gebhart/patrepeval huggingface dataset:
Transcriptional Repression of AIB1 by FoxG1 Leads to Apoptosis in Breast Cancer Cells (2013)

The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator that is overexpressed in various types of human cancers. However, the molecular mechanisms controlling AIB1 expression in the majority of cancers remain unclear. In this study, we identified a novel interacting protein of AIB1, forkhead-box protein G1 (FoxG1), which is an evolutionarily conserved forkhead-box transcriptional corepressor. We show that FoxG1 expression is low in breast cancer cell lines and that low levels of FoxG1 are correlated with a worse prognosis in breast cancer. We also demonstrate that transient overexpression of FoxG1 can suppress endogenous levels of AIB1 mRNA and protein in MCF-7 breast cancer cells. Exogenously expressed FoxG1 in MCF-7 cells also leads to apoptosis that can be rescued in part by AIB1 overexpression. Using chromatin immunoprecipitation, we determined that FoxG1 is recruited to a region of the AIB1 gene promoter previously characterized to be responsible for AIB1-induced, positive autoregulation of transcription through the recruitment of an activating, multiprotein complex, involving AIB1, E2F transcription factor 1, and specificity protein 1. Increased FoxG1 expression significantly reduces the recruitment of AIB1, E2F transcription factor 1 and E1A-binding protein p300 to this region of the endogenous AIB1 gene promoter. Our data imply that FoxG1 can function as a pro-apoptotic factor in part through suppression of AIB1 coactivator transcription complex formation, thereby reducing the expression of the AIB1 oncogene.
Post-functionalized iridium–Zr-MOF as a promising recyclable catalyst for the hydrogenation of aromatics (2014)

The multifunctional heterogeneous catalyst iridium–Zr-based MOF effectively catalyzes the hydrogenation of aromatic compounds in high yields under mild conditions.
Modeling and implementation of tandem polymer solar cells using wide‐bandgap front cells (2019)

Abstract Tandem device architectures offer a route to greatly increase the maximum possible power conversion efficiencies (PCEs) of polymer solar cells, however, the complexity of tandem cell device fabrication (such as selecting bandgaps of the front and back cells, current matching, thickness, and recombination layer optimization) often result in lower PCEs than are observed in single‐junction devices. In this study, we analyze the influence of front cell and back cell bandgaps and use transfer matrix modeling to rationally design and optimize effective tandem solar cell structures before actual device fabrication. Our approach allows us to estimate tandem device parameters based on known absorption coefficients and open‐circuit voltages of different active layer materials and design devices without wasting valuable time and materials. Using this approach, we have investigated a series of wide bandgap, high voltage photovoltaic polymers as front cells in tandem devices with PTB7‐Th as a back cell. In this way, we have been able to demonstrate tandem devices with PCE of up to 12.8% with minimal consumption of valuable photoactive materials in tandem device optimization. This value represents one of the highest PCE values to date for fullerene‐based tandem solar cells.
Enhancer of zeste homolog 2 blockade by RNA interference is implicated with inhibited proliferation, invasion and promoted apoptosis in endometrial carcinoma (2018)

Endometrial carcinoma is the most common gynecological malignancy of the female genital tract worldwide (2012). Enhancer of zeste homolog 2 (EZH2), a critical component of the polycomb repressive complex 2, has been found to be associated with multiple biological processes and is overexpressed in multiple types of cancer. Previous studies have demonstrated that EZH2 is associated with endometrial carcinoma. The present study investigated the expression and biology function of EZH2 in endometrial cancer (EC). It was found that EZH2 levels were markedly increased in endometrial cancer tissues compared with that in adjacent normal tissues. EZH2 was significantly overexpressed in 3 separate endometrial cancer cell lines (Ishikawa, RL95-2 and HEC1-A) when compared with the normal endometrial cell line ESC. Additionally, small interfering RNA was used to investigate the role of EZH2 in endometrial carcinoma cell proliferation, and the results showed that EZH2 knockdown suppressed the proliferation of endometrial carcinoma cells <i>in vitro</i>. Furthermore, EZH2 knockdown induced apoptosis of human EC cells by promoting the expression of pro-apoptosis protein caspase 3, caspase 9, BCL2 associated X and decreasing the expression of anti-apoptosis protein Bcl-2. Finally, the present study demonstrated that EZH2 knockdown suppressed the invasion of EC cells through downregulation of the epithelial-mesenchymal transition. Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma.
Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models (2021)

