gebhart/patrepeval huggingface dataset:
The p65 subunit of NF-kappa B is redundant with p50 during B cell proliferative responses, and is required for germline CH transcription and class switching to IgG3. (1999)

B cells lacking individual NF-kappa B/Rel family members exhibit defects in activation programs. We generated small resting B cells lacking p65 or p50 alone, or lacking both p50 and p65, then evaluated the ability of these cells to proliferate, secrete Ig, and undergo Ig class switching. B cells lacking p65 proliferated well in response to all stimuli tested. However, these cells demonstrated an isolated defect in switching to IgG3, which was associated with a decrease in gamma 3 germline CH gene expression. Whereas, previously reported, B cells lacking p50 alone had a severe proliferative defect in response to LPS, a moderate defect in response to CD40 ligand (CD40L), and normal proliferation to Ag receptor cross-linking using dextran-conjugated anti-IgD Abs (alpha delta-dex), B cells lacking both p50 and p65 exhibited severely impaired proliferation in response to LPS, alpha delta-dex, and CD40L. This defect could be overcome by simultaneous administration of alpha delta-dex and CD40L. In response to this latter combination of stimuli, B cells lacking both p50 and p65 secreted Ig and underwent isotype switching to IgG1 as efficiently as B cells lacking p50 alone. These data demonstrate a role for the p65 subunit of NF-kappa B in germline CH gene expression as well as functional redundancy between p50 and p65 during proliferative responses.
Treatment in the absence of disease reclassification among men on active surveillance for prostate cancer (2021)

This analysis of men on active surveillance for prostate cancer shows that approximately 1 in 10 men will decide to be treated within 4 years of their diagnosis even if their cancer is stable. These choices may be related in part to quality-or-life or spousal concerns.
Abstract 8987: Prostacyclin Reduction Upregulates Tissue Factor and Predisposes COX-2 Knockout Mice to Thrombosis (2011)

Selective inhibitors of cyclooxygenase-2 (COX-2) increase the risk of myocardial infarction and athero-thrombotic events, but the mechanisms responsible for these effects are not fully understood. To assess the role of COX-2 in arterial thrombosis, a well-studied model of ferric chloride-induced carotid artery injury was applied to COX-2 knockout (COX-2KO) mice and data were compared with those obtained in wild-type (WT) mice. We found that thrombus formation was significantly greater in COX-2-null compared to WT mice. We then explored the role of platelets in this model. Platelets isolated from blood of COX-2KO mice showed enhanced aggregation responses to collagen and ADP together with greater thromboxane production than WT platelets. Interestingly, cyclooxygenase-1 and thromboxane synthase protein levels were similar in both animal groups. In cross-transfusion experiments, we found that platelets from COX-2KO mice behaved similarly to WT platelets in terms of in vivo thrombus formation. Importantly, we observed that the activity of tissue factor (TF), initiator of blood coagulation, was elevated both in concentrated microparticles derived from plasma and in leukocytes or in the carotid arteries of COX-2KO mice. Furthermore, the arterial wall of COX-2KO mice expressed higher levels of TF mRNA compared to WT animals, and these levels correlated with both reduced prostacyclin synthase mRNA levels and decreased prostacyclin production. In addition, treatment with CA10441, a prostacyclin receptor (IP) antagonist, increased TF activity in WT mice. Conversely, carbaprostacyclin, a stable IP agonist, reduced TF activity in COX-2KO mice. Overall, these findings reveal for the first time that the propensity to thrombosis observed in association with COX-2 inhibition is consequent to the impairment in the generation of prostacyclin by vascular endothelium, which in turn results in increased TF expression and activity.
Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders (2020)

Abstract BACKGROUND Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS We conducted the largest to date genome-wide genotype–by–sex (GxS) interaction of risk for these disorders, using 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH. RESULTS Across disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815; p =3.2×10 −8 ), that interacts with sodium/potassium-transporting ATPase enzymes implicating neuronal excitability. Three additional loci showed evidence ( p &lt;1×10 −6 ) for cross-disorder GxS interaction (rs7302529, p =1.6×10 −7 ; rs73033497, p =8.8×10 −7 ; rs7914279, p =6.4×10 −7 ) implicating various functions. Gene-based analyses identified GxS interaction across disorders ( p =8.97×10 −7 ) with transcriptional inhibitor SLTM . Most significant in SCZ was a MOCOS gene locus (rs11665282; p =1.5×10 −7 ), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509; p =1.1×10 −7 ) in a locus containing IDO2 , a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD ( p FDR &lt;0.05). CONCLUSIONS In the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.
Automatic Machine Learning by Pipeline Synthesis using Model-Based Reinforcement Learning and a Grammar (2019)

