gebhart/patrepeval huggingface dataset:
Immunoglobulin E, a pathogenic factor in Plasmodium falciparum malaria (1997)

Most children and adults living in areas where the endemicity of Plasmodium falciparum malaria is high have significantly elevated levels of both total immunoglobulin E (IgE) and IgE antimalarial antibodies in blood. This elevation is highest in patients with cerebral malaria, suggesting a pathogenic role for this immunoglobulin isotype. In this study, we show that IgE elevation may also be seen in severe malaria without cerebral involvement and parallels an elevation of tumor necrosis factor alpha (TNF). IgE-containing serum from malaria immune donors was added to tissue culture plates coated with rabbit anti-human IgE antibodies or with P. falciparum antigen. IgE-anti-IgE complexes as well as antigen-binding IgE antibodies induced TNF release from peripheral blood mononuclear cells (PBMC). Nonmalaria control sera with no IgE elevation induced significantly less of this cytokine, and the TNF-inducing capacity of malaria sera was also strongly reduced by passing them over anti-IgE Sepharose columns. The cells giving rise to TNF were adherent PBMC. The release of this cytokine probably reflects cross-linking of their low-affinity receptors for IgE (CD23) by IgE-containing immune complexes known to give rise to monocyte activation via the NO transduction pathway. In line with this, adherent monocytic cells exposed to IgE complexes displayed increased expression of CD23. As the malaria sera contained IgG anti-IgE antibodies, such complexes probably also play a role in the induction of TNF in vivo. Overproduction of TNF is considered a major pathogenic mechanism responsible for fever and tissue lesions in P. falciparum malaria. This overproduction is generally assumed to reflect a direct stimulation of effector cells by certain parasite-derived toxins. Our results suggest that IgE elevation constitutes yet another important mechanism involved in excessive TNF induction in this disease.
Decreased natural killer cell activity in atopic eczema. (1985)

We have studied NK cell activity in atopic and non-atopic subjects using a standard 51Cr-release assay and K562 target cells. In atopics (AT) with allergic rhinitis and/or asthma, NK cell activity was similar to that in non-atopic (N) subjects, whilst patients with severe atopic eczema (AE) had depressed NK cell activity compared to AT or N subjects. In addition, circulating T-cell numbers and Con A responsiveness was decreased in AE, although neither parameter was correlated with decreased NK cell activity. However, decreased NK cell activity in atopic eczema was positively correlated with decreased numbers of Fc gamma + lymphocytes (P = 0.01) and decreased effector: target cell binding (P = 0.05), and negatively correlated with increased monocytes in AE (P = 0.09). AE NK cell activity was equally or more sensitive to the inhibitory effects of drugs such as dibutyryl cyclic AMP, prostaglandins (PG) D2,E2 and histamine. The relative percentage increase in NK cell activity by the interferon inducer poly I:C was similar in AE patients and controls. The results suggest that reduced numbers of circulating NK cells and pre-NK cells account for the depressed level of NK cell activity in subjects with severe atopic eczema.
Expression and immunogenicity of the extracellular domain of the human immunodeficiency virus type 1 envelope glycoprotein, gp160 (1989)

The envelope glycoprotein of human immunodeficiency virus type 1 is synthesized as a precursor, gp160, that subsequently is cleaved to yield mature gp120 and gp41. In these studies, the gene encoding gp160 was mutagenized so as direct the synthesis of a truncated protein consisting of the extracellular domains of both gp120 and gp41. The variant protein, termed sgp160, consisted of 458 amino acids of gp120 and 172 amino acids of gp41. To facilitate protein purification, the normal polyglycoprotein processing site between gp120 and gp41 was deleted through the use of site-directed mutagenesis. This allowed for the synthesis of a molecule that could be purified by affinity chromatography, using acid elution, without dissociation of the gp120 polypeptide from the gp41 polypeptide. The conformation of the sgp160 variant appeared to be functionally relevant, as reflected by its ability to bind to CD4 with an affinity comparable to that of the variant rgp120. The structure of the sgp160-containing polypeptide differed from that of rgp120 in that it tended to form high-molecular-weight aggregates that could be dissociated to monomers and dimers in the presence of reducing agents. Antibodies against the sgp160 protein reacted with authentic virus-derived gp160, gp120, and gp41; neutralized viral infectivity; and inhibited the binding of rgp120 to CD4. Rabbit antibodies to the sgp160 protein differed from those raised against rgp120 in that they were enriched for populations that blocked CD4 binding but did not prevent human immunodeficiency virus type 1-induced syncytium formation.
The STAT3-independent Signaling Pathway by Glycoprotein 130 in Hepatic Cells (1999)

