gebhart/patrepeval huggingface dataset:
DHA-SBT-1214 Taxoid Nanoemulsion and Anti–PD-L1 Antibody Combination Therapy Enhances Antitumor Efficacy in a Syngeneic Pancreatic Adenocarcinoma Model (2019)

The goal of this study was to evaluate combination of a novel taxoid, DHA-SBT-1214 chemotherapy, in modulating immune checkpoint marker expression and ultimately in improving antibody-based checkpoint blockade therapy in pancreatic adenocarcinoma (PDAC). DHA-SBT-1214 was encapsulated in an oil-in-water nanoemulsion and administered systemically in Panc02 syngeneic PDAC-bearing C57BL/6 mice. Following treatment with DHA-SBT-1214, expression levels of PD-L1 were measured and anti-PD-L1 antibody was administered in combination. The effects of combination therapy on efficacy and the molecular basis of synergistic effects were evaluated. PD-L1 expression was lower on Panc02 pancreatic tumor cells <i>in vitro</i>, which significantly increased after exposure to different chemotherapy drugs. Administration of DHA-SBT-1214, gemcitabine, and PD-L1 antibody alone failed to increase CD8<sup>+</sup> T-cell infiltration inside tumors. However, combination of anti-PD-L1 therapy with a novel chemotherapy drug DHA-SBT-1214 in nanoemulsion (NE-DHA-SBT-1214) significantly enhanced CD8<sup>+</sup> T-cell infiltration and the therapeutic effects of the anti-PD-L1 antibody. Furthermore, in the Panc02 syngeneic model, the NE-DHA-SBT-1214 combination therapy group reduced tumor growth to a higher extend than paclitaxel, nab-paclitaxel (Abraxane), gemcitabine, or single anti-PD-L1 antibody therapy groups. Our results indicate that NE-DHA-SBT-1214 stimulated immunogenic potential of PDAC and provided an enhanced therapeutic effect with immune checkpoint blockade therapy, which warrants further evaluation.
EV (Extracellular Vesicle)‐associated miRNAs as Biomarkers of Toxicity (2022)

Exosomes are secreted into the body fluids by various types of cells and organs. Recent studies have demonstrated that exosomes secreted by tumor cells are transported to surrounding cells and participate in metastasis and infiltration. Since these tumor-derived exosomes containing cancer cell-specific miRNAs and mRNAs are secreted into the body fluids, the miRNAs and mRNAs in cancer cell-derived exosomes have come to be used as diagnostic biomarkers for early stage cancers. In parallel, miRNAs contained in exosomes released into the blood from tissues and organs in response to adverse events, such as exposure to chemical substances and drugs, are expected to be useful as novel biomarkers for toxicity assessment. In this chapter we will introduce the latest findings on exosomes, including the newly appreciated biological significance of exosomes, for instance in exosome-mediated horizontal gene transfer, and explain the potential use of exosomes as biomarkers of toxicity.
S131022 Vision-based measurement of motion errors for machine tools (2011)

This paper presents vision-based measurement of two-dimensional positioning errors of machine tools. A pre-calibrated grid plate is used as an artifact. The position of a grid point is measured in an image captured by a charge coupled device (CCD) camera attached to a spindle. Unlike conventional two-dimensional digital scales, the vision-based measurement can target the artifact in any orientation, and thus can be applied to error calibration of a rotary axis. The paper demonstrates experimental applications of the vision-based measurement to the measurement of 1) static error motions of linear axes, 2) static radial error motion of a rotary axis, and 3) dynamic radial error motion of a rotary axis.
Hematopoietic growth factors-An overview (1990)

The hematopoietic growth factors are a family of glycoprotein hormones that regulate hematopoietic cell proliferation and mature blood cell function. The list of colony-stimulating factors and interleukins known to stimulate blood cell production is now quite long; these hormones are produced in quantity by recombinant molecular methodologies and most have entered clinical trials. We will shortly have the power to regulate the numbers and function of the circulating blood cells, and the challenge of the coming decade will be in dissecting how these growth factors can be used optimally in therapeutic practice. A central theme of their use will be the enhancement of host defense, opening an area of medical therapy of great potential to reduce the morbidity and mortality of cancer, infectious diseases and immune deficiency states.
Next generation manufacturing in Singapore (2002)

