gebhart/patrepeval huggingface dataset:
Overcoming EGFRG724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors (2018)

The emergence of acquired resistance against targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. In a subgroup of these patients we identified an association between selection of EGFR<sup>T790M</sup>-negative but EGFR<sup>G724S</sup>-positive subclones and osimertinib resistance. We demonstrate that EGFR<sup>G724S</sup> limits the activity of third-generation EGFR inhibitors both in vitro and in vivo. Structural analyses and computational modeling indicate that EGFR<sup>G724S</sup> mutations may induce a conformation of the glycine-rich loop, which is incompatible with the binding of third-generation TKIs. Systematic inhibitor screening and in-depth kinetic profiling validate these findings and show that second-generation EGFR inhibitors retain kinase affinity and overcome EGFR<sup>G724S</sup>-mediated resistance. In the case of afatinib this profile translates into a robust reduction of colony formation and tumor growth of EGFR<sup>G724S</sup>-driven cells. Our data provide a mechanistic basis for the osimertinib-induced selection of EGFR<sup>G724S</sup>-mutant clones and a rationale to treat these patients with clinically approved second-generation EGFR inhibitors.
Molecular analysis of the cumulus matrix: insights from mice with O -glycan-deficient oocytes (2015)

During follicle development, oocytes secrete factors that influence the development of granulosa and cumulus cells (CCs). In response to oocyte and somatic cell signals, CCs produce extracellular matrix (ECM) molecules resulting in cumulus expansion, which is essential for ovulation, fertilisation, and is predictive of oocyte quality. The cumulus ECM is largely made up of hyaluronan (HA), TNF-stimulated gene-6 (TSG-6, also known as TNFAIP6), pentraxin-3 (PTX3), and the heavy chains (HCs) of serum-derived inter-α-inhibitor proteins. In contrast to other in vivo models where modified expansion impairs fertility, the cumulus mass of C1galt1 Mutants, which have oocyte-specific deletion of core 1-derived O-glycans, is modified without impairing fertility. In this report, we used C1galt1 Mutant (C1galt1(FF):ZP3Cre) and Control (C1galt1(FF)) mice to investigate how cumulus expansion is affected by oocyte-specific deletion of core 1-derived O-glycans without adversely affecting oocyte quality. Mutant cumulus-oocyte complexes (COCs) are smaller than Controls, with fewer CCs. Interestingly, the CCs in Mutant mice are functionally normal as each cell produced normal levels of the ECM molecules HA, TSG-6, and PTX3. However, HC levels were elevated in Mutant COCs. These data reveal that oocyte glycoproteins carrying core 1-derived O-glycans have a regulatory role in COC development. In addition, our study of Controls indicates that a functional COC can form provided all essential components are present above a minimum threshold level, and thus some variation in ECM composition does not adversely affect oocyte development, ovulation or fertilisation. These data have important implications for IVF and the use of cumulus expansion as a criterion for oocyte assessment.
Toward Open Integrated Access and Backhaul with O-RAN (2023)

Millimeter wave (mmWave) communications has been recently standardized for use in the fifth generation (5G) of cellular networks, fulfilling the promise of multi-gigabit mobile throughput of current and future mobile radio network generations. In this context, the network densification required to overcome the difficult mmWave propagation will result in increased deployment costs. Integrated Access and Backhaul (IAB) has been proposed as an effective mean of reducing densification costs by deploying a wireless mesh network of base stations, where backhaul and access transmissions share the same radio technology. However, IAB requires sophisticated control mechanisms to operate efficiently and address the increased complexity. The Open Radio Access Network (RAN) paradigm represents the ideal enabler of RAN intelligent control, but its current specifications are not compatible with IAB. In this work, we discuss the challenges of integrating IAB into the Open RAN ecosystem, detailing the required architectural extensions that will enable dynamic control of 5G IAB networks. We implement the proposed integrated architecture into the first publicly-available Open-RAN-enabled experimental framework, which allows prototyping and testing Open-RAN-based solutions over end-to-end 5G IAB networks. Finally, we validate the framework with both ideal and realistic deployment scenarios exploiting the large-scale testing capabilities of publicly available experimental platforms
Clustering aggregation (2007)

