gebhart/patrepeval huggingface dataset:
Two Listeria monocytogenes Vaccine Vectors That Express Different Molecular Forms of Human Papilloma Virus-16 (HPV-16) E7 Induce Qualitatively Different T Cell Immunity That Correlates with Their Ability to Induce Regression of Established Tumors Immortalized by HPV-16 (2001)

Two recombinant Listeria monocytogenes (rLm) strains were produced that secrete the human papilloma virus-16 (HPV-16) E7 protein expressed in HPV-16-associated cervical cancer cells. One, Lm-E7, expresses and secretes E7 protein, whereas a second, Lm-LLO-E7, secretes E7 as a fusion protein joined to a nonhemolytic listeriolysin O (LLO). Lm-LLO-E7, but not Lm-E7, induces the regression of the E7-expressing tumor, TC-1, established in syngeneic C57BL/6 mice. Both recombinant E7-expressing rLm vaccines induce measurable anti-E7 CTL responses that stain positively for H-2D(b) E7 tetramers. Depletion of the CD8+ T cell subset before treatment abrogates the ability of Lm-LLO-E7 to impact on tumor growth. In addition, the rLm strains induce markedly different CD4+ T cell subsets. Depletion of the CD4+ T cell subset considerably reduces the ability of Lm-LLO-E7 to eliminate established TC-1 tumors. Surprisingly, the reverse is the case for Lm-E7, which becomes an effective anti-tumor immunotherapeutic in mice lacking this T cell subset. Ab-mediated depletion of TGF-beta and CD25+ cells improves the effectiveness of Lm-E7 treatment, suggesting that TGF-beta and CD25+ cells are in part responsible for this suppressive response. CD4+ T cells from mice immunized with Lm-E7 are capable of suppressing the ability of Lm-LLO-E7 to induce the regression of TC-1 when transferred to tumor-bearing mice. These studies demonstrate the complexity of L. monocytogenes-mediated tumor immunotherapy targeting the human tumor Ag, HPV-16 E7.
Rolling Circle Amplification: Applications in Nanotechnology and Biodetection with Functional Nucleic Acids (2008)

Rolling circle amplification (RCA) is an isothermal, enzymatic process mediated by certain DNA polymerases in which long single-stranded (ss) DNA molecules are synthesized on a short circular ssDNA template by using a single DNA primer. A method traditionally used for ultrasensitive DNA detection in areas of genomics and diagnostics, RCA has been used more recently to generate large-scale DNA templates for the creation of periodic nanoassemblies. Various RCA strategies have also been developed for the production of repetitive sequences of DNA aptamers and DNAzymes as detection platforms for small molecules and proteins. In this way, RCA is rapidly becoming a highly versatile DNA amplification tool with wide-ranging applications in genomics, proteomics, diagnosis, biosensing, drug discovery, and nanotechnology.
Phylogenomics of Sterol Synthesis: Insights into the Origin, Evolution, and Diversity of a Key Eukaryotic Feature (2009)

The availability of complete genomes from a wide sampling of eukaryotic diversity has allowed the application of phylogenomics approaches to study the origin and evolution of unique eukaryotic cellular structures, but these are still poorly applied to study unique eukaryotic metabolic pathways. Sterols are a good example because they are an essential feature of eukaryotic membranes. The sterol pathway has been well dissected in vertebrates, fungi, and land plants. However, although different types of sterols have been identified in other eukaryotic lineages, their pathways have not been fully characterized. We have carried out an extensive analysis of the taxonomic distribution and phylogeny of the enzymes of the sterol pathway in a large sampling of eukaryotic lineages. This allowed us to tentatively indicate features of the sterol pathway in organisms where this has not been characterized and to point out a number of steps for which yet-to-discover enzymes may be at work. We also inferred that the last eukaryotic common ancestor already harbored a large panel of enzymes for sterol synthesis and that subsequent evolution over the eukaryotic tree occurred by tinkering, mainly by gene losses. We highlight a high capacity of sterol synthesis in the myxobacterium Plesiocystis pacifica, and we support the hypothesis that the few bacteria that harbor homologs of the sterol pathway have likely acquired these via horizontal gene transfer from eukaryotes. Finally, we propose a potential candidate for the elusive enzyme performing C-3 ketoreduction (ERG27 equivalent) in land plants and probably in other eukaryotic phyla.
Effect of <i>L</i>-Arginine Infusion on Infants with Persistent Pulmonary Hypertension of the Newborn (1995)

