gebhart/patrepeval huggingface dataset:
Phosphorylation of Ewing's sarcoma protein (EWS) and EWS-Fli1 in response to DNA damage (2008)

In Ewing's sarcomas, chromosomal translocations cause the N-terminal domain of the EWS (Ewing's sarcoma protein) to fuse with the DNA-binding domains of the Ets (E26 transformation-specific) family of transcription factors. Here we show that EWS and EWS-Fli1 (Friend leukaemia virus integration 1), the fusion most frequently found in Ewing's sarcomas, become phosphorylated at Thr(79) in response to either mitogens or DNA-damaging agents. The much weaker mitogen-induced phosphorylation of EWS is catalysed by the MAPKs (mitogen-activated protein kinases) ERK1 (extracellular signal-regulated kinase 1) and ERK2, whereas the much stronger phosphorylation of EWS induced by the DNA alkylating agent MMS (methyl methanesulphonate) can be catalysed by JNK (c-Jun N-terminal kinase) and at least one other protein kinase distinct from ERK1/ERK2. In contrast, the phosphorylation of EWS-Fli1 induced by MMS was largely mediated by p38alpha/p38beta MAPKs. MMS induced a much stronger phosphorylation of EWS-Fli1 than EWS in heterodimers comprising both proteins.
Thermoflow multiplicity in a packed‐bed reactor: Conduction and cooling effects (1989)

Abstract Steady states with different flow rates and temperature profiles may exist in different tubes of a multitube packed‐bed reactor due to the coupling among the species, energy and momentum balances, and the change of physical properties with temperature and pressure. Under typical operating conditions if no axial conduction of heat occurs thermoflow multiplicity can be found only for unrealistically high heats of reaction and/or over a very narrow range of exit pressures. However, accounting for the finite but small heat conduction in the reactor tubes leads to multiplicity for typical parameters and a reasonable range of exit pressures. Cooling tends to decrease the region of parameters for which the multiplicity occurs.
Unique features of bovine lymphocytes exposed to a staphylococcal enterotoxin (2006)

We previously demonstrated that stimulation of bovine peripheral blood mononuclear cells (PBMCs) with staphylococcal enterotoxin C (SEC), led to an inversion of the CD4(+):CD8(+)T cell ratio and generation of an atypical CD8(+)T cell subpopulation expressing CD26. In the present study, we examined T cell apoptosis and proliferation profiles of PBMC subpopulations in cultures stimulated with SEC. Unlike when stimulated with concanavalin A, nucleic acid synthesis in bovine PBMC cultures stimulated with SEC was low during the first four days but increased greatly on day 5. In contrast, nucleic acid synthesis in human PBMC cultures stimulated with SEC increased continuously. To investigate the mechanism of delayed bovine T cell proliferation, various cell phenotypes were monitored. The inversion of the bovine CD4(+):CD8(+)T cell ratio in PBMC cultures stimulated by SEC was associated with higher proliferation and lower apoptosis of CD8(+)T cells compared to CD4(+)T cells. The mRNA levels for interleukin (IL)-4 and IL-13 were sustained over 4 days but IL-12 mRNA levels dropped to background on day 2. These data suggest that SEC induces a prolonged Th-2- biased microenvironment, and together with the inversion of the bovine CD4(+):CD8(+)T cell ratios in bovine PBMC cultures with SEC, may in part explain the inability of the mammary immune system to establish an effective response to Staphylococcus aureus infections.
The value of revision surgery after initial amputation of an upper or lower limb (1987)

The value of revision surgery when carried out more than six weeks after initial amputation of the upper or lower limb was assessed. When performed for stump and/or phantom limb pain alone, only 33/95 (35%) obtained satisfactory results after one revision; 25/95 (26%) of the patients required four or more surgical procedures without relief of pain. However, when carried out for local specific pathology, the results of surgical revision were 100% successful, even if the procedure had to be repeated once in 15% (28/189) of this group of patients. Transcutaneous nerve stimulation appeared to offer no long lasting relief of pain following amputation surgery.
Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody–positive individuals (2021)

Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.
Passivation of Amorphous Oxide Semiconductors Utilizing a Zinc–Tin–Silicon–Oxide Barrier Layer (2012)

Sputter-deposited amorphous zinc-tin-silicon-oxide (ZTSO) is demonstrated to be a viable electronic passivation layer for bottom-gate thin-film transistors (TFTs) with amorphous zinc-tin-oxide and indium-gallium-zinc-oxide channels. ZTSO allows for successful passivation of these semiconductors without significant changes in turn-on voltage, hysteresis, or channel mobility that is commonly associated with unsuccessful passivation of amorphous oxide semiconductors (AOSs). Passivation of AOS TFTs using ZTSO significantly increases electrical stability under negative-bias illumination stress testing conditions compared with unpassivated AOS TFTs. ZTSO also acts as a barrier layer allowing for additional postprocessing (e.g., plasma-enhanced chemical vapor deposition processes) that in some cases can negatively effect an unprotected AOS layer.
A General Route to Fully Terminally tert‐Butylated Linear Polyenes (2010)

Starting from the readily available α,β-unsaturated ketone, 3-tert-butyl-4,4-dimethyl-2-pentenal, higher vinylogues, and fully terminally tert-butylated polyolefins with up to 13 consecutive conjugated double bonds have been prepared by either McMurry dimerization or Wittig chain-elongation routes. The highly unsaturated conjugated π systems, which show a remarkable stability, have been characterized by spectroscopic methods and, in many cases, by X-ray structural analysis. The yields are high enough to allow for thorough chemical reactivity studies.
Abstract B101: Engineered PD-1 variants as immunotherapies for cancer (2016)

Abstract Immunotherapies represent the next generation of treatments for cancer. The recent clinical successes of immunotherapies have highlighted the potential to achieve stunning efficacy against otherwise intractable cancers. One such clinically validated immunotherapy target is the T-cell surface receptor PD-1 (programmed cell death protein 1), which inhibits T-cell cytotoxicity upon ligation with PD-L1 (programmed death-ligand 1) on a target cell. Antibody therapies targeting PD-1/PD-L1 can be strikingly effective cancer treatments, as demonstrated in the clinic by the recently approved pembrolizumab and nivolumab. However, antibody therapies have significant drawbacks as agents against this pathway. Due to their large size (~150 kDa), antibodies have limited tissue penetrance. Furthermore, due to the presence of the prophagocytic Fc domain, antibodies bound to PD-1 or PD-L1 on the T-cell cause counterproductive lymphocyte depletion. We hypothesized that a small engineered protein capable of blocking PD-1:PD-L1 signaling could avoid these issues and function as a superior immunotherapy. To accomplish this goal, we used yeast display-based directed evolution to affinity-mature a soluble form of the PD-1 ectodomain to increase its affinity for human PD-L1. After several rounds of selection from two generations of mutant libraries, we identified a high-affinity PD-1 variant. By surface plasmon resonance, high-affinity PD-1 binds to human PD-L1 with 110 pM affinity and a half-life of binding of &amp;gt;40 minutes, a dramatic improvement from wild-type PD-1. Direct in vivo binding assays demonstrate that this small protein penetrates solid tissues much more effectively than an anti-PD-L1 monoclonal antibody. Unlike anti-PD-L1 antibodies, high-affinity PD-1 does not lead to the depletion of effector T-cells. Consistent with these advantages, in syngeneic CT26 tumor models, high affinity PD-1 was effective in treating both small (~50 mm3) and large tumors (&amp;gt;150 mm3), whereas the activity of anti-PD-L1 antibodies was completely abrogated against large tumors. Furthermore, radiolabeling of high-affinity PD-1 enabled us to utilize our reagent as a non-invasive tracer for PET imaging. Taken together, our data demonstrates the benefits of using small, non-antibody therapeutics as cancer immunotherapy and immune diagnostic agents. Citation Format: Sydney R. Gordon, Roy Maute, Aaron Mayer, Melissa McCracken, Arutselvan Natarajan, Nan Guo, Richard Kimura, Jonathan M. Tsai, Aashish Manglik, Andrew Kruse, Sanjiv Gambhir, Irving L. Weissman, Aaron M. Ring. Engineered PD-1 variants as immunotherapies for cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B101.
Why is my smartphone slow? On the fly diagnosis of underperformance on the mobile Internet (2013)

