gebhart/patrepeval huggingface dataset:
Robust Factor IX Expression Following ZFN-Mediated Genome Editing in An Adult Mouse Model of Hemophilia B (2011)

Abstract Abstract 668 As a therapeutic strategy, site-specific modification of the genome has the potential to avoid some of the disadvantages of traditional gene replacement approaches such as insertional mutagenesis and lack of endogenous regulatory control of expression. We have recently reported that zinc finger nuclease (ZFN) driven gene correction can be achieved in vivo in a neonatal mouse model of hemophilia by combining AAV-mediated delivery of both the ZFNs and a Factor IX donor template with homology to the targeted F.IX gene (Li et al., Nature, 2011). The mouse model carries a mutant human F.IX mini-gene (hF9mut) knocked into the ROSA26 locus and ZFN-mediated cleavage followed by donor-dependent repair results in restoration of functional F.IX expression. AAV-ZFN and AAV-Donor vectors were administered to neonatal mice, where the rapid proliferation of hepatocytes in the growing animal may promote genome editing through homology directed repair (HDR). Here we sought to investigate whether ZFN-mediated genome editing is feasible in adult animals with predominantly quiescent hepatocytes. Tail vein injection of the AAV-ZFN and AAV-Donor, containing a promoterless wild type factor IX insert flanked by arms of homology to the target site, into adult (8 week old) mice (n=17) resulted in stable (&gt;10wk) circulating F.IX levels of 730–1900 ng/mL (15-38% of normal), whereas mice receiving ZFN alone (n=9) exhibited F.IX levels below detection (&lt;15 ng/mL). Co-delivery of AAV-Mock (luciferase expressing) &amp; AAV-Donor (n=9), yielded &lt;65 ng/mL F.IX. Importantly, mice lacking the hF9mut gene averaged less than 100 ng/mL after receiving AAV-ZFN and AAV-Donor (n=8), suggesting that F.IX expression was derived from on-target genome editing. To eliminate the potential for hF.IX expression resulting from episomal (non-integrated) AAV genomes we performed a two-thirds partial hepatectomy two days after AAV administration. Liver regeneration following hepatectomy is known to substantially reduce expression from non-integrated AAV genomes yet no significant differences in transgene expression were observed compared to non-hepatectomized mice: circulating F.IX levels in the AAV-ZFN + AAV-Donor group (n=13) ranged between 678–1240 ng/mL, whereas mice receiving ZFN alone (n=8) or Mock + AAV-Donor (n=8) had no detectable F.IX expression, or &lt;100 ng/mL F.IX, respectively. Taken together, these data suggest that the F.IX expression in ZFN + Donor treated mice was derived from stable correction of the genome at the intended target site. In summary, we have shown that synchronized cell proliferation of hepatocytes, either in neonatal mice or following partial hepatectomy, is not necessary to achieve highly efficient genome editing and resultant high levels of transgene expression in vivo. These findings substantially expand the potential of ZFN-mediated genome editing as a therapeutic modality. Disclosures: Doyon: Sangamo Biosciences: Employment. Gregory:Sangamo Biosciences: Employment. Holmes:Sangamo Biosciences: Employment.
Plots of the percent change in tumor volume and normalized ADC (ADC) for each of the treatment groups in <i>Study 2</i>. (2015)

&lt;p&gt;Presented are treatment groups (A) Control, (B) irradiation (IR), (C) gemcitabine (GEM) and (D) combination gemcitabine and irradiation (GEM+IR). Data is presented over the first week of the study as the mean ± SEM.&lt;/p&gt;
Relations plantes-microorganismes : synthese asymetrique de la (+) pisatine et d'analogues, inhibiteurs potentiels de la pisatine demethylase (1992)