3D models of cancer have the potential to improve basic, translational, and clinical studies. Patient-derived xenografts, spheroids, and organoids are broad categories of 3D models of cancer, and to date, these 3D models of cancer have been established for a variety of cancer types. In lung cancer, for example, 3D models offer a promising new avenue to gain novel insights into lung tumor biology and improve outcomes for patients afflicted with the number one cancer killer worldwide. However, the adoption and utility of these 3D models of cancer vary, and demonstrating the fidelity of these models is a critical first step before seeking meaningful applications. Here, we review use cases of current 3D lung cancer models and bioinformatic approaches to assessing model fidelity. Bioinformatics approaches play a key role in both validating 3D lung cancer models and high dimensional functional analyses to support downstream applications.
Synthesis and biological activity of GnRH antagonists modified at position 3 with 3‐(2‐methoxy‐5‐pyridyl)‐alanine* (2005)

Degarelix is a potent very long-acting GnRH antagonist after subcutaneous administration. In this paper, we describe the synthesis of two analogs of degarelix incorporating racemic 3-(2-methoxy-5-pyridyl)-alanine (2-OMe-5Pal, 5) at position 3. The two diastereomers were separated by reverse-phase high-performance liquid chromatography (RP-HPLC) and the absolute stereochemistry at position 3 in the peptides was determined by enzymatic digestion with proteinase K. These analogs were tested in vitro for their ability to antagonize the GnRH receptor and in vivo for duration of action in a castrated male rat assay. Analog 7 with D2-OMe-5Pal was potent in vitro (IC50 = 5.22 nM); however, analog 8 with L2-OMe-5Pal at position 3 in degarelix lost potency as an antagonist of the human GnRH receptor (IC50 = 36.95 nM). Both the analogs were found to be short-acting in vivo.
Fabrication of porous calcium phosphate cements using gelatin as porogen (2010)

Porous calcium phosphate cements (CPCs) were fabricated using gelatin granules as the porogen. As the amount of gelatin was increased from 0 to 43 vol%, the porosity notably increased from 3 to 47 vol%, while the compressive strength decreased from 23 to 14 MPa; however, these values are still expected to be reasonably high for applications in bone tissue engineering. In addition, osteoblastic cells grew favorably on the surfaces of the CPCs prepared using gelatin of 11 and 43 vol%, which contained well interconnected pores with a size of several hundreds of microns, indicating excellent biocompatibility of the porous CPC samples produced in this study.
ChemInform Abstract: Asymmetric Synthesis of α‐Alkylated N‐Sulfinyl Imidates as New Chiral Building Blocks. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Genomic characterization of viral integration sites in HPV‐related cancers (2016)

Persistent infection with carcinogenic human papillomaviruses (HPV) causes the majority of anogenital cancers and a subset of head and neck cancers. The HPV genome is frequently found integrated into the host genome of invasive cancers. The mechanisms of how it may promote disease progression are not well understood. Thoroughly characterizing integration events can provide insights into HPV carcinogenesis. Individual studies have reported limited number of integration sites in cell lines and human samples. We performed a systematic review of published integration sites in HPV-related cancers and conducted a pooled analysis to formally test for integration hotspots and genomic features enriched in integration events using data from the Encyclopedia of DNA Elements (ENCODE). Over 1,500 integration sites were reported in the literature, of which 90.8% (N = 1,407) were in human tissues. We found 10 cytobands enriched for integration events, three previously reported ones (3q28, 8q24.21 and 13q22.1) and seven additional ones (2q22.3, 3p14.2, 8q24.22, 14q24.1, 17p11.1, 17q23.1 and 17q23.2). Cervical infections with HPV18 were more likely to have breakpoints in 8q24.21 (p = 7.68 × 10(-4) ) than those with HPV16. Overall, integration sites were more likely to be in gene regions than expected by chance (p = 6.93 × 10(-9) ). They were also significantly closer to CpG regions, fragile sites, transcriptionally active regions and enhancers. Few integration events occurred within 50 Kb of known cervical cancer driver genes. This suggests that HPV integrates in accessible regions of the genome, preferentially genes and enhancers, which may affect the expression of target genes.
A semantics-based approach to malware detection (2008)

