gebhart/patrepeval huggingface dataset:
Abstract 638: Novel Role of 4-Hydroxy-2-Nonenal Mediated Mitochondrial Stress Signaling in Ischemia and Reperfusion Injury (2017)

Myocardial infarction is the single most prevalent cause of morbidity and mortality among adults. Excess generation of reactive oxygen species plays a major role in the cellular response to cardiac ischemia/reperfusion (I/R) injury. Accumulated evidence indicates that oxidative stress in mitochondria plays an important role in I/R injury, but how mitochondrial redox mechanisms are involved in cardiac dysfunction remains unclear. Manganese Superoxide Dismutase (MnSOD), an antioxidant enzyme that catalyzes the conversion of superoxide radicals (O 2 •-) in mitochondria. The absence of SOD2 (a gene that encodes MnSOD) is found to be embryonic lethal in animal models due to impairment of mitochondrial function, most noticeably in the heart. In our investigation, we found MnSOD mimetic, MnTnBuOE-2-PyP 5+ distributed 3-fold more in mitochondria than in cytosol. The exceptional ability of MnTnBuOE-2-PyP 5+ to dismute O 2 •- parallels its ability to reduce ONOO– and CO3–. Based on our initial results, we have generated mice that specifically lack MnSOD in cardiomyocytes (Mhy6-SOD2 Δ ). These mice showed early mortality ~6 months due to cardiac mitochondrial dysfunction. FACS analyses using Mito-Tracker Green indicated that the mass of mitochondria per cell was slightly decreased in the Mhy6-SOD2 Δ to the wild type. We then examined oxidative phosphorylation levels in Mhy6-SOD2 Δ v.s. wild type using a Seahorse XF analyzer. The rate of oxygen consumption per cells was significantly lower in Mhy6-SOD2 Δ cardiomyocytes than that in wild type. The most noticeable difference in the O 2 consumption was found in the presence of FCCP (H+ ionophore/uncoupler). 4-hydroxy-2-nonenal (HNE) adduction of mitochondrial apoptosis-inducing factor (AIFm2) inactivates the NADH oxidoreductase activity of AIFm2 and facilitates its translocation from mitochondria. His 174 on AIFm2 is the critical target of HNE adduction that triggers this functional switch. HNE adduction and translocation of AIFm2 from mitochondria following I/R injury are attenuated by superoxide dismutase mimetics. These results identify a previously unrecognized role of the MnSOD-HNE-AIFm2 axis, with important consequences for mitochondrial stress signaling, especially in cardiac I/R injury.
Use of an ex vivo multiplexed signal pathway inhibitor treatment to reveal sensitivity of myeloma and nonmyeloma bone marrow cell populations. (2010)

e18532 Background: Myeloma cells are admixed with normal cells in the bone microenvironment. A great need exists to understand the differential effect of treatment on myeloma as well as the non-myeloma cells. We designed a study to rapidly screen ex vivo treatment combinations to predict treatment efficacy. Methods: A panel of signal pathway inhibitor treatments was applied to fresh bone marrow aspirate samples from patients undergoing standard of care hematological work up for multiple myeloma. Bone marrow aspirates (n=22 to date), not required for diagnosis, were immediately subdivided and treated ex vivo with a panel of molecular targeted inhibitors, including combinations thereof, that target a wide range of cellular pathways (autophagy, proteosome, angiogenesis, protein degradation, proliferation/survival, insulin response, and translation). Up to 48 different treatment conditions could be studied for an aspirate volume of 5mL. After 8 hours incubation the samples were placed in a preservative that suppresses fluctuations in kinase pathway proteins. CD138 positive cells (plasma cells) were separated from CD138 negative cells via immunomagnetic sorting. Reverse phase protein microarrays were used to quantitatively map up to 75 cell signaling pathway endpoints in both cell populations. Results: Accrual has included untreated patients with MGUS, smoldering myeloma, treatment naïve, or advanced stage pre-treated myeloma. Individual samples and disease stages differed widely at the level of cellular signaling in response to ex vivo treatment and combination of drug treatments. In some samples specific kinase inhibitors were found to suppress their expected targets to a higher degree in CD138 positive vs CD138 negative cells. In other samples the same inhibitor was associated with compensatory activation of down stream pathways. However, in many cases the specific inhibitor had a much greater effect on the non-CD138 positive cells compared to the CD138 positive cells. Conclusions: Choices for individualized and/or combination therapy should take into consideration the differential effect of therapy on the non-myeloma cells compared to the myeloma cells. No significant financial relationships to disclose.
ChemInform Abstract: Facile Reduction of Malonate Derivatives Using NaBH4/Br2: An Efficient Route to 1,3‐Diols. (2008)

