gebhart/patrepeval huggingface dataset:
Amyloidogenesis. One serum amyloid A isotype is selectively removed from the circulation. (1986)

The deposits of fibrils found in amyloidosis of the A type are derived from only one of the three serum amyloid A (SAA) gene products, namely SAA2. In order to explore the mechanism of SAA isotype-specific amyloid protein AA deposition, the molecular kinetics of the serum amyloid proteins were examined in CBA mice during casein induction of amyloidosis. The presence of SAA mRNA in spleen was searched for; hepatic SAA1 and SAA2 mRNA levels, rates of specific protein synthesis and secretion by hepatocytes, and serum levels were measured during a 20-d period of amyloid induction. We observed the following: small amounts of amyloid substance appeared in the spleen by day 5 and increased steadily over the ensuing 15 d to occupy nearly 30% of splenic volume by day 20. No SAA mRNA was detected in spleen at any time during induction of amyloid formation. Total serum SAA levels peaked 1 d after we began casein treatment, and thereafter declined. This decline was accounted for entirely by a dramatic fall in SAA2, while SAA1 levels remained nearly constant throughout. The ratios of hepatic SAA2:SAA1 mRNA, as determined by in vitro translation, remained constant during the 20-d period, as did amounts of SAA1 and SAA2 synthesized and secreted by freshly isolated hepatocytes. These data indicate that the deposition of amyloid A protein derived from SAA2 is not due to local SAA production in spleen, nor excessive SAA2 production compared with SAA1, but involves the selective and accelerated removal of SAA2 from the circulating pool of both SAA1 and SAA2.
Multiple Beneficial Roles of Repressor of Estrogen Receptor Activity (REA) in Suppressing the Progression of Endometriosis (2015)

Endometriosis is an estrogen-dependent, inflammation-driven gynecologic disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, leading to pelvic pain and impaired fertility. Although dysregulated estrogen receptor (ER) signaling has been implicated, understanding of this disease is incomplete and current therapies are of limited benefit. Using an immunocompetent syngeneic murine model, we used combinations of donor uterine tissue and/or recipient host mice with partial genetic deletion of the ER coregulator, repressor of ER activity (REA) (also known as prohibitin 2), to investigate roles of REA in the contributions of donor uterine tissue and host cell influences on endometriosis establishment and progression. Ectopic lesions derived from donor tissue with half the wild-type gene dosage of REA (REA(+/-)) grown in REA(+/-) hosts displayed enhanced proliferation, vascularization, and markedly increased neuron innervation and inflammatory responses, including elevated cytokine production, nuclear factor kappa B activation, cyclooxygenase-2 expression, and immune cell infiltration. Although lesion progression was greatest when REA was reduced in both donor tissue and host animals, other donor/host combinations indicated that distinct stimulatory inputs were derived from ectopic tissue (proliferative signals) and host cells (inflammatory signals). Importantly, depletion of REA in primary human endometriotic stromal cells led to elevated proliferation and expression of cell cycle regulators. Notably, REA was significantly lower in human endometriotic tissue versus normal human endometrium. Thus, REA modulates cross talk among multiple cell types in the uterine tissue and host background, serving as a brake on the estradiol-ER axis and restraining multiple aspects that contribute to the pathologic progression of endometriosis.
ChemInform Abstract: Fourfold Suzuki—Miyaura and Sonogashira Cross‐Coupling Reactions on Tetrahedral Methane and Adamantane Derivatives. (2011)

Abstract A systematic study on Suzuki—Miyaura or Sonogashira cross coupling reactions for the synthesis of tectons with tetrahedral methane or adamantane core is presented.
A novel p.A191D matrilin-3 variant in a Vietnamese family with multiple epiphyseal dysplasia: a case report (2020)

This is the first Vietnamese MED family attributed to p.A191D matrilin-3 variant, and our clinical, radiological and molecular data suggest that the novel de novo missense variant in MATN3 contributed to MED.
KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET‐expressing tumor cells (2015)

