gebhart/patrepeval huggingface dataset:
In vitro and in vivo reversal of chloroquine resistance in Plasmodium falciparum with promethazine. (1998)

The effect of combining promethazine with chloroquine was examined against Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays from volunteers given promethazine. The combination of chloroquine plus promethazine (1 x 10(-6) M) reversed chloroquine resistance in standard P. falciparum clones and patient parasite isolates from Nigeria. The combination reduced the 50% inhibitory concentrations (IC50s) for chloroquine against resistant parasites by 32-92%. Coadministration of promethazine with chloroquine also demonstrated a dose-dependent effect in Aotus monkeys infected with chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20 mg/kg of body weight for seven days), which normally has no effect on parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one monkey, parasitemia was suppressed at the lowest promethazine dose, but re-treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some animals followed by recrudescence. Re-treatment at higher doses cured one monkey and resulted in initial clearance and delayed recrudescence 28 or 63 days after treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10 parasites/microl of blood) and subsequently cleared without re-treatment. An in vitro bioassay model was developed to examine the effects of clinically achievable doses of promethazine on parasites susceptibilities in vitro. Plasma samples taken at hourly intervals from patients given a single oral dose of 25 mg of promethazine decreased the IC50 values for chloroquine by 20-58% with the most significant reductions occurring in plasma obtained from volunteers 3-4 hr after ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug demonstrated no effect on chloroquine susceptibility, suggesting that study of the pharmacokinetic disposition and potential interaction is warranted to optimize the dose regimen in patients for antimalarial efficacy. Historic use of this drug combination for treatment or prevention of chloroquine-associated pruritus or as an antiemetic suggest that the combination is safe and effective when used at standard dosages. The results from this study demonstrate that promethazine is a potent modulator of chloroquine resistance. Clinical evaluation of therapeutic regimens is required to validate clinical efficacy of this promising combination for treatment of uncomplicated chloroquine-resistant malaria.
Characterization of two-sided output vertical-cavity laser diodes by external optical feedback modulation (2002)

We have fabricated 5.6 nm wavelength tunable vertical-cavity laser diodes with record low CW threshold currents of 650 /spl mu/A. Laser output power depends on mirror reflectivities as well as intrinsic loss and effective internal efficiency which gives the conversion of carriers into photons of the lasing mode. To optimize laser mirror design for maximum output power it is important to know the loss and efficiency values. With in-plane lasers these intrinsic device parameters are commonly determined by measuring the threshold currents of equally processed devices of different cavity lengths. Obviously, this is impossible for vertical-cavity lasers even if in-plane lasers are made of epitaxial multilayers grown for vertical-cavity lasers due to different waveguiding mechanism. Therefore we have modulated the effective reflectivity of the vertical-cavity laser Bragg mirrors by external reflection to obtain the intrinsic parameters. We applied the technique for the first time to vertical-cavity laser diodes with two-sided light output but it can be applied to devices with one-sided output as well.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An Energy-Efficient Wirelessly Powered Millimeter-Scale Neurostimulator Implant Based on Systematic Codesign of an Inductive Loop Antenna and a Custom Rectifier (2018)

In this work, a switched-capacitor-based stimulator circuit that enables efficient energy harvesting for neurostimulation applications is presented, followed by the discussion on the optimization of the inductive coupling front-end through a codesign approach. The stimulator salvages input energy and stores it in a storage capacitor, and, when the voltage reaches a threshold, releases the energy as an output stimulus. The dynamics of the circuit are automatically enabled by a positive feedback, eliminating any stimulation control circuit blocks. The IC is fabricated in a 180 nm CMOS process and achieves a quiescent current consumption of 1.8 μA. The inductive coupling front-end is optimized as a loaded resonator, in which the input impedance of the custom rectifier directly loads the inductive loop antenna. The loaded quality factor and the rectifier's efficiency determine the reception sensitivity of the stimulator, while a balance should be achieved for the robustness of the system against dielectric medium variations by increasing the reception bandwidth. The finalized stimulator adopts a 4.9 mm × 4.9 mm inductive loop antenna and achieves an overall assembly dimension of 5 mm × 7.5 mm. Operating at the resonant frequency of 198 MHz, the stimulator works at a 14 cm distance from the transmitter in the air. An animal experiment was performed, in which a fully implanted stimulator excited the sciatic nerve of a rat that consequently triggered the movement of the limb.
A RENIN‐SECRETING TUMOUR SENSITIVE TO CHANGES IN CENTRAL BLOOD VOLUME (PRESUMABLY VIA SYMPATHETICS) BUT NOT TO CIRCULATING ANGIOTENSIN II (1990)