Automatic machine learning is an important problem in the forefront of machine learning. The strongest AutoML systems are based on neural networks, evolutionary algorithms, and Bayesian optimization. Recently AlphaD3M reached state-of-the-art results with an order of magnitude speedup using reinforcement learning with self-play. In this work we extend AlphaD3M by using a pipeline grammar and a pre-trained model which generalizes from many different datasets and similar tasks. Our results demonstrate improved performance compared with our earlier work and existing methods on AutoML benchmark datasets for classification and regression tasks. In the spirit of reproducible research we make our data, models, and code publicly available.
Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma (2004)

The expression and function in growth and apoptosis of the renin-angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT(2) and/or AT(1) mRNAs and proteins determined by RT-PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1-14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy.
Understanding and Treating Iatrogenic Nerve Injuries in Shoulder Surgery (2019)

As surgical techniques and technology continue to advance in shoulder surgery along with the increased use of regional anesthesia, it is important to remember that iatrogenic nerve injuries remain a possible complication. Iatrogenic nerve injuries associated with shoulder surgery lead to patient disability and distress, increased healthcare costs, and possibly additional procedures. To obtain the best possible outcome for the patient after the nerve injury has been discovered, a timely appreciation of the management options is necessary rather than expectant management. Early recognition, appropriate neurodiagnostic testing, and prompt treatment or referral are mandatory for optimal outcomes.
Not I subtraction and Not I-specific microarrays to detect copy number and methylation changes in whole genomes (2002)

Methylation, deletions, and amplifications of cancer genes constitute important mechanisms in carcinogenesis. For genome-wide analysis of these changes, we propose the use of NotI clone microarrays and genomic subtraction, because NotI recognition sites are closely associated with CpG islands and genes. We show here that the CODE (Cloning Of DEleted sequences) genomic subtraction procedure can be adapted to NotI flanking sequences and to CpG islands. Because the sequence complexity of this procedure is greatly reduced, only two cycles of subtraction are required. A NotI-CODE procedure can be used to prepare NotI representations (NRs) containing 0.1-0.5% of the total DNA. The NRs contain, on average, 10-fold less repetitive sequences than the whole human genome and can be used as probes for hybridization to NotI microarrays. These microarrays, when probed with NRs, can simultaneously detect copy number changes and methylation. NotI microarrays offer a powerful tool with which to study carcinogenesis.
Cast Steel Replaceable Modular Links for Eccentrically Braced Frames (2017)

This paper presents an investigation into the use of cast steel replaceable links for eccentrically braced frames (EBFs). While conventional EBFs can be designed with a large response modification factor, and are thus very economical seismic-force-resisting systems (SFRS) in high-seismic regions, they can also be prone to damage states such as fracture at stiffener welds, local buckling, and lateral torsional buckling. They are also difficult to repair after an earthquake event since the EBF links are integrated into the floor beam of the seismic force-resisting frame. It is proposed that these drawbacks of conventional EBFs could be mitigated by using replaceable cast steel yielding links, since demand critical welds are avoided and damaged links can be replaced after an earthquake. Additionally, the cast steel EBF links are uncoupled from the beam sections and thus the most economical beam and link can both be specified. This paper presents sample building designs for a variety of building locations, using a newly developed cast steel EBF link concept that can be used to achieve more economical designs while also improving the performance of EBF frames.
Role of the ICOS-B7h Costimulatory Pathway in the Pathophysiology of Chronic Allograft Rejection (2005)

These data suggest that the ICOS-B7h pathway is critical in the activation of effector/memory T cells that are necessary for the progression of chronic rejection and provide the rationale to develop novel and specific therapies to prevent this process.
Intrusive probes in riser applications (2017)

Many of the probes used to understand hydrodynamics in circulating fluidized bed risers intrude into the environment they are measuring, although assumptions are typically asserted that the intrusive probes do not affect the data collected. This could be a poor assumption in some cases and conditions. We found that intrusive fiber‐optic probe measurements consistently mis‐predicted the solids concentration compared to the nonintrusive pressure drop measurements outside the fully developed flow region of a riser containing fluid catalytic cracking catalyst or glass bead particles. The discrepancy was sensitive to superficial gas velocity, solid circulation rate, probe position, and flow direction. Barracuda VR™ computational fluid dynamics simulations confirmed this, and indicated that particle momentum was lost at the leading edge of the probe and particles were spilling over to the probe tip. Accordingly, new probe designs were proposed to mitigate the intrusiveness of a fiber‐optic probe for more accurate characterization. © 2017 American Institute of Chemical Engineers AIChE J , 63: 5361–5374, 2017
Believe it or not! (2010)

