gebhart/patrepeval huggingface dataset:
Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity (2015)

Here we report a "configuration-dependent" mechanism of action for IL-15:IL-15Rα (heterodimeric IL-15 or hetIL-15) where the manner by which IL-15:IL-15Rα molecules are presented to target cells significantly affects its function as a vaccine adjuvant. Although the cellular mechanism of IL-15 trans-presentation via IL-15Rα and its importance for IL-15 function have been described, the full effect of the IL-15:IL-15Rα configuration on responding cells is not yet known. We found that trans-presenting IL-15:IL-15Rα in a multivalent fashion on the surface of antigen-encapsulating nanoparticles enhanced the ability of nanoparticle-treated dendritic cells (DCs) to stimulate antigen-specific CD8(+) T cell responses. Localization of multivalent IL-15:IL-15Rα and encapsulated antigen to the same DC led to maximal T cell responses. Strikingly, DCs incubated with IL-15:IL-15Rα-coated nanoparticles displayed higher levels of functional IL-15 on the cell surface, implicating a mechanism for nanoparticle-mediated transfer of IL-15 to the DC surface. Using artificial antigen-presenting cells to highlight the effect of IL-15 configuration on DCs, we showed that artificial antigen-presenting cells presenting IL-15:IL-15Rα increased the sensitivity and magnitude of the T cell response, whereas IL-2 enhanced the T cell response only when delivered in a paracrine fashion. Therefore, the mode of cytokine presentation (configuration) is important for optimal immune responses. We tested the effect of configuration dependence in an aggressive model of murine melanoma and demonstrated significantly delayed tumor progression induced by IL-15:IL-15Rα-coated nanoparticles in comparison with monovalent IL-15:IL-15Rα. The novel mechanism of IL-15 transfer to the surface of antigen-processing DCs may explain the enhanced potency of IL-15:IL-15Rα-coated nanoparticles for antigen delivery.
Human prostasomes contain chromosomal DNA (2009)

Human prostasomes contain chromosomal DNA. Both nuclease treatment and differential DNA stainings indicated an inside location of the prostasomal DNA. Our findings suggest a DNA-delivery function of prostasomes to sperm cells.
Viruses and Bacteria in the Etiology of the Common Cold (1998)

Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.
Alzheimer’s Disease Is Associated with a Low Prevalence of Hypertension (2012)

The prevalence of HT was lower in patients with AD compared to subjects without AD. Physicians who deal with AD patients must keep in mind that the need for antihypertensive medication may decline during the dementia process.
Stimulation latency and comparison of cycling regimens in women using sacral neuromodulation (2016)

Sacral neuromodulation patients should allow a 2-week trial before attributing symptoms to a new setting. With additional information, many opt for energy-conserving settings. A 1-hr on, 2-hr off regimen warrants further study. Neurourol. Urodynam. 36:486-489, 2017. © 2016 Wiley Periodicals, Inc.
Lasers: The Next Bit (2006)

Abstract Since the early twentieth century rotary drilling has revolutionized the procedure of extraction of crude oil replacing conventional methods like cable tool drilling. However with the advent of new technology it is time to look at future alternative, more efficient drilling methods. This paper acts as an eye opener to the feasibility of using laser drilling over modern currently used drilling techniques. The design and operation of a new laser-mechanical bit is put forth by the medium of this paper. This innovative bit shows probability of reducing rig time and increasing efficiency in drilling. The possible changes to be implemented in the present day drill string due to incorporation of this new bit is accounted for and an analysis of the possible advantages and disadvantages of this bit if implemented is also highlighted.
Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size and Microglial Number in hAPP(751)SL Mice (2011)

Together, this study suggests that while hAPP(751)(SL) mice show increases in microglial number and plaque load, they fail to exhibit elevated markers of neuroinflammation consistent with AD at 8 months of age, which may be a limitation of this animal model. Despite absence of clear neuroinflammation, apocynin was still able to reduce both plaque size and microglial number, suggesting that apocynin may have additional therapeutic effects independent of anti-inflammatory characteristics.
Synthesis, Structure, and Properties of Model Organic Surfaces (1992)

Interest in the properties of thin-film organic materials, especially regard­ ing organized monoand multilayer assemblies, has grown enormously in recent years. The impetus for this renaissance-the relevance of such structures and materials to biological interfaces and membranes, corrosion protection, electrochemistry, wetting, adhesion, and microelectronic cir­ cuit fabrication, for example-has been discussed extensively (1,2). Such materials are clearly contributing significantly to our more general under­ standing of the physics and chemistry of complex surfaces and interfaces. In this article, we provide a general overview of areas in which this has been persuasively demonstrated and, in so doing, suggest the intellectual issues that drive current research in this field. Until recently, there were no generally applicable methods to construct well-ordered, organic surface phases by using any rational synthetic scheme. Metal, semiconductor, and oxide surfaces can be easily prepared by orienting, cutting (or cleaving), and polishing single-crystal substrates followed by cleaning in ultrahigh vacuum (URV) (i.e. by ion bom-
Androgen signaling and its interactions with other signaling pathways in prostate cancer (2007)

Abstract Prostate cancer is the most frequently diagnosed non‐skin cancer and the third leading cause of cancer mortality in men. In the initial stages, prostate cancer is dependent on androgens for growth, which is the basis for androgen ablation therapy. However, in most cases, prostate cancer progresses to a hormone refractory phenotype for which there is no effective therapy available at present. The androgen receptor (AR) is required for prostate cancer growth in all stages, including the relapsed, “androgen‐independent” tumors in the presence of very low levels of androgens. This review focuses on AR function and AR‐target genes and summarizes the major signaling pathways implicated in prostate cancer progression, their crosstalk with each other and with AR signaling. This complex network of interactions is providing a deeper insight into prostate carcinogenesis and may form the basis for novel diagnostic and therapeutic strategies. BioEssays 29:1227–1238, 2007. © 2007 Wiley Periodicals, Inc.
Rat brain serotonin receptors in Xenopus oocytes are coupled by intracellular calcium to endogenous channels. (1987)

Serotonin activates chloride currents in Xenopus oocytes injected with a subfraction of rat brain poly(A)+ mRNA. Patch-clamp recordings from cell-attached patches showed that serotonin, applied locally outside the patch, caused the opening of channels of approximately equal to 3 pS conductance and an average lifetime of approximately equal to 100 msec. The extrapolated reversal potential indicated that the channels are chloride-selective. Single-channel currents with similar characteristics were observed in inside-out patches from native oocytes in response to elevated calcium concentrations on the cytoplasmic side. Measurements of intracellular calcium concentration ([Ca2+]i) by fura-2 fluorescence showed approximately equal to 10-fold increases in [Ca2+]i in response to serotonin application in both normal and calcium-free Ringer solution in mRNA-injected oocytes. Little or no response to serotonin was observed in native oocytes. These results suggest that serotonin activation of receptors that are inserted into the oocyte membrane following injection of rat brain poly(A)+ mRNA can induce calcium release from intracellular stores. The increase in [Ca2+]i subsequently activates calcium-dependent chloride channels. Because calcium-dependent chloride channels and a receptor-controlled mechanism of internal calcium release have been shown to exist in native oocytes, we conclude that the newly inserted serotonin receptors utilized the endogenous second-messenger-mediated calcium release to activate endogenous calcium-dependent chloride channels.
Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease (2018)

Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.
Time course of increased cellular proliferation in collateral arteries after administration of vascular endothelial growth factor in a rabbit model of lower limb vascular insufficiency. (1995)

Proliferation of vascular cells has been previously shown to contribute to spontaneous development of coronary collaterals. Recent studies from several laboratories have established that collateral artery growth in both the heart and limb can be enhanced by administration of angiogenic growth factors, or therapeutic angiogenesis. In this study, we sought (1) to define the extent and time course of endothelial cell (EC) and smooth muscle cell (SMC) proliferation accompanying spontaneous collateral development during limb ischemia and (2) to determine the extent to which proliferative activity of ECs and SMCs is augmented during therapeutic angiogenesis with vascular endothelial growth factor (VEGF), a heparin-binding EC-specific mitogen. Ten days after induction of limb ischemia by surgically excising the femoral artery of rabbits, either VEGF (500 to 1000 micrograms) or saline was administered as a bolus into the iliac artery of the ischemic limb. Cellular proliferation was evaluated by bromodeoxyuridine labeling for 24 hours at day 0 (immediately before VEGF administration) and at days 3, 5, and 7 after VEGF, EC proliferation in the midzone collaterals of VEGF-treated animals increased 2.8-fold at day 5 (P < 0.05 versus control), and returned to baseline levels by day 7. SMC proliferation in midzone collaterals also increased 2.7-fold in response to VEGF (P < 0.05). No significant increase in EC or SMC proliferation was observed in either the stem or re-entry collaterals of VEGF-treated animals compared with untreated ischemic control animals. Reduction of hemodynamic deficit in the ischemic limb measured by lower limb blood pressure was documented at day 7 after VEGF (P < 0.01 versus untreated, ischemic control). These data thus (1) establish the contribution of cellular proliferation to collateral vessel development in limb ischemia and (2) support the concept that augmented cellular proliferation contributes to the enhanced formation of collateral vessels after therapeutic angiogenesis with VEGF.
Limb-Girdle Muscular Dystrophy (2009)

Abstract Slow progression of proximal weakness in an adult may suggest Becker muscular dystrophy but limb girdle muscular dystrophy needs to be considered. This chapter discusses a diagnostic approach which includes the utility of ever evolving genetic tests. Management considerations are also outlined.
Immunochemotherapy with interleukin-2, interferon- α and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study (2000)

In patients with metastatic renal cell carcinoma response rates of 7-26% have been achieved with immunotherapy. A high response rate of 48% in 35 patients has been reported for treatment with the combination of interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien et al (1993a) Eur J Cancer29A: S6-8). We conducted a multicentre phase II study to confirm these results. Metastatic renal cell carcinoma patients were treated as outpatients with an 8-week treatment cycle. Recombinant human IL-2 20 MU m(-2) was administered subcutaneously (s.c.) three times a week (t.i.w) in weeks 1 and 4 and 5 MU m(-2) t.i.w. in weeks 2 and 3. Recombinant human IFN-alpha 2a 6 MU m(-2) was administered s.c. once in weeks 1 and 4 and t.i.w. in weeks 2 and 3, and 9 MU m(-2) t.i.w. in weeks 5-8. 5-FU (750 mg m(-2)) was given as a bolus injection intravenous once a week in weeks 5-8. The treatment cycle was repeated once in case of response or minor response. Fifty-two patients entered the study. All had undergone a nephrectomy and had progressive metastatic disease. The median WHO-performance status was 1, the median number of metastatic sites was 2 (range 1-5) and the median time between the diagnosis of the primary tumour and the start of treatment was 12.9 months (range 1-153). Among the 51 patients, including four patients with early progressive disease, who were evaluable for response, the response rate was 11.8% (95% confidence interval (CI) 2.9-20.7%), with no complete responses. Median duration of response was 8.3 (range 3.8-22.4+) months. Median survival was 16.5 (range 1.8-30.5+) months. Grade 3/4 toxicity (WHO) occurred in 29/52 (55.8%) of the patients in cycle 1 and in 6/16 (37.5%) of the patients in cycle 2. It consisted mainly of anorexia, fatigue, nausea, fever and leucocytopenia. We cannot confirm the high response rate in patients with metastatic renal cell carcinoma treated with the combination of IFN-alpha, IL-2 and 5-FU, as described by Atzpodien et al.
Characterization of Metabolites of Hydroxycinnamates in the in Vitro Model of Human Small Intestinal Epithelium Caco-2 Cells (2003)

Hydroxycinnamic acids are antioxidant phenolic compounds which are widespread in plant foods, contribute significantly to total polyphenol intakes, and are absorbed by humans. The extent of their putative health benefit in vivo depends largely on their bioavailability. However, the mechanisms of absorption and metabolism of these phenolic compounds have not been described. In this study, we used the in vitro Caco-2 model of human small intestinal epithelium to investigate the metabolism of the major dietary hydroxycinnamates (ferulate, sinapate, p-coumarate, and caffeate) and of diferulates. The appearance of metabolites in the medium versus time was monitored, and the various conjugates and derivatives produced were identified by HPLC-DAD, LC/MS, and enzyme treatment with beta-glucuronidase or sulfatase. Enterocyte-like differentiated Caco-2 cells have extra- and intracellular esterases able to de-esterify hydroxycinnamate and diferulate esters. In addition, intracellular UDP-glucuronosyltransferases and sulfotransferases existing in Caco-2 cells are able to form the sulfate and the glucuronide conjugates of methyl ferulate, methyl sinapate, methyl caffeate, and methyl p-coumarate. However, only the sulfate conjugates of the free acids, ferulic acid, sinapic acid, and p-coumaric acid, were detected after 24 h. The O-methylated derivatives, ferulic and isoferulic acid, were the only metabolites detected following incubation of Caco-2 cells with caffeic acid. These results show that the in vitro model system differentiated Caco-2 cells have the capacity to metabolize dietary hydroxycinnamates, including various phase I (de-esterification) and phase II (glucuronidation, sulfation, and O-methylation) reactions, and suggests that the human small intestinal epithelium plays a role in the metabolism and bioavailability of these phenolic compounds.
Standard Protocols for the Construction of scFv Libraries (2003)

Since the generation of the first human antibodies (Abs) by phage display (,), technology has evolved to allow the creation of large, nonimmunized fully human scFv repertoires that yield Abs with comparable affinities to those obtained using hybridoma technology (,). Using a variety of selection and screening strategies, the same single-pot library can be used to simultaneously derive many high-affinity Abs with different specificities in only a few weeks. Abs isolated from such large, fully human scFv repertoires have a multitude of applications, from immunological reagents for enzyme-linked immunosorbant assay, immunocytochemistry, Western blotting, or epitope mapping, to therapy. The first fully human therapeutic monoclonal Abs isolated from a phagedisplayed library for the treatment of rheumatoid arthritis and ocular scarring are currently progressing through late-stage clinical trials (). Construction of such scFv libraries from naturally rearranged V genes in a phagemid vector ensures natural diversity in the length of the VH CDR3, a higher number of functional scFvs, and soluble scFv expression without the need for subcloning (). Furthermore, phage-display technology also provides a means by which a selected Ab can, if necessary, be affinity-matured for improved neutralization potency or binding kinetics. Maximum diversity is generated by amplifying V genes from peripheral blood lymphocytes (PBL) or lymphoid tissue isolated from several nonimmunized donors using polymerase chain reaction (PCR) primers that correspond to all known VH, Vκ, and Vλ gene sequences. These are principally based on those published previously () with further information on the most recent VH sequences obtained from the V-BASE directory (Tomlinson et al., MRC Centre for Protein Engineering). To ensure that all five Ab classes are likely to be represented and increase the overall size of the final library, random hexamers are employed in the primary first-strand cDNA synthesis from PBL mRNA. Component VH and VL gene segments are amplified in separate PCR reactions, and initially cloned into two different vectors, pCANTAB6 and pCANTAB3his6 (see Figure 1). The latter is used for cloning the VL repertoire because it has the appropriate polylinker cloning sites for the digested VL fragments; the VH repertoire is cloned into pCANTAB6. A short linker from an existing scFv is cloned (together with an irrelevant or “dummy” VH) into the VL repertoire, upstream of the VL fragments. The VH and linker-VL repertoires are then amplified from their vectors, and the scFv construct is prepared using a simple two-fragment PCR assembly procedure. This construct is then cloned into pCANTAB6 to create the large naïve scFv library ().
Modeling and design study of nanocrystal memory devices (2002)

Semiconductor memory for the future demand high density/low cost and low power consumption cell design. Compared with DRAM, flash memory with floating gate structure consume less power and they can also achieve much high array density. However, the tunnel oxide must be less than 25 Å in order to achieve 100 ns write/erase time for a reasonable programming voltage (<10 V). Unfortunately, the retention time of a floating-gate device with 20 Å tunnel oxide is less than 1 ms. To achieve a better retention/programming time ratio, a semiconductor memory with nanocrystal embedded in the gate dielectric was proposed. Although a nanocrystal memory device has been experimentally investigated, no theory is available to guide its design or to predict its performance limits, especially the nanocrystal size scaling limit. In this paper, the write/erase and retention time of semiconductor nanocrystal memory devices at room temperature are modeled using single-charge tunneling theory with quantum confinement and Coulomb blockade effects. The impact of nanocrystal size and tunnel-oxide thickness are studied, and the suitability of nanocrystal memory devices for nonvolatile memory and DRAM applications is discussed.
HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer (1998)

The HLA-E class Ib molecule constitutes a major ligand for the lectin-like CD94/NKG2 natural killer (NK) cell receptors. Specific HLA class I leader sequence-derived nonapeptides bind to endogenous HLA-E molecules in the HLA-defective cell line 721.221, inducing HLA-E surface expression, and promote CD94/NKG2A-mediated recognition. We compared the ability of NK clones which expressed either inhibitory or activating CD94/NKG2 receptors to recognize HLA-E molecules on the surface of 721.221 cells loaded with a panel of synthetic nonamers derived from the leader sequences of most HLA class I molecules. Our results support the notion that the primary structure of the HLA-E-bound peptides influences CD94/ NKG2-mediated recognition, beyond their ability to stabilize surface HLA-E. Further, CD94/ NKG2A+ NK clones appeared more sensitive to the interaction with most HLA-E-peptide complexes than did effector cells expressing the activating CD94/NKG2C receptor. However, a significant exception to this pattern was HLA-E loaded with the HLA-G-derived nonamer. This complex triggered cytotoxicity very efficiently over a wide range of peptide concentrations, suggesting that the HLA-E/G-nonamer complex interacts with the CD94/NKG2 triggering receptor with a significantly higher affinity. These results raise the possibility that CD94/NKG2-mediated recognition of HLA-E expressed on extravillous cytotrophoblasts plays an important role in maternal-fetal cellular interactions.
Text compression using variable‐to fixed‐length encodings (1982)

Abstract Many methods have been suggested for representing text for storage on magnetic media or for transmission down telecommunication channels with fewer bits then are required by a conventional fixed‐length character representation. These methods are reviewed, and attention is drawn to the advantages of techniques in which variable‐length character strings are represented by a fixed number of bits. Such techniques are described in more detail. The advantages and disadvantages of implementing text compression in storage and telecommunications are discussed, and an indication is given of the types of hardware which may be used. The extent to which text may be compressed with the methods discussed, and approximate timings, are stated.