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.
Data from Inhibition of Mammalian Target of Rapamycin Is Required for Optimal Antitumor Effect of HER2 Inhibitors against HER2-Overexpressing Cancer Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; A significant fraction of HER2-overexpressing breast cancers exhibit resistance to the HER2 antibody trastuzumab. Hyperactivity of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway confers trastuzumab resistance, and mammalian target of rapamycin (mTOR) is a major downstream effector of PI3K/AKT. Therefore, we examined whether mTOR inhibitors synergize with trastuzumab.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Immunocompetent mice bearing HER2&lt;sup&gt;+&lt;/sup&gt; mammary tumors were treated with trastuzumab, the mTOR inhibitor rapamycin, or the combination. Mice were imaged for tumor cell death using an optical Annexin-V probe and with [&lt;sup&gt;18&lt;/sup&gt;F]FDG positron emission tomography. The signaling and growth effects of the mTOR inhibitor RAD001 on HER2&lt;sup&gt;+&lt;/sup&gt; cells treated with trastuzumab or lapatinib were evaluated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Treatment of mice with trastuzumab plus rapamycin was more effective than single-agent treatments, inducing complete regression of 26 of 26 tumors. The combination induced tumor cell death (Annexin-V binding) and inhibited FDG uptake. Rapamycin inhibited mTOR and tumor cell proliferation as determined by phosphorylated S6 and Ki-67 immunohistochemistry, respectively. In culture, the combination of RAD001 plus trastuzumab inhibited cell growth more effectively than either drug alone. Trastuzumab partially decreased PI3K but not mTOR activity. Knockdown of &lt;i&gt;TSC2&lt;/i&gt; resulted in HER2-independent activation of mTOR and dampened the response to trastuzumab and lapatinib. Treatment with the HER2 inhibitor lapatinib decreased phosphorylated S6 and growth in &lt;i&gt;TSC2&lt;/i&gt;-expressing cells but not in &lt;i&gt;TSC2&lt;/i&gt;-knockdown cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Inhibition of PI3K and mTOR are required for the growth-inhibitory effect of HER2 antagonists. These findings collectively support the combined use of trastuzumab and mTOR inhibitors for the treatment of HER2&lt;sup&gt;+&lt;/sup&gt; breast cancer. (Clin Cancer Res 2009;15(23):7266–76)&lt;/p&gt;&lt;/div&gt;
Enhanced Nucleation of Atomic Layer Deposited Contacts Improves Operational Stability of Perovskite Solar Cells in Air (2019)

Abstract Metal‐halide perovskites show promise as highly efficient solar cells, light‐emitting diodes, and other optoelectronic devices. Ensuring long‐term stability is now a major priority. In this study, an ultrathin (2 nm) layer of polyethylenimine ethoxylated (PEIE) is used to functionalize the surface of C 60 for the subsequent deposition of atomic layer deposition (ALD) SnO 2 , a commonly used electron contact bilayer for p–i–n devices. The enhanced nucleation results in a more continuous initial ALD SnO 2 layer that exhibits superior barrier properties, protecting Cs 0.25 FA 0.75 Pb(Br 0.20 I 0.80 ) 3 films upon direct exposure to high temperatures (200 °C) and water. This surface modification with PEIE translates to more stable solar cells under aggressive testing conditions in air at 60 °C under illumination. This type of “built‐in” barrier layer mitigates degradation pathways not addressed by external encapsulation, such as internal halide or metal diffusion, while maintaining high device efficiency up to 18.5%. This nucleation strategy is also extended to ALD VO x films, demonstrating its potential to be broadly applied to other metal oxide contacts and device architectures.
Systematic Study of Causes of Death and Allograft Loss After Pancreas Transplantation in the Modern Era. (2014)

