gebhart/patrepeval huggingface dataset:
<i>In Vivo</i> Molecular Imaging (2017)

In vivo molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Among the methodologies used in in vivo molecular imaging, two methodologies are of great interest from the view of high sensitivity. One is nuclear medical imaging, and distribution and kinetics of a radiolabeled molecular probe are measured using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The other is optical molecular imaging, and distribution and kinetics of a fluorescent probe are measured using a fluorescent imaging instrument. In this review, the development of imaging probes for these two methodologies is briefly discussed. In nuclear medical molecular imaging, based on structure-activity-biodistribution relationship studies for small molecule and the concept of "functional unit-binding multifunctional molecular probe" containing 3 functional units (target recognition unit, signal-releasing unit, linker unit) for peptides and proteins, we developed radiolabeled probes with high and specific accumulation to the target for neuroreceptors, β-amyloid plaques, and tau aggregates in the brain, tumors, atherosclerotic plaques, pancreatic β-cell, myocardial sympathetic nerves, and so on. We also discuss the progression of molecular imaging toward therapy (radiotheranotics). In in vivo optical molecular imaging, taking into account the characteristics of optical imaging, we designed tumor-specific optical imaging probes with characteristic imaging mechanism, including near-infrared (NIR) fluorescent probes and activatable probes. Furthermore, we developed a photoacoustic imaging probe, which enables highly sensitive and high-resolution imaging in deep tissues.
Microwave absorbing properties of ferrite-based nanocomposites (2007)

A study of the microwave absorbing properties of polymer (epoxy) based nanocomposites is presented. The ferrite nanoparticles employed as filler materials were produced by a co-precipitation method, which was designed for production of large amounts at low cost. The absorbing properties of different kinds of ferrite nanoparticles, soft (manganese) and hard (cobalt) magnetic nanoparticles, are compared. In addition, the impact of high and low densities of the respective ferrite type has been investigated. Our analysis of the microwave absorbing properties is made over a wide frequency band including both MHz and GHz regions, which is of high interest for a number of different applications both military and civilian.
Antiarrhythmic Drug Target Choices and Screening (2003)

Most antiarrhythmic drugs are ion channel blockers, and to date, those tested in large randomized placebo-controlled clinical trials have shown no decrease in mortality outcome. This apparent lack of survival benefit may result from the significant liabilities associated with these agents that offset any long-term benefit. Despite the current success of implantable defibrillators and the future promise of gene therapy, there is still a pressing need for new antiarrhythmic drugs. An improved understanding of cardiac ion channels and novel approaches to target selection and compound screening will provide new opportunities for drug discovery in the near future. Here, we briefly review the multiple mechanisms of arrhythmia, the history of drug failures, and the possibilities that evolving technologies may provide in the search for more efficacious and safer antiarrhythmic drugs.
Development and Validation of a Comprehensive Synchronous Machine Model for a Real-Time Environment (2010)

A comprehensive model of a salient-pole synchronous machine is developed for a real-time environment. By obtaining the effective specific permeance of the machine from simple experimental measurements and the exact geometry of the rotor pole arc, a model is developed that includes the exact distribution of windings and operating-point-dependent saturation. This model offers a superior simulated response of the machine for fault transients, as well as for steady-state harmonic behavior, and is suitable for the closed-loop testing of relays and controls. The inductances of the machine are computed using the modified winding function approach and validated using finite-element analysis. Finally, the performance of the model is validated under healthy and faulted conditions by comparison with tests on an actual machine.
Critical proline residues of the cytoplasmic domain of the IL-5 receptor α chain and its function in IL-5-mediated activation of JAK kinase and STAT5 (1996)

