gebhart/patrepeval huggingface dataset:
Tyrosine Kinase Inhibitors Display Potent Activity against Cryptosporidium parvum (2022)

The protozoan parasite <i>Cryptosporidium</i> is a leading cause of diarrheal disease (cryptosporidiosis) and death in young children. Cryptosporidiosis can be life-threatening in individuals with weak immunity such as HIV/AIDS patients and organ transplant recipients. There is currently no effective drug to treat cryptosporidiosis in the pediatric and immunocompromised population. Therefore, there is an urgent need to expedite the drug discovery process in order to develop new and effective therapies to reduce the global disease burden of cryptosporidiosis. In this study, we employed a drug repurposing strategy to screen a library of 473 human kinase inhibitors to determine their activity against Cryptosporidium parvum. We have identified 67 new anti-cryptosporidial compounds using phenotypic screening based on a transgenic C. parvum strain expressing a luciferase reporter. Further, dose-response assays led to the identification of 11 hit compounds that showed potent inhibition of C. parvum at nanomolar concentration. Kinome profiling of these 11 prioritized hits identified compounds that displayed selectivity in targeting specific families of kinases, particularly tyrosine kinases. Overall, this study identified tyrosine kinase inhibitors that hold potential for future development as new drug candidates against cryptosporidiosis. <b>IMPORTANCE</b> The intestinal parasite Cryptosporidium parvum is a major cause of diarrhea-associated morbidity and mortality in children, immunocompromised people, and young ruminant animals. With no effective drug available to treat cryptosporidiosis in humans and animals, there is an urgent need to identify anti-parasitic compounds and new targets for drug development. To address this unmet need, we screened a GSK library of kinase inhibitors and identified several potent compounds, including tyrosine kinase inhibitors, that were highly effective in killing C. parvum. Overall, our study revealed several novel compounds and a new family of kinases that can be targeted for anti-cryptosporidial drug development.
Cellular Uptake and Trafficking of a Prototypical Magnetic Iron Oxide Label In Vitro (1995)

The mechanism of cellular uptake of a prototypical opsonized iron oxide label is consistent with receptor-mediated endocytosis. Immediately after cell contact, RMA localizes to the lysosomal compartment and at long time points reside in vesicles that by morphology and distribution appear to be terminal lysosomes. Iron oxides therefore demonstrate metabolism via the lysosomal pathway.
Coronary artery narrowing in rats: mechanical alterations of left and right myocardium (1991)

To determine the effects of chronic coronary artery narrowing on myocardial contractile performance, nonocclusive constriction of the left coronary artery near its origin was surgically induced in rats and global cardiac hemodynamics, left and right myocardial mechanics, and the magnitude and distribution of tissue damage and interstitial fibrosis in the left ventricular wall were analyzed 1 mo later. Reductions in coronary artery luminal diameter of 55% resulted in left ventricular failure as characterized by decreases in systemic arterial pressures, systolic ventricular pressure, rise and decay in first derivative of left ventricular pressure (+/- dP/dt), and an increase in left ventricular end-diastolic pressure. Right side dysfunction was also present as documented by an elevation in right ventricular end-diastolic pressure and a reduction in -dP/dt. In vitro measurements of papillary muscle mechanics revealed a biventricular reduction in isometric developed tension and peak rates of tension rise and decay. Moreover, the kinetic parameters of isometric contraction duration, time to peak tension and time to one-half relaxation, were significantly shorter in left muscles from coronary artery-narrowed animals. Isotonically, peak muscle shortening was reduced in the left muscle, whereas time to peak shortening was prolonged in the right myocardium. In addition, the velocities of muscle shortening and relengthening were decreased in both ventricles. Foci of replacement fibrosis and diffuse interstitial fibrosis were found in the epimyocardium, midmyocardium, and endomyocardium, demonstrating that a significant amount of myocyte loss occurred throughout the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract B45: Pancreatic cancers depend on a non-canonical glutamine metabolism pathway (2015)

Abstract Cancer cells exhibit metabolic dependencies that distinguish them from their normal counterparts. Among these addictions is an increased utilization of the amino acid glutamine (Gln) to fuel anabolic processes. Recently, we reported the identification of a non-canonical pathway of Gln utilization in human pancreatic cancer cells that is required for tumor growth. While most cells utilize glutamate dehydrogenase (GLUD1) to convert Gln-derived glutamate (Glu) into alpha-ketoglutarate (alpha-KG) in the mitochondria to fuel the tricarboxylic acid cycle, pancreatic cancer cells rely on a distinct pathway that integrates the mitochondrial and cytosolic aspartate aminotransferases GOT2 and GOT1. By generating alpha-KG from Glu (in conjunction with the conversion of oxaloacetate into aspartate), GOT2 fuels anaplerosis in place of GLUD1. The Asp created is released into the cytosol and acted on by GOT1. This is subsequently used through a series of reactions to yield cytosolic NADPH from malic enzyme. Importantly, we have demonstrated that pancreatic cancers are strongly dependent on this series of reactions to maintain redox homeostasis which enables proliferation. Herein, we detail the subcellular compartmentalization and consequences of the aforementioned reactions on pancreatic cancer metabolism. We have also investigated the essentiality of this pathway in other contexts and find that pancreatic cancers have a uniform and unique reliance on this pathway, which may provide novel therapeutic approaches to treat these refractory tumors. Citation Format: Costas A. Lyssiotis, Jaekyoung Son, Joesph D. Mancias, Haoqiang Ying, Lewis C. Cantley, Alec C. Kimmelman. Pancreatic cancers depend on a non-canonical glutamine metabolism pathway. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B45.
Synthesis and reactivity of allyl nickel(II) N‐heterocyclic carbene enolate complexes (2007)

Abstract Two new N ‐heterocyclic carbene enolate nickel(II) allyl complexes have been prepared and their activity towards ethylene polymerization was investigated. It was found that in the presence of diethyl zinc, the carbene enolate complex bearing a nitro substituent produces highly linear polyethylene of modest molecular weight and high polydispersity. The influence of the reaction parameters on catalytic activity and the characteristics of the resulting polymer were investigated through systematic variation of the time, temperature, and diethyl zinc concentration. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45:3637–3647, 2007
Enantioselective Catalytic Addition of N‐Acyl Radicals: In Batch and In Flow Organophotoredox α‐Amination of Aldehydes (2023)

Abstract The organophotoredox catalytic enantioselective addition of N ‐acyl radicals to aldehydes, to afford enantioenriched N ‐acyl 1,2 aminoalcohols was studied. Under the best conditions, in batch, the product was isolated in up to 52 % yield and 85 % e.e ., using a low cost and commercially available chiral imidazolidinone as organocatalyst. The reaction was then studied in flow, exploring different experimental setups and photoreactors. Although modest yields were obtained, the in‐flow process afforded the product in higher productivities (up to 60 times higher) and improved space time yields (increased up to 113 times) compared to the batch reaction, with no loss of stereoselectivity.
High speed localized cooling using SiGe superlattice microrefrigerators (2003)

In this paper, thin film based SiGe superlattice microrefrigerators are fabricated and characterized in terms of maximum cooling, power density and transient response. The localized cooling and fast transient response, less than 40 /spl mu/s, demonstrate the potential for hot spot cooling of optoelectronics, microprocessor and IC chips.
Residual Stress Improvement Mechanism on Metal Material by Underwater Laser Irradiation. (2000)

Residual stress improvement technology for component surface by underwater pulsed laser irradiation has been developed as a method of preventing stress corrosion cracking (SCC) of core components in nuclear reactors. In order to optimize the laser irradiation conditions based on a complete understanding of the mechanism, the propagation of a shock wave induced by the impulse of laser irradiation and the dynamic response of the irradiated material were analyzed through time-dependent elasto-plastic calculations with a finite element program. The calculated results are compared with the measured results obtained by experiments in which laser pulses with an energy of 200mJ are focused to a diameter of 0.8mm on a water-immersed test piece of 20% cold-worked Type 304 austenitic stainless steel to simulate neutron irradiation hardening. A residual compressive stress, which is nearly equivalent to the yield stress of the processed material, remains on the material surface after passage of the shock wave with enough amplitude to induce a permanent strain. Multiple irradiation of laser pulses extends the stress-improved depth to about 1mm, which would be the limit corresponding to the three-dimensional dispersion effect of the shock wave.
The biomechanics of proximal humeral fractures: Injury mechanism and cortical morphology (2018)

This study has shown that arm position during a fall influences fracture configuration of the proximal humerus. Correlating fracture pattern and mechanism of injury will allow more appropriate fracture reduction techniques to be devised.
Annexin A9 (ANXA9) biomarker and therapeutic target in epithelial cancer (2023)

Amplification of the ANXA9 gene in human chromosomal region 1q21 in epithelial cancers indicates a likelihood of both in vivo drug resistance and metastasis, and serves as a biomarker indicating these aspects of the disease. ANXA9 can also serve as a therapeutic target. Interfering RNAs (iRNAs) (such as siRNA and miRNA) and shRNA adapted to inhibit ANXA9 expression, when formulated in a therapeutic composition, and delivered to cells of the tumor, function to treat the epithelial cancer.
Genetics ofHeliothisandHelicoverparesistance to chemical insecticides and toBacillus thuringiensis (1997)

Genetic linkage maps of Heliothis virescens and Helicoverpa armigera are being used to identify and characterize resistance-conferring genes. The insensitive acetylcholinesterase conferring resistance to organophosphorus insecticides and the insensitive sodium channel conferring resistance to pyrethroids have both been mapped in H. virescens. The linkage mapping approach permits a genetic dissection of resistance, even when the mode of action and lethal target are not precisely known, such as for the insecticidal toxins from the bacterium Bacillus thuringiensis (Bt). We have identified and mapped a major Bt-resistance locus in a strain of H. virescens exhibiting up to 10000-fold resistance to Cry1Ac toxin and are currently developing a linkage map for H. armigera with a set of ‘anchor’ loci to facilitate comparison with H. virescens. Both species are currently experiencing their first significant selective pressure in the field by transgenic cotton expressing Cry1Ac, and timely identification of resistance mechanisms and their underlying genetic basis will be essential in successfully managing the Bt resistance that will eventually appear. ©1997 SCI
Effect of Insufficient Light Exposure on Polymerization Kinetics of Conventional and Self-adhesive Dual-cure Resin Cements (2016)

For both conventional and self-adhesive dual-cure resin cements, insufficient light exposure (20 seconds of light-curing time) through thick ceramic restoration (4 mm thick) resulted in a DC even lower than that of self-curing alone.
Lower Extinction Risk in Sleep‐or‐Hide Mammals (2008)

An ever larger proportion of Earth's biota is affected by the current accelerating environmental change. The mismatches between organisms and their environments are now increasing in both magnitude and frequency, resulting in lowered fitness and hence the decline of populations. Under this scenario, species with behavioral and/or physiological traits that provide them shelter from the environment are predicted to be less vulnerable to population declines than species that are always exposed to the elements. Here, we coded 4,536 living mammal species for sleep-or-hide (SLOH) behavior, including hibernation, torpor, and the use of burrows, among other related traits. We demonstrate that species that exhibit SLOH behavior are underrepresented in high-risk International Union for Conservation of Nature Red List categories. We found that SLOH behavior contributes to lowering extinction risk even after we accounted for other factors that directly or indirectly buffer species against extinction, such as larger geographic ranges and smaller body sizes. This result is robust to analyses using phylogenetically independent contrasts. Sleep-or-hide behavior, made possible by a related suite of physiological adaptations, allows mammals to function at lower metabolic rates and/or buffer them from changing physical elements. Mammals with SLOH behavior have a greater propensity to survive in the current extinction crisis and probably also in past crises because of reduced exposure to environmental stress.
Virological andserological aspectsofhepatitis B andthedelta agent (1993)

Thehepatitis B virus(HBV)belongs toa groupofviruses termedhepadnaviruses. The3-2kbgenomeencodes foravariety ofproteins involved inviralreplication (p-gene), transactivation (x-gene), or encodesforstructural proteins (c-and s-genes). Severalviraland non-viral functions determine theclinical courseof HBV infection. The hepatitis D virus resembles aviroid andrequires theHBV asahelper virus. Theinteraction between theviruses isnotweliunderstood. More information on theinteraction between thehumanhostandviruses isneededto helpimprovethetreatment. (Gut1993; supplement: S-S5) Fiveidentified andatleast twoadditional unidentified agents mayberesponsible forthe clinical features ofacutehepatitis. Identified agents havebeentermed viruses A,B,C,D, andE.Whereas chronic disease courses have notbeenreported inhepatitis A andE, chronicity occurs atdifferent rates inhepatitis B,C,andD.Theclinical features linked to viral persistence arehighly variable andspan fromasymptomatic subjects withnormal liver enzymeactivities topatients withprogressive liverdisease.' Serious lateoutcomesof chronicity include liver cirrhosis andprimary livercellcarcinoma.' 2 This review concentrates on virological andserological aspects ofhepatitis B andthedelta agent with special emphasis ontheir clinical significance.
Investigating the Migratory Behavior of Soybean Looper, a Major Pest of Soybean, through Comparisons with the Corn Pest Fall Armyworm Using Mitochondrial Haplotypes and a Sex-Linked Marker (2023)

The Noctuid moth soybean looper (SBL), <i>Chrysodeixis includens</i> (Walker), is an economically important pest of soybean (<i>Glycine max</i> (Linnaeus) Merrill). Because it is not known to survive freezing winters, permanent populations in the United States are believed to be limited to the southern regions of Texas and Florida, yet its geographical range of infestations annually extend to Canada. This indicates annual migrations of thousands of kilometers during the spring and summer growing season. This behavior is like that of the fall armyworm (FAW), <i>Spodoptera frugiperda</i> (J.E. Smith), also a Noctuid that is a major global pest of corn. SBL and FAW are projected to have very similar distributions of permanent populations in North America based on climate suitability modeling and the overlap in the distribution of their preferred host plants (corn and soybean). It therefore seems likely that the two species will display similar migratory behavior in the United States. This was tested by identifying genetic markers in SBL analogous to those successfully used to delineate FAW migratory pathways and comparing the distribution patterns of the markers from the two species. Contrary to expectations, the results indicate substantial differences in migratory behavior that appear to be related to differences in the timing of corn and soybean plantings. These findings underscore the importance of agricultural practices in influencing pest migration patterns, in particular the timing of host availability relative to mean seasonal air transport patterns.
Endomicroscopy of the human cochlea using a micro-optical coherence tomography catheter (2021)

Sensorineural hearing loss (SNHL) is one of the most profound public health concerns of the modern era, affecting 466 million people today, and projected to affect 900 million by the year 2050. Advances in both diagnostics and therapeutics for SNHL have been impeded by the human cochlea's inaccessibility for in vivo imaging, resulting from its extremely small size, convoluted coiled configuration, fragility, and deep encasement in dense bone. Here, we develop and demonstrate the ability of a sub-millimeter-diameter, flexible endoscopic probe interfaced with a micro-optical coherence tomography (μOCT) imaging system to enable micron-scale imaging of the inner ear's sensory epithelium in cadaveric human inner ears.
Silicon Mach-Zehnder Interferometer modulator with PAM-4 data modulation at 64 Gb/s (2015)

This paper outlines the co-design and simulation of the photonics and electronics circuits for an optical modulator implementing a 4-level phase amplitude modulation scheme at 64 Gb/s. The photonics circuit is designed for an SOI process with a 300 nm top Si layer and is based on a Mach-Zehnder Interferometer architecture modulator using carrier depletion. The CMOS driver circuit employs two on-chip PRBS sources and tunable delay pre-driver segments. This driver is flip-chip bonded to the photonics die to complete the packaging. Details of the model are outlined below and a simulated optical eye diagram is presented.
Deregulated Aiolos Expression in Common Variable Immunodeficiency (2009)

Common variable immunodeficiency (CVID), a frequent primary immunodeficiency disease, is characterized, by defects involving T and B cells. The Aiolos transcription factor plays an important role in the control of B cell differentiation and proliferation and is modulated through alternative splicing. In order to assess the role of Aiolos in this human pathology, we analyzed the Aiolos isoforms distribution and expression. We demonstrated that the major Aiolos isoform expressed in PBMC's of healthy donors and CVID patients is hAio1, whereas the rest of the Aiolos isoforms showed homogenous distribution. In addition, we detected three new Aiolos isoforms in CVID patients that were non-detectable in healthy donors. Furthermore, we quantified Aiolos expression in T and B cells from CVID patients, given that both cell populations are altered in this pathology. Our results show an up-regulation of Aiolos expression in T and B cells from CVID patients compared to healthy donors that was confirmed at the protein level. Finally, we show a different cellular distribution of Aiolos in CVID patients compared to that found in healthy donors.
Temperature-programmed desorption spectra of oxygen from transition metal ion-exchanged Y-type zeolites (1976)

Temperature-programmed desorption spectra of oxygen from several metal ion-exchanged Y-type zeolites show that oxygen is adsorbed on them in various states and in various amounts depending on the metal ion species exchanged; CuIIY, an exceedingly active catalyst for oxidation, adsorbs markedly large amounts of oxygen which reflects on the importance of such adsorbed oxygen in the catalytic oxidation reactions.
Conserved but nonessential interaction of SRP RNA with translation factor EF-G (2004)

4.5S RNA is essential for viability of Escherichia coli, and forms a key component of the signal recognition particle (SRP), a ubiquitous ribonucleoprotein complex responsible for cotranslational targeting of secretory proteins. 4.5S RNA also binds independently to elongation factor G (EF-G), a five-domain GTPase that catalyzes the translocation step during protein biosynthesis on the ribosome. Point mutations in EF-G suppress deleterious effects of 4.5S RNA depletion, as do mutations in the EF-G binding site within ribosomal RNA, suggesting that 4.5S RNA might play a critical role in ribosome function in addition to its role in SRP. Here we show that 4.5S RNA and EF-G form a phylogenetically conserved, low-affinity but highly specific complex involving sequence elements required for 4.5S binding to its cognate SRP protein, Ffh. Mutational analysis indicates that the same molecular structure of 4.5S RNA is recognized in each case. Surprisingly, however, the suppressor mutant forms of EF-G bind very weakly or undetectably to 4.5S RNA, implying that cells can survive 4.5S RNA depletion by decreasing the affinity between 4.5S RNA and the translational machinery. These data suggest that SRP function is the essential role of 4.5S RNA in bacteria.
Lupus Anticoagulant and Stroke-Reply (1987)

<h3>In Reply.</h3> —We thank Drs Levine and Welch for their interest, for their letter, and for sharing with us a preprint of their article<sup>1</sup>on the subject of the lupuslike anticoagulant or lupus inhibitor and its presumptive association with cerebral infarcts. Our recent publication<sup>2</sup>agrees with the concluding paragraph of their letter: the lupuslike anticoagulant appears to be associated with an increased risk for stroke, and other factors (perhaps even those as yet unknown) may contribute to this risk. Since it is theoretically impossible to ever know<i>all</i>of the potential risk factors for stroke, their last point—that it is unclear if the presence of the lupuslike anticoagulant alone, in the absence of other risk factors, can increase the probability of cerebral infarction—seems obvious. Our case report presented a young (31-year-old) man with a stroke who had a lupuslike anticoagulant in the absence of other<i>known</i>risk factors for infarction;
Opportunities and challenges in the diagnostic utility of dermal interstitial fluid (2023)

The volume of interstitial fluid (ISF) in the human body is three times that of blood. Yet, collecting diagnostically useful ISF is more challenging than collecting blood because the extraction of dermal ISF disrupts the delicate balance of pressure between ISF, blood and lymph, and because the triggered local inflammation further skews the concentrations of many analytes in the extracted fluid. In this Perspective, we overview the most meaningful differences in the make-up of ISF and blood, and discuss why ISF cannot be viewed generally as a diagnostically useful proxy for blood. We also argue that continuous sensing of small-molecule analytes in dermal ISF via rapid assays compatible with nanolitre sample volumes or via miniaturized sensors inserted into the dermis can offer clinically advantageous utility, particularly for the monitoring of therapeutic drugs and of the status of the immune system.