The perceived end-to-end performance of the mobile Internet can be impacted by multiple factors including websites, devices, and network components. Constant changes in these factors and network complexity make identifying root causes of high latency difficult. In this paper, we propose a multidimensional diagnosis technique using passive IP flow data collected at ISPs for investigating factors that impact the performance of the mobile Internet. We implement and evaluate our technique over four days of data from a major US cellular provider's network. Our approach identifies several combinations of factors affecting performance. We investigate four combinations indepth to confirm the latency causes chosen by our technique. Our findings include a popular gaming website showing poor performance on a specific device type for over 50% of the flows and web browser traffic on older devices accounting for 99% of poorly performing traffic. Our technique can direct operators in choosing factors having high impact on latency in the mobile Internet.
Data from Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10 (2023)

&lt;div&gt;Abstract&lt;p&gt;ONC201/TIC10 is a small-molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway–inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small-molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes, including the multikinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib cotreatment to enhance anticancer responses. &lt;i&gt;Cancer Res; 75(8); 1668–74. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs (2015)

Several proteins and RNAs expressed by mammalian viruses have been reported to interfere with RNA interference (RNAi) activity. We investigated the ability of the HIV-1-encoded RNA elements Trans-Activation Response (TAR) and Rev-Response Element (RRE) to alter RNAi. MicroRNA let7-based assays showed that RRE is a potent suppressor of RNAi activity, while TAR displayed moderate RNAi suppression. We demonstrate that RRE binds to TAR-RNA Binding Protein (TRBP), an essential component of the RNA Induced Silencing Complex (RISC). The binding of TAR and RRE to TRBP displaces small interfering (si)RNAs from binding to TRBP. Several stem-deleted RRE mutants lost their ability to suppress RNAi activity, which correlated with a reduced ability to compete with siRNA-TRBP binding. A lentiviral vector expressing TAR and RRE restricted RNAi, but RNAi was restored when Rev or GagPol were coexpressed. Adenoviruses are restricted by RNAi and encode their own suppressors of RNAi, the Virus-Associated (VA) RNA elements. RRE enhanced the replication of wild-type and VA-deficient adenovirus. Our work describes RRE as a novel suppressor of RNAi that acts by competing with siRNAs rather than by disrupting the RISC. This function is masked in lentiviral vectors co-expressed with viral proteins and thus will not affect their use in gene therapy. The potent RNAi suppressive effects of RRE identified in this study could be used to enhance the expression of RNAi restricted viruses used in oncolysis such as adenoviruses.
High‐resolution mapping of neuronal activation with balanced SSFP at 9.4 tesla (2015)

High spatial and temporal resolution balanced SSFP at 9.4T to detect functional activation is feasible. Activation patterns and signal changes are stable and reproducible across subjects within the visual cortex, and comparable to reported values of SE-EPI at 7T and 9.4T. Magn Reson Med 76:163-171, 2016. © 2015 Wiley Periodicals, Inc.
Identification and structural characterisation of a partially arabinosylated lipoarabinomannan variant isolated from a Corynebacterium glutamicum ubiAmutant (2007)

Arabinan polysaccharide side-chains are present in both Mycobacterium tuberculosis and Corynebacterium glutamicum in the heteropolysaccharide arabinogalactan (AG), and in M. tuberculosis in the lipoglycan, lipoarabinomannan (LAM). Herein, we show by quantitative sugar and glycosyl linkage analysis that C. glutamicum possesses a much smaller LAM version, Cg-LAM, characterised by single t-Araf residues linked to the
Direct deposition of SrBi2Ta2O9 Film on IrO2 electrode using liquid source CVD method (1999)

Abstract SrBi2Ta2O9 (SBT) thin films were directly deposited on IrO2 electrode using liquid source CVD (LS-CVD) method. Bi deficient region in the SBT films, which existed near the conventional Pt bottom electrode, was successfully eliminated using IrO2 bottom electrode. X-ray diffraction analysis showed our SBT films on IrO2 have good crystalline quality. Satisfactory electric properties (6 μC/cm2 of 2Pr and 10−6 A/cm2 of leakage current) were obtained Key Words: SrBi2Ta2O9 SBTLS-CVDIrO2
Band 4.1-like proteins of the bovine lens. Effects of differentiation, distribution and extraction characteristics (1984)

Bovine lens epithelium, cortex and nucleus were screened for the presence of red-cell-membrane band 4.1-like proteins by using an immunoblot method. Lens epithelial cells were found to contain proteins of Mr 78 000 and higher (approximately 150 000) that cross-reacted with anti-(protein 4.1) sera. Fibre cells of the superficial cortex were also found to contain these two proteins, as well as an additional protein of approx. 80 000 Mr. In contrast, deep layers of the cortex and the lens nucleus contained no detectable cross-reactive protein at these Mr values. Treatment of a crude membrane fraction prepared from superficial bovine cortices with a low-ionic-strength buffer resulted in release of the high-Mr band 4.1-like protein. The 80 000- and 78 000-Mr proteins remained with the membrane fraction in low-ionic-strength buffer, but were released into solution by high-ionic-strength-buffer treatment. We have also demonstrated that the human red-blood-cell membrane, like lens epithelial cells and fibre cells, also contains a high-Mr band 4.1-like protein that is released from membranes by low-ionic-strength-buffer treatment.
Constitutive expression of Botrytis aclada laccase in Pichia pastoris (2012)

The heterologous expression of laccases is important for their large-scale production and genetic engineering—a prerequisite for industrial application. Pichia pastoris is the preferred expression host for fungal laccases. The recently cloned laccase from the ascomycete Botrytis aclada (BaLac) has been efficiently expressed in P. pastoris under the control of the inducible alcohol oxidase (AOX1) promoter. In this study, we compare these results to the constitutive expression in the same organism using the glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter. The results show that the amounts of BaLac produced with the GAP system (517 mgL-1) and the AOX1 system (495 mgL-1) are comparable. The constitutive expression is, however, faster, and the specific activity of BaLac in the culture supernatant is higher (41.3 Umg-1 GAP, 14.2 Umg-1 AOX1). In microtiter plates, the constitutive expression provides a clear advantage due to easy manipulation (simple medium, no methanol feeding) and fast enzyme production (high-throughput screening assays can already be performed after 48 h).
Quantitative evaluation of hemiplegic gait characteristic using wearable measurement device (2017)

Many people who have gait disorder in an accident need a rehabilitation therapy, and a therapy for gait disorder is often needed in therapies. However the parts and degrees of the disorder are various, so therapists should treat it by using the most suitable methods, and the indexes such as grand reaction forces and joint angles for therapy are needed. In the therapy for gait disorder, the machine such as force sensors and optical marker systems fixed in a laboratory has been used for a long time. However, it has many restrictions to measure gait and cannot measure continuous walking in under daily life environments for a long time. Therefore we developed a wearable gait measurement device, which consists of instrumented shoes with force transducers and inertial sensors, transmitters and attitude sensors. Compared with the conventional devices, it can measure gait under a condition without restrictions, and it can be used more easily and more generally. So it is thought that it can be used to measure the gait of people with gait disorder, which is difficult to measure by using the previous devices. The objective of this research is to measure the gait of a healthy subject and a hemiplegia subject with the wearable gait measurement device, evaluate their gait characteristic quantitatively and examine whether the hemiplegia gait is discriminative or not. The result is as follows. Ground reaction forces in the anterior-posterior direction and the vertical direction can show the hemiplegia gait characteristic. Also, ankle, knee and hip joint angles can show it, too. Moreover, by checking peaks of joint angles and comparing them, therapeutic effects on people with gait disorder can be evaluated quantitatively.
Natural history of pituitary carcinoma with metastasis to the cervical spine: illustrative case (2023)

