gebhart/patrepeval huggingface dataset:
Tumor-Targeted Salmonella: Strain Development and Expression of the HSV-tK Effector Gene (2003)

Gene therapy approaches to cancer treatment have been limited by the ability of the delivery vectors to achieve specific high-level expression within tumor cells or the tumor environment following systemic administration. Numerous physical barriers exist in the delivery of therapeutic agents (including drugs, viruses, and liposomes) to solid tumors that can compromise the effectiveness (1), thus stimulating the search for alternative methods of delivery. Whereas it has been known for some time that spores of anaerobic Clostridium can germinate within the necrotic spaces of human tumors, they are limited to larger hypoxic tumors and are inaccessible to smaller metastases (2,3). The ability of motile, facultatively anaerobic Salmonella to target tumors following systemic administration, preferentially amplify within them, and express effector genes such as the herpes simplex virus thymidine kinase (HSV-TK) makes them an attractive alternative to Clostridia, liposome and viral-based delivery vectors (4). These Salmonella were attenuated by poly-auxotrophic mutations, which limited their pathogenesis in normal tissues, but retained high-level replication within tumors, resulting in tumor suppression of both primary and metastatic tumors (4,5). The attenuating mutations were added stepwise following in vitro and in vivo selection and screening methods. Although live-attenuated vectors for use in humans requires defined genetic mutations, our experience has shown that combinations of point-mutations and frame-shift mutations allows for rapid isolation of strains with multiple mutations having desirable properties, which can later be defined and/ or stabilized. Bearing this in mind, we present the basic methodology for the development of tumor-targeting facultative anaerobes with effector gene delivery capabilities that we applied to Salmonella.
Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies (2005)

Epigenetic regulation of gene expression is mediated through alterations in the DNA methylation status, covalent modifications of core nucleosomal histones, rearrangement of histones, and by RNA interference. It is now abundantly clear that deregulation of epigenetic mechanisms cooperates with genetic alterations in the development and progression of cancer and leukemia. Epigenetic deregulation affects several aspects of tumor cell biology, including cell growth, cell cycle control, differentiation, DNA repair, and cell death. This raises the strong possibility that reversing deregulated epigenetic mechanisms may be an effective treatment strategy for leukemia and cancer. This treatment strategy may either be designed to separately or collectively target the specific perturbations in the epigenetic mechanisms found in human hematologic malignancies. The following review describes our current understanding of the important deregulated epigenetic mechanisms and the preclinical and clinical development of epigenetic and chromatin modifiers in the therapy of these disorders.
Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings (2009)

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; >/=15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.
Omega-3 fatty acids in cancer (2013)

Combination of chemotherapy and omega-3 supplementation appears an effective strategy to enhance the clinical outcome of cancer patients in their curative and palliative clinical trajectory.
The Use of Combinations of Caries Preventive Procedures (2001)

There are now a number of different approaches to preventing dental caries available to the clinician. Caries preventive methods are frequently used in combination. This paper reviews the potential effectiveness of combinations of preventive methods. Three groups of studies are reviewed; combinations of fluoride procedures; fluoride and fissure sealants; chlorhexidine and other agents. The review indicates that there is considerable benefit to be derived from using more than one fluoride procedure. Further research is required in the effectiveness of combining chlorhexidine with other agents. The most promising combination programme currently appears to be the use of fluoride with fissure sealing. The relevance of combination therapy for adults needs to be investigated.
Vote3Deep: Fast object detection in 3D point clouds using efficient convolutional neural networks (2017)

This paper proposes a computationally efficient approach to detecting objects natively in 3D point clouds using convolutional neural networks (CNNs). In particular, this is achieved by leveraging a feature-centric voting scheme to implement novel convolutional layers which explicitly exploit the sparsity encountered in the input. To this end, we examine the trade-off between accuracy and speed for different architectures and additionally propose to use an L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> penalty on the filter activations to further encourage sparsity in the intermediate representations. To the best of our knowledge, this is the first work to propose sparse convolutional layers and L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> regularisation for efficient large-scale processing of 3D data. We demonstrate the efficacy of our approach on the KITTI object detection benchmark and show that Vote3Deep models with as few as three layers outperform the previous state of the art in both laser and laser-vision based approaches by margins of up to 40% while remaining highly competitive in terms of processing time.
Reconstitution of human Fc gamma RIII cell type specificity in transgenic mice. (1996)

