gebhart/patrepeval huggingface dataset:
Supplementary Movie 5 from The Anaplastic Lymphoma Kinase Controls Cell Shape and Growth of Anaplastic Large Cell Lymphoma through Cdc42 Activation (2023)

Supplementary Movie 5 from The Anaplastic Lymphoma Kinase Controls Cell Shape and Growth of Anaplastic Large Cell Lymphoma through Cdc42 Activation
Purification and partial characterization of PfHRP-II protein of Plasmodium falciparum. (2003)

The human malarial parasite Plasmodium falciparum secretes various intra-and extra-cellular proteins during its asexual life cycle in human RBC. Histidine rich protein-II (HRP-II) is one of the most prominent proteins, found to be secreted by P. falciparum throughout the asexual cycle with the peak during mature schizont stage of the parasite development in human IRBC. The high histidine content (35% of the total amino acids in protein) of this protein suggested the potential to bind divalent metal ions. We have demonstrated by metal chelate chromatography, an extraordinary capacity of HRP-II to bind nickel ions (Ni++) and employed this characteristic to purify the extra-cellular HRP-II protein secreted by P. falciparum from culture supernatant. The identity of the purified protein was verified by the relative molecular weight on SDS-PAGE, by reacting with polyclonal antibodies directed against it using Western blot technique.
Targeted Theranostic 111In/Lu-Nanotexaphyrin for SPECT Imaging and Photodynamic Therapy (2021)

Theranostic nanoparticles aim to integrate diagnostic imaging and therapy to facilitate image-guided treatment protocols. Herein, we present a theranostic nanotexaphyrin for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and focal photodynamic therapy (PDT) accomplished through the chelation of metal isotopes (In, Lu). To realize nanotexaphyrin's theranostic properties, we developed a rapid and robust <sup>111</sup>In/Lu-nanotexaphyrin radiolabeling method using a microfluidic system that achieved a high radiochemical yield (>90%). The optimized metalated nanotexaphyrin displayed excellent chemical, photo, and colloidal stabilities, potent singlet oxygen generation, and favorable plasma circulation half-life <i>in vivo</i> (<i>t</i><sub>1/2</sub> = 6.6 h). Biodistribution, including tumor accumulation, was characterized by NIR fluorescence, SPECT/CT imaging, and γ counting. Inclusion of the PSMA-targeting ligand enabled the preferential accumulation of <sup>111</sup>In/Lu-nanotexaphyrin in PSMA-positive (PSMA+) prostate tumors (3.0 ± 0.3%ID/g) at 48 h with tumor vs prostate in a 2.7:1 ratio. In combination with light irradiation, the PSMA-targeting nanotexaphyrin showed a potent PDT effect and successfully inhibited PSMA+ tumor growth in a subcutaneous xenograft model. To the best of our knowledge, this study is the first demonstration of the inherent metal chelation-driven theranostic capabilities of texaphyrin nanoparticles, which, in combination with PSMA targeting, enabled prostate cancer imaging and therapy.
Biochemical Characterization of Human ZIP13 Protein (2011)

The human SLC39A13 gene encodes ZIP13, a member of the LZT (LIV-1 subfamily of ZIP zinc transporters) family. The ZIP13 protein is important for connective tissue development, and its loss of function is causative for the spondylocheiro dysplastic form of Ehlers-Danlos syndrome. However, this protein has not been characterized in detail. Here we report the first detailed biochemical characterization of the human ZIP13 protein using its ectopic expressed and the purified recombinant protein. Protease accessibility, microscopic, and computational analyses demonstrated that ZIP13 contains eight putative transmembrane domains and a unique hydrophilic region and that it resides with both its N and C termini facing the luminal side on the Golgi. Analyses including cross-linking, immunoprecipitation, Blue Native-PAGE, and size-exclusion chromatography experiments indicated that the ZIP13 protein may form a homo-dimer. We also demonstrated that ZIP13 mediates zinc influx, as assessed by monitoring the expression of the metallothionein gene and by detecting the intracellular zinc level with a zinc indicator, FluoZin-3. Our data indicate that ZIP13 is a homo-dimerized zinc transporter that possesses some domains that are not found in other LZT family members. This is the first biochemical characterization of the physiologically important protein ZIP13 and the demonstration of homo-dimerization for a mammalian ZIP zinc transporter family member. This biochemical characterization of the human ZIP13 protein provides important information for further investigations of its structural characteristics and function.
How to Improve Cloud Services Availability? Investigating the Impact of Power and It Subsystems Failures (2018)