1. A 17 year old female presented with severe hypertension, hypokalaemia and elevated levels of plasma renin activity due to a renin-secreting tumour. 2. Renin was responsive to posture, low sodium diet, saline infusion and frusemide, but relatively unresponsive to raising or lowering circulating levels of angiotensin II. 3. Renal venous renin levels lateralized to the side of the tumour with good contralateral suppression when measured with control of posture and avoidance of prior stimulation, with and without angiotensin converting enzyme inhibition. 4. Levels of atrial natriuretic peptide were elevated and responsive to posture, saline infusion and angiotensin infusion. 5. The tumour was evident on computerized tomography, but not on intravenous pyelography or renal angiography. 6. Responsiveness of renin secretion to normal stimuli in reninoma may make diagnosis difficult, and renal vein sampling under controlled conditions is necessary.
Activation of Rabbit Platelets by Platelet-Activating Factor Derived from IgE-Sensitized Basophils (1977)

Platelet-activating factor (PAF) is liberated from antigen-stimulated, IgE-sensitized rabbit basophils and induces aggregation of platelets and secretion of their content of vasoactive amines. Experiments were performed to determine the relationship between these two platelet responses to this stimulus.(a) Aggregation was initiated by appreciably lower concentrations of PAF than were required to produce even minimal release of constituents. PAF-induced aggregation was also resistant to agents which destroy ADP, such as creatine phosphate/creatine phosphokinase or apyrase, and occurred with platelets made unresponsive (refractory) to ADP. It was concluded that PAF can induce aggregation by a mechanism which is distinguishable from the release reaction and from the aggregating effect of ADP.(b) Secretion can probably occur independently of aggregation because incubation without agitation resulted in secretion without detectable aggregation.(c) Despite the suggestion that the two platelet responses can be independent, they may be induced by the same stimulus. This was indicated by experiments in which platelets specifically desensitized to PAF-induced secretion were also found to be unresponsive to PAF-stimulated aggregation. Moreover, identical levels of inhibition and identical inhibition profiles were obtained for both responses with serine esterase inhibitor, diisopropylphosphofluoridate, and with amino acid esters. It was concluded that the same stimulus-specific activable protease (esterase) was most likely involved in PAF-induced aggregation and secretion.
Toll-like receptor 2 signaling modulates the functions of CD4 + CD25 + regulatory T cells (2006)

Toll-like receptors (TLRs) are primary sensors of both innate and adaptive immune systems and play a pivotal role in response against structurally conserved components of pathogens. Synthetic bacterial lipoprotein (BLP) Pam3Cys-SK4 is a TLR2 agonist that is capable of modulating T cell immune responses. We show here that BLP, together with anti-CD3 antibody [T cell receptor (TcR) activation], induced proliferation of both CD4+ CD25+ regulatory T cells (Tregs) and CD4+ CD25- (effector) T cells in the absence of antigen-presenting cells. The expanded Tregs showed a transient loss of suppressive activity. Moreover, BLP rendered effectors resistant to the suppression of Tregs by increasing IL-2 secretion. BLP also transiently suppressed the induction of Foxp3 (X-linked forkhead/winged helix transcription factor) mRNA in Tregs at the first 8-15 h after T cell receptor activation. Consistent with this observation, BLP-stimulated Tregs regained their inhibitory activity and prevented spontaneous colitis induced by effectors in severe combined immunodeficient mice. Our results demonstrate a previously unrecognized pathway by which TLR expressed on T cells may directly modulate the immune response. Thus, during an acute bacterial infection, BLP may rapidly increase the host's adaptive immunity by expanding effectors and also by attenuating the suppressive activity of Tregs. In the process, BLP also expands the Tregs, which recover their suppressive activity when the infection has subsided, in time to limit potential autoimmunity that might result from the overactivated effectors.
Characterization of Ephrin-A1 and Ephrin-A4 as Ligands for the EphA8 Receptor Protein Tyrosine Kinase (1999)

The Eph receptors are the largest known family of receptor protein tyrosine kinases, which play important roles with their ligands called ephrin in the neural development, angiogenesis, and vascular network assembly. It was previously shown that ephrin-A2, -A3 and -A5 bind to, and activate the EphA8 receptor tyrosine kinase, respectively. In this study, we have examined if there are other additional ephrin ligands interacting with the EphA8 receptor tyrosine kinase expressed in NIH3T3 fibroblasts. For this purpose, we have constructed chimeric ephrin-A1, -A4, -B1, -B2 or -B3 ligands consisting of the Fc portion of human IgG fused to their carboxyl-terminus. Both ephrin-A1 and ephrin-A4 chimeric ligands efficiently bound to the EphA8 receptor expressed in NIH3T3 fibroblasts, whereas the transmembrane ligands including ephrin-B1, -B2 and -B3 did not. Additionally we have demonstrated that both the EphA8-TrkB chimeric receptor and the EphA8 receptor expressed in NIH3T3 fibroblasts are efficiently tyrosine-phosphorylated upon stimulating with epthin-A1 or -A4 but none of transmembrane ephrin-B proteins. These results strongly indicate that the EphA8 receptor functions exclusively as an glycosyl phosphatidylinositol (GPI)-linked ephrin ligand-dependent receptor protein tyrosine kinase.
Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys (1997)

