gebhart/patrepeval huggingface dataset:
Phase I/II trial of bevacizumab plus erlotinib for patients with recurrent non-small cell lung cancer: Correlation of treatment response with mutations of the EGFR tyrosine kinase gene (2005)

7092 Background: Bevacizumab (Avastin) is a recombinant, humanized anti-VEGF monoclonal antibody. Erlotinib (Tarceva) is a potent, reversible, selective HER1/EGFR tyrosine-kinase (TK) inhibitor. Preclinical studies have shown that a combination of anti-VEGF and anti-HER1/EGFR therapies has at least an additive effect. We previously reported results of a phase I/II trial in which a combination of bevacizumab and erlotinib was given to 40 patients (pts) with advanced refractory NSCLC; the response rate was 20% and the median survival was 12.6 months. Given recent evidence of a somatic mutation in the gene encoding the EGFR TK domain, we analyzed available archival tissue from our study for the presence of this mutation. Methods: EGFR exons 18–21 and 23 were sequenced in tumors from 9 pts. Outcomes were correlated with EGFR mutations. Results: By RECIST criteria, the best treatment responses were 3 pts with partial responses (PR), 3 with stable disease, and 3 with progressive disease. Baseline characteristics for the PR pts are summarized in the table. An EGFR TK mutation in exon 20 (P772 H773insNS; H773Y) was found in 1 tumor. Conclusions: Although a high degree of correlation between response to TK inhibitor therapy and the EGFR TK mutation has been noted, we have thus far identified the mutation in only 1 of 3 tumors. Although these results are preliminary, they suggest that the combination of bevacizumab and erlotinib may provide benefit in a broader population than each agent individually. A 3-arm phase II trial of bevacizumab plus erlotinib and bevacizumab plus docetaxel vs docetaxel plus bevacizumab or placebo is currently underway. We plan to examine archival tissue from this study to establish the prognostic/predictive value of the EGFR TK mutation for combination therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech Genentech
Amplification and overexpression of Aurora kinase A (AURKA) in immortalized human ovarian epithelial (HOSE) cells (2005)

Immortalization is an early and essential step of human carcinogenesis. Amplification of chromosome 20q has been shown to be a common event in immortalized cells and cancers. We have previously reported that gain and amplification of chromosome 20q is a non-random and common event in immortalized human ovarian surface epithelial (HOSE) cells. The chromosome 20q harbors genes including TGIF2 (20q11.2-q12), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and AURKA (20q13.2-q13.3), which were previously reported to be amplified and overexpressed in ovarian cancers. Some of these genes may be involved in immortalization of HOSE cells and represent crucial premalignant changes in ovarian surface epithelium. Investigation of the involvement of these genes was examined in four pairs of pre-crisis (preimmortalized) and post-crisis (immortalized) HOSE cells. Overexpression of AURKA (Aurora kinase A), also known as BTAK and STK15, by both real time-quantitative polymerase chain reaction (RT-QPCR) and Western blotting was detected in all the four immortalized HOSE cells examined while overexpression of AIB1 and ZNF217 was observed in two of four immortalized HOSE cells examined. Overexpression of TGIF2 and PTPN1 was not significant in our immortalized HOSE cell systems. The degree of overexpression of AURKA was shown to be closely associated with the amplification of chromosome 20q in immortalized HOSE cells. Fluorescence in situ hybridization (FISH) with labeled P1 artificial clone (PAC) confirmed the amplification of the chromosomal region (20q13.2-13.3) where AURKA resides. DNA amplification of AURKA was also confirmed using semi-quantitative PCR. Our study showed that amplification and overexpression of AURKA is a common and significant event during immortalization of HOSE cells and may represent an important premalignant change in ovarian carcinogenesis.
Principles of Design for Large Scale Neural Simulators (2004)