Interleukin (IL)-6 is a major regulator of hepatic acute-phase plasma protein (APP) genes. The membrane-proximal 133-amino acid cytoplasmic domain of glycoprotein (gp) 130, containing one copy of the Box3 motif, is sufficient to transmit a productive signal to endogenous APP genes in rat hepatoma H-35 cells. In contrast, a mutant gp130 domain lacking the Box3 motif activates Janus kinases to a normal level but fails to activate signal transducer and activator of transcription 3 and to up-regulate a number of APP genes, including thiostatin, fibrinogen, hemopexin, and haptoglobin. However, in the absence of Box3, gp130 still stimulates the expression of alpha2-macroglobulin and synergizes with IL-1 to up-regulate alpha1-acid glycoprotein. The Box3 motif is not required for activation of the SH2-containing protein tyrosine phosphatase 2 or the mitogen-activated protein kinase (MAPK), nor is the immediate induction of egr-1 and junB significantly altered. Surprisingly, gp130 without any functional Box3 stimulates prolonged activation of MAPK, leading to an extended period of up-regulation of egr-1 and to an extracellularly regulated kinase-mediated reduction in the IL-6-stimulated production of thiostatin. IL-6 reduces proliferation of H-35 cells through signaling by the Box3. In addition, cells expressing Box3-deficient gp130 showed distinct morphologic changes upon receptor activation. Taken together, these results indicate that Box3-derived and Box3-independent signals cooperate in the control of hepatic APP genes and that Box3 may be involved in the modulation of MAPK activity in gp130 signaling.
Integration and synchronization of input modes during multimodal human-computer interaction (1997)

Our ability to develop robust multimodal systems will depend on knowledge of the natural integration patterns that typify people’s combined use of different input modes. To provide a foundadon for theory and design, the present research analyzed multimodal interaction while people spoke and wrote to a simulated dynamic map system. Task analysis revealed that multimodal interaction occurred most frequently during spatial location commands, and with intermediate tiequency during selection commands. In addition, microanalysis of input signals identified sequential, simultaneous, point-and-speak, and compound integration patterns, as well as data on the temporal precedence of modes and on inter-modal lags. In synchronizing input streams, the temporal pecedence of writing over speech was a major theme, with pen input conveying location information first in a sentence. Linguistic analysis also revealed that the spoken and written modes consistently supplied complementary semantic information, rather than redundant. One long-term goal of this research is the development of predictive models of natural modality integration to guide the design of emerging multimodal architectures.
Heathrow-experience and evolution (1990)

Through the installation of fiber to residential customers in the community of Heathrow, Florida, Southern Bell, Northern Telecom, and BNR are working to evolve fiber loop technology for large-scale deployment. The system at Heathrow delivers POTS (plain old telephone system), ISDN (integrated services digital network), and video transport for CATV (cable television). POTS was cut into service in June 1988, followed by ISDN in November 1988, and video in June 1989. It is noted that the design and operation of the system have influenced not only the technology and architecture of future systems but also provisioning methods, splicing techniques, and installation of the fiber-optic-network interface at the customer's premises.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modularly designed lightweight anthropomorphic robot hand (2006)

In this paper, the modular design of artificial hands is presented. The modular concept shall be introduced based on the example of the artificial anthropomorphic hand prototype, which is part of the project for the development of a human assistive robot. Particular attention shall be dedicated to details of modular construction and servicing of the hand prototype. Prototype components, functional activities, technical characteristics, and the control system of the hand shall be introduced as well. Additionally, two hand prototypes were attached to a humanoid service robot and first experience gained from their operation will be presented in conclusion
Simultaneous transfer of four functional genes from the HLA class II region into mammalian cells by fusion with yeast spheroplasts carrying an artificial chromosome (1993)