In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV-89.6) expressing the human immunodeficiency virus type 1 (HIV-1) tat, rev, vpu, and env genes generated pathogenic viruses (SHIV-89.6P) inducing rapid CD4+ lymphocyte depletion and AIDS-like illness in rhesus monkeys (K. Reimann, J. T. Li, R. Veazey, M. Halloran, I.-W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin, J. Virol. 70:6922-6928, 1996). To characterize the molecular changes responsible for this increase in virulence, infectious proviral clones of SHIV-89.6P isolates were derived. Viruses generated from some of these clones caused a rapid and profound decline of CD4+ lymphocytes in a high percentage of inoculated monkeys. Nucleotide changes potentially responsible for the increased virulence of SHIV-89.6P were limited to the env, tat, or long terminal repeat sequences, with most of the observed changes in env. Nucleotide changes in env altered 12 amino acids in the gp120 and gp41 exterior domains, and a 140-bp deletion in env resulted in the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for that of the HIV-1 gp41 glycoprotein. The availability of pathogenic proviral clones should facilitate dissection of the molecular determinants of SHIV-89.6P virulence.
Particle–Film Plasmons on Periodic Silver Film over Nanosphere (AgFON): A Hybrid Plasmonic Nanoarchitecture for Surface-Enhanced Raman Spectroscopy (2015)

Plasmonic systems based on particle-film plasmonic couplings have recently attracted great attention because of the significantly enhanced electric field at the particle-film gaps. Here, we introduce a hybrid plasmonic architecture utilizing combined plasmonic effects of particle-film gap plasmons and silver film over nanosphere (AgFON) substrates. When gold nanoparticles (AuNPs) are assembled on AgFON substrates with controllable particle-film gap distances, the AuNP-AgFON system supports multiple plasmonic couplings from interparticle, particle-film, and crevice gaps, resulting in a huge surface-enhanced Raman spectroscopy (SERS) effect. We show that the periodicity of AgFON substrates and the particle-film gaps greatly affects the surface plasmon resonances, and thus, the SERS effects due to the interplay between multiple plasmonic couplings. The optimally designed AuNP-AgFON substrate shows a SERS enhancement of 233 times compared to the bare AgFON substrate. The ultrasensitive SERS sensing capability is also demonstrated by detecting glutathione, a neurochemical molecule that is an important antioxidant, down to the 10 pM level.
Real time and full-range complex fourier domain optical coherence tomography (2005)

High speed complex full-range Fourier domain optical coherence tomography (FD-OCT) is demonstrated. This FD-OCT requires only a single A-scan for each single transversal position for full-range Fourier domain optical coherence tomography. The Fourier transform method is applied along the direction of the B-scan to reconstruct complex spectra, and the complex spectra compose a full-range OCT image.
Primary structure of rat brain sodium channel III deduced from the cDNA sequence (1988)

The complete amino acid sequence of a third sodium channel (designated sodium channel III) from rat brain has been deduced by cloning and sequence analysis of the cDNA. This protein is homologous in amino acid sequence and shares characteristic structural features with other sodium channels.
Mouse Cristin/R-spondin Family Proteins Are Novel Ligands for the Frizzled 8 and LRP6 Receptors and Activate β-Catenin-dependent Gene Expression (2006)

Wnt signaling plays critical biological roles during normal embryonic development and homeostasis in adults. In the canonical pathway, binding of Wnt ligands to the Frizzled (Fzd) receptor and the low density lipoprotein-related receptor (LRP) 5 or LRP6 coreceptor initiates downstream signaling events leading to gene activation by beta-catenin and the T-cell factor (TCF)-lymphoid enhancer factor (LEF) family transcription factor complex. In this study, we provide several lines of evidence that the mouse Cristin/R-spondin family proteins function as Fzd8 and LRP6 receptor ligands and induce the canonical Wnt/beta-catenin signaling pathway, leading to TCF-dependent gene activation. First, conditioned medium containing Cristin/R-spondin proteins effectively induced reporter activity in a TCF-binding site-dependent manner. Second, stimulation of cells with Cristin/R-spondin was accompanied by stabilization of endogenous beta-catenin proteins and induction of canonical Wnt target genes. Third, Cristin/R-spondin proteins physically interacted with the extracellular domains of the LRP6 and Fzd8 receptors in vivo and in vitro. Interestingly, unlike canonical Wnt ligands, Cristin/R-spondin failed to form a ternary complex with both LRP6 and Fzd8 receptors, suggesting that R-spondin may activate the canonical Wnt signaling pathway by different mechanisms. Furthermore, Cristin/R-spondin proteins possess an intriguing positive modulatory activity on Wnt ligands, possibly through a direct interaction. Our findings expand the repertoire of ligands that induce beta-catenin/TCF-dependent gene activation and implicate the presence of active beta-catenin-dependent gene activation in a Wnt-free biological context.
Norbornenes and [n]polynorbornanes as molecular scaffolds for anion recognition (2010)

