gebhart/patrepeval huggingface dataset:
The overall fatty acid absorption controlled by basolateral chylomicron excretion under regulation of p-JNK1 (2017)

Suppression of fatty acid absorption is one goal to fight obesity. However, the responsible molecular mechanism is poorly understood. Aim of the present study was the search for the key regulator of the overall fatty acid absorption mechanism and its pharmaceutical modulation. As experimental tool we employed the polarized human intestinal tumor derived cell line CaCo2. Here we showed that influx of fatty acids is mediated by an apical heterotetrameric plasma membrane protein complex of which the calcium-independent membrane phospholipase A<sub>2</sub> (iPLA<sub>2</sub>ß) is one constituent. The newly synthesized bile acid-phospholipid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) blocked iPLA<sub>2</sub>ß, which structurally disrupted the fatty acid-uptake complex. Furthermore, the inhibition of iPLA<sub>2</sub>ß lead to reduction of cytosolic lysophosphatidylcholine (LPC) production which suppressed p-JNK1, as a central regulator of metabolism. In a concerted action low p-JNK1 levels prohibited synthesis of the members of the fatty acid uptake complex as well as of apolipoprotein B and the connected members of the basolateral vesicular chylomicron excretion machinery, thereby inhibiting cellular lipid excretion. The basolateral chylomicron release was shown to determine the overall fatty acid-absorption capacity as rate limiting step, whereas apical uptake replenishes the cellular stores, enabling continuous transcellular movement of fatty acids. In conclusion, the UDCA-LPE mediated inhibition of p-JNK1 represents a powerful tool to control intestinal absorption of fatty acids and, thus may be employed as a drug to treat obesity.
Chemical Surface Modification of Alumina and Titania for Improved Admix of Xerographic Toners (2001)

Nanosize silica, titania and alumina metal oxide particles are common xerographic toner additives for control of flow, charge, development and transfer. Typically the oxides are rendered hydrophobic by reaction of the surface hydroxyl groups with organosilanes. This treatment leads to improved flow and charging properties but also typically gives unacceptably long admix charging times. It is shown that admix times on alumina and titania can be dramatically reduced by adsorption of amines such as triethylamine. The most acidic hydroxyl groups of alumina and titania undergo a proton transfer to form a salt with the triethylamine: it is this species that gives rise to improved admix. In effect, the formation of the quaternary salt on the surface mimics the performance of traditional ionic charge control agents. Alternatively, the same decrease on admix can be achieved by incorporating covalently bound sulfate species on the oxide surface. The sulfate groups increase the ionic character through an enhancement of the Bronsted acidity of the oxide. Only a relatively few hydroxyl groups need to be converted to an ionic form (either by amine addition or sulfate incorporation) to dramatically improve admix. A majority of the hydroxyl groups remain unaffected. These remaining groups can then be reacted with an organosilane to yield an oxide with increased negative charge and improved flow. The decrease in admix time with amine pretreatment is independent of the effects of subsequent hydrophobic treatments. In this case, the shorter admix times generated by the quaternary amine salt is retained.
Facile Synthesis, Geometry, and 2′-Substituent-Dependent in Vivo Activity of 5′-(E)- and 5′-(Z)-Vinylphosphonate-Modified siRNA Conjugates (2018)

(E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5'-end of the antisense strand, enhances the in vivo potency of siRNA. Here we describe a straightforward synthetic approach to incorporate a nucleotide carrying a vinylphosphonate (VP) moiety at the 5'-end of oligonucleotides under standard solid-phase synthesis and deprotection conditions by utilizing pivaloyloxymethyl (POM) protected VP-nucleoside phosphoramidites. The POM protection enhances scope and scalability of 5'-VP-modified oligonucleotides and, in a broader sense, the synthesis of oligonucleotides modified with phosphonate moieties. Trivalent N-acetylgalactosamine-conjugated small interfering RNA (GalNAc-siRNA) comprising (E)-geometrical isomer of VP showed improved RISC loading with robust RNAi-mediated gene silencing in mice compared to the corresponding (Z)-isomer despite similar tissue accumulation. We also obtained structural insights into why bulkier 2'-ribosugar substitutions such as 2'-O-[2-(methylamino)-2-oxoethyl] are well tolerated only when combined with 5'-(E)-VP.
The ferroin test: a sensitive and convenient probe of internal versus external silver in microporous materials: application to silver sodalites (1991)

