gebhart/patrepeval huggingface dataset:
Single-Molecule Magnet with True Axial Symmetry (2013)

The synthesis and properties are reported of a rare example of a Mn12 single-molecule magnet (SMM) in truly axial symmetry (tetragonal, I4 (Mn12O12(O2CCH2Bu t )16(MeOH)4)·MeOH (3·MeOH) was synthesized by carboxylate substitution on (Mn12O12(O2CMe)16(H2O)4)·2MeCO2H·4H2 O( 1). The complex was found to possess an S = 10 ground state, as is typical for the Mn12 family, and displayed both frequency-dependent out-of-phase AC susceptibility signals and hysteresis loops in single-crystal magnetization vs DC field sweeps. The loops also exhibited quantum tunneling of magnetization steps at periodic field values. Single-crystal, high-frequency electron paramagnetic resonance spectra on 3·MeOH using frequencies up to 360 GHz revealed perceptibly sharper signals than for 1. Moreover, careful studies as a function of the magnetic field orientation did not reveal any satellite peaks, as observed for 1, suggesting that the crystals of 3 are homogeneous and do not contain multiple Mn12 environments. In the single-crystal 55 Mn NMR spectrum in zero applied field, three well- resolved peaks were observed, which yielded hyperfine and quadrupole splitting at three distinct sites. However, observation of a slight asymmetry in the Mn 4+ peak was detectable, suggesting a possible decrease in the local symmetry of the Mn 4+ site. Spin− lattice (T1) relaxation studies were performed on single crystals of 3·MeOH down to 400 mK in an effort to approach the quantum tunneling regime, and fitting of the data using multiple functions was employed. The present work and other recent studies continue to emphasize that the new generation of truly high-symmetry Mn12 complexes are better models for thorough investigation of the physical properties of SMMs than their predecessors such as 1.
Data from Intrinsic Resistance to Immune Checkpoint Blockade in a Mismatch Repair–Deficient Colorectal Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;Immunotherapy with checkpoint inhibitors, such as the programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab, are effective in a variety of tumors, yet not all patients respond. Tumor microsatellite instability-high (MSI-H) has emerged as a biomarker of response to checkpoint blockade, leading to the tissue agnostic approval of pembrolizumab in MSI-H cancers. Here we describe a patient with MSI-H colorectal cancer that was treated with this immune checkpoint inhibitor and exhibited progression of disease. We examined this intrinsic resistance through genomic, transcriptional, and pathologic characterization of the patient's tumor and the associated immune microenvironment. The tumor had typical MSI-H molecular features, including a high neoantigen load. We also identified biallelic loss of the gene for β&lt;sub&gt;2&lt;/sub&gt;-microglobulin (&lt;i&gt;B2M&lt;/i&gt;), whose product is critical for antigen presentation. Immune infiltration deconvolution analysis of bulk transcriptome data from this anti-PD-1–resistant tumor and hundreds of other colorectal cancer specimens revealed a high natural killer cell and M2 macrophage infiltration in the patient's cancer. This was confirmed by single-cell transcriptome analysis and multiplex immunofluorescence. Our study provides insight into resistance in MSI-H tumors and suggests immunotherapeutic strategies in additional genomic contexts of colorectal cancer.&lt;/p&gt;&lt;/div&gt;
Effect of Pretreatment of Intact `Gala' Apple with Ethanol Vapor, Heat, or 1-Methylcyclopropene on Quality and Shelf Life of Fresh-cut Slices (2004)

