gebhart/patrepeval huggingface dataset:
In vitroandin vivoprotein - DNA interactions on the rat erythroid-specific L′ pyruvate kinase gene promoter (1992)

The rat L-type pyruvate kinase gene possesses two alternative tissue-specific promoters, located 472 bp apart; the upstream L' promoter is erythroid-specific and the downstream L promoter is hepatocyte-specific. The erythroid-specific L' promoter is strongly active in fetal liver at day 17 of gestation, while its activity rapidly decreases thereafter. A L' promoter fragment spanning from nucleotide -320 to +10 with respect to the cap site is able to direct a weak but erythroid-specific transcription in a cell-free system. We have used DNAse I footprinting and gel mobility shift assays to characterize and identify the binding of nuclear factors from both 17-day-old fetal liver and adult liver nuclear extracts to a 320 bp fragment of the 5' flanking region of the gene in vitro. Two clusters of erythroid-specific interactions were found. The proximal cluster consists of two GATA-1 binding sites at -50 bp and -65 bp from the transcription initiation site, immediately downstream of a CACC motif and two G/C-rich elements. The distal cluster of cis-elements, located 130 bp upstream, corresponds to two GATA-1 sequences. These two sequences overlap NF1 motifs interacting with ubiquitous NF1 transcriptional factors in presence of adult hepatic extracts. Furthermore, we have examined in vivo protein-DNA interactions by DMS footprinting in livers of 17-day-old rat fetuses and adult rats. We found that the sites characterized in vitro are occupied in vivo. Therefore, in adult liver the L' promoter, although inactive, nevertheless interacts with ubiquitous factors.
Delivery of loaded MR1 monomer results in efficient ligand exchange to host MR1 and subsequent MR1T cell activation (2022)

Abstract MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 antigen presentation pathways. To investigate ligand exchange pathways for MR1, we used MR1 monomers and tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) to deliver the antigen. Using MR1-deficient cells reconstituted with wild-type MR1 or MR1 molecules that cannot bind 5-OP-RU, we show that presentation of monomer-delivered 5-OP-RU is dependent on cellular MR1 and requires the transfer of ligand from the soluble molecule onto MR1 expressed by the antigen presenting cell. This mode of antigen delivery strengthens the evidence for post-ER ligand exchange pathways for MR1, which could represent an important avenue by which MR1 acquires antigens derived from endocytosed pathogens.
Genesis and shape of natural solution cavities within salt deposits (2008)

Since the genesis and shape of natural deep‐seated cavities within a salt body are insufficiently understood, the current study tries to shed some light on this topic. To this end, freshwater was pumped slowly through a horizontal borehole in rock salt cores. Owing to fast halite dissolution kinetics, high solubility, and slow inflow rate, halite dissolution took place only in the inflow of the rock salt cylinder. The shape of the created cavities is an approximately symmetrical half cone with a horizontal base facing upward. A conceptual model is presented that is inspired by the experimental results and based on theoretical hydraulic‐geochemical considerations, as well as on field observations. It proposes that triangular prism or conically shaped cavities develop within salt under confined conditions, where aggressive water flows upward along a fracture/conduit from an insoluble aquifer into the soluble stratum. Such cavity enlargements may cause land subsidence and structure collapse.
Deformation behavior during thermo-mechanical fatigue of a nickel-based single crystal superalloy (2011)

The deformation and damage mechanisms of a single crystal nickel-based superalloy CMSX-4 have been investigated under out-of-phase thermo-mechanical fatigue (OP TMF) condition. The failure mechanism was oxide-layered surface initiated crack followed by its planar growth along <100> γ channel. However, the deformation was highly localized to area near crack tip, where multiple groups of parallel twin plates on {111} planes formed during the high temperature-compressive half cycle. The localized twins provided a preferential path for crack propagation. OP TMF deformation was dominated by partial dislocation movement with {111}<112> slip system, resulting in the formation and propagation of deformation twins.
High-Speed Thin Client Technology for Mobile Environment: Mobile RVEC (2013)

