gebhart/patrepeval huggingface dataset:
IL‐12 immunotherapy of murine leukaemia: comparison of systemic <i>versus</i> gene modified cell therapy (2008)

The ability of IL-12 to initiate anti-leukaemia immune responses has been well established; however clinical outcomes fail to recapitulate the therapeutic benefits observed in the laboratory. To address this, we compared two systems of IL-12 therapy that elicit protective immune responses against the murine acute lymphoblastic leukaemia (ALL) cell line, 70Z/3. These systems differ in the method of IL-12 administration and ultimately result in leukaemia clearance by distinct mechanisms, emphasizing the importance of treatment vehicle. Injecting low-dose IL-12 was sufficient to elicit long-term protective immunity against an established leukaemia burden, mediated by both CD4(+) and CD8(+) T cells. These findings agree with the standard model of IL-12 activity. We compared this protocol to a cell-based approach in which a novel lentiviral vector (LV) expressing murine IL-12 was created, 70Z/3 cells transduced, and clones selected that stably secrete different amounts of IL-12. We found that only a small proportion (1%) of IL-12 secreting cells were required for rejection but that the amount of IL-12 produced per cell was critical for successful therapy. Importantly, the levels of IL-12 required were found to be higher than the levels reported to date in the human clinical trial literature. We found that the cell-based approach led to protective immunity that was both long-term and specific but dependent primarily on a CD4(+) cellular subset alone. Our results highlight that the mode of IL-12 delivery has a distinct impact on the immune response initiated, leading to leukaemia clearance by disparate mechanisms. We also establish a new and critical parameter, IL-12 production/cell, which may have significant implications for future therapeutic design.
Large-Bowel Obstruction in the Adult: Classic Radiographic and CT Findings, Etiology, and Mimics (2015)

Large-bowel obstruction is an abdominal emergency with high morbidity and mortality rates if left untreated. Although abdominal radiography is usually the initial imaging study performed in patients suspected of having large-bowel obstruction, it may not be sufficient to distinguish obstruction from other causes of colonic dilatation. Computed tomography is the imaging method of choice as it can establish the diagnosis and cause of large-bowel obstruction. A contrast agent enema may be used to confirm or exclude large-bowel obstruction. In this review, the imaging findings in multiple causes of large-bowel obstruction are illustrated and compared with acute colonic pseudo-obstruction.
Tumor Imaging and Therapy Using Radiolabeled Somatostatin Analogues (2009)

Molecular imaging plays an essential role in balancing the clinical benefits and risks of radionuclide-based cancer therapy. To effectively treat individual patients, careful assessment of biodistribution, dosimetry, and toxicity is essential. In this Account, we describe advances that combine features of molecular imaging and radionuclide therapy to provide new avenues toward individualized cancer treatment. Selective receptor-targeting radiopeptides have emerged as an important class of radiopharmaceuticals for molecular imaging and therapy of tumors that overexpress peptide receptors on the cell membrane. After such peptides labeled with gamma-emitting radionuclides bind to their receptors, they allow clinicians to visualize receptor-expressing tumors non-invasively. Peptides labeled with beta-particle emitters could also eradicate receptor-expressing tumors. The somatostatin receptors, which are overexpressed in a majority of neuroendocrine tumors, represent the first and best example of targets for radiopeptide-based imaging and radionuclide therapy. The somatostatin analogue (111)In-octreotide permits the localization and staging of neuroendocrine tumors that express the appropriate somatostatin receptors. Newer modified somatostatin analogues, including Tyr(3)-octreotide and Tyr(3)-octreotate, are successfully being used for tumor imaging and radionuclide therapy. Because there are few effective therapies for patients with inoperable or metastasized neuroendocrine tumors, this therapy is a promising novel treatment option for these patients. Peptide receptor imaging and radionuclide therapy can be combined in a single probe, called a "theranostic". To select patients who are likely to benefit from this type of intervention, we first use a peptide analogue labeled with a diagnostic radionuclide to obtain a scan. Selected patients will be treated using the same or a similar peptide analogue labeled with a therapeutic radionuclide. The development of such theranostics could greatly advance the development of personalized treatments. Apart from patient selection for radionuclide therapy, other imaging applications of targeted radiopeptides include localization of primary tumors, detection of metastatic disease (staging/restaging), dosimetry (prediction of response and radiotoxicity), monitoring effects of surgery, radio(nuclide)therapy or chemotherapy, and detection of progression of disease or relapse (follow up). For further evaluation of tumor receptor expression and to increase the value of cancer targeting using radiopeptides, researchers have introduced and evaluated different radiolabeled analogues of other peptide families, such as cholecystokinin (CCK), gastrin, bombesin, substance P, vasoactive intestinal peptide (VIP), and neuropeptide (NP)-Y analogues. We expect improvements in the development of new peptide analogues: such advances could reduce side effects and allow for the use of combination therapy (for example, combining radiopeptide analogues with chemotherapeutics).
Prosthetic Osteomyelitis With Special Reference to the Knee: Risks, Treatment and Costs (1993)

