gebhart/patrepeval huggingface dataset:
4-1BB Ligand, a Member of the TNF Family, Is Important for the Generation of Antiviral CD8 T Cell Responses (1999)

4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.
Nonablative Allogeneic Stem-Cell Transplantation for Advanced/Recurrent Mantle-Cell Lymphoma (2003)

Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.
Detergent solubilization of the interleukin 1 receptor. (1987)

Interleukin 1 (IL 1) receptors were solubilized from membranes prepared from murine EL-4 thymoma cells with the zwitterionic detergent 3[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS). Binding of IL 1 to the solubilized receptor was detected by a polyethylene glycol (PEG) precipitation procedure. Concentrations of CHAPS from 4 to 8 mM were effective in solubilizing the IL 1 receptor. At 10 mM CHAPS, there was some loss in binding activity, whereas 2 mM CHAPS was completely ineffective in solubilizing the receptor. Detergent concentrations of 4 mM were routinely used. The solubilized receptor retains the ability to bind 125I-IL 1 in a specific and saturable manner. Scatchard analysis reveals a single type of high affinity binding site having an apparent dissociation constant (KD) of approximately 1.2 X 10(-10) M. Nearly identical KD values are observed for membrane fractions. There are approximately 400 to 500 fmol receptor/mg protein in the detergent extract, corresponding to a two- to threefold enrichment in the Bmax observed for membranes. There is no loss in receptor activity as determined by complete recovery of the total number of binding sites from membranes after solubilization. Binding kinetics show that apparent steady state for the solubilized receptor is reached after 60 min at 37 degrees C. The binding of 125I-IL 1 is essentially irreversible because relatively little bound ligand can be dissociated from the receptor on the addition of excess unlabeled IL 1 at 37 degrees C. Both human IL 1 alpha and IL 1 beta compete for binding of 125I-IL 1 to the soluble receptor, confirming that IL 1 alpha and IL 1 beta bind to the same receptor. Other recombinant proteins, including interferon-alpha A, interferon-gamma, and interleukin 2 have no inhibitory effect.
Differentiation of Chlamydia spp. by sequence determination and restriction endonuclease cleavage of RNase P RNA genes (1996)

The amplification of DNA from Chlamydia trachomatis by PCR with degenerated primers yielded a 345-bp fragment of the putative RNase P RNA gene. From the deduced DNA sequence of this gene in C. trachomatis, a modified primer pair was designed. The primer pair was subsequently used to obtain the corresponding gene products from Chlamydia pneumoniae and Chlamydia psittaci. Sequence comparisons revealed similarities of 76.6% between C. trachomatis and C. pneumoniae, 79.5% between C. trachomatis and C. psittaci, and 84.7% between C. pneumoniae and C. psittaci. Furthermore, the three species were differentiated by fragment length polymorphism analysis after restriction enzyme cleavage of the PCR products. Sequence variations among 14 serotypes of C. trachomatis were confined to one purine base substitution in the putative RNase P RNA gene of lymphogranuloma venereum strains L1 to L3. Complete sequence similarity was found for nine strains of C. pneumoniae of different geographic origins. Taken together, our results indicate a possibility of the general application of this method in clinical bacteriology. Analysis of the secondary structures of the putative RNase P RNA genes from the different Chlamydia species suggested that a novel structural element in the domain of RNase P RNA is involved in base pairing with the 3'-terminal CCA motif of a tRNA precursor. This structure has not previously been found among RNase P RNAs of members of the division Bacteria.
Inhibition of Amyloid β Protein Fibrillation by Polymeric Nanoparticles (2008)

Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (Abeta). We found that these nanoparticles affect mainly the nucleation step of Abeta fibrillation. The elongation step is largely unaffected by the particles, and once the Abeta is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of Abeta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that Abeta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric Abeta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of Abeta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.
Surface‐active properties of antifungal lipopeptides produced byBacillus subtilis (1992)

The interfacial behavior of antifungal lipopetides of the iturinic group was studied in comparison with that of surfactin, an anionic lipopeptide. All these lipopeptides were isolated from various strains of Bacillus subtilis ; each strain produced surfactin and one antifungal compound. The iturinic compounds differ from surfactin by their lower surfactant properties. The critical micelle concentration (CMC) values were dependent on the nature of the peptide moiety in the iturinic compounds. The highest values were observed for anionic antibiotics. The arrangement of lipopeptides at the air‐water interface was largely dependent on the size of the lipid moiety; surfactin, which has a C 14 or C 15 β‐hydroxy fatty acid, iturins A, C, and bacillomycins D, L, which have a C 14 or C 15 β‐amino fatty acid, occupied a smaller area than mycosubtilin and bacillomycin F, which have a C 16 or C 17 β‐amino fatty acid. These data can be related to bioactivity of these lipopeptides.
Fair division from cake-cutting to dispute resolution (1996)