Thin client systems on smart devices have been attracting interest from mobile workers because they do not need to contain any important business data, leading to improved security and business efficiency. In order to use a virtual desktop smoothly in various mobile environments with fluctuating bandwidth and packet loss ratio, it is essential for smart devices to have a stable mechanism for transferring images over an unstable network and smooth touchscreen operation. To meet these requirements, Fujitsu Laboratories Ltd. has developed new technologies called Mobile RVEC. They consist of an adaptive image transfer mechanism that considers variations in network bandwidth on a real-time basis, a data transfer protocol for unstable networks, and a touchscreen-based user interface for mobile thin clients. These technologies promise to open up new applications such as interactive product demonstrations at customer premises on mobile thin clients.
Design of 8×8 Butler Matrix Antenna for 5G Small Cell Beamforming Repeaters (2019)

In this paper, we propose a phased array antenna design for 5G mobile communication repeater. The proposed antenna has a gain of more than 10 dBi in the entire beam scanning range and has robustness against the interference problem with the adjacent device or deterioration due to the environment change, and thus has high portability and scalability.
Effects of Propionyl Triglyceride on Lipid Metabolism in Rats. (1997)

プロピオン酸トリグリセリド (PTG) 1, 3, 5%添加飼料でラットを14日間飼育し, 血清, 肝臓および糞の各脂質含量, ならびに糞と盲腸内容物の有機酸含量を調べた。1) ラットの体重増加は, 5%PTG群が最も低値を示したが, 食餌効率は各群間で差がなかった。2) PTG群の血清総コレステロール濃度は対照群より低かった。また, PTG群の血清トリグリセリド濃度は, 対照群に比較して低かったが, 1%および3%PTG添加群では有意差はなく, 5%PTGのみで有意に低かった。HDL-コレステロール濃度は各群でほとんど差がなかった。3) 5%PTG群における肝の全脂質, 総コレステロールおよびトリグリセリド含量は, いずれも対照群より有意に低かった。しかし, リン脂質の平均含量はいずれも対照群より高値を示した。4) 1%および3%PTG群における糞の全脂質排泄量は対照群より高値であった。しかし, 5%PTG群は対照群より低値を示した。また, 中性ステロール排泄量は, いずれのPTG群も対照群より高値であった。5) 糞および盲腸内容物中の酢酸, プロピオン酸および酪酸含量は各群でほとんど差が認められなかったが, 糞中の乳酸含量はPTG含量の高い群ほど低値を示した。
Organization and efferent connections of transplanted suprachiasmatic nuclei (1988)

The hypothalamic suprachiasmatic nucleus (SCh) is the principal brain structure involved in the generation of circadian rhythms. In the present study, we have employed immunohistochemical techniques to evaluate the development of the fetal SCh following its transplantation to the brain of adult host animals. Donor hypothalami were obtained from normal Long-Evans fetuses and transplanted to the lateral, third, or fourth ventricle of Brattleboro rats. Neuronal aggregations exhibiting the organotypic features of the SCh were present in over 90% of the grafts recovered at each transplantation site. Like the normal endogenous SCh, SCh-like cell groups identified within the transplants contained a prominent population of parvicellular (9-13 micron), neurophysin-containing neurons that were immunopositive for vasopressin (VP) but not oxytocin. These SCh-like cell groups also invariably contained similar small neurons that were immunoreactive for vasoactive intestinal polypeptide (VIP). Typically, VP and VIP immunoreactive perikarya were concentrated in contiguous, complementary parts of the grafted SCh, but fibers immunoreactive for either peptide were distributed throughout the extent of the nucleus. Because the brain of the Brattleboro rat is deficient in vasopressin, it was possible to evaluate the projection of the vasopressinergic component of the transplanted SCh to the host brain. Although SCh were identified in grafts recovered from each intraventricular transplantation site, an appreciable input to the host brain could be identified only when the fetal tissue was grafted to the third ventricle. Here, grafted SCh established efferent connections with periventricular diencephalic structures which ordinarily receive a projection from the in situ SCh. Specifically, VP immunoreactive fibers originating from transplanted SCh were identified in the medial preoptic area, the periventricular and dorsomedial hypothalamic nuclei, the paraventricular nuclei of the thalamus and hypothalamus, and in the retrochiasmatic area, arcuate nucleus, and suprachiasmatic nucleus of the host brain. These results demonstrate that the fetal SCh not only survives transplantation but also retains its distinguishing cytological features and the capacity to form an appropriately restricted set of efferent connections with the brain of adult host animals.
A model of epithelial and neutrophil responses to cystic fibrosis microbes (2022)