The high-affinity receptor (R) for IL-5 consists of a unique alpha chain (IL-5R alpha) and a beta chain (beta c) that is shared with the receptors for IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF). We defined two regions of IL-5R alpha for the IL-5-induced proliferative response, the expression of nuclear proto-oncogenes, and the tyrosine phosphorylation of cellular proteins including beta c, SH2/SH3-containing proteins and JAK2 kinase. In the studies described here, we demonstrate that IL-5, IL-3 or GM-CSF stimulation induces the tyrosine phosphorylation of JAK2, and to a lesser extent JAK1, and of STAT5. Mutational analysis revealed that one of the proline residues, particularly Pro352 and Pro355, in the membrane-proximal proline-rich sequence (Pro352-Pro353-X-Pro355) of the cytoplasmic domain of IL-5R alpha is required for cell proliferation, and for both JAK1 and JAK2 activation. In addition, transfectants expressing chimeric receptors which consist of the extracellular domain of IL-5R alpha and the cytoplasmic domain of beta c responded to IL-5 for proliferation and tyrosine phosphorylation of JAK1. Intriguingly, electrophoretic mobility shift assay analysis revealed that STAT5 was activated in cells showing either JAK1 or JAK2 tyrosine phosphorylation. These results indicate that activation of JAK1, JAK2 and STAT5 is critical to coupling IL-5-induced tyrosine phosphorylation and ultimately mitogenesis, and that Pro352 and Pro355 in the proline-rich sequence appear to play more essential roles in cell growth and in both JAK1/STAT5 and JAK2/STAT5 activation than Pro353 does.
Ab initio study of Diels-Alder reactions of cyclopentadiene with ethylene, isoprene, cyclopentadiene, acrylonitrile, and methyl vinyl ketone (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAb initio study of Diels-Alder reactions of cyclopentadiene with ethylene, isoprene, cyclopentadiene, acrylonitrile, and methyl vinyl ketoneWilliam L. Jorgensen, Dongchul Lim, and James F. BlakeCite this: J. Am. Chem. Soc. 1993, 115, 7, 2936–2942Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/ja00060a048https://doi.org/10.1021/ja00060a048research-articleACS PublicationsRequest reuse permissionsArticle Views2245Altmetric-Citations174LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The hair follicle enigma (2017)

The hair follicle is a mini-organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome-mediated cell-cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology.
The Regulatory Landscape of Osteogenic Differentiation (2014)

Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral part of bone development and homeostasis, and may when improperly regulated cause disease such as bone cancer or osteoporosis. Using unbiased high-throughput methods we here characterize the landscape of global changes in gene expression, histone modifications, and DNA methylation upon differentiation of human MSCs to the osteogenic lineage. Furthermore, we provide a first genome-wide characterization of DNA binding sites of the bone master regulatory transcription factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts, revealing target genes associated with regulation of proliferation, migration, apoptosis, and with a significant overlap with p53 regulated genes. These findings expand on emerging evidence of a role for RUNX2 in cancer, including bone metastases, and the p53 regulatory network. We further demonstrate that RUNX2 binds to distant regulatory elements, promoters, and with high frequency to gene 3' ends. Finally, we identify TEAD2 and GTF2I as novel regulators of osteogenesis.
CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity (2008)

The transmembrane protein CD83 has been initially described as a maturation marker for dendritic cells. Moreover, there is increasing evidence that CD83 also regulates B cell function, thymic T cell maturation, and peripheral T cell activation. Herein, we show that CD83 expression confers immunosuppressive function to CD4(+) T cells. CD83 mRNA is differentially expressed in naturally occurring CD4(+)CD25(+) regulatory T cells, and upon activation these cells rapidly express large amounts of surface CD83. Transduction of naive CD4(+)CD25(-) T cells with CD83 encoding retroviruses induces a regulatory phenotype in vitro, which is accompanied by the induction of Foxp3. Functional analysis of CD83-transduced T cells in vivo demonstrates that these CD83(+)Foxp3(+) T cells are able to interfere with the effector phase of severe contact hypersensitivity reaction of the skin. Moreover, adoptive transfer of these cells prevents the paralysis associated with experimental autoimmune encephalomyelitis, suppresses proinflammatory cytokines IFN-gamma and IL-17, and increases antiinflammatory IL-10 in recipient mice. Taken together, our data provide the first evidence that CD83 expression can contribute to the immunosuppressive function of CD4(+) T cells in vivo.
Urological Oncology (2005)

In a large urological oncology section this month the topics of cancer of the prostate, bladder, kidney and testis are covered. To mention but a few of these, authors from New York report that the time from biopsy to surgery in the case of prostate cancer did not influence the probability of biochemical recurrence for men who had a radical prostatectomy within a year of diagnosis. A paper from Boston reports several pregnancies which occurred after brachytherapy for prostate cancer. Incidentally, there is a letter to the Editor at the end of this month's issue, from a UK author, which deals with the same topic. There are two papers from the USA presenting data on the use of nilutamide in hormone-refractory prostate cancer, and a third from Japan using flutamide in the same setting. A report from New York correlates urine cytology findings before and after flexible cystoscopy, finding that cytology immediately after flexible cystoscopy correlates well with that before cystoscopy.



OBJECTIVE

To evaluate whether the time from biopsy to radical prostatectomy (RP) predicts the biochemical recurrence (BCR) after RP, as men diagnosed with clinically localized prostate cancer have several available treatment options and investigating these alternatives may delay the initiation of definitive therapy.