\n\t\t\t\t\tIn total, 18 novel norbornene and [n]polynorbornane based anion receptors were synthesised and evaluated. The host:guest complexes examined were influenced by the position and number of available recognition sites within each binding cleft. It was concluded that [n]polynorbornane scaffolds are ideal for studying the fundamental concepts of supramolecular chemistry.\n\t\t\t\t
Epidemiologic features of von Willebrand's disease in Doberman Pinschers, Scottish Terriers, and Shetland Sheepdogs: 260 cases (1984-1988) (1992)

During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.
Domains of invasion organelle proteins from apicomplexan parasites are homologous with the Apple domains of blood coagulation factor XI and plasma pre‐kallikrein and are members of the PAN module superfamily (2001)

Micronemes are specialised organelles, found in all apicomplexan parasites, which secrete molecules that are essential for parasite attachment to and invasion of host cells. Regions of several microneme proteins have sequence similarity to the Apple domains (A-domains) of blood coagulation factor XI (FXI) and plasma pre-kallikrein (PK). We have used mass spectrometry on a recombinant-expressed, putative A-domain from the microneme protein EtMIC5 from Eimeria tenella, to demonstrate that three intramolecular disulphide bridges are formed. These bridges are analogous to those that stabilise A-domains in FXI and PK. The data confirm that the apicomplexan domains are structural homologues of A-domains and are therefore novel members of the PAN module superfamily, which also includes the N-terminal domains of members of the plasminogen/hepatocyte growth factor family. The role of A-domains/PAN modules in apicomplexan parasites is not known, but their presence in the microneme suggests that they may be important for mediating protein-protein or protein-carbohydrate interactions during parasite attachment and host cell invasion.
Changes in Bronchial Epithelium in Relation to Cigarette Smoking and in Relation to Lung Cancer (1961)

IN 1957 two of us (O.A. and A.P.S.), with several collaborators, presented a report of progress on a study of the relative frequency of carcinoma in situ, squamous metaplasia, stratification and basal-cell hyperplasia in the lungs of nonsmokers and light and heavy smokers of cigarettes.1 The study was carried out on the lungs of 117 male patients dying with and without lung cancer by means of step sections of the entire tracheobronchial tree, totaling 208 sections per case. This was done in conformity with a rigidly observed plan, the details of which are fully described in the preceding publication. . . .
Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers (2002)

Expression of the Wilms' tumor gene WT1 in de novo lung cancer was examined using quantitative real-time RT-PCR and immunohistochemistry. Overexpression of the WT1 gene was detected by RT-PCR in 54/56 (96%) de novo non-small cell lung cancers examined and confirmed by detection of WT1 protein with an anti-WT1 antibody. Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. Furthermore, when the WT1 gene was examined for mutations by direct sequencing of genomic DNA in 7 lung cancers, no mutations were found. These results suggest that the nonmutated, wild-type WT1 gene plays an important role in tumorigenesis of de novo lung cancers and may provide us with the rationale for new therapeutic strategies for lung cancer targeting the WT1 gene and its products.
Upstream Sequences Required for Efficient Expression of a Soybean Heat Shock Gene (1986)

A soybean gene (Gmhsp17.5-E) encoding a small heat shock protein was introduced into primary sunflower tumors via T-DNA-mediated transformation. RNA blot hybridizations and S1-nuclease hybrid protection studies indicated that the heat shock gene containing 3.25 kilobases of 5'-flanking sequences was strongly transcribed in a thermoinducible (40 degrees C) manner. Transcriptional induction also occurred to a lesser extent upon treatment of whole tumors with sodium arsenite and CdCl2. Basal (26 degrees C) transcription was not detected in soybean seedlings, but it was quite evident in transformed tumor tissue. A 5' deletion to -1,175 base pairs with respect to the CAP site had no effect on the levels of thermoinducible transcription, but it resulted in a large increase in basal transcription. Further removal of DNA sequences (including the TATA-distal heat shock consensus element) to -95 base pairs reduced thermoinducible transcription by 95% and also greatly decreased basal transcription. The termini of the Gmhsp17.5-E RNA in the tumor were generally the same as those present in soybean RNA, with the exception of several additional 3' termini.