Nitric oxide (NO) is thought to be a primary mediator of the reduction in pulmonary vascular resistance which occurs in the newborn period. L-arginine is the precursor for the formation of nitric oxide in the pulmonary endothelium. Low serum arginine levels have been reported in infants with persistent pulmonary hypertension of the newborn (PPHN). We infused a single L-arginine dose of 500 mg/kg over 30 min to 5 consecutive infants with PPHN. Ninety minutes after infusion we observed an associated rise in PaO2 of 37 to 84 mm Hg and, in 4 of 5 infants, a reduction in oxygenation index (OI) of 33-50% over the 5-hour period following infusion. Infusion was not associated with adverse effects. These observations suggest that L-arginine administration may be an effective therapeutic alternative in infants with PPHN.
Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment (2012)

Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.
Digital audio and internet radio broadcasting systems under a QoS perspective (2005)

Abstract:- Examination of the Quality of Service (QoS) at the end-user level of multimedia broadcasting systems is necessary in order to retain the overall performance and the user’s satisfaction level from the provided services, by revealing the possible weaknesses of the systems ’ specifications. Accordingly we examine Digital Audio Broadcasting (DAB) system’s characteristics at the services level, with a view to propose some extensions to the DAB system and to examine QoS specifications for Internet radio broadcasting.
Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds (2010)

In this paper, we demonstrate for the first time that the detailed cutaneous blood flow at capillary level within dermis of human skin can be imaged by optical micro-angiography (OMAG) technique. A novel scanning protocol, i.e. fast B scan mode is used to achieve the capillary flow imaging. We employ a 1310nm system to scan the skin tissue at an imaging rate of 300 frames per second, which requires only ~5 sec to complete one 3D imaging of capillary blood flow within skin. The technique is sensitive enough to image the very slow blood flows at ~4 microm/sec. The promising results show a great potential of OMAG's role in the diagnosis, treatment and management of human skin diseases.
Abnormal Cardiac Structure and Function in Mice Expressing Nonphosphorylatable Cardiac Regulatory Myosin Light Chain 2 (1999)

A role for myosin phosphorylation in modulating normal cardiac function has long been suspected, and we hypothesized that changing the phosphorylation status of a cardiac myosin light chain might alter cardiac function in the whole animal. To test this directly, transgenic mice were created in which three potentially phosphorylatable serines in the ventricular isoform of the regulatory myosin light chain were mutated to alanines. Lines were obtained in which replacement of the endogenous species in the ventricle with the nonphosphorylatable, transgenically encoded protein was essentially complete. The mice show a spectrum of cardiovascular changes. As previously observed in skeletal muscle, Ca(2+) sensitivity of force development was dependent upon the phosphorylation status of the regulatory light chain. Structural abnormalities were detected by both gross histology and transmission electron microscopic analyses. Mature animals showed both atrial hypertrophy and dilatation. Echocardiographic analysis revealed that as a result of chamber enlargement, severe tricuspid valve insufficiency resulted in a detectable regurgitation jet. We conclude that regulated phosphorylation of the regulatory myosin light chains appears to play an important role in maintaining normal cardiac function over the lifetime of the animal.
Multimedia semantic indexing using model vectors (2003)