We present a review of design principles that are to be used for large-scale neural simulators. This paper emphasizes the most important problems encountered in the simulation of biologically plausible neural systems and provides some solutions derived from modern simulation techniques. We stress upon the idea that a modern simulator should be able to perform generic simulations of as many as possible neural architectures, with various neural models. At the same time the amount of processing effort should be tunable, with the possibility of using various simulation methods simultaneously (e.g. iterative and event-driven). The neuroscientist should be able to use different types of electrophysiological models with complete inter-operability. We provide an example of a neural simulator that complies with modern design guidelines: ”The Neocortex Simulation Environment”.
REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus (2001)

The REF family of evolutionarily conserved heterogeneous ribonucleoprotein (hnRNP)-like proteins consists of one central RNP-type RNA binding domain flanked by Arg-Gly-rich regions of variable length. Members of this protein family bind directly to RNA and the mRNA export factor TAP/Mex67p, and it has been suggested that they facilitate the recruitment of TAP/Mex67p to cellular mRNPs. We show that the variable regions are necessary for binding of REFs to RNA and to TAP. Antibodies specific to REFs prevent their interaction with RNA in vitro. After microinjection into Xenopus oocytes, these antibodies inhibit mRNA nuclear export. This inhibition of export is observed whether or not the mRNAs are generated by splicing. The antibodies do not interfere with pre-mRNA splicing or with the nuclear export of constitutive transport element (CTE)-containing RNAs (directly mediated by TAP), so REF proteins must play a critical role in mRNA nuclear export, acting downstream of splicing and upstream of TAP/Mex67p. We also show that recombinant REFs stimulate directly the export of mRNAs that are otherwise exported inefficiently. Together, our data indicate that REFs are directly implicated in the export of mRNAs from the nucleus. More generally, we show that spliced and unspliced mRNAs use common export factors to reach the cytoplasm.
Leptomeningeal anti-tumor immunity follows unique signaling principles (2023)

Metastasis to the cerebrospinal fluid (CSF)-filled leptomeninges, or leptomeningeal metastasis (LM), represents a fatal complication of cancer. Proteomic and transcriptomic analyses of human CSF reveal a substantial inflammatory infiltrate in LM. We find the solute and immune composition of CSF in the setting of LM changes dramatically, with notable enrichment in IFN-γ signaling. To investigate the mechanistic relationships between immune cell signaling and cancer cells within the leptomeninges, we developed syngeneic lung, breast, and melanoma LM mouse models. Here we show that transgenic host mice, lacking IFN-γ or its receptor, fail to control LM growth. Overexpression of <i>Ifng</i> through a targeted AAV system controls cancer cell growth independent of adaptive immunity. Instead, leptomeningeal IFN-γ actively recruits and activates peripheral myeloid cells, generating a diverse spectrum of dendritic cell subsets. These migratory, CCR7+ dendritic cells orchestrate the influx, proliferation, and cytotoxic action of natural killer cells to control cancer cell growth in the leptomeninges. This work uncovers leptomeningeal-specific IFN-γ signaling and suggests a novel immune-therapeutic approach against tumors within this space.
The functional demands on the intact limb during walking for active transfemoral and transtibial amputees (2000)

The aim of this study was to investigate the loading demands placed on the intact limb in terms of joint moments and power for active trans-femoral and trans-tibial amputees in comparison to a group of able-bodied subjects. Four (4) trans-tibial, 4 trans-femoral amputees and 10 able-bodied subjects walked at 1.2m.s(-1) along a walkway whilst kinematic data from both the intact and prosthetic limbs, and kinetic data from the intact limb only were collected. A Panasonic VHS video camera was used to film subjects walking in the sagittal plane with simultaneous force data collected from a Kistler force platform. The amputees were found to compensate for the functional loss of one or more joints by increasing net joint moments and power output on their intact limb compared to able-bodied subjects. At the intact limb ankle, the range of motion, peak dorsiflexor moment and power generation at toe-off increased. At the intact limb knee, power generation during stance and extensor moments and power absorption at toe-off increased. At the intact limb hip, extensor moment and power absorption during stance, and hip flexor moment and power generation at toe-off increased. These findings were partly attributed to the prostheses used but mainly to adaptation mechanisms displayed by trans-femoral and trans-tibial amputees. They have implications for the mobility of amputees and the long term health of their joints. It was recommended that prosthesis design, prosthesis fitting and training in the use of the prosthesis were all factors which could be investigated with a view to minimising intact limb loading.
Cloning synthetic talking heads. (1998)

