gebhart/patrepeval huggingface dataset:
Abnormal regulation of renal kallikrein in experimental diabetes. Effects of insulin on prokallikrein synthesis and activation. (1987)

The effects of streptozotocin (STZ) diabetes and insulin on regulation of renal kallikrein were studied in the rat. 1 and 2 wk after STZ injection, diabetic rats had reduced renal levels and urinary excretion of active kallikrein. Tissue and urinary prokallikrein levels were unchanged, but the rate of renal prokallikrein synthesis relative to total protein synthesis was reduced 30-45% in diabetic rats. Treatment of diabetic rats with insulin prevented or reversed the fall in tissue level and excretion rate of active kallikrein and normalized prokallikrein synthesis rate. To further examine insulin's effects, nondiabetic rats were treated with escalating insulin doses to produce hyperinsulinemia. In these rats, renal active kallikrein increased. Although renal prokallikrein was not increased significantly by hyperinsulinemia, its synthesis was increased. As this was accompanied by proportionally increased total protein synthesis, relative kallikrein synthesis rate was not changed. Excretion of active kallikrein was unchanged, but prokallikrein excretion was markedly reduced. Therefore, increased tissue active kallikrein seen with hyperinsulinemia can be explained not only by increased synthesis but also by retention and increased activation of renal prokallikrein. These studies show that STZ diabetes produces an impairment in renal kallikrein synthesis and suggest that this disease state also impairs renal prokallikrein activation. The findings also suggest that insulin modulates renal kallikrein production, activation, and excretion.
Current Strategies in Whole-brain Radiation Therapy for Brain Metastases (2005)

Whole-brain radiation therapy (WBRT) has been the primary treatment for patients with brain metastases for more than 50 years and provides effective palliative relief in most patients. Although advancements in radiotherapeutic technique continue to improve local and locoregional control, median survival for patients treated with WBRT monotherapy remains fixed at approximately 4 to 6 months. Key issues in the use of WBRT include optimizing its efficacy when it is used in conjunction with surgery, radiosurgery, radiosensitizers, and new chemotherapeutic agents. These multimodal approaches to brain metastases have resulted in significant increases in the median survival time in many patients. Radiosurgery is part of a continuing effort to improve the effects of radiation therapy, especially in brain metastases. The optimal combination of WBRT and radiosurgery remains to be elucidated, including appropriate timing or sequence and use in conjunction with other modalities. Newer radiosensitizing agents (e.g., efaproxiral [RSR-13] and motexafin gadolinium) have shown promise in the treatment of brain tumors, especially in specific patient subsets. Recently developed systemic chemotherapy agents, such as temozolomide, which crosses the blood-brain barrier, have a synergistic effect on brain metastases when used in conjunction with radiation. In addition, the use of interstitial chemotherapy agents provides highly focused local chemotherapy in the brain without increasing systemic toxicity; carmustine polymer wafer, in combination with WBRT, has shown promising results in treating brain metastases.
695. An AAV8 Mutant with Better Transduction in Murine Muscle and Nasal Airway Than AAV8 (2016)

Adeno-associated virus (AAV)-based gene therapy is showing increasing promise, stimulated by encouraging results from clinical trials in recent years. To advance the platform, we have been exploring AAV capsid manipulation. By combining three mutations at hyper-variable regions (HVRs) I, IV, and VIII of the AAV8 capsid - mutations isolated from saturation mutagenesis followed by several rounds of in vivo selection - we created an AAV8 mutant, referred to as AAV8.Triple. In vitro, the AAV8.Triple mutant showed resistance to various antisera of monkey and human, as well as human IVIG (titers that are at levels 2 to 4 fold that of AAV8, with respect to human IVIG). All three mutations contributed to the observed resistance. In mice, the liver transduction efficiency of AAV8.Triple was reduced compared with AAV8, however its muscle transduction was higher than that of AAV8 by approximately 10 fold. In addition, AAV8.Triple demonstrated a higher heparin affinity than AAV8. Interestingly, reducing the positive charges of the HVR.IV mutation decreased the vector's heparin affinity while liver transduction was partially restored. Similar to the trend observed in muscle, intranasal administration of AAV8.Triple resulted in a transduction efficiency 2 to 3 fold greater than that of AAV8, which was further improved to levels approximately 10 fold greater than AAV8 by swapping the VP1 unique region of AAV8.Triple with that of another AAV serotype. Overall, our findings indicate that AAV capsid manipulation was able to generate an AAV8 mutant with improved transduction in both murine muscle and nasal airway compared with wild-type AAV8. These findings may be relevant to disease models where high-efficiency intramuscular or intranasal gene delivery and resistance to pre-existing neutralizing antibodies are desired.
Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine (2022)

Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected monkeys from SARS-CoV-2 WA-1 infection. Here, we demonstrate SARS-CoV-2 RBD-scNP immunization induces potent neutralizing antibodies in non-human primates (NHPs) against all eight SARS-CoV-2 variants tested including the Beta, Delta, and Omicron variants. The Omicron variant was neutralized by RBD-scNP-induced serum antibodies with a mean of 10.6-fold reduction of ID50 titers compared to SARS-CoV-2 D614G. Immunization with RBD-scNPs protected NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protected mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect NHPs and mice from multiple different SARS-related viruses. Such a vaccine could provide the needed immunity to slow the spread of and reduce disease caused by SARS-CoV-2 variants such as Delta and Omicron.
Morphological and immunocytochemical study of rat pancreatic beta cell changes induced by cyclizine (1984)

Wistar rats were treated daily with cyclizine (50-75 mg kg-1) and autopsied every week until the eighth week of the treatment. Although no evident change could be detected by either serum analysis or by light microscopy from the first week to the fourth week, electron microscopy revealed that beta cells showed depletion of secretory granules and cystic dilation of the rough endoplasmic reticulum from the first week. A significantly higher level of plasma glucose and a lower level of plasma insulin than those of untreated rats were recognized from the fifth week. A diabetic pattern was also observed in the glucose tolerance test which was conducted at the seventh week. From the sixth week, large cytoplasmic vacuoles were observed light microscopically in islet cells. Electron microscopic examination revealed that the vacuoles originated from the rough endoplasmic reticulum in beta cells, while no prominent change was found on the Golgi apparatus. In addition to the above findings, immunocytochemical study with anti-insulin serum demonstrated that the staining intensity of the beta cell cytoplasm became weaker (as judged by light microscopy) from the fifth week, but large cytoplasmic vacuoles were stained positively under both the light microscope (PAP method) and the electron microscope (enzyme-labelled antibody method). These findings suggested that the depletion of secretory granules and accumulation of insulin or its precursor in the rough endoplasmic reticulum occurred in beta cells. The diabetogenic effect of cyclizine on rats is discussed with reference to the immunocytochemical findings.
Interaction between the homeodomain proteins Cdx2 and HNF1α mediates expression of the lactase-phlorizin hydrolase gene (2000)

Lactase-phlorizin hydrolase is a brush-border enzyme which is specifically expressed in the small intestine where it hydrolyses lactose, the main carbohydrate found in milk. We have previously demonstrated in transgenic mice that the tissue-specific and developmental expression of lactase is controlled by a 1 kb upstream region of the pig lactase gene. Two homeodomain transcription factors, caudal-related homeodomain protein (Cdx2) and hepatic nuclear factor 1alpha (HNF1alpha), are known to bind to regulatory cis elements in the promoters for several intestine-specific genes, including lactase, and are present in mammalian intestinal epithelia from an early stage in development. In the present study, we examined whether Cdx2 and HNF1alpha physically interact and co-operatively activate transcription from the lactase-phlorizin hydrolase promoter. We show that the presence of both factors leads to a much higher level of transcription than the sum of the activation by either factor alone. The N-terminal activation domain of Cdx2 is required for maximal synergy with HNF1alpha. With the use of pull-down assays, we demonstrate a direct protein-protein interaction between Cdx2 and HNF1alpha. The interaction domain includes the homeodomain region of both proteins. This is the first demonstration of a functional interaction between two transcription factors involved in the activation of a number of intestine-specific genes. Synergistic interaction between tissue-restricted factors is likely to be an important mechanism for reinforcing developmental and tissue-specific gene expression within the intestine.
Use of the BendMeister Rod Bender for Occipitocervical Fusion: Technical Note (1998)