The regional economic crisis and the more recent terrorist attacks have been watershed events for Singapore. Although Singapore emerged relatively unscathed from these upheavals, the economic challenges remain ever-daunting and furthermore, the playing field has been elevated from regionalization to globalization. Therefore, as part of the restructuring strategy, Singapore has identified manufacturing and services as the main engines for growth in the near future. However, by merely attracting manufacturers here to invest is no longer sufficient. It was realized that the much more value has to be added through upgrading the entire manufacturing sector by developing a new set of skills and capabilities, collectively known as Next Generation Manufacturing (NGM). Thus, the main aim of this report is to investigate how NGM can be applied to the Singapore context in preparation for tougher competition in the years to come.
Simultaneous Inference and Training Using On-FPGA Weight Perturbation Techniques (2018)

We present an FPGA-optimized implementation of online neural network training based on weight perturbation (WP) techniques. When compared to the classic backpropagation (BP) algorithm, WP is capable of delivering competitive performance while occupying minimal area resources. Perturbation-based methods have been demonstrated as viable training techniques and are suitable for on-line learning applications which adapt to changing conditions. The viability of applying WP-based on-chip training for low-precision fixed-point hardware is demonstrated on two distinct MLP benchmarks: the Iris dataset classification network and an RF anomaly detector. When synthesized to a Xilinx Kintex-7 XC7K410T FPGA, WP offers a 3-10x area savings with <;1% degradation in accuracy compared with backpropagation. Compared with an inference-only implementation the overhead of introducing on-chip learning is approximately 30%.
Atomic Force Microscopy for the Characterisation of the Effects and Treatment of Infectious Parasites (2013)

In this talk the utility of atomic force microscopy (AFM) for research into infectious parasites will be discussed. AFM has grown from relatively recent beginnings to become an extremely powerful technique in the life sciences, coupling high resolution imaging with a range of non-imaging experiments. Importantly, these experiments can be performed in situ , even on individual molecules or on live cells. The two examples discussed relate to the important diseases leishmaniasis and malaria. Leishmaniasis is a disease caused by the protozoan parasite of the Leishmania genera, and causes approximately 60,000 deaths per year. Despite the high death toll, the disease has been the subject of relatively little research and little treatment is available, probably because the most severe cases are confined to developing nations. The most severe form, visceral leishmaniasis is caused by the species known as Leishmania infantum ( syn . L. chagasi) . A promising new anti-leishmania drug, DS01 has been recently isolated from amphibian secretions and can kill L. infantum in low concentrations. We were able to culture and prepare for microscopy L. infantum promastigotes for the first time, as well as to study the effects of DS01 on cell morphology and membrane integrity. The results from both AFM and SEM are highly complementary and illustrate the possibility of membrane-focussed activity as well as the possibility of attack on the flagella (figure 1). Malaria is one of the most deadly diseases in the world, killing more than 600,000 people per year, mostly in low-income countries. It is caused by Plasmodium parasites, and the most commonly studied stage is that in which the parasite invades the blood. Prior to blood invasion, the parasites infect hepatocytes in the liver, with formation of a parasitophorous vacuole, where they develop into exoerythrocytic forms and multiply to generate thousands of merozoites, later released into the bloodstream and causing disease. However, infection of liver cells, which is clinically silent, is required for disease progression. We studied infection of liver cells by Plasmodium using combined epifluorescence and atomic force microscopy. We observed significant changes in cell morphology as infection progressed (figure 2). Furthermore we made nanoindentation measurements with the AFM, to determine cellular stiffness. We observed stiffening of the cells after 48 hours of infection compared to uninfected cells. This was a cellular response to the Plasmodium infection, rather than a result of the stiffness of the invading parasites themselves. This stiffening may be caused by reinforcement of cytoskeletal structures, and we believe this may reflect a self-defence mechanism by the cell itself.
Bevacizumab combination therapy in recurrent, platinum‐refractory, epithelial ovarian carcinoma (2006)