Cutting a cake, dividing up the property in an estate, determining the borders in an international dispute - such problems of fair division are ubiquitous. Fair Division treats all these problems and many more through a rigorous analysis of a variety of procedures for allocating goods (or 'bads' like chores), or deciding who wins on what issues, when there are disputes. Starting with an analysis of the well-known cake-cutting procedure, 'I cut, you choose', the authors show how it has been adapted in a number of fields and then analyze fair-division procedures applicable to situations in which there are more than two parties, or there is more than one good to be divided. In particular they focus on procedures which provide 'envy-free' allocations, in which everybody thinks he or she has received the largest portion and hence does not envy anybody else. They also discuss the fairness of different auction and election procedures
Lack of Th2 cytokine increase during spontaneous remission of experimental allergic encephalomyelitis (1998)

The mechanisms underlying spontaneous remission of autoimmune diseases are presently unknown, though regulatory T cells are believed to play a major role in this process. We tested the hypothesis that Th2 and/or other T cell regulatory cytokines cause the spontaneous remission of experimental allergic encephalomyelitis (EAE), a model of Th1-mediated autoimmunity. We analyzed the cytokine profile of lymph node and central nervous system-infiltrating cells in individual SJL mice at different stages of proteolipid protein (PLP) 139 – 151 peptide-induced EAE. We found that IFN-γ slowly fades away after clinical recovery, whereas IL-4, IL-10 and transforming growth factor-β remain low or undetectable. Our peptide-results therefore suggest that regulatory T cells producing anti-inflammatory cytokines are not involved in spontaneous remission of EAE and challenge the view that the Th1/Th2 balance has a key role in EAE regulation.
Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice (2010)

Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus.
Therapeutic use of growth factors in renal failure. (1994)

Polypeptide growth factors regulate kidney development, growth, and function and participate in processes of repair after renal injury. The use of one or more growth factors as therapeutic agents has been proposed in the settings of acute and chronic renal failure. In animal models of acute renal injury, the administration of epidermal growth factor, insulin-like growth factor I (IGF-I), or hepatocyte growth factor accelerates the restoration of kidney function and the normalization of histology post-acute renal injury and reduces mortality. The mechanisms by which the growth factors act in acute renal failure include the stimulation of anabolism, the maintenance of glomerular filtration, and the enhancement of tubular regeneration. IGF-I has been safely administered to humans with chronic renal failure. The growth factor enhances GFR and RPF in these individuals. Further studies will be required to establish a role for IGF-I or other growth factors as therapeutic agents for acute renal failure in humans and to define the utility of IGF-I as a medical therapy for chronic renal insufficiency.
Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice. (1994)

The mouse alpha-lactalbumin gene has been replaced with the human gene by two consecutive rounds of gene targeting in hypoxanthine phosphoribosyltransferase (HPRT)-deficient feeder-independent murine embryonic stem (ES) cells. One mouse alpha-lactalbumin allele was first replaced by an HPRT minigene which was in turn replaced by human alpha-lactalbumin. The end result is a clean exchange of defined DNA fragments with no other DNA remaining at the target locus. Targeted ES cells at each stage remained capable of contributing efficiently to the germ line of chimeric animals. Double replacement using HPRT-deficient ES cells and the HPRT selection system is therefore a powerful and flexible method of targeting specific alterations to animal genes. A typical strategy for future use would be to generate a null mutation which could then be used to produce multiple second-step alterations at the same locus.
The crystal structure of chorismate lyase shows a new fold and a tightly retained product (2001)

