gebhart/patrepeval huggingface dataset:
Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer (2007)

There is now considerable evidence that using a combination of synthetic progestins and estrogens in hormone replacement therapy (HRT) increases the risk of breast cancer compared with estrogen alone. Furthermore, the World Health Organization has recently cited combination contraceptives, which contain synthetic progestins, as potentially carcinogenic to humans, particularly for increased breast cancer risk. Given the above observations and the current trend toward progestin-only contraception, it is important that we have a comprehensive understanding of how progestins act in the millions of women worldwide who regularly take these medications. While synthetic progestins, such as medroxyprogesterone acetate (MPA), which are currently used in both HRT and oral contraceptives were designed to act exclusively through the progesterone receptor, it is clear from both clinical and experimental settings that their effects may be mediated, in part, by binding to the androgen receptor (AR). Disruption of androgen action by synthetic progestins may have serious deleterious side effects in the breast, where the balance between estrogen signaling and androgen signaling plays a critical role in breast homeostasis. Here, we review the role of androgen signaling in the normal breast and in breast cancer and present new data demonstrating that androgen receptor function can be perturbed by low doses of MPA, similar to doses achieved in serum of women taking HRT. We propose that the observed excess of breast malignancies associated with combined HRT may be explained, in part, by synthetic progestins such as MPA acting as endocrine disruptors to negate the protective effects of androgen signaling in the breast. Understanding the role of androgen signaling in the breast and how this is modulated by synthetic progestins is necessary to determine how combined HRT alters breast cancer risk, and to inform the development of optimal preventive and treatment strategies for this disease.
Elevation of Inner Ear Antibody Levels Following Direct Antigen Challenge of the Endolymphatic Sac (1989)

The effect of direct antigen challenge of the endolymphatic sac (e.sac) on inner ear antibody levels was investigated in guinea pigs. Two weeks following e.sac antigen inoculation, perilymph antibody levels to keyhole limpet hemocyanin (KLH) were found to be significantly elevated in the challenged ear of those animals compared to the unchallenged, opposite ear. Moreover, when the endolymphatic duct (e.duct) in a group of animals were obstructed prior to antigen challenge of their e.sac then the rise in perilymph antibody was prevented. The local accumulation of plasma cells and lymphocytes in the perisaccular space and e.sac lumen was seen following these antigen injections. These experiments suggest that inner ear antibody emanates from the e.sac and reaches the perilymphatic compartment along the route of the e.duct. Furthermore, these findings emphasize the central role of the e.sac in inner ear immunity.
Hydrogen detachment from B<sub>12</sub>H<i><sub>n</sub></i><sup>+</sup> clusters by kinetic energy (2010)

B12H16+ clusters were mainly grown through ion-molecule reactions of the diborane (B2H6) molecules in an external quadrupole static attraction ion trap. The composition of the clusters was confirmed from the mass spectrum. The structure of B12H16+ is considered to be nido structure. When trapped ions collide with neutral molecules, a part of kinetic energy is converted to the internal energy of trapped ion. The mean kinetic energy of trapped ions increased by adding DC voltage of the EQSIT. The analysis of mass spectrum of B12Hn+ clusters showed that the amount of B12H8+ increased. In order to increase the collision rate, He buffer gas was introduced into the EQSIT. As a result, B12H8+ was mainly produced. The required energy to form icosahedral B12Hn+ by the detachment of hydrogen molecule from B12Hn+2+ calculated at PBE0/6-311+G(d)//B3LYP/6-31G(d) level of theory showed that the required energy changes significantly between n≥8 and n≤6. This result explains the experimental result that B12H8+ is mainly produced by increasing kinetic energy of trapped ions.
Axisymmetric waves in dielectric corrugated rods and systems of periodic dielectric rings (2002)

A method for simulating axisymmetric waves of electric and magnetic type in dielectric or magnetic corrugated rods and systems of rings are developed. Such electrodynamic systems are attractive for application in relativistic microwave electronics and fiber optics devices and systems. The method described in this article is based on one-dimensional integral equations of the second kind with kernels having logarithmic singularities. A method is suggested for separating desired solutions from others, whose appearance is typical for problems pertaining to finding the eigenvalues for the integral equations under consideration. The results of the simulation of dispersion properties for dielectric rods with sinusoidal corrugation and a series of dielectric circular rings are presented.
Palladium Thin Films Grown by CVD from (1,1,1,5,5,5‐Hexafluoro‐2,4‐pentanedionato) Palladium(II) (1997)

