gebhart/patrepeval huggingface dataset:
The immunology and serology of leishmanisis IV. Results of ouchterlony double diffusion tests (1966)

Journal Article The immunology and serology of leishmanisis IV. Results of ouchterlony double diffusion tests Get access R.S. Bray, R.S. Bray Department of Parasitology, London School of Hygiene and Tropical Medicine, Keppel St., London, W.C.1 UK Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Lainson R. Lainson Department of Parasitology, London School of Hygiene and Tropical Medicine, Keppel St., London, W.C.1 UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 60, Issue 5, 1966, Pages 605–609, https://doi.org/10.1016/0035-9203(66)90006-X Published: 01 January 1966
Lysosomal Storage Disease: Revealing Lysosomal Function and Physiology (2010)

The discovery over five decades ago of the lysosome, as a degradative organelle and its dysfunction in lysosomal storage disorder patients, was both insightful and simple in concept. Here, we review some of the history and pathophysiology of lysosomal storage disorders to show how they have impacted on our knowledge of lysosomal biology. Although a significant amount of information has been accrued on the molecular genetics and biochemistry of lysosomal storage disorders, we still do not fully understand the mechanistic link between the storage material and disease pathogenesis. However, the accumulation of undegraded substrate(s) can disrupt other lysosomal degradation processes, vesicular traffic, and lysosomal biogenesis to evoke the diverse pathophysiology that is evident in this complex set of disorders.
Hybridoma Produces Protective Antibodies Directed Against the Sporozoite Stage of Malaria Parasite (1980)

Hybrid cells secreting antibodies against sporozoites of Plasmodium berghei were obtained by fusion of plasmacytoma cells with immune murine spleen cells. The monoclonal antibodies bound to a protein with an apparent molecular weight of 44,000 (Pb44), which envelopes the surface membrane of sporozoites. Incubation of sporozoites in vitro with antibodies to Pb44 abolished their infectivity.
Fe doping and preparation of semi insulating InP by wafer annealing under Fe phosphide vapor pressure (2002)

Semi-insulating (SI) InP has been industrially produced by doping Fe atoms as deep acceptors. Fe concentrations in InP are, however, largely varied from top to tail along the crystal growth axis because of impurity segregation. In the present work, we have examined the possibility of vapor phase doping for producing 50 mm diameter SI InP wafers with constant Fe concentrations by using a wafer annealing procedure. Small amount of Fe was charged with red phosphorus in ampoules in which InP wafers were annealed. It was found that the vapor phase doping is effective for Fe doping in InP. The present technology can be applied for the production of low Fe doped SI InP wafers with the same Fe concentration for all wafers from one InP ingot.
Mutations of Serine 236−237 and Tyrosine 302 Residues in the Human Lipoxin A4 Receptor Intracellular Domains Result in Sustained Signaling (2000)

Lipoxin A(4) (LXA(4)) is a potent negative modulator of the inflammatory response. The antiinflammatory activities of LXA(4), such as inhibition of agonist-induced polymorphonuclear cell (PMN) chemotaxis and upregulation of beta-2 integrins, require the expression of a G-protein-coupled, high-affinity LXA(4) receptor (LXA(4)R). We now report that stimulation of PMN with proinflammatory agonist N-formyl peptides (FMLP), calcium ionophore A(23187), or phorbol mirystate acetate (PMA) is followed by marked downregulation of LXA(4) binding (B(max) decrease of approximately 45%) and decreased activation of phospholipases A(2) (PLA(2)) and D (PLD). Elucidation of the mechanisms underlying these effects was addressed by structure-function analyses of the intracellular domains of LXA(4)R. Mutant molecule, S236/S237 --> A/G (LXA(4)R(pk)) and Y302 --> F (LXA(4)R(tk)) were obtained by site-directed mutagenesis to yield receptors lacking the putative targets for serine/threonine kinase- or tyrosine kinase-dependent phosphorylation. Expression of wild-type and mutated LXA(4)R sequences in CHO and HL-60 cells was used to examine LXA(4) ligand-receptor interactions and signal transduction events. Results indicated that cells expressing LXA(4)R(pk) or LXA(4)R(tk) displayed sustained activation of PLA(2) and PLD in contrast to the transient ones obtained with LXA(4)R(wt) (peak activation at 2-3 min). Moreover, inhibition of LXA(4)-dependent PLA(2) activity by PMA in LXA(4)R(wt) transfected CHO cells was not observed in cells expressing LXA(4)R(pk). Phosphopeptide immunoblotting revealed that the functional differences between wild-type and mutant LXA(4) receptors are accompanied by distinct changes in the receptor protein phosphorylation pattern. Further characterization of these and related LXA(4)R intracellular domains will help to better understand specific events that regulate the antiinflammatory activities of LXA(4).
Adenovirus Type 5 Rupture of Lysosomes Leads to Cathepsin B-Dependent Mitochondrial Stress and Production of Reactive Oxygen Species (2011)