We consider the following problem: given a set of clusterings, find a single clustering that agrees as much as possible with the input clusterings. This problem, clustering aggregation , appears naturally in various contexts. For example, clustering categorical data is an instance of the clustering aggregation problem; each categorical attribute can be viewed as a clustering of the input rows where rows are grouped together if they take the same value on that attribute. Clustering aggregation can also be used as a metaclustering method to improve the robustness of clustering by combining the output of multiple algorithms. Furthermore, the problem formulation does not require a priori information about the number of clusters; it is naturally determined by the optimization function. In this article, we give a formal statement of the clustering aggregation problem, and we propose a number of algorithms. Our algorithms make use of the connection between clustering aggregation and the problem of correlation clustering . Although the problems we consider are NP-hard, for several of our methods, we provide theoretical guarantees on the quality of the solutions. Our work provides the best deterministic approximation algorithm for the variation of the correlation clustering problem we consider. We also show how sampling can be used to scale the algorithms for large datasets. We give an extensive empirical evaluation demonstrating the usefulness of the problem and of the solutions.
51.4: Quantitative Analysis of LCD Motion Blur and Performance of Existing Approaches (2005)

Abstract LCD Motion blur is a well known problem. Although many solutions have been proposed, some fundamental questions have not been answered yet. In this paper, we try to answer such questions. Specifically, we calculate the waveform and its blur width of a moving edge perceived on LCD screen for current LCD and the proposed four solutions of hold‐type motion blur. We found that the slow response of current LCD is not a dominant factor of motion blur. The slow response of current LCD only contributes to 30% of the motion blur, while the hold‐type rendering mode of LCD contributes to 70%. Therefore, fast LCD such as OCB itself does not significantly reduce motion blur. Fast LCD, on the other hand, is critical to the proposed three solutions of hold‐type blur to avoid the ghosting artifact. With fast LCD, black data insertion and frame rate doubling can provide 50% reduction of motion blur. With both fast response LCD and fast backlight, backlight flashing can provide much higher reduction of motion blur.
CKB inhibits epithelial-mesenchymal transition and prostate cancer progression by sequestering and inhibiting AKT activation (2021)

Epithelial-mesenchymal transition (EMT) contributes to tumor invasion, metastasis and drug resistance. AKT activation is key in a number of cellular processes. While many positive regulators for either EMT or AKT activation have been reported, few negative regulators are established. Through kinase cDNA screen, we identified brain-type creatine kinase (CKB or BCK) as a potent suppressor for both. As a ubiquitously expressed kinase in normal tissues, CKB is significantly downregulated in several solid cancer types. Lower CKB expression is significantly associated with worse prognosis. Phenotypically, CKB overexpression suppresses, while its silencing promotes, EMT and cell migration, xenograft tumor growth and metastasis of prostate cancer cells. AKT activation is one of the most prominent signaling events upon CKB silencing in prostate cancer cells, which is in line with prostate cancer TCGA data. EMT enhanced by CKB silencing is abolished by AKT inhibition. Mechanistically, CKB interacts with AKT and sequestrates it from activation by mTOR. We further elucidated that an 84aa fragment at C-terminus of CKB protein interacts with AKT's PH domain. Ectopic expression of the 84aa CKB fragment inhibits AKT activation, EMT and cell proliferation. Interestingly, molecular dynamics simulation on crystal structures of AKT and CKB independently demonstrates that AKT's PH domain and CKB's 84aa fragment establish their major interaction interface. In summary, we have discovered CKB as a negative regulator of EMT and AKT activation, revealing a new mode of their regulation . We have also demonstrated that CKB downregulation is a poor prognosticator, which is sufficient to promote prostate cancer progression.
ChemInform Abstract: Recent Developments in the Use of Enzyme‐Catalyzed Reactions in Organic Synthesis, Resulting from Work at Exeter University (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
<title>Speech compression using wavelet packet and vector quantizer with 8-msec delay</title> (1995)

