gebhart/patrepeval huggingface dataset:
Fedratinib in myelofibrosis (2020)

Following the discovery of the JAK2V617F mutation in myeloproliferative neoplasms in 2005, fedratinib was developed as a small molecular inhibitor of JAK2. It was optimized to yield low-nanomolar activity against JAK2 (50% inhibitory concentration = 3 nM) and was identified to be selective for JAK2 relative to other JAK family members (eg, JAK1, JAK3, and TYK2). It quickly moved into clinical development with a phase 1 clinical trial opening in 2008, where a favorable impact on spleen and myelofibrosis (MF) symptom responses was reported. A phase 3 trial in JAK2 inhibitor treatment-naive MF patients followed in 2011 (JAKARTA); a phase 2 trial in MF patients resistant or intolerant to ruxolitinib followed in 2012 (JAKARTA-2). Clinical development suffered a major setback between 2013 and 2017 when the US Food and Drug Administration (FDA) placed fedratinib on clinical hold due to the development of symptoms concerning for Wernicke encephalopathy (WE) in 8 of 608 subjects (1.3%) who had received the drug. It was ultimately concluded that there was no evidence that fedratinib directly induces WE, but clear risk factors (eg, poor nutrition, uncontrolled gastrointestinal toxicity) were identified. In August 2019, the FDA approved fedratinib for the treatment of adults with intermediate-2 or high-risk MF. Notably, approval includes a "black box warning" on the risk of serious and fatal encephalopathy, including WE. FDA approval was granted on the basis of the JAKARTA studies in which the primary end points (ie, spleen and MF symptom responses) were met in ∼35% to 40% of patients (JAKARTA) and 25% to 30% of patients (JAKARTA-2), respectively.
A link between micro-LED simulation and Bayesian reasoning (2023)

We present an overview of kriging benefits when dealing with optical simulations of non-coherent light emitting µLED. Such device is composed of quantum wells (QW) forming a surface embedded in high index material and connected by metallic electrodes. The traditional way to simulate such object is using FDTD with a discretized QW surface into multiple dipoles. It leads to tremendous computational effort when conducting a parameter space exploration in order to optimize the µLED optical behaviour. To diminish the required number of one-dipole simulations, we propose to build a metamodel using Bayesian inference with Gaussian process iteratively building a non-uniform dipole grid more adapted to the QW surface. Gaussian process inference also enables calculating an estimate of the final result’s error margin to provide a stopping criteria for the simulation : it allows to considerably reduce the number of simulations one theoretically needs to perform.
Data from Toward the Prognostic Significance and Therapeutic Potential of HER3 Receptor Tyrosine Kinase in Human Colon Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Abnormal accumulation and dysregulation of the epidermal growth factor receptor family member HER3 is associated with the development of various human cancers including those of the breast, lung, and ovary. We have previously shown that in melanoma HER3 is frequently overexpressed and is associated with poor prognosis. However, the importance of HER3 in colon cancer and its putative prognostic significance is still unknown.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; HER3 expression was analyzed in primary colon tumors from 110 patients by immunohistochemistry and correlated with time of progression. Parallel to this, the influence of HER3 overexpression on cell proliferation, migration, invasion, and apoptosis was investigated in four different colon cancer cell lines including DLD-1, LoVo, CaCO2, and T-84.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; HER3 was detected at high frequency and exclusively at the membrane of the primary tumors. Elevated HER3 expression levels may serve as a putative prognostic marker because it associates with cell proliferation and decreased time to disease progression. High HER3 protein expression as well as phosphorylation levels were detected in tested cells. &lt;i&gt;HER3&lt;/i&gt; downregulation by RNA interference abrogated cell proliferation, migration, and invasion. In addition, suppression of &lt;i&gt;HER3&lt;/i&gt; resulted in a G&lt;sub&gt;2&lt;/sub&gt;–M cell-cycle arrest, induced apoptosis, and led to morphologic changes in colon cancer cell lines. Furthermore, application of a monoclonal antibody specific to the extracellular portion of the receptor reduced heregulin-β1–induced migration and invasion and also induced apoptosis in colon cancer cell lines.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; We postulate that HER3 is critically involved in colon cancer progression and may serve as a novel target for therapeutic intervention. &lt;i&gt;Clin Cancer Res; 18(4); 956–68. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Unsupervised Learning of Mixture Models with a Uniform Background Component. (2018)

