gebhart/patrepeval huggingface dataset:
'Glutamine(amide): 2-Oxoglutarate Amino Transferase Oxido-reductase (NADP)', an Enzyme Involved in the Synthesis of Glutamate by Some Bacteria (1970)

SUMMARY: Ammonia-limited Aerobacter aerogenes, Erwinia carotovora, Pseudomonas fluorescens, Bacillus subtilis and B. megaterium synthesized glutamate from NH3 and 2-oxoglutarate by a process that involved first the synthesis of glutamine and then the reductive transfer of the glutamine amide-nitrogen to the 2-position of 2-oxoglutarate. The latter step required the recently reported enzyme ‘glutamine(amide): 2-oxoglutarate amino-transferase oxido-reductase (NADP)&apos;, some further properties of which are described here. This enzyme, from different organisms, always had a well-defined maximum activity at a pH value between 7·5 and 8·0; it had an apparent Km for 2-oxoglutarate between 0·1 and 2·0 mm and an apparent Km for glutamine between 0·2 and 1·8 mm. Glutamate (the metabolic end-product) and Mg2+ strongly inhibited the enzyme from Gram-negative bacteria but less so that from Gram-positive species. Synthesis of glutamate by this enzyme required NADPH, and NADH was inactive; pyruvate, oxaloacetate, 2-oxobutyrate and 2-oxoisovalerate could not substitute for 2-oxoglutarate, nor could the requirement for glutamine be met by asparagine, citrulline, arginine or urea. Although conditions that favoured the synthesis of this enzyme generally also favoured synthesis of glutamine synthetase and caused suppression of glutamate dehydrogenase formation, a close correlation between the bacterial contents of these different enzymes was not apparent.
Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. A comparison with IL-4-mediated signaling. (1988)

Resting tonsillar B lymphocytes were shown to enlarge and become more buoyant when exposed to either IL-4 or a mAb (G28-5) to the 50-kDa CDw40 Ag. A striking feature of activation through CDw40 was the promotion of strong homotypic adhesions which did not occur in populations cultured with IL-4. Whereas the CDw40 antibody down-regulated its target Ag, an increased expression of CDw40 accompanied IL-4 stimulation. Similarly, only IL-4, and not the CDw40 antibody, was able to induce the appearance of CD23 on the resting B cell surface. Functionally, the major consequence of ligating CDw40 on resting B cells was that they remained alert to subsequent mitogenic signaling--cells incubated with IL-4 developed the same sluggish response as noted in control cultures. Together, IL-4 and the CDw40 antibody provoked a small, but significant, level of DNA synthesis in tonsillar B cells which was enhanced dramatically by the inclusion of low m.w. B cell growth factor. This latter agent had no discernible direct effect on resting B lymphocytes. The different pathways which have been observed for triggering resting B cells are discussed.
Increased microvascular permeability contributes to preferential accumulation of Stealth liposomes in tumor tissue. (1993)

Stealth liposomes have recently emerged as a promising antitumor drug delivery system, yet no studies have been reported to examine their dynamic behavior at the microcirculatory level. In this investigation, we have used in vivo fluorescence videomicroscopy to study the decay in plasma concentration and the interstitial accumulation of Stealth and conventional liposomes in tumor and granulating tissue microcirculatory preparations. Fluorescently labeled Stealth or conventional liposomes were injected i.v. into rats bearing dorsal skinflap window chambers, some of which contained a vascularized mammary adenocarcinoma. After injection, fluorescent light intensities arising from liposomes within blood vessels and the interstitium were measured over time. These measurements were used to derive plasma pharmacokinetics and vascular permeability coefficients for each liposome species in both tumor and granulating normal tissues. Within the first 90 min after injection, Stealth liposome accumulation in the tumor interstitium was 3-4-fold that for conventional liposomes. The percentage of administered liposomes remaining in the circulation at the end of 90 min was 60.2% for Stealth and 20.4% for conventional liposomes. Tumor vascular permeability was 3.42 +/- 0.78 x 10(-7)cm/s for Stealth and 1.75 x 0.38 x 10(-7)cm/s for conventional liposomes. In normal granulating tissues permeability for the 2 constructs was equivalent at 0.8-0.9 x 10(-7)cm/s. In conclusion, preferential accumulation of Stealth liposomes in tumors was attributable to a combination of slower plasma clearance and higher vascular permeability relative to conventional liposomes. Our method of combining in vivo microscopy with a tumor microcirculatory model provides a unique approach to study quantitatively the delivery of liposomes to tumor tissues, since it can be used to study the process in real time at the microcirculatory level.
Heterodimeric IL15 Treatment Enhances Tumor Infiltration, Persistence, and Effector Functions of Adoptively Transferred Tumor-specific T Cells in the Absence of Lymphodepletion (2016)