`Gala' apples [ Malus silvestris (L.) var. domestica (Borkh.) Mansf.] were treated with ethanol vapor (5 mL·kg -1 fruit for 24 hours at 25 °C), heat (4 days at 38 °C and &gt;98% RH), or 1-methylcyclopropene (1-MCP; 1 or 0.625 μL·L -1 for 18 hours at 20 °C) before processing into slices, then dipped in anti-browning solutions or coatings, drained, and packaged in perforated polyethylene bags. Residual effects of pretreatments on fresh-cut slice physiological and quality attributes were investigated during storage for up to 19 days at 5.5 °C. Ethylene production was reduced by ethanol, heat, and 1-MCP pretreatments, while ethanol and heat also reduced slice respiration. Heat and 1-MCP pretreatments inhibited slice texture changes, while ethanol had no effect on instrumental texture measurements but reduced sensory firmness. Ethanol pretreatment increased the contents of ethanol and ethyl esters in slices but reduced acidity, while heat reduced both acidity and aroma volatile levels. Both ethanol and heat pretreatments led to lower sensory scores for apple flavor and ethanol-pretreated slices also received higher scores for altered flavor, although all scores were in the acceptable range. Slice acidity was best maintained by 1-MCP pretreatment. Shelf life based on appearance was 15 to 16 days for ethanol-pretreated slices and 12 days for heat-pretreated slices compared to that of control, which was 8 to 9 days, while 1-MCP pretreatment promoted decay development on the cut surface, which reduced the shelf life to 7 to 8 days. Obvious separations were determined between ethanol- and heat-pretreated slices and untreated control by canonical discriminant analysis of headspace volatile levels determined by GC and electronic nose. Therefore, pretreatments with ethanol and heat are very effective for prolonging visual shelf life at the expense of aroma quality.
Indications of Immunodepression in Chickens Infected with Various Strains of Marek's Disease Virus (1988)

The effect of infection by various strains of Marek's disease virus (MDV) on the immune function of 3-week-old chickens was examined. MDV strains of low (CU-2, RB-7) and high (RB-3, MD-5, and MD-11) pathogenicity were compared with prototype JM-10 strain of moderate pathogenicity. Mortality, whole body weight, relative weights of lymphoid organs, histopathology, humoral antibody responses to thymus-dependent and -independent antigens, and in vitro lymphocyte responses to mitogen stimulation were investigated at 1, 2, and 3 weeks postinfection. MDV strains of high pathogenicity significantly depressed responses at 3 weeks postinfection, seeming to indicate the ability of these viruses to induce severe immunodepression. However, the fact that the moderately pathogenic and even some of the low-pathogenicity strains induced immunodepression suggests that other viral mechanisms are also important in its determination.
Molecular recognition in biological systems: From activation to inhibition (1993)

Conference Article| August 01 1993 Molecular recognition in biological systems: From activation to inhibition Anthony A. Kossiakoff; Anthony A. Kossiakoff 1Department of Protein Engineering, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Thomas Hynes; Thomas Hynes 1Department of Protein Engineering, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Abraham de Vos Abraham de Vos 1Department of Protein Engineering, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1993) 21 (3): 614–618. https://doi.org/10.1042/bst0210614 Article history Received: March 30 1993 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Anthony A. Kossiakoff, Thomas Hynes, Abraham de Vos; Molecular recognition in biological systems: From activation to inhibition. Biochem Soc Trans 1 August 1993; 21 (3): 614–618. doi: https://doi.org/10.1042/bst0210614 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: GH, growth hormone, PRL, prolactin; PL, placental lactogen, ECD extracellular domain, BPTI, basic pancreatic-trypsin inhibitor, APPI, Alzheimer's amyloid β-protein precursor inhibitor (Kunitz domain); h, human This content is only available as a PDF. © 1993 Biochemical Society1993 Article PDF first page preview Close Modal You do not currently have access to this content.
When Computers Decide: European Recommendations on Machine-Learned Automated Decision Making (2018)

Over the past two decades, the ability of machines to challenge and beat humans at complex games has made “quantum” leaps, rhetorically if not in technical computing terms. In 1997, IBM's Deep Blue supercomputer used “brute force” computing power to out-calculate Grand Master Garry Kasparov at chess. In 2011, the company's Watson employed “machine learning” (ML) techniques to beat several former Jeopardy champions at their own game. In early 2016, Google's DeepMind AlphaGo program-trained by a massive game history-repeatedly defeated the reigning European champion at Go: a game that has more possible board configurations than there are atoms in the universe [1]. It reached this milestone by employing two neural networks powered by sophisticated “automated decision making” (ADM) algorithms. And, in 2017, AlphaGo Zero became the strongest Go player on the planet-human or machine-after just a few months of game-play training alone. Incredibly, it was programmed initially only with the rules of the game [2]. Automated decision making concerns decision making by purely technological means without human involvement. Article 22(1) of the European General Data Protection Regulation (GDPR) enshrines the right of data subjects not to be subject to decisions, which have legal or other significant effects, being based solely on automatic individual decision making. As a consequence, in this paper we consider applications of ADM to applications other than those based on personal information, for example the game-playing discussed above. We discuss other aspects of GDPR later in the paper. Whilst the game-playing results are impressive, the consequences of machine learning and automated decision making are themselves, however, no game. As of this writing, they have progressed to enable computers to rival humans' ability at even more challenging, ambiguous, and highly skilled tasks with profound “real world” applications, such as: recognizing images, understanding speech, and analysing X-rays among many others. As these techniques continue to improve rapidly, many new and established companies are utilizing them to build applications that reliably perform activities that previously were done (and doable) only by people. Today, such systems can both augment human decision making and, in some cases, replace it with a fully autonomous system. In this report, we review the principal implications of the coming widespread adoption of MLdriven automated decision making with a particular emphasis on its technical, ethical, legal, economic, societal and educational ramifications. We also make a number of recommendations that policy makers might wish to consider.
(Digital Presentation) On the Origin of High Resistance at the Interface between Lithium Metal and Sulfide Solid Electrolytes (2022)

Sulfide materials have been extensively studied as solid-state electrolytes (SSEs) for all-solid-state lithium metal batteries (ASSLMBs) because of their high ionic conductivity, wide electrochemical window, and appropriate mechanical properties. However, they suffer from the high interfacial resistance with Li metal anode, besides poor stability when exposed to air, hindering the application of sulfide-based SSEs in ASSLMBs. Sulfide materials are well known to undergo reaction with Li metal, leading to solid-electrolyte interphase layer formation at the SSE/Li metal interface. The side reactions could be primarily responsible for the high resistance at the interface between SSE and Li metal anode, but the underlying mechanisms still remain unclear. To better understand the structure and property changes of the sulfide SSE due to the reaction with Li metal, we took β-Li 3 PS 4 (LPS) as a model system and systematically analyzed the structural, electronic, transport, and mechanical properties of lithiated LPS with varying Li contents using first-principles methods. Moreover, we examined the compositional and structural evolution at the LPS/Li metal interface using ab initio molecular dynamics (AIMD) simulations. Our results unequivocally show that Li incorporation leads to decomposition of PS 4 3- to Li 2 S and Li 3 P when fully lithiated. With lithiation, Li-ion conductivity is predicted to remain in the same order of magnitude despite the significant structural and compositional changes. Both the band gap and density of the lithiated LPS becomes smaller than those of the unlithiated LPS. More importantly, we found the formation of voids at the LPS/Li metal interface. In this talk, based on our results we will discuss the mechanisms responsible for the high interfacial impedance as often observed in previous experimental studies.
NSABP FC-9: Phase II study of dual immune checkpoint blockade (ICB) with durvalumab (D) plus tremelimumab (T) following palliative hypofractionated radiotherapy (SBRT) in patients (pts) with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) progressing on chemotherapy. (2018)

e15681 Background: Monotherapy with ICB has not been effective in MSS mCRC. Preclinical data demonstrated that immunomodulators synergize with radiotherapy (RT) resulting in tumor regression at irradiated sites and rarely at non-irradiated sites. Anecdotal reports in pts have confirmed an abscopal effect of RT and ICB. This phase II, open-label, single-arm study tests dual ICBs following SBRT in pts with MSS mCRC who have progressed on chemotherapy. Preliminary efficacy and safety results of the NSABP FC-9 will be reported. Methods: Eligible pts have MSS mCRC and progressed on prior oxaliplatin and irinotecan-based regimens, measurable lesions with at least one amenable to SBRT and another for core biopsy, and performance status ECOG < 2. Following 3 doses of SBRT at 9 Gy (D −2, −1, and D 0 prior to Cycle 1), pts received the combination of T (75 mg IV infusion) and D (1500 mg IV infusion) on D 1 of Cycles 1-4. Beginning with Cycle 5 -Cycle 12, pts received D alone on D 1 q 28d. Tumor response at non-irradiated target lesions was measured at baseline and every 2 cycles using RECIST 1.1. Toxicity was graded according to the NCI CTCAE v 4.0. Sample size will be between 12 and 21 evaluable pts with a Simon two-stage design. Primary aim is to determine objective response rate (ORR). Secondary objectives are clinical benefit rate, duration of response, tolerability, and correlates of response. Results: The trial has opened at six academic centers. Between October 2017 and January 31, 2018, 14 pts were enrolled in the first stage; two pts were not evaluable and were replaced. Median age is 58 yrs (range, 37-71). Without regard to attribution, there were 5 grade 3 toxicities: anemia 1, fatigue 1, dehydration 1, peripheral neuropathy 1, and thromboembolism 1. There were no grade 4 or 5 toxicities. Response data will be presented. Conclusions: To date, no unexpected toxicities have been observed with SBRT followed by dual ICB. We will report the response observations in the first stage of this phase II trial. Support: Astra-Zeneca Clinical trial information: NCT03007407.
Abstract 1998: Transcriptome analysis of hypoxic head and neck cancer cells uncovers intron retention in EIF2B5 as a mechanism to reduce protein synthesis (2017)

Abstract Hypoxia is a key feature of solid tumors that contributes to resistance to therapy and reduced overall survival. Cellular adaptation to the hypoxic tumor microenvironment involves attenuation of energy-consuming processes such as macromolecular synthesis. We have identified RNA processing as another major process which is globally downregulated under hypoxic stress. By sequencing RNA of normoxic and hypoxic head and neck cancer cells, we observed widespread repression of genes that regulate RNA splicing and processing. As a result, we observed over 1,000 changes in relative mRNA isoform expression, including a significant increase in hypoxia-induced intron retention in nearly 100 genes. Genes observed to undergo intron retention in hypoxia included major regulators of RNA processing and protein synthesis, such as the translation initiation factor EIF2B5. Surprisingly, hypoxia-induced intron retention in EIF2B5 creates a premature termination codon, which results in a truncated protein isoform of eIF2Bϵ. We provide evidence that this isoform acts in opposition to the full-length protein to inhibit translation under stringent hypoxic conditions. Moreover, this intron is expressed in solid cancers known to contain hypoxic fractions and is overexpressed in head and neck cancer in a stage-dependent manner compared to normal tissue. To investigate how this intron is retained, we are examining the role of hypoxia-mediated changes in phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. Our data suggest that increased phosphorylation of the CTD may lead to transcriptional pausing and subsequent retention of intron 12 in EIF2B5. Furthermore, distinct sequence features at this locus, such as a weak splice site at the intron12:exon13 junction, may explain how this intron is selectively retained in hypoxic cells. These results implicate mRNA splicing as a key mechanism to induce alternate transcripts and subsequent protein isoforms under hypoxia that influence cellular adaptation to stress. Citation Format: Lauren K. Brady, Hejia Wang, Caleb Radens, Milan Radovich, Amit Maity, Cristina Ivan, Mircea Ivan, Yoseph Barash, Constantinos Koumenis. Transcriptome analysis of hypoxic head and neck cancer cells uncovers intron retention in EIF2B5 as a mechanism to reduce protein synthesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1998. doi:10.1158/1538-7445.AM2017-1998
Detection of the Small Magellanic Cloud in gamma-rays with <i>Fermi</i>/LAT (2010)