Gaussian Mixture Models are one of the most studied and mature models in unsupervised learning. However, outliers are often present in the data and could influence the cluster estimation. In this paper, we study a new model that assumes that data comes from a mixture of a number of Gaussians as well as a uniform background component assumed to contain outliers and other non-interesting observations. We develop a novel method based on robust loss minimization that performs well in clustering such GMM with a uniform background. We give theoretical guarantees for our clustering algorithm to obtain best clustering results with high probability. Besides, we show that the result of our algorithm does not depend on initialization or local optima, and the parameter tuning is an easy task. By numeric simulations, we demonstrate that our algorithm enjoys high accuracy and achieves the best clustering results given a large enough sample size. Finally, experimental comparisons with typical clustering methods on real datasets witness the potential of our algorithm in real applications.
2D scalable optical controlled phased-array antenna system (2006)

A novel optoelectronically-controlled wideband 2-D phased-array antenna system is demonstrated. The inclusion of WDM devices makes a highly scalable system structure. Only (M+N) delay lines are required to control a M×N array. The optical true-time delay lines are combination of polymer waveguides and optical switches, using a single polymeric platform and are monolithically integrated on a single substrate. The 16 time delays generated by the device are measured to range from 0 to 175 ps in 11.6 ps. Far-field patterns at different steering angles in X-band are measured.
Agonists and Antagonists for P2 Receptors (2006)

Recent work has identified nucleotide agonists selective for P2Y1, P2Y2 and P2Y6 receptors and nucleotide antagonists selective for P2Y1, P2Y12 and P2X1 receptors. Selective non-nucleotide antagonists have been reported for P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, P2X(2/3)/P2X3 and P2X7 receptors. For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non-nucleotide antagonist A-317491 is selective for P2X(2/3)/P2X3 receptors. Nucleotide analogues in which the ribose moiety is substituted by a variety of novel ring systems, including conformationally locked moieties, have been synthesized as ligands for P2Y receptors. The focus on conformational factors of the ribose-like moiety allows the inclusion of general modifications that lead to enhanced potency and selectivity. At P2Y1,2,4,11 receptors, there is a preference for the North conformation as indicated with (N)-methanocarba analogues. The P2Y1 antagonist MRS2500 inhibited ADP-induced human platelet aggregation with an IC50 of 0.95 nM. MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency (EC50) of 0.4nM at the P2Y1 receptor, with >10000-fold selectivity in comparison to P2Y12 and P2Y13 receptors. At P2Y6 receptors there is a dramatic preference for the South conformation. Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three-dimensional structures of P2X receptors have not yet been proposed.
Supplementary Figures 1-5, Table 1 from Transforming Growth Factor β Subverts the Immune System into Directly Promoting Tumor Growth through Interleukin-17 (2023)

Supplementary Figures 1-5, Table 1 from Transforming Growth Factor β Subverts the Immune System into Directly Promoting Tumor Growth through Interleukin-17
Nonlinear PHMMs for the interpretation of parameterized gesture (2002)

Recently we modified the hidden Markov model (HMM) framework to incorporate a global parametric variation in the output probabilities of the states of the HMM. Development of the parametric hidden Markov model (PHMM) was motivated by the task of simultaneously recognizing and interpreting gestures that exhibit meaningful variation. With standard HMMs, such global variation confounds the recognition process. The original PHMM approach assumes a linear dependence of output density means on the global parameter. In this paper we extend the PHMM to handle arbitrary smooth (nonlinear) dependencies. We show a generalized expectation-maximization (GEM) algorithm for training the PHMM and a GEM algorithm to simultaneously recognize the gesture and estimate the value of the parameter. We present results on a pointing gesture, where the nonlinear approach permits the natural azimuth/elevation parameterization of pointing direction.
Supplementary Figures from Oncogenic ERG Represses PI3K Signaling through Downregulation of IRS2 (2023)