In this paper, we evaluate performance of a real-world image processing application that uses a cross-correlation algorithm to compare a given image with a reference one. We implement this algorithm on a nVidia GTX 285 GPU using CUDA, and also parallelize it for the Intel Xeon (Nehalem) and IBM Power7 processors, using both manual and automatic techniques. Pthreads and OpenMP with SSE and VSX vector intrinsics are used for the manually parallelized version, while a state-of-the-art optimization framework based on the polyhedral model is used for automatic compiler parallelization and optimization. The best performing versions on the Power7, Nehalem, and GTX 285 run in 1.02s, 1.82s, and 1.22s, respectively. The performance of this algorithm on the nVidia GPU suffers from: (1) a smaller shared memory, (2) unaligned device memory access patterns, (3) expensive atomic operations, and (4) weaker single-thread performance. These results conclusively demonstrate that, under certain conditions, it is possible for a FLOP-intensive structured application running on a multi-core processor to match or even beat the performance of an equivalent GPU version.
Superoxide Ion Encaged in Nanoporous Crystal 12CaO·7Al2O3 Studied by Continuous Wave and Pulsed Electron Paramagnetic Resonance (2004)

Continuous wave and pulsed electron paramagnetic resonance studies were performed on the superoxide ion, O2-, encaged in the nanoporous crystal 12CaO·7Al2O3 (C12A7). Hyperfine splitting due to 17O in O2- was observed in C12A7 heated in 40% 17O-enriched O2 gas at 550 °C, providing solid evidence that encaged O2- derives from gaseous O2 in the atmosphere via reactions with free oxygen ions in the cage. Angular variations of g values, 17O hyperfine splitting in the single crystal at 20 K, and 27Al electron spin−echo envelope modulation pattern for the powder at 4 K clarified that an O2- is encaged in a subnanometer-sized cage of C12A7 and adsorbed on a Ca2+ ion forming a part of the cage wall. Further, two oxygen atoms in the O2- ion are equivalent in the cage, indicating that the O2- ion takes a “side-on” configuration. Then, the O−O bond is perpendicular to the 2-fold rotation axis (C2 || 〈100〉) across the center of the cage and directed to two oxygen ions forming the cage wall. Variation in the g values with temperature indicates that the O2- may be regarded as solidlike below ∼20 K and above this temperature the rocking motion of the O−O bond about the C2 axis is activated with an increase in temperature, but the anisotropy in the motion remains even at 400 K. This result may be explained by a view that Coulombic interaction of the Ca2+ with the fully occupied π orbital in the O2- is stronger than that with the semioccupied π orbital, controlling the dynamics.
Advances in Two-Dimensional Dopant Profiling and Imaging of 4H-SiC Devices (2006)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Abstract 2654: Transferrin receptor targeting PRINT® nanoparticles: Chemotherapeutic-free nanomedicine for B-cell lymphoma (2010)

Abstract Transferrin receptor (TfR, CD71) is an essential protein involved in cellular iron uptake and regulation of cell growth. This study is to convert PRINT® nanoparticles to targeted drug delivery system by conjugating TfR ligands to particle surface, taking advantage of TfR overexpression on many types of malignant tissues. 200 nm × 200 nm cylindrical PRINT nanoparticles with poly(ethylene glycol)-based composition were fabricated and labeled with transferrin receptor antibody (mouse anti-human TfR mAb, clone OKT-9) or human transferrin (hTf) via biotin-avidin binding or direct chemical conjugation strategies. Nanoparticles coated with OKT9 or hTf, but not isotype control mouse IgG1 or bovine transferrin (bTf), showed highly specific TfR-mediated uptake by all human tumor cell lines tested in this study, including solid tumors and disseminating B cell lymphomas. Non-cancerous HEK293 cell that expresses low level of surface TfR, in contrast, took up particles at much lower rate during short exposure to TfR-targeting particles. The targeting efficiency was dependent on particle concentration, ligand density, particle dosing time and cell surface receptor level. Interestingly, the PRINT nanoparticles coated with OKT9 or hTf showed little cytotoxicity on all solid tumor cell lines tested but were toxic to Ramos B-cell lymphoma. More than 70% of the Ramos cells were killed by OKT9 or hTf coated nanoparticles at a concentration of 100 µg/mL. In contrast, free OKT9 or hTf did not induce death of Ramos cells. There was a strong correlation between TfR ligand density on particle surface and cell viability. Elevated caspase 3 activity indicates the activation of apoptosis pathways upon particle treatment. Iron supplementation suppressed toxicity of NP-OKT9 but not NP-hTf, suggesting different mechanisms by which hTf and OKT9 exerts cytotoxicity on Ramos cells. Further study of cell death mechanism through DNA microarray analysis is under way. Overall, we have shown that human transferrin and transferrin receptor antibodies can be useful targeting ligands for nanoparticle delivery to tumors. More importantly, non-toxic transferrin and TfR antibodies can be turned into a potential chemotherapeutic-free medicine for B-cell lymphoma through multiplexing with PRINT nanoparticles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2654.
High resolution vacuum ultraviolet Stark measurement of the dipole moment of A 1A″ HCN (1992)

We report here the first measurement of the electric dipole moment of the Ã 1A″ state of HCN. Fluorescence excitation spectra of the Ã←X̃ 210K10 band were recorded using narrow band (&amp;lt;0.1 cm−1) vacuum ultraviolet (VUV) produced by four-wave sum mixing in an improved strontium heat pipe. Accurate (±0.007 cm−1) term values for this band are reported. Surprisingly, we found that the asymmetry doubling of the upper state does not extrapolate to zero at J=0. We suggest that the most plausible explanation for this anomalous asymmetry doubling is a spin–orbit perturbation by a nearly degenerate level of the 1 3A′ state. The a component of the dipole moment has been determined by the Stark splitting of the Q(1) transition as a function of electric field in a novel Stark cell capable of sustaining high electric fields (41 kV/cm) at pressures of 50 mTorr. The observed value of the dipole moment μa=0.99(10) D is in agreement with simple molecular orbital expectations and a semiempirical study.
Figure S1 from A KDM5 Inhibitor Increases Global H3K4 Trimethylation Occupancy and Enhances the Biological Efficacy of 5-Aza-2′-Deoxycytidine (2023)

&lt;p&gt;KDM5i increases H3K4 trimethylation alone and in combination with DAC.&lt;/p&gt;
A Minoxidil-Related Compound Lacking a C6 Substitution Still Exhibits Strong Anti-Lysyl Hydroxylase Activity in vitro (1996)

It has been previously reported that minoxidil inhibits the activity of lysyl hydroxylase (LH), an enzyme which catalyzes the formation of hydroxylysine, which is necessary for proper maturation of collagen at the transcriptional and enzymatic levels. Using the reverse transcriptase-polymerase chain reaction, we confirmed that this inhibition occurred at least at the transcriptional level. Furthermore, we took advantage of this sensitive and rapid method to perform a quantitative structure activity relation study using several compounds structurally related to minoxidil. We found that when the C6 of the pyrimidinyl moiety was substituted, it had to be by a tertiary nitrogen, i.e. an N-piperidin ring for the inhibition of LH mRNA synthesis to be observed. Surprisingly, however, we found that 2,4-diamino-pyrimidin-3-oxide, a new compound lacking an organic moiety para to the nitroxide oxygen, also retained a high inhibitory effect on LH mRNA expression, comparable to that of minoxidil. We thus conclude that the presence of a substituent para to the nitroxide oxygen is dispensable for inhibition of LH mRNA to be observed in vitro. This brings new insights into the design of therapeutic agents useful in any condition where an overproduction of mature collagen is unwanted, i.e. accelerated wound healing, keloids and localized scleroderma.
Formulation Strategy for the Delivery of Cyclosporine A: Comparison of Two Polymeric Nanospheres (2015)

A wide range of nanoparticles has been explored for the delivery of highly hydrophobic drugs, but very few publications provide comparative data of the performance of different nanoparticles. To address this need, this publication compares poly(lactic-co-glycolic acid) (PLGA) nanoparticles and nanospheres made from tyrosine-derived tri-block copolymers (termed TyroSpheres) for their respective performance as carriers for cyclosporine A (CSA). Using previously reported data on PLGA, we followed similar experimental protocols to evaluate the in vitro characteristics of TyroSpheres. Although there are some similarities between the two particle systems for the delivery of CSA, such as effective encapsulation and epidermal skin penetration, several differences were notable. First, the methods of preparation were different, i.e., self-assembly and emulsion-diffusion-evaporation process for TyroSpheres and PLGA, respectively. Second, TyroSpheres provided 7-day diffusion-controlled release, whereas PLGA nanoparticles provided >21-day erosion-controlled release. Third, the size of TyroSpheres was measured to be ~60-70 nm irrespective of drug loading, whereas the size of PLGA nanoparticles (~100-250 nm) was dependent on drug loading and the method of preparation. Overall, this publication provides a direct comparison between two different types of nanoparticles and illuminates the respective advantages and disadvantages, using CSA as a model for the release of highly hydrophobic drugs.