A subset of neutrophils in cystic fibrosis (CF) airways abundantly release tissue damaging neutrophil elastase (NE), causing lung damage. Triggers of this subset are unknown, limiting intervention. How CF airway microbes may be responsible&nbsp;is not&nbsp;well studied. To explore this, we developed a laboratory pipeline to characterise responses of airway tissue and neutrophils to virus and bacteria. Differentiated primary airway epithelial cell cultures were challenged individually, or co-infected, with rhinovirus and bacteria representative of pathogens and oral flora found in CF airways (<i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Neisseria lactamica</i>, and <i>Prevotella nigrescens</i>). After infection, cultures were washed apically with medical saline to sample infection milieus and assess epithelial cytokine release, and washes also applied to an <i>in vitro</i> model of neutrophil transmigration to the airways. Epithelial infection microenvironments were characterised by increased antiviral signals with exclusive rhinovirus infection, including MIG and IP-10, while <i>P. aeruginosa</i> uniquely increased pro-inflammatory cytokines IL-1α and β (10 fold, p&lt;0.001). Neutrophils migrating into washes primed by <i>P. aeruginosa</i> and <i>P. nigrescens</i> had elevated CD63 (7 fold, p&lt;0.001), a marker of NE release, and reduced expression of phagocytic receptor CD16 (0.4 fold, p&lt;0.001). These changes are reflective of neutrophils seen in CF airways. Findings indicate that primary and secondary infections by specific bacterial species trigger neutrophil exocytosis. A role for the anaerobe <i>P. nigrescens</i> in CF airway neutrophil pathology is intriguing. Ongoing studies seek to identify reprogramming mechanisms and potential therapeutic targets.
Complement C4d-specific antibodies for the diagnosis of lung cancer (2017)

Development of molecular markers that help to identify high-risk individuals or diagnose indeterminate pulmonary nodules could have a major impact on lung cancer clinical management. In this study, we evaluated the diagnostic potential of a newly-developed ELISA that specifically detects complement C4d. We measured this marker in five independent cohorts of plasma and bronchoalveolar lavage samples from lung cancer patients and controls. In case-control studies, the area under the ROC curve for the diagnosis of lung cancer was 0.82 (95%CI = 0.72-0.92) in plasma samples, and 0.80 (95%CI = 0.69 to 0.90) in bronchoalveolar lavage fluids. In a set of plasma samples from the MILD CT-screening trial, the assay was unable to discriminate between asymptomatic high-risk individuals with or without early stage lung cancer. On the contrary, in two independent cohorts of individuals with indeterminate pulmonary nodules, plasma samples from patients with lung cancer nodules presented higher levels of C4d than those from patients with benign nodules. Using a target population of patients with 8 to 30 mm nodules, the test identified likely benign lung nodules with 84% negative predictive value and 54% positive predictive value, at 89% specificity and 44% sensitivity. In conclusion, the specific determination of C4d may serve as an adjunct to current clinical practice in the diagnosis of indeterminate pulmonary nodules.
Phase-Dependent Dielectric Laser Acceleration of 99keV Electrons with Symmetrically Driven Silicon Dual Pillar Gratings (2018)

We present phase-dependent laser acceleration and deflection of electrons using a symmetrically driven silicon dual pillar grating. We demonstrate cosh accelerator modes and sinh deflecting modes at gradients of 200 MeV/m over 15 μm distance.
O82 A phase 1 dose escalation study of PRS-343, a HER2/4–1BB bispecific molecule, in patients with HER2-positive malignancies (2020)

<h3>Background</h3> Anticalin® proteins are recombinantly engineered human proteins based on lipocalins. PRS-343 is a first-in-class bispecific antibody-Anticalin fusion protein targeting the oncogenic tumor antigen HER2 and the costimulatory immune receptor 4-1BB on T and other immune cells. Here, we report the results of a phase 1 single-agent dose escalation trial in patients with HER2+ solid tumors. <h3>Methods</h3> PRS-343 has been evaluated in sequential dose cohorts from 0.0005 to 8 mg/kg i.v. Doses were administered Q3W and the 8 mg/kg dose was also given Q2W. An accelerated titration design was utilized for the initial dose escalation followed by a modified 3+3 design and the option to back-fill cohorts. Dose-limiting toxicities (DLTs) were reported during the first cycle of each schedule. The primary study objectives include the safety profile and RP2D of PRS-343. Secondary objectives include ORR and DCR, PD biomarker response and PK profile. PD response was assessed in tumor biopsies (CD8+ T cell IHC) pre- and post- PRS-343 treatment. <h3>Results</h3> 51 patients (median age 61.2 years, 61% female, 82% caucasian, 57% with more than three lines of prior therapy) with a variety of solid tumor indications [gastric/GEJ (n=19); BC (n=12); gynecological cancer (n=6); CRC (n=5); BTC (n=4); UC (n=2); melanoma, pancreatic and salivary duct (n=1 each)] have been treated with PRS-343. Based on pharmacokinetic analyses and observed kinetics of the CD8+ T cell expansion post-treatment, the low end of the active dose range is considered 2.5 mg/kg. 19 patients treated at active dose levels before the data cut-off on 09-06-2019 were evaluable for response [DCR 58% (11% confirmed PR) as per RECIST 1.1]. At the active doses, we observed significant and pronounced post-treatment expansion of CD8+ T cells particularly in the tumor nests, consistent with the MoA of PRS-343, while there was no increase in the doses below 2.5 mg/kg. The post-treatment expansion of CD8+ T cells was more pronounced in patients with a confirmed PR or prolonged SD. PRS-343 was very well tolerated, with no SAEs reported. The most frequent TRAEs were fatigue (9%), chills (6%) and diarrhea (5%) of mild to moderate severity. None qualified as a DLT. <h3>Conclusions</h3> PRS-343 is the first molecule of its kind to demonstrate encouraging evidence of safety and clinical benefit with a correlative PD effect in a heavily pre-treated population. These initial data suggest that PRS-343, the first 4-1BB bispecific to enter clinical development, merits further investigation in clinical trials. <h3>Trial Registration</h3> NCT03330561
Quantum dot/antibody conjugates for in vivo cytometric imaging in mice (2015)

Multiplexed, phenotypic, intravital cytometric imaging requires novel fluorophore conjugates that have an appropriate size for long circulation and diffusion and show virtually no nonspecific binding to cells/serum while binding to cells of interest with high specificity. In addition, these conjugates must be stable and maintain a high quantum yield in the in vivo environments. Here, we show that this can be achieved using compact (∼15 nm in hydrodynamic diameter) and biocompatible quantum dot (QD) -Ab conjugates. We developed these conjugates by coupling whole mAbs to QDs coated with norbornene-displaying polyimidazole ligands using tetrazine-norbornene cycloaddition. Our QD immunoconstructs were used for in vivo single-cell labeling in bone marrow. The intravital imaging studies using a chronic calvarial bone window showed that our QD-Ab conjugates diffuse into the entire bone marrow and efficiently label single cells belonging to rare populations of hematopoietic stem and progenitor cells (Sca1(+)c-Kit(+) cells). This in vivo cytometric technique may be useful in a wide range of structural and functional imaging to study the interactions between cells and between a cell and its environment in intact and diseased tissues.
Marginal crack after intravitreal bevacizumab for myopic choroidal neovascularization (2008)

The contraction-associated hypofluorescence line, namely marginal crack line, indicates the early damage of retinal pigment epithelium and seems to lead to expanding macular chorioretinal atrophy typically seen in mCNV.
Cyclic Melanotropins. VI. Reverse Phase HPLC Studies (1984)

Abstract The chromatographic behavior of 17 cyclic melanocyte stimulating hormone (α-MSH, α-melanotropin) analogs were studied on two reversed phase columns (Altech and Vydac) using several mobile phases. It was observed that analogs which contain a D-amino acid were always eluted earlier than the corresponding L-amino acid-containing analogues. Substitution of penicillamine for cysteine in the 4 position led to a more lipophilic compound as expected, but when penicillamine was substituted in the 10 position, apparently a less lipophilic compound resulted. These observations can be interpreted as a result of a conformational change in the molecule caused by the particular substitution. Furthermore, decreasing the size of the intramolecular disulfide ring led to a decrease in lipophilicity (i.e. retention time). The carba modification of the disulfide bridge had a similar effect as previously seen in oxytocin and vasopressin, that is, a decrease in retention time.
Reviewer bias in single- versus double-blind peer review (2017)