The MET receptor tyrosine kinase is often deregulated in human cancers and several MET inhibitors are evaluated in clinical trials. Similarly to EGFR, MET signals through the RAS-RAF-ERK/MAPK pathway which plays key roles in cell proliferation and survival. Mutations of genes encoding for RAS proteins, particularly in KRAS, are commonly found in various tumors and are associated with constitutive activation of the MAPK pathway. It was shown for EGFR, that KRAS mutations render upstream EGFR inhibition ineffective in EGFR-positive colorectal cancers. Currently, there are no clinical studies evaluating MET inhibition impairment due to RAS mutations. To test the impact of RAS mutations on MET targeting, we generated tumor cells responsive to the MET inhibitor EMD1214063 that express KRAS G12V, G12D, G13D and HRAS G12V variants. We demonstrate that these MAPK-activating RAS mutations differentially interfere with MET-mediated biological effects of MET inhibition. We report increased residual ERK1/2 phosphorylation indicating that the downstream pathway remains active in presence of MET inhibition. Consequently, RAS variants counteracted MET inhibition-induced morphological changes as well as anti-proliferative and anchorage-independent growth effects. The effect of RAS mutants was reversed when MET inhibition was combined with MEK inhibitors AZD6244 and UO126. In an in vivo mouse xenograft model, MET-driven tumors harboring mutated RAS displayed resistance to MET inhibition. Taken together, our results demonstrate for the first time in details the role of KRAS and HRAS mutations in resistance to MET inhibition and suggest targeting both MET and MEK as an effective strategy when both oncogenic drivers are expressed.
Characteristics of patients with early gastric cancer who had undergone surgery in single institute (2008)

15535 Background: The incidence of early gastric cancer (EGC) has been increasing worldwide owing to advances with diagnositic techniques and screening programs. Radical gastrectomy with lymph node dissection is still the gold-standard treatment for EGC. The present study was designed to investigate the characteristics of EGC patients who had undergone surgery. Methods: According to the Japanese classification of gastric carcinoma, EGC is defined as a lesion confined to the mucosa or submucosa, regardless of the presence of regional lymph node metastasis. We reviewed 529 patients with gastric cancer who had undergone gastrectomy at Ulsan University Hospital, Ulsan, Korea, from December 2002 to December 2005. Results: Two hundred sixty-one patients (49%) were diagnosed as EGC (155 intramucosal EGC (mEGC), 106 intrasubmucosal EGC (smEGC), 123 differentiated EGC, and 138 undifferentiated EGC). One hundred sixty-one patients (61.7%) were male and median age was 55. The mean diameter of tumor was 2.49 ± 1.55 cm (2.18 ± 1.45 cm in mEGC and 2.94 ± 1.60 cm in smEGC, p=0.000). The incidence of lymph node metastasis was 11.5% (30 out of 261 patients). Univariate analysis revealed that a tumor larger than 2 cm (17.6% vs. 6.3%), submucosal invasion (20.8% vs. 5.2%), and the presence of lymphovascular invasion (LVI) (33.3% vs. 6.6%) were significantly associated with a higher lymph node metastasis rate. There were no significant associations between lymph node metastasis and differentiation, age, gender, tumor location, macroscopic type, CEA level,or CA19- 9 level. In multivariate analysis, LVI was independent predictive factor for lymph node metastasis (p=0.005), while submucosal invasion was marginally predictive (p=0.069) and tumor size was not (p=0.208). At a median follow-up of 1023 days, only 2 patients relapsed and 1 patient died due to disease progression. Conclusions: LVI was independent predictive factor for lymph node metastasis. In cases that LVI was present after endoscopic resection, radical gastrectomy should be recommended. Endoscopic resection data will be analyzed and compared with surgery data. No significant financial relationships to disclose.
Buildup of thermoset and crystallization of thermoplastics studied by electrical techniques (1997)