The cloud data center is a complex system composed of power, cooling, and IT subsystems. The power subsystem is crucial to feed the IT equipment. Power disruptions may result in service unavailability. This paper analyzes the impact of the power subsystem failures on IT services regarding different architecture configurations based on TIA-942 standard such as non-redundant, redundant, concurrently maintainable, and fault tolerant. We model both subsystems, power and IT, through Stochastic Petri Net (SPN). The availability results show that a fault tolerant power and IT configuration reduces the downtime from 54.1 to 34.5 hours/year when compared to a non-redundant architecture. The sensibility analysis results show that the failure and repair rates of the server component in a fault tolerant system present the highest impact on overall data center availability.
Analysis of BRCA1-related functional associations in sporadic triple negative breast cancer: A network-based approach. (2016)

1070 Background: Sporadic triple negative breast cancers (TNBC) are aggressive malignancies that present a yet unaddressed clinical challenge. They are refractory to hormonal and HER2-targeted therapy, leaving chemotherapy as the mainstay of systemic treatment. Their striking resemblance to BRCA1-mutated hereditary breast cancers has led to the speculation that BRCA1 pathway derangement underlies sporadic TNBC and could be exploited therapeutically. BRCA1 has been implicated in multiple cellular processes via interactions with diverse partner proteins. Methods: To search for TNBC-specific aberrations within the complex array of BRCA1-related functional associations, we devised a strategy that takes into account the versatility of the BRCA1 protein and combines database mining, literature curation, network modeling, and transcriptome analysis. Results: We used database- and literature-derived data on protein-protein interactions, co-complex memberships, and biochemical modifications involving BRCA1 to build a BRCA1-centered Interaction network of 157 known BRCA1 partners. We applied functional linkage analysis to add predicted functional links and generate a highly-connected Shell network of 1137 nodes and 2941 edges, directly or indirectly associated with BRCA1. We next used a curated compendium of 14 datasets comprising 2022 uniformly subtyped sporadic primary breast cancers to compute, meta-analytically, the relative expression of the network components in TNBC vs non-TNBC subtypes. Lastly, we derived TNBC-specific subnetworks of significantly hyperactive or suppressed BRCA1-functionally associated genes. Conclusions: Via network analysis, we have identified presumptive signatures of BRCA1 pathway deregulation in sporadic TNBC. We will assess their prognostic/predictive value and potential use for patient stratification. Where relevant, we will also employ them as hypothesis-generating tools to prioritize BRCA1-related genes/proteins and pathways for in-depth analyses and to search for therapeutically exploitable vulnerabilities. These studies can help to inform therapy selection and tailored treatment and, hence, guide clinical trial design.
Human pluripotent reprogramming with CRISPR activators (2018)

CRISPR-Cas9-based gene activation (CRISPRa) is an attractive tool for cellular reprogramming applications due to its high multiplexing capacity and direct targeting of endogenous loci. Here we present the reprogramming of primary human skin fibroblasts into induced pluripotent stem cells (iPSCs) using CRISPRa, targeting endogenous OCT4, SOX2, KLF4, MYC, and LIN28A promoters. The low basal reprogramming efficiency can be improved by an order of magnitude by additionally targeting a conserved Alu-motif enriched near genes involved in embryo genome activation (EEA-motif). This effect is mediated in part by more efficient activation of NANOG and REX1. These data demonstrate that human somatic cells can be reprogrammed into iPSCs using only CRISPRa. Furthermore, the results unravel the involvement of EEA-motif-associated mechanisms in cellular reprogramming.
Innenrücktitelbild: Amine‐Rich Nitrogen‐Doped Carbon Nanodots as a Platform for Self‐Enhancing Electrochemiluminescence (Angew. Chem. 17/2017) (2017)

Kohlenstoffnanopunkte sind die jüngsten Mitglieder der Familie der Kohlenstoffnanomaterialien, und sie wecken große Erwartungen aufgrund ihrer faszinierenden Eigenschaften. M. Prato, L. De Cola et al. demonstrieren in der Zuschrift auf S. 4835 ff. die Verwendung von aminreichen stickstoffdotierten Kohlenstoffnanopunkten als Coreaktanten des Luminophors [Ru(bpy)3]2+ in Elektrochemilumineszenz(ECL)-Prozessen. Das kovalent verknüpfte Hybrid wirkt als selbstverstärkendes ECL-System und zeigt eine höhere Emission als die Kombination der Einzelkomponenten.
Fault-Tolerant Hastings-Haah Codes in the Presence of Dead Qubits (2023)

We develop protocols for Hastings-Haah Floquet codes in the presence of dead qubits.
Optimization and Evaluation of Pretreatment Method for sp-ICP-MS to Reveal the Distribution of Silver Nanoparticles in the Body (2019)