Peer review may be "single-blind," in which reviewers are aware of the names and affiliations of paper authors, or "double-blind," in which this information is hidden. Noting that computer science research often appears first or exclusively in peer-reviewed conferences rather than journals, we study these two reviewing models in the context of the 10th Association for Computing Machinery International Conference on Web Search and Data Mining, a highly selective venue (15.6% acceptance rate) in which expert committee members review full-length submissions for acceptance. We present a controlled experiment in which four committee members review each paper. Two of these four reviewers are drawn from a pool of committee members with access to author information; the other two are drawn from a disjoint pool without such access. This information asymmetry persists through the process of bidding for papers, reviewing papers, and entering scores. Reviewers in the single-blind condition typically bid for 22% fewer papers and preferentially bid for papers from top universities and companies. Once papers are allocated to reviewers, single-blind reviewers are significantly more likely than their double-blind counterparts to recommend for acceptance papers from famous authors, top universities, and top companies. The estimated odds multipliers are tangible, at 1.63, 1.58, and 2.10, respectively.
Electric Conduction in Mineral Oil based ZnONanofluids under Intense Electric Fields (2019)

The electric conduction processes in mineral oil based ZnO–C18 nanofluids under intense electric fields are investigated. For this, conduction currents are measured usinga needle-plane electrode co ...
On the hybrid beamforming with shared array antenna for mmWave MIMO-OFDM systems (2014)

Along with the attention drawn to the millimeter-wave frequency bands for the drastically increased data rate support for the next generation (5G) mobile communications, the hybrid beamforming architectures combining analog beamforming and digital precoding have been investigated as potential candidates to provide good compromise between the complexity and the performance. Among the different hybrid beamforming architectures, the architecture with so-called shared array antenna is analyzed with respect to the peak-to-mean envelope power ratio over antenna elements and the total average transmission power constraint upon multi-beam transmissions. It is shown that the non-trivial normalization coefficients should be applied to the hybrid beamforming architecture under consideration to achieve the average transmission power within the total power constraint. Taking into account the total power normalization for the hybrid beamforming architecture with shared array antenna, various simulation results are provided to show the performance of the multi-beam transmission diversity against the single-beam analog beamforming.
Cooperative Announcement-Based Caching for Video-on-Demand Streaming (2016)

Recently, video-on-demand (VoD) streaming services like Netflix and Hulu have gained a lot of popularity. This has led to a strong increase in bandwidth capacity requirements in the network. To reduce this network load, the design of appropriate caching strategies is of utmost importance. Based on the fact that, typically, a video stream is temporally segmented into smaller chunks that can be accessed and decoded independently, cache replacement strategies have been developed that take advantage of this temporal structure in the video. In this paper, two caching strategies are proposed that additionally take advantage of the phenomenon of binge watching, where users stream multiple consecutive episodes of the same series, reported by recent user behavior studies to become the everyday behavior. Taking into account this information allows us to predict future segment requests, even before the video playout has started. Two strategies are proposed, both with a different level of coordination between the caches in the network. Using a VoD request trace based on binge watching user characteristics, the presented algorithms have been thoroughly evaluated in multiple network topologies with different characteristics, showing their general applicability. It was shown that in a realistic scenario, the proposed election-based caching strategy can outperform the state-of-the-art by 20% in terms of cache hit ratio while using 4% less network bandwidth.
Inovação didática no Ensino de Física em Nível Superior: o caso da disciplina Applied Physics50 da Universidade de Harvard (2021)

No contexto das disciplinas introdutórias de Física em nível superior, o modelo de transmissão de informação em aulas expositivas continua predominante, apesar de seus resultados inferiores, em comparação a metodologias ativas de ensino. No presente artigo, apresentamos uma metodologia ativa vinculada à Aprendizagem Baseada em Projetos, criada no contexto da disciplina Applied Physics 50 (AP50) da Universidade de Harvard, explicitando seus princípios pedagógicos, técnicas e estratégias como estímulo para reflexão sobre possibilidades de reinvenção do ensino de Física em nível introdutório, consideradas as especificidades de cada contexto educacional.