Gene transfer using yeast artificial chromosome (YAC) clones provides an opportunity to study the expression of several linked genes within an environment more closely approximating their normal chromosomal context. A YAC clone spanning 330 kb of the HLA class II region from centromeric of TAP 1 to telomeric of HLA-DQA1 was retrofitted by homologous recombination with a neomycin plasmid targeted either to an Alu repeat sequence within the YAC genomic insert or to the Ura-3 gene within the right arm of the YAC vector. The modified YAC clones were transferred to Chinese hamster ovary or L cells by spheroplast fusion. Eight of 14 Alu-retrofitted and 10 of 15 right arm-retrofitted neomycin clones retained the six human loci known to be encoded by the YAC as well as portions of the left and right YAC vector arms. All tested L cell transformants showed IFN-gamma-inducible TAP 1 and TAP 2 mRNA expression. Two of eight analyzed clones expressed HLA-DQB mRNA and one of four expressed HLA-DQA. Cells expressing both the HLA-DQA and -DQB mRNA showed HLA-DQ cell surface expression. These studies establish the feasibility of introducing groups of functional genes into mammalian cells by spheroplast fusion with a single YAC clone.
Role for the oligodendrocyte cytoskeleton in myelination (1989)

Abstract Enriched cultures of rat brain oligodendrocytes were extracted with a buffer that separated the cells into a Triton X‐100—soluble fraction and an insoluble cytoskeleton (CSK) residue. The buffer was optimised so that intact microtubules were preserved in the CSK residue. The partition of four myelin proteins between the soluble and the CSK fractions was determined by immunoblotting and immunofluorescence. Immunoblotting showed that two integral membrane proteins of myelin, the proteolipid protein (PLP) and the DM‐20 protein, were completely extracted under these conditions. By contrast, a substantial amount of myelin basic protein (MBP) and to a lesser extent 2,3‐cyclic nucleotide‐3‐phosphohydrolase (CNP) remained associated with the CSK residue. The association of these proteins with the CSK was confirmed by immunofluorescence. A remarkable difference in the distribution of microfilaments and microtubules was observed in oligodendrocytes. Immature cells possessed many fine processes that were rich in microfilaments. The cell body of these oligodendrocytes was devoid of microfilaments but did contain microtubules. Furthermore, a close association between CNP and microfilaments and between MBP and microtubules was revealed after detergent lysis. The strong interaction between CNP and filamentous actin was underlined by their concomitant disappearance from the extremeties of the cell at a later stage of development when extensive membrane sheets had formed. Mature cells had fewer, thicker processes than younger cells and their processes contained microtubules, not microfilaments. MBP was present throughout the thick processes and the membrane sheets. These observations suggest roles for CNP and MBP at distinct stages of myelin process formation and support a directive role for the oligodendrocyte's CSK in the formation of myelin.
Treatment of Small Intestine Bacterial Overgrowth with Rifaximin, a Non-Absorbable Rifamycin (1988)

In twelve patients affected by small bowel bacterial overgrowth, diagnosed by means of the lactulose hydrogen breath test, the therapeutic efficacy of a non-absorbable derivative of rifamycin, rifaximin, was evaluated. This study showed that this drug has a satisfactory therapeutic efficacy in contaminated small bowel syndrome and, at the doses tested, is free of side-effects.
Neutropenia (2015)