In response to viral infection, reactive oxygen species (ROS) mediate innate immune signaling or generate danger signals to activate immune cells. The mechanisms of virally induced ROS are poorly defined, however. We demonstrate that ROS are produced within minutes of adenovirus type 5 (Ad5) infection of macrophages and that oxidative stress supports Ad5-induced cytokine secretion. We show that short hairpin RNA (shRNA) knockdown of TLR9 has no effect on ROS production despite observed decreases in Ad-induced cytokine secretion. A major source of ROS in macrophages is NADPH oxidase. However, shRNA knockdown of the NADPH oxidase subunit NOX2 does not attenuate Ad-induced ROS. Induction of ROS is not observed in cells infected with a temperature-sensitive mutant of Ad2, ts1, which is defective in endosomal membrane penetration during cell entry. Further, Ad5, but not ts1, induces the release of lysosomal cathepsin B into the cytoplasm of infected cells. In agreement with this finding, we observe a loss of mitochondrial membrane potential upon Ad infection which requires Ad endosomal membrane penetration and cathepsin B activity. Overexpression of Bcl-2 attenuates Ad5-induced ROS, further supporting the role for mitochondrial membrane destabilization as the source of ROS in response to Ad5 infection. Together, these data suggest that ROS produced in response to Ad5 infection depends on the virally induced endosomal membrane rupture to release lysosomal cathepsins. Furthermore, the release of cathepsins leads to mitochondrial membrane disruption and thus the release of ROS from the mitochondria.
Expression of M‐cadherin protein in myogenic cells during prenatal mouse development and differentiation of embryonic stem cells in culture (1994)

Molecules regulating morphogenesis by cell-cell interactions are the cadherins, a class of calcium-dependent adhesion molecules. One of its members, M-cadherin, has been isolated from a myoblast cell line (Donalies et al. [1991] Proc. Natl. Acad. Sci. U.S.A. 88:8024-8028). In mouse development, expression of M-cadherin mRNA first appears at day 8.5 of gestation (E8.5) in somites and has been postulated to be down-regulated in developing muscle masses (Moore and Walsh [1993] Development 117:1409-1420). Affinity-purified polyclonal M-cadherin antibodies, detecting a protein of approximately 120 kDa, were used to study the cell expression pattern of M-cadherin protein. It was first visualized in somites at E10 1/3 and could be confined to desmin positive, myotomal cells. At all subsequent prenatal stages, M-cadherin was only found in myogenic cells of somitic origin. The detection of the protein at E10 1/3 suggests a translational delay of M-cadherin mRNA of 1 to 2 days (E8.5 vs. E10 1/3). This was further supported by the finding that during differentiation of ES cell line BLC6 into skeletal muscle cells in culture, expression of M-cadherin mRNA can be detected 2 days prior to M-cadherin protein. During prenatal development, the pattern of M-cadherin expression changes: In E10 1/3 embryos and also in myotomal cells of later stages, M-cadherin is evenly distributed on the cell surface. In developing muscle masses (tested at E16 to E18), however, M-cadherin protein becomes clustered most likely at sites of cell-cell contact as indicated by double-labelling experiments: M-cadherin-staining is the positive image of laminin negative areas excluding the presence of a basal lamina at M-cadherin positive sites. Furthermore, M-cadherin is coexpressed with the neuronal cell adhesion molecule N-CAM which has been shown to mediate cell-cell contact in myogenic cells. In summary, our results are in line with the idea that M-cadherin might play a central role in myogenic morphogenesis.
Assessment of Electrode Placement and Audiological Outcomes in Bilateral Cochlear Implantation (2011)