Malware detection is a crucial aspect of software security. Current malware detectors work by checking for signatures , which attempt to capture the syntactic characteristics of the machine-level byte sequence of the malware. This reliance on a syntactic approach makes current detectors vulnerable to code obfuscations, increasingly used by malware writers, that alter the syntactic properties of the malware byte sequence without significantly affecting their execution behavior. This paper takes the position that the key to malware identification lies in their semantics. It proposes a semantics-based framework for reasoning about malware detectors and proving properties such as soundness and completeness of these detectors. Our approach uses a trace semantics to characterize the behavior of malware as well as that of the program being checked for infection, and uses abstract interpretation to “hide” irrelevant aspects of these behaviors. As a concrete application of our approach, we show that (1) standard signature matching detection schemes are generally sound but not complete, (2) the semantics-aware malware detector proposed by Christodorescu et al. is complete with respect to a number of common obfuscations used by malware writers and (3) the malware detection scheme proposed by Kinder et al. and based on standard model-checking techniques is sound in general and complete on some, but not all, obfuscations handled by the semantics-aware malware detector.
Risk of QTc prolongation among cancer patients treated with tyrosine kinase inhibitors (2020)

QTc interval prolongation can lead to life-threatening complications such as Torsade de Pointes (TdP), ventricular tachycardia (VT) and sudden cardiac death (SCD). It can occur with tyrosine kinase inhibitors (TKIs) but comparative real-world analyses on the incidence and complication rates are scarce. We retrospectively reviewed all cancer patients treated with TKI therapy at Mayo Clinic between January 2005 and December 2018 and had at least two ECGs (before and after TKI). For each TKI type, we determined the administration rate and incidence of QTc prolongation. QTc prolongation was defined as a corrected QT interval (by Fridericia formula) ≥450 ms in men and ≥470 ms in women. A total of 618 cancer patients were included with 902 TKI administrations, of which 654 (72.5%) were accounted for by pazopanib, sunitinib, imatinib, nilotinib and dasatinib. QTc prolongation (any grade) was reported in 28.8%, most commonly with nilotinib (38.7%) and dasatinib (41.7%). A QTc interval ≥500 ms and a QTc increase ≥60 ms was documented in 46 and 63 administrations, respectively. Life-threatening toxicity was seen in 14 cases (5.4% of QTc prolongation cases) including VT in 9, SCD in 3 and TdP in two administrations. The response to QTc prolongation was: discontinuation in 68%, dose reduction in 13.5%, temporary hold in 8.1% and no action in 10.4%. In conclusion, QTc prolongation with TKI therapy is very common (∼1/3 of cases) and in 5% (1.7% overall) associated with life-threatening complications. These data support recommendations for careful ECG monitoring in cancer patients undergoing TKI therapy.
Few-Shot Adversarial Domain Adaptation (2017)