Background: The aim of the study is to identify specific causes of mortality and pancreas allograft loss of the three pancreas transplantation (PT) types in the modern era with ATG induction and tacrolimus based triple immunosuppression. Methods: We performed a retrospective review of 262 adult patients who received PT at our institution from 01/01/1998 to 12/31/2009. The causes of death and graft loss were determined by reviewing clinical and histologic information. Results:89 recipients from the cohort died during the median follow-up of 8 years (IQR 4.1 to 11.2 years). The most common causes of death were infection/sepsis (20%) and cardio/cerebrovascular disease (25 %). Among patients that died, the cause of death was not different among the three PT types (p=0.50). 133 of 279 (48%) grafts were lost, and 10 recipients (4%) lost more than one allograft. Graft losses due to death with a functioning graft (DWF)(37%) and graft thrombosis (17% early and 7% late) were the most common causes. Within the first year post PT, early thrombosis was the most common cause of all graft loss (53%). Immunologic factors became most common causes censoring for death beyond one year post PT (50%). Graft survival was higher in Simultaneous Pancreas Kidney transplantation (SPK) than that in Pancreas transplantation alone (PTA) or Pancreas after kidney transplantation (PAK) recipients, most likely because of the relative low incidence of DWF and graft loss due to immunologic factors in SPK recipients. Conclusion: PT may not change the distribution of underlying causes of death in patients with long-standing diabetes. Early thrombosis and rejection remain the main targets in our efforts to improve long term pancreas allograft survival.
Polyglycerol Surfmers and Surfactants for Direct and Inverse Miniemulsion (2017)

Poly(ethylene glycol)-based surfactants are a prominent example for nonionic surfactants. Poly(glycerol) (PG) is discussed as a polyfunctional alternative, however, it is not yet used to stabilize miniemulsions. The anionic polymerization of glycidyl ethers is used to prepare surfactants for direct or inverse emulsions and ambident surfactants by adjusting the copolymer composition. Orthogonal-protected poly(glycerol) block copolymers, using ethoxyethyl glycidyl ether and allyl glycidyl ether (AGE) or tert-butyl glycidyl ether (tBuGE), are synthesized. After cleavage of the acetal groups, these all-polyglycerol surfactants (PG-b-PtBuGE) or multifunctional surfmers (PG-b-PAGE), are used in direct and inverse miniemulsion polymerizations. Polystyrene nanoparticles are obtained by free-radical miniemulsion polymerization, in which the allyl-functionalized copolymers act as surfmer. In inverse miniemulsion, hydroxyethyl starch nanocarriers are synthesized with PG-b-PAGE as surfmer, transferred into aqueous PG-b-PtBuGE solution, and functionalized by thiol-ene addition. The PG-b-PtBuGE with equal block length ratio is used as a surfactant for direct and inverse miniemulsions. With the PG being covalently bound to the nanocarriers, a desorption during protein adsorption does not occur. It is believed that these surfactants are promising alternatives to conventional surfactants with additional functionality.
Staphylococcus aureus Clumping Factor A Remains a Viable Vaccine Target for Prevention of S. aureus Infection (2016)

In a recent article, X. Li et al. [mBio 7(1):e02232-15, 2016, http://dx.doi.org/10.1128/mBio.02232-15] investigate the utility of a vaccine composed of the Staphylococcus aureus protein clumping factor A (ClfA) in protecting mice from S. aureus infection. ClfA, one of the first proteins to be identified as a potential vaccine antigen for S. aureus prophylaxis, is currently a component of several investigational vaccines. The authors conclude that ClfA may not be effective for S. aureus prophylaxis. In contrast, previously published papers reporting positive data suggested that ClfA was potentially an important vaccine target to prevent invasive S. aureus disease. This commentary addresses the observed differences between the findings of Li et al. and those from other publications, highlighting the importance for preclinical vaccine antigen assessments to reflect the biological role of said antigen in virulence and, consequently, the importance of choosing appropriate preclinical disease models to test such antigens.
Open-Label Study to Evaluate the Safety & Tolerability of Telaprevir in Combination with Sofosbuvir in Naive Subjects with HCV Genotype 1 Short Title: Telaprevir & Sofosbuvir in HCV Genotype 1 (2015)

Background & Aims : Sofosbuvir is a potent hepatitis C NS5B polymerase inhibitor that has led to high-sustained viral response rates when combined with other direct-acting antivirals. To date, no data exists on the combination of sofosbuvir with the NS3 protease inhibitor, telaprevir. The safety, tolerability, and efficacy of an all-oral 12-week regimen of telaprevir in combination with sofosbuvir were evaluated in this open-label, phase 2 study. Methods: Twenty adults with genotype 1 hepatitis C infection who were non-cirrhotic and naive to therapy received telaprevir 1125 mg orally twice-daily plus sofosbuvir 400 mg once daily for 12 weeks. Results : Telaprevir plus sofosbuvir was generally well tolerated, with all 20 subjects completing treatment. The five most common adverse events were nausea, rash, headache, ano-rectal symptoms, and pruritus. Two subjects required discontinuation of telaprevir after week 4 but were maintained on sofosbuvir till the end of treatment. Sustained virologic response 12 weeks after the end of treatment was 95%. Conclusion : The results provide valuable information regarding the safety, tolerability and efficacy of telaprevir combined with sofosbuvir as dual therapy in naive non-cirrhotic genotype 1 patients.
Finite-state models for speech-based search on mobile devices (2011)

Abstract In this paper, we present techniques that exploit finite-state models for voice search applications. In particular, we illustrate the use of finite-state models for encoding the search index in order to tightly integrate the speech recognition and the search components of a voice search system. We show that the tight integration mutually benefits Automatic Speech Recognition and improves the search. In the second part of the paper, we discuss the use of finite-state techniques for spoken language understanding, in particular, to segment an input query into its component semantic fields so as to improve search as well as to extend the functionality of the system and be able to execute the user's request against a backend database.
Electrooptic effect calculations: simplified procedure for arbitrary cases (1988)

To aid in the design of electrooptic devices, a simplified procedure is introduced for determining the principal indices of refraction and the orientations of the index ellipsoid when an electric field is applied. The approach employs the general Jacobi method, and it is applicable to an arbitrary isotropic, uniaxial, or biaxial crystal class with an arbitrary direction of applied field. It includes a straightforward approach for labeling the new principal dielectric axes so as to produce the minimum global rotation of the ellipsoid from the zerofield principal dielectric axes. The necessary calculations can be easily implemented with a pocket calculator and are often found to be more accurate than those obtained with larger computers using standard library math packages. Furthermore, for analyzing device performance, simple analytic expressions for the orientations of the fast and slow polarization axes and the fast and slow indices of refraction are derived for a given arbitrary direction of optical propagation and any arbitrary direction of applied electric field. The calculational procedure is applicable to linear and quadratic electrooptic effects and the photoelastic effect in isotropic, uniaxial, and biaxial crystals. Illustrative examples for GaAs, LiNbO(3), and KDP are presented.
Interference Mitigation for WLAN Devices Using Spectrum Sensing (2008)

The concept of spectrum sensing is, in the broad sense, the ability to detect and interpret other signals in the band and take appropriate actions by implementing adaptive techniques in the upper layers in addition to traditional interference cancellation techniques applied in the PHY layer. In this paper we present algorithms to detect interference from microwave oven for WLAN devices in the 2.4 GHz spectrum and methods to mitigate the impact from the interference. The concept can be extended to other coexistence issues as well as spectrum sharing between primary and secondary users.
Dielectric function of a model insulator (1993)

We have calculated a dielectric response function \ensuremath{\epsilon}(q,\ensuremath{\omega}) using the random-phase approximation for a model insulator originally proposed by Fry [Phys. Rev. 179, 892 (1969)]. We treat narrow and wide band-gap insulators for the purpose of using results in the simulation of secondary-electron emission from insulators. Therefore, it is important to take into account the contribution of the first and second conduction bands. For the real part of the dielectric function we perform a numerical principal value integration over the first and second Brillouin zone. For the imaginary part we perform a numerical integration involving the \ensuremath{\delta} function that results from the conservation of energy. In order to check the validity of our numerical integration methods we perform a Kramers-Kronig transform of the real part and compare it with the directly calculated imaginary part and vice versa. We discuss fitting the model to the static dielectric constant and the f-sum rule. Then we display the wave number and frequency dependence for solid argon, KCl, and model Si.
Alkanethiol self-assembled monolayers as the dielectric of capacitors with nanoscale thickness (1998)

Alkanethiol self-assembled monolayers (SAMs) on a mercury surface are used to build a junction consisting of two opposing mercury surfaces with interposed SAMs: Hg-SAM/SAM-Hg. The liquid mercury surface provides a support for the SAM that is smooth, compliant, free of defects, and without the incommensurate lattice properties that characterize solid metal surfaces. The thickness of the dielectric (∼30–90 Å) in this junction can be easily changed by using alkanethiols with different lengths. From capacitance measurements, a dielectric constant of 2.7±0.3 is calculated for the SAMs. The conductivity of SAMs on the Hg surface is σ=6±2×10−15 Ω−1 cm−1, a value close to that of bulk polyethylene. The junction sustains an electric field of 6 MV/cm.
Syntheses and Crystal Structures of dmso‐Coordinated Tungstoantimonates(III) and ‐bismuthates(III) (2009)