We have assessed electrode placement and correlated it with audiological outcome. The presence of the electrodes solely in the ST was not predictive of outcome. We estimate that it would take analyzing data of thousands of CI patients before any valid correlations can be made.
Objective response rate in a phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC) which has progressed during treatment with T (2007)

1004 Background: T and P bind to different epitopes on the extra cellular domain of HER2. Unlike T, P binds to the dimerization domain and blocks homo- and hetero-dimerization of HER2 with other HER kinase family members. Xenograft models support the hypothesis that the complementary mechanisms of action could result in augmented efficacy when T and P are combined. Methods: Two-stage design, criteria to proceed to the 2 nd stage were: ≥ 2 partial responses (PR) or 1 PR and 12 stable disease (SDs) or 13 SDs. Eligibility included: measurable, centrally-tested HER2 positive breast cancer; up to 3 lines of prior chemotherapy plus T (including adjuvant chemotherapy plus T); disease progression during T as most recent treatment for metastatic disease; baseline left ventricular ejection fraction (LVEF) ≥ 55% and no decrease of LVEF to below 50% during prior T treatment. Consenting Pts received T i.v. weekly or every 3 weeks at 2 mg/kg or 6 mg/kg respectively (with re-loading dose if required) plus 420mg fixed dose of P i.v. every 3 weeks following loading dose 840mg. Study treatment was initiated within 9 weeks of the last dose of T given as most recent therapy. An independent data safety monitoring board has overseen the 1 st stage safety data. Results: Recruitment into 1 st stage is complete. The main adverse events were diarrhea (71%), fatigue (46%), nausea/vomiting (38%) and rash (25%). Most AE’s were mild to moderate (there was 1 case of Grade 3 diarrhea) and none was treatment-limiting. There were no clinical cardiac events, and central review revealed no case of fall in LVEF of ≥10% and to ≤50%. Response status: 5 confirmed PR (21%); 12 SD (50%). Responses have been observed in lymph node and liver metastases. Recruitment into the 2 nd stage of the trial has commenced. Conclusions: The combination of the P and T is active and well tolerated in patients with pre-treated HER2 positive breast cancer which has progressed during treatment with T. No significant financial relationships to disclose.
Left Ventricular Diastolic Function in Hypertension and Role of Plasma Glucose and Insulin (1996)

Hypertension is associated with increased diastolic stiffness of the left ventricle, which is enhanced by moderate obesity, and abnormal carbohydrate metabolism. Experimentally and in humans, hypertension is associated with interstitial fibrosis of mycardium, the presumed basis for the diastolic dysfunction. Chamber stiffness in group 4 hypertensives was similar to that in the lean diabetics but less than that in the obese diabetics. Although the latter exhibited a correlation with plasma hemoglobinAIC, the large rise in stiffness suggests a potential role for growth factors in further alteration of myocardial composition.
Readers panel (2004)

A court has banned a persistently abusive patient from every NHS facility in England and Wales. We asked our readers panel if they thought this was the right decision
15.1: Invited Paper: A 46‐inch TFT‐LCD HDTV Technology with Color Management and Image Quality Enhancement (2004)

Abstract We have developed a 46‐inch TFT‐LCD HDTV (high definition television — 1080p) with digital color management and image enhancement technologies. The panel uses premium MVA (multi‐domain vertical alignment liquid crystals, and is fabricated on generation‐5 glass substrates with ODF process ( o ne d rop f illed liquid crystal process). It adopts the true wide format of 16:9. The viewing angle at a CR (contrast ratio) of 10:1 is greater than 170° in all directions. In the normal direction, CR is above 800. For conventional color management and image quality enhancement, we optimized the color performance between color‐filters and backlight units as well as the properties of VA LC and polarizers. The outcomes include high color gamut (75% of NTSC) and brightness (&gt; 600 nits). More advanced digital color management techniques include the application of vivid color mapping, and gamma correction by signal processing. For the quality of fast moving pictures, we have developed a new driving approach in conjunction with advanced VA LC's to achieve a response speed of 8 ms in average. The new approach compensates the slow transition between gray levels.
Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells (1990)

