gebhart/patrepeval huggingface dataset:
Functional Analysis of 114 Exon-Internal AONs for Targeted DMD Exon Skipping: Indication for Steric Hindrance of SR Protein Binding Sites (2005)

As small molecule drugs for Duchenne muscular dystrophy (DMD), antisense oligonucleotides (AONs) have been shown to restore the disrupted reading frame of DMD transcripts by inducing specific exon skipping. This allows the synthesis of largely functional dystrophin proteins and potential conversion of severe DMD into milder Becker muscular dystrophy (BMD) phenotypes. We have previously described 37 exon-internal AONs that induce skipping of 14 DMD exons in human control myotube cultures. Here, we report 77 new AONs, effectively targeting an additional 21 exons. Of the 114 AONs thus far tested, 72 (67%) were effective. AON design initially was based on a partial overlap with predicted open secondary structures in the target RNA. We have analyzed various AON and target exon parameters in retrospect. Interestingly, we observed significantly higher SF2/ASF, SC35, and SRp40 values (as predicted by ESEfinder) for effective AONs when compared with ineffective AONs. In addition, the distance to the 3' splice site was significantly smaller for effective AONs. No other significant correlations were observed. Our results suggest that effective exon-internal AONs primarily act by blocking SR binding sites (which often correspond to open structures) and that ESEfinder may be used to refine AON design for DMD and other genes.
Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel 18F-Labeled Tracer for Imaging Myocardial Innervation (2014)

A novel <sup>18</sup>F-labeled ligand for the norepinephrine transporter (<i>N</i>-[3-bromo-4-(3-<sup>18</sup>F-fluoro-propoxy)-benzyl]-guanidine [LMI1195]) is in clinical development for mapping cardiac nerve terminals in vivo using PET. Human safety, whole-organ biodistribution, and radiation dosimetry of LMI1195 were evaluated in a phase 1 clinical trial. <b>Methods:</b> Twelve healthy subjects at 3 clinical sites were injected intravenously with 150–250 MBq of LMI1195. Dynamic PET images were obtained over the heart for 10 min, followed by sequential whole-body images for approximately 5 h. Blood samples were obtained, and heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. Residence times were determined from multiexponential regression of organ region-of-interest data normalized by administered activity (AA). Radiation dose estimates were calculated using OLINDA/EXM. Myocardial, lung, liver, and blood-pool standardized uptake values were determined at different time intervals. <b>Results:</b> No adverse events due to LMI1195 were seen. Blood radioactivity cleared quickly, whereas myocardial uptake remained stable and uniform throughout the heart over 4 h. Liver and lung activity cleared relatively rapidly, providing favorable target-to-background ratios for cardiac imaging. The urinary bladder demonstrated the largest peak uptake (18.3% AA), followed by the liver (15.5% AA). The mean effective dose was 0.026 ± 0.0012 mSv/MBq. Approximately 1.6% AA was seen in the myocardium initially, remaining above 1.5% AA (decay-corrected) through 4 h after injection. The myocardium-to-liver ratio was approximately unity initially, increasing to more than 2 at 4 h. <b>Conclusion:</b> These preliminary data suggest that LMI1195 is well tolerated and yields a radiation dose comparable to that of other commonly used PET radiopharmaceuticals. The kinetics of myocardial and adjacent organ activity suggest that cardiac imaging should be possible with acceptable patient radiation dose.
Adipocyte LDL receptor–related protein–1 expression modulates postprandial lipid transport and glucose homeostasis in mice (2007)