Abstract The precursor (1,1,1,5,5,5‐hexafluoro‐2,4‐pentanedionato) palladium(II) [Pd(hfac) 2 ] was used to deposit high‐purity, polycrystalline palladium films under low‐pressure CVD conditions at high growth rates (1000–4000 Å/min) over a substrate temperature range of 80–200°C in the presence of H 2 . Mixing of the precursor and H 2 streams near the substrate was required to avoid reactions of the precursor with H 2 at locations other than the substrate surface. Auger electron spectroscopy (AES) showed that the films were impurity free when sufficient H 2 was used. Resistivity values of 20 μΩcm were obtained at the higher deposition temperatures (∼200 °C) while high values of 50 μΩ cm were observed at the lower deposition temperatures (∼ 90 °C). The deposition rate was feed‐rate limited even at the lowest deposition temperatures and highest precursor delivery rates, suggesting that even higher deposition rates could be obtained with higher feed rates. A high precursor conversion of 50–60 % was observed. The high surface reaction probability of Pd(hfac) 2 in the presence of H 2 was reflected qualitatively by trench fill studies which showed a greater film thickness on the top of sub‐micrometer trenches than in the bottom.
Enhancement of Enantioselectivity by THF in Asymmetric Mo‐Catalyzed Olefin Metathesis. Catalytic Enantioselective Synthesis of Cyclic Tertiary Ethers and Spirocycles. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Two-port S-parameter characterization of high electron mobility transistors at millimeter wave and microwave frequencies (2003)

The two-port S-parameters of 0.1- mu m gate length AlGaAs/GaAs high-electron-mobility transistors (HEMTs) at W-band (75 to 115-GHz) frequencies were found using a specially constructed six-port network analyzer. In conjunction with the millimeter-wave measurements, cryogenic microwave characterizations were also performed on 0.25- mu m-gate-length HEMTs (made with similar materials and fabrication technology as the 0.1- mu m HEMTs) to determine the extent to which the frequency range could be increased by cooling. A gas helium refrigerator was used to cool the transistors down to 50 K, and the S-parameters were measured from 2 to 18 GHz with an automatic network analyzer. The maximum available gains of a typical HEMT at room temperature and 50 K are shown. Small-signal transistor models were derived from the measured S-parameters to determine the projected maximum unity-gain frequency, f/sub max/. For this transistor, f/sub max/ increased from 33 to 45 GHz on cooling.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Agile sensor tasking for CoIST using natural language knowledge representation and reasoning (2014)

We describe a system architecture aimed at supporting Intelligence, Surveillance, and Reconnaissance (ISR) activities in a Company Intelligence Support Team (CoIST) using natural language-based knowledge representation and reasoning, and semantic matching of mission tasks to ISR assets. We illustrate an application of the architecture using a High Value Target (HVT) surveillance scenario which demonstrates semi-automated matching and assignment of appropriate ISR assets based on information coming in from existing sensors and human patrols operating in an area of interest and encountering a potential HVT vehicle. We highlight a number of key components of the system but focus mainly on the human/machine conversational interaction involving soldiers on the field providing input in natural language via spoken voice to a mobile device, which is then processed to machine-processable Controlled Natural Language (CNL) and confirmed with the soldier. The system also supports CoIST analysts obtaining real-time situation awareness on the unfolding events through fused CNL information via tools available at the Command and Control (C2). The system demonstrates various modes of operation including: automatic task assignment following inference of new high-importance information, as well as semi-automatic processing, providing the CoIST analyst with situation awareness information relevant to the area of operation.
Characterization of a Novel Human MUTYH Variant Causing Colonic Polyposis through Disruption of the Fe-S Cluster. (2015)