In this paper we propose a novel method for multimedia semantic indexing using model vectors. Model vectors provide a semantic signature for multimedia documents by capturing the detection of concepts broadly across a lexicon using a set of independent binary classifiers. While recent techniques have been developed for detecting simple generic concepts such as indoors, outdoors, nature, manmade, faces, people, speech, music, and so forth [W.H. Adams et al., November 2002], these labels directly support only a small number of queries. Model vectors address the problem of answering queries for which relationships to specific concepts is either unknown or indirect by developing a basis across across the lexicon. In the simplest case, each model vector dimension corresponds to the confidence score by which a corresponding concept from the lexicon is detected. However, we show how other information such as relevance, reliability and concept correlation can also be incorporated. Overall, the model vectors can be used in a variety of methods for multimedia indexing, including model-based retrieval, relevance feedback searching and concept querying. In this paper, we present the model vector method and study different strategies for computing and comparing model vectors. We empirically evaluate the retrieval effectiveness of the model vector approach compared to other search methods in a large video retrieval testbed.
Selective Cell Uptake of Modified Tat Peptide–Fluorophore Conjugates in Rat Retina in Ex Vivo and In Vivo Models (2006)

A specific pattern of uptake for modified Tat peptides was consistently seen in the rodent retina. Given the preferential uptake of these peptides by RGCs and the potential to conjugate diverse moieties, modified Tat peptides may be useful for delivery of therapeutic agents or molecular imaging probes to RGCs.
Catalytic Cracking of Plastic Pyrolysis Waxes with Vacuum Gasoil: Effect of HZSM-5 Zeolite in the FCC Catalyst (2006)

Catalytic cracking of waste plastics is an interesting option for selectively recovering raw materials or for obtaining fuels. In this paper, a new recycling strategy is proposed, which consists of upgrading the waxes obtained by flash pyrolysis of polyolefins in a FCC (Fluidized Catalytic Cracking) unit. The waxes have been obtained by flash pyrolysis of polypropylene at 500 ºC and they have been dissolved (20 wt% wax) in the vacuum gasoil (VGO) of a FCC unit. The runs have been carried out in a CREC-UWO Riser Simulator Reactor (atmospheric pressure; 500-550 ºC; C/O = 5.5; contact times, 3-12 s). A commercial catalyst and a hybrid one (containing HZSM-5 zeolite) have been used. The cracking of the mixture leads to higher yield of gasoline than in the cracking of VGO with a higher content of olefins. The results of the effect of the operating conditions (temperature and contact time) are qualitatively similar to those corresponding to standard feed. Consequently, no difficulties inherent to the presence of waxes in the feed are expected in the treatment of mixtures at industrial conditions. The presence of HZSM-5 zeolite in the catalyst causes a significant increase in the amount of LPG (especially C3-C4 olefins), at the expense of a decrease in the gasoline fraction, whose RON is 1-2 points higher than that corresponding to the commercial catalyst. The gasoline obtained also has a higher content of olefins (especially C5-C7) and benzene at the expense of a decrease in the amount of C6-C10 i-paraffins.
Analytical Model for Surface Electrical Field of Double RESURF LDMOS with Field Plate (2006)

An analytical model for surface electrical field distribution along the drift region of double RESURF LDMOS with the gate and the drain field plates is presented, which takes the influence of non-uniformly doping concentration into account. Based on the 2D Poisson equation, the model provides an closed solution of electrical field distribution including the off-state and the on-state under different bias. The analytical results are verified by the semiconductor device simulator MEDICI and are analyzed based on optimization devices
Characterization of Competitive Inhibitors for the Transferase Activity of Pseudomonas aeruginosa Exotoxin A (2002)