<b>Purpose:</b> Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer. Host lymphodepletion is associated with favorable ACT therapy outcomes, but it may cause detrimental effects in humans. We tested the hypothesis that IL15 administration enhances ACT in the absence of lymphodepletion. We previously showed that bioactive IL15 <i>in vivo</i> comprises a stable complex of the IL15 chain with the IL15 receptor alpha chain (IL15Rα), termed heterodimeric IL15 (hetIL15).<b>Experimental Design:</b> We evaluated the effects of the combination regimen ACT + hetIL15 in the absence of lymphodepletion by transferring melanoma-specific Pmel-1 T cells into B16 melanoma-bearing mice.<b>Results:</b> hetIL15 treatment delayed tumor growth by promoting infiltration and persistence of both adoptively transferred Pmel-1 cells and endogenous CD8<sup>+</sup> T cells into the tumor. In contrast, persistence of Pmel-1 cells was severely reduced following irradiation in comparison with mice treated with hetIL15. Importantly, we found that hetIL15 treatment led to the preferential enrichment of Pmel-1 cells in B16 tumor sites in an antigen-dependent manner. Upon hetIL15 administration, tumor-infiltrating Pmel-1 cells showed a "nonexhausted" effector phenotype, characterized by increased IFNγ secretion, proliferation, and cytotoxic potential and low level of PD-1. hetIL15 treatment also resulted in an improved ratio of Pmel-1 to Treg in the tumor.<b>Conclusions:</b> hetIL15 administration improves the outcome of ACT in lymphoreplete hosts, a finding with significant implications for improving cell-based cancer immunotherapy strategies. <i>Clin Cancer Res; 23(11); 2817-30. ©2016 AACR</i>.
Ion Transport in Nanofluidic Funnels (2010)

We report fabrication of nanofluidic channels with asymmetric features (e.g., funnels) that were cast in high modulus poly(dimethylsiloxane) and had well-defined geometries and dimensions. Masters used to cast the funnels were written in the negative tone resist SU-8 by electron beam lithography. Replicated funnels had taper angles of 5, 10, and 20 degrees and were 80 nm wide at the tip, 1 microm wide at the base, and 120 nm deep. The planar format permitted easy coupling of the funnels to microfluidic channels and simultaneous electrical and optical characterization of ion transport. All three designs rectified ion current, and the 5 degrees funnel exhibited the highest rectification ratio. Fluorescence measurements at the funnel base showed that an anionic probe was enriched and depleted in the high and low conductance states, respectively.
Indexed retrieval by shape appearance (2000)

Efficient retrieval by content of visual information requires that visual content descriptors and similarity models are combined with efficient index structures. This problem is particularly challenging in the case of retrieval by shape similarity. The paper discusses retrieval by shape similarity, using local features and effective indexing. Shapes are partitioned into tokens following curvature analysis and each token is modelled by a set of perceptually salient attributes. Two distinct distance functions are used to model token similarity and shape similarity. Shape indexing is obtained by arranging tokens into an M-tree index structure. Examples from a prototype system and computational experiences are reported for both retrieval accuracy and indexing efficiency.
Biomechanical Motor Patterns in Normal Walking (1983)