The human low affinity receptors for the Fc domain of immunoglobulin G, Fc gamma RIII, are encoded by two genes (IIIA and IIIB) which share >95% sequence identity in both coding and flanking sequences. Despite this extraordinary sequence conservation, IIIA is expressed in natural killer (NK) cells and macrophages and is absent in neutrophils, whereas IIIB is expressed only in neutrophils. To determine the molecular basis for this differential expression, we have generated transgenic mice using the genomic sequences of IIIA and IIIB. IIIA and IIIB transgenic mice show faithful reconstitution of this human pattern of cell type specificity. To determine the cis acting sequence elements that confer this specificity, we constructed chimeric genes in which 5.8 kb of 5' sequences of the IIIB gene has been replaced with a homologous region from the IIIA gene, and conversely, IIIA 5' sequences have been substituted for the analogous region of the IIIB gene. Promoter swap transgenic mice that carry IIIA 5' flanking sequences express Fc gamma RIII in macrophages and NK cells. In contrast, promoter swap transgenic mice that contain IIIB 5' sequences express Fc gamma RIII in neutrophils only. These studies define the elements conferring the cell type-specific expression of the human Fc gamma RIII genes within the 5' flanking sequences and first intron of the human Fc gamma RIIIA and Fc gamma RIIIB genes.
Degrees-of-Freedom Region of the MISO Broadcast Channel with General Mixed-CSIT (2012)

In the setting of the two-user broadcast channel, recent work by Maddah-Ali and Tse has shown that knowledge of prior channel state information at the transmitter (CSIT) can be useful, even in the absence of any knowledge of current CSIT. Very recent work by Kobayashi et al., Yang et al., and Gou and Jafar, extended this to the case where, instead of no current CSIT knowledge, the transmitter has partial knowledge, and where under a symmetry assumption, the quality of this knowledge is identical for the different users' channels. Motivated by the fact that in multiuser settings, the quality of CSIT feedback may vary across different links, we here generalize the above results to the natural setting where the current CSIT quality varies for different users' channels. For this setting we derive the optimal degrees-of-freedom (DoF) region, and provide novel multi-phase broadcast schemes that achieve this optimal region. Finally this generalization incorporates and generalizes the corresponding result in Maleki et al. which considered the broadcast channel with one user having perfect CSIT and the other only having prior CSIT.
NUTRITIONAL CONTROL OF GENE EXPRESSION: How Mammalian Cells Respond to Amino Acid Limitation (2005)

The amino acid response (AAR) pathway in mammalian cells is designed to detect and respond to amino acid deficiency. Limiting any essential amino acid initiates this signaling cascade, which leads to increased translation of a "master regulator," activating transcription factor (ATF) 4, and ultimately, to regulation of many steps along the pathway of DNA to RNA to protein. These regulated events include chromatin remodeling, RNA splicing, nuclear RNA export, mRNA stabilization, and translational control. Proteins that are increased in their expression as targets of the AAR pathway include membrane transporters, transcription factors from the basic region/leucine zipper (bZIP) superfamily, growth factors, and metabolic enzymes. Significant progress has been achieved in understanding the molecular mechanisms by which amino acids control the synthesis and turnover of mRNA and protein. Beyond gaining additional knowledge of these important regulatory pathways, further characterization of how these processes contribute to the pathology of various disease states represents an interesting aspect of future research in molecular nutrition.
Targeting E2F1–DNA complexes with microgonotropen DNA binding agents (1997)

Microgonotropen (MGT) DNA binding drugs, which consist of an A+T-selective DNA minor groove binding tripyrrole peptide and polyamine chains attached to a central pyrrole that extend drug contact into the DNA major groove, were found to be extraordinarily effective inhibitors of E2 factor 1 (E2F1) association with its DNA promoter element (5'-TTTCGCGCCAAA). The most active of these drugs, MGT-6a, was three orders of magnitude more effective than distamycin and inhibited complexes between E2F1 and the dihydrofolate reductase promoter by 50% at 0.00085 microM. A relationship was found between the measured equilibrium constants for binding of MGTs to the A+T region of d(GGCGA3T3GGC)/d(CCGCT3A3CCG) and their inhibition of complex formation between E2F1 and the DNA promoter element. A representative of the potent MGT inhibitors was significantly more active on inhibition of E2F1-DNA complex formation compared with disruption of a preexisting complex.
Oligomers of the Arginine-rich Motif of the HIV-1 TAT Protein Are Capable of Transferring Plasmid DNA into Cells (2003)