The creation of various curves in bendable metallic rods remains difficult. We describe a simple instrument that uses two bending levers to provide the mechanical advantage required to easily shape up to 5.5 mm diameter bendable metallic rods with precision, control, and minimal nicking or scratching of the metal surface. We have successfully used this tool to contour primary and secondary curvatures in threaded Steinmann pins and grooved titanium rods for occipitocervical fusion.
SiN/SOI Sub-dB Butt-Coupling Scheme in the O-Band (2022)

The monolithic integration of micro-metric silicon nitride and silicon-on-insulator platforms is presented. We demonstrate an interconnection of sub-dB coupling loss and less than -16dB back-reflection for operation in the O-band.
Concurrent Dual-Band Low Intermediate Frequency Receiver Based on the Multiport Correlator and Single Local Oscillator (2018)

A concurrent dual-band low intermediate frequency receiver, which is based on the multiport correlator, is proposed in this letter. Only one single local oscillator signal is used to demodulate the dual-band RF signals at the same time, which greatly reduce the receiver complexity. The system configuration, output power theory, as well as the power spectrum are analyzed in detail, and then an appropriate baseband signal recovery theory is put forward. Finally, a concurrent dual-band six-port receiver is tested under the long-term evolution signals with 3- and 5-MHz bandwidths. The measured error vector magnitudes are all lower than 2%, which verify the proposed system structure and the signal recovery theory.
A multi-energy X-ray backscatter system for explosives detection (2013)

Most luggage inspection systems are based on X-ray transmission technologies, such as radiography and computed tomography. These techniques have limitations, especially with large or dense objects or objects which are placed close to a wall not allowing access to the rear side for radiography (for instance with abandoned luggage). Portable systems using backscattered X-rays could be an alternative solution when analyzing a suspicious object from one side only, without contact, particularly for homeland security applications. However, portable systems are not currently available. X-ray backscatter imaging, unlike X-ray radiography, reveals low Z materials such as explosives, which may be hidden inside luggage or behind a screen. Specific analysis of backscattered spectra can provide further information about the suspect material in the backscatter image. This can help discriminate between explosive and inert materials. In this article, we detail this discrimination process and the associated developed laboratory prototype. Experimental results are presented, demonstrating the system's performance.
Preliminary in vitro functional analysis of the DEAD‐box protein DDX3 (2012)

DEAD‐box proteins are integral to RNA processing in cells, including the transcription, splicing, export, and translation of messenger RNA, assembly of ribosomes, and chaperoning of RNA folding. The DEAD‐box protein DDX3 (yeast Ded1) is implicated in facilitating transcription, splicing, nuclear export, and translational control, and is additionally thought to potentiate interferon production resulting from cytoplasmic pattern recognition receptor signaling. DDX3 is also hijacked by pathogens including HIV and HCV, transforms breast cells in culture, and is dysregulated in hepatocellular carcinoma. However, little is known regarding the precise mechanism of DDX3 in any of these processes. The aim of this work is to illuminate DDX3 function and regulation using structural and biochemical methods. We present preliminary in vitro reconstitution experiments determining the association of DDX3 with protein cofactors and their functional implications. This work builds a foundation to examine the function of DDX3.
Building Human Capital To Meet the Demands in Well Intervention (2006)

The pace of activity, maturing profiles, incoming workforce expectations, and increasingly focused requirements on the industry’s well intervention needs, is demanding a new approach to building human capital. Today’s challenge is to build the required expertise in a fraction of the time previously available. This paper will provide an overview of current and future skill requirements to determine the most effective way to develop those skills, and a review of on-going programs to develop the required skill levels. Additionally, a review will be completed on the current learning tools as well as the integration of those tools in a comprehensive and accelerated development program.
6‐(3‐Carbamoylbicyclo[2.2.1]hept‐2‐yl)hexansäuren, eine neue Klasse von TxA2‐Antagonisten (1987)

Abstract Die Synthese der Prostanoide 20–27, 40a, b und 45a, b aus den Edukten 1a, b und 31 wird beschrieben. Die bezüglich der 2‐ und 3‐Stellung am Bicyclus beobachteten Konfigurationsänderungen wurden durch 13 C‐NMR‐Spektroskopie geklärt und auch für die Herstellung der vier exo/endo ‐Derivate genutzt. 25 und 26 erwiesen sich als stark wirksame TxA 2 ‐Antagonisten.
Ultra-linear traveling wave tube development (1999)

Summary form only given. Traveling wave tubes (TWT) intended for telecommunications applications are increasingly required to have high linearity and good intermodulation performance, especially for use as modern multi-carrier power amplifiers (MCPA) and in systems that use digital signal encryption. The linearity of a TWT can be improved by optimization of the taper of the helix circuit to reduce the gain compression and phase shift of the output signal as the drive level is increased, and by operation of the tube significantly backed off from saturation in the linear region of the AM/AM and AM/PM transfer curves. However, backed off operation at a given output power level requires increased beam current and power handling capabilities compared to a design operating at saturation, and also results in a greatly reduced efficiency of the TWT. At Hughes, we have developed L-band and S-band TWTs for telecommunication applications that provide good intermodulation performance and high efficiency compared to solid-state amplifiers of similar power levels. To date, the TWTs have produced up to 150 W of continuous output power with an 8-tone continuous-random-phase signal intermodulation level of about -30 dBc and an efficiency of over 20%. At similar power levels, a comparable solid state MCPA has an efficiency well below 10% and nearly twice the cost. These low-frequency communications tubes are normally operated 9 to 10 dB backed off from saturation, and they utilize an optimized helix taper and multi-stage depressed collector design to increase the overall TWT performance and efficiency. The characteristics and intermodulation performance of several TWTs that operate in the 1.5 to 2.4 GHz frequency range will be presented.
ChemInform Abstract: Flash Vacuum Pyrolysis of Sulfonyl‐Stabilized Phosphorus Ylides: Generation and Reactivity of Sulfonyl Carbenes. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
The Genetics of Pituitary Adenomas (2019)

The genetic landscape of pituitary adenomas (PAs) is diverse and many of the identified cases remain of unclear pathogenetic mechanism. Germline genetic defects account for a small percentage of all patients and may present in the context of relevant family history. Defects in <i>AIP</i> (mutated in Familial Isolated Pituitary Adenoma syndrome or FIPA), <i>MEN1</i> (coding for <i>menin</i>, mutated in Multiple Endocrine Neoplasia type 1 or MEN 1), <i>PRKAR1A</i> (mutated in Carney complex), <i>GPR101</i> (involved in X-Linked Acrogigantism or X-LAG), and <i>SDHx</i> (mutated in the so called "3 P association" of PAs with pheochromocytomas and paragangliomas or 3PAs) account for the most common familial syndromes associated with PAs. Tumor genetic defects in <i>USP8</i>, <i>GNAS</i>, <i>USP48</i> and <i>BRAF</i> are some of the commonly encountered tissue-specific changes and may explain a larger percentage of the developed tumors. Somatic (at the tumor level) genomic changes, copy number variations (CNVs), epigenetic modifications, and differential expression of miRNAs, add to the variable genetic background of PAs.
Setting Anchor in the Minor Groove: in Silico Investigation into Formamido N-Methylpyrrole and N-Methylimidazole Polyamides Bound by Cognate DNA Sequences (2010)

Tricyclic N-methylpyrrole (Py) and N-methylimidazole (Im) containing polyamide monocations are known to bind as stacked dimers within the minor groove of DNA, and those with N-terminal formamido (f) substituents bind in a staggered configuration with high specificity over a range of affinities. Although binding constants have been reported, there is not a clear understanding of why such constants vary significantly for polyamide dimers and their respective cognate DNA sequences. By employing computational tools, the following homodimer complexes have been addressed in this study: f-PyPyIm in complex with 5'-d(GAACTAGTTC)-3', f-ImPyPy in complex with 5'-d(GAATGCATTC)-3', and f-ImPyIm in complex with 5'-d(GAACGCGTTC)-3'. These complexes were selected based on their 10- to 100-fold differences in binding constants. From this study, it was possible to determine how polyamides anchor themselves within the minor groove of specific DNA sequences. This is done through several interactions that provide stability for specific recognition: (i) Py groups secure themselves between DNA base pairs, (ii) lone-pair-Π interactions are formed between DNA deoxyribose O4' and Im groups nearest f, (iii) minor groove bases hydrogen bond to Im groups and amides of the polyamide backbone, (iv) f substituents rotate without leaving the minor groove of DNA and with this rotation form specific hydrogen bonds with electron-rich sites on the floor of the minor groove, and (v) flexible charged N,N-dimethylaminoalkyl substituents reside favorably in the minor groove of DNA. Results displayed the greatest amount of interactions and stability for dimer f-ImPyIm in complex with 5'-d(GAACGCGTTC)-3' and the least amount in dimer f-PyPyIm in complex with 5'-d(GAACTAGTTC)-3'. Hence, for cognate DNA sequences, the relative binding strength of compounds was determined as f-ImPyIm > f-ImPyPy > f-PyPyIm. This force-field-based computational study is in agreement with experimental results and provides a molecular rational for the binding constant values.
Antibodies to Influenza A Viruses in Gulls at Delaware Bay, USA (2016)

Gulls are the known reservoir for H13 and H16 influenza A viruses (IAV) but also host a diversity of other IAV subtypes. Gulls also share habitats with both ducks and shorebirds, increasing the potential for cross-species IAV transmission. We serologically tested laughing gulls (Leucophaeus atricilla) collected at Delaware Bay during May when they were in direct contact with IAV-infected shorebirds; both species feed on horseshoe crab (Limulus polyphemus) eggs on beaches during this month. From 2010 to 2014, antibody prevalence as determined by competitive blocking enzyme-linked immunosorbent assay ranged from 25%-72%. Antibodies to H13 and H16 were detected by hemagglutination inhibition (HI) tests in 12% and 24% of tested gulls, respectively. Results from virus microneutralization (MN) tests for antibodies to H1-H12, H14, and H15 varied among years but the highest prevalence of neutralizing antibodies was detected against H1 (24%), H5 (25%), H6 (35%), H9 (33%), and H11 (42%) IAV. The subtype diversity identified by serology in gulls was dominated by Group 1 HA subtypes and only partially reflected the diversity of IAV subtypes isolated from shorebirds.
Reliability Evaluation of Erasure-coded Storage Systems with Latent Errors (2022)

Large-scale storage systems employ erasure-coding redundancy schemes to protect against device failures. The adverse effect of latent sector errors on the Mean Time to Data Loss (MTTDL) and the Expected Annual Fraction of Data Loss (EAFDL) reliability metrics is evaluated. A theoretical model capturing the effect of latent errors and device failures is developed, and closed-form expressions for the metrics of interest are derived. The MTTDL and EAFDL of erasure-coded systems are obtained analytically for (i) the entire range of bit error rates; (ii) the symmetric, clustered, and declustered data placement schemes; and (iii) arbitrary device failure and rebuild time distributions under network rebuild bandwidth constraints. The range of error rates that deteriorate system reliability is derived analytically. For realistic values of sector error rates, the results obtained demonstrate that MTTDL degrades, whereas, for moderate erasure codes, EAFDL remains practically unaffected. It is demonstrated that, in the range of typical sector error rates and for very powerful erasure codes, EAFDL degrades as well. It is also shown that the declustered data placement scheme offers superior reliability.
Rejuvenation of ATP during storage does not reverse effects of the hypothermic storage lesion (2013)

The results of our study demonstrate a cold rejuvenation of RBCs during HS increases intracellular ATP, but that this change does not ameliorate, or exacerbate, the metabolic or biochemical symptoms of the storage lesion.