Ferroin can be used as a sensitive redox active indicator to distinguish conveniently between internally confined and externally located silver aggregates, in a range of silver sodalites, of current interest in advanced materials science applications.
Targeted Methods for Finding Quantitative Trait Loci (2011)

Conventional genetic mapping methods typically assume parametric models with Gaussian errors, and obtain parameter estimates through maximum likelihood estimation. We propose a general semiparametric model to map quantitative trait loci (QTL) in experimental crosses. In contrast with widely-used interval mapping (IM) derived methods, our model requires fewer assumptions and also accommodates various machine learning algorithms. Estimation using both targeted maximum likelihood and collaborative targeted maximum likelihood methods is compared to a composite interval mapping (CIM) approach. We demonstrate with simulations and real data analyses that, on average, our semiparametric targeted learning approach produces less biased QTL effect estimates than those from parametric models.
Phorbol Ester-induced Transcription of a Fibroblast Growth Factor-binding Protein Is Modulated by a Complex Interplay of Positive and Negative Regulatory Promoter Elements (1998)

Earlier studies from our laboratory showed that a secreted binding protein for fibroblast growth factors (FGF-BP) is expressed at high levels in squamous cell carcinoma (SCC) cell lines. Overexpression studies or conversely reduced expression of FGF-BP by ribozyme targeting have elucidated a direct role of this protein in angiogenesis during tumor development. We have also observed a significant up-regulation of FGF-BP during TPA (12-O-tetradecanoylphorbol-13-acetate) promotion of skin cancer. Here we investigate the mechanism of TPA induction of FGF-BP gene expression in the human ME-180 SCC cell line. We found that TPA increased FGF-BP mRNA levels in a time- and dose-dependent manner mediated via the protein kinase C signal transduction pathway. Results from actinomycin D and cycloheximide experiments as well as nuclear transcription assays revealed that TPA up-regulated the steady-state levels of FGF-BP mRNA by increasing its rate of gene transcription independently of de novo protein synthesis. We isolated the human FGF-BP promoter and determined by deletion analysis that TPA regulatory elements were all contained in the first 118 base pairs upstream of the transcription start site. Further mutational analysis revealed that full TPA induction required interplay between several regulatory elements with homology to Ets, AP-1, and CAATT/enhancer binding protein C/EBP sites. In addition, deletion or mutation of a 10-base pair region juxtaposed to the AP-1 site dramatically increased TPA induced FGF-BP gene expression. This region represses the extent of the FGF-BP promoter response to TPA and contained sequences recognized by the family of E box helix-loop-helix transcription factors. Gel shift analysis showed specific and TPA-inducible protein binding to the Ets, AP-1, and C/EBP sites. Furthermore, distinct, specific, and TPA-inducible binding to the imperfect E box repressor element was also apparent. Overall, our data indicate that TPA effects on FGF-BP gene transcription are tightly controlled by a complex interplay of positive elements and a novel negative regulatory element.
Microfluidic production of 18F-labeled TSPO ligands (2011)

1512 Objectives Radiolabeling of candidate compounds is a bottleneck within the molecular imaging probe development paradigm. Microfluidic preparation of radiopharmaceuticals is an alternative approach to classical, box-based radiosyntheses. The high-throughput nature of microfluidic approaches enables rapid optimization and evaluation of various radiochemical conditions, which may subsequently inform the feasibility of larger scale production. We have evaluated microfluidic radiolabeling of known (i.e., 18F-PBR06 and 18F-DPA714) and novel TSPO ligands typically prepared using traditional means. Methods The Advion NanoTekTM LF system was used to perform microfluidic radiolabeling of a variety of aryloxyanilide and pyrazolo-pyrimidine based TSPO ligands with fluorine-18. The labeling parameters optimized were reaction temperature, solvent, and residence time. Radiochemical yield was estimated through TLC analysis while specific activities were calculated using a HPLC derived standard curve. Results We found that optimizing reaction temperatures had a major impact on radiochemical yield. Labeling efficiencies up to and greater than 90% could be achieved for all compounds characterized when carried out at optimal temperature. Use of solvent, including ACN and DMF, also had a profound effect on the observed radiochemical yield for pyrazolo-pyrimidines. Importantly, optimized microfluidic conditions were informative towards the accelerated development of high-specific activity, large-scale production methodologies developed in a GE Tracer Labs FX module. Conclusions Microfluidic radiochemistry appears to be a useful component of PET probe development. Given the improved throughput and effectiveness of this approach, we envision its utility for determining labeling feasibility, probe stability, and optimal reaction conditions prior to transitioning to full-scale hot-cell based production. This pre-production optimization could drastically streamline probe development capabilities achievable by traditional radiochemistries
Lateralized Response of Dynorphin A Peptide Levels after Traumatic Brain Injury (2012)