We present an algorithm for speech compression which uses the wavelet packet transform, vector quantization, entropy coding and postfiltering of the decoded speech. We address the following issue: obtaining the best speech quality for a given bit rate with minimal algorithmic delay (applying it on the possible shortest segment). The wavelet packet transform provides good compression since it is based on a very close relation between the transform and the actual physical processes in the human ear. The experimental results demonstrate that we can compress speech by factor of 6 - 10 and still have reasonable intelligibility and perceivability of the output speech using an algorithmic delay of 8 msec (64 speech samples). In addition, the proposed algorithm fits well DSP architecture and can be easily ported into any current 40MIPS DSP. By comparing the proposed algorithm in this paper with new CELP-oriented algorithm one can conclude that the former has less delay with higher compression ratio. The postfiltering was found to improve the quality of the decoded speech. We see that by using fixed size segments with 64 samples with wrap-around in the segments border does not degrade the performance in comparison to FIR-implementation without wrap-around. In addition, it is useful to implement different filter in each level of the decomposition.
Synthesis and Mixed Lineage Kinase Activity of Pyrrolocarbazole and Isoindolone Analogs of (+)K-252a (2007)

Structural modification of the indolecarbazole natural product (+)K-252a identified structural requirements for MLK activity and a novel series of potent fused pyrrolocarbazole MLK1/3 inhibitors. The SAR revealed that the lactam regiochemistry, the shape of the heterocycle, and aryl rings B and F are important to MLK activity. Heteroatom and alkyl replacement of the N-12 and/or N-13 indole nitrogen atoms identified the nonplanar dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7-one (8) and corresponding 5,7-dione (7) as potent cell-permeable MLK1/3 family-selective leads with in vitro activity comparable to that of (+)K-252a and determined them to be 2- to 3-fold more potent than the aglycone natural product K-252c.
P2–037: Age‐dependent impairment of hilar GABAergic interneurons and cognitive function in Apolipoprotein E‐ε4 knock‐in mice is modified by sex (2013)

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD). ApoE4 has sex-dependent effects, whereby the risk of developing AD is higher in apoE4-expressing females than males. However, the mechanism underlying the sex difference, in relation to apoE4, is unknown. Previous findings indicate that apoE4 causes age-dependent impairments of hilar GABAergic interneurons in female mice, leading to learning and memory deficits. Here, we investigate whether the detrimental effects of apoE4 on hilar GABAergic interneurons are sex-dependent using apoE knock-in (KI) mice across different ages. Cognitive function was analyzed in 12-month and 16-month old male and female apoE-KI mice. Immunohistochemical studies were conducted on apoE-KI mice at various ages, and positive cells in the hippocampal region and cortex were subsequently quantified by design-based stereology. We found that in female apoE-KI mice, there was an age-dependent depletion of hilar GABAergic interneurons, whereby GAD67- or somatostatin-positive-but not NPY- or parvalbumin-positive-interneuron loss was exacerbated by apoE4. This effect was recapitulated in female mice expressing apoE4 in CNS neurons. Loss of these neuronal populations was correlated with the severity of spatial learning deficits at 16 months of age in female apoE4-KI mice; however, this phenotype was not observed in female apoE3-KI mice. In contrast, we found an increase in the numbers of hilar GABAergic interneurons with advancing age in male apoE-KI mice, regardless of apoE genotype. Moreover, male apoE-KI mice showed a consistent ratio of hilar inhibitory GABAergic interneurons to excitatory mossy cells approximating 1.5 that is independent of apoE genotype and age, whereas female apoE-KI mice exhibited an age-dependent decrease in this ratio, which was exacerbated by apoE4. Accordingly, female apoE4-KI mice exhibited greater susceptibility to drug-induced seizures than male apoE4-KI mice. Interestingly, there are no apoE genotype effects on GABAergic interneurons in the CA1 and CA3 subregions of the hippocampus as well as the entorhinal and auditory cortexes. These findings suggest that the sex-dependent effects of apoE4 on developing AD is in part attributable to inherent sex-based differences in the numbers of hilar GABAergic interneurons, which is further modulated by apoE genotype.
Computation-Enabled Lensless Imaging & Deep-Brain Microscopy (2019)

We show imaging using only a CMOS image sensor, and fluorescence microscopy inside the mouse brain using a surgical needle and an image sensor, both enabled by computation including machine learning. © 2019 The Author(s)
Fast Decoders for Topological Quantum Codes (2010)

We present a family of algorithms, combining real-space renormalization methods and belief propagation, to estimate the free energy of a topologically ordered system in the presence of defects. Such an algorithm is needed to preserve the quantum information stored in the ground space of a topologically ordered system and to decode topological error-correcting codes. For a system of linear size l, our algorithm runs in time logl compared to l{6} needed for the minimum-weight perfect matching algorithm previously used in this context and achieves a higher depolarizing error threshold.
Measurement of charged pion, kaon, and proton production in proton-proton collisions at s=13  TeV (2017)

Transverse momentum spectra of charged pions, kaons, and protons are measured in proton-proton collisions at ffiffi ffi s p 13 TeV with the CMS detector at the LHC. The particles, identified via their energy loss in the silicon tracker, are measured in the transverse momentum range of p T 0.1-1.7 GeV=c and rapidities jyj < 1. The p T spectra and integrated yields are compared to previous results at smaller ffiffi ffi s p and to predictions of Monte Carlo event generators. The average p T increases with particle mass and charged particle multiplicity of the event. Comparisons with previous CMS results at ffiffi ffi s p 0.9, 2.76, and 7 TeV show that the average p T and the ratios of hadron yields feature very similar dependences on the particle multiplicity in the event, independently of the center-of-mass energy of the pp collision.
Cellular and molecular mechanisms regulating the development of tertiary lymphoid structures in tumor (2018)

Abstract Tertiary lymphoid structures (TLS) have been described in association with several tumor types, and they are usually associated with enhanced patient survival. However, mechanisms regulating their formation remain unknown. We found that intra- and peri-tumoral TLS develop in intraperitoneal (IP) but not subcutaneously (SC) implanted tumors. These TLS are characterized by a robust accumulation of B cells, and an associated reticular network of podoplanin+ fibroblasts expressing high levels of CXCL12, CXCL13, and the B-cell survival factors BAFF and APRIL. These results suggest that IP tumor-associated fibroblasts are polarized into organizer cells that orchestrate TLS formation. We’ve previously demonstrated that CD8 T effectors induce the development of lymph node-like vasculature in IP tumors. To determine whether these cells also regulate TLS development, we evaluated IP tumors grown in Rag1−/− mice and Rag1−/− mice repleted with bulk CD8 T cells. CD8 T cells upregulated the number of podoplanin+ fibroblasts and CXCL12 expression. However, CXCL13, BAFF and APRIL expression was not dependent on CD8 T cells. Thus, the representation of podoplanin+ fibroblasts and their expression of CXCL12 is regulated by adaptive immunity, while their expression of CXCL13, BAFF and APRIL is mediated by an innate element within the IP tumor microenvironment. We also found that increasing the load of the model tumor antigen ovalbumin led to an increased formation of peri-tumoral TLS with a classical organization, on top of the non-classical intratumoral structures evident at a low antigen load. These results identify novel mechanisms regulating different elements involved in organizing tumor-associated TLS.
Organic–inorganic hybrid gate dielectric for solution-processed ZnO thin film transistors (2013)

The preparation of a hybrid dielectric film was carried out by blending sol–gel-derived sodium beta alumina (SBA) and poly(4-vinylphenol) (PVP) to enhance the capacitance of a gate dielectric film. PVP-SBA was cured at a temperature sufficiently low enough to apply to a plastic substrate, while maintaining good electrical properties and uniformity. Addition of sol–gel-derived SBA improved the film density, resulting in good PVP-SBA thermal stability. The prepared PVP-SBA was used for high-performance aqueous solution-based ZnO transistors at 200 °C.
Temperature-Controlled Direct Imprinting of Ag Ionic Ink: Flexible Metal Grid Transparent Conductors with Enhanced Electromechanical Durability (2017)