The overall incidence of osteomyelitis following primary knee arthroplasty is 1-2%. Major risk factors are large prostheses, rheumatoid arthritis, postoperative wound-healing complications, skin infections, and prior deep infections. The major infecting organism is Staphylococcus aureus. Healing of the infection is to be expected in 20% when systemic antibiotics alone are used, in 24% when soft tissue surgery is used, in 50% when resection arthroplasty is used, in 76% when revision arthroplasty is used, in 90% when arthrodesis is used, and in 100% when amputation is used. The direct medical costs average US$ 62,100 for an infected patient and US$ 8600 for a non-infected patient. Attention should focus on prophylactic measures directed towards the soft tissue problems: by avoiding conflicting skin incisions, by gentle handling of the periarticular soft tissues, by avoiding the use of constrained prostheses and oversized compartmental prostheses, by letting wound healing take priority over motion in knees with compromised soft tissues, and by using prophylactic antibiotic treatment for skin ulcers until these have healed.
Enhanced Thermal Stability in Perpendicular Top-Pinned Magnetic Tunnel Junction With Synthetic Antiferromagnetic Free Layers (2013)

Synthetic antiferromagnetic (SAF) free layers consisting of [Co (0.3 nm)/Pd (0.7 nm)] <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</sub> /Ru/Ta/CoFeB were investigated for use in the free layers of top-pinned magnetic tunnel junctions (MTJs). We found that interlayer exchange coupling properly provides thermal stability when the saturation magnetization of the CoPd layer is less than that of the CoFeB layer. Furthermore, we demonstrated that the thermal stability factor of the top-pinned MTJ with [Co (0.3 nm)/Pd (0.7 nm)] <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n=1/</sub> Co (0.3 nm)/Ru/Ta/CoFeB- SAF free layers was improved without increasing the intrinsic switching current.
Insig-1 “brakes” lipogenesis in adipocytes and inhibits differentiation of preadipocytes (2003)

We have examined gene expression in the fat tissue of normal mice at the onset of diet-induced obesity. Insulin-induced gene 1 (insig-1) mRNA rose progressively with a high-fat diet and declined on a restricted diet. Because insig-1 binds sterol regulatory element-binding protein cleavage-activating protein in the endoplasmic reticulum, thereby blocking proteolytic processing required for sterol regulatory element-binding protein activation, we tested its influence on lipogenesis. In differentiating 3T3-L1 cells, insig-1 and -2 rose in parallel with aP2 mRNA during differentiation. The mRNA of the lipogenic transcription factor, carbohydrate response element-binding protein, was undetectable in undifferentiated 3T3-L1 preadipocytes but rose dramatically during differentiation in 25 mM, but not in 5 mM, glucose. Transfection of mouse or human insig-1 into 3T3-L1 preadipocytes completely prevented oil red O staining and blocked upregulation of aP2, peroxisome proliferator-activated receptor gamma2, and carbohydrate response element-binding protein, while reducing down-regulation of preadipocyte factor 1. The results suggest that insig-1 expression restricts lipogenesis in mature adipocytes and blocks differentiation in preadipocytes.
Medical imaging by NMR (1977)