This work provides a framework for addressing the problem of supervised domain adaptation with deep models. The main idea is to exploit adversarial learning to learn an embedded subspace that simultaneously maximizes the confusion between two domains while semantically aligning their embedding. The supervised setting becomes attractive especially when there are only a few target data samples that need to be labeled. In this few-shot learning scenario, alignment and separation of semantic probability distributions is difficult because of the lack of data. We found that by carefully designing a training scheme whereby the typical binary adversarial discriminator is augmented to distinguish between four different classes, it is possible to effectively address the supervised adaptation problem. In addition, the approach has a high speed of adaptation, i.e. it requires an extremely low number of labeled target training samples, even one per category can be effective. We then extensively compare this approach to the state of the art in domain adaptation in two experiments: one using datasets for handwritten digit recognition, and one using datasets for visual object recognition.
Solution-processed electrophosphorescent devices with a thin fluoropolymer at the hole transport interfacial layer (2011)

Electrophosphorescent devices with ionomer-type hole transport layers were investigated. On top of the 3,4-ethylenedioxy thiophene:poly(4-styrene sulfonate) [PEDOT:PSS] structures, fluoropolymer interfacial layers (FPIs) with different side chain lengths were introduced. Both for the PEDOT:PSS/FPI (layered) and PEDOT:PSS (mixed) structures with soluble phosphorescent emitters, the short-side-chain FPIs showed higher efficiency. The difference in the electrical properties of the two FPIs for bipolar (light-emitting) devices was not clear, but the hole-only device clearly showed the favored hole injection at the PEDOT:PSS/FPI structure with a shorter side chain, a copolymer of tetrafluoroethylene and sulfonyl fluoride vinyl ether.
Anisotropy measurements of FePt thin films (2011)

We report on anisotropy measurements of FePt thin films prepared at different temperatures and find that the anisotropy increases with increasing chemical ordering. Within measurement accuracy, we conclude that the second-order anisotropy constant K2 is negligibly small compared to the first-order anisotropy constant K1. We assert that the presence of a small hard-axis hysteresis causes spatial fluctuations of the field direction within the sample, which changes the shape of the hard-axis loop, such that it is misinterpreted as a K2 in the Sucksmith–Thompson formalism.
Distributed Channel Assignment in Cognitive Radio Networks: Stable Matching and Walrasian Equilibrium (2015)

We consider a set of secondary transmitter-receiver pairs in a cognitive radio setting. Based on channel sensing and access performances, we consider the problem of assigning channels orthogonally to secondary users through distributed coordination and cooperation algorithms. Two economic models are applied for this purpose: matching markets and competitive markets. In the matching market model, secondary users and channels build two agent sets. We implement a stable matching algorithm in which each secondary user, based on his achievable rate, proposes to the coordinator to be matched with desirable channels. The coordinator accepts or rejects the proposals based on the channel preferences which depend on interference from the secondary user. The coordination algorithm is of low complexity and can adapt to network dynamics. In the competitive market model, channels are associated with prices and secondary users are endowed with monetary budget. Each secondary user, based on his utility function and current channel prices, demands a set of channels. A Walrasian equilibrium maximizes the sum utility and equates the channel demand to their supply. We prove the existence of Walrasian equilibrium and propose a cooperative mechanism to reach it. The performance and complexity of the proposed solutions are illustrated by numerical simulations.
Intravaginal DHEA, by a strictly local action, exerts beneficial effects on both vaginal atrophy symptoms and sexual dysfunction (2010)

The present data indicate that combined androgenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues.
P113 EVALUATION OF THE EFFICACY OF TOFACITINIB IN PATIENTS WITH ULCERATIVE COLITIS UTILIZING THE MODIFIED MAYO SCORE: DATA FROM THE OCTAVE PROGRAM (2020)

Abstract Introduction Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib were evaluated in 2 Phase 3 induction studies (OCTAVE Induction 1 &amp; 2, NCT01465763 &amp; NCT01458951), a 52-week (wk), Phase 3 maintenance study (OCTAVE Sustain, NCT01458574),1 and an ongoing open-label, long-term extension study (NCT01470612).2 In these trials, endpoint definitions were based on the conventional Mayo score comprising 4 subscores (stool frequency, rectal bleeding, endoscopic findings, Physician Global Assessment [PGA]). The FDA recommend the use of a modified Mