gebhart/patrepeval huggingface dataset:
Inhibition of the Human Double Minute (HDM)-2 E3 Ubiquitin Ligase Activates Different Programmed Cell Death (PCD) Pathways in Models of Non-Hodgkin Lymphoma (NHL) with Wild Type (wt) and Mutant (mut) p53 (2008)

Abstract Background: The ubiquitin-proteasome pathway has been validated as a target for NHL with the recent approval of bortezomib for mantle cell lymphoma (MCL). In addition to anti-tumor activity, however, proteasome inhibitors have pleiotropic effects, including activation of anti-apoptotic heat shock proteins, and their use clinically is complicated by toxicities such as peripheral neuropathy. By targeting E3 ubiquitin ligases, which are involved in ubiquitination of only a small subset of cellular proteins, it may be possible to achieve more specific anti-tumor effects with a better therapeutic index. One attractive target is HDM-2, which is responsible for ubiquitination of the p53 tumor suppressor. Methods: To evaluate the therapeutic potential of agents targeting HDM-2, we studied the impact of the small molecule JNJ-26854165, an inhibitor of HDM-2-function, in both p53 wt and mut cell line models. Results: Treatment of wt p53 NHL cell lines with JNJ-26854165 induced a dose- and time-dependent inhibition of proliferation, with an IC50 in the 0.02–0.3 μM range. Cell death, which was typically seen within 48 hours of HDM-2 inhibition, occurred through induction of type I PCD, as judged by the appearance of increased staining with Annexin V and activation of caspase 3. While cell lines with mut p53 were generally less sensitive than their wt p53 counterparts, JNJ-26854165 remained potent, with an IC50 in the 0.05–0.6 μM range. The latter cell lines showed a longer kinetics of death, with PCD being seen within 72 hours of drug exposure. Notably, in these mut p53 cell lines, very little Annexin V staining or caspase 3 activation was seen, consistent with a minor role for type I PCD. Instead, mut p53 cell lines demonstrated an increased content of acidic vacuoles by acridine orange staining, increased expression of Beclin 1 and Sequestosome 1/p62, and conversion of microtubule-associated protein 1 light chain 3 form I to form II, consistent with activation of type II PCD, or autophagy. Also, electron microscopy showed an increased presence of autophagosomes and autolysosomes, further supporting the activation of this pathway. Combinations of JNJ-26854165 with other agents, including rapamycin, doxorubicin, and an inhibitor of Bcl 2, showed enhanced anti-proliferative effects in a sequence-dependent fashion, which were greatest when the chemotherapeutic preceded the HDM-2 inhibitor. Combination index analysis revealed that these interactions met criteria for synergy. Conclusions: Inhibition of the function of HDM-2 using JNJ-26854165 is a promising approach that is effective against both wt and mut p53 models by activating type I and type II PCD, respectively. The effectiveness of JNJ-26854165 was enhanced in combination with currently used chemotherapeutics in a sequence specific manner, providing a rationale for translation of this novel approach into the clinic.
Identification of L-Tryptophan Derivatives with Potent and Selective Antagonist Activity at the NK1 Receptor (1994)

As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines. Optimization of substitution on the benzyl ester led to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 26 as a potent and selective substance P receptor antagonist. Compound 26 blocked substance P induced dermal extravasation in vivo and was the most potent compound from this structurally novel class of antagonists which further adds to the diversity of small molecules that bind to the (NK1) receptor.
Properties of Cysteine‐Added Soy Protein‐Wheat Gluten Films (1999)

ABSTRACT Soy and wheat proteins as film ingredients are advantageous due to relative abundance, biodegradability, and their renewable nature. Research objectives were to evaluate effectiveness of gluten and cysteine addition in improving properties of soy protein‐based films. Thickness, mechanical, and barrier properties were evaluated. Gluten addition and pH 3.0 lowered water vapor permeability and thickness. Mechanical properties were enhanced at pH 7.0 with cysteine addition. Cysteine increased tensile strength of some treatments due to increase in disulfide bond formation. Best compromise between barrier and mechanical properties was observed for the cysteine‐added soy:gluten (4:1) film at pH 7.0. These films could find application as primary packaging for low moisture foods.
A Reconfigurable Wing for Biomimetic Aircraft (2013)

A biomimetic composite reconfigurable wing for small unmanned air systems has been designed and tested experimentally in a wind tunnel. Actuation of the wing results in a 30% reduction of wing planform area and 34% decrease in span mimicking wing sweeping motion used by birds for flight control. The wing uses a thin cambered airfoil along the span. Wing sweep motion of 56° was demonstrated under static aerodynamic loads at angles of attack between -5 and +15° at 10 m/s. The wing was fabricated using a variety of materials including carbon fiber and fiberglass composite morphing skins and direct manufactured plastic frame structures. The large shear displacement required by the skin to achieve large wing sweep angles was managed by folding large sections of the skin, similar to folding of bird feathers.
Al-2.29 Deprotection (2021)

As increasingly smaller molecular materials and material structures are devised or developed for technological applications, the demands on the processes of lithography now routinely include feature sizes that are of the order of 10 nm. In reaching such a fine level of resolution, the methods of lithography have increased markedly in sophistication and brought into play 2terminology that is unfamiliar, on the one hand, to scientists tasked with the development of new lithographic materials or, on the other, to the engineers who design and operate the complex equipment that is required in modern-day processing. Publications produced by scientists need to be understood by engineers and vice versa, and these commonly arise from collaborative research that draws heavily on the terminology of two or more of the traditional disciplines. It is developments in polymer science and material science that lead progress in areas that cross traditional boundaries, such as microlithography. This document provides the exact definitions of a selection of unfamiliar terms that researchers and practitioners from different disciplines might encounter.
c-Myc alters the DNA damage-induced G2/M arrest in human mammary epithelial cells (2003)

Effects of c-Myc overexpression on the DNA damage-induced G2/M checkpoint were studied in finite lifespan, normal human mammary epithelial cells (HMECs). Previously, we showed that c-Myc attenuates G1/S arrest and leads to an inappropriate entry of cells with damaged DNA into the S phase, following treatment with ionising radiation (IR). Here we show that, in striking contrast to control cells, c-Myc-overexpressing HMECs demonstrate a significant attenuation of the G2/M arrest, following IR, and enter into inappropriate mitoses. At the molecular level, ectopic overexpression of c-Myc leads to an unusually high level of expression of cyclin B1, and the elevated levels of cyclin B1 were maintained, after gamma-irradiation. Introduction of DNA damage in c-Myc-overexpressing, normal mammary epithelial cells eventually induces apoptosis, indicating a dramatic sensitisation by c-Myc of DNA damage-induced apoptosis. These two remarkable phenotypes, checkpoint attenuation and sensitisation to apoptosis, resulting from a deregulation of the protooncogene c-myc, may produce a unique pattern of alternating cycles, consisting first of amplification of DNA damage, followed by apoptosis-assisted selective pressure. The result of this alternating pattern of damage apoptosis could facilitate the selection of certain genomic alterations required for cellular survival and cellular transformation.
Aminocatalysis-Mediated on-Resin Ugi Reactions: Application in the Solid-Phase Synthesis of N-Substituted and Tetrazolo Lipopeptides and Peptidosteroids (2015)

A new solid-phase protocol for the synthesis of N-substituted and tetrazolo peptides is described. The strategy relies on the combination of aminocatalysis-mediated on-resin Ugi reactions and peptide couplings for the N-alkylation of peptides at selected sites, including the N-terminal double lipidation, the simultaneous lipidation/biotinylation, and the steroid/lipid conjugation via tetrazole ring formation. The solid-phase Ugi four-component reactions were enabled by on-resin transimination steps prior to addition of the acid and isocyanide components. The strategy proved to be suitable for the feasible incorporation of complex N-substituents at both termini and at internal positions, which is not easily achievable by other solid-phase methods.
Data from Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors (2023)

&lt;div&gt;Abstract&lt;p&gt;Aberrant RAS/MAPK signaling is a common driver of oncogenesis that can be therapeutically targeted with clinically approved MEK inhibitors. Disease progression on single-agent MEK inhibitors is common, however, and combination therapies are typically required to achieve significant clinical benefit in advanced cancers. Here we focused on identifying MEK inhibitor-based combination therapies in neuroblastoma with mutations that activate the RAS/MAPK signaling pathway, which are rare at diagnosis but frequent in relapsed neuroblastoma. A genome-scale CRISPR-Cas9 functional genomic screen was deployed to identify genes that when knocked out sensitize RAS-mutant neuroblastoma to MEK inhibition. Loss of either CCNC or CDK8, two members of the mediator kinase module, sensitized neuroblastoma to MEK inhibition. Furthermore, small-molecule kinase inhibitors of CDK8 improved response to MEK inhibitors &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; in RAS-mutant neuroblastoma and other adult solid tumors. Transcriptional profiling revealed that loss of CDK8 or CCNC antagonized the transcriptional signature induced by MEK inhibition. When combined, loss of CDK8 or CCNC prevented the compensatory upregulation of progrowth gene expression induced by MEK inhibition. These findings propose a new therapeutic combination for RAS-mutant neuroblastoma and may have clinical relevance for other RAS-driven malignancies.&lt;/p&gt;Significance:&lt;p&gt;Transcriptional adaptation to MEK inhibition is mediated by CDK8 and can be blocked by the addition of CDK8 inhibitors to improve response to MEK inhibitors in RAS-mutant neuroblastoma, a clinically challenging disease.&lt;/p&gt;&lt;/div&gt;
The Modern Treatment of WilsonÃ¢ÂÂs Disease (2014)

Wilson’s disease is an inherited defect in biliary copper excretion, causing a buildup of copper and copper toxicity, primarily in liver and brain. Presentation with liver disease and/or neurological disease usually occurs in the second and third decades of life. Recognition of the disease is often delayed, which is unfortunate, because once appropriate treatment is started, progression of the disease can be halted, and further damage avoided. Regarding current treatment, many physicians are only aware of penicillamine, because it was the first orally effective drug developed. However, penicillamine has outlived its usefulness, being more toxic than more recently developed drugs. For the hepatic presentation, a combination of trientine and zinc should be used for 4-6 months, then trientine stopped and zinc used for lifelong maintenance therapy. For the neurological presentation, tetrathiomolybdate should be used if available for 8-16 weeks, then zinc for maintenance. If tetrathiomolybdate is not available, zinc should be used. For presymptomatic patients, zinc should be used from the beginning. Zinc should also be used for pregnant and pediatric patients, with a reduced dose for the latter. Zinc causes gastric intolerance in some patients, so in all cases where zinc is the favored therapy, if it is not tolerated, then trientine should be used as second choice. In too many cases, patients are put on zinc, compliance not monitored, and then papers are written about “zinc failures”. There are no zinc failures, just noncompliance problems.
Giant magnetic domains in amorphous SmCo thin films (2014)

The potential for tuning of magnetic properties and the exceptional uniformity are among the features that make amorphous magnetic materials attractive for technology. Here it is shown that the magnetization reversal in amorphous SmCo thin films takes place through the formation of giant magnetic domains, over a centimeter across. The domain structure is found to be dictated by the direction of the imprinted in-plane easy axis and the film boundaries. This is a consequence of the size of the anisotropy and the structural uniformity of the films, which also allows the movement of millimeter-long domain walls over distances of several millimeters. The results demonstrate the possibility of tailoring the magnetic domain structure in amorphous magnets over a wide range of length scales, up to centimeters. Moreover, they highlight an important consequence of the structural perfection of amorphous films.
Metrics for Local Community Planning and Evaluation: The Case for Observational Measurement of High Risk Rural Sub-Populations in Occupant Safety (2013)

The observational survey results from this study support research showing that rural teens have lower safety belt usage rates than adults or urban teens. Despite efforts to target rural areas, programs must specifically target sub populations, especially rural male teens, in order to hold any traction. Because of the wide gap between measured safety belt use in rural Georgia (79.9%) and the studied rural high schools (38.6%), local program planners must assess actual safety belt usage in their high risk rural teen population in order to use accurate metrics for intervention and education efforts.
Strategic enhancement of anomalous Nernst effect in Co2MnAl1-xSix Heusler compounds (2018)

The anomalous Nernst effect (ANE), a thermoelectric phenomenon in magnetic materials, has potential for novel energy harvesting applications because its orthogonal relationship between the temperature gradient and the electric field enables us to utilize the large area of non-flat heat sources. In this study, the required thermopower of ANE for practical energy harvesting applications is evaluated in simulations of electric power obtainable from ANE using a low-temperature heat source. A strategy for finding magnetic materials having large ANEs is proposed, which suggests that a large ANE originates from the constructive relationship between large Seebeck, anomalous Hall, and transverse Peltier effects. This strategy leads us to investigate the electric and thermoelectric properties in Co2MnAl1-xSix. As a result, it is found that Co2MnAl0.63Si0.37 has the largest ANE thermopower ever reported, 6.2 uV/K. A first principles calculation of the anomalous Hall conductivity and transverse Peltier coefficient in B2 and L21-ordered Co2MnAl0.63Si0.37 shows close agreement with the experimental results, indicating that the observed large ANE arises from the intrinsic Berry phase curvature of Co2MnAl1-xSix. This study can be a guide for developing materials for new thermoelectric applications using ANE.
Privacy: personal information, threats, and technologies (2005)

The three primary thrusts of this paper are: first, that people do not think enough about their own privacy, in particular, they may not know enough about their privacy that they can really make informed decisions about sharing information; second, that technologies exist that can mitigate some of the problems associated with information sharing; and third, that services (in addition to to technologies) might be a reasonable way to think about addressing the privacy problem.
Laparoscopic Ureterocalicostomy: A Feasibility Study (2003)

Laparoscopic ureterocalicostomy is technically feasible in the porcine model and it effectively duplicates the established principles of open surgery. Our technique further extends the application of laparoscopic surgery for difficult ureteropelvic junction obstruction.
Some Novel Liquid Partitioning Systems:  Water−Ionic Liquids and Aqueous Biphasic Systems (2003)

Partition coefficients, as values of log P, between water and two room-temperature ionic liquids and between water and an aqueous biphasic system have been correlated with Abraham's solute descriptors to yield linear free energy relationships that can be used to predict further values of log P, to ascertain the solute properties that lead to increased or decreased log P values, and to characterize the partition systems. It is shown that, in all three of the systems, an increase in solute hydrogen-bond basicity leads to a decrease in log P and an increase in solute volume leads to an increase in log P. For the two ionic liquid systems, an increase in solute hydrogen-bond acidity similarly decreases log P, but for the aqueous biphasic system, solute hydrogen-bond acidity has no effect on log P. These effects are rather smaller than those observed in traditional water−solvent systems. However, the ionic liquids appear to have an increased affinity for polyaromatic hydrocarbons as compared to traditional organic solvents. Principal component analysis and nonlinear mapping show that the three unconventional partition systems are considerably different from conventional water−organic solvent systems.
Preferred Orientations of NiO Films Prepared by Plasma-Enhanced Metalorganic Chemical Vapor Deposition (1996)

Thin films of nickel oxide (NiO) with NaCl-type structure were prepared on glass substrates at 400°C by plasma-enhanced metalorganic chemical vapor deposition using nickel acetylacetonate as a source material. The relationship between O 2 flow rate, and preferred orientation and microstructure of the NiO films was investigated. Highly crystalline NiO film with (111) orientation was obtained at O 2 flow rates as low as 3 cm 3 /min. As the O 2 flow rate increased from 3 to 70 cm 3 /min, the orientation of NiO films changed from (111) to (100) and deposition rate decreased from 17 to 11 nm/min. Films with both (111) and (100) orientation had columnar structure. The origin of the preferred orientation of the NiO films was discussed.
Synthetic Triterpenoid Cyano Enone of Methyl Boswellate Activates Intrinsic, Extrinsic, and Endoplasmic Reticulum Stress Cell Death Pathways in Tumor Cell Lines (2011)

We explored the effect of a novel synthetic triterpenoid compound cyano enone of methyl boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD(50)) values in 10 of 10 tumor cell lines tested. CEMB-induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using short interfering RNAs (siRNA), we show evidence that knockdown of caspase 8, DR4, Apaf-1, and Bid impairs CEMB-induced cell death. Similar to other proapoptotic synthetic triterpenoid compounds, CEMB-induced apoptosis involved endoplasmic reticulum stress, as shown by partial rescue of tumor cells by siRNA-mediated knockdown of expression of genes involved in the unfolded protein response such as IRE1α, PERK, and ATF6. Altogether, our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy.
Multifunctional Cellulosic Scaffolds from Modified Cellulose Nanocrystals (2017)

A biobased cellulosic scaffold material was made through freeze-drying ice-templating of functionalized cellulosic nanomaterials. The resulting interconnected highly porous scaffold was primarily composed of highly esterified, strong network of ultrathin cellulosic layers. The prepared cellulosic scaffold material displayed multifunctional properties of hydrophobicity, oleophilicity and lipophilicity, which could selectively absorb milkfat, hydrophobic proteins, various organic solvents and oils. Diverse potential for the structural and medical applications, such as tissue engineering, drug delivery, and oil and fat accumulation are proposed.
LADIC-CAV: a flexible, programmable, high-speed laser driver IC for optical recording (2002)

A high-speed integrated laser driver and controller circuit in standard CMOS technology works flexibly with optical recording formats such as CD-R/RW, DVD+RW, DVD write-once and DVR. It supports both constant angular velocity (CAV) and constant linear velocity (CLV) writing modes, and features a new laser power control method.
Measuring temporal stability of positron emission tomography standardized uptake value bias using long-lived sources in a multicenter network (2018)

Positron emission tomography (PET) is a quantitative imaging modality, but the computation of standardized uptake values (SUVs) requires several instruments to be correctly calibrated. Variability in the calibration process may lead to unreliable quantitation. Sealed source kits containing traceable amounts of [Formula: see text] were used to measure signal stability for 19 PET scanners at nine hospitals in the National Cancer Institute's Quantitative Imaging Network. Repeated measurements of the sources were performed on PET scanners and in dose calibrators. The measured scanner and dose calibrator signal biases were used to compute the bias in SUVs at multiple time points for each site over a 14-month period. Estimation of absolute SUV accuracy was confounded by bias from the solid phantoms' physical properties. On average, the intrascanner coefficient of variation for SUV measurements was 3.5%. Over the entire length of the study, single-scanner SUV values varied over a range of 11%. Dose calibrator bias was not correlated with scanner bias. Calibration factors from the image metadata were nearly as variable as scanner signal, and were correlated with signal for many scanners. SUVs often showed low intrascanner variability between successive measurements but were also prone to shifts in apparent bias, possibly in part due to scanner recalibrations that are part of regular scanner quality control. Biases of key factors in the computation of SUVs were not correlated and their temporal variations did not cancel out of the computation. Long-lived sources and image metadata may provide a check on the recalibration process.