Les phytoalexines, substances fongitoxiques, synthetisees par les plantes a la suite d'une attaque fongique, peuvent etre detoxifiees enzymatiquement par les champignons pathogenes. Notre but est de savoir si cette pathogenicite est anihilee lorsque la detoxification est bloquee au moyen d'inhibiteurs. Nous avons choisi d'etudier le pois dont la degradation de la phytoalexine, la (+) pisatine, par son champignon pathogene, nectria haematococca, est une demethylation qui met en jeu une monooxygenase a cytochrome p450. Les inhibiteurs de cette enzyme que nous avons choisis sont de type pterocarpanolique et pterocarpanique. Trois precurseurs communs (3-arylcoumarines; 2,3-diarylprop-2-ene-1-ols et isoflavenes) se degagent de la strategie de synthese de ces deux types de composes optiquement actifs que nous avons choisie. Apres les avoir prepares, nous nous sommes consacres a la synthese des pterocarpanols. Nous avons d'abord teste les differentes voies asymetriques imaginees dans le but d'acceder a la (+) pisatine. La preparation de celle-ci a ete finalement possible en appliquant sur un isoflavene la reaction de dihydroxylation de sharpless. Cette strategie a ensuite ete appliquee avec succes a la preparation d'un analogue optiquement pur: la (+) vinylpisatine. Enfin, nous nous sommes consacres aux pterocarpanes dont nous avons pu preparer le precurseur racemique: la () maackiaine, via l'hydroboration d'un isoflavene ou d'une 3-arylcoumarine
Hemorrhage control by microsecond electrical pulses (2013)

Non-compressible hemorrhages are the most common preventable cause of death on battlefield or in civilian traumatic
injuries. We report the use of sub-millisecond pulses of electric current to induce rapid constriction in femoral and
mesenteric arteries and veins in rats. Extent of vascular constriction could be modulated by pulse duration, amplitude
and repetition rate. Electrically-induced vasoconstriction could be maintained at steady level until the end of
stimulation, and blood vessels dilated back to their original size within a few minutes after the end of stimulation. At
higher settings, a blood clotting could be introduced, leading to complete and permanent occlusion of the vessels. The
latter regime dramatically decreased the bleeding rate in the injured femoral and mesenteric arteries, with a complete
hemorrhage arrest achieved within seconds. The average blood loss from the treated femoral artery was about 7 times
less than that of a non-treated control. This new treatment modality offers a promising approach to non-damaging
control of bleeding during surgery, and to efficient hemorrhage arrest in trauma patients.
Efficient decision rule for spectrum sensing performance improvement in cognitive radio (2009)

According to dramatic increase of wireless communication demand, more spectrum resources are needed to support considerable and various wireless services. However, limited spectrum resources are regulatory assigned to licensed user and no interference needs to occur from unlicensed user to licensed user. In this paper, we propose efficient decision rule in order to get better chance to detect the unused spectrum assigned licensed user and improve reliability of spectrum sensing performance. Each secondary user receives the signal from licensed user and input to and energy detector. Then, each sensing results are combined and used to make a decision whether primary user is presence or not. In order to make the reliable decision, we apply to efficient decision rule that is named the Majority rule in this paper. The simulation results show that sensing performance proposed decision rule is more reasonable and efficient than conventional decision rules.
A Novel Converter Topology for a Primary-Side Controlled Wireless EV Charger With a Wide Operation Range (2020)

The full-bridge commonly employed in the primary of an SAE J2954 compliant inductive power transfer (IPT) based wireless electric vehicle (EV) charger possesses many challenges. To alleviate these issues, expensive switches, and extra components are employed together with secondary-side regulation. As an alternative, this article proposes a new topology, termed integrated boost multilevel converter (IBMC). An IBMC consists of series-connected half-bridge submodules (SMs) in each arm, and the dc supply is connected to each arm through a dc inductor. When an IBMC is used as the primary converter, its ability to generate a boosted multilevel output voltage, enables it to regulate the power flow efficiently over a wide load/coupling range without requiring a secondary-side regulator. This article focuses on the operating principles of this new IBMC under steady-state conditions and discusses a modulation scheme that can be used to regulate the power flow while balancing the SM voltages. The benefits of the IBMC is experimentally validated using an SAE J2954 WPT2/Z2 compliant prototype. This prototype used an IBMC built with low-cost switching devices on the primary-side to regulate the power flow to 7.7 kW as the coupling factor changed between 0.11 and 0.25 while maintaining the system efficiency between 90.4% and 91.9%.
The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies (2019)

Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.
ChemInform Abstract: A Convergent Radical‐Based Route to Biaryls. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Targeting transcription of MCL-1 sensitizes HER2-amplified breast cancers to HER2 inhibitors (2021)

Human epidermal growth factor receptor 2 gene (HER2) is focally amplified in approximately 20% of breast cancers. HER2 inhibitors alone are not effective, and sensitizing agents will be necessary to move away from a reliance on heavily toxic chemotherapeutics. We recently demonstrated that the efficacy of HER2 inhibitors is mitigated by uniformly low levels of the myeloid cell leukemia 1 (MCL-1) endogenous inhibitor, NOXA. Emerging clinical data have demonstrated that clinically advanced cyclin-dependent kinase (CDK) inhibitors are effective MCL-1 inhibitors in patients, and, importantly, well tolerated. We, therefore, tested whether the CDK inhibitor, dinaciclib, could block MCL-1 in preclinical HER2-amplified breast cancer models and therefore sensitize these cancers to dual HER2/EGFR inhibitors neratinib and lapatinib, as well as to the novel selective HER2 inhibitor tucatinib. Indeed, we found dinaciclib suppresses MCL-1 RNA and is highly effective at sensitizing HER2 inhibitors both in vitro and in vivo. This combination was tolerable in vivo. Mechanistically, liberating the effector BCL-2 protein, BAK, from MCL-1 results in robust apoptosis. Thus, clinically advanced CDK inhibitors may effectively combine with HER2 inhibitors and present a chemotherapy-free therapeutic strategy in HER2-amplified breast cancer, which can be tested immediately in the clinic.
PC-based ultrasound imaging system in a probe (2002)

Teratech Corporation has created the Terason/sup TM/ 2000 Handheld Ultrasound System-an ultrasound system that provides excellent image quality while being much smaller in size and lower in cost than conventional systems. Unlike conventional machines with proprietary system architecture, the Terason 2000 deploys an open architecture that supports direct access to image data files and facilitates seamless integration into the emerging realm of digital radiology, including Internet-based teleradiology, medical informatics systems, and digital image archiving and retrieval. To achieve these goals, Teratech leveraged its unique silicon system-on-a-chip capability, and dramatically reduced the typical rack-mounted conventional system to a Terason SmartProbe/sup TM/ weighing approximately 10 ounces (0.28 kg). Employing Teratech's proprietary charge domain processing, the beamformer supports a continuous computation throughput of 10.2 billion operations/s and a delay update rate of 10 billion bits/s while consuming less than 1 W, providing more than 10-fold savings in power and weight compared to the conventional implementation. The system is linked to a host PC through an IEEE 1394 (a.k.a. FireWire) serial cable. The PC, running Windows NT or 2000 with plug-and-play standard compatibility, allows the system to utilize all of the control, display, videorecording, and networking capabilities currently available for PCs.
Synthesis and Electrochemical Performance of a Lithium Titanium Phosphate Anode for Aqueous Lithium-Ion Batteries (2011)

