that specifically activated the c-Jun N-terminal kinase (JNK) signaling pathway when transfected into 293T cells, but it did not stimulate either the extracellular signal-regulated kinase or p38 kinase pathway. HGK also increased AP-1-mediated transcriptional activity in vivo. HGK-induced JNK activation was inhibited by the dominant-negative MKK4 and MKK7 mutants. The dominant-negative mutant of TAK1, but not MEKK1 or MAPK upstream kinase (MUK), strongly inhibited HGK-induced JNK activation. TNF-alpha activated HGK in 293T cells, as well as the dominant-negative HGK mutants, inhibited TNF-alpha-induced JNK activation. These results indicate that HGK, a novel activator of the JNK pathway, may function through TAK1, and that the HGK --> TAK1 --> MKK4, MKK7 --> JNK kinase cascade may mediate the TNF-alpha signaling pathway.
Pleiotrophin Enhances Clonal Growth and Long-Term Expansion of Human Embryonic Stem Cells (2007)

To identify additional growth factors for optimizing propagation of human embryonic stem cells (hESCs), we mined publicly available data sets for the transcriptomes of murine and human ESCs and feeder cells, thereby generating a list of growth factors and complementary receptors. We identified the major pathways previously reported to be important, as well as several new ones. One pathway is the Pleiotrophin (PTN)-Pleiotrophin receptor (PTPRZ1) axis. Murine fibroblasts secrete Ptn, whereas hESCs expressed PTPRZ1, which is downregulated upon differentiation. Depletion of PTPRZ1 resulted in decreased colony formation and lower recovery of hESCs. Supplementation of chemically defined medium for feeder-free propagation of hESCs with PTN allowed higher recovery of hESCs without loss of pluripotency. PTN-PTPRZ1 functions here predominantly via an antiapoptotic effect mediated in part by the activation of Akt. These findings reveal the underlying importance of PTN in hESC survival and its usefulness in the clonal manipulation and large-scale propagation of hESCs. Disclosure of potential conflicts of interest is found at the end of this article.
Mcl-1 Is a Relevant Therapeutic Target in Acute and Chronic Lymphoid Malignancies: Down-Regulation Enhances Rituximab-Mediated Apoptosis and Complement-Dependent Cytotoxicity (2007)

These results show that Mcl-1 is a relevant therapeutic target for ALL and CLL, and its down-regulation has the potential to enhance the therapeutic effect of rituximab in CD20-bearing lymphoid cells.
Synthesis of Well-Defined Amphiphilic Block Copolymers Having Phospholipid Polymer Sequences as a Novel Biocompatible Polymer Micelle Reagent (2005)

To realize safer and effective drug administration, novel well-defined and biocompatible amphiphilic block copolymers containing phospholipid polymer sequences were synthesized. At first, the homopolymer of 2-methacryloyloxyethylphosphorylcholine (MPC) was synthesized in water by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. The "living" polymerization was confirmed by the fact that the number-average molecular weight increased linearly with monomer conversion while the molecular weight distribution remained narrow independent of the conversion. The poly(MPC) thus prepared is end-capped with a dithioester moiety. Using the dithioester-capped poly(MPC) as a macro chain transfer agent, AB diblock copolymers of MPC and n-butyl methacrylate (BMA) were synthesized. Associative properties of the amphiphilic block copolymer (pMPC(m)-BMA(n)) with varying poly(BMA) block lengths were investigated using NMR, fluorescence probe, static light scattering (SLS), and quasi-elastic light scattering (QELS) techniques. Proton NMR data in D2O indicated highly restricted motions of the n-butyl moieties, arising from hydrophobic associations of poly(BMA) blocks. Fluorescence spectra of N-phenyl-1-naphthylamine indicated that the probes were solubilized in the polymer micelles in water. The formation of polymer micelles comprising a core with poly(BMA) blocks and shell with hydrophilic poly(MPC) blocks was suggested by SLS and QELS data. The size and mass of the micelle increased with increasing poly(BMA) block length. With an expectation of a pharmaceutical application of pMPC(m)-BMA(n), solubilization of a poorly water-soluble anticancer agent, paclitaxel (PTX), was investigated. PTX dissolved well in aqueous solutions of pMPC(m)-BMA(n) as compared with pure water, implying that PTX is incorporated into the hydrophobic core of the polymer micelle. Since excellent biocompatible poly(MPC) sequences form an outer shell of the micelle, pMPC(m)-BMA(n) may find application as a promising reagent to make a good formulation with a hydrophobic drug.
Growth-inhibitory effects of epidermal growth factor and overexpression of its receptors on human squamous cell carcinomas in culture. (1986)