The enzyme chorismate lyase (CL) catalyzes the removal of pyruvate from chorismate to produce 4-hydroxy benzoate (4HB) for the ubiquinone pathway. In Escherichia coli, CL is monomeric, with 164 residues. We have determined the structure of the CL product complex by crystallographic heavy-atom methods and report the structure at 1.4-A resolution for a fully active double Cys-to-Ser mutant and at 2.0-A resolution for the wild-type. The fold involves a 6-stranded antiparallel beta-sheet with no spanning helices and novel connectivity. The product is bound internally, adjacent to the sheet, with its polar groups coordinated by two main-chain amides and by the buried side-chains of Arg 76 and Glu 155. The 4HB is completely sequestered from solvent in a largely hydrophobic environment behind two helix-turn-helix loops. The extensive product binding that is observed is consistent with biochemical measurements of slow product release and 10-fold stronger binding of product than substrate. Substrate binding and kinetically rate-limiting product release apparently require the rearrangement of these active-site-covering loops. Implications for the biological function of the high product binding are considered in light of the unique cellular role of 4HB, which is produced by cytoplasmic CL but is used by the membrane-bound enzyme 4HB octaprenyltransferase.
Cough reflex induced by capsaicin inhalation in patients with dysphagia (2010)

The control group showed a cough reflex at a capsaicin concentration of 2.61 μM (0.98-7.80), while patients with mild dysphagia did so at 7.28 μM (1.95-15.6), those with moderate dysphagia at 22.07 μM (15.6-62.5), and those with severe dysphagia at 71.75 μM (31.2-250). Control vs mild p < 0.01, control vs moderate p < 0.01, control vs severe p < 0.01, mild vs moderate p < 0.01, mild vs severe p < 0.01, moderate vs severe p < 0.05. There was a significant correlation between the grade of dysphagia and the threshold capsaicin concentration that provoked a cough reflex (ρ = -0.796, p < 0.001).
An Application of Yield Management to the Hotel Industry Considering Multiple Day Stays (1995)

In this paper we study optimal strategies for renting hotel rooms when there is a stochastic and dynamic arrival of customers from different market segments. We formulate the problem as a stochastic and dynamic programming model and characterize the optimal policies as functions of the capacity and the time left until the end of the planning horizon. We consider three features that enrich the problem: we make no assumptions concerning the particular order between the arrivals of different classes of customers; we allow for multiple types of rooms and downgrading; and we consider requests for multiple nights. We also consider implementations of the optimal policy. The properties we derive for the optimal solution significantly reduce the computational effort needed to solve the problem, yet in the multiple product and/or multiple night case this is often not enough. Therefore, heuristics, based on the properties of the optimal solutions, are developed to find “good” solutions for the general problem. We also derive upper bounds which are useful when evaluating the performance of the heuristics. Computational experiments show a satisfactory performance of the heuristics in a variety of scenarios using real data from a medium size hotel.
Soft, Skin-Integrated Multifunctional Microfluidic Systems for Accurate Colorimetric Analysis of Sweat Biomarkers and Temperature (2019)

Real-time measurements of the total loss of sweat, the rate of sweating, the temperature of sweat, and the concentrations of electrolytes and metabolites in sweat can provide important insights into human physiology. Conventional methods use manual collection processes (e.g., absorbent pads) to determine sweat loss and lab-based instrumentation to analyze its chemical composition. Although such schemes can yield accurate data, they cannot be used outside of laboratories or clinics. Recently reported wearable electrochemical devices for sweat sensing bypass these limitations, but they typically involve on-board electronics, electrodes, and/or batteries for measurement, signal processing, and wireless transmission, without direct means for measuring sweat loss or capturing and storing small volumes of sweat. Alternative approaches exploit soft, skin-integrated microfluidic systems for collection and colorimetric chemical techniques for analysis. Here, we present the most advanced platforms of this type, in which optimized chemistries, microfluidic designs, and device layouts enable accurate assessments not only of total loss of sweat and sweat rate but also of quantitatively accurate values of the pH and temperature of sweat, and of the concentrations of chloride, glucose, and lactate across physiologically relevant ranges. Color calibration markings integrated into a graphics overlayer allow precise readout by digital image analysis, applicable in various lighting conditions. Field studies conducted on healthy volunteers demonstrate the full capabilities in measuring sweat loss/rate and analyzing multiple sweat biomarkers and temperature, with performance that quantitatively matches that of conventional lab-based measurement systems.
Age-Specific Adjuvant Synergy: Dual TLR7/8 and Mincle Activation of Human Newborn Dendritic Cells Enables Th1 Polarization (2016)

Due to functionally distinct cell-mediated immunity, newborns and infants are highly susceptible to infection with intracellular pathogens. Indeed, neonatal Ag-presenting dendritic cells (DCs) demonstrate impaired Th1 responses to many candidate adjuvants, including most TLR agonists (TLRAs). Combination adjuvantation systems may provide enhanced immune activation but have typically been developed without regard to the age of the target population. We posited that distinct combinations of TLRAs and C-type lectin receptor agonists may enhance Th1 responses of newborn DCs. TLRA/C-type lectin receptor agonist combinations were screened for enhancement of TNF production by human newborn and adult monocyte-derived DCs cultured in 10% autologous plasma or in newborn cord, infant, adult, and elderly whole blood. Monocyte-derived DC activation was characterized by targeted gene expression analysis, caspase-1 and NF-κB studies, cytokine multiplex and naive autologous CD4<sup>+</sup> T cell activation. Dual activation of newborn DCs via the C-type lectin receptor, macrophage-inducible C-type lectin (trehalose-6,6-dibehenate), and TLR7/8 (R848) greatly enhanced caspase-1 and NF-κB activation, Th1 polarizing cytokine production and autologous Th1 polarization. Combined activation via TLR4 (glycopyranosyl lipid adjuvant aqueous formulation) and Dectin-1 (β-glucan peptide) acted synergistically in newborns and adults, but to a lesser extent. The degree of synergy varied dramatically with age, and was the greatest in newborns and infants with less synergy in adults and elders. Overall, combination adjuvant systems demonstrate markedly different immune activation with age, with combined DC activation via Macrophage-inducible C-type lectin and TLR7/8 representing a novel approach to enhance the efficacy of early-life vaccines.
Disintegrins (2004)

The existence of disintegrins, non-enzymatic, small molecular weight proteins from viper venom, has been known for 2 decades, and their impact on cellular research has been substantial and far-reaching. Disintegrins have been the molecular scaffold used in the design of therapeutics for the prevention of thrombosis and cancer. Their sequencing has provided insights into the evolution of proteins over millennia. Production of recombinant disintegrin mutants and fusion proteins has allowed investigations into molecular mechanisms at work in cell-extracellular matrix interactions. Structural homologies with non-snake proteins have shown disintegrin-like molecules in species ranging from slime mold to humans. Intracellular signaling events have been elucidated through the use of venom disintegrins, including events related to programmed cell death, motility, cell proliferation and viral pathogenesis. Disintegrin sequences (protein or genes) have been placed in microbubbles and liposomes and been found to target neovascular endothelium and metastatic tumors in two mouse models. The purpose of this review is to highlight the members of this disintegrin family discovered since 1998 as well as the increased understanding of their usefulness in therapeutics and technical assays.
Radiation-induced DNA content variability in mouse sperm. (1983)

Mouse sperm collected from the cauda epididymidis 35 days after acute testicular X-ray exposure and fluorescently stained for DNA show dose-dependent increases in the coefficient of variation (CV) of flow cytometrically obtained fluorescence distributions. By comparing dose-response curves obtained with three protocols which overcome the optical and cytochemical difficulties of sperm measurement in different ways we conclude the response is due to X-ray-induced DNA content variability. In the range between 0 and 600 rad the dose dependence of the square of CV of the DNA content variability, delta CV2D, is described by delta CV2D = Bx + Cx2, with 0 less than or equal to B less than or equal to 0.23 X 10(-2) and C = (0.44 +/- 0.06) X 10(-4). The dose x is measured in rad and delta CVD is expressed in percent. Computer modeling of the shapes of the fluorescence distributions show that at 600 rad 30 to 40% of the sperm have abnormal DNA content. Some have errors as large as two whole chromosomes, but it is not clear whether they are due to whole chromosome nondisjunction or a finer fragmentation of the genome. Exposures to benzo(a)pyrene and mitomycin C cause no detectable DNA content variability. We conclude mouse sperm DNA content measurements are not sensitive to small amounts of aneuploidy and as such will only be useful in detecting agents that produce substantial DNA content variability. Another animal with a smaller number of chromosomes might be more favorable. These sperm measurement techniques may find additional application in other areas of reproductive biology, such as the determination of the relative numbers of X and Y chromosome-bearing sperm in semen that may be artificially enriched in one population.
The physiological regulation of toll‐like receptor expression and function in humans (2005)

Eleven mammalian toll-like receptors (TLRs 1-11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14(+) monocytes following activation with specific TLR ligands was greater (P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34 degrees C). Strenuous exercise resulted in a decrease (P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14(+) monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14(+) monocytes following activation with specific TLR ligands was decreased (P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.