gebhart/patrepeval huggingface dataset:
Process Development and Scale‐up of PF‐03941275, a Novel Antibiotic (2003)

With the increase in bacterial resistance to available therapies, the development of new antibacterials with novel modes of action has become increasingly important. This chapter describes the development of a process used to prepare kilogram quantities of PF-03941275. This compound is previously prepared on gram scale to support early toxicology studies using essentially the medicinal chemistry procedure. The starting material, 5-bromo-2,4-difluorobenzaldehyde, is purchased from outside vendors and is originally of variable quality. The Suzuki—Miyaura coupling between boronate ester and 2-bromo-5-methyl-1,3,4-thiadiazole is significantly more demanding than the borylation. Final process for the large-scale preparation of PF-03941275 is summarized.
Making Decisions with Shuffled Bits (2019)

Unlabeled detection is an emerging paradigm for modern decentralized decision systems faced with big-data applications, and for all those applications in which data must be fused without exploiting their identity, due to the lack of provenance labels, or to uncontrolled data shuffling. Our focus here is on binary alphabets, and we ask: If our data have been shuffled in an unknown way, can a reliable decision about the underlying state of nature be made? Should the decision be made after an attempt to estimate the lost labels? And do there exist easily implementable decision rules? In answering these questions, we gain much insight: We show that two greedy algorithms previously introduced in the literature are equivalent to the GLRT, whose performance can be quite poor, and the detector known as ULR is equivalent to a simple counting rule. A new detector based on the central limit theorem is simply implementable and offers close-to-optimal performance in many scenarios of practical interest.
Shape Deviation Generator--A Convolution Framework for Learning and Predicting 3-D Printing Shape Accuracy (2020)

The 3-D shape accuracy is a critical performance measure for products built via additive manufacturing (AM). With advances in computing and increased accessibility of AM product data, machine learning for AM (ML4AM) has become a viable strategy for enhancing 3-D printing performance. A proper description of the 3-D shape formation through the layer-by-layer fabrication process is critical to ML4AM, such as feature selection and AM process modeling. The physics-based modeling and simulation approaches present voxel-level description of an object formation from points to lines, lines to surfaces, and surfaces to 3-D shapes. However, this computationally intensive modeling framework does not provide a clear structure for machine learning of AM data. Significant progress has been made to model and predict the shape accuracy of planar objects under data analytical frameworks. In order to predict, learn, and compensate for 3-D shape deviations using shape measurement data, we propose a shape deviation generator (SDG) under a novel convolution formulation to facilitate the learning and prediction of 3-D printing accuracy. The shape deviation representation, individual layer input function, and layer-to-layer transfer function for the convolution modeling framework are proposed and derived. A deconvolution problem for identifying the transfer function is formulated to capture the interlayer interaction and error accumulation effects in the layer-by-layer fabrication processes. Physics-informed sequential model estimation is developed to fully establish the SDG models. The Gaussian process regression is adopted to capture spatial correlations. The printed 2-D and 3-D shapes via a stereolithography (SLA) process are used to demonstrate the proposed modeling framework and derive new process insights for AM processes. Note to Practitioners-With advances in computing and increased availability of product data, machine learning for additive manufacturing (ML4AM) has become a viable strategy for enhancing 3-D printing accuracy. This work establishes the shape deviation generator (SDG) as a novel data analytical framework through a convolution formulation to model the 3-D shape formation in the AM process. This new engineering-informed machine-learning framework will facilitate the learning of AM data to establish models for geometric shape accuracy prediction and control.
Treatment of thromboembolism in cancer patients (2010)

Low-molecular-weight heparin remains the best treatment option for initial and long term treatment of VTE in cancer patients.
Endoscopic management of orbital tumors (2015)

A multidisciplinary team approach, including an oculoplastic surgeon, is an essential component for the surgical planning and management. As the cumulative surgical experience increases, the indications for this approach will likely continue to expand.
Pannexin 1: a novel regulator of acute hypoxic pulmonary vasoconstriction (2021)