Motor patterns in normal human gait are evident in several biomechanical and EMG analyses over the stride period. Some of these patterns are invariant over the stride period with changes of cadence, whole others are closely correlated with speed changes. The findings for slow, natural, and fast walking are summarized: 1. Joint angle patterns over the stride period are quite invariant, and do not change with cadence; 2. Moment of force patterns at the ankle are least variable and quite consistent at all speeds; 3. A recently defined support moment is quite consistent at all speeds. 4. Moments at the knee and hip are highly variable at all cadences but decrease their variability as cadence increases; 5. Mechanical power patterns at all joints show consistent timing over the stride period; 6. EMG profiles of 5 muscles show consistent timing over the stride, but the amplitude increases as walking speed increases. Arguments are presented to support the concept that walking speed is largely controlled by gain and that the timing of the motor patterns, which is extremely tightly synchronized with the anatomical position, is under major afferent control.
Staphylococcal virulence. Towards vaccination against infectious arthritis and sepsis (1999)

Staphylococcus aureus is a common cause of disease in humans representing a particular threat to immunocompromised patients. Several potential virulence factors have been described. The emergence of antibiotic resistant strains has prompted the development of new therapeutic and prophylactic regimens. Fundamental knowledge of staphylococcal virulence factors and their role in disease will enable the rational design of specific therapeutics. The aims of this thesis are to elucidate the role of particular staphylococcal virulence factors in septic arthritis and septicaemia, and to assess the efficacy of the use of recombinant antistaphylococcal vaccines. A set of isogenic S. aureus strains was used in a murine model to assess the role of defined virulence factors in the pathogenesis, of sepsis and arthritis. This set of mutants included strain defective in: a) global virulence regulator gene b) capsular polysaccharide genes; c) alpha- beta- and gamma-hemolysin genes. Induction of protective antibodies via vaccination may provide an effective means of preventing sepsis and septic arthritis. Collagen adhesin is expressed by most staphylococcal strains inducing septic arthritis. Vaccination with a recombinant fragment of collagen adhesin protected mice against sepsis-induced death. Antibodies against this fragment interfered with bacterial binding to host tissue and promoted phagocytic uptake and intracellular killing of bacteria. Superantigens produced by many S. aureus strains are potent stimulators of host inflammatory response. Induction of immunity against native superantigens is not feasible, since this would trigger severe inflammation, potentially leading to septic shock. Vaccination of mice with an engineered enterotoxin, devoid of superantigenic properties, significantly increased survival following challenge with S. aureus. In summary, this thesis defines bacterial components crucial to staphylococcal pathogenesis and indicates potential candidate antigens which might be incorporated into a future vaccine against septic arthritis and sepsis. Ideally, this vaccine would be multifactorial and should inhibit bacterial adhesion to matrix proteins, promote phagocytosis, and neutralise toxins
Perspectives in the medical treatment of glaucoma (1999)

Many advances in medical therapy for chronic glaucoma have taken place in the past few years that have altered previous concepts of stepwise medical therapy for glaucoma. beta-adrenergic blockers are still the most common medicine prescribed as monotherapy. However, latanoprost and brimonidine are often given as monotherapy as well as early adjunctive therapy. In addition, newer treatments that are used as early adjunctive therapy are dorzolamide, brinzolamide, apraclonidine, and the combination products, consisting of dorzolamide/timolol maleate and pilocarpine/timolol maleate. Older adjunctive treatments are now often prescribed as late adjunctive therapy including pilocarpine, epinephrine compounds, and acetazolamide. The extent of maximum tolerated medical therapy and the decision to perform either laser or conventional filtration surgery depend on the physician's judgment and on the patient's needs and preferences. In the future, newer medical therapies that may protect the health of the optic nerve directly could be developed including blood flow-based, neuroprotective, and genetically based agents.
Analog Baseband-IC for Dual Mode Direct Conversion Receiver (1996)

This paper presents a circuit design and implementation for the analogous filter and amplifier sections of a direct conversion receiver. Dual-mode operation is achieved by switching the LP-filters&amp;apos; cut-off frequency to meet DECT and DCS 1800 specifications alternatively. An op-amp-based integrator loop filter structure is used to perform low-noise, low-voltage and low-power operation. The circuit is fabricated using a 1.5 BiCMOS process. Including a DECT demodulator and a RSSI circuit the whole two-channel circuit drains 4 mA from a 3 V power supply. 1 Introduction The increasing number of available mobile communication networks offers the necessity to provide equipment for several standards. It&amp;apos;s desirable from the user&amp;apos;s point of view to communicate in different networks like GSM, DCS 1800 and DECT with only one single handset. Primarily it is intended to combine the access to a mobile communication network offering complete attainment with the access to a local cordless envi...
Visual aspects of air collision avoidance: Computer studies on pilot warning indicator specifications (1972)