Diet-induced obesity and its serious consequences such as diabetes, cardiovascular disease, and cancer are rapidly becoming a major global health threat. Therefore, understanding the cellular and molecular mechanisms by which dietary fat causes obesity and diabetes is of paramount importance in order to identify preventive and therapeutic strategies. Increased dietary fat intake results in high plasma levels of triglyceride-rich lipoproteins (TGRL). Tissue uptake of TGRL has been shown to promote glucose intolerance. We generated mice with an adipocyte-specific inactivation of the multifunctional receptor LDL receptor-related protein-1 (LRP1) to determine its role in mediating the effects of TGRL on diet-induced obesity and diabetes. Knockout mice displayed delayed postprandial lipid clearance, reduced body weight, smaller fat stores, lipid-depleted brown adipocytes, improved glucose tolerance, and elevated energy expenditure due to enhanced muscle thermogenesis. We further demonstrated that inactivation of adipocyte LRP1 resulted in resistance to dietary fat-induced obesity and glucose intolerance. These findings identify LRP1 as a critical regulator of adipocyte energy homeostasis, where functional disruption leads to reduced lipid transport, increased insulin sensitivity, and muscular energy expenditure.
Mixed valence complexes of ruthenium ammines with 4,4'-bipyridine as bridging ligand (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMixed valence complexes of ruthenium ammines with 4,4'-bipyridine as bridging ligandGlenn M. Tom, Carol Creutz, and Henry TaubeCite this: J. Am. Chem. Soc. 1974, 96, 25, 7827–7829Publication Date (Print):December 1, 1974Publication History Published online1 May 2002Published inissue 1 December 1974https://doi.org/10.1021/ja00832a045RIGHTS & PERMISSIONSArticle Views553Altmetric-Citations110LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (404 KB) Get e-Alertsclose Get e-Alerts
Urban Freeway Traffic Flow Prediction: Application of Seasonal Autoregressive Integrated Moving Average and Exponential Smoothing Models (1998)

The application of seasonal time series models to the single-interval traffic flow forecasting problem for urban freeways is addressed. Seasonal time series approaches have not been used in previous forecasting research. However, time series of traffic flow data are characterized by definite periodic cycles. Seasonal autoregressive integrated moving average (ARIMA) and Winters exponential smoothing models were developed and tested on data sets belonging to two sites: Telegraph Road and the Woodrow Wilson Bridge on the inner and outer loops of the Capital Beltway in northern Virginia. Data were 15-min flow rates and were the same as used in prior forecasting research by B. Smith. Direct comparisons with the Smith report findings were made and it was found that ARIMA (2, 0, 1)(0, 1, 1) 96 and ARIMA (1, 0, 1)(0, 1, 1) 96 were the best-fit models for the Telegraph Road and Wilson Bridge sites, respectively. Best-fit Winters exponential smoothing models were also developed for each site. The single-step forecasting results indicate that seasonal ARIMA models outperform the nearest-neighbor, neural network, and historical average models as reported by Smith.
Alternating phase focused IH-DTL for heavy-ion medical accelerators (2006)

Compact linacs, consisted of a Radio-Frequency-Quadrupole (RFQ) linac and Interdigital H-mode Drift-Tube-Linac (IH-DTL) having the same operating frequency of 200 MHz, were designed for an injector of heavy-ion medical accelerators. For beam focusing of IH-DTL, the method of Alternating-Phase-Focusing (APF) was applied. The total length of the RFQ linac and APF IH-DTL is approximately 6 m. With the two linacs, carbon ions produced by an ECR Ion-Source (ECRIS) could be accelerated up to 4.0 MeV/u. The compact linacs were constructed and installed in NIRS. We have succeeded to accelerate carbon ions with the APF linac for the first time. The present status of the compact linacs as well as results of acceleration tests was presented.
Binding of Candida albicans yeast cells to mouse popliteal lymph node tissue is mediated by macrophages (1993)