Combination bevacizumab therapy demonstrated activity in heavily pretreated women with ovarian cancer. Gastrointestinal perforations were identified in 9%. Despite the toxicity of the regimen, prospective studies, particularly in less heavily pretreated patients, are warranted.
Synthesis of Triphenylamine-Containing Poly(methacrylamide) and Its Application to Organic Electroluminescent Devices. (1995)

ホール輸送性のトリフェニルアミンを側鎖に有するN-置換ポリメタクリルアミド (PTPAMA) を合成し, 積層型有機エレクトロルミネッセント素子 (EL素子) のホール輸送層として使用した. 陽極にインジウムースズ酸化物 (ITO), 陰極にマグネシウム-銀 (10: 1), 発光層に電子輸送性のトリス (8-キノリノラト) アルミニウム (III) 錯体 (Alq) を使用した二層型素子 (ITO/PTPAMA/Alq/Mg: Ag) から10Vで6000 cd/m2の高輝度が得られ, このポリマーが高いホール輸送性を有し, 有機EL素子のホール輸送層として有効であることが示された.
Improved Thermoelectric Generator Performance Using High Temperature Thermoelectric Materials (2017)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Thermoelectric generator (TEG) has received more and more attention in its application in the harvesting of waste thermal energy in automotive engines. Even though the commercial Bismuth Telluride thermoelectric material only have 5% efficiency and 250°C hot side temperature limit, it is possible to generate peak 1kW electrical energy from a heavy-duty engine. If being equipped with 500W TEG, a passenger car has potential to save more than 2% fuel consumption and hence CO&lt;sub&gt;2&lt;/sub&gt; emission reduction. TEG has advantages of compact and motionless parts over other thermal harvest technologies such as Organic Rankine Cycle (ORC) and Turbo-Compound (TC). Intense research works are being carried on improving the thermal efficiency of the thermoelectric materials and increasing the hot side temperature limit. Future thermoelectric modules are expected to have 10% to 20% efficiency and over 500°C hot side temperature limit. This paper presents the experimental synthesis procedure of both p-type and n-type skutterudite thermoelectric materials and the fabrication procedure of the thermoelectric modules using this material. These skutterudite materials were manufactured in the chemical lab in the University of Reading and then was fabricated into modules in the lab in Cardiff University. These thermoelectric materials can work up to as high as 500°C temperature and the corresponding modules can work at maximum 400°C hot side temperature. The performance loss from materials to modules has been investigated and discussed in this paper. By using a validated TEG model, the performance improvement using these modules has been estimated compared to commercial Bisemous Telluride modules.&lt;/div&gt;&lt;/div&gt;
Current in vitro and in silico models of blood-brain barrier penetration: a practical view. (2009)

Predictive, cost effective and fast evaluation of CNS penetration or unbound brain levels of NCEs, or both, presents a considerable challenge in preclinical screening in the pharmaceutical industry. It is evident that neither a single in vitro model nor a set of physicochemical parameters is capable of predicting complex in vivo measures, such as brain distribution or blood-brain barrier (BBB) penetration, accurately. Various in vitro and in silico strategies have been developed to model drug action as a function of BBB properties, with models that provide sufficient predictivity, reliability and throughput to be favored by the pharmaceutical industry. This review gives a practical summary of in vitro and in silico approaches to evaluate BBB penetration.
Generation of a Transgenic BALB/c Mouse Line With Selective Expression of Human Mesothelin in Thyroid Gland: Application in Mesothelin-targeted Immunotherapy (2019)

Despite encouraging clinical results with immune checkpoint inhibitors and other types of immunotherapies, the rate of failure is still very high. The development of proper animal models which could be applied to the screening of effective preclinical antitumor drugs targeting human tumor antigens, such as mesothelin (MSLN), is a great need. MSLN is a 40 kDa cell-surface glycoprotein which is highly expressed in a variety of human cancers, and has great value as a target for antibody-based therapies. The present study reports the establishment of an immunocompetent transgenic mouse expressing human MSLN (hMSLN) only in thyroid gland by utilizing an expression vector containing a thyroid peroxidase (TPO) promoter. These mice do not reject genetically modified tumor cells expressing hMSLN on the cell membrane, and tolerate high doses of hMSLN-targeted immunotoxin. Employing this TPO-MSLN mouse model, we find that the combination treatment of LMB-100 and anti-CTLA-4 induces complete tumor regression in 91% of the mice burdened with 66C14-M tumor cells. The combination therapy provides a significant survival benefit compared with both LMB-100 and anti-CTLA-4 monotherapy. In addition, the cured mice reject tumor cells when rechallenged, indicating the development of long-term antitumor immunity. This novel TPO-MSLN mouse model can serve as an important animal tool to better predict tumor responses to any immunomodulatory therapies that target MSLN.
Lateral Column Calcaneal Lengthening, Flexor Digitorum Longus Transfer, and Opening Wedge Medial Cuneiform Osteotomy for Flexible Flatfoot: A Biomechanical Study (2007)

Lateral column lengthening increased lateral forefoot pressures in a severe flatfoot model. An added medial cuneiform osteotomy provided increased deformity correction and decreased pressure under the lateral forefoot.
Characterization of dental pulp defect and repair in a canine model. (2011)

Reparative dentin formation was more pronounced for defect sizes up to 2/1 mm3 when treated with CH, and completely bridged the surgically created dentin defects only after 30 days. However, reparative dentin upon CH treatment failed to completely bridge pulp chamber exposure for 2/2 defects. By contrast, TM treatment only yielded mild reparative dentin bridging for defects up to 1/1, but not for either 2/1 or 2/2 defects at 30 days. Inflammatory responses of the exposed dental pulp tissue were more robust with the TM group than with the CH group. Thus, dental pulp tissue possesses a capacity for spontaneous repair by the formation of reparative dentin in this preclinical model, but only up to a defect size of -2 mm in diameter and 1 mm in depth. All observations are based on 30 days post-treatment in the canine model. These findings may serve as baseline for regenerative endodontic studies.
Comparison of Global versus Epidermal Growth Factor Receptor Pathway Profiling for Prediction of Lapatinib Sensitivity in Bladder Cancer (2009)

Chemotherapy for metastatic bladder cancer is rarely curative. The recently developed small molecule, lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor-2 receptor tyrosine kinase inhibitor, might improve this situation. Recent findings suggest that identifying which patients are likely to benefit from targeted therapies is beneficial, although controversy remains regarding what types of evaluation might yield optimal candidate biomarkers of sensitivity. Here, we address this issue by developing and comparing lapatinib sensitivity prediction models for human bladder cancer cells. After empirically determining in vitro sensitivities (drug concentration necessary to cause a 50% growth inhibition) of a panel of 39 such lines to lapatinib treatment, we developed prediction models based on profiling the baseline transcriptome, the phosphorylation status of EGFR pathway signaling targets, or a combination of both data sets. We observed that models derived from microarray gene expression data showed better prediction performance (93%-98% accuracy) compared with models derived from EGFR pathway profiling of 23 selected phosphoproteins known to be involved in EGFR-driven signaling (54%-61% accuracy) or from a subset of the microarray data for transcripts in the EGFR pathway (86% accuracy). Combining microarray data and phosphoprotein profiling provided a combination model with 98% accuracy. Our findings suggest that transcriptome-wide profiling for biomarkers of lapatinib sensitivity in cancer cells provides models with excellent predictive performance and may be effectively combined with EGFR pathway phosphoprotein profiling data. These results have significant implications for the use of such tools in personalizing the approach to cancers treated with EGFR-directed targeted therapies.
Study of the Surface Cleaning of GOI and SGOI Substrates for Ge Epitaxial Growth (2006)