Next-generation transparent conductors (TCs) require excellent electromechanical durability under mechanical deformations as well as high electrical conductivity and transparency. Here we introduce a method for the fabrication of highly conductive, low-porosity, flexible metal grid TCs via temperature-controlled direct imprinting (TCDI) of Ag ionic ink. The TCDI technique based on two-step heating is capable of not only stably capturing the Ag ionic ink, but also reducing the porosity of thermally decomposed Ag nanoparticle structures by eliminating large amounts of organic complexes. The porosity reduction of metal grid TCs on a glass substrate leads to a significant decrease of the sheet resistance from 21.5 to 5.5 Ω sq<sup>-1</sup> with an optical transmittance of 91% at λ = 550 nm. The low-porosity metal grid TCs are effectively embedded to uniform, thin and transparent polymer films with negligible resistance changes from the glass substrate having strong interfacial fracture energy (~8.2 J m<sup>-2</sup>). Finally, as the porosity decreases, the flexible metal grid TCs show a significantly enhanced electromechanical durability under bending stresses. Organic light-emitting diodes based on the flexible metal grid TCs as anode electrodes are demonstrated.
Data from Measurement of Tumor VEGF-A Levels with <sup>89</sup>Zr-Bevacizumab PET as an Early Biomarker for the Antiangiogenic Effect of Everolimus Treatment in an Ovarian Cancer Xenograft Model (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The mTOR pathway is frequently activated in ovarian cancers. mTOR inhibitors, such as everolimus, can reduce VEGF-A production by cancer cells. We investigated whether early everolimus treatment effects could be monitored by positron emission tomography (PET) with &lt;sup&gt;89&lt;/sup&gt;Zr-bevacizumab.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; The effect of everolimus on VEGF-A secretion was determined in a panel of human ovarian cancer cell lines and in A2780&lt;sup&gt;luc+&lt;/sup&gt; ovarian cancer cells xenografted subcutaneously in BALB/c mice. Mice received daily 10 mg/kg everolimus intraperitoneally (i.p.) for 14 days. PET scans with the tracer &lt;sup&gt;89&lt;/sup&gt;Zr-labeled bevacizumab were conducted before and after treatment. &lt;i&gt;Ex vivo&lt;/i&gt;&lt;sup&gt;89&lt;/sup&gt;Zr-bevacizumab biodistribution and correlative tissue analyses were conducted. Tumor VEGF-A levels were measured with ELISA and mean vascular density (MVD) was determined with immunohistochemistry.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Everolimus treatment reduced VEGF-A levels in the supernatant of all cell lines. Everolimus lowered &lt;sup&gt;89&lt;/sup&gt;Zr-bevacizumab tumor uptake by 21.7% ± 4.0% [mean standardized uptake value (SUV&lt;sub&gt;mean&lt;/sub&gt;) 2.3 ± 0.2 vs. 2.9 ± 0.2, &lt;i&gt;P&lt;/i&gt; &lt; 0.01]. &lt;i&gt;Ex vivo&lt;/i&gt; biodistribution also showed lower tracer uptake in the tumors of treated as compared with control animals (7.8 ± 0.8%ID/g vs. 14.0 ± 1.7%ID/g, &lt;i&gt;P&lt;/i&gt; &lt; 0.01), whereas no differences were observed for other tissues. This coincided with lower VEGF-A protein levels in tumor lysates in treated versus untreated tumors (&lt;i&gt;P&lt;/i&gt; = 0.04) and reduced MVD (&lt;i&gt;P&lt;/i&gt; &lt; 0.01).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Tumor VEGF-A levels are decreased by everolimus. &lt;sup&gt;89&lt;/sup&gt;Zr-bevacizumab PET could be used to monitor tumor VEGF-A levels as an early biomarker of the antiangiogenic effect of mTOR inhibitor therapy. &lt;i&gt;Clin Cancer Res; 18(22); 6306–14. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Interleukin-12–Activated Natural Killer Cells Recognize B7 Costimulatory Molecules on Tumor Cells and Autologous Dendritic Cells (1998)

Activation of natural killer (NK) cells in the presence of interleukin-12 (IL-12) augments the capacity of these effector cells to recognize B7-1- and B7-2-expressing target cells. These effector cells also efficiently lyse autologous B7-positive progenitor or organ-derived dendritic cells, suggesting a physiologic regulatory pathway between IL-12, NK cells, and B7-expressing antigen-presenting cells. Although IL-12-activated NK cells secreted higher levels of interferon-gamma, this cytokine did not play a role in synergistic effects of IL-12 and B7 on NK activation. The B7-counterreceptor was found to be selectively upregulated on IL-2/IL-12 as compared with IL-2-activated NK cells. CD28 is functionally involved in the recognition of B7 on target cells since IL-2/IL-12-activated NK cells derived from CD28 knockout mice were strongly reduced in their capacity to lyse syngeneic B7-positive tumor cells as well as antigen-presenting cells. However, recognition of B7 on allogeneic targets did not require the expression of CD28 on the IL-2/IL-12-activated NK cells. Hence, IL-12 triggers the expression of both CD28-dependent and CD28-independent mechanisms that allow NK cells to eliminate B7-positive target cells including autologous dendritic cells.