Traumatic brain injury (TBI) induces a cascade of primary and secondary events resulting in impairment of neuronal networks that eventually determines clinical outcome. The dynorphins, endogenous opioid peptides, have been implicated in secondary injury and neurodegeneration in rodent and human brain. To gain insight into the role of dynorphins in the brain's response to trauma, we analyzed short-term (1-day) and long-term (7-day) changes in dynorphin A (Dyn A) levels in the frontal cortex, hippocampus, and striatum, induced by unilateral left-side or right-side cortical TBI in mice. The effects of TBI were significantly different from those of sham surgery (Sham), while the sham surgery also produced noticeable effects. Both sham and TBI induced short-term changes and long-term changes in all three regions. Two types of responses were generally observed. In the hippocampus, Dyn A levels were predominantly altered ipsilateral to the injury. In the striatum and frontal cortex, injury to the right (R) hemisphere affected Dyn A levels to a greater extent than that seen in the left (L) hemisphere. The R-TBI but not L-TBI produced Dyn A changes in the striatum and frontal cortex at 7 days after injury. Effects of the R-side injury were similar in the two hemispheres. In naive animals, Dyn A was symmetrically distributed between the two hemispheres. Thus, trauma may reveal a lateralization in the mechanism mediating the response of Dyn A-expressing neuronal networks in the brain. These networks may differentially mediate effects of left and right brain injury on lateralized brain functions.
A novel low-complexity frequency offset estimator for OFDM systems (2008)

The frequency offset estimation is one of the most important tasks in orthogonal frequency division multiplexing (OFDM) systems. To estimate frequency offset, a periodogram-based estimator has been proposed by Ren. The method consists of three estimation steps and gives an accurate result. However, in the second and third estimation steps, the maximum frequency offset range that can be estimated is limited to a subcarrier spacing. This range is insufficient compared with the overall signal bandwidth, making the first estimation step require high complexity. In this paper, we propose a low-complexity frequency offset estimation method, which can efficiently extend the estimation ranges without loss of accuracy.
Low-Complexity Algorithm for Radio Astronomy Observation Data Transport in an Integrated NGSO Satellite Communication and Radio Astronomy System (2021)

An integrated non-geostationary orbit (NGSO) satellite communication and radio astronomy system (SCRAS), was recently proposed in 51 as a new coexistence paradigm. In SCRAS, the transportation of the radio astronomical observation (RAO) data from the space to the ground stations is an important problem, for which 51 proposed a linear programming optimization based algorithm. However, the computational complexity of this algorithm is quite high which is exacerbated by the need to re-compute the algorithm frequently due to the time-varying characteristics of the observing satellites, the Earth stations, and the RAO region. In this paper, to address this high complexity issue, we develop a low-complexity RAO data transport algorithm. In addition to the static resource constraint scenario considered in the existing work, we introduce a dynamic resource constraint scenario to exploit the knowledge of the satellite communication system (SCS) traffic statistics. We also present a modified version of the algorithm in 51 for the dynamic resource constraint scenario. In addition to the number of inter-satellite link (ISL) hops as the RAO data transport cost metric, we also evaluate the metric of the sum of the squared ISL hop distances which reflects the transmission energy cost. Furthermore, computational complexity analysis and data transport costs of the algorithms are presented. Our results show that the proposed algorithm yields several orders of computational complexity saving over the existing method while incurring a modest increase in the data transport cost. Our proposed dynamic resource constraint scenario provides plausible reduction of the RAO data transport cost.
Role of Mixed Lineage Kinase Inhibition in Neonatal Hypoxia-Ischemia (2009)

Hypoxic-ischemic brain injury is often delayed and involves both apoptotic and immunoregulatory mechanisms. In this study, we used a neonatal model of hypoxia-ischemia to examine the effect of the mixed lineage kinase (MLK) inhibitor CEP-1347 on brain damage, apoptosis and inflammation. The tissue volume loss was reduced by 28% (p = 0.019) in CEP-1347-treated versus vehicle-treated rats and CEP-1347 significantly attenuated microgliosis at 7 days (p = 0.038). CEP-1347 decreased TUNEL-positive staining as well as cleaved caspase 3 immunoreactivity. CEP-1347 did not affect the expression of pro-inflammatory cytokines IL-1 beta, IL-6 and MCP-1, nor did it affect the expression of OX-42 (CR3) and OX-18 (MHC I) 24 h after the insult. In conclusion, the MLK inhibitor CEP-1347 has protective effects in a neonatal rat model of hypoxia-ischemia, which is mainly related to reduced apoptosis.
ARTIFICIAL TUNABLE ENVIRONMENTS FOR SUPERCONDUCTING QUAN- TUM BITS (2012)

We report our recent work on developing artificial electromagnetic environments for superconducting devices. Previously, we have showed that single-photon heat conduction between two resistors embedded in a superconducting cavity can be achieved [1]. Here, we modify this setup to provide in-situ control of the photonic heat power [2] and open up the possibility to tune the coupling strength between the artificial environment and the desired component in the cavity by several orders of magnitude. Our results provide an efficient pathway to control the lifetime of a superconducting quantum bit, qubit, allowing for rapid initialization to the ground state at will and unhindered normal operation as desired [3].
Polymer-Based Integrated Photonic Devices for Highly Parallel Optical Interconnects (1997)

Abstract : We have solved the crosslinker crystallization problem which has been a major bottleneck for several years. A new method of electrooptic measurenment is invented which has the advantage of being able to accurately measure r33 and r13 separately with a high accuracy. A theory of TE-TM mode conversion in tilted-poled NLO waveguides is developed. A new polarization-independent Mach-Zehnder modulator is designed and fabricated by using this theory. This device uses continuous modulation electrodes, thereby allowing the employment of traveling-wave modulation to achieve extremely high speed. Primary polarization-independent devices and directional-coupler devices have been fabricated. Further design and fabrication of new high performance electrooptic devices are under investigation.
Advanced energy storage : creating impact for next-generation lithium-ion batteries and supercapacitors : energy (2015)

Lithium-ion batteries and supercapacitors are critical energy storage systems that power our smart phones, laptop computers, electric vehicles, smart grids and even our homes. They also play a role in decreasing the necessity for load shedding by alleviating the pressure on the national grid. The CSIR is developing the next-generation lithium-ion batteries and supercapacitors using some of the country's abundant mineral resources.
Design and Synthesis of New Pyrazole‐Based Heterotricycles and their Derivatization by Automated Library Synthesis (2020)

Small-molecule heterocycles bearing orthogonal functionality have the potential to deliver diverse structural motifs that aid the drug-discovery effort. This work highlights how a readily assembled N-hydroxyethyl pyrazole trifluoroborate offers rapid access to architecturally distinct 5-6-6- and 5-7-6-fused tricyclic compounds. This chemistry is not only amenable to single compound synthesis, but also to high-throughput experimentation. It gives easy access to diverse compound arrays with various physicochemical and ADME profiles by fully automated library synthesis. The combination of the high-throughput experimentation with rapid testing of the compounds in an integrated physicochemical and ADME profiling workflow allows accelerated design of novel lead compounds in drug-discovery projects.
Development and Characterization of a Preclinical Model for the Evaluation of CD205-Mediated Antigen Delivery Therapeutics in Type 1 Diabetes (2019)

Dendritic cells (DCs) are crucial for the production of adaptive immune responses to disease-causing microbes. However, in the steady state (i.e., in the absence of an infection or when Ags are experimentally delivered without a DC-activating adjuvant), DCs present Ags to T cells in a tolerogenic manner and are important for the establishment of peripheral tolerance. Delivery of islet Ags to DCs using Ag-linked Abs to the DC endocytic receptor CD205 has shown promise in the NOD mouse model of type 1 diabetes (T1D). It is important to note, however, that all myeloid DCs express CD205 in humans, whereas in mice, only one of the classical DC subsets does (classical DC1; CD8α<sup>+</sup> in spleen). Thus, the evaluation of CD205-targeted treatments in mice will likely not accurately predict the results observed in humans. To overcome this challenge, we have developed and characterized a novel NOD mouse model in which all myeloid DCs transgenically express human CD205 (hCD205). This NOD.hCD205 strain displays a similar T1D incidence profile to standard NOD mice. The presence of the transgene does not alter DC development, phenotype, or function. Importantly, the DCs are able to process and present Ags delivered via hCD205. Because Ags taken up via hCD205 can be presented on both class I and class II MHC, both CD4<sup>+</sup> and CD8<sup>+</sup> T cells can be modulated. As both T cell subsets are important for T1D pathogenesis, NOD.hCD205 mice represent a unique, patient-relevant tool for the development and optimization of DC-directed T1D therapies.
Phase I dose-escalation study of 225Ac-J591 for progressive metastatic castration resistant prostate cancer (mCRPC). (2018)

TPS399 Background: PC is a radiosensitive disease. PSMA is overexpressed in advanced PC with upregulation by androgen receptor (AR) pathway dysregulation; limited expression exists in other organs. A series of sequential studies of beta-emitting radiolabeled anti-PSMA monoclonal antibody (mAb) J591 have demonstrated accurate targeting, efficacy with dose-response effect, and safety with predictable, reversible dose-limiting myelosuppression. Alpha emitters are significantly more potent with a shorter range than beta emitters. Though there is no direct tumor-targeting, the bone-targeting alpha emitter Ra223 is approved. Anecdotal reports of PSMA small molecule targeted alpha emitters have hinted at efficacy but are limited by xerostomia and in mouse models may lead to long-term renal damage. Intact mAb J591 has comparatively no to minimal distribution in salivary glands and kidneys. Preclinical studies demonstrated purity, immunoreactivity, and stability with efficacy in a xenograft model [AACR 2017]. Methods: Men with progressive mCRPC following at least 1 potent AR-targeted agent (e.g. abi/enza) and docetaxel (or unfit/refuse chemo) without limit of # prior therapies (excluding beta-emitting bone-targeted radioisotopes) provided adequate organ function will undergo imaging with 68 Ga-PSMA-11 PET/CT followed by a single dose of 225 Ac-J591. Single-subject cohorts will be enrolled until grade &gt; 1 attributable toxicity, then transition to 3+3 design. Cohort 1 = 13.3 KBq/kg with planned escalation up to 93.3 KBq/kg of 225 Ac with fixed 20 mg J591. Dose-limiting toxicity (DLT) is defined as attributable grade 4 heme toxicity or grade 3/4 non-heme toxicity. Planned cohort expansion will occur at recommended phase 2 dose (RP2D) in a 2-stage design. The primary endpoint is determination of DLT and RP2D. Secondary endpoints include toxicity, PSA decline rate, RECIST response, PFS, rPFS, OS, and patient reported outcomes (FACT-P and BPI-SF). Correlatives include baseline/follow up PSMA imaging, CTC count (CellSearch) changes, tissue and circulating genomic assessment, and immune studies. Enrollment began in October, 2017. Clinical trial information: NCT03276572.
CT of the liver after cryotherapy of hepatic metastases: imaging findings. (1995)

Cryotherapy is the in situ destruction of abnormal tissue using subzero temperatures (Fig. 1). Recent studies have demonstrated the technical feasibility, safety, and effectiveness of hepatic cryotherapy in the treatment of liver tumors [1, 2]. Such treatment can be precisely focused on the tumor, thereby preserving surrounding normal tissue. In addition, because major vessels with flowing blood are protected from cryoablation, tumors adjacent to these vessels can be treated without sacrificing vasculature. Hepatic cryoablation is therefore particularly suitable for patients who do not qualify for surgical resection because of multiple metastases involving both lobes of the liver, or because of lesions close to major blood vessels. After the procedure, CT during arterioportography is of little value in distinguishing cryolesion from malignant tumor (Fig. 2), and CT with IV contrast enhancement is recommended for follow-up. It is important to distinguish CT findings of successful and unsuccessful treatment, treatment complications such as abscess and cholestasis, and recurrent tumor. The purpose of this essay is to illustrate the findings on CT with IV contrast enhancement in various situations, emphasizing features that are useful in making accurate differential diagnosis.