We constructed multimers of the TAT-(47-57) peptide. This polycationic peptide is known to be a protein and particle transduction domain and at the same time to comprise a nuclear localization function. Here we show that oligomers of the TAT-(47-57) peptide compact plasmid DNA to nanometric particles and stabilize DNA toward nuclease degradation. At optimized vector compositions, these peptides mediated gene delivery to cells in culture 6-8-fold more efficiently than poly-L-arginine or the mutant TAT(2)-M1. When DNA was precompacted with TAT peptides and polyethyleneimine (PEI), Superfect, or LipofectAMINE was added, transfection efficiency was enhanced up to 390-fold compared with the standard vectors. As early as after 4 h of transfection, reporter gene expression mediated by TAT-containing complexes was higher than the 24-h transfection level achieved with a standard PEI transfection. When cells were cell cycle-arrested by serum starvation or aphidicolin, TAT-mediated transfection was 3-fold more efficient than a standard PEI transfection in proliferating cells. In primary nasal epithelial cells and upon intratracheal instillation in vivo, TAT-containing complexes were superior to standard PEI vectors. These data together with confocal imaging of TAT-DNA complexes in cells support the hypothesis that the TAT nuclear localization sequence function is involved in enhancing gene transfer.
Asynchronous Magnetic Bead Rotation Microviscometer for Rapid, Sensitive, and Label-Free Studies of Bacterial Growth and Drug Sensitivity (2012)

The long turnaround time in antimicrobial susceptibility testing (AST) endangers patients and encourages the administration of wide spectrum antibiotics, thus resulting in alarming increases of multidrug resistant pathogens. A method for faster detection of bacterial proliferation presents one avenue toward addressing this global concern. We report on a label-free asynchronous magnetic bead rotation (AMBR) based viscometry method that rapidly detects bacterial growth and determines drug sensitivity by measuring changes in the suspension's viscosity. With this platform, we observed the growth of a uropathogenic Escherichia coli isolate, with an initial concentration of 50 cells per drop, within 20 min; in addition, we determined the gentamicin minimum inhibitory concentration (MIC) of the E. coli isolate within 100 min. We thus demonstrated a label-free, microviscometer platform that can measure bacterial growth and drug susceptibility more rapidly, with lower initial bacterial counts than existing commercial systems, and potentially with any microbial strains.
Glucagon‐like peptide‐1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high‐fat diet in nonalcoholic steatohepatitis (2011)

GLP-1 has a direct effect on hepatocytes, by activating genes involved in fatty acid β-oxidation and insulin sensitivity. GLP-1 analogues could be a promising treatment approach to improve hepatic insulin resistance in patients with NAFLD/NASH.
The HIV-1 Protease as a Therapeutic Target for AIDS (1992)

HIV produces a small , dimeric aspartyl protease which specifically cleaves the polyprotein precursors encoding the structural proteins and enzymes of the virus. This proteolytic activity is absolutely required for the production of mature, infectious virions and is therefore an attractive target for therapeutic intervention. This review summarizes the strategies and multidisciplinary efforts that have been applied to date to the identification of specific inhibitors of this critical viral enzyme. These inhibitors include rationally designed peptide substrate analogs, compounds conceived from tertiary structure information on the enzyme and natural products. Future directions in the discovery and development of HIV-1 protease inhibitors are also discussed.
Low-loss CPW lines on surface stabilized high-resistivity silicon (1999)

The authors propose a solution to the surface conduction problem in silicon monolithic microwave integrated circuits (MMIC's). An LPCVD polycrystalline silicon layer is deposited over the surface of a high-resistivity silicon wafer which is then covered with a silicon dioxide layer. The polycrystalline silicon layer effectively removes, through traps, any free electrons or holes that may have been induced at the oxide-silicon interface. The CPW lines with 1.25-μm aluminum metallization on passivated HRS substrates have an attenuation loss at 30 GHz of only 1.08 dB/cm.
Differential effect of Photofrin II on growth of human smooth muscle cells from nonatherosclerotic arteries and atheromatous plaques in vitro. (1990)