PATIENTS AND METHODS

We identified 3969 consecutive patients who had RP for clinically localized prostate cancer from 1987 to 2002; those eligible for the study had RP within a year of diagnosis. The interval between biopsy and RP was analysed both as a continuous and as a dichotomous variable (divided at 3 months). Multivariate analysis was used to evaluate the impact of time to RP on BCR. Subsets were also analysed for the effect of time to RP in patients considered to be at high risk of recurrence, with group 1 having a prostate specific antigen (PSA) level of ≥ 20 ng/mL, a biopsy Gleason score of ≥ 8, or clinical stage ≥ T2c; and group 2 assessed as having a >40% probability of BCR using a preoperative nomogram.



RESULTS

In all, 3149 patients met the inclusion criteria and had a mean (interquartile range) follow-up after RP of 5.4 (2.2–7.9) years. Multivariate analysis showed that the year of biopsy, PSA level before biopsy, clinical stage and biopsy Gleason score (all P < 0.001) were significantly associated with BCR after RP. The time to RP, treated either as a continuous variable (P = 0.252) or when categorized at 3 months (P = 0.939), failed to predict BCR. Further, the time to RP was not an independent predictor of BCR for patients at high risk of recurrence in group 1 (P = 0.147) or group 2 (P = 0.548).



CONCLUSIONS

The time from biopsy to RP did not influence the probability of BCR for men who had RP within a year of diagnosis, even for those considered to be at high risk of BCR. Instead, the clinical and pathological features of the cancer provided the best estimate of the risk of BCR.
Modeling of Eddy-Current Loss of Electrical Machines and Transformers Operated by Pulsewidth-Modulated Inverters (2008)

Pulsewidth-modulated (PWM) inverters are used more and more to operate electrical machines and to interface renewable energy systems with the utility grid. However, there are abundant high-frequency harmonics in the output voltage of a PWM inverter, which increase the iron losses and result in derating of the machine or transformer connected to them. Predicting the iron losses caused by the PWM supply is critical for the design of electrical machines and transformers operated by PWM inverters. These losses are primarily attributed to eddy-current loss caused by the PWM supply. In this paper, after analyzing the harmonic components of PWM voltage, we derive the effects of different parameters of PWM switching on the eddy-current loss. We compare the iron losses modeled with the proposed analytical methods on a three-phase transformer, a dc motor, and an induction motor with the results of time-stepping finite-element analysis and experiments. We provide detailed equations for the prediction of iron losses. These equations can be directly applied in the design and control of PWM converters and electric motors to improve energy efficiency in electrical machines and transformers operated from PWM converters.
Compact associative-memory architecture with fully parallel search capability for the minimum Hamming distance (2002)

An associative-memory architecture for a fully parallel minimum Hamming distance search is proposed, which uses digital circuitry for bit comparison and fast analog circuitry for word comparison as well as winner-take-all (WTA) functionality. Following this original approach allows compact and high-performance integration in conventional CMOS technology. First, static encoding of word-comparison results as a current-sink capability reduces word-comparison circuitry to the theoretical minimum, namely, one transistor per bit and one signal line per word. Second, a new WTA principle, which we call self-adapting winner line-up amplification (WLA), regulates the winner row output automatically into the narrow maximum-gain region of a distance amplifier. Third, winner search circuit complexity scales linear with reference-word number and not quadratic as inevitable for digital approaches. Due to static distance encoding and WLA regulation, transient noise and fabrication process variations are largely tolerated. Only relative chip-internal transistor-parameter variations, creating effective mismatch of matched transistors, limit winner search result correctness. Practical feasibility is verified.
Haggle Testbed: a Testbed for Opportunistic Networks (2011)

Opportunistic networks are constructed by devices carried by people and vehicles. The devices use short range radio to communicate. Since the network is mobile and often sparse in terms of node contacts, nodes store messages in their buffers, carrying them, and forwarding them upon node encounters. This form of communication leads to a set of challenging issues that we investigate: congestion, transfer ordering, and resilience.Congestion occurs in opportunistic networks when a node's buffers becomes full. To be able to receive new messages, old messages have to be evicted. We show that buffer eviction strategies based on replication statistics perform better than strategies that evict messages based on the content of the message.We show that transfer ordering has a significant impact on the dissemination of messages during time limited contacts. We find that transfer strategies satisfying global requests yield a higher delivery ratio but a longer delay for the most requested data compared to satisfying the neighboring node's requests.Finally, we assess the resilience of opportunistic networks by simulating different types of attacks. Instead of enumerating all possible attack combinations, which would lead to exhaustive evaluations, we introduce a method that use heuristics to approximate the extreme outcomes an attack can have. The method yields a lower and upper bound for the evaluated metric over the different realizations of the attack. We show that some types of attacks are harder to predict the outcome of and other attacks may vary in the impact of the attack due to the properties of the attack, the forwarding protocol, and the mobility pattern.
Abstract 2461: Design and synthesis of AZD3463, a novel orally bioavailable dual ALK and IGF1R inhibitor, inhibits growth of crizotinib resistance cell lines with multiple mechanisms of acquired resistance. (2013)