A series of small, nonpolar compounds were tested for their ability to inhibit the ADP-ribosyl transferase activity of Pseudomonas aeruginosa exotoxin A. The IC50 values for the compounds tested ranged from 87 nM to 484 microM for NAP and CMP12, respectively. It was demonstrated that NAP was a competitive inhibitor of the ADPRT reaction for the NAD+ substrate with a Ki of 45 +/- 5 nM, which was in good agreement with the dissociation constant determined independently (KD = 56 +/- 6 nM). The IC50 value for NAP was 87 +/- 12 nM, which strongly correlated with the Ki and KD values. Furthermore, NAP was shown to noncovalently associate with the exotoxin A active site using exhaustive dialysis, NMR, and electrospray mass spectrometry. Finally, a computer molecular model using the X-ray structure of the substrate-bound toxin was generated with NAP bound to the active site of exotoxin A at the nicotinamide-binding site. This model is consistent with the X-ray structure of the catalytic domain of poly-ADP-ribose polymerase complexed with 4-amino-naphthalimide (Compound 4) that was included in this study.
Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells (2015)

Ribosomal protein L34 (RPL34) was reported to be involved in the regulation of cell proliferation of prokaryotes, plant and animal cells. In the present study, we analyze the expression and function of RPL34 in NSCLC. Immunohistochemical analysis, qPCR and Western blot were used to detect the expression of RPL34 in NSCLC tissues and cells lines. Flow cytometry was used to detect cell activity of NSCLC cell line H1299 under lentivirus-mediated RNAi on RPL34. Cell proliferation and colony formation assays were used to analyze the role of RPL34 in NSCLC cell proliferation. We found that expression of ribosomal protein RPL34 was significantly up-regulated in NSCLC tissues compared to adjacent normal tissues. Lentivirus-mediated shRNA knockdown of RPL34 in NSCLC cell line H1299 resulted in a strong decrease of proliferation, and a moderate but significant increase of apoptosis and S-phase arrest. These data indicate that over-expressed RPL34 may promote malignant proliferation of NSCLC cells, thus playing an important role in development and progress of NSCLC.
Pipelined architecture for fast CMOS buffer RAMs (1990)

A novel pipeline architecture for CMOS static RAMs (SRAMs) that allows operation at very high clock rates is described. Basic requirements for achieving high speed are the implementation of a hierarchical architecture and a memory cell with separate READ and WRITE data lines. The access speed of hierarchically organized memory blocks was between 2.5 and 3.5 ns. The maximum operating frequency of a 16 K pipelined hierarchical SRAM (PHSRAM) is in the range of 300 MHz. The hierarchical architecture and a seven-transistor memory cell provide a circuit using digital swings all over. Key advantages of the full-swing static logic circuitry are robustness with respect to fabrication tolerances and a high-noise immunity. Moreover, the circuit can be reduced to finer structure sizes without any redesign, since there are no critical analog circuit parts.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Rapid cycle DNA amplification: time and temperature optimization. (1991)

Rapid temperature cycling with hot air allows rigorous optimization of the times and temperatures required for each stage of the polymerase chain reaction. A thermal cycler based on recirculating hot air was used for rapid temperature control of 10-microliters samples in thin glass capillary tubes with the sample temperature monitored by a miniature thermocouple probe. The temperatures and times of denaturation, annealing and elongation were individually optimized for the amplification of a 536-base pair beta-globin fragment from human genomic DNA. Optimal denaturation at 92 degrees-94 degrees C occurred in less than one second; yield decreased with denaturation times greater than 30 seconds. Annealing for one second or less at 54 degrees-56 degrees C gave the best product specificity and yield. Non-specific amplification was minimized with a rapid denaturation to annealing temperature transition (9 seconds) as compared to a longer transition (25 seconds). An elongation temperature of 75 degrees-79 degrees C gave the greatest yield and increased yields were obtained with longer elongation times. Product specificity was improved with rapid air cycling when compared to slower conventional heat block cycling. Rapid thermal control of the temperature-dependent reactions in DNA amplification can improve product specificity significantly while decreasing the required amplification time by an order of magnitude.
Re-induction with ipilimumab, gp100 peptide vaccine, or a combination of both from a phase III, randomized, double-blind, multicenter study of previously treated patients with unresectable stage III or IV melanoma. (2010)