We previously reported that Candida albicans yeast cells adhere to the macrophage-rich medullary and subcapsular sinus areas of mouse lymph node tissue. To determine whether the yeast cell-lymph node interaction is mediated by macrophages, the effect of specific elimination of macrophages on yeast cell binding was studied, and yeast cell adherence was correlated with the ingestion of India ink by lymph node cells. Macrophage elimination was done by use of liposome-containing dichloromethylene diphosphonate (L-Cl2MDP). Mice were injected in the hind footpads with the L-Cl2MDP preparation, popliteal lymph nodes were removed 5 days later, and yeast cell adherence was determined by an ex vivo binding assay. As controls, lymph nodes from mice that received footpad injections of either phosphate-buffered saline (PBS) alone or liposome-containing PBS were used. Use of macrophage- and neutrophil-specific monoclonal antibodies in tissue immunostaining showed that the L-Cl2MDP treatment eliminated macrophages but not neutrophils from the medullary and subcapsular sinus areas of the popliteal lymph nodes. A striking reduction of yeast cell adherence occurred with lymph nodes from L-Cl2MDP-treated mice compared with lymph nodes from control animals. The lymph node-yeast cell binding patterns of L-Cl2MDP-treated and control mice were the same regardless of mouse strain, sex, or T-cell competency. Results of India ink experiments, in which India ink was injected into footpads of mice and was rapidly taken up by popliteal lymph node macrophages, showed a strong correlation between yeast adherence and India ink staining of cells. In addition, the interaction of yeast cells with lymph node tissue from normal mice was not significantly affected by the addition of two extracellular matrix proteins, fibronectin and laminin, during the ex vivo adherence assay. These data indicate that medullary and subcapsular sinus lymph node macrophages express an adhesion system similar to that described for mouse splenic marginal zone macrophages.
Binding of Human Alpha-Interferons to Natural Killer Cells (1986)

It has previously been shown that recombinant DNA-derived human leukocyte interferon IFN-alpha J, which is active on human cells in antiviral and antiproliferative assays, substantially lacks the ability of other purified leukocyte IFN (e.g., IFN-alpha A) to enhance natural killer (NK) activity. IFN-alpha J can, however, block the boosting of NK activity by IFN-alpha A, suggesting that IFN-alpha J can occupy the IFN-alpha receptor on NK cells. We demonstrate here directly that IFN-alpha J can bind to NK cells and can compete with [125I]IFN-alpha A for binding sites. The equilibrium dissociation constant (Kd) for IFN-alpha J is no more than 20-30 times greater than for IFN-alpha A. The relative Kd values for IFN-alpha A and IFN-alpha J are similar when measured with Daudi cells, where both IFN-alphas have potent antiproliferative effects. This suggests that the difference in receptor binding on NK cells in terms of equilibrium binding constants does not explain the inactivity of IFN-alpha J relative to IFN-alpha A on NK cells following a 2-h incubation.
Visa Scheme for Inter-Organization Network Security (1987)

In this paper we describe a visa scheme for implementing access control in Inter-Organization Network (ION) gateways. The purpose of the scheme is to allow an organization to modify and trust only them internal system that require ION access all other internal system can not communicate with the outside. Control is distributed among the ION participants so that each may make its own design tradeoffs between performance and trust.
Magnetic Oscillations Driven by the Spin Hall Effect in 3-Terminal Magnetic Tunnel Junction Devices (2012)

We show that a direct current in a tantalum microstrip can induce steady-state magnetic oscillations in an adjacent nanomagnet through spin torque from the spin Hall effect (SHE). The oscillations are detected electrically via a magnetic tunnel junction (MTJ) contacting the nanomagnet. The oscillation frequency can be controlled using the MTJ bias to tune the magnetic anisotropy. In this 3-terminal device, the SHE torque and the MTJ bias therefore provide independent controls of the oscillation amplitude and frequency, enabling new approaches for developing tunable spin torque nano-oscillators.
Immunogenic Cell Death in Cancer Therapy (2012)

Depending on the initiating stimulus, cancer cell death can be immunogenic or nonimmunogenic. Immunogenic cell death (ICD) involves changes in the composition of the cell surface as well as the release of soluble mediators, occurring in a defined temporal sequence. Such signals operate on a series of receptors expressed by dendritic cells to stimulate the presentation of tumor antigens to T cells. We postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies. Hence, suboptimal regimens (failing to induce ICD), selective alterations in cancer cells (preventing the emission of immunogenic signals during ICD), or defects in immune effectors (abolishing the perception of ICD by the immune system) can all contribute to therapeutic failure. We surmise that ICD and its subversion by pathogens also play major roles in antiviral immune responses.
PD-1 Blockade and OX40 Triggering Synergistically Protects against Tumor Growth in a Murine Model of Ovarian Cancer (2014)