Up to now, few techniques were available that allowed nondestructive in situ characterization of polymerization during the curing of a thermoset resin. Dynamic dielectric measurements made over a wide range of frequencies provide a sensitive and convenient control to follow up the epoxy-amine cure or to follow the formation of the thermoplastic materials. The direct current measurements and the time of flight measurements were developed to confirm interpretation of the electrical techniques in terms of correlations of the evolution of the conductivity and the network formation and also to evaluate the real value of the ion mobility and its evolution in a course of reaction. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65: 2529–2543, 1997
Different Munc13 Isoforms Function as Priming Factors in Lytic Granule Release from Murine Cytotoxic T Lymphocytes (2013)

In order to fuse lytic granules (LGs) with the plasma membrane at the immunological synapse, cytotoxic T lymphocytes (CTLs) have to render these LGs fusion-competent through the priming process. In secretory tissues such as brain and neuroendocrine glands, this process is mediated by members of the Munc13 protein family. In human CTLs, mutations in the Munc13-4 gene cause a severe loss in killing efficiency, resulting in familial hemophagocytic lymphohistiocytosis type 3, suggesting a similar role of other Munc13 isoforms in the immune system. Here, we investigate the contribution of different Munc13 isoforms to the priming process of murine CTLs at both the mRNA and protein level. We demonstrate that Munc13-1 and Munc13-4 are the only Munc13 isoforms present in mouse CTLs. Both isoforms rescue the drastical secretion defect of CTLs derived from Munc13-4-deficient Jinx mice. Mobility studies using total internal reflection fluorescence microscopy indicate that Munc13-4 and Munc13-1 are responsible for the priming process of LGs. Furthermore, the domains of the Munc13 protein, which is responsible for functional fusion, could be identified. We conclude from these data that both isoforms of the Munc13 family, Munc13-1 and Munc13-4, are functionally redundant in murine CTLs.
SERMs Attenuate Estrogen-Induced Malignant Transformation of Human Mammary Epithelial Cells by Upregulating Detoxification of Oxidative Metabolites (2014)

The risk of developing hormone-dependent cancers with long-term exposure to estrogens is attributed both to proliferative, hormonal actions at the estrogen receptor (ER) and to chemical carcinogenesis elicited by genotoxic, oxidative estrogen metabolites. Nontumorigenic MCF-10A human breast epithelial cells are classified as ER(-) and undergo estrogen-induced malignant transformation. Selective estrogen receptor modulators (SERM), in use for breast cancer chemoprevention and for postmenopausal osteoporosis, were observed to inhibit malignant transformation, as measured by anchorage-independent colony growth. This chemopreventive activity was observed to correlate with reduced levels of oxidative estrogen metabolites, cellular reactive oxygen species (ROS), and DNA oxidation. The ability of raloxifene, desmethylarzoxifene (DMA), and bazedoxifene to inhibit this chemical carcinogenesis pathway was not shared by 4-hydroxytamoxifen. Regulation of phase II rather than phase I metabolic enzymes was implicated mechanistically: raloxifene and DMA were observed to upregulate sulfotransferase (SULT 1E1) and glucuronidase (UGT 1A1). The results support upregulation of phase II metabolism in detoxification of catechol estrogen metabolites leading to attenuated ROS formation as a mechanism for inhibition of malignant transformation by a subset of clinically important SERMs.
A Phase I Trial of the ABCB1 Inhibitor, Oral Valspodar, in Combination With Paclitaxel in Patients With Advanced Solid Tumors (2023)

Paclitaxel at 70 mg/m 2 was administered safely with valspodar. Limited efficacy in hematologic and solid tumors resulted in discontinuation of its clinical development and other transporter inhibitors. Recently, the development of ATP-binding cassette transporter inhibitors has been reconsidered to mitigate resistance to antibody-drug conjugates.
STAT1 is essential for the inhibition of hepatitis C virus replication by interferon-λ but not by interferon-α (2016)

Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7.5 human hepatoma cells. These responses are only partially attenuated by knockout of STAT1 but are abolished by knockout of STAT2. In contrast, the inhibition of HCV replication by IFN-λ is abolished by knockout of STAT1 or STAT2. Microarray analysis reveals that IFN-α but not IFN-λ can induce expression of the majority of ISGs in STAT1 knockout cells. These findings suggest that IFN-α can inhibit HCV replication through a STAT2-dependent but STAT1-independent pathway, whereas IFN-λ induces ISG expression and inhibits HCV replication exclusively through a STAT1- and STAT2-dependent pathway.
Intention Reading from a Fuzzy-Based Human Engagement Model and Behavioural Features (2012)

This paper presents a novel approach for a quantitative appraisal model to identify human intent so as to interact with a robot and determine an engagement level. To efficiently select an attention target for communication in multi-person interactions, we propose a fuzzy-based classification algorithm which is developed by an incremental learning procedure and which facilitates a multi-dimensional pattern analysis for ambiguous human behaviours. From acquired participants' non-verbal behaviour patterns, we extract the dominant feature data, analyse the generality of the model and verify the effectiveness for proper and prompt gaze behaviour. The proposed model works successfully in multiple people interactions.
EUROTOP : CAS D'APPLICATION DE LA COMPTABILITÉ D'ACTIVITÉS (ABC) AVEC EXPERTIZERS (2009)

Expertizers is an original method for ananlyzing data extracted from ERP or coming from several sources. This approach can be useful for process and cost modelisations. We use the Eurotop case study presenting an activity based costing problem. This case is first resolved with the Expertizers software, and then compared with an implementation using Microsost Excel, which represents a less specialized environment. We then use a qualitative data analysis in order to abstract the students' impressions using the Expertizers method and software.
Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors (2004)

During the past several years much new evidence has accumulated regarding the molecular and biochemical mechanisms underlying cardiac responses to hypoxia and to ischemia/reperfusion injury. Studies have involved cell culture, and ex vivo and in vivo preparations. This review focuses on regulation of two transcription factors that are thought to be important in these processes, hypoxia-inducible factor1alpha (HIF-1alpha) and heat shock factor (HSF). Both of these molecules are expressed acutely and chronically in response to hypoxia and ischemia/reperfusion, and both have numerous targets that comprise part of integrated response to ischemic injury aimed at promoting cell survival. Emphasis is placed on new mechanisms of action that regulate HIF-1alpha, HSF, and heat shock proteins as key responses to hypoxia and ischemia, and possible approaches to therapy based on these data are discussed.
Attention in individuals with aphasia: Performance on the Conners’ Continuous Performance Test – 2nd edition (2018)

Studies suggest that individuals with aphasia present with impairments in attention. However, most research has been conducted with small sample sizes using experimental protocols that lack established psychometric properties. We examined the attention performance of 114 individuals with chronic post-stroke aphasia using a standardised, norm-referenced assessment of attention, the Conners' Continuous Performance Test-II (CPT-II; Conners, C. K. (2000). <i>Conners' Continuous Performance Test II</i>. Toronto: Multi-Health Systems Inc). Participants completed the CPT-II and the Western Aphasia Battery-Revised (WAB-R; Kertesz, A. (2007). <i>Western Aphasia Battery-Revised</i>. San Antonio, TX: PsychCorp). As a group, variable performance on selected CPT-II measures was observed. Participants demonstrated impairments on omissions (48.2%) and hit reaction time (67.5%), with 11.4% demonstrating atypically slow performance and over half of the sample (56.1%) performing atypically fast. The Confidence Index, a summary score, was also within the impaired range for the majority of participants. However, there were also measures in which a greater percentage of participants demonstrated performance within normal limits. Using the WAB-R Aphasia Quotient (AQ) as a measure of severity, there was significantly worse performance in participants with more severe (AQ < 50) compared to less severe (AQ ≥ 50) aphasia. No significant differences in attention were identified between participants with fluent versus non-fluent aphasia. The CPT-II is a feasible measure for persons with aphasia, which may assist in identifying attention performance deficits that potentially affect language.
The dynamics of a PWM boost converter with resistive input (1999)

