gebhart/patrepeval huggingface dataset:
Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy (2022)

Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or "cancer-killing" viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.
ChemInform Abstract: Stereoselective Transformations of Polyhydroxyazepanes to Piperidine and Pyrrolidine Derivatives — Efficient Glycosidase Inhibitors. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
MMSE-based local ML detection of linearly precoded OFDM signals (2004)

Linear precoding is a well known effective technique to boost the performance of orthogonal frequency-division multiplexing (OFDM) systems. A drawback of linearly precoded OFDM (LP-OFDM) systems is the high computational complexity required by maximum-likelihood (ML) detection, which is mandatory to capture all the channel diversity. Conversely, low-complexity techniques, such as the linear minimum mean-squared error (MMSE) detection, suffer from nonnegligible performance loss with respect to the ML performance. This paper proposes a detection technique that performs a local ML (LML) search in the neighborhood of the output provided by the MMSE detector. The trade-off between performance and complexity of the proposed LML-MMSE detector, which fall between the ones of the MMSE and ML detectors, can be nicely adjusted by appropriately setting the neighborhood size. Simulation results show that the LML-MMSE detector with minimum neighborhood size outperforms a block decision-feedback equalization (DFE) approach, while preserving a similar complexity.
MP02-17 COMPUTER EXTRACTED NUCLEAR FEATURES FROM FEULGEN AND H&E IMAGES PREDICT BIOCHEMICAL RECURRENCE IN PROSTATE CANCER PATIENTS FOLLOWING RADICAL PROSTATECTOMY (2016)

develop a novel biomarker which can discriminate PCa from other benign lesions with improved specificity. We have previously reported that structural changes of glycan on PSA are promising biomarker. (Glycobiology, 2004 and 2008) LacdiNAc-PSA is an aberrant glycosylation isoform of PSA which has GalNAcb1-4GlcNAc (LacdiNAc) structure on its N-linked glycan. In this study, we evaluated diagnostic accuracy of LacdiNAc-PSA using an automated immunoassay system (Konica Minolta, Inc.), which utilizes one of the most sensitive fluorescence detection technologies; Surface Plasmon Field-enhanced Fluorescence Spectroscopy (SPFS) (Konica Minolta, Inc. (Anal. Cnem. 2015, Kaya et. al.)).
Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis (2017)

Infants listed for heart transplantation experience high waitlist and early post-transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual-level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model. CART analysis was used to create a model which, at the time of listing, would predict which infants listed for heart transplantation would survive at least 3 months post-transplantation. A total of 48 infants were included; 13 died while waiting, and six died within 3 months of heart transplant. CART analysis identified RRT, blood urea nitrogen, and hematocrit as terminal nodes with alanine transaminase as an intermediate node predicting death. No patients listed on RRT (n = 10) survived and only three of 12 (25%) patients listed on ECLS survived >3 months post-transplant. CART analysis overall accuracy was 83%, with sensitivity of 95% and specificity 76%. This study shows that CART analysis can be used to generate accurate prediction models in small patient populations. Model validation will be necessary before incorporation into decision-making algorithms used to determine transplant candidacy.
Effect of Tip Gap and Squealer Geometry on Measured Heat Transfer Over a HPT Rotor Blade Tip (2003)

The present study explores the effects of gap height and tip geometry on heat transfer distribution over the tip surface of a HPT first stage rotor blade. The pressure ratio (inlet total pressure to exit static pressure for the cascade) used was 1.2, and the experiments were run in a blow-down test rig with a four-blade linear cascade. A transient liquid crystal technique was used to obtain the tip heat transfer distributions. Pressure measurements were made on the blade surface and on the shroud for different tip geometries and tip gaps to characterize the leakage flow and understand the heat transfer distributions. Two different tip gap-to-blade span ratio of 1% and 2.6% are investigated for a plane tip and a deep squealer with depth-to-blade span ratio of 0.0416. For a shallow squealer with depth-to-blade span ratio of 0.0104, only 1% gap-to-span ratio is considered. The presence of the squealer alters the tip gap flow field significantly and produces lower overall heat transfer coefficients. The effects of different partial squealer arrangements are also investigated for the shallow squealer depth. These simulate partial burning off of the squealer in real turbine blades. Results show that in some cases, partial burning of squealers along the pressure surface may be beneficial in terms of overall reduction in heat transfer coefficients over the tip surface compared to the plain tip.
Preclinical Corrective Gene Transfer in Xeroderma Pigmentosum Human Skin Stem Cells (2011)

Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>10(40) cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients.
Proteomic similarities in Alzheimer’s disease and epilepsy brains highlight the important role of tau (2020)

Abstract Background Alzheimer's Disease (AD) patients are more likely to experience epileptic seizures, and cognitive impairment is a frequent comorbidity in patients with epilepsy. Emerging findings indicate a common link between epilepsy and AD, however our understanding of the pathological changes shared between these two diseases is limited. Therefore, our aim was to determine whether there are common protein changes associated with both epilepsy and AD using an unbiased proteomics approach. Method We used label‐free mass‐spectrometry to quantify protein differences in the human epileptic hippocampus (epilepsy vs controls; n=14/group) and compared these results to differentially expressed proteins in AD generated by a meta‐analysis of the 10 most comprehensive AD proteomics studies. Result 777 proteins were significantly altered in the hippocampus in epilepsy. A significant proportion of these protein changes were also observed in AD (263/777 similar protein changes; p&lt;0.0001). Proteins altered in both epilepsy and AD were predominantly excitatory neuron specific proteins (enrichment p&lt;0.0001). Network analysis showed that proteins altered in both epilepsy and AD were most significantly involved in remodelling of epithelial adherens junctions (17/57 proteins, p=2.37x10 ‐16 ), clathrin‐mediated endocytosis signalling (21/160 proteins, p=2.98x10 ‐12 ) and phagosome maturation (17/114 proteins, p=4.81x10 ‐11 ), suggesting that the endosomal/lysosomal system dysfunction is a key factor for both epilepsy and AD pathogenesis. Shared protein alterations also indicated a decrease in synaptic proteins (enrichment p=6.52x10 ‐21 ), confirming that synapse loss or dysfunction is a common feature of both diseases. Interestingly, tau was identified as the most significant upstream regulator of proteins altered in both epilepsy and AD (p=4.53x10 ‐36 ). Furthermore, there was a significant overlap between proteins altered in both epilepsy and AD and proteins present in our recently generated phosphorylated tau interactome (32/125 pTau interactome proteins, p&lt;0.0001). Together, this suggests that tau may have an important pathological role in both epilepsy and AD. Conclusion AD and epilepsy have many common protein changes in the brain. Tau may have an important role in mediating many of these common protein changes in AD and epilepsy.
Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study (2019)

Patients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.
Augmentation of research and analysis capabilities for timely support of automotive fuel economy activities. Final report Oct 77-Jan 78 (1981)

A series of studies were conducted in support of the Office of Research and Development of the NHTSA in areas of automotive design and technology that could affect fuel economy. Nine such studies were carried out and included assessments of spark ignition engine; fuel economy improvement potential; potential of changes in rolling resistance, aerodynamic drag, accessory load and lubricants. Other studies included a study of the potential of alternate engines, a compilation of literature, and a preliminary assessment of diesel particulates. In addition to conducting studies based on a literature review and analysis, there were two hardware studies conducted in the form of teardown studies of selected passenger car (Ford Fairmont) and light truck (Chevy Luv) models.
High volume hemofiltration (2000)

The use of continuous hemofiltration has increased dramatically since its first description in 1977. It is now the dominant form of renal replacement therapy in Australia and is fast reaching a similar status in many European countries. Its growing use and the frequent observation of its beneficial effects in septic patients has directed the attention of researchers toward its application in the field of blood purification for sepsis. In this context, experimental studies have suggested that increasing the volume of ultrafiltrate produced may increase the beneficial effects of continuous hemofiltration. This so-called high-volume hemofiltration (HVHF) has now been demonstrated to have striking beneficial effects on hemodynamics in porcine septic shock. It has also been shown to attenuate gastrointestinal mucosal reperfusion injury in a model of gut ischemia. Furthermore, the infusion of ultrafiltrate obtained during HVHF into healthy pigs induces profound hypotension and myocardial depression, suggesting that vasodilatory and myocardial depressant substances may be removed during the procedure. Such animal experiments have led clinicians to conduct their first interventions with HVHF in humans with the multi-organ dysfunction syndrome and septic shock. The initial results are promising. They open up a new area for the investigation of HVHF as an adjuvant therapy in the management of severe sepsis, septic shock, and the multi-organ dysfunction syndrome.
Role of Electron-Deficient Imidazoles in Ion Transport and Conductivity in Solid-State Polymer Electrolytes (2022)

Solid-state polymer electrolytes offer a safer alternative to traditional lithium-ion batteries based on organic electrolytes. The focus is here on imidazole(Im)-functionalized polymer electrolytes, where the Im ligand promotes salt dissolution, while its functionalization allows tuning the dynamic interactions between the cations in solution and the Im ligand tethered to the polymer backbone. Although careful choice of a polymer backbone and Im linker functionality have resulted in polymer electrolytes with increased total ionic conductivities and a boost in the Li+ ion contribution, improvements in performance through modifications of the Im heterocycle remain underexplored. In this work, we systematically investigate poly(methylsiloxane) polymers functionalized with a series of halogen-substituted imidazoles and show that Li+ ion conduction can be tuned by an electron-deficient heterocycle ligand. When the number of halogen substituents increases, the Li+ ion mobility also increases as measured by pulsed-field-gradient nuclear magnetic resonance (NMR) and NMR relaxometry. Although beneficial for Li+ transport, electron-deficient Im ligands result in clustering, as indicated by wide-angle X-ray scattering, and poor salt dissolution, which in turn impedes the overall ionic transport. This work highlights the importance of synthetic design and the necessity for high salt solvation and weak cation–polymer binding to obtain high Li+ transport numbers.
Experimental Modeling Of Hypothyroidism: Principles, Methods, Several Advanced Research Directions In Cardiology (2021)

Hypothyroidism is one of the most common pathological conditions in modern clinical practice. Due to the fact that the targets of thyroid hormones are virtually all organs and tissues, the morphological and clinical manifestations arising with a deficiency of thyroid hormones are quite diverse. Experimental models of hypothyroidism in laboratory animals are widely used for preclinical study of the fundamental pathophysiological mechanisms underlying hypothyroidism, as well as for assessing the effectiveness of treatment-and-prophylactic effects. Currently, several groups of effective models of hypothyroidism have been developed: dietary, surgical, medicamentous, genetic, radioactive and immunological. Each of the specified models is based on different principles, has advantages and disadvantages, and can be used depending on the goals and objectives of the experiment. In this review, we will consistently consider hypothyroidism modeling methods and indicate some promising areas of their use in cardiology.
Fuzzy structures analysis of aircraft panels in NASTRAN (2001)

This paper concerns an application of the fuzzy structures analysis (FSA) procedures of Soize to prototypical aerospace panels in MSC/NASTRAN, a large commercial finite element program. A brief introduction to the FSA procedures is first provided. The implementation of the FSA methods is then disclosed, and the method is validated by comparison to published results for the forced vibrations of a fuzzy beam. The results of the new implementation show excellent agreement to the benchmark results. The ongoing effort at NASA Langley and Penn State to apply these fuzzy structures analysis procedures to real aircraft panels is then described.
ChemInform Abstract: Head‐to‐Tail Assemblies of Dipolar, Piperazine‐Linked Chromophores: Synthesis, X‐Ray Structure, and Dielectric Characterization. (1990)

Abstract A dimer (III), its model compound (VIII), and a mixture of oligomers of acceptor‐substituted anilines are prepared.
The Short- and Long-Term Effects of Seprafilm®on Peripheral Nerves: A Histological and Functional Study (2009)

Extraneural scar reduction is an important goal in peripheral nerve microsurgery. The use of biosynthetic materials, such as Seprafilm , reduces postoperative adhesions in abdominopelvic gynecologic and orthopedic surgery. The study evaluates the safety of Seprafilm in proximity to nerve tissue in a noninjury (phase 1) and injury (phase 2) model. Phase 1 groups were: (1) sciatic nerve exposure and neurolysis (n = 15), (2) Seprafilm placement superficial to the nerve (n = 15), and (3) circumferentially wrapping Seprafilm around the nerve (n = 15). Outcome measures at 45 and 90 days included wound inspection, histomorphometry, and stereological analysis of vascularity. Phase II groups were: (1) sciatic nerve cut and repair alone (n = 15) or (2) nerve wrapped with Seprafilm (n = 15). Nerves were evaluated at 18, 32, and 42 days postoperatively, and animals underwent biweekly functional walking tracks. In phase I, no significant differences were detected between groups. In phase II, fewer perineural scar bands were seen with Seprafilm . Histomorphometric differences favoring Seprafilm at 18 days and favoring control at 42 days were noted ( P < 0.05), though no differences in functional outcomes were detected. Qualitatively less perineural scar tissue was seen when using Seprafilm . No functional or histological deleterious effects were noted from placing Seprafilm on intact nerves or cut and repaired nerves.
The Integrated MiniMed Paradigm Real-Time Insulin Pump and Glucose Monitoring System: Implications for Improved Patient Outcomes (2009)

The MiniMed Paradigm REAL-Time system (Medtronic Diabetes, Northridge, CA) was launched in 2006 and integrates real-time continuous glucose monitoring (CGM) with an insulin delivery device. The perceived advantages of such a system include the ability for patients to view and be alerted of glucose information in real-time and affords them a method to adjust insulin delivery in response to these data. Moreover, glucose, insulin, and meal information stored in the system can be uploaded by the patient to a computer using the web-based CareLink Personal Therapy Management software, or similarly by their Health Care Professional (HCP) using CareLink Pro software. The Paradigm REAL-Time system offers two distinct capabilities over conventional multiple daily injection therapy with self-monitoring of blood glucose, mainly the abilities to observe and react to glucose changes in a timely and appropriate manner using the Bolus Wizard calculator feature of the pump and to retrospectively review integrated glucose sensing and insulin delivery data. Retrospective review of uploaded data allows patients and HCPs the opportunity to modify insulin therapy and to potentially improve glycemic control without the use of a traditional glucose diary. When using CGM, the review of CareLink data can highlight interactions among meals, insulin delivery, and resulting glucose levels and supports an overall assessment of glycemic control as well as aid in the adjustment of insulin therapy regimens. Although the Paradigm REAL-Time system does not automatically adjust insulin delivery based on sensor glucose data in its current embodiment, this integrated system forms the basic platform for future generations of products in which the sensor will modify insulin dosing in semi- and ultimately fully closed-loop modalities.
Expression of the cancer testis antigen IGF2BP3 in colorectal cancers; IGF2BP3 holds promise as a specific immunotherapy target (2015)

IGF2BP3 mRNA was over expressed in 43% of the tumors whereas the protein was noted in 50% of samples. No correlation between mRNA expression and disease severity was noted. This protein holds promise as a vaccine target, however, a larger study that assesses a more diverse population of patients (Stage 1-4) as well as a study of preoperative serum samples for auto-antibodies to IGF2BP3 are needed to pursue this concept.
Novel Aryl and Heteroaryl Acyl Sulfamide Synthesis via Microwave-Assisted Palladium-Catalyzed Carbonylation (2010)

A novel, simple synthesis of aryl and heteroaryl acyl sulfamides has been developed via palladium-catalyzed carbonylation of aryl or heteroaryl halides in the presence of sulfamide nucleophiles. A range of reactions illustrating the wide scope of this reaction was carried out under microwave irradiation in a vessel equipped with a gas inlet adapter and proceeded in good to excellent yields.
Investigation of the Thermal Stability of 2-D Patterns of Au Nanoparticles (2007)

Nanoparticles can serve as useful components or sub-assemblies, i.e., building blocks, in the design and fabrication of more complex structures needed for rapid prototyping using layered nanofabrication (LNF) or for use in nanoelectromechanical systems (NEMS). This paper describes investigations of the thermal stability of simple 2-D patterns of thiol-coated, 5-nm gold nanoparticles deposited on the native oxide surface of a Si(100) single crystal substrate. The changes in the particle structure and location on the surface were probed by using atomic force microscopy (AFM) before and after heating in ambient air. Experiments were carried out on the as-deposited nanoparticles and on patterns of nanoparticles that had been pretreated (prior to heating) by a 10-min exposure in a UV-ozone ashing chamber. All individual particles and 2-D patterns were stable up to 550 degrees C. Higher temperatures caused first a reduction in particle height and eventually a loss of the particle from the field of view (presumably by rather long-range diffusion).