Application of the new nuclear magnetic resonance (NMR) method of fast scan proton imaging is described. Cross sectional proton scans of a human finger in vivo are measured and reveal considerable anatomical detail, particularly of the soft tissue regions. Imaging of tumour tissue is also briefly discussed.
C-BIRD: content-based image retrieval from digital libraries using illumination invariance and recognition kernel (2002)

With huge amounts of multimedia information connected to the global information network (Internet), efficient and effective image retrieval from large image and video repositories has become an imminent research issue. This article presents our research in the C-BIRD (Content-Based Image Retrieval from Digital libraries) project. In addition to the use of common features such as keywords, color texture, shape and their conjuncts, it is shown that (a) the color-channel-normalization enables search by illumination invariance, and (b) the multi-level recognition kernel facilitates search by object model in image and video databases.
A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum (2022)

Potent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the Pf circumsporozoite protein (PfCSP). Although most attention has focused on antibodies to repeat motifs on PfCSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted α-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved β-sheet face of the ctCSP (denoted β-ctCSP). Antibodies to the β-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of P. falciparum whereas antibodies to the α-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the β-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design.
<scp>GPCR</scp>Homology Model Development and Application (2010)

Abstract G‐protein‐coupled receptors (GPCRs) are a very important class of proteins for drug discovery. Exciting progress has been made recently in the determination of X‐ray crystal structures. However, despite this, structural coverage of the receptor family is still thin. We lack direct structural knowledge of many important subfamilies, we have only modest detail of the conformational changes associated with receptor activation and we lack robust crystallographic systems for the rapid determination of ligand binding modes. As a consequence, the ability to build and apply homology models for drug discovery at these targets is very valuable. The accuracy of the models has improved in parallel with the increase in available structural data and the models have been successfully applied to a wide range of lead generation and optimization problems.
Nicotine regulates 5‐HT<sub>1A</sub> receptor gene expression in the cerebral cortex and dorsal hippocampus (2001)

The 5-HT(1A) receptor has previously been shown to be important in mediating the behavioural effects of nicotine. It is possible that nicotine administration might regulate the levels of 5-HT receptors in limbic and cortical regions, and such regulations may underlie adaptive responses to nicotine in the central nervous system. The effects of acute and chronic systemic (--)-nicotine administration on 5-HT(1A) receptor gene expression were measured by in situ hybridization, in the rat cerebral cortex, dorsal hippocampus and lateral septum. In the cortex, acute nicotine (0.5 mg/kg i.p.) significantly increased the expression of 5-HT(1A) receptor mRNA 2 h and 24 h after injection. Similarly, acute nicotine significantly increased 5-HT(1A) receptor mRNA in the dentate gyrus (DG), CA3 and CA1 regions of the dorsal hippocampus 2 h and 24 h after injection. Acute nicotine was without effect in the lateral septum. Chronic nicotine (0.5 mg/kg i.p; twice daily for 7 days) significantly decreased 5-HT(1A) receptor mRNA in the cortex 2 h after the final injection, but was without effect at 24 h or 72 h. Chronic nicotine caused no changes in 5-HT(1A) mRNA in the lateral septum or dorsal hippocampus. These data demonstrate that nicotine regulates 5-HT(1A) receptor gene expression in the cortex and hippocampus. The rapid regulation of expression of 5-HT(1A) receptor mRNA leads to the hypothesis that nicotine-induced 5-HT release may alter the postsynaptic sensitivity to 5-HT.
An analysis of TCP processing overhead (1989)

The transport layer of the protocol suite, especially in connectionless protocols, has considerable functionality and is typically executed in software by the host processor at the end points of the network. It is thus considered a likely source of processing overhead. However, a preliminary examination has suggested to the authors that other aspects of networking may be a more serious source of overhead. To test this proposition, a detailed study was made of the Transmission Control Protocol (TCP), the transport protocol from the Internet protocol suite. In this set of protocols, the functions of detecting and recovering lost or corrupted packets, flow control, and multiplexing are performed at the transport level. The results of that study are presented. It is concluded that TCP is in fact not the source of the overhead often observed in packet processing, and that it could support very high speeds if properly implemented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Microbial models of soil metabolism: biotransformations of danofloxacin (1997)

Danofloxacin is a new synthetic fluoroquinolone antibacterial agent under development for exclusive use in veterinary medicine. Such use could lead to deposition of low levels of danofloxacin residues in the environment in manure from treated livestock. This study was conducted to evaluate the potential for indigenous soil microorganisms to metabolize danofloxacin. Cultures of 72 soil microorganisms representing a diverse panel of bacteria, fungi and yeast were incubated with danofloxacin mesylate substrate and samples analyzed periodically by high performance liquid chromatography for loss of danofloxacin and formation of metabolites. Some samples were further analyzed by liquid chromatography-mass spectrometry and mass spectrometry to confirm metabolite identification. Twelve organisms, representing eight different genera, biotransformed danofloxacin to metabolites detectable by the chromatographic methods employed. Two Mycobacterium species, two Pseudomonas species, and isolates of Nocardia sp, Rhizopus arrhizus and Streptomyces griseus all formed N-desmethyldanofloxacin. The formation of the 7-amino danofloxacin derivative, 1-cyclopropyl-6-fluoro-7-amino-4-oxo-1,4-dihydroquinoline-3-carboxylic acid by cultures of Candida lipopytica, Pseudomonas fluorescens, two Mycobacterium species and three Penicillium species demonstrates the propensities of these cultures to completely degrade the piperazine ring. At least two additional and unidentified metabolite peaks were observed in chromatograms of Aspergillus nidulans and Penicillium sp cultures. Radiolabled [2-14C]danofloxacin added to cultures of the fungus Curvularia lunata was apparently mineralized, with approximately 31% of the radiolabel recovered as volatile metabolites after 24 h of incubation, indicating the susceptibility of the quinolone ring to microbial metabolic degradation.
Comparison of analytical and measured performance results on network coding in IEEE 802.11 ad-hoc networks (2012)

Network coding is a promising technology that has been shown to improve throughput in wireless mesh networks. In this paper, we compare the analytical and experimental performance of COPE-style network coding in IEEE 802.11 ad-hoc networks. In the experiments, we use a lightweight scheme called CATWOMAN that can run on standard WiFi hardware. We present an analytical model to evaluate the performance of COPE in simple networks, and our results show the excellent predictive quality of this model. By closely examining the performance in two simple topologies, we observe that the coding gain results from the interaction between network coding and the MAC protocol, and the gap between the theoretical and practical gains is due to the different channel qualities of sending nodes. This understanding is helpful for design of larger mesh networks that use network coding.
Seismic Stratigraphy and Global Changes of Sea Level, Part 1&lt;subtitle&gt;Overview&lt;xref ref-type="fn" rid="ch03-1fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;&lt;/subtitle&gt; (1977)

Papers from a research symposium at the 1975 American Association of Petroleum Geologists and supplemented by later reports became "Seismic Stratigraphy Applications to Hydrocarbon Exploration", one of AAPG's best-selling book publications. Dramatic improvements in seismic imaging were demonstrated, a result of developments in seismic data quality and the processing capability of electronic technology. Twenty-eight articles are grouped into three sections. The first describes principles that both permit and also limit interpretations. The second section presents sixteen articles that describe the qualitative approach to stratigraphic interpretations of reflection records, and the final section presents techniques and examples of modeling. Of particular interest are a series of eleven papers in the second section under the subject heading of "Seismic stratigraphy and global changes of sea level". Prepared by P. R. Vail, R. M. Mitchum and others from Exxon, they describe the regional unconformities and stratigraphic changes resulting from sea level fluctuations, and the manner in which these changes can be interpreted from seismic surveys. For many individuals within the oil industry who purchased this book, it was their first introduction to the modern concept of sequence stratigraphy that would have a major impact on the methodology of petroleum exploration.
<i>In Vitro</i> Selection of Modified RNA Aptamers Against CD44 Cancer Stem Cell Marker (2013)

Cancer stem cells (CSCs) are a subset of tumor cells that has the ability to self-renew and to generate the diverse cells that comprise the tumor mass. The cell-surface glycoprotein CD44 is one of the most common surface markers used to identify CSCs. Aptamers are synthetic oligonucleotides selected from pools of random sequences that can bind to a wide range of targets with high affinity and specificity. In this study, the systematic evolution of ligands by exponential enrichment (SELEX) technology was used to isolate RNA aptamers using human recombinant full-length CD44 protein and 2'-F-pyrimidine modified RNA library with a complexity of around 10(14) different molecules. Following 11 iterative rounds of SELEX, the selected aptamers were cloned and sequenced. Three different sequences were identified. The binding specificities for one of these RNA aptamers was assessed using representative breast cancer cell lines expressing CD44; namely, MDA-MB-231, MCF7, and T47D. The selected RNA aptamer (Apt1) was found to interact specifically with such cancer cells when analyzed by flow cytometry and fluorescent microscopy, with different intensities of fluorescence reflecting the level of CD44 expression on the surface of these cells. It can be concluded that the selected aptamers can be used to target CD44 positive cells, including cancer stem cells, for detection, sorting, and enrichment and for drug delivery purposes.
The Effect of Various Inactivating Agents on the Viral and Ribonucleic Acid Infectivities of Foot-and-Mouth Disease Virus and on its Attachment to Susceptible Cells (1963)

SUMMARY Foot-and-mouth disease (FMD) virus was partially inactivated by several methods: incubation with dilute formaldehyde or acetylethylene-imine, ultraviolet (U.V.) irradiation, heating, or by mixing with type specific antiserum, trypsin or extracts from cells susceptible to the virus. The serological properties of the treated virus preparations were studied by complement-fixation and agar diffusion tests and their content of infective ribonucleic acid (RNA) determined by phenol extraction. The ability of the treated preparations to attach to susceptible cultivated pig kidney cells was examined. The decrease in viral infectivity when FMD virus was treated with formaldehyde or acetylethyleneimine, U.V., or heat at 25° or 37° was proportional to the loss of infective RNA, with little impairment of its serological properties or its ability to attach to susceptible cells. In contrast, loss of viral infectivity on mixing with antiserum, trypsin or cell extracts was due to the failure of the virus to attach to susceptible cells; the viral RNA is still present in an infective form in these mixtures.
Application of the cross wavelet transform and wavelet coherence to geophysical time series (2004)

Abstract. Many scientists have made use of the wavelet method in analyzing time series, often using popular free software. However, at present there are no similar easy to use wavelet packages for analyzing two time series together. We discuss the cross wavelet transform and wavelet coherence for examining relationships in time frequency space between two time series. We demonstrate how phase angle statistics can be used to gain confidence in causal relationships and test mechanistic models of physical relationships between the time series. As an example of typical data where such analyses have proven useful, we apply the methods to the Arctic Oscillation index and the Baltic maximum sea ice extent record. Monte Carlo methods are used to assess the statistical significance against red noise backgrounds. A software package has been developed that allows users to perform the cross wavelet transform and wavelet coherence (www.pol.ac.uk/home/research/waveletcoherence/).