&lt;p&gt;The supplementary figures provide additional data demonstrating that ERG represses RTK-PI3K signaling through direct transcriptional repression of IRS2 across multiple model systems. Additional data is provided showing the biologic role of ERG and PI3K signaling in promoting cell proliferation and migration.&lt;/p&gt;
Synthesis of Polyaniline Particles via Inverse and Direct Miniemulsion (2003)

Polyaniline (PANI) latex particles have been synthesized using both inverse and direct miniemulsion polymerization techniques. It is shown that inverse miniemulsions of anilinium hydrochloride can be oxidized by simple H2O2, thus resulting under optimized conditions in highly crystalline PANI particles dispersed in hydrocarbons with high volume fraction. The resulting structure is identified as emeraldine, which however crystallizes in a new crystal morphology. Oxidation of aniline miniemulsions in water with diverse oxidants from the continuous phase also leads to highly crystalline PANI, which however has a low colloidal stability. Additional employment of a costabilizer in this case leads to stable aqueous PANI dispersions with for water-based systems otherwise unreached local structural order.
Data Processing and Analysis for Protein Microarrays (2011)

Protein microarrays are a high-throughput technology capable of generating large quantities of proteomics data. They can be used for general research or for clinical diagnostics. Bioinformatics and statistical analysis techniques are required for interpretation and reaching biologically relevant conclusions from raw data. We describe essential algorithms for processing protein microarray data, including spot-finding on slide images, Z score, and significance analysis of microarrays (SAM) calculations, as well as the concentration dependent analysis (CDA). We also describe available tools for protein microarray analysis, and provide a template for a step-by-step approach to performing an analysis centered on the CDA method. We conclude with a discussion of fundamental and practical issues and considerations.
Role of Surface Tension in Adhesive Contact between a Rigid Sphere and a Soft Elastic Substrate (2014)

The surface tension of compliant materials such as gels provides resistance to deformation in addition to and sometimes surpassing that due to elasticity. This article studies how surface tension changes the contact mechanics of a small hard sphere indenting a soft elastic substrate. Previous studies have examined the special case where the external load is zero, so contact is driven by adhesion alone. Here we tackled the much more complicated problem where, in addition to adhesion, deformation is driven by an indentation force. We presented an exact solution based on small strain theory. The relation between indentation force (displacement) and contact radius is found to depend on two dimensionless parameters: the elasto-capillary number $\alpha=\sigma/(2\mu R)$ and the normalized work of adhesion $W_{\textrm{ad}}/(\mu R)$, where $\mu$ is the shear modulus of the substrate, $R$ the sphere radius, $\sigma$ the surface tension of substrate-air interface and $W_{\textrm{ad}}$ is the interfacial work of adhesion. Our theory reduces to the Johnson-Kendall-Roberts theory in the limit of small elasto-capillary number and in the limit of large elasto-capillary number compares well with experimental data.
Soft Handover in Adaptive MIMO-OFDM Cellular System with Cooperative Processing (2006)

The joint cooperative processing of transmitted signal from several multiple-input multiple-output (MIMO) base station (BS) antenna heads is considered for users located within a soft handover (SHO) region. Downlink space-frequency bit and power allocation problem with different BS power constraints is studied for the considered adaptive MIMO-OFDM system. The performance of the proposed heuristic loading method is shown to be close to the optimal convex optimization method with per BS power constraints. It is shown that the highest SHO gains are achieved with a small power imbalance between the received BS powers at low signal-to-noise ratio (SNR), where the achievable rates can be even doubled. On the other hand, the gain from joint processing in SHO quickly diminishes as the imbalance increases, especially at low SNR. Moreover, the results indicate that the joint processing can be even detrimental for the system performance if a coarse phase synchronization between BS antenna head is not guaranteed, as some additional fading on the target SNR values is introduced
ESR‐Spektroskopischer Beweis für die C–C‐Dissoziation von Hexakis(organylthio)äthanen und die S–C‐Dissoziation von Tetrakis(organylthio)methanen. Tris(organylthio)methyl‐Radikale (1972)