The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses and prevent autoimmunity, however, tumors exploit this pathway to escape from immune destruction. The co-stimulatory receptor OX40 is upregulated on T cells following activation and increases their clonal expansion, survival and cytokine production when engaged. Although antagonistic anti-PD-1 or agonistic anti-OX40 antibodies can promote the rejection of several murine tumors, some poorly immunogenic tumors were refractory to this treatment. In the present study, we evaluated the antitumor effects and mechanisms of combinatorial PD-1 blockade and OX40 triggering in a murine ID8 ovarian cancer model. Although individual anti-PD-1 or OX40 mAb treatment was ineffective in tumor protection against 10-day established ID8 tumor, combined anti-PD-1/OX40 mAb treatment markedly inhibited tumor outgrowth with 60% of mice tumor free 90 days after tumor inoculation. Tumor protection was associated with a systemic immune response with memory and antigen specificity and required CD4(+) cells and CD8(+) T cells. The anti-PD-1/OX40 mAb treatment increased CD4(+) and CD8(+) cells and decreased immunosuppressive CD4(+)FoxP3(+) regulatory T (Treg) cells and CD11b(+)Gr-1(+) myeloid suppressor cells (MDSC), giving rise to significantly higher ratios of both effector CD4(+) and CD8(+) cells to Treg and MDSC in peritoneal cavity; Quantitative RT-PCR data further demonstrated the induction of a local immunostimulatory milieu by anti-PD-1/OX40 mAb treatment. The splenic CD8(+) T cells from combined mAb treated mice produced high levels of IFN-γ upon tumor antigen stimulation and exhibited antigen-specific cytolytic activity. To our knowledge, this is the first study testing the antitumor effects of combined anti-PD-1/OX40 mAb in a murine ovarian cancer model, and our results provide a rationale for clinical trials evaluating ovarian cancer immunotherapy using this combination of mAb.
Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy (2007)

Repeated implantation failure in some oocyte recipients is associated with an intrinsic defect in the expression of multiple genes in their endometrium. Significantly decreased levels of several transcripts in endometria without manifest abnormalities is demonstrated for the first time and shown to be associated with implantation failure.
Relative resistance of the F-42-stabilized classical pathway C3 convertase to inactivation by C4-binding protein. (1980)

The sera of some patients with SLE contain an IgG antibody (F-42) directed against the classical pathway C3 convertase (C-42), which is capable of stabilizing C42 in a dose-dependent manner. The half-life (T 1/2) of C42 is prolonged by F-42. In order to determine whether C4-binding protein was capable of reversing stabilization of C42, stabilized and unstabilized cell-bound C42 were exposed to purified C4-bp and the convertase activity was assessed. C4-bp was capable of accelerating the decay of C42 in a dose-dependent manner; 2 microgram/ml C4-bp reduced the T 1/2 of C42 from 5 to 2.5 min at 30 degrees C. On the other hand, 16 microgram C4-bp could reverse stabilization of C42 by F-42 from T 1/2 = 78 min to a T 1/2 - 40 min; 128 microgram C4-bp reduced the T 1/2 of stabilized C42 to 4 min. Functional inactivation of C42 occurs via enhanced decay-dissociation of C2 from the convertase by C4-bp, as shown by the release of 125I-C2i from the cell-bound convertase. Stabilization of C42 by F-42 is caused by prevention of decay-dissociation of 125I-C2. F-42 was also capable of stabilizing C4oxy2 even further, as shown by prolongation of the T 1/2 of cell-bound C4 oxy2 to a T 1/2 of at least 300 min at 30 degrees C.
Atrial fibrillation and stroke. Three new studies, three remaining questions (1994)