Abstract Neutropenia is a decrease in the number of neutrophilic leucocytes in the blood. Neutropenia is defined as an absolute neutrophil count or ANC (total white blood cells per litre multiplied by the percentage of neutrophils) more than two standard deviations below the normal mean. The ANC is usually more than 2.0 × 10 9 L −1 . Neutropenia is graded as mild, moderate or severe; severe is less than 0.5 × 10 9 L −1 . Severe neutropenia predisposes to a high risk of bacterial and fungal infections. Neutropenia occurs both as an acquired and as an inherited disorder. Drugs and autoimmune diseases are the common causes of acquired neutropenia. There are many hereditary causes of neutropenia; all of these are rare conditions, but some are quite severe. Proper treatment depends on understanding the cause of neutropenia and its expected duration. Short periods of neutropenia can be managed with careful observation or antibiotics. Patients with severe chronic neutropenia benefit from long‐term treatment with granulocyte colony‐stimulating factor (G‐CSF). Key Concepts Neutrophils are critical for normal defence from infections by bacteria on body surfaces. Blood neutrophil levels below normal, that is, neutropenia, predispose to bacterial and fungal infections. The bone marrow produces neutrophils from haematopoietic stem cells through an orderly process that takes about 10–14 days. Neutropenia is usually due to acquired or intrinsic/hereditary disorders affecting bone marrow production of these cells. When neutrophil production is interrupted by drugs or diseases recovery often takes several days. The risk of infection in patients with neutropenia depends on the severity of neutropenia and its duration. With a brief period, that is, 1–3 days, the risk is relatively low. Severe neutropenia lasting longer is associated with a steadily increasing risk of severe infection and even death. Proper management of neutropenia requires understanding its cause and the expected duration of neutropenia. When it is due to drugs, either cancer chemotherapy or as an idiosyncratic reaction to other drugs, the duration is usually relatively brief and can be managed with observation or antibiotics. Neutropenia lasting more than about 5–7 days and more chronic neutropenia predispose patients to a much higher risk of bacterial and fungal infections. These patients benefit from treatment with granulocyte colony‐stimulating factor (G‐CSF). It is now possible to identify the genetic cause for severe chronic neutropenia in many patients through deoxyribonucleic acid (DNA) sequencing studies. Understanding of the molecular and cellular basis for these disorders is growing rapidly.
Alirocumab: an investigational treatment for hypercholesterolemia (2015)

Click to increase image sizeClick to decrease image size Additional informationNotes on contributorsKausik K RayKausik Kumar Ray is visiting Professor of Cardiovascular Disease Prevention in the Division of Cardiovascular Sciences, University of London, London, UK. Professor Ray received his medical education (MB ChB, 1991) at the University of Birmingham Medical School, UK, his MD (2004) at the University of Sheffield, UK, a postdoctoral fellowship at Harvard Medical School, Massachusetts, USA, and finally an MPhil in Epidemiology (2007) from the University of Cambridge, UK. A Fellow of the American College of Cardiology, the European Society of Cardiology, the American Heart Association and the Royal College of Physicians, Professor Ray is also a member of the British Cardiovascular Society. Professor Ray has been the national lead investigator, served on the committees or been Principal Investigator for several major medical trials, including T-EMERGE 8, SOLID TIMI 52, SAVOR TIMI 54, DAL OUTCOMES II, DAL-ACUTE, ODYSSEY and DECLARE TIMI 58. Professor Ray’s research interests have focused on the prevention and reduction of coronary events. He has investigated the early benefits of statin therapy, the advantages of more/less intensive glycaemic control, and the risks/benefits of aspirin therapy. He continues to investigate the role of lipids, lipoproteins, diabetes, inflammation and thrombosis in recurrent coronary events. He has received numerous research grants including from the British Heart Foundation and the Wellcome Trust Project. At St George’s University of London he developed the Integrated Care Pathway for patients with ACS.
Frequent detection of human papillomavirus 16 E2-specific T-helper immunity in healthy subjects. (2002)

The incidence of genital human papillomavirus (HPV) infections is high in young, sexually active individuals. Most infections are cleared within 1 year after infection. The targets for the cellular immune response in this process of viral clearance remain to be identified, but the expression pattern of the E2 protein in early infection and low-grade cervical intraepithelial neoplasia renders this early protein a candidate antigen. Therefore, we studied the HPV16 E2-specific T-cell responses in more detail. Very strong proliferative responses against one or more peptide-epitopes derived from this antigen can be found in peripheral blood mononuclear cell cultures of approximately half of the healthy donors. Additional analysis revealed that at least a majority of these responses represent reactivity by memory CD4(+) T-helper (Th) 1-type cells capable of secreting IFN-gamma on antigenic stimulation. Interestingly, all of the E2 peptides against which strong responses were detected are clustered in the key functional domains of the E2 protein, which are conserved to considerable extent between HPV types. This suggests that HPV16 E2-specific Th memory may be installed through encounter with HPV types other than HPV16. Indeed, one HPV16 E2-specific Th clone was found to cross-react against homologuous peptides from other HPV types, but three other Th clones failed to show similar cross-reactivity. Therefore, part of the HPV16 E2-specific Th memory may relate to previous encounter of other HPV types, whereas the majority of the immune repertoire concerned is most likely established through infection with HPV16 itself. Our data are the first to reveal that the T-cell repertoire of healthy donors can contain particularly high frequencies of E2-specific memory Th cells and suggest that boosting of this immunity can be used for preventive and therapeutic vaccination against HPV-induced lesions.
Small-signal analysis of the phase-shifted zero-voltage switched PWM converter (1991)