Techniques of computer calculations used to analyze the potential for improving visual acquisition of collision threats by means of Pilot Warning Indicator systems (PWI) are described. The quantitative effects of PWI resolution and effective range upon the average cumulative probability of detection are presented.
Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia (1995)

Five multicenter, randomized, double-blind, placebo-controlled studies were conducted in France to compare the efficacy and safety of once-daily simvastatin treatment (10-40 mg/day) with conventional therapy with gemfibrozil 900 mg/day, ciprofibrate 100 mg/day, bezafibrate 400 mg/day, and fenofibrate 300 or 400 mg/day in a total of 800 patients with hypercholesterolemia. Simvastatin was associated with statistically significantly greater (p < or = 0.01) mean percent reductions in plasma low-density lipoprotein (LDL) cholesterol compared with each of the five fibrate regimens, even when administered at its recommended starting dose of 10 mg/day. Furthermore, approximately 90% of patients treated once daily with simvastatin experienced an at least 20% decrease in plasma LDL cholesterol compared with only 36 to 68% of patients treated with the individual fibrate agents (p < or = 0.05). The effectiveness of simvastatin in reducing LDL cholesterol did not differ as a function of the baseline plasma concentrations of total cholesterol or triglycerides. In contrast, the effectiveness of fibrate therapy in lowering plasma LDL cholesterol levels was significantly diminished (p < or = 0.05) among patients with triglyceride concentrations > 1.7 mmol/l. Plasma high-density lipoprotein (HDL) cholesterol levels were increased by approximately 10% after treatment with simvastatin or the fibrates. Although fibrate therapy was more effective overall in lowering plasma triglyceride levels, the effectiveness of simvastatin in reducing plasma triglyceride levels was generally 2- to 4-fold greater in patients with hypercholesterolemia associated with triglyceride levels > or = 2.3 mmol/l than in those with hypercholesterolemia associated with triglyceride levels < 2.3 mmol/l. The results of these studies confirm the superiority of simvastatin to standard fibrate therapy in reducing plasma levels of total and LDL cholesterol. They further indicate that once-daily treatment with simvastatin is effective in patients with isolated hypercholesterolemia or hypercholesterolemia associated with elevated triglyceride levels.
A permutational approach toward protein-DNA recognition. (1994)

The cI repressor of bacteriophage 434, known as 434 repressor, binds to 14-bp operator sequences by means of a helix-turn-helix motif. To probe the requirements for selective DNA recognition by this class of DNA binding proteins, as well as to generate new proteins with altered specificities, a library of approximately 3 x 10(6) mutants was generated that contains all permutations of five residues in the recognition helix (helix 3) of the repressor. These mutants were then selected in vivo for their ability to bind both wild-type (WT) and mutant operator sequences. The results of the selection demonstrate that four of these residues--Gln28, Gln29, Ser30, and Gln33--play a critical role in recognition of the WT operator. A number of repressors with mutations at Thr27 showed altered DNA binding affinities and specificities. The approach described here may also prove useful in studies of DNA recognition by other classes of DNA binding proteins.
Discovery and Synthesis of [6-Hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]- 2-(4-hydroxyphenyl)]benzo[b]thiophene:  A Novel, Highly Potent, Selective Estrogen Receptor Modulator (1997)