The prevalent use of engineered nanoparticles (ENPs) has increased our exposure to these particles. The current available analytical techniques fail to simultaneously quantify and analyze the physical properties of ENPs in biological tissues. Therefore, new methods are required to evaluate the exposure conditions to ENPs. Single particle inductively coupled plasma-mass spectrometry (sp-ICP-MS) is an attractive approach that can perform quantitative and qualitative analyses of ENPs. However, the application of this approach for biological samples is limited because of the lack of pretreatment methods for effectively recovering ENPs from biological tissues. In this study, we evaluated various pretreatment methods and identified the optimal pretreatment conditions for sp-ICP-MS analyses of ENPs in biological tissues using silver nanoparticles (nAg) as a model. We screened five reagents as pretreatment solvents (sodium hydroxide, tetramethylammonium hydroxide, nitric acid, hydrochloric acid, and proteinase K). Our results showed that treatment with sodium hydroxide was optimal for detecting nAg in the mouse liver. Moreover, this pretreatment method can be applied to other organs, such as the heart, lung, spleen, and kidney. Finally, we evaluated the applicability of this method by analyzing the quantity and physical properties of silver in the mouse blood and liver, after intravenous administration of nAg or silver ion. Our sp-ICP-MS method revealed that nAg administered into the blood was partially ionized and tended to be distributed in the particle form (approximately 80%) in the liver and in ionic form (approximately 95%) in the blood. In conclusion, we optimized pretreatment strategies for sp-ICP-MS evaluation of ENPs in biological tissues and demonstrated its applicability by evaluating the changes in the physical properties of nAg in the liver and blood. We also showed that partial changes from the particle form to the ionic form of nAg influences their kinetics and distribution when administered to mice.
Evaluation of two commercial and two non-commercial immunoassays for the detection of prior infection to SARS-CoV-2 (2020)

Background Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. Methods We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result. Results The Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9-14 days (67-100%) and 15-21 days (69-100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH IgG assays were less sensitive during early disease, particularly among immunosuppressed individuals. Conclusions The Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives.
Brain connectivity and activity during Alzheimer’s disease progression in a mouse model by manganese‐‐enhanced MRI in living brain correlated with post‐mortem histopathology. (2020)

Alzheimer’s disease (AD) arises from inherited mutations in genes associated with plaque formation: amyloid precursor protein (APP), tau, and presenilin, or sporadically without these mutations. Studies of mice expressing these familial Alzheimer’s disease (FAD)‐associated mutations has led to new insights into the biological processes in sporadic AD. We study a mouse model in which expression of the FAD protein, APP SwInd , can be suppressed after plaque formation. This mouse thus corresponds to sporadic Alzheimer’s disease, where plaques are present in the absence of mutated protein. We use manganese‐enhanced magnetic resonance imaging (MEMRI), an emerging technology, coupled with histopathology of serial sections to investigate how plaques affect connectivity, neural activity degeneration throughout the whole brain as the mouse ages. MEMRI can be used in two ways: to determine axonal transport dynamics and to map neural activity in living mice. Stereotactic intracranial injection of Mn 2+ traces transport in hippocampus occurring over 24h in the awake behaving mouse. Systemic Mn 2+ enters active neurons in the brain of freely moving mice over 24h and is imaged retrospectively. Amyloid precursor protein (APP) is the precursor to A□eta plaques. The cytoplasmic domain of APP mediates cargo‐motor attachments for axonal transport. Our results show that in APP‐KO mice, axonal transport on Mn 2+ is decreased demonstrating the APP plays a role in Mn 2+ transport. In old transgenic mice APP SwInd , with both over‐expression of mutated protein and plaques, axonal transport is altered, as detected by time‐lapse manganese‐enhanced magnetic resonance imaging (MEMRI) of the brain in living mice. Time‐lapse MR images were captured before and successive time points after stereotactic injection of Mn 2+ (3–5nL) into CA3 of the hippocampus. Images of multiple individuals from the two groups (with plaques and no expression, or without plaques) were aligned and processed with our automated computational pipeline, and voxel‐wise statistical parametric mapping (SPM) performed. Whole brain neural activity was decreased in 3yr old mice with plaque and expressing APP SwInd compared to non‐expressing littermates, particularly in the hippocampus. Brains were harvested after MEMRI for biochemistry, or fixed, embedded and serially sectioned for histopathology. Histopathology detected mouse p‐tau–positive dystrophic neurites, decreases in the volume of septal nuclei, decrease in dentate gyrus width and cell death. Thus, plaque alone depresses transport in the important hippocampal to basal forebrain memory circuit, and decreases neural activity in the aging mouse. Support or Funding Information Supported by NINDS RO1 NS062184 and The Harvey Family Endowment.
Multi-Level Diffractive Lenses for Real-Time Long-Wave IR Imaging (2019)