Abstract Four new organic–inorganic hybrid compounds based on dmso‐coordinated heteropolytungstates as [Ru(bpy) 3 ] 2+ (Rubpy) salts {[Ru(bpy) 3 ] 2 Na 2 [Sb 2 W 22 (dmso) 4 O 72 ] · 4dmso · 4H 2 O ( 1a ), [Ru(bpy) 3 ] 2 Na 2 [Bi 2 W 22 (dmso) 4 O 72 ] · 4dmso · 4H 2 O ( 2a ), [Ru(bpy) 3 ] 2 [Sb 2 W 20 Fe 2 (dmso) 8 O 68 ] · 9dmso · 12H 2 O ( 3a ), [Ru(bpy) 3 ] 2 [Bi 2 W 20 Fe 2 (dmso) 8 O 68 ] · 9dmso · 12H 2 O ( 4a )} have been synthesized and characterized by IR spectroscopy, elemental analysis, thermogravimetry, cyclic voltammetry, X‐ray powder diffraction and single‐crystal X‐ray diffraction. The structural analyses indicate that the dmso molecules are coordinated onto the polyanion frameworks through four W–O–S(CH 3 ) 2 bonds for 1a and 2a , six Fe–O–S(CH 3 ) 2 and two W–O–S(CH 3 ) 2 bonds for 3a and 4a . The compounds 1a – 4a represent novel members of dmso‐coordinated tungstoantimonates and tungstobismuthates prepared by routine synthetic reactions in the mixed solutions with dmso/H 2 O (1:1, v/v). The cyclic voltammetry studies of 1a – 4a in dmso/H 2 SO 4 medium using the glassy carbon electrode as a working electrode show the respective electrochemical behaviors of the W and Ru centers within 1a and 2a , and the W, Fe and Ru centers within 3a and 4a .(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions (2013)

The E3 transcription unit of human adenoviruses (Ads) encodes immunomodulatory proteins. Interestingly, the size and composition of the E3 region differs considerably among Ad species, suggesting that distinct sets of immunomodulatory E3 proteins may influence their interaction with the human host and the disease pattern. However, to date, only common immune evasion functions of species C E3 proteins have been described. Here we report on the immunomodulatory activity of a species D-specific E3 protein, E3/49K. Unlike all other E3 proteins that act on infected cells, E3/49K seems to target uninfected cells. Initially synthesized as an 80- to 100-kDa type I transmembrane protein, E3/49K is subsequently cleaved, with the large ectodomain (sec49K) secreted. We found that purified sec49K exhibits specific binding to lymphoid cell lines and all primary leukocytes, but not to fibroblasts or epithelial cells. Consistent with this binding profile and the molecular mass, the sec49K receptor was identified as the cell surface protein tyrosine phosphatase CD45. Antibody-blocking studies suggested that sec49K binds to the membrane proximal domains present in all CD45 isoforms. Functional studies showed that sec49K can suppress the activation and cytotoxicity of natural killer cells as well as the activation, signaling, and cytokine production of T cells. Thus, we have discovered an adenovirus protein that is actively secreted and describe immunomodulatory activities of an E3 protein uniquely expressed by a single Ad species.
Sequential events in the pathogenesis of streptococcal cell wall-induced arthritis and their modulation by bis(5-amidino-2-benzimidazolyl)methane (BABIM). (1990)

This report builds on the authors' earlier discovery of bis(5-amidino-2-benzimidazolyl)methane (BABIM) as a strong suppressive agent for streptococcal cell wall fragment-induced arthritis in the Lewis rat. As a synthetic inhibitor of trypsinlike proteases, BABIM opens up a new route to the control of inflammatory joint disease. To gain a deeper insight into the function of the compound, the authors have now studied its influence on the sequential development of the joint changes and the associated lesions in spleen and liver. Bis(5-amidino-2-benzimidazolyl)methane is shown to block acute synovitis, to retard and reduce granuloma formation in spleen and liver, to decrease neutrophilic leukocytosis, and to diminish hemopoietic hyperplasia in the bone, and thus also to mitigate the distinctive osteoclastic and chondroclastic events. The compound does not interfere with the splenic immune response, the temporary rise in hepatocytic mitotic activity, or the organ deposition of streptococcal cell walls.