8509 Background: Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has demonstrated clinical activity against advanced melanoma. In prior studies, gp100 vaccine showed immunological and clinical responses, and enhanced clinical activity when combined with other immunotherapy. Safety and efficacy of ipilimumab, ipilimumab + gp100 vaccine, and gp100 vaccine were evaluated in this study. Methods: Eligible patients were randomized 1:3:1, respectively, to receive an induction course of 4 doses of study drug: ipilimumab (3 mg/kg q3w × 4 doses) + placebo; ipilimumab + gp100 (peptides 209-217 [210M] and 280-288 [288V]); or gp100 (1 mg q3w × 4 doses) + placebo. Re-induction was allowed within 28 days of documented progression, provided the response to the initial cycle of therapy was SD lasting ≥3 months from week 12, CR, or PR. Patients were re-induced with 1 to 3 additional courses of the originally assigned regimen. Results: Of 643 patients initially treated, 32 were re-induced per protocol (8 with ipilimumab, 23 with combination therapy and 1 with gp100 [6.1%, 7.3%, and 0.8%, respectively, of the total who received initial therapy with each]) and their responses reassessed. Efficacy results are presented below. An acceptable safety profile was demonstrated in all 3 treatment arms and was similar to that of the initial induction treatment. Conclusions: In patients who progressed following an initial response to the induction course of therapy, the disease control rate in the ipilimumab arms was 65%-75% compared to 0% in the gp100 arm upon re-induction. These findings may have implications for the use of ipilimumab therapy in the long-term management of advanced melanoma. Induction, n Best overall response Ipilimumab + gp100 (n = 23*) Ipilimumab (n = 8) gp100 (n = 1) Total (n = 32) CR 0 0 0 0 PR 7 2 1 10 SD 15 6 0 21 Unknown 1 0 0 1 Re-induction, n (%) CR 0 1 (12.5) 0 1 (3.1) PR 4 (17.4) 2 (25.0) 0 6 (18.8) SD 11 (47.8) 3 (37.5) 0 14 (43.8) PD 8 (34.8) 2 (25.0) 1 (100.0) 11 (34.4) Unknown 0 0 0 0 * 5 additional pts were re-induced in error and are not part of the analysis. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex Bristol-Myers Squibb Bristol-Myers Squibb, Medarex Bristol-Myers Squibb Bristol-Myers Squibb, Medarex
High level expression of a truncated chicken progesterone receptor in Escherichia coli. (1990)

Using a novel Escherichia coli system we have successfully overexpressed a region of the chicken progesterone receptor which encodes both the DNA- and hormone-binding domains. The expression system produces the truncated receptor fragment as an in-frame fusion with ubiquitin. This strategy greatly enhances both the solubility and stability of fusion proteins expressed in E. coli. Synthesis has been further improved by induction of the lambda PL promoter with nalidixic acid at low growth temperatures (less than or equal to 30 degrees C) rather than use of conventional heat induction protocols. We can produce 10 mg of receptor fragment/liter of cells using this system, and we estimate that at least 0.3 mg of this receptor material is biologically active, as assessed by DNA-binding and hormone-binding assays. Receptor produced in this manner is almost indistinguishable from authentic oviduct progesterone receptor using the criteria of hormone-binding specificity and affinity and binding to a progesterone response element. This expression system offers a cheap convenient method for the production of mg amounts of biologically active derivatives of progesterone receptor for biochemical studies.
Impact of cell threshold voltage distribution in the array of flash memories on scaled and multilevel flash cell design (2002)

This paper, for the first time, describes the analytical expressions which explicitly relate single-cell characteristics to Flash array behaviour including statistical consideration. Since the bitline leakage current caused by over-erased cells and/or broad threshold voltage (Vt) distribution generates read/verify circuitry malfunctions and a degraded programming due to voltage drop, and charge-pump circuitry failure, this leakage are extensively analyzed to find the optimum operation biases, array Vt design, their allowed variations and bitline segmentation in the scaled multilevel cell generation.