Abstract Beim Erhitzen von Hexakis(arylthio)äthanen wie 1 (100°) und von Tetrakis(arylthio)methanen wie 3 (140°) treten instabile Tris(arylthio)methyle vom Typ 2 auf, deren Identität ESR‐spektroskopisch gesichert wurde. Das Singulett‐Signal von 2 wird nach 13 C‐Markierung am Methylkohlenstoff in ein Dublett (43.7‐Gauss) aufgespalten; im Spektrum des 33 S‐markierten 2 treten die erwarteten Aufspaltungen durch drei Schwefelkerne ein ( a ( 33 S)  4.2 Gauss). Bei der Pyrolyse des „gemischten”︁ Orthokohlensäureesters 7 bzw. des entsprechenden Äthans 9 beobachtet man das Signal des Methylthiobis(phenylthio)methyls ( 8 ), das eine Methyl‐Quartettaufspaltung a (CH 3 ) von 2.1 Gauss zeigt. Nach den gemessenen Parametern ist das ungepaarte Elektron überwiegend am zentralen Kohlenstoff von 2 lokalisiert. Für die leichte Homolyse der Bindungen in 1 und 3 ist somit sterische Hinderung im nicht dissoziierten Molekül und nicht Mesomerie‐Stabilisierung der Radikale verantwortlich zu machen. Hierfür sprechen auch die Ergebnisse an entsprechenden Äthanen mit sterisch anspruchsvolleren Substituenten.
Research and Development of Functional Fluid Mechatronics, Rehabilitation Systems, and Mechatronics of Flexible Drive Systems (2016)

[abstFig src='/00280001/01.jpg' width=""260"" text='PLEMO-P3 Developed by Furusho Lab at Osaka Univ.' ]We conducted many research and development activities on functional fluid mechatronics, rehabilitation systems, and servo drive systems. In this review, studies on the development of magnetorheological fluid devices, electrorheological effects of liquid crystalline polymers on one-sided pattern electrodes, and vibration control using control theory and liquid crystalline polymer are introduced. In addition, applications of rehabilitation systems for upper and lower extremities employing functional fluids for individuals suffering from stroke, cerebellar ataxia, and Guillain-Barre syndrome are also introduced.
815-P: Enhanced Disulphide Bond Stability Contributes to the Once Weekly PD Profile of Insulin Icodec (2023)

Insulin icodec is a novel basal insulin analogue with a long half-life (196 hours) that is in clinical development for the treatment of diabetes with once weekly dosing. Insulin icodec was developed based on the hypothesis that lowering the insulin receptor affinity in the presence of a strong HSA-binding moiety would result in a long half-life, provided that non-receptor mediated clearance is diminished. The observation that insulin icodec retains its full potency over weeks has been attributed to low non-insulin receptor mediated clearance as well as to limited degradation in circulation, due to the amino acid modifications in insulin icodec that confer proteolytically-stabilization. Here, we report a previously undescribed insulin clearance mechanism, resulting in splitting insulin molecules into A- and B-chains by a thiol-disulfide exchange reaction. We found that the amino acid substitution of Tyr in A14 to Glu provided a major stabilization of insulin against such degradation while only minor improvements were introduced by the Tyr in B16 to His and Phe in B25 to His substitutions. These results correlate with improvements in the folding stability and likely reflect reduced exposure of insulin icodec's disulfide bonds to the thiol-disulfide exchange reaction. Even though insulin icodec's amino acid substitutions significantly limit its susceptibility to this new clearance mechanism, some free B-chain has been observed in plasma samples from minipigs and people with type 2 diabetes. In summary, we have identified thiol-disulfide exchange reactions as an additional insulin clearance mechanism and minimizing insulin icodec's susceptibility to this process has significantly contributed to its long PD, making it suitable for once weekly dosing. Disclosure F.Hubalek: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. C.Cramer: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. H.Helleberg: Employee; Novo Nordisk A/S. E.Johansson: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. G.Schluckebier: Employee; Novo Nordisk. D.B.Steensgaard: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk. J.Sturis: Employee; Novo Nordisk A/S, Other Relationship; Novozymes, Stock/Shareholder; Novo Nordisk A/S. T.Kjeldsen: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk.
Biofabrication: reappraising the definition of an evolving field (2016)

Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in terminology. This article aims at clarifying the position of Biofabrication as a research field with a special focus on its relation to and application for Tissue Engineering and Regenerative Medicine. Within this context, we propose a refined working definition of Biofabrication, including Bioprinting and Bioassembly as complementary strategies within Biofabrication.
Methylation-Dependent Binding of the Epstein-Barr Virus BZLF1 Protein to Viral Promoters (2020)

The switch between latent and lytic Epstein-Barr virus (EBV) infection is mediated by the viral immediate-early (IE) protein, BZLF1 (Z). Z, a homologue of c-jun that binds to AP1-like motifs (ZREs), induces expression of the BRLF1 (R) and BRRF1 (Na) viral proteins, which cooperatively activate transcription of the Z promoter and thereby establish a positive autoregulatory loop. A unique feature of Z is its ability to preferentially bind to, and activate, the methylated form of the BRLF1 promoter (Rp). To date, however, Rp is the only EBV promoter known to be regulated in this unusual manner. We now demonstrate that the promoter driving transcription of the early BRRF1 gene (Nap) has two CpG-containing ZREs (ACGCTCA and TCGCCCG) that are only bound by Z in the methylated state. Both Nap ZREs are highly methylated in cells with latent EBV infection. Z efficiently activates the methylated, but not unmethylated, form of Nap in reporter gene assays, and both ZREs are required. Z serine residue 186, which was previously shown to be required for Z binding to methylated ZREs in Rp, but not for Z binding to the AP1 site, is required for Z binding to methylated Nap ZREs. The Z(S186A) mutant cannot activate methylated Nap in reporter gene assays and does not induce Na expression in cells with latent EBV infection. Molecular modeling studies of Z bound to the methylated Nap ZREs help to explain why methylation is required for Z binding, and the role of the Z Ser186 residue. Methylation-dependent Z binding to critical viral promoters may enhance lytic reactivation in latently infected cells, where the viral genome is heavily methylated. Conversely, since the incoming viral genome is initially unmethylated, methylation-dependent Z activation may also help the virus to establish latency following infection.
Replication and cross‐phenotype study based upon schizophrenia GWASs data in the Japanese population: Support for association of MHC region with psychosis (2014)

Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified several susceptibility genes and suggested shared genetic components between SCZ and bipolar disorder (BD). We conducted a genetic association study of single nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032 SCZ, 1,012 BD, and 993 controls) and second-set replication samples ("significant" SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and 2,321 controls). We assessed allelic associations between the selected SNPs and the three phenotypes (SCZ, BD, and "psychosis" [SCZ + BD]). Nine SNPs revealed nominal association signals for all comparisons (P(uncorrected) < 0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication samples. The associations were confirmed for rs7759855 (P(corrected) = 0.026 for psychosis; P(corrected) = 0.032 for SCZ), although the direction of effect was opposite to that in the original GWAS of the Chinese population. Finally, a meta-analysis was conducted using our two samples and using our data and data from Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect. SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes (best P = 6.8 × 10(-5) for psychosis: present plus PGC results). These data support shared risk SNPs between SCZ and BD in the Japanese population and association between MHC and psychosis.