gebhart/patrepeval huggingface dataset:
Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies (2009)

Recombinant immunotoxins are proteins composed of fragments of monoclonal antibodies fused to truncated protein toxins. No agents of this class are approved yet for medical use, although a related molecule, denileukin diftitox, composed of interleukin-2 fused to truncated diphtheria toxin, is approved for relapsed/refractory cutaneous T-cell lymphoma. Recombinant immunotoxins which have been tested in patients with chemotherapy-pretreated hematologic malignancies include LMB-2 (anti-CD25), BL22 (CAT-3888, anti-CD22) and HA22 (CAT-8015, anti-CD22), each containing an Fv fragment fused to truncated Pseudomonas exotoxin. Major responses were observed with LMB-2 in adult T-cell leukemia, chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma, Hodgkin's disease, and hairy cell leukemia (HCL). BL22 resulted in a high complete remission rate in patients with HCL, particularly those without excessive tumor burden. HA22, an improved version of BL22 with higher affinity to CD22, is now undergoing phase I testing in HCL, CLL, non-Hodgkin's lymphoma, and pediatric acute lymphoblastic leukemia.
Iron oxide nanoparticles for neuronal cell applications: uptake study and magnetic manipulations (2016)

Applying mechanical forces via magnetic mediators is a useful approach for biomedical applications. We have examined several types of MNPs and studied the uptake behavior optimized for magnetic neuronal manipulations.
Plasma membrane damage toCandida albicanscaused by chlorine dioxide (ClO2) (2008)

These insights into membrane damages are helpful in understanding the action mode of ClO(2).
Quantum repeaters for communication (1998)

In quantum communication via noisy channels, the error probability scales exponentially with the length of the channel. We present a scheme of a quantum repeater that overcomes this limitation. The central idea is to connect a string of (imperfect) entangled pairs of particles by using a novel nested purification protocol, thereby creating a single distant pair of high fidelity. The scheme tolerates general errors on the percent level.
Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway. (1976)

In this study the physiological role of properdin and the differential subunit composition of the solid phase enzymes of the pathway have been explored. Cell-bound C3 and C5 convertase differ in their C3b requirement. Apparently one molecule of C3b is sufficient to allow formation of C3 convertase (C3b,B), whereas two or more are required for generation of C5 convertase (C3bn,B). This conclusion was drawn from results indicating the critical role of the spacial distribution of C3b molecules on the cell surface in enzyme formation. While the C3/C5 convertase is fully capable of acting on C5 and thereby initiating the assembly of the cytolytic membrane attack complex, it is exceedingly labile and vulnerable to destruction by the C3b inactivator. It is the apparent role of properdin to confer a degree of stability upon the labile enzyme and to protect its C3 convertase function against enzymatic destruction. To achieve these effects, precursor properdin (pre-P) is recruited in a binding-activation reaction by the labile C3/C5 convertase. Multiple C3b molecules appear to be needed for the formation of properdin-activating principle. Three modes of regulation have been described, which involve spontaneous dissociation enzymatic degradation by C3b inactivator and disassembly by beta1H. The functional differences of pre-P and activated properdin (P) were delineated, pre-P displaying a weak affinity for C3b and P the capacity of strong interaction, P generating a soluble C3 convertase in serum and pre-P being unable to do so. Because of the profound differences between native pre-P and the laboratory product P, the question was raised as to whether soluble P represents an unphysiological form of the protein. On the basis of this and other studies, the conclusion was reached that in vitro properdin recruitment constitutes the terminal event of the properdin pathway, and that properdin augments the function of C3/C5 convertase without changing its substrate specificity.
AN IN-VEHICLE DATA LOGGER (1982)

As the complexity of the motor vehicle and the amount of its associated legislation has increased, the quantity of test and development data required from a vehicle, together with the speed of collection, has increased to such an extent that it is no longer practical to employ traditional analogue techniques for the measurement of vehicle parameters. This paper discusses the advantages of data logging and the clean sheet approach to the specification of the In-vehicle Data Logging System, its philosophy and subsequent development. The reasons for the choice of a proprietory logger with software modifications, mass storage medium, graphics package and the desk-top computer used for analysis, are discussed together with the means of coping with extremes of ambient operating temperatures.
Electrically tuneable lateral leakage loss in liquid crystal clad shallow-etched silicon waveguides (2015)