Abstract Although the ALK inhibitor crizotinib has clinical efficacy in selected ALK positive NSCLC patients, the majority of patients who initially respond eventually relapse. Several mechanisms of resistance have been proposed including amplification, resistance mutations, as well as alternative pathway drivers including EGFR, cKIT and IGF1R. We report here the discovery of a novel scaffold of ALK inhibitors and optimization effort that led to the discovery of AZD3463 a novel dual in vivo active ALK and IGF1R inhibitor. An in house subset screening of kinase inhibitors and de novo studies identified 4-(1H-indol-3-yl)pyrimidin-2-amine analogs as potent ALK inhibitors. Modeling studies were utilized to guide the SAR strategy around the aminopyrimidine group which afforded several lead compounds. Early SAR efforts quickly determined that smaller substituents, chloro and methyl, were optimal in the C5 position of the pyrimidine, and that aniline is preferred over several other amino heterocycles investigated. Parallel medicinal chemistry strategies were executed for the optimization of the aniline and indole. These studies suggested that a 2,4-substituted aniline provided optimal potency and selectivity in conjunction with a variety of heterocycles in C4 position of the pyrimdine. Cyclic amines in the C4 position of the aniline led to simultaneous improvement of potency and metabolic stability. The inhibition of IGF1R in vitro was maintained and modulation of glucose levels in vivo was observed with the optimized compounds and AZD3463. AZD3463 demonstrated superior potency to crizotinib in vivo (H3122 PD unbound EC50=0.16 nM). In summary, detailed SAR studies were executed on the 4-(1H-indol-3-yl)pyrimidin-2-amine template that produced potent inhibitors of ALK with improved physical chemical and ADME properties, and identified AZD3463, a novel equipotent ALK and IGF1R inhibitor, potent in ALK-driven preclinical models and in a variety of crizotinib-resistant models. We present herein the design and synthesis of AZD3463 as well as its overall properties. Citation Format: Jamal C. Saeh, Bin Yang, Tim Pontz, Kumar Thakur, Bo Peng, Lisa Drew, Caroline Rivard, Dan Widzowski, Jane Cheng, Douglas Ferguson, Brenda McDermott, Minhui Shen, John McNulty, Ryohei Katayama, Jeffrey Engleman, Alice Shaw, Daniel Russell, Graeme Smith. Design and synthesis of AZD3463, a novel orally bioavailable dual ALK and IGF1R inhibitor, inhibits growth of crizotinib resistance cell lines with multiple mechanisms of acquired resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2461. doi:10.1158/1538-7445.AM2013-2461
Learning probabilistic dependencies among events for proactive security auditing in clouds (2018)

Security compliance auditing is a viable solution to ensure the accountability and transparency of a cloud provider to its tenants. However, the sheer size of a cloud, coupled with the high operational complexity implied by the multi-tenancy and self-service nature, can easily render existing runtime auditing techniques too expensive and non-scalable. To this end, a proactive approach, which prepares for the auditing ahead of critical events, is a promising solution to reduce the response time to a practical level. However, a key limitation of such approaches is their reliance on manual efforts to extract the dependency relationships among events, which greatly restricts their practicality. What makes things worse is the fact that, as the most important input to security auditing, the logs and configuration databases of a real world cloud platform can be unstructured and not ready to be used for efficient security auditing. In this paper, we first propose a log processing technique, which prepares raw cloud logs for different analysis purposes, and then design a learning-based proactive security auditing system, namely, [Formula: see text]. To this end, we conduct case studies on current log formats in different real-world OpenStack (a popular cloud platform) deployments, and identify major challenges in log processing. Later, we design a stand-alone log processor for clouds, which may potentially be used for various log analyses. Consequently, we leverage the log processor outputs to extract probabilistic dependencies from runtime events for the dependency models. Finally, through these dependency models, we proactively prepare for security critical events and prevent security violations resulting from those critical events. Furthermore, we integrate [Formula: see text] to OpenStack and perform extensive experiments in both simulated and real cloud environments that show a practical response time (e.g., 6 ms to audit a cloud of 100,000 VMs) and a significant improvement (e.g., about 50% faster) over existing proactive approaches. In addition, we successfully and efficiently apply our log processor outputs to other learning techniques (e.g., executing sequence pattern mining algorithms within 18 ms for 50,000 events).