Calcium ions serve as intracellular messengers in 2 activities of hair cells: in conjunction with Ca2(+)-activated K+ channels, they produce the electrical resonance that tunes each cell to a specific frequency of stimulation, and they trigger the release of a chemical synaptic transmitter. Our experiments indicate that both of these functions are conducted within a region that extends a few hundred nanometers around each presynaptic active zone. In focal electrical recordings from the plasma membranes of isolated anuran hair cells, we found nearly all of a cell's Ca2+ channels and Ca2(+)-activated K+ channels clumped at a fixed ratio in an average of 20 clusters on the basolateral membrane surface. Because serial-section electron microscopy indicated that each hair cell has approximately 19 afferent synaptic contacts with a similar distribution upon its basolateral surface, we conclude that the channel clusters coincide with synaptic active zones. Ensemble-variance analysis of current fluctuations indicated that each cell has a total of approximately 1800 Ca2+ channels and approximately 700 Ca2(+)-activated K+ channels; if these are uniformly divided, we estimate that each channel cluster contains approximately 90 Ca2+ and approximately 40 Ca2(+)-activated K+ channels. Freeze-fracture electron microscopy demonstrated an average of 133 large intramembrane particles in the presynaptic membrane at each active zone, an observation that suggests that the particles are the clustered channels. We used the K+ channel's sensitivity to intracellular Ca2+ to assay the concentration of free Ca2+ in the presynaptic cytoplasm, which we found to vary between 10 microM and 1 mM over the physiological range of membrane potentials. The inferred concentrations agreed with the values predicted for free diffusion of Ca2+ away from Ca2+ channels scattered randomly within a 300-nm-diameter synaptic active zone. The close association among Ca2+ channels, Ca2(+)-activated K+ channels, and synaptic active zones is necessary both for the rapid activation of K+ currents required in electrical resonance and for the transmission at afferent synapses of information about the phases of high-frequency stimuli.
High-transconductance InAs/AlSb heterojunction field-effect transistors with delta -doped AlSb upper barriers (1992)

The authors report the fabrication and temperature-dependent characterization of InAs/AlSb quantum-well heterojunction field-effect transistors (HFETs). Devices with electron sheet concentrations of 3.8*10/sup 12/ cm/sup -2/ and low-field electron mobilities of 21000 cm/sup 2//V-s have been realized through the use of Te delta -doping sheets in the upper AlSb barrier. One device with a 2.0- mu m gate length showed a peak extrinsic transconductance of 473 mS/mm at room temperature. Gate leakage current, operating current density, and extrinsic transconductance were found to decrease with decreasing temperature.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reducing the optical power penalty for electronicallydispersion compensated LED pulse transmission by using multi-bit shift decision feedback (2000)

The large power penalties encountered in the linear electronic compensation of dispersion induced LED pulse distortion can be reduced by using an electronic decision feedback equalisation scheme. It is shown that with multi-bit shift feedback the residual penalty is comparable to that achieved when using a dispersion compensating fibre.
SubClonal Hierarchy Inference from Somatic Mutations: automatic reconstruction of cancer evolutionary trees from multi-region next generation sequencing (2014)