This paper investigates the large- and small-signal response issues and, in particular, the inner loop gain and outer loop response of an indirect control method for active power-factor correction. The control scheme is based on sensing the average inductor current and generating a D/sub OFF/ (the complement of the switch duty cycle) which is proportional to the current. The method is demonstrated by considering the performance of a boost-type active power-factor corrector (APFC) that does not need to sense the input voltage. Theoretical and experimental results confirm the validity of the approach and demonstrate that the proposed method can be useful in the design of robust APFC with low total harmonic distortion. The indirect control method investigated in this paper is also compared to the classical direct APFC control method, pointing to the differences between the two.
Evaluating shallow and deep networks for ransomware detection and classification (2017)

Ransomware is one type of malware that covertly installs and executes a cryptovirology attack on a victims computer to demand a ransom payment for restoration of the infected resources. This kind of malware has been growing largely in recent days and causes tens of millions of dollars losses to consumers. In this paper, we evaluate shallow and deep networks for the detection and classification of ransomware. To characterize and distinguish ransomware over benign and various other families of ransomwares, we leverage the dominance of application programming interface (API) invocations. To select a best architecture for the multi-layer perceptron (MLP), we done various experiments related to network parameters and structures. All the experiments are run up to 500 epochs with a learning rate in the range [0.01-0.5]. Result obtained on our data set is more promising to distinguish ransomware not only from benign from its families too. On distinguishing the .EXE as either benign or ransomware, MLP has attained highest accuracy 1.0 and classifying the ransomware to their categories obtained highest accuracy 0.98. Moreover, MLP has performed well in detecting and classifying ransomwares in comparison to the other classical machine learning classifiers.
5G Control Channel Design for Ultra-Reliable Low-Latency Communications (2018)

The fifth generation (5G) of wireless systems holds the promise of supporting a wide range of services with different communication requirements. Ultra-reliable low-latency communications (URLLC) is a generic service that enables mission-critical applications, such as industrial automation, augmented reality, and vehicular communications. URLLC has stringent requirements for reliability and latency of delivering both data and control information. In order to meet these requirements, the Third Generation Partnership Project (3GPP) has been introducing new features to the upcoming releases of the cellular system standards, namely releases 15 and beyond. This article reviews some of these features and introduces new enhancements for designing the control channels to efficiently support the URLLC. In particular, a flexible slot structure is presented as a solution to detect a failure in delivering the control information at an early stage, thereby allowing timely retransmission of the control information. Finally, some remaining challenges and envisioned research directions are discussed for shaping the 5G new radio (NR) as a unified wireless access technology for supporting different services.
The Relative Power of Family-Based and Case-Control Designs for Linkage Disequilibrium Studies of Complex Human Diseases. II. Individual Genotyping (1999)

In this paper we consider test statistics based on individual genotyping. For sibships without parents, but with unaffected as well as affected sibs, we introduce a new test statistic (referred to as TDS), which contrasts the allele frequency in affected sibs versus that estimated for the parents from the entire sibship. For sibships without parents, this test is analogous to the TDT and is completely robust to nonrandom mating patterns. The efficiency of the TDS test is comparable to that of the THS test (which compares affected vs. unaffected sibs and was based on DNA pooling), for sibships with one affected child. However, as the number of affected sibs in the sibship grows, the relative efficiency of the TDS test versus the THS test also increases. For example, for sibships with three affected, one-third fewer families are required; for families with four affected, nearly half as many are required. Thus, when sibships contain multiple affected individuals, the TDS test provides both an increase in power and robustness to nonrandom mating.