We demonstrate electrical tuning of the lateral leakage loss of TM-like modes in nematic liquid crystal (LC) clad shallow-etched Silicon-on-Insulator (SOI) waveguides. The refractive index of the LC layer can be modulated by applying a voltage over it. This results in a modulation of the effective index of the SOI waveguide modes. Since the leakage loss is linked to these effective indices, tunable leakage loss of the waveguides is achieved. We switch the wavelength at which the minimum in leakage loss occurs by 39.5nm (from 1564nm to 1524.5nm) in a 785nm wide waveguide. We show that the leakage loss in this waveguide can either be increased or decreased by modulating the refractive index of the LC cladding at a fixed wavelength.
与Bob对话:Teacup(英文) (2005)

Dear Friends,I would like to begin this column with a story that tells ussomething about life.It is a story about a teacup.I don’t knowthe author.Here is the story.A customer in an expensive antique shop saw an unusualteacup,and askedMay I see that?I have never seen such abeautiful teacup.As the proprietor handed it to him,the teacup
Intranasal Vaccination with a Secreted Chlamydial Protein Enhances Resolution of GenitalChlamydia muridarumInfection, Protects against Oviduct Pathology, and Is Highly Dependent upon Endogenous Gamma Interferon Production (2006)

There is currently no licensed vaccine against Chlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Conventional vaccination attempts using surface-exposed chlamydial antigens have achieved only partial success. We have employed a novel vaccination strategy using a secreted protein, chlamydial protease-like activity factor (CPAF), which has been shown to degrade host major histocompatibility complex transcription factors and keratin-8 and therefore may allow immune evasion and establishment of a productive infection. Intranasal immunization using recombinant CPAF (rCPAF) plus interleukin-12 (IL-12) (rCPAF+IL-12 immunization) was used to assess the protective immunity against genital Chlamydia muridarum infection in BALB/c mice. rCPAF+IL-12 immunization induced robust gamma interferon (IFN-gamma) production and minimal IL-4 production by splenocytes upon in vitro recall with rCPAF. The total and immunoglobulin G2a (IgG2a) anti-rCPAF antibody levels in serum were significantly elevated after rCPAF+IL-12 vaccination, as were the total antibody, IgG2a, and IgA levels in bronchoalveolar lavage and vaginal fluids when the animals were compared to animals that received rCPAF alone. rCPAF+IL-12-vaccinated mice displayed significantly reduced bacterial shedding upon chlamydial challenge and accelerated resolution of infection compared to mock-immunized (phosphate-buffered saline) animals. Moreover, rCPAF+IL-12-immunized animals exhibited protection against pathological consequences of chlamydial infection, including the development of hydrosalpinx and oviduct dilatation. This vaccination regimen also reduced the development of fibrosis and the influx of neutrophils into the upper genital tract when the animals were compared to mock-immunized (phosphate-buffered saline) animals after bacterial challenge. rCPAF+IL-12-mediated resolution of the bacterial infection and protection against Chlamydia-induced inflammatory disease were highly dependent on endogenous IFN-gamma production. Together, these results demonstrate that secreted chlamydial antigens may be novel vaccine candidates to induce protective immunity.
Syntaxin Requirement for Ca2+-Triggered Exocytosis in Neurons and Endocrine Cells Demonstrated with an Engineered Neurotoxin (2011)

Botulinum neurotoxins cleave synaptic SNAREs and block exocytosis, demonstrating that these proteins function in neurosecretion. However, the function of the SNARE syntaxin remains less clear because no neurotoxin cleaves it selectively. Starting with a botulinum neurotoxin that cleaves both syntaxin and SNAP-25, we engineered a version that retains activity against syntaxin but spares SNAP-25. These mutants block synaptic release in neurons and norepinephrine release in neuroendocrine cells, thus establishing an essential role for syntaxin in Ca2+-triggered exocytosis. These mutants can generate syntaxin-free cells as a useful experimental system for research and may lead to pharmaceuticals that target syntaxin selectively.
The involvement of Fc gamma receptor gene polymorphisms in Kawasaki disease (2006)