Abstract Recent improvements in next-generation sequencing of tumor samples and the ability to identify somatic mutations at low allelic fractions have opened the way for new approaches to model the evolution of individual cancers. The power and utility of these models is increased when tumor samples from multiple sites are sequenced. Temporal ordering of the samples may provide insight into the etiology of both primary and metastatic lesions and rationalizations for tumor recurrence and therapeutic failures. Additional insights may be provided by temporal ordering of evolving subclones – cellular subpopulations with unique mutational profiles. Current methods for subclone hierarchy inference tightly couple the problem of temporal ordering with that of estimating the fraction of cancer cells harboring each mutation. We present a new framework that includes a rigorous statistical hypothesis test and a collection of tools that make it possible to decouple these problems, which we believe will enable substantial progress in the field of subclone hierarchy inference. The methods presented here can be flexibly combined with methods developed by others addressing either of these problems. We provide tools to interpret hypothesis test results, which inform phylogenetic tree construction, and we introduce the first genetic algorithm designed for this purpose. The utility of our framework is systematically demonstrated in simulations. For most tested combinations of tumor purity, sequencing coverage, and tree complexity, good power (≥ 0.8) can be achieved and Type 1 error is well controlled when at least three tumor samples are available from a patient. Using data from three published multi-region tumor sequencing studies of (murine) small cell lung cancer, acute myeloid leukemia, and chronic lymphocytic leukemia, in which the authors reconstructed subclonal phylogenetic trees by manual expert curation, we show how different configurations of our tools can identify either a single tree in agreement with the authors, or a small set of trees, which include the authors’ preferred tree. Our results have implications for improved modeling of tumor evolution and the importance of multi-region tumor sequencing. Author Summary Cancer is a genetic disease, driven by DNA mutations. Each tumor is composed of millions of cells with differing genetic profiles that compete with each other for resources in a process similar to Darwinian evolution. We describe a computational framework to model tumor evolution on the cellular level, using next-generation sequencing. The framework is the first to apply a rigorous statistical hypothesis test designed to inform a new search algorithm. Both the test and the algorithm are based on evolutionary principles. The utility of the framework is shown in computer simulations and by automated reconstruction of the cellular evolution underlying murine small cell lung cancers, acute myeloid leukemias and chronic lymophocytic leukemias, from three recent published studies.
Viral P21 Ki‐RAS protein: A potent intracellular mitogen that stimulates adenylate cyclase activity in early G1 phase of cultured rat cells (1987)

Rat kidney (NRK) cells infected with a temperature-sensitive mutant of the Kirsten sarcoma virus were arrested in the G0/G1 phase of their cell cycle by incubation in serum-deficient medium at a p21-inactivating temperature of 41 degrees C. These quiescent ts K-NRK cells were then stimulated to transit G1 and initiate DNA replication by lowering the temperature to 36 degrees C, which rapidly reactivated p21. Reactivating the viral Ki-RAS protein by temperature shift led to an increase in adenylate cyclase activity in early G1 phase. The Ki-RAS protein increased the sensitivity of adenylate cyclase to guanyl nucleotides by a mechanism that seemed to involve inactivation of the enzyme's inhibitory G1 regulatory protein.
Porous silicon photonic crystals for detection of infections (2012)

In this paper we demonstrate the possibility of modifying porous silicon (PSi) particles with surface chemistry and immobilizing a biopolymer, gelatin for the detection of protease enzymes in solution. A rugate filter, a one-dimensional photonic crystal, is fabricated that exhibits a high-reflectivity optical resonance that is sensitive to small changes in the refractive index. To immobilize gelatin in the pores of the particles, the hydrogen-terminated silicon surface was first modified with an alkyne, 1,8-nonadiyne <i>via </i>hydrosilylation to protect the silicon surfaces from oxidation. This modification allows for further functionality to be added such as the coupling of gelatin. Exposure of the gelatin modified particles to the protease subtilisin in solution causes a change in the refractive index, resulting in a shift of the resonance to shorter wavelengths, indicating cleavage of organic material within the pores. The ability to monitor the spectroscopic properties of microparticles, and shifts in the optical signature due to changes in the refractive index of the material within the pore space, is demonstrated.
Development and Applications of a Practical Continuous Flow Microwave Cell (2004)

A series of synthetic transformations were successfully and safely scaled up to multigram quantities using focused microwave irradiation with a continuous flow reaction cell that was developed in-house and which can be easily adapted to commercially available instrumentation. The representative reactions that were investigated included aromatic nucleophilic substitution (SNAr), esterification, and the Suzuki cross-coupling reaction. In general, the product yields were equivalent to or greater than those run under conventional thermal heating conditions.