In the present study, we identify Panx1 as novel regulator of HPV. Yet, the role of Panx1 in HPV was not attributable to ATP release and downstream signalling via P2Y receptors or TRPV4 activation, but relates to a role of Panx1 as direct or indirect modulator of the PASMC Ca2+ response to hypoxia. Panx1 did not affect the development of chronic hypoxic PH.
Evaluation of Transanal Hemorrhoidal Dearterialization as a Minimally Invasive Therapeutic Approach to Hemorrhoids (2010)

Transanal hemorrhoidal dearterialization appears to be a very effective minimally invasive option to treat hemorrhoids and can be performed in a day-surgery setting. Future controlled trials comparing transanal hemorrhoidal dearterialization with other procedures will show the real potential of transanal hemorrhoidal dearterialization and define adequate indications for this approach.
Apolipoprotein E: Far More Than a Lipid Transport Protein (2000)

First recognized as a major determinant in lipoprotein metabolism and cardiovascular disease, apolipoprotein (apo) E has emerged as an important molecule in several biological processes not directly related to its lipid transport function, including Alzheimer's disease and cognitive function, immunoregulation, and possibly even infectious diseases. ApoE is a polymorphic protein arising from three alleles at a single gene locus. The three major isoforms, apoE4, apoE3, and apoE2, differ from one another only by single amino acid substitutions, yet these changes have profound functional consequences at both the cellular and molecular levels. ApoE3 seems to be the normal isoform in all known functions, while apoE4 and apoE2 can each be dysfunctional. Isoform (allele)-specific effects include the association of apoE2 with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis and the association of apoE4 with increased risk for both atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth; isoform-specific differences in cellular signaling events may also exist. Functional differences in the apoE isoforms that affect (or did affect) survival before the reproductive years probably account, at least in part, for the allele frequencies of the present day.
Effect of pH on the properties of barium titanate slurries with an aniomic dispersant (2006)

Abstract The colloidal stability of barium titanate (BT) aqueous suspensions with poly(acrylamide/4‐carboxylamino‐4‐oxo‐2‐butenate) (PAAM/COB) at pH 7, 9, and 12 has been investigated by means of ζ potential, adsorption, sedimentation, and particle size measurements. The isoelectric point of BT powder is at pH 4.6 and the value of ζ potential decreases as the pH of suspensions increases. The adsorption of PAAM/COB onto BT particles follows the Langmuir adsorption isotherm. The saturated amount of adsorbed polymer decreases with increasing pH. In general, BT particles in basic solutions with PAAM/COB are more stabilized, and less agglomerated than those without any dispersant present. As pH is increased, the resulting ζ potential becomes more negative, although lower polymer concentration is required for monolayer coverage of particle surface. Consequently, the resulting suspensions become more stabilized, and contain powder with smaller particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1082–1088, 2006
Expression of the c-Met proto-oncogene and its possible involvement in liver invasion in adult T-cell leukemia. (2003)

c-Met is a tyrosine kinase receptor for hepatocyte growth factor and suggested to be involved in oncogenesis ormetastatic phenotypes in many malignancies. Adult T-cell leukemia (ATL) is a neoplasia characterized by massive invasion of the leukemic cells into various organs. Recently, we have reported frequent hepatic involvement and the relationship between liver invasion and the poor prognosis in ATL. In the present study, we investigated the expression of c-Met in ATL cells and its relation to liver dysfunction. In three of four human T-cell lymphotrophic virus-I-positive T-cell lines, c-Met was expressed both at mRNA and protein levels, whereas it was not expressed in human T-cell lymphoma virus-I-negative T-cell lines. The expressed c-Met should be functional, because hepatocyte growth factor could induce the autophosphorylation of c-Met. Although the viral-transactivating protein Tax has been shown to be involved in the deregulated expression of cellular genes, Tax mRNA was not detected in c-Met mRNA-expressed cell lines. From freshly isolated peripheral blood mononuclear cells, the expression of c-Met mRNA was detected in 10 of 16 ATL patients but not from healthy individuals. Finally, serum transaminase levels were significantly increased in c-Met-positive ATL cases, and all of the infiltrated c-Met-positive cells into liver were shown to be multilobularly nucleated phenotype. Taken together, these data suggest for the first time that c-Met is involved in the liver invasive phenotype of ATL.
Adaptive Duty Cycling for Place-Centric Mobility Monitoring using Zero-Cost Information in Smartphone (2014)