An effective wet cleaning process, optimized for low temperature Ge epitaxy on thin Ge or SiGe structures with reduced surface roughening, is proposed. It is found that the HF+HCl cleaning is the most effective wet cleaning method that is applicable to the low temperature thermal cleaning. It is also found that temperature of the thermal cleaning appropriate for thin Germanium on Insulator (GOI) substrates is approximately 450ºC. Moreover, the successful formation of the strained-GOI structures is demonstrated by applying these wet and thermal cleaning processes to thin Silicon-Germanium on Insulator (SGOI) substrates.
Inhibition of PC1/3 and PC2 by 2,5‐dideoxystreptamine derivatives (2012)

The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in proteolytic maturation of peptide hormone precursors and implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases. In this work, we screened 45 compounds obtained by derivatization of a 2,5‐dideoxystreptamine scaffold. We found four promising PC1/3 competitive inhibitors and three PC2 inhibitors exhibiting various inhibition mechanisms with sub‐ and low micromolar inhibitory potency against a fluorogenic substrate. Low micromolar concentrations of certain compounds blocked the processing of the physiological substrate proglucagon. Interestingly, we identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity. Molecular modeling studies revealed interactions of the PC1/3 inhibitors with the active site that suggest structural modifications to further enhance potency. In support of experimental data suggesting that PC2 inhibition likely occurs via an allosteric mechanism, we identified several possible allosteric binding sites using computational searches. This work was supported by DA050854 to Iris Lindberg.
Evaluation of the Tensile Strength of Unidirectional Fiber Reinforced Metals by Monte-Carlo Simulation. Application of Finite Element Method. (1991)

A Monte-Carlo simulation method for evaluating the tensile strength of the unidirectional fiber reinforced metal matrix composites is proposed on the basis of the elastic-plastic finite element method. In this simulation model, the two one-dimensional line elements representing the reinforcing fibers are incorporated into two sides along the y-axis of a 4-nodes isoparametric element (plane stress), which represents the metal matrix. Furthermore, for estimating reasonably each element stress increment necessary to the fiber-break, the γmin method is applied to the simulation procedure. This simulation is performed for boron/alumium composite monolayer. The simulated result shows the larger stress concentration around the broken fiber than that of the previously proposed simulation by means of the shear-lag model. Therefore, the former simulation lowers the mean values of tensile strength and increases its scatter, as compared with the later. Such a statistical tendency is in good agreement with the results obtained by comparing the previous experiment with the shear-lag simulation method.
The Ubiquitous Human Skin Commensal Staphylococcus hominis Protects against Opportunistic Pathogens (2022)

Staphylococcus hominis is frequently isolated from human skin, and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique autoinducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator (<i>agr</i>) quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned medium by mass spectrometry and then validated synthetic AIP activity against all S. aureus <i>agr</i> classes. Synthetic AIPs also inhibited the conserved <i>agr</i> system in a related species, Staphylococcus epidermidis. We determined the distribution of S. hominis <i>agr</i> types on healthy human skin and found S. hominis <i>agr</i>-I and <i>agr</i>-II were highly represented across subjects. Further, synthetic AIP-II was protective <i>in vivo</i> against S. aureus-associated dermonecrotic or epicutaneous injury. Together, these findings demonstrate that a ubiquitous colonizer of human skin has a fundamentally protective role against opportunistic damage. <b>IMPORTANCE</b> Human skin is home to a variety of commensal bacteria, including many species of coagulase-negative staphylococci (CoNS). While it is well established that the microbiota as a whole maintains skin homeostasis and excludes pathogens (i.e., colonization resistance), relatively little is known about the unique contributions of individual CoNS species to these interactions. Staphylococcus hominis is the second most frequently isolated CoNS from healthy skin, and there is emerging evidence to suggest that it may play an important role in excluding pathogens, including Staphylococcus aureus, from colonizing or infecting the skin. Here, we identified that S. hominis makes 6 unique peptide inhibitors of the S. aureus global virulence factor regulation system (<i>agr</i>). Additionally, we found that one of these peptides can prevent topical or necrotic S. aureus skin injury in a mouse model. Our results demonstrate a specific and broadly protective role for this ubiquitous, yet underappreciated skin commensal.
Dementia with Impaired Temporal Glucose Metabolism in Late-Onset Metachromatic Leukodystrophy (2001)

An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism.