gebhart/patrepeval huggingface dataset:
IMMU-59. ALTERNATING ELECTRIC FIELDS (TTFIELDs) INDUCE IMMUNOGENIC CELL DEATH RESULTING IN ENHANCED ANTITUMOR EFFICACY WHEN COMBINED WITH ANTI-PD-1 THERAPY (2017)

Tumor Treating Fields (TTFields) are an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. TTFields are employed as a local treatment modality with the intent to kill tumor cells and reduce local recurrence. This therapy is approved for the treatment of patients with glioblastoma. Previous investigations have shown that TTFields disrupt formation of the mitotic spindle, leading to abnormal chromosome segregation and various modes of cell death. In this study we evaluated whether TTFields-induced cell death can be perceived as immunogenic by the immune system. We demonstrate that cancer cells that die under TTFields application exhibit release of the chromatin-binding protein high mobility group B1(HMGB-1), endoplasmic reticulum (ER) stress leading to Calreticulin translocation to the cell surface, and autophagy leading to decreased intracellular levels of adenosine triphosphate (ATP), all of which are cardinal signs of immunogenic cell death. In vivo, the combined treatment of lung tumor-bearing mice with TTFields plus the immune checkpoint inhibitor anti-programmed death 1 (PD-1) led to a significant decrease in tumor volume compared to anti-PD-1 alone or to the control group. Significant increases in CD45+ tumor infiltrating cells were observed in the TTFields plus anti-PD-1 group. These infiltrating cells, specifically macrophages (F4/80+CD11b+) and dendritic (CD11c+) cells, demonstrated a significant upregulation of surface PD-L1 expression as compared to infiltrating immune cells in the control group. Our results demonstrate the potential of TTFields therapy to induce immunogenic cell death in vitro which may lead enhanced immune response against cancer cells. We also demonstrate significant efficacy of concurrent application of TTFields and anti PD-1 therapy in vivo. These data suggest that combining TTFields with anti-PD-1 might achieve tumor control by further enhancing antitumor immunity.
Surveillance for avian influenza viruses in wild birds at live bird markets, Egypt, 2014‐2016 (2019)

Our data show significant diversity of AIVs in Anserifromes sold at live bird markets in Egypt. This allows for genetic exchanges between imported and enzootic viruses and put the exposed humans at a higher risk of infection.
Dislocation structure and microstrain evolution during spinodal decomposition of reactive magnetron sputtered heteroepixatial c-(Ti0.37,Al0.63)N/c-TiN films grown on MgO(001) and (111) substrates (2019)

Heteroepitaxial c-(Ti0.37,Al0.63)N thin films were grown on MgO(001) and MgO(111) substrates using reactive magnetron sputtering. High resolution high-angle annular dark-field scanning transmission electron micrographs show coherency between the film and the substrate. In the as-deposited state, x-ray diffraction reciprocal space maps show a strained epitaxial film. Corresponding geometric phase analysis (GPA) deformation maps show a high stress in the film. At elevated temperature (900 °C), the films decompose to form iso-structural coherent c-AlN- and c-TiN-rich domains, elongated along the elastically soft &amp;lt;100&amp;gt; directions. GPA analysis reveals that the c-TiN domains accommodate more dislocations than the c-AlN domains. This is because of the stronger directionality of the covalent bonds in c-AlN compared with c-TiN, making it more favorable for the dislocations to accumulate in c-TiN. The defect structure and strain generation in c-(Ti,Al)N during spinodal decomposition is affected by the chemical bonding state and elastic properties of the segregated domains.
Stoffwechselprodukte von Mikroorganismen, 214 Viocristin, Isoviocristin und Hydroxyviocristin. — Struktur und Synthese natürlich vorkommender 1,4‐Anthrachinone (1982)

Abstract Neben mehreren 9,10‐Anthrachinonen produziert der Schimmelpilz Aspergillus cristatus die Pigmente Viocristin ( 19a ), Isoviocristin ( 18a ) und Hydroxyviocristin ( 13 ), die der bisher in Naturstoffen nicht aufgefundenen 1,4‐Anthrachinonreihe angehören. Ihre Synthese und die weiterer Modellverbindungen wird beschrieben.
A simple model for threshold voltage of surrounding-gate MOSFET's (1998)

We propose a threshold voltage model for surrounding-gate MOSFETs. The model treats the ends and the double-gate regions of the channel as separate devices operating in parallel. The threshold voltage for the full device is obtained as the perimeter-weighted sum of the threshold voltages of the two parts enabling simple analytic threshold models to be used. Short channel effects and drain-induced barrier lowering are also modeled in this manner.
Improving Topology Optimization using Games (2013)

Topology optimization has had, and still has, a great impact on the design of structures and mechanical elements. Even though computers and topology optimization algorithms are able to find good solutions to most problems, it is also important for users of such programs to have a good intuition for whether a structure is optimal. We hypothesize that human intuition regarding topology optimization is often led astray. Our goal is to collect data in order to test this hypothesis and at the same time to actively train users (in particular students of mechanical engineering) in designing optimal structures. Consequently, we have created a game, the TopOptGame, which improves the player's topology optimization intuition in a fun and engaging way while collecting data about the users performance. Technically, the TopOptGame builds on the TopOptApp [1] - an interactive topology optimization application designed for hand-held devices. The TopOptApp solves the 2D minimum compliance problem with interactive control of loads, supports and volume fraction, and thus the TopOptApp allows the user to change the problem on the y and watch the design evolve to a new optimum in real time. TopOptApp is available free of charge on iOS and Android devices1. The TopOptGame is inspired by puzzle-games (a genre of computer games), which constantly challenges the players and gives rewards when progress is made. This engagement loop will take the player on a journey starting with simple problems with few supports and a single load and gradually increase the difficulty by adding more loads, restrictions on the design domain, distributed loads and multiple load cases. The goal is to distribute material in a discretized design domain, under some volume and time constrains, while searching for a good solution (minimum compliance). A visualization of the strain energy density will help the player nding a feasible solution. Besides training the player in topology optimization, the game also tracks the progress of each player and sends this progress in anonymized form to a database. When enough data has been collected, this will allow us to analyze the data to measure human performance of topology optimization and more importantly, in which cases people's intuition succeed or fail. The game is currently a working prototype and is scheduled for final release on both iOS and Android before WCSMO-10.
Supplemental Figure 2 from BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer (2023)

&lt;p&gt;Direct comparison of various BET inhibitors in prostate cancer cells.&lt;/p&gt;
From the notebooks of a troubled inventor (2006)

Contemporary inventors and investors are faced with new challenges and difficulties that have not been experienced by past generations of inventors. This basically is the result of the exponential increase in the amount of knowledge and the tough global competition. A magic formula for success does not exist, but following some basic rules to be discussed here, will greatly increase the inventor / entrepreneur's chance for success. Two examples, the Video capsule and a 3D imaging Camera that are based on the author's past inventions are described and analyzed to demonstrate some of the rules.
The effects of the mechanical performance and alignment of the Atacama Cosmology Telescope on the sensitivity of microwave observations (2008)

The Atacama Cosmology Telescope is a six meter, off-axis Gregorian telescope for measuring the cosmic microwave background at arcminute resolutions. The Millimeter Bolometer Array Camera (MBAC) is its current science instrument. Erected in the Atacama Desert of Chile in early 2007, it saw first light with the MBAC on 22 October 2007. In this paper we review its performance after one month of observing, focusing in particular on issues surrounding the alignment of the optical system that impact the sensitivity of the experiment. We discuss the telescope motion, pointing, and susceptibility to thermal distortions. We describe the mirror alignment procedure, which has yielded surface deviations of 31 &mu;m rms on the primary and 10 &mu;m rms on the secondary. Observations of planets show that the optical performance is consistent with the telescope design parameters. Preliminary analysis measures a solid angle of about 215 nanosteradians with a full width at half maximum of 1.44 arcminutes at 145 GHz.
Pathophysiology of Cytokines (1986)

Toxic shock syndrome toxin-1 (TSST-1) induces IL-1 production from macrophages/monocytes of various species. Susceptibility of the mouse strains to TSST-1 is parallel to the IL-1 production. IL-1 has multibiological activities for T cells, hepatocytes, neutrophils, fibroblasts and other cells, resulting in induction of acute phase responses. PI 5 IL-1 (IL-1 alpha) and PI 7 (IL-1 beta) are cloned in both the human and the mouse cases (1_??_3). The recombinant IL-1's confirm the multiple biological properties of the purified IL-1 including fever. IFN-alpha is also an endogenous pyrogen. Recombinant tumor necrosis factor (TNF) possesses almost the same biological function of IL-1. However, TNF induces IL-1 production from human mononuclear cells while IL-1 production by IL-1 itself has never been reported, yet. Differently from IL-1, TNF does not augment T cell proliferation. Although TSST-1 induces only IL-1, endotoxin stimulates both IL-1 and TNF production. A quantitative relationship among these endogenous pyrogens remains unsolved in each disease.1) Auron, et al.: Proc. Natl. Acad. Sci. USA, 81: 7907, 1984.2) Lomedico, et al.: Nature, 312: 458, 1984.3) Gubler, et al.: J. Immunol, 136: 2492, 1986.
Dielectric barrier discharge plasma treatment of modified SU-8 for biosensing applications (2018)

In this work we demonstrate the use of a dielectric barrier discharge plasma for the treatment of SU-8. The resulting hydrophilic surface displays a 5° contact angle and (0.40 ± 0.012) nm roughness. Using this technique we also present a proof of concept of IgG and prostate specific antigen biodetection on a thin layer of SU-8 over gold via surface plasmon resonance detection.
Highly Enantioselective Cascade Transformations by Merging Heterogeneous Transition Metal Catalysis with Asymmetric Aminocatalysis (2012)

The concept of combining heterogeneous transition metal and amine catalysis for enantioselective cascade reactions has not yet been realized. This is of great advantage since it would allow for the recycling of expensive and non-environmentally friendly transition metals. We disclose that the use of a heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst allows for highly enantioselective cascade transformations. The preparative power of this process has been demonstrated in the context of asymmetric cascade Michael/carbocyclization transformations that delivers cyclopentenes bearing an all carbon quaternary stereocenters in high yields with up to 30:1 dr and 99% ee. Moreover, a variety of highly enantioselective cascade hetero-Michael/carbocyclizations were developed for the one-pot synthesis of valuable dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous Pd and chiral amines as co-catalysts.
An Escherichia coli trap in human serum albumin microtubes (2014)

We describe the template synthesis of human serum albumin microtubes (MTs) and highlight their Escherichia coli (E. coli) trapping capability with extremely high efficiency. The E. coli was loaded into the one-dimensional pore space interior of the tubule. Similar MTs including an Fe3O4 layer also captured E. coli and were manipulated by exposure to a magnetic field.
Future vaccines for a globalized world (2012)

Vaccination continues to have a major impact on the health of humans and animals. Furthermore, vaccination of animals is proving to be effective in reducing transmission to humans. Understanding linkages between innate and adaptive immunity are improving formulations of new, as well as existing, vaccines, making them more effective.
Prolonged re-expression of the hypermethylated geneEPB41L3using artificial transcription factors and epigenetic drugs (2015)

Epigenetic silencing of tumor suppressor genes (TSGs) is considered a significant event in the progression of cancer. For example, EPB41L3, a potential biomarker in cervical cancer, is often silenced by cancer-specific promoter methylation. Artificial transcription factors (ATFs) are unique tools to re-express such silenced TSGs to functional levels; however, the induced effects are considered transient. Here, we aimed to improve the efficiency and sustainability of gene re-expression using engineered zinc fingers fused to VP64 (ZF-ATFs) or DNA methylation modifiers (ZF-Tet2 or ZF-TDG) and/or by co-treatment with epigenetic drugs [5-aza-2'-deoxycytidine or Trichostatin A (TSA)]. The EPB41L3-ZF effectively bound its methylated endogenous locus, as also confirmed by ChIP-seq. ZF-ATFs reactivated the epigenetically silenced target gene EPB41L3 (∼ 10-fold) in breast, ovarian, and cervical cancer cell lines. Prolonged high levels of EPB41L3 (∼ 150-fold) induction could be achieved by short-term co-treatment with epigenetic drugs. Interestingly, for otherwise ineffective ZF-Tet2 or ZF-TDG treatments, TSA facilitated re-expression of EPB41L3 up to twofold. ATF-mediated re-expression demonstrated a tumor suppressive role for EPB41L3 in cervical cancer cell lines. In conclusion, epigenetic reprogramming provides a novel way to improve sustainability of re-expression of epigenetically silenced promoters.
Development of a High‐Throughput Screen for Protein Catalysts: Application to the Directed Evolution of Antibody Aldolases (2003)

Ein halbautomatisiertes Hochdurchsatz-System zur Expression und Reinigung von Proteinen und als Test auf ihre katalytische Aktivität wurde entwickelt. Damit lassen sich Aktivität, Selektivität und Expressionsgrad der Proteine direkt oder in Kombination mit Selektionen verfolgen. Zur Demonstration des Potenzials des Systems wurde es auf die gerichtete Evolution katalytischer Antikörper mit Aldolaseaktivität angewandt. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2003/z52117_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility (2017)

Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel susceptibility factors, 39 rare truncating mutations, identified in 189 Northern Finnish hereditary breast cancer patients in parallel sequencing of 796 DDR genes, were studied for disease association. Mutation screening was performed for Northern Finnish breast cancer cases (n = 578-1565) and controls (n = 337-1228). Mutations showing potential cancer association were analyzed in additional Finnish cohorts. c.7253dupT in TEX15, encoding a DDR factor important in meiosis, associated with hereditary breast cancer (p = 0.018) and likely represents a Northern Finnish founder mutation. A deleterious c.2715 + 1G > A mutation in the Fanconi anemia gene, FANCD2, was over two times more common in the combined Finnish hereditary cohort compared to controls. A deletion (c.640_644del5) in RNF168, causative for recessive RIDDLE syndrome, had high prevalence in majority of the analyzed cohorts, but did not associate with breast cancer. In conclusion, truncating variants in TEX15 and FANCD2 are potential breast cancer risk factors, warranting further investigations in other populations. Furthermore, high frequency of RNF168 c.640_644del5 indicates the need for its testing in Finnish patients with RIDDLE syndrome symptoms.
Search for supersymmetry using Higgs boson to diphoton decays at $$ \sqrt{s} $$ = 13 TeV (2019)

A bstract A search for supersymmetry (SUSY) is presented where at least one Higgs boson is produced and decays to two photons in the decay chains of pair-produced SUSY particles. Two analysis strategies are pursued: one focused on strong SUSY production and the other focused on electroweak SUSY production. The presence of charged leptons, additional Higgs boson candidates, and various kinematic variables are used to categorize events into search regions that are sensitive to different SUSY scenarios. The results are based on data from proton-proton collisions at the Large Hadron Collider at a center-of-mass energy of 13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 77.5 fb − 1 . No statistically significant excess of events is observed relative to the standard model expectations. We exclude bottom squark pair production for bottom squark masses below 530 GeV and a lightest neutralino mass of 1 GeV; wino-like chargino-neutralino production in gauge-mediated SUSY breaking (GMSB) for chargino and neutralino masses below 235 GeV with a gravitino mass of 1 GeV; and higgsino-like chargino-neutralino production in GMSB, where the neutralino decays exclusively to a Higgs boson and a gravitino for neutralino masses below 290 GeV.
Loss-of-function screening by randomized intracellular antibodies: Identification of hnRNP-K as a potential target for metastasis (2007)

We have developed a loss-of-function screening system on the basis of intracellular expression of single domain antibodies. We demonstrate its use in identification of potential targets of metastasis of human cancerous cells. Randomized intracellular antibodies were expressed in highly metastatic cells, and a derivative pool of cells with loss of migration phenotype in chemotaxis assay was isolated. Isolation of antibodies from cells with loss of migration phenotype and identification of their target proteins revealed the involvement of the heterogeneous nuclear ribonucleoprotein K (hnRNP-K), a multifunctional signaling protein, in metastasis. Furthermore, we found that the cytoplasmic accumulation of hnRNP-K is crucial for its role in metastasis. The results demonstrate (i) the advantages of our functional interference screening over the gene-knockouts and gene-silencing, (ii) hnRNP-K as a potential target of metastasis, and (iii) a potential anti-metastasis peptide validated in in vitro cell migration assays.
An Efficient Synthesis of Isoxazoles and Isoxazolines (1985)

d c h l o r i d e and dipolarophile.
Network analysis uncovers the communication structure of SARS-CoV-2 spike protein identifying sites for immunogen design (2022)

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered myriad efforts to understand the structure and dynamics of this complex pathogen. The spike glycoprotein of SARS-CoV-2 is a significant target for immunogens as it is the means by which the virus enters human cells, while simultaneously sporting mutations responsible for immune escape. These functional and escape processes are regulated by complex molecular-level interactions. Our study presents quantitative insights on domain and residue contributions to allosteric communication, immune evasion, and local- and global-level control of functions through the derivation of a weighted graph representation from all-atom MD simulations. Focusing on the ancestral form and the D614G-variant, we provide evidence of the utility of our approach by guiding the selection of a mutation that alters the spike's stability. Taken together, the network approach serves as a valuable tool to evaluate communication "hot-spots" in proteins to guide design of stable immunogens.
Repetitive prenatal glucocorticoid therapy reduces oxidative stress in the lungs of preterm lambs (1998)

Repetitive courses of maternal prenatal glucocorticoids are often used in high-risk pregnancies with threatening preterm labor to induce lung maturation, but the effects on the cellular oxidant-antioxidant balance in the fetal lung have not been evaluated. We investigated the effect of repetitive treatment with glucocorticoids, beginning early in gestation, on oxidative stress in the preterm ovine lung. Pregnant ewes were randomized to receive one, two, three, or four doses of 0.5 mg/kg betamethasone or saline placebo at 7-day intervals on 104, 111, 118, and 124 days gestation (n = 11 for each group). All lambs were delivered preterm at 125 days gestation, and lung tissue was assayed for antioxidant enzymes, lipid hydroperoxides, and carbonyl proteins. Lung manganese superoxide dismutase, catalase, and glutathione peroxidase activity increased after 1 dose of betamethasone given at 104 days gestation, whereas copper-zinc superoxide dismutase activity increased after 2 doses given at 104 and 111 days gestation. The activity of all four antioxidant enzymes further increased with additional doses and was maximal after four doses of betamethasone. Lung lipid hydroperoxide levels and carbonyl protein content decreased stepwise after each dose of betamethasone and were lowest after four doses. Repetitive prenatal glucocorticoid therapy increases antioxidant enzyme activity and reduces oxidative stress in the lungs of preterm lambs, and these effects begin early in gestation and persist for 2-3 wk.