The quality of Text-to-Visual-Speech synthesis is judged by how well it matches the visual perception of speech articulators with acoustic speech perception. Concurrently, di erent viewers often prefer di erent head models for subjective reasons. Traditional facial animation approach tied the parameterization of animation directly to the model. Switching the head model is di cult because a lengthy training process is required. In this paper, we present a method that creates a new talking head from an existing one without repeating the training process. It is assumed in this work that the visible motion of speech articulators can be described by a small set of feature points. By mapping the 3D trajectories of the feature points from the existing model to the new one, we can transfer the motion of articulators. A morphing algorithm is then used to animate a new talking head from these trajectories of feature points on the new model. The new talking head, though looking di erent, preserves the perceptual quality of the original one.
Energy-optimal mobile application execution: Taming resource-poor mobile devices with cloud clones (2012)

In this paper, we propose to leverage cloud computing to tame resource-poor mobile devices. Specifically, mobile applications can be executed in the mobile device (known as mobile execution) or offloaded to the cloud clone for execution (known as cloud execution), with an objective to conserve energy for mobile device. The energy-optimal execution policy is obtained by solving two constrained optimization problems, i.e., how to optimally configure the clock frequency to complete CPU cycles for mobile execution, and how to optimally schedule the data transmission for cloud execution in order to achieve the minimal energy within time delay. Closed-form solutions are obtained for both cases and applied to decide the optimal condition under whether the local execution or the remote execution is more energy-efficient for the mobile device. Moreover, numerical results illustrate that a significant amount of energy (e.g., up to 13 times for a typical mobile application profile) can be saved by optimally offloading the mobile application to the cloud clone.
Classification of Plant Electrophysiology Signals for Detection of Spider Mites Infestation in Tomatoes (2021)

Herbivorous arthropods, such as spider mites, are one of the major causes of annual crop losses. They are usually hard to spot before a severe infestation takes place. When feeding, these insects cause external perturbation that triggers changes in the underlying physiological process of a plant, which are expressed by a generation of distinct variations of electrical potential. Therefore, plant electrophysiology data portray information of the plant state. Analyses involving machine learning techniques applied to plant electrical response triggered by spider mite infestation have not been previously reported. This study investigates plant electrophysiological signals recorded from 12 commercial tomatoes plants contaminated with spider mites and proposes a workflow based on Gradient Boosted Tree algorithm for an automated differentiation of the plant’s normal state from the stressed state caused by infestation. The classification model built using the signal samples recorded during daylight and employing a reduced feature subset performs with an accuracy of 80% in identifying the plant’s stressed state. Furthermore, the Hjorth complexity encloses the most relevant information for discrimination of the plant status. The obtained findings open novel access towards automated detection of insect infestation in greenhouse crops and, consequently, more optimal prevention and treatment approaches.
Carbon catabolite repression of maltase synthesis in Saccharomyces carlsbergensis (1983)

Carbon catabolite repression of maltase gene expression is brought about by the addition of glucose, resulting in a drastic inhibition of the induction of maltase. When added to induced cells, glucose leads to the inhibition of maltase synthesis within 30 min, which can be accounted for by the disappearance of hybridizable maltase RNA sequences. The loss of maltase-specific RNA due to catabolite repression can be traced to the combined effects of a 15-fold decrease in the rate of transcription of the maltase structural gene 15 to 20 min after the addition of glucose and a change in the half-life of maltase mRNA. However, the stability of maltase, once induced, is not affected by the addition of glucose.
Iron Depletion Is Associated With Daytime Bottle-feeding in the Second and Third Years of Life (2006)

In the second and third years of life, there is an almost 2-fold association between iron depletion and daytime bottle-feeding compared with cup feeding. The child's age may be a modifier, and milk volume consumed may be a mediator, of this association. Duration of bottle use is a potentially modifiable practice.
A Convenient Risk Prediction Score for COVID-19 for Determining Whether or Not Hospitalization Is Recommended: Kanagawa Admission Priority Assessment Score (2022)