This case underscores the importance of long-term monitoring of hormone levels and having a high clinical suspicion for metastatic disease to the spine in patients presenting with acute myelopathy or radiculopathy in the setting of previously treated invasive secreting pituitary adenoma.
Involvement of pRB family in TGF beta-dependent epithelial cell hypertrophy. (1995)

Although renal hypertrophy is often associated with the progressive loss of renal function, the mechanism of hypertrophy is poorly understood. In both primary cultures of rabbit proximal tubules and NRK-52E cells (a renal epithelial cell line), transforming growth factor beta 1 (TGF beta) converted epidermal growth factor (EGF)-induced hyperplasia into hypertrophy. TGF beta did not affect EGF-induced increases in c-fos mRNA abundance or cyclin E protein abundance, but inhibited EGF-induced entry into S, G2, and M phases. EGF alone increased the amount of hyperphosphorylated (inactive) pRB; TGF beta blocked EGF-induced pRB phosphorylation, maintaining pRB in the active form. To determine the importance of active pRB in TGF beta-induced hypertrophy, NRK-52E cells were infected with SV40 large T antigen (which inactivates pRB and related proteins and p53), HPV16 E6 (which degrades p53), HPV16 E7 (which binds and inactivates pRB and related proteins), or both HPV16 E6 and E7. In SV40 large T antigen expressing clones, the magnitude of EGF + TGF beta-induced hypertrophy was inhibited and was inversely related to the magnitude of SV40 large T antigen expression. In the HPV16-infected cells, EGF + TGF beta-induced hypertrophy was inhibited in E7- and E6E7-expressing, but not E6-expressing cells. These results suggest a requirement for active pRB in the development of EGF + TGF beta-induced renal epithelial cell hypertrophy. We suggest a model of renal cell hypertrophy mediated by EGF-induced entry into the cell cycle with TGF beta-induced blockade at G1/S, the latter due to maintained activity of pRB or a related protein.
Structure of 9-amino-2,7-di-tert-butylacridine (1992)

C 21 H 28 N 2 + .Cl - .H 2 O cristallise dans P3 1 avec a=11.086, c=14.367A, Z=3; affinement jusqu'a R=0.063. Dans ce compose existe un reseau etendu de liaisons hydrogene centre sur les ions chlorure positionnes sur les axes d'ordre trois. Dans le canal ainsi cree, les groupes amino sont diriges et lies par des liaisons hydrogene aux ions chlorure.
Isolation and Transcriptional Profiling of Purified Hepatic Cells Derived from Human Embryonic Stem Cells (2008)

The differentiation of human embryonic stem cells (hESCs) into functional hepatocytes provides a powerful in vitro model system for studying the molecular mechanisms governing liver development. Furthermore, a well-characterized renewable supply of hepatocytes differentiated from hESCs could be used for in vitro assays of drug metabolism and toxicology, screening of potential antiviral agents, and cell-based therapies to treat liver disease. In this study, we describe a protocol for the differentiation of hESCs toward hepatic cells with complex cellular morphologies. Putative hepatic cells were identified and isolated using a lentiviral vector, containing the alpha-fetoprotein promoter driving enhanced green fluorescent protein expression (AFP:eGFP). Whole-genome transcriptional profiling was performed on triplicate samples of AFP:eGFP+ and AFP:eGFP- cell populations using the recently released Affymetrix Exon Array ST 1.0 (Santa Clara, CA, http://www.affymetrix.com). Statistical analysis of the transcriptional profiles demonstrated that the AFP:eGFP+ population is highly enriched for genes characteristic of hepatic cells. These data provide a unique insight into the complex process of hepatocyte differentiation, point to signaling pathways that may be manipulated to more efficiently direct the differentiation of hESCs toward mature hepatocytes, and identify molecular markers that may be used for further dissection of hepatic cell differentiation from hESCs. Disclosure of potential conflicts of interest is found at the end of this article.
Molecular Target Characterization and Antimyeloma Activity of the Novel, Insulin-like Growth Factor 1 Receptor Inhibitor, GTx-134 (2011)

These studies support the potential therapeutic efficacy of GTx-134 in MM. Further, they provide a rationale for clinical application in combination with established antimyeloma treatments and novel targeted therapies.