Recently the field of metalenses has experienced an upsurge as evidenced by the growing number of publications in the area with each passing year. In-turn diffractive lenses have been used as thin-lenses since the late 19th century. Here, we show that multi-level diffractive lenses (MDLs), when appropriately designed, can perform comparably to metalenses. Furthermore, MDLs can be designed and fabricated with larger constituent features, making them accessible to low-cost, large area / volume manufacturing, which is generally challenging for metalenses in particular at IR and visible wavelengths. Based on this approach, we demonstrate computationally designed MDLs in real-time still and video imaging in the long-wave infrared regime (8 - 12 μm).
Non-linear Label Ranking for Large-scale Prediction of Long-Term User\n Interests (2016)

We consider the problem of personalization of online services from the\nviewpoint of ad targeting, where we seek to find the best ad categories to be\nshown to each user, resulting in improved user experience and increased\nadvertisers' revenue. We propose to address this problem as a task of ranking\nthe ad categories depending on a user's preference, and introduce a novel label\nranking approach capable of efficiently learning non-linear, highly accurate\nmodels in large-scale settings. Experiments on a real-world advertising data\nset with more than 3.2 million users show that the proposed algorithm\noutperforms the existing solutions in terms of both rank loss and top-K\nretrieval performance, strongly suggesting the benefit of using the proposed\nmodel on large-scale ranking problems.\n
Autophagic Inhibition via Lysosomal Integrity Dysfunction Leads to Antitumor Activity in Glioma Treatment (2020)

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.
Enhanced Two-Photon Fluorescence Imaging and Therapy of Cancer Cells via Gold@Bridged Silsesquioxane Nanoparticles (2014)

A two-photon photosensitizer with four triethoxysilyl groups is synthesized through the click reaction. This photosensitizer allows the design of bridged silsesquioxane (BS) nanoparticles through a sol-gel process; moreover, gold core BS shells or BS nanoparticles decorated with gold nanospheres are synthesized. An enhancement of the two-photon properties is noted with gold and the nanoparticles are efficient for two-photon imaging and two-photon photodynamic therapy of cancer cells.
Aspirin enhances doxorubicin-induced apoptosis and reduces tumor growth in human hepatocellular carcinoma cells in vitro and in vivo (2012)

Combined therapy with multiple drugs is a common practice in the treatment of cancer, which can achieve better therapeutic effects than a single drug, and can reduce the side effects as well as drug resistance. This study aimed to determine whether aspirin (ASA) shows synergism with doxorubicin (DOX) in HepG2 human hepatocellular carcinoma cells in vitro and in a HepG2 cell xenograft model in BALB/c nude mice. When treated in combination, DOX (0.25 nmol/ml) and ASA (5 µmol/ml) produced strong synergy in growth inhibition, cell cycle arrest and importantly, apoptosis in vitro in comparison to single treatments. Moreover, ASA (100 mg/kg/day orally) and DOX (1.2 mg/kg biweekly ip) induced synergistic antitumor activity in the HepG2 cell xenograft model in nude mice. Therefore, the combination of ASA and DOX could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of hepatocellular carcinoma.
Direct Imaging ofSc2@C84Molecules Encapsulated Inside Single-Wall Carbon Nanotubes by High Resolution Electron Microscopy with Atomic Sensitivity (2003)

Intramolecular structure of the scandium dimetallofullerene (Sc(2)@C(84)) has been clearly revealed by high resolution transmission electron microscopy with the single-atom sensitivity. Direct observation of two Sc atoms inside each fullerene molecule has led to a successful determination of the molecular symmetry among the three possible structural isomers for the Sc(2)@C(84). The present work introduces a new electron microscopic approach to investigate individual molecular structures and demonstrates the possibility for determining the molecular isomer on a single-molecular basis.
Amorphous Carbon-promoted Low-temperature Crystallization of Silica (2006)

Abstract Heating of mesoporous silica hybridized with self-assembled disc-like molecules such as hexabenzocoronene and triphenylene derivatives at ≥900 °C under N2 resulted in low-temperature crystallization of its amorphous silicate framework into cristobalite, a form of crystalline silica that appears in a much higher temperature range in the phase diagram.
Universal Receiver for Weighted Circularly Convolved OFDM/OQAM (2015)

The weighted circularly convolved OFDM/OQAM (WCC-OFDM/OQAM), a variant of OFDM/OQAM without time-domain tail overhead, is investigated in a doubly dispersive fading environment. A new receiver is proposed that resolves the self-interference present at a regular WCC-OFDM/OQAM receiver when the channel variations are too fast compared to the signal burst duration. This is achieved by exploiting the channel state information (CSI) available at the receiver to compensate for the channel discontinuity that appears in the receiver's circular operations. The proposed receiver is universal in two regards: first, it performs equally well for a wide range of speeds and modulation and coding schemes (MCSs), and second, it does not require any change to the WCC-OFDM/OQAM signal structure, and thus, is transparent to the transmitter.