e12514 Background: MUTYH is a human DNA repair enzyme functioning to abscise adenine residues mispaired with 8-oxo-7,8-dihydroguanine (8-oxoG) in oxidatively damaged DNA. This repair activity prevents occurrence of G:C to T:A transversions and subsequent carcinogenesis. MUTYH gene mutations underlie the autosomal, recessive cancer syndrome MUTYH-Associated Polyposis (MAP). MUTYH variants are common, and their interpretation and functional assessment inform patient management. Presently, we report a novel MUTYH variant, c.918C > G (p.C306W), occurring within the protein’s Fe-S cluster region. Functional analysis of the MUTYH Fe-S cluster has not previously been reported. We provide a functional assessment of the c.918C > G MUTYH variant relative to wild type and two well-known MUTYH mutants. Methods: Highly pure wild type, mutant and variant p.C306W MUTYH proteins were prepared with fast protein liquid chromatography (FPLC). Adenine abscission and binding activities were assessed employing capillary electrophoresis and biolayer interferometry (BLI), respectively. Integrity of the Fe-S cluster was determined with inductively coupled plasma-high resolution mass spectroscopy (ICP-HRMS). Results: The novel p.C306W MUTYH variant exhibited severe compromise of abscission and DNA binding activity. Furthermore, the Fe-S cluster of the p.C306W variant was nearly completely lacking in iron content. Conclusions: This investigation establishes the pathologic status of the MUTYH variant c.918C > G which contributes to the MAP phenotype. Additionally, this study, for the first time, investigates the Fe-S cluster region in MUTYH DNA repair and documents this region as an essential functional domain required for repair activity.
Design and Synthesis of Orally Bioavailable Benzimidazole Reverse Amides as Pan RAF Kinase Inhibitors (2014)

Benzimidazole reverse amides were designed and synthesized as Pan RAF kinase inhibitors. Investigation of the structure-activity relationship of the compounds revealed that they were potent in vitro and exhibited desirable in vivo properties.
Noise generated from two flat plates in tandem configuration in turbulent mean flow (2023)

View Video Presentation: https://doi.org/10.2514/6.2023-3507.vid This work is a fundamental investigation of the noise radiated by two flat plates in a tandem configuration in a turbulent flow. It is shown that this configuration is capable of significantly reducing turbulence-aerofoil interaction noise at low frequencies. The current study presents far-field noise experimental data and detailed high-resolution numerical simulations based on a spanwise vortex impinging on a flat-plate aerofoil at a zero angle of attack. The noise reduction spectra of tandem plates exhibit peaks of strong noise reduction at non-dimensional frequencies of $fl_d/U_c=n$, where $l_d$ is the distance between the leading edges of the two flat plates, $U_c$ is the convection velocity and $n$ is an integer. It is proposed that these are caused by interference between the two leading edges radiating with a phase shift of 180$^\circ$. In addition to the edge-to-edge interference, it is found that noise reductions are also caused by an effective shortening of the chord which leads to generally weaker radiation. These two mechanisms were recently proposed by the authors for aerofoils with downstream porosity and are investigated numerically in detail here for the case of flat plates in tandem configuration.
Power-law Kinetics and Determinant Criteria for the Preclusion of\n Multistationarity in Networks of Interacting Species (2012)

We present determinant criteria for the preclusion of non-degenerate multiple\nsteady states in networks of interacting species. A network is modeled as a\nsystem of ordinary differential equations in which the form of the species\nformation rate function is restricted by the reactions of the network and how\nthe species influence each reaction. We characterize families of so-called\npower-law kinetics for which the associated species formation rate function is\ninjective within each stoichiometric class and thus the network cannot exhibit\nmultistationarity. The criterion for power-law kinetics is derived from the\ndeterminant of the Jacobian of the species formation rate function. Using this\ncharacterization we further derive similar determinant criteria applicable to\ngeneral sets of kinetics. The criteria are conceptually simple, computationally\ntractable and easily implemented. Our approach embraces and extends previous\nwork on multistationarity, such as work in relation to chemical reaction\nnetworks with dynamics defined by mass-action or non-catalytic kinetics, and\nalso work based on graphical analysis of the interaction graph associated to\nthe system. Further, we interpret the criteria in terms of circuits in the\nso-called DSR-graph\n
Design rules for a capillary gripper in microassembly (2006)

The specificities of microassembly allow to turn oneself to new, and already validated, handling principles like capillary forces. This paper aims at quantifying the influence of major parameters like surface tension, contact angles, gripper geometry, volume of liquid, handling strategy, etc. Therefore, it presents both the numerical and the experimental methodologies that have been used in order to extract design rules of a capillary gripper, to improve the picking capacities on the one hand and the releasing strategies on the other hand
New organic nitrates. II. Synthesis of 2H‐pyrido[2,3‐e]‐1,3‐oxazine‐2,4(3H)‐diones, 2H‐pyrido[4,3‐e]‐1,3‐oxazine‐2,4(3H)‐diones, 2H‐pyrido[4,3‐e]‐1,3‐oxazin‐4(3H)‐ones, 2H‐thieno[2,3‐e]‐1,3‐oxazin‐4(3H)‐ones and 2H‐thieno[3,4‐e]‐1,3‐oxazin‐2,4(3H)‐diones (1995)

Abstract The preparation and the physico‐chemical characterization of 2 H ‐pyrido[2,3‐ e ]‐1,3‐oxazine‐2,4(3 H )‐diones, 2 H ‐pyrido[4,3‐ e ]‐1,3‐oxazine‐2,4(3 H )‐diones, 2 H ‐pyrido[4,3‐ e ]‐1,3‐oxazin‐4(3 H )‐ones, 2 H ‐thieno[2,3‐ e ]‐1,3‐oxazin‐4(3 H )‐ones and 2 H ‐thieno[3,4‐ e ]‐1,3‐oxazine‐2,4(3 H )‐diones are reported.
Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review (2015)

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader.
Ultrasound Images For Accurate Epidural Needle Insertion (2017)

This work presents development and testing of image processing algorithms for the automatic detection of landmarks within ultrasound images. The aim was to automate ultrasound analysis, for use during the process of epidural needle insertion. For epidural insertion, ultrasound is increasingly used to guide the needle into the epidural space. Ultrasound can improve the safety of epidural and was recommended by the 2008 NICE guidelines (National Institute for Health and Care Excellence). Without using ultrasound, there is no way for the anaesthetist to observe the location of the needle within the ligaments requiring the use of their personal judgment which may lead to injury. If the needle stops short of the epidural space, the anaesthetic is ineffective. If the needle proceeds too deep, it can cause injuries ranging from headache, to permanent nerve damage or death. Ultrasound of the spine is particularly difficult, because the complex bony structures surrounding the spine limit the ultrasound beam acoustic windows. Additionally, the important structures for epidural that need to be observed are located deeper than other conventional procedures such as peripheral nerve block. This is why a low frequency, curved probe (2-5 MHz) is used, which penetrates deeper but decreases in resolution. The benefits of automating ultrasound are to enable real-time ultrasound analysis on the live video, mitigate human error, and ensure repeatability by avoiding variation in perception by different users.
A SU2C catalyst randomized phase II trial of pembrolizumab with or without paricalcitol in patients with stage IV pancreatic cancer who have been placed in best possible response. (2018)

TPS4154 Background: Pancreatic cancer remains a deadly disease and despite advances in chemotherapy treatment, survival for most patients is still less than one year. Refractory pancreatic cancer has not been responsive to checkpoint inhibitors and only in the small population of MSI high pancreatic cancers have we seen activity. The microenvironment plays an important role in limiting the immune response and researchers from the Salk Institute demonstrated that vitamin D receptor agonists sensitize both primary and metastatic pancreatic cancer lesions to checkpoint blockade. Our trial evaluates the role of maintenance immunotherapy and paricalcitol after best response to cytotoxic chemotherapy. Methods: This SU2C Catalyst trial will be conducted at Honor Health Research Institute, City of Hope National Medical Center and University of California San Diego Moores Cancer Center. Patients with metastatic pancreatic cancer receiving standard first line chemotherapy are eligible to be randomized after achieving best response defined as stable disease or partial response for 2 months with no further shrinkage of ≥ 20% on scan and no further decrease of ≥ 10% in the tumor markers while on chemotherapy. Patients with a serum vitamin D level ≥ 50 ng/mL are excluded. The primary endpoint of this study is to estimate the percentage of patients progressing at 6 months while on maintenance therapy. Secondary objectives evaluate the toxicity of the combination, overall survival and tumor mutational landscape. Twenty-four patients are planned to be randomized 1:1 to either pembrolizumab 200 mg every 3 weeks plus paricalcitol 25 mcg 3 times per week or pembrolizumab plus placebo. Archival tumor tissue is required and optional biopsies are allowed to further explore biomarkers of response to therapy. ClinicalTrials.gov Identifier: NCT03331562 Support: Stand Up To Cancer (SU2C) Catalyst Merck Grant Clinical trial information: NCT03331562.
Intravascular OCT polarimetry: Progress, prospects, and challenges (2022)