Context. The flux of gamma rays with energies greater than 100 MeV is dominated by diffuse emission coming from cosmic-rays (CRs) illuminating the interstellar medium (ISM) of our Galaxy through the processes of Bremsstrahlung, pion production and decay, and inverse-Compton scattering. The study of this diffuse emission provides insight into the origin and transport of cosmic rays. Aims. We searched for gamma-ray emission from the Small Magellanic Cloud (SMC) in order to derive constraints on the cosmic-ray population and transport in an external system with properties different from the Milky Way. Methods. We analysed the first 17 months of continuous all-sky observations by the Large Area Telescope (LAT) of the Fermi mission to determine the spatial distribution, flux and spectrum of the gamma-ray emission from the SMC. We also used past radio synchrotron observations of the SMC to study the population of CR electrons specifically. Results. We obtained the first detection of the SMC in high-energy gamma rays, with an integrated >100 MeV flux of (3.70.7)10 - ph cm -2 s -1 , with additional systematic uncertainty of 16%. The emission is steady and from an extended source 3 in size. It is not clearly correlated with the distribution of massive stars or neutral gas, nor with known pulsars or supernova remnants, but a certain correlation with supergiant shells is observed. Conclusions. The observed flux implies an upper limit on the average CR nuclei density in the SMC of 15% of the value measured locally in the Milky Way. The population of high-energy pulsars of the SMC may account for a substantial fraction of the gamma-ray flux, which would make the inferred CR nuclei density even lower. The average density of CR electrons derived from radio synchrotron observations is consistent with the same reduction factor but the uncertainties are large. From our current knowledge of the SMC, such a low CR density does not seem to be due to a lower rate of CR injection and rather indicates a smaller CR confinement volume characteristic size.
A Raman and Computational Study of Two Dithienyl Naphthodithiophenes:  Synthesis and Characterization of New Polymers Showing Low Band Gap Optical and Electroactive Features (2004)

Two isomeric dithienyl naphthodithiophenes and their corresponding polymers have been thoroughly studied by using a combination of spectroscopic, electrochemical, and quantum chemistry techniques. The change between the syn and anti configuration of the sulfur atoms of the core translates into important differences in their optical and electrochemical properties. This study reveals the existence in the syn isomer of a bonding interaction, while in the anti isomer there exists a more delocalized π-electron distribution. The full assignment of the Raman spectra of the monomers has allowed to interpret, assign, and correlate the spectra of the polymers. Upon polymerization the Raman data indicate an increment of the bond length relaxation pattern for the electronic structure of the polymer regarding the monomers. The two polymers are surprisingly strong amphoters, showing very stable oxidation and reduction waves at relatively low potentials at the same time that they behave as low band gap polymers. From a material point of view, these polymers are very interesting substrates for electrically active layers with relevant photophysical properties.
Computerized Classification Method for Molecular Subtypes in Glioma with Multi-Scale 3D-Attention Branch Networks Analyzing Multi-Sequence Brain MRI Images (2023)

The purpose of this study was to develop a computerized classification method for molecular subtypes in low-grade gliomas (LGGs) with multi-scale 3D-at-tention branch networks analyzing multi-sequence brain MRI images. Our dataset consisted of brain T1-weighted and T2-weighted MRI im-ages for 217 patients (58 Astrocytoma IDH-mutant, 49 Astrocytoma IDH-wildtype, and 110 Oligodendroglioma). The proposed method was constructed from a feature extractor, an attention branch, and a perception branch. In the feature extractor, the feature maps were extracted from brain T1-weighted and T2-weighted MRI images, respectively. The attention branch focused on a tumor region and generated the attention maps normalized to 0.0 - 1.0. The feature maps were then multiplied by the attention maps to weight features on LGG in the feature maps. The molecular subtype in LGG was evaluated in the perception branch. The classification accuracy for the proposed method was 63.6%, showing an improvement when compared with the conven-tional method using only single sequence (T2-weighted) MRI images (59.9%).
Изучение нейропротекторной активности конъюгата ГАМК с арахидоновой кислотой в условиях локальной перманентной ишемии головного мозга у крыс (2015)

Исследовано влияние конъюгата ГАМК с арахидоновой кислотой на морфологическое состояние ткани головного мозга крыс после перевязки левой средней мозговой артерии. Проведенное исследование позволило установить, что курсовое введение в течение 6 и 12 дней конъюгата ГАМК с арахидоновой кислотой в дозе 2 мг/кг (внутрибрюшинно) крысам, перенесшим локальную перманентную ишемию головного мозга, приводило к существенным восстановительным процессам в мозговой ткани. Морфологическая картина мозговой ткани в группе животных, получающих конъюгат ГАМК с арахидоновой кислотой в течение 12 дней, практически приближалась к показателям нормальной ткани.