Objective Coronavirus disease 2019 (COVID-19) has caused a collapse of the medical care system, with effective triage proving vital. The Kanagawa admission priority assessment score, version-1 (KAPAS-1) and version-2 (KAPAS-2), was developed to determine the need for hospitalization. Patients with a high KAPAS (≥5) are recommended for hospitalization. We retrospectively investigated the correlation between the KAPAS and oxygen requirement during hospitalization. Methods We collected the clinical data of COVID-19 patients admitted between February 5 and December 6, 2020. Patients were divided into two groups: those who required oxygen therapy during hospitalization (OXY) and those who did not (NOXY). We assessed the correlations between the groups and KAPAS-1 and KAPAS-2. Results Overall, 117 COVID-19 patients were analyzed, including 20 OXY and 97 NOXY and 54 high KAPAS-1 and 63 high KAPAS-2. The median KAPAS-1 and KAPAS-2 were significantly higher in OXY than in NOXY (6.5 vs. 3, and 9 vs. 4, respectively). The areas under the receiver operating characteristic curves of KAPAS-1 and KAPAS-2 for oxygen requirement were 0.777 and 0.825, respectively, and the maximum values of Youden's index were 4 and 6, respectively. The proportions of high KAPAS-1 and high KAPAS-2 were significantly higher in OXY than in NOXY (90.0% vs. 37.1%, and 90.0% vs. 46.4%, respectively). Conclusion The KAPAS was significantly correlated with oxygen requirement. Furthermore, the KAPAS may be useful for deciding which patients are most likely to require hospitalization and for selecting non-hospitalized patients who should be carefully monitored.
ULTRASONIC DETECTION OF ANOMALOUS MACHINING DAMAGE (2009)

During manufacture, rotating jet‐engine components are shaped into their final configurations by machining operations which may include turning, drilling and broaching. Anomalous machining conditions, such as a loss of lubricant or a damaged cutting tool, can result in an altered near‐surface microstructure, shortening the useful life of the component. In this paper we report on preliminary attempts to detect anomalous machining damage using ultrasonic surface acoustic waves (SAWs). Two pulse/echo immersion setups are considered: normal‐incidence acoustic microscopy (Method 1); and oblique‐incidence SAW backscatter (Method 2). Each method is applied to pairs of Ti 6‐4 turned coupons, one manufactured using accepted best practices; and one purposely damaged using abusive machining conditions. Representative results are presented for each method. Method 1 is very sensitive to changes in surface topology; thus near‐surface damage that is accompanied by surface topology changes can be readily detected. For detecting microstructural damage in the absence of topology changes, Method 2 is preferable. In Method 2 the transducer tilt angle is found which results in the maximum backscattered SAW “noise.” This angle is dependent on the effective surface wave speed, which in turn is influenced by the near‐surface microstructure. For a set twenty Ti 6‐4 turned coupons, Method 2 was generally able to distinguish damaged from undamaged surfaces.
Vitamin D As Predictor Of Multiple Sclerosis Activity And Progression In Patients With CIS Treated Early With Interferon beta-1b (P5.016) (2014)