The effect of dihematoporphyrin-ester or -ether (DHE), a photosensitizing porphyrin with different amounts of aggregates, on the growth of cultured smooth muscle cells obtained from nonatherosclerotic arteries and from atheromatous plaques (primary stenosing and restenosing lesions) was examined without photoactivation of the drug. Clinically relevant DHE concentrations ranging from 0.1 to 25 micrograms/ml were used. In all proliferation studies with cells of second and third passage (approximately 10 cumulative population doublings in vitro), the growth rates decreased in a dose-dependent manner. Smooth muscle cells from atherosclerotic lesions were significantly more sensitive than smooth muscle cells from normal arteries. Cells derived from restenosing lesions retained their increased sensitivity even after eight passages in culture (approximately 20 cumulative population doublings). Cell size measurements showed that the decreased proliferative activity mainly occurred in smooth muscle cell subpopulations consisting of small cells. A cytotoxic effect of DHE was observed at concentrations above 5 micrograms/ml, causing cytoplasmic protrusions, vacuoles, and even complete cell lysis. At a DHE concentration of 5 micrograms/ml, the number of viable cells was 73% +/- 14% (means +/- SD) for smooth muscle cells from nonatherosclerotic arterial media and only 38% +/- 11% (means +/- SD) for smooth muscle cells from atherosclerotic plaques. In all experiments, no significant difference in response to DHE treatment was observed between cells from primary stenosing and restenosing lesions, suggesting a specific mechanism for plaque-derived cells causing an increased sensitivity in comparison to smooth muscle cells from nonatherosclerotic arteries. The pronounced sensitivity of plaque cells against DHE treatment suggests that this drug--even without photoactivation--is potentially valuable in vivo as a therapeutic approach to vascular stenoses.
Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients (2005)

Teduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.
Design Tradeoffs in Applying Content Addressable Storage to Enterprise-scale Systems Based on Virtual Machines (2018)

This paper analyzes the usage data from a live deployment of an enterprise client management system based on virtual machine (VM) technology. Over a period of seven months, twenty-three volunteers used VM-based computing environments hosted by the system and created over 800 checkpoints of VM state, where each checkpoint included the virtual memory and disk states. Using this data, we study the design tradeoffs in applying content addressable storage (CAS) to such VM-based systems. In particular, we explore the impact on storage requirements and network load of different privacy properties and data granularities in the design of the underlying CAS system. The study clearly demonstrates that relaxing privacy can reduce the resource requirements of the system, and identifies designs that provide reasonable compromises between privacy and resource demands.
The Effects of Measurement System Dynamics in Vibration Tests (1990)

Experimental vibration tests typically involve exciting a structure into vibration and measuring the force and acceleration produced. The vibration characteristics of the structure are usually different from those in the absence of the exciters and transducers. This paper examines the effects of the transducer mass, exciter dynamics and stinger dynamics and gives methods that can reduce or correct for them. Also considered are ways in which the electrical inputs to the exciter can be measured and the force and acceleration applied to the test structure derived from them.
Isolation of a clone coding for the alpha-subunit of a mouse acetylcholine receptor (1985)

The mouse cell line BC3H-I synthesizes an acetylcholine receptor (AChR) with the pharmacological properties of a muscle nicotinic cholinergic receptor. We have purified mRNA from this cell line and used the size-fractionated poly(A)+RNA to produce a cDNA library of approximately 50,000 clones. The library was screened with a subclone containing genomic sequences coding for the putative acetylcholine-binding site of the alpha-subunit of chicken AChR. We obtained a plasmid, pMAR alpha 15, with a 1,717-base pair insert. The insert cDNA has 26 nucleotides at the 5'-end which code for a portion of the signal peptide followed by a single open reading frame of 1,311 nucleotides which code for a protein of 49,896 daltons. The insert has 377 bases of 3'-untranslated sequence with 3 polyadenylation sites. Radiolabeled plasmid DNA has been used to identify homologous RNA species of about 2 kilobases in Northern blot analyses of poly(A)+ selected RNA from BC3H-I cells. A similar size mRNA is seen in innervated mouse diaphragm and leg muscle, and both mouse and rat brain. Comparisons of the deduced amino acid sequence of the mouse AChR alpha-subunit with Torpedo marmorata, T. californica, chicken, human, and calf sequences show overall homologies of 80%, 80%, 86%, 96%, and 95%, respectively. More detailed analyses reveal a non-random distribution of amino acid substitutions in several structural domains. Based on the absolute conservation of cysteine residues, a new model for the arrangement of the disulfide bonds in the extracellular portion of the alpha-subunit is proposed.
Studies on polynucleotides, 88. Enzymatic joining of chemically synthesized segments corresponding to the gene for alanine-tRNA. (1968)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Folding DNA into Twisted and Curved Nanoscale Shapes (2009)

We demonstrate the ability to engineer complex shapes that twist and curve at the nanoscale from DNA. Through programmable self-assembly, strands of DNA are directed to form a custom-shaped bundle of tightly cross-linked double helices, arrayed in parallel to their helical axes. Targeted insertions and deletions of base pairs cause the DNA bundles to develop twist of either handedness or to curve. The degree of curvature could be quantitatively controlled, and a radius of curvature as tight as 6 nanometers was achieved. We also combined multiple curved elements to build several different types of intricate nanostructures, such as a wireframe beach ball or square-toothed gears.
An experimental study of future “natural” multimodal human-computer interaction (1993)

No abstract available.