Smartphones enable the collection of mobility data using various sensors. The key challenge in the collection of continuous data is to overcome the limited battery capacity of the device. While extensive research has been conducted to solve energy issues in continuous mobility learning, we argue that previous works have not reached optimal performance. In this paper, we propose an energy-efficient mobility monitoring system, FreeTrack, to collect place-centric mobility data with minimum energy consumption in everyday life. We first analyzed the regularity of life patterns, cellular connection patterns, and battery charging behaviors of 94 smartphone users to examine important features related to human mobility. Based on our findings, we design an adaptive duty cycling scheme that uses zero-cost information (i.e., regular mobility, cell connection, and battery state) as low-level sensing to infer location change without the need to activate sensors. We model the location inference on the Hidden Markov Model and optimize the sensing schedule of individual smartphones for real-time operation. Our extensive experiment with 48 smartphone users shows that the proposed system achieves an energy saving of about 68% over previous works, yet still correctly traces 97% of mobility with 0.2±0.5 places misses in a day.
<title>Temperature influence on the mode distribution in SM fiber nearby the cutoff normalized frequency</title> (2006)

The optical fiber cutoff frequency is by one of its critical parameters, which couple working wavelength of lights, optical fiber dimension and refractive indexes of core and cladding into one numerical parameter. If the operational wavelength of the light source will be shorter than the cut-off wavelength is, then the fiber will support except fundamental mode the propagation of several higher modes too. Such fibers conserve themselves the advantageous characteristics for telecommunication application (small auenuation, slight dispersion), but it is possible to use them for sensor-based applications utilizing the mode coupling among guided modes. For the external influences plotting (e.g. temperature) causing on telecommunication fiber along the transmission route then the attenuation shift is not applicable because it impends the transmission in its principle either by an BER increase with keeping the transmission rate constant or by transmission rate fall with constant BER conservation. None of these implications is acceptable in optical backbones. Once from among few possibilities how to solve this problem is to set the operating conditions of the SM fiber nearby cutoff normalized frequency. In the paper the basic theory together with the simulation of the mode distribution will be shown for particular types of optical fibers for temperature changes within the interval O°C-80°C.
Metabolic adaptation of MDCK cells to different growth conditions: Effects on catalytic activities of central metabolic enzymes (2011)

Lactate and ammonia are the most important waste products of central carbon metabolism in mammalian cell cultures. In particular during batch and fed-batch cultivations these toxic by-products are excreted into the medium in large amounts, and not only affect cell viability and productivity but often also prevent growth to high cell densities. The most promising approach to overcome such a metabolic imbalance is the replacement of one or several components in the culture medium. It has been previously shown that pyruvate can be substituted for glutamine in cultures of adherent Madin-Darby canine kidney (MDCK) cells. As a consequence, the cells not only released no ammonia but glucose consumption and lactate production were also reduced significantly. In this work, the impact of media changes on glucose and glutamine metabolism was further elucidated by using a high-throughput platform for enzyme activity measurements of mammalian cells. Adherent MDCK cells were grown to stationary and exponential phase in six-well plates in serum-containing GMEM supplemented with glutamine or pyruvate. A total number of 28 key metabolic enzyme activities of cell extracts were analyzed. The overall activity of the pentose phosphate pathway was up-regulated during exponential cell growth in pyruvate-containing medium suggesting that more glucose-6-phosphate was channeled into the oxidative branch. Furthermore, the anaplerotic enzymes pyruvate carboxylase and pyruvate dehydrogenase showed higher cell specific activities with pyruvate. An increase in cell specific activity was also found for NAD(+)-dependent isocitrate dehydrogenase, glutamate dehydrogenase, and glutamine synthetase in MDCK cells grown with pyruvate. It can be assumed that the increase in enzyme activities was required to compensate for the energy demand and to replenish the glutamine pool. On the other hand, the activities of glutaminolytic enzymes (e.g., alanine and aspartate transaminase) were decreased in cells grown with pyruvate, which seems to be related to a decreased glutamine metabolism.
Data from Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms (2023)

&lt;div&gt;Abstract&lt;p&gt;Antiangiogenic therapy used in treatment of metastatic colorectal cancer (mCRC) inevitably succumbs to treatment resistance. Upregulation of MET may play an essential role to acquired anti-VEGF resistance. We previously reported that cabozantinib (XL184), an inhibitor of receptor tyrosine kinases (RTK) including MET, AXL, and VEGFR2, had potent antitumor effects in mCRC patient-derived tumor explant models. In this study, we examined the mechanisms of cabozantinib sensitivity, using regorafenib as a control. The tumor growth inhibition index (TGII) was used to compare treatment effects of cabozantinib 30 mg/kg daily versus regorafenib 10 mg/kg daily for a maximum of 28 days in 10 PDX mouse models. &lt;i&gt;In vivo&lt;/i&gt; angiogenesis and glucose uptake were assessed using dynamic contrast-enhanced (DCE)-MRI and [&lt;sup&gt;18&lt;/sup&gt;F]-FDG-PET imaging, respectively. RNA-Seq, RTK assay, and immunoblotting analysis were used to evaluate gene pathway regulation &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt;. Analysis of TGII demonstrated significant antitumor effects with cabozantinib compared with regorafenib (average TGII 3.202 vs. 48.48, respectively; &lt;i&gt;P&lt;/i&gt; = 0.007). Cabozantinib significantly reduced vascularity and glucose uptake compared with baseline. Gene pathway analysis showed that cabozantinib significantly decreased protein activity involved in glycolysis and upregulated proteins involved in autophagy compared with control, whereas regorafenib did not. The combination of two separate antiautophagy agents, SBI-0206965 and chloroquine, plus cabozantinib increased apoptosis &lt;i&gt;in vitro&lt;/i&gt;. Cabozantinib demonstrated significant antitumor activity, reduction in tumor vascularity, increased autophagy, and altered cell metabolism compared with regorafenib. Our findings support further evaluation of cabozantinib and combinational approaches targeting autophagy in colorectal cancer. &lt;i&gt;Mol Cancer Ther; 17(10); 2112–22. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
May the Force Be with You (Or Not): The Immune System under Microgravity (2021)

All terrestrial organisms have evolved and adapted to thrive under Earth's gravitational force. Due to the increase of crewed space flights in recent years, it is vital to understand how the lack of gravitational forces affects organisms. It is known that astronauts who have been exposed to microgravity suffer from an array of pathological conditions including an impaired immune system, which is one of the most negatively affected by microgravity. However, at the cellular level a gap in knowledge exists, limiting our ability to understand immune impairment in space. This review highlights the most significant work done over the past 10 years detailing the effects of microgravity on cellular aspects of the immune system.
Guidelines for the specification of models to be used in design-oriented simulations (2010)

Simulation-based design requires models at many levels of detail. In the early stages, models must approximate the coarse behavior of the system across many domains -- power, efficiency, cost, size, and weight. In later stages, the models must represent the system with increasing accuracy -- including dynamic performance, controllability, and other more-subtle manifestations. In this work, we focus on specification of the models for a simulation-based design of ship power systems. We address the issues of levels of detail in models, definition of model ports to support substitution of models at increasing levels of detail, and the application of multiple analyses to one set of simulation models. Eventually, we tackle very detailed issues such as insulation coordination and grounding scheme that are not at all important in the conceptual stages of design.
Associations of Global Country Profiles and Modifiable Risk Factors with COVID-19 Cases and Deaths (2020)

Abstract Modifiable risk factors affect SARS-CoV-2 infection and mortality raising the possibility that lifestyle modification could play a role. This has not been studied at a global level. We analysed publicly available data from countries reporting COVID-19 cases and deaths. Associations of modifiable risk factors with total cases and excess deaths were determined with and without adjustment for confounders. 4,670,832 cases and 311,384 deaths were reported by 181 countries by 18th May 2020. Wealthier countries had the greatest caseload. Obesity was the primary modifiable risk factor for infection and greater age, male sex, physical inactivity and low salt consumption were associated with excess deaths. Obesity was less influential on mortality than physical inactivity. Globally, obesity confers vulnerability to SARS-CoV-2 infection and physical inactivity likely explains the greater mortality in the obese. High salt consumption may induce reductions in tissue ACE2 expression and subsequently reduce mortality rates.
SU‐F‐T‐244: Radiotherapy Risk Estimation Based On Expert Group Survey (2016)

Purpose: To evaluate the reliability of RPN (Risk Priority Number) decided by expert group and to provide preliminary data for adapting FMEA in Korea. Methods: 1163 Incidents reported in ROSIS for 11 years were used as a real data to be compared with, and were categorized into 146 items. The questionnaire was composed of the 146 items and respondents had to valuate ‘occurrence (O)’, ‘severity (S)’, ‘detectability (D)’ of each item on a scale from 1 to 10 according to the proposed AAPM TG‐100 rating scales. 19 medical physicists from 19 different organizations in Korea had participated in the survey. Because the number of ROSIS items was not evenly spread enough to be classified into 10 grades, 1–5 scale was chosen instead of 1–10 and survey result was also fit to 5 grades to compare. Results: The average O,S,D were 1.77, 3.50, 2.13, respectively and the item which had the highest RPN(32) was ‘patient movement during treatment’ in the survey. When comparing items ranked in the top 10 of each survey(O) and ROSIS database, two items were duplicated and ‘Simulation’ and 'Treatment’ were the most frequently ranked RT process in top 10 of survey and ROSIS each. The Chronbach α of each RT process were ranged from 0.74 to 0.99 and p‐value was &lt;0.001. When comparing O*D, the average difference was 1.4. Conclusion: This work indicates the deviation between actual risk and expectation. Considering that the respondents were Korean and ROSIS is mainly composed of incidents happened in European countries and some of the top 10 items of ROSIS cannot be applied in radiotherapy procedure in Korea, the deviation could have been came from procedural difference. Moreover, if expert group was consisted of experts from various parts, expectation might have been more accurate. Therefore, further research on radiotherapy risk estimation is needed.
Nerve growth factor regulates the expression and activity of p33cdk2 and p34cdc2 kinases in PC12 pheochromocytoma cells. (1994)

In the absence of serum, nerve growth factor (NGF) promotes the survival and differentiation of the PC12 pheochromocytoma cell line. In the presence of serum, NGF acts primarily as a differentiation factor and negative regulator of cell cycling. To investigate NGF control of cell cycling, we have analyzed the regulation of cyclin dependent kinases during PC12 cell differentiation. NGF treatment leads to a reduction in the steady-state protein levels of p33cdk2 and p34cdc2, two key regulators of cell cycle progression. The decrease in p33cdk2 and p34cdc2 coincides with a decrease in the enzymatic activity of cyclinA-p34cdc2, cyclinB-p34cdc2, cyclinE-p33cdk2, and cyclinA-p33cdk2 kinases. The decline in p33cdk2 and p34cdc2 kinase activity in response to NGF is accelerated in cells that over-express the p140trk NGF receptor, suggesting that the timing of the down- regulation is dependent on the level of p140trk and the strength of the NGF signal. The level of cyclin A, a regulatory subunit of p33cdk2 and p34cdc2, is relatively constant during PC12 differentiation. Nevertheless, the DNA binding activity of the cyclinA-associated transcription factor E2F/DP decreases. Thus, NGF down-regulates the activity of cyclin dependent kinases and cyclin-transcription factor complexes during PC12 differentiation.