OBJECTIVE: To examine the predictive effects of 25(OH)D on disease activity and prognosis in patients starting IFNB-1b at the CIS and the effect of 25(OH)D on the occurrence of flu-like symptoms (FLS) during treatment. BACKGROUND: The BENEFIT study examined the effects of interferon beta-1b (IFNB-1b) in clinically isolated syndrome (CIS). In prior analyses 25-hydroxyvitamin D (25[OH]D) contributed to the prediction of rate of conversion to clinically definite multiple sclerosis (CDMS), MS activity, and rate of progression up to 5-years after CIS. DESIGN/METHODS: Patients with a first clinical demyelinating event and >=2 clinically silent brain MRI lesions randomized to early IFNB-1b treatment with serum 25(OH)D concentration measurements at baseline, 6, 12, and 24 months were included. Clinical and MRI follow-up lasted for 5 years. Cox proportional hazard models or generalized mixed effects models related season-adjusted 25(OH)D concentrations to outcomes. Occurrence of FLS was compared by Chi-Square. RESULTS: Patients were dichotomized into high (>=50 nmol/L) and low (<50 nmol/L) 25(OH)D groups based on season-adjusted 25(OH)D up to 12 months. From Year 1 to Year 5, patients with high 25(OH)D had a lower probability of conversion to CDMS (RR [95% CI]: 0.47 [0.28;0.80], score [logrank] test=8.14 on 1 df, p=0.0043, N=187), cumulative number of new lesions (RR [95% CI]: 0.70 [0.54;0.90], p=0.0055, N=216), percent change in T2 volume (high vs. low: -10 [-19;-2], p=0.016, N=213), and percent change in brain volume (high vs. low: 0.43 [0.14;0.72], p=0.0037, N=170). Occurrence of FLS did not differ between groups at Months 6, 12, and 24 (p>0.28). CONCLUSIONS: Among patients who started IFNB-1b treatment right after CIS, low 25(OH)D levels were a strong risk factor for long-term MS activity and severity but not for the occurrence of FLS, suggesting a role of vitamin D supplementation as an add-on to IFNB-1b in early treatment of patients with MS. Study Supported by: Bayer HealthCare Pharmaceuticals
Linear Time-Varying Dynamic Systems Optimization via Higher-Order Method Using Shifted Chebyshev’s Polynomials (1999)

For optimization of classes of linear time-varying dynamic systems with n states and m control inputs, a new higher-order procedure was presented by the authors that does not use Lagrange multipliers. In this new procedure, the optimal solution was shown to satisfy m 2p-order differential equations with time-varying coefficients. These differential equations were solved using weighted residual methods. Even though solution of the optimization problem using this procedure was demonstrated to be computation efficient, shifted Chebyshev’s polynomials are used in the paper to solve the higher-order differential equations. This further reduces the computations and makes this algorithm more appropriate for real-time implementation.
Inhibition of CXCR7 extends survival following irradiation of brain tumours in mice and rats (2014)

These results indicate that CXCR7 inhibitors could block GBM tumour recurrence after IR, perhaps by interfering with CSCs.
SYNTHESIZED IRON OXIDES USED AS A TOOL FOR DOCUMENTING REDUCING CONDITIONS IN SOILS (2008)

Recently, a new technology known as indicator of reduction in soils (IRIS) has emerged for documenting reducing conditions in soils. An iron (Fe) oxide paint is applied to polyvinyl chloride tubing that is subsequently placed within the soil. Under reducing conditions, the Fe oxides gain electrons, become soluble, and are stripped from the tubing. This study was initiated to address two questions that have emerged regarding the manufacture and use of IRIS tubes: (i) Why is a mixture of goethite (Gt) and ferrihydrite (minimum 30%-40% Gt) required for the Fe oxide paint to adhere and remain durable when applied to polyvinyl chloride tubing? and (ii) What is represented by the development of pale yellow areas that sometimes are observed on the IRIS tubes? To address these questions, Fe oxide coatings were examined using X-ray diffraction and Mössbauer techniques, by differential chemical extractions, and using scanning electron microscopy. Based on X-ray diffraction and scanning electron microscopy, we conclude that the transformation of ferrihydrite to Gt during paint synthesis results in large Gt crystals with an elongated lath-shaped habit that appear to produce an interlocking network of particles that enhances the durability of the paint. Differential extractions and Mössbauer data indicate that the development of pale yellow zones on the IRIS tubes represents a preferential dissolution of ferrihydrite over Gt, which is consistent with thermodynamic predictions of the relative stability of these two minerals in wetland soil environments.
Ultrastable iridium–ceria nanopowders synthesized in one step by solution combustion for catalytic hydrogen production (2014)

Solution combustion generates mesoporous ceria with strongly anchored Ir nanoparticles, which are efficient methane reforming catalysts.