Kawasaki disease is an acute febrile syndrome in infancy, characterized by vasculitis of medium-sized arteries. Without treatment the disease can lead to coronary artery lesions (CAL) in approximately 25% of the children. Therapy consists of intravenous immunoglobulins (IVIG), leading to a decrease of complications to 5-16%. Little is known about the working mechanisms of IVIG. In this study we evaluated the involvement of Fcgamma receptors (FcgammaRs) in Kawasaki disease by the determination of the frequency of known single nucleotide polymorphisms (SNPs) in the genes coding for the FcgammaRs and compared this with frequencies in a cohort of healthy controls. There was no difference in the distribution of the functionally relevant genotypes for FcgammaRIIa-131H/R, FcgammaRIIb-232I/T, FcgammaRIIIa-158 V/F and FcgammaRIIIb-NA1/NA2 between the patient group and the healthy controls. Furthermore, there were no polymorphisms linked to the disease severity as indicated by the absence or development of CAL during the disease. Altered transcription or expression of FcgammaR on specific cell types of the immune system may still play a role in susceptibility and treatment success, but at a level different from the functional SNPs in FcgammaR genes tested in this study.
The hormonal and metabolic responses to prolonged hypoglycemia. (1993)

The purpose of this review was to summarize some of the recent advances that have been made in the understanding of the physiology involved in the counter-regulatory response to prolonged hypoglycemia. It is hoped that this review may stimulate thought and increase awareness that other factors, in addition to the glycemic level, can affect the counterregulatory response. However, if the goal of tight metabolic control is to be achieved in subjects with diabetes, the spectre of severe hypoglycemia must be removed. Thus further work is needed to understand the physiologic mechanisms controlling hypoglycemic counterregulation in normal subjects and the syndromes of abnormal counterregulatory responses present in subjects with IDDM.
Listeria monocytogenes Infection Induces Prosurvival Metabolic Signaling in Macrophages (2011)

Host cells use metabolic signaling through the LXRα nuclear receptor to defend against Listeria monocytogenes infection. 25-Hydroxycholesterol is a natural ligand of LXRs that is produced by the enzyme cholesterol 25-hydroxylase (CH25H). We found that expression of Ch25h is upregulated following L. monocytogenes infection in a beta interferon (IFN-β)-dependent fashion. Moreover, increased Ch25h expression promotes survival of L. monocytogenes-infected cells and increases sensitivity of the host to infection. We determined that expression of Cd5l, a prosurvival gene, is controlled by CH25H. In addition, we found that CD5L inhibits activation of caspase-1, promoting survival of infected macrophages. Our results reveal a mechanism by which an intracellular pathogen can prolong survival of infected cells, thus providing itself with a protected environment in which to replicate.
Isolation and characterization of anti-Fc RIII (CD16) llama single-domain antibodies that activate natural killer cells (2007)

FcgammaRIII (CD16) plays an important role in the anti-tumor effects of therapeutic antibodies. Bi-specific antibodies (bsAbs) targeting FcgammaRIII represent a powerful alternative to the recruitment of the receptor via the Fc fragment, but are not efficiently produced. Single-domain antibodies (sdAbs) endowed with many valuable structural features might help to bypass this problem. In the present work, we have isolated anti-FcgammaRIII sdAbs (C21 and C28) from a phage library generated from a llama immunized with FcgammaRIIIB extra-cellular domains. These sdAbs bind FcgammaRIIIA+ NK cells and FcgammaRIIIB+ polymorphonuclear cells, but not FcgammaRI+ or FcgammaRII+ cells, as detected by indirect immunofluorescence. Competition experiments showed that C21 and C28 sdAbs bind different FcgammaRIII epitopes, with C21 recognizing a linear and C28 a conformational epitope of the receptor. Surface plasmon resonance experiments showed that C21 and C28 sdAbs bind FcgammaRIII with a K(D) in the 10 and 80 nM range, respectively. Importantly, the engagement by both molecules of FcgammaRIIIA expressed by transfected Jurkat T cells or by NK cells derived from peripheral blood induced a strong IL-2 and IFN-gamma production, respectively. These anti-FcgammaRIII sdAbs represent versatile tools for generating bsAbs under various formats, able to recruit FcgammaRIII killer cells to target and destroy tumor cells.
Rational Use of Analgesic and Antiinflammatory Drugs (2001)

“Take two aspirin and call me in the morning”? Clinical decision making is no longer so straightforward. Millions of patients take analgesic and antiinflammatory medications regularly. The reasons are simple: these drugs are effective in relieving pain and inflammation,1 and aspirin provides protection from cardiovascular thrombosis.2,3 Osteoarthritis and other painful chronic conditions occur in a population of patients who often have coexisting medical conditions, including conditions associated with an increased risk of cardiovascular disease. Thus, aspirin is frequently prescribed for patients taking other analgesic and antiinflammatory agents. Since the mechanism of action of all these drugs is the inhibition . . .
Evaluation of New Scaffolds of Myeloperoxidase Inhibitors by Rational Design Combined with High-Throughput Virtual Screening (2012)

Myeloperoxidase (MPO) is a major player of the innate immune defense system of human neutrophils and catalyzes the production of strong oxidizing and halogenating antimicrobial products. Because of its role in pathogenesis of many (inflammatory) diseases, there is great interest in the development of efficient and specific inhibitors. Here, using the X-ray structure of MPO, high-throughput molecular docking of 1350000 compounds was performed. From this virtual screening process, 81 were tested for inhibition of the chlorination activity of MPO, finally ending up with eight inhibiting candidates of different chemical structures. These were tested for inhibiting MPO-mediated low-density lipoprotein oxidation and for interacting with the relevant redox intermediates of MPO. The best inhibitors were bis-2,2'-[(dihydro-1,3(2H,4H)-pyrimidinediyl)bis(methylene)]phenol and 8-[(2-aminoethyl)amino]-3,7-dihydro-3-methyl-7-(3-phenoxypropyl)-1H-purine-2,6-dione. Both did not irreversibly inactivate the enzyme but efficiently trapped it in its compound II state. We discuss the mechanism of inactivation as well as pros and cons of the performed selection process.
Insertional gene fusion technology (1999)

The classical 'end to end' gene fusion technique has widely been used for monitoring gene expression, biological screening and purification of recombinant proteins. Recent progress with the 'insertional' gene fusion approach, on the other hand, has demonstrated that this technique can be utilized for membrane protein topology analysis, display of randomized protein libraries and design of biosensor proteins. In this review, we describe examples of insertional gene fusion and compare the old and new gene fusion techniques.
GestureBar (2009)

GestureBar is a novel, approachable UI for learning gestural interactions that enables a walk-up-and-use experience which is in the same class as standard menu and toolbar interfaces. GestureBar leverages the familiar, clean look of a common toolbar, but in place of executing commands, richly discloses how to execute commands with gestures, through animated images, detail tips and an out-of-document practice area. GestureBar's simple design is also general enough for use with any recognition technique and for integration with standard, non-gestural UI components. We evaluate GestureBar in a formal experiment showing that users can perform complex, ecologically valid tasks in a purely gestural system without training, introduction, or prior gesture experience when using GestureBar, discovering and learning a high percentage of the gestures needed to perform the tasks optimally, and significantly outperforming a state of the art crib sheet. The relative contribution of the major design elements of GestureBar is also explored. A second experiment shows that GestureBar is preferred to a basic crib sheet and two enhanced crib sheet variations.
Determination of the mitochondrial protonmotive force in isolated hepatocytes. (1980)

The intracellular distribution of lipophilic ions and weak acids and bases was studied in intact hepatocytes as indicators of gradients of pH and membrane potential. Mitochondrial and plasma membrane potentials of 161 and 32.8 mV (negative inside), respectively, were calculated from the intracellular accumulation of triphenylmethylphosphonium (TPMP+) and thiocyanate in the intact hepatocyte, assuming a two-compartment model. The predominantly mitochondrial localization of TPMP+ was confirmed using disruption procedures that selectively break the plasma membrane but not the mitochondrial membrane. The intracellular distribution of 5,5-dimethyloxazolidine-2,4-dione and methylamine was studied with similar techniques. A cytosolic pH of 6.95 to 7.00 and a mitochondrial delta pH of 0.97 units was observed. From these results, a total mitochondrial protonmotive force in the intact cell in excess of -200 mV was obtained.
Privacy, Confidentiality, and Electronic Medical Records (1996)

The enhanced availability of health information in an electronic format is strategic for industry-wide efforts to improve the quality and reduce the cost of health care, yet it brings a concomitant concern of greater risk for loss of privacy among health care participants. The authors review the conflicting goals of accessibility and security for electronic medical records and discuss nontechnical and technical aspects that constitute a reasonable security solution. It is argued that with guiding policy and current technology, an electronic medical record may offer better security than a traditional paper record.
The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases (2008)

Advances in the understanding of the cells of the hematopoietic system have provided a rich basis for improving clinical hematopoietic cell transplants; finding and using proteins and molecules to amplify or suppress particular blood cell types; understanding the stepwise progression of preleukemic stages leading first to chronic myeloid disorders, then the emergence of acute blastic leukemias; and treating malignant and nonmalignant diseases with cell subsets. As a result of intense scientific investigation, hematopoietic stem cells (HSCs) have been isolated and their key functional characteristics revealed-self-renewal and multilineage differentiation. These characteristics are now found to be present in all tissue/organ stem cell studies, and even in the analysis of pluripotent embryonic, nuclear transfer, and induced pluripotent stem cells. Studies on HSC have identified hematopoiesis as one of the best systems for studying developmental cell lineages and as the best for understanding molecular changes in cell fate decision-making and for finding preclinical and clinical platforms for tissue and organ replacement, regeneration, and oncogenesis. Here we review the steps, from our viewpoint, that led to HSC isolation and its importance in self-nonself immune recognition.
Computer-aided design of pseudoexhaustive BIST for semiregular circuits (2002)

The authors propose a special class of hierarchy, the sensitizable hierarchy, to handle simultaneously both circuit partitioning and test pattern delivery for pseudoexhaustive BIST (built-in self-test). Instead of developing specialized tools for different cases in an unsensitizable hierarchy, they attempt to reconstructure the hierarchy to make it sensitizable. In order to verify the sensitizability of a hierarchy and restructure an unsensitizable hierarchy, the authors study the characteristics of hierarchical circuits and conclude that there are three usable semiregular properties, namely, the separation of data and control signals, the availability of functional units and functional descriptions, and frequent use of array structure. On the basis of these properties, the following are derived: a structure recognition process to identify the implicit array and functional unit structure; a hierarchical, multilevel, multiple-path sensitization algorithm to sensitize paths for test application and response observation; a restructuring process to obtain a sensitizable hierarchy; and a straightforward procedure for pseudoexhaustive BIST for a sensitizable hierarchy. All of these processes and procedures use a common knowledge base and are integrated by use of a frame-based system implemented with Franz Lisp.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ultramicroelectrodes in Electrochemistry (1993)

Abstract In the 1950s and 1960s fundamental developments in electrochemical methods included voltammetry and low signal techniques. A generation later, the discovery of the unusual properties of ultramicroelectrodes has opened new possibilities of analyzing electrode processes. The changes in mass transport conditions bring about extremely high current densities at ultramicroelectrodes, whereas the currents themselves become very small. This little‐noticed phenomenon allows for many electroanalytical applications that are not possible with conventional electrodes, especially experiments in solutions with very low electrolyte concentrations, in nonpolar solvents, in solids, and even in gases. In addition, two factors— changes in the experimental time scale at low scan rates because of the size of the electrode, and insignificant iR effects at very high scan rates—make it possible to study very fast homogeneous and heterogeneous electrode processes.