The role of epidermal growth factor (EGF) and its receptors in human cancers was studied using 24 human cell cultures including 15 of squamous cell carcinoma (SCC) of the skin, oral cavity, and esophagus. EGF was found to inhibit the growth and colony formation of all the SCC cells at doses that are mitogenic in many other cells, including epidermal keratinocytes and dermal fibroblasts. This inhibitory effect of EGF on SCCs was specific, because EGF did not inhibit and in some cases slightly stimulated the growth of other tumor cells, such as adenocarcinomas of the stomach, cervix, and breast and sarcomas. The amounts of EGF receptors on these SCC cells were measured by immunoprecipitation of labeled proteins with anti-EGF receptor polyclonal antibody and binding assay of membrane preparations using 125I-EGF. Of 13 SCC cell cultures tested, all except 3 of esophageal SCC showed higher levels of EGF receptor than normal epidermal keratinocytes, which contain 1.5 X 10(5) binding sites/cell. In general, SCCs of the skin and oral cavity had large amounts of EGF receptor on the order of 10(6)/cell, whereas the receptor of esophageal SCCs was on the order of 10(5)/cell. Some SCC cells had about twice as many EGF receptors as A431 cells. The values for the equilibrium dissociation constant (Kd) of these cells were on the order of nM. The sensitivity to the inhibitory effect of EGF correlated well with the elevated level of EGF receptors in 12 SCC cell lines, and higher significance was obtained when data on esophageal SCCs were excluded. The present observations suggest that EGF and EGF receptors play a role in the development of SCCs.
Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease (2007)

Hydroxyurea (HU) is not infrequently used in patients with sickle cell disease and myeloproliferative disorders. Despite murine data showing adverse effects on sperm counts, motility and morphology, there is little information on the effect of HU on human spermatogenesis. A retrospective review of four adult men who had semen analysis during HU therapy and in three cases after its cessation suggests that HU generally reduces sperm counts and motility and results in abnormal morphology. Cessation of HU in one case with azoospermia resulted in recovery of spermatogenesis; in two of the three cases, however, sperm morphology and mobility remained impaired. Recommendations for fertility management in adult men receiving long-term HU therapy are proposed.
Spectroscopy on Two Coupled Superconducting Flux Qubits (2005)

We have performed spectroscopy measurements on two coupled flux qubits. The qubits are coupled inductively, which results in a sigma(z)(1)sigma(z)(2) interaction. By applying microwave radiation, we observe resonances due to transitions from the ground state to the first two excited states. From the position of these resonances as a function of the applied magnetic field, we observe the coupling of the qubits. The coupling strength agrees with calculations of the mutual inductance.
Occurrence of Sialic Acids in Drosophila melanogaster (1992)

Sialylated oligosaccharides, which are cell type-specific and developmentally regulated, have been implicated in a variety of complex biological events. Their broad functional importance is reflected by their presence in a wide variety of phyla extending from Echinodermata through higher vertebrates. Here, sialic acids are detected throughout development in an insect, Drosophila. Homopolymers of alpha 2,8-linked sialic acid, polysialic acid, are developmentally regulated and only expressed during early Drosophila development.