Intravascular polarimetry with optical coherence tomography measures polarization effects arising from tissue anisotropy. This affords insight into the microstructure and physical orientation of collagen or smooth muscle cells and provides metrics to quantify scattering properties of lipid-rich plaques. We present insights from clinical pilot studies with intravascular polarimetry, discuss its prospects for improving our mechanistic understanding of plaque progression and help patient management, and explain our progress with alleviating the hardware requirements to enable intravascular polarimetry.
Genetic causes of hearing loss at children (2015)

Hearing loss is a major public health problem, with an incidence of about 1 in 1,000 newborns. The causes which determine the loss of hearing are multiple and can be of genetic or non-genetic causes. Among child hearing loss, 50% are caused by genetic causes. A significant importance is given to the GJB2 (connexin 26) gene which is responsible for more than half of causes of hearing loss determined by genetic factors. The authors expose an overview of the main significant genetic factors for the hearing loss at pediatric population.
Parallel synthesis with fluorous reagents and reactants (1999)

Fluorous reagents and reactants provide emerging new options in parallel synthesis because they are easily prepared, reacted, and then separated from the desired reaction products. Some background information on fluorous reaction and separation techniques is provided, and the utility of fluorous reagents and reactants is illustrated with a number of case studies that feature both liquid-liquid and solid-solid separations.
Lentiviral vector induces high-quality memory T cells via dendritic cells transduction (2021)

We report a lentiviral vector harboring the human β2-microglobulin promoter, with predominant expression in immune cells and minimal proximal enhancers to improve vector safety. This lentiviral vector efficiently transduces major dendritic cell subsets in vivo. With a mycobacterial immunogen, we observed distinct functional signatures and memory phenotype in lentiviral vector- or Adenovirus type 5 (Ad5)-immunized mice, despite comparable antigen-specific CD8<sup>+</sup> T cell magnitudes. Compared to Ad5, lentiviral vector immunization resulted in higher multifunctional and IL-2-producing CD8<sup>+</sup> T cells. Furthermore, lentiviral vector immunization primed CD8<sup>+</sup> T cells towards central memory phenotype, while Ad5 immunization favored effector memory phenotype. Studies using HIV antigens in outbred rats demonstrated additional clear-cut evidence for an immunogenic advantage of lentiviral vector over Ad5. Additionally, lentiviral vector provided enhance therapeutic anti-tumor protection than Ad5. In conclusion, coupling lentiviral vector with β2-microglobulin promoter represents a promising approach to produce long-lasting, high-quality cellular immunity for vaccinal purposes.
Evaluation of hypotensive mechanisms of Captopril in addition to its inhibition of the converting enzyme in spontaneously hypertensive rats. (1982)

In spontaneoulsy hypertensive rats (SHR), the hypotensive effect of captopril (30 mg/kg/day per os for 4 days), which inhibits the converting enzyme when given orally was significantly potentiated rather than suppressed by aprotonin (100,000 KIU/day s.c. for 7 days), but was not affected by indomethacin. These findings suggest that neither the kallikrein-kinin system nor the prostaglandin system is involved in any of the hypotensive actions of captopril in SHR other than the inhibition of the converting enzyme.
Mechanisms of Ion Diffusion as a Function of Microstructure in Ionomer Melts (2019)

Abstract not provided.