The specific circuit effects in the phase-shifted, zero-voltage switched, pulse width modulated (PS-ZVS-PWM) converter and their impact on the converter dynamics are analyzed. The small-signal model is derived incorporating the effects of phase-shift control and the utilization of transformer leakage inductance and power FETs junction capacitances to achieve zero-voltage resonant switching. The thesis explains the differences in the dynamic characteristics of the PS-ZVS-PWM converter and its PWM counterpart. Model predictions are confirmed by experimental measurements.
The Src-selective Kinase Inhibitor PP1 Also Inhibits Kit and Bcr-Abl Tyrosine Kinases (2003)

4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]- pyrimidine (PP1) was identified as an Src-selective tyrosine kinase inhibitor and has been used extensively to investigate signaling pathways involving Src kinases, including events downstream of the stem cell factor (SCF) receptor c-Kit. While investigating the role of Src kinases in SCF signaling, we found that PP1 completely abrogated the proliferation of M07e cells in response to SCF. PP1 inhibited SCF-induced c-Kit autophosphorylation in intact cells and blocked the activation of mitogen-activated protein kinase and Akt. In vitro kinase assays using immunoprecipitated c-Kit confirmed direct inhibition by PP1. SCF-induced c-Kit phosphorylation was also inhibited by the related inhibitor 4-amino-5- (4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP2) and by STI571 but not by the Src inhibitor SU6656. PP1 inhibited the activity of mutant constitutively active forms of c-Kit (D814V and D814Y) found in mast cell disorders, and triggered apoptosis in the rat basophilic leukemia cell line RBL-2H3 that expresses mutant c-Kit. In addition, PP1 (and PP2) inhibited the in vitro kinase activity and autophosphorylation in whole cells of p210 Bcr-Abl. PP1 reduced the constitutive activation of signal transducer and activators of transcription 5 and mitogen-activated protein kinase and triggered apoptosis in FDCP1 cells expressing Bcr-Abl. These results have implications for the use of PP1 in investigating intracellular signaling and suggest that PP1 or related compounds may be useful in the treatment of malignant diseases associated with dysregulated c-Kit or Abl tyrosine kinase activity.
Time‐resolved contrast‐enhanced 3D MR angiography (1996)

An MR angiographic technique, referred to as 3D TRICKS (3D time-resolved imaging of contrast kinetics) has been developed. This technique combines and extends to 3D imaging several previously published elements. These elements include an increased sampling rate for lower spatial frequencies, temporal interpolation of k-space views, and zero-filling in the slice-encoding dimension. When appropriately combined, these elements permit reconstruction of a series of 3D image sets having an effective temporal frame rate of one volume every 2-6 s. Acquiring a temporal series of images offers advantages over the current contrast-enhanced 3D MRA techniques in that it I) increases the likelihood that an arterial-only 3D image set will be obtained. II) permits the passage of the contrast agent to be observed, and III) allows temporal-processing techniques to be applied to yield additional information, or improve image quality.
Improved timing recovery loop in laser communication (2016)

Timing recovery is one of the key technologies of space laser communication and measurement. Its accuracy directly affects the performance of the whole system. Timing recovery loop based on Gardner timing error detect algorithm is easy to be interfered by timing jitter. This paper proposes an improved timing recovery loop. Simulation results show that the improved timing recovery loop can effectively reduce the timing jitter to improve the tracking precision and have faster acquisition establish time.
2.5 Tb/s (64/spl times/42.7 Gb/s) transmission over 40/spl times/100 km NZDSF using RZ-DPSK format and all-Raman-amplified spans (2002)

We report 2.5 Tb/s (64 /spl times/ 42.7-Gb/s) WDM transmission over 4000 km (forty 100-km spans) of non-zero dispersion-shifted fiber. This capacity /spl times/ distance record of 10 petabit-km/s for 40-Gb/s systems is achieved in a single 53-nm extended L band using return-to-zero differential-phase-shift-keyed modulation, balanced detection, and distributed Raman amplification.