Raloxifene,[2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]phenyl]methanone hydrochloride (2), is representative of a class of compounds known as selective estrogen receptor modulators (SERMs) that possess estrogen agonist-like actions on bone tissues and serum lipids while displaying potent estrogen antagonist properties in the breast and uterus. As part of ongoing SAR studies with raloxifene, we found that replacement of the carbonyl group with oxygen ([6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]b enzo[b]thiophene hydrochloride, 4c) resulted in a substantial (10-fold) increase in estrogen antagonist potency relative to raloxifene in an in vitro estrogen dependent cell proliferation assay (IC50 = 0.05 nM) in which human breast cancer cells (MCF-7) were utilized. In vivo, 4c potently inhibited the uterine proliferative response to exogenous estrogen in immature rats following both sc and oral dosing (ED50 of 0.006 and 0.25 mg/kg, respectively). In ovariectomized aged rats, 4c produced a significant maximal decrease (45%) in total cholesterol at 1.0 mg/kg (p.o.) and showed a protective effect on bone relative to controls with maximal efficacy at 1.0 mg/kg (p.o.). These data identify 4c as a novel SERM with greater potency to antagonize estrogen in uterine tissue and in human mammary cancer cells compared to raloxifene, tamoxifen or ICI-182,780.
Interferometric observation of femtosecond free induction decay (1994)

Femtosecond free induction decay of cobalt–phthalocyanine in pyridine and of octaethyl porphine in pyridine was observed by use of a white-light interferometer with a resolution time of 6 fs. Also, frequency-domain complex optical constants of the samples were obtained by Fourier-transform analysis of the phase-sensitive interferograms.
Elicitors, Effectors, and R Genes: The New Paradigm and a Lifetime Supply of Questions (2007)

The plant basal immune system can detect broadly present microbe-associated molecular patterns (MAMPs, also called PAMPs) and induce defenses, but adapted microbes express a suite of effector proteins that often act to suppress these defenses. Plants have evolved other receptors (R proteins) that detect these pathogen effectors and activate strong defenses. Pathogens can subsequently alter or delete their recognized effectors to avoid defense elicitation, at risk of a fitness cost associated with loss of those effectors. Significant research progress is revealing, among other things, mechanisms of MAMP perception, the host defense processes and specific host proteins that pathogen effectors target, the mechanisms of R protein activation, and the ways in which pathogen effector suites and R genes evolve. These findings carry practical ramifications for resistance durability and for future resistance engineering. The present review uses numerous questions to help clarify what we know and to identify areas that are ripe for further investigation.
Immunohistochemical detection of the Wilms’ tumour gene WT1 in desmoplastic small round cell tumour (1997)

The desmoplastic small round cell tumour (DSRCT) is a rare, highly malignant neoplasm usually presenting in the abdomen of adolescent males. A characteristic translocation between the Ewing's sarcoma gene on chromosome 22 and the Wilms' tumour gene WT1 on chromosome 11 has been described, producing a fusion gene with expression of the DNA binding area of WT1. Some Wilms' tumour antibodies recognize epitopes of this part of the WT1 protein. All four cases of DSRCT examined showed strong staining of the tumours with an anti-WT1 antibody, suggesting this may be useful in the diagnosis of these tumours.
Mitochondria as a Target for Neurotoxins and Neuroprotective Agents (2003)

Mitochondrial permeability transition pores represent a multiprotein complex that includes components of both inner and outer membrane. The pores regulate transport of ions and peptides in and out of mitochondria, and their regulation is associated with a general mechanism for maintaining Ca(2+) homeostasis in the cell and apoptosis. Various pathologic factors may induce a pathologic activation of the permeability transition and an irreversible opening of mitochondria pores. This event is a major step in the development of neurotoxicity and neurodegeneration. This paper explores the effect of MPP(+) and beta-amyloid fragment 25-35, neurotoxins that are known to generate Parkinson's-like syndrome and Alzheimer's disease, on the regulation of the mitochondrial pores. Both neurotoxins induce opening of mitochondrial pores, which is prevented by cyclosporin A, a specific inhibitor of the permeability transition. The effect of MPP(+) and beta-amyloid may be also prevented by an endogenous precursor of melatonin, N-acetylserotonin, by an anti-Alzheimer's medication tacrine, and by dimebon, which is in development as an agent for the therapy of Alzheimer's disease and other types of dementia. The paper illustrates that the effect on mitochondrial pores is an important aspect of the mechanism of neurotoxicity. Substances that may prevent opening of mitochondrial pores induced by neurotoxins may preserve the mitochondrial function and, thus, may have potential as neuroprotective agents.