Lithium-ion batteries that use aqueous electrolytes offer safety and cost advantages when compared to today's commercial cells that use organic electrolytes. The equilibrium reaction potential of lithium titanium phosphate is -0.5 V with respect to the standard hydrogen electrode, which makes this material attractive for use as a negative electrode in aqueous electrolytes. This material was synthesized using a Pechini type method. Galvanostatic cycling of the resulting lithium titanium phosphate showed an initial discharge capacity of 115 mAh/g and quite good capacity retention during cycling, 84% after 100 cycles, and 70% after 160 cycles at a 1 C cycling rate in an organic electrolyte. An initial discharge capacity of 113 mAh/g and capacity retention of 89% after 100 cycles with a coulombic efficiency above 98% was observed at a C/5 rate in pH -neutral 2 M Li2 S O4. The good cycle life and high efficiency in an aqueous electrolyte demonstrate that lithium titanium phosphate is an excellent candidate negative electrode material for use in aqueous lithium-ion batteries. © 2011 The Electrochemical Society.
Feature-Rich Language-Independent Syntax-Based Alignment for Statistical Machine Translation (2011)

We present an accurate word alignment algorithm that heavily exploits source and target-language syntax. Using a discriminative framework and an efficient bottom-up search algorithm, we train a model of hundreds of thousands of syntactic features. Our new model (1) helps us to very accurately model syntactic transformations between languages; (2) is language-independent; and (3) with automatic feature extraction, assists system developers in obtaining good word-alignment performance off-the-shelf when tackling new language pairs. We analyze the impact of our features, describe inference under the model, and demonstrate significant alignment and translation quality improvements over already-powerful baselines trained on very large corpora. We observe translation quality improvements corresponding to 1.0 and 1.3 BLEU for Arabic-English and Chinese-English, respectively.
Abstract 19694: Adjunct Intracardiac Echocardiography is Associated With Reduced Fluoroscopy and Procedural Time in the Ablation of Cavotricuspid Isthmus-Dependent Atrial Flutter (2016)

Introduction: With the routine use of contact force-sensing ablation catheters, the additional utility of intracardiac echocardiography (ICE) in the ablation of typical right atrial flutter (AFL) i...
Experimental Investigation on Crosstalk of FSK Supervisory Signal in ROADM networks (2015)

The crosstalk of FSK supervisory signal encoded on 80×128Gbit/s DP-QPSK WDM channels in CNCG-ROADM networks was experimentally and theoretically estimated. The simulation results confirm that 30-cascaded ROADM could be supported with proper FSK signal decoder parameters.
Cytotoxicity of Paclitaxel in Breast Cancer Is due to Chromosome Missegregation on Multipolar Spindles (2014)

The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, most mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patients. These results demonstrate that mitotic arrest is not responsible for the efficacy of paclitaxel, which occurs because of chromosome missegregation on highly abnormal, multipolar spindles. This mechanistic insight may be used to improve selection of future antimitotic drugs and to identify a biomarker with which to select patients likely to benefit from paclitaxel.
Novel Regiocontrolled Protection of 1,2- and 1,3-Diols via Mild Cleavage of Methylene Acetals (2009)

The regiocontrolled protection of unsymmetrical 1,2- and 1,3-diols has been developed. Different types of protected diols are available from the methylene acetal in a one-pot procedure. Highly regioselective protection of diols with a silyl group at the less hindered hydroxy group as well as with a MOM group at the more hindered one were achieved. The reaction conditions are mild without affecting other functional groups including acid-labile function.
Ultrasound in Food Processing (2017)

In this chapter the most outstanding applications of ultrasound (US) on reactions and processes involving carbohydrates have been reviewed and discussed, paying special attention to the mechanisms involved and the US conditions selected as optimal. Sonophysical effects have been widely described in relation to carbohydrate depolymerization, modification of their bioactive/technological properties and processes such as crystallization and their application in carbohydrate chemistry. Depolymerization has been described as the main application of sonochemical effects, and different biotechnological processes assisted by US, such as enzymatic depolymerisation, enzymatic synthesis of carbohydrate derivatives, fermentation, etc., have also been reviewed. To conclude, US is presented as a promising emerging technique for the modification of structure and functionality of carbohydrates. The scale‐up of US techniques and the further development of sonochemistry applications are presented as future trends.
Supplementary Figure Legends from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen (2023)