There new studies help clarify important clinical issues regarding antithrombotic therapy for stroke prevention in patients with atrial fibrillation. The European Atrial Fibrillation Trial compared the efficacy of oral anticoagulation, aspirin, and placebo for stroke prevention in patients with atrial fibrillation with a recent stroke or transient ischemic attack. The results of the Stroke Prevention in Atrial Fibrillation II trial, which compared the efficacy of warfarin and aspirin, provide new information regarding the risk of intracranial hemorrhage in elderly patients with atrial fibrillation. Finally, an analysis of pooled data from the first five randomized trials identified clinical features that are predictive of stroke risk in individual patients with atrial fibrillation. These studies address unanswered questions regarding atrial fibrillation and stroke and have significant implications for patient management. (Arch Intern Med. 1994;154:1443-1448)
A FPGA and ASIC implementation of rate 1/2, 8088-b irregular low density parity check decoder (2004)

This paper presents an implementation of irregular low density parity check decoder using both FPGA and ASIC. The considered low density parity check code has code rate 1/2, codeword length of 8088 bits and parallel factor of 24. The partly parallel structure, memory management, message alignment and addressing generation schemes needed to realize the underlying graph connectivity will be discussed. With the target FPGA device Xilinx XC2V8000 and maximum number of 25 iterations, the information decoding throughput could achieve up to 40 Mbps. By using the same configuration and Texas Instruments' GS-40 0.11 /spl mu/m ASIC process technology, decoder data rate of 188 Mbps could be achieved for this decoder.
Managing neurologic complications in cervical spine surgery (2005)

Purpose of review: Cervical spine surgical techniques and instrumentation continue to evolve, while the neurologic complication rates continue to decline steadily. Currently, this remains at approximately 0-3.7%. The purpose of this manuscript is to review neurologic complications secondary to cervical spine surgery and provide evidenced-based management strategies to be used when complications do occur. Recent findings: The most important recent advancements in the treatment and prevention of neurologic complications in cervical spine surgery have come in the areas of advanced intraoperative neuromonitoring techniques and pharmacological management of spinal cord and nerve root injuries with agents such as GM-1 ganglioside, tirilizad, and others. Summary: An understanding of the pathophysiology, specifically the primary and secondary phases, of neural injury will ultimately improve prevention and management of these injuries.
A simple and sensitive in vivo luciferase assay for tRNA-mediated nonsense suppression (1990)

We present a rapid assay for tRNA suppression in living Escherichia coli. An amber, ochre, or opal nonsense mutation in a cloned luxB gene from the bacterium Vibrio harveyi was suppressed. Because luciferase (Lux) activity depends completely on the appearance of the full-length luxB gene product, the amount of light produced was proportional to tRNA-mediated nonsense suppression in the cell. This luminometric assay was notably quicker, easier, and more sensitive than a traditional colorimetric assay employing beta-galactosidase. Assays required only one addition to a growing culture and were complete within 1 min. Light output was directly proportional to the amount of bacterial luciferase in a sample over a range of greater than or equal to 40,000-fold. Fewer than 100 cells were required for detection of Lux with ordinary instrumentation; assays were 80-fold more sensitive than simultaneous beta-galactosidase measurements. Assayed cells survived and could be recovered as colony formers. The beta-galactosidase colorimetric assay and the luciferase assay were similarly reproducible. Light from colonies expressing Lux was visible to the dark-adapted eye and useful for screening. A rapid assay that does not depend on the formation of permanent transformants can be based on electroporation followed by luminometry.
Principles and Practice of Pharmacology for Anaesthetists (2008)

Foreword to the First Edition. Preface. 1 Drug Absorption, Distribution and Elimination. 2 Pharmacokinetics. 3 Drug Action. 4 Drug Interaction. 5 Variability in Drug Response. 6 Adverse Drug Reactions. 7 Intravenous Anaesthetic Agents. 8 Inhalational Anaesthetic Agents. 9 Local Anaesthetics. 10 Drugs that act on the Neuromuscular Junction. 11 Analgesic Drugs. 12 Drugs used in Premedication and Antiemetic Agents. 13 Drugs and the Autonomic Nervous System. 14 Antihypertensive Agents: Drugs that Are Used to Induce Hypotension. 15 Antiarrhythmic and Antianginal Drugs. 16 Antiplatelet Drugs, Anticoagulants and Fibrinolytic Agents. 17 Corticosteroids and Hypoglycaemic Agents. Glossary. Index