Supplementary Figure Legends from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen
Prolonged activation of the baroreflex decreases arterial pressure in the presence of chronic adrenergic blockade (2007)

Prolonged baroreflex activation (PBA) by electrical stimulation of the carotid sinus baroreceptors produces sustained reductions in mean arterial pressure (MAP) and suppression of the sympathetic nervous system. The goal of this study was to determine whether PBA lowers MAP when α‐1 and β‐adrenoceptors are blocked by high doses of adrenergic antagonists (AB). This was studied in 6 dogs under control conditions, following administration of prazosin (α‐1 antagonist, 5mg/kg/d, tid) + propranolol (nonselective β‐blocker, 10mg/kg/d, IV infusion) for 7 days (AB), and then for an additional 7 days during AB+PBA. MAP and heart rate (HR) responses to bolus injections of phenylephrine (MAP=+44±3 mmHg; HR=−29±2 bpm) and isoproterenol (HR=+59±8 bpm) were completely blocked during AB. Chronic MAP, HR, and plasma norepinephrine (NE, pg/ml) responses to AB and AB+PBA were: image MAP decreased substantially during AB despite increased central sympathetic outflow as evidenced by increased NE. Moreover, in the presence of AB, MAP decreased further during PBA. This further decline in MAP in response to central sympathoinhibition by PBA may reflect suppression of cotransmitter release from adrenergic neurons or altered hormonal secretion. (HL‐51971)
Shale Reservoir Characterization Using 3D Markov Field Classification (2013)

Classification of seismic attributes (Sonneland et al. 1994) is commonly used as a methodology for partitioning a seismic volume into a set of discrete classes of similar underlying nature (e.g., lithology, fluid, structure). A new field of application is the characterization of shale reservoirs, for sweet spot detection and optimized well placement (Sonneland et al. 2012). A novel approach to seismic classification is presented in this paper, utilizing pre-existing results from an advanced well log classification, where the log classes are related to underlying statistics of rock properties obtained from cored wells. A Markov field spatial model is defined, incorporating log derived information on the sorting of classes. This model enables a consistent propagation of the classes observed in 1D well logs into a 3D volume based on the multi-dimensional distribution of prestack inverted seismic attributes. Through the relationship of the classes to the core observations, this provides, e.g., estimates of the 3D extent of the high TOC% (total organic carbon) classes.
Compact and ultra-broadband all-silicon TM-pass and TE-reflected polarizer using grating based weakly coupled nanowires (2022)

On-chip silicon polarizers with broad operating bandwidth and compact footprint have recently attracted increasing attention for their applications in large capacity and high density integrated optical systems. However, strong waveguide dispersion usually limits the bandwidth of the silicon polarizers, especially for the TM-pass polarizers. In this paper, we overcome the bandwidth limit of the TM polarizer by utilizing a novel waveguide structure composed of two weakly coupled nanowires with gratings sandwiched in between. Such a structure can effectively enlarge the bandgap for the undesired TE polarized light, while act as a low loss subwavelength metamaterial for TM polarized light over an extremely large wavelength range. In simulation, we obtain a compact polarizer of 13.6 µm × 1.3 µm in size with an ultra-broad operating bandwidth of ∼362 nm for extinction ratios (ERs) >21 dB and insertion losses (ILs) <1 dB, which covers E-, S-, C-, L-, and U-bands and part of O-band. The measurements of fabricated devices show that the device performed well in the test wavelength range from 1300 to 1600 nm with an ER >15 dB and an average IL ∼1 dB, consistent with the simulation results. This work paves a new way for designing compact and ultra-broadband on-chip polarizers.
Deep learning for vessel-specific coronary artery calcium scoring: validation on a multi-centre dataset (2021)

Our results demonstrate that fully automated total and vessel-specific CAC scoring is feasible using a DL-based algorithm. There was a high agreement with the manually assessed total CAC from a multi-centre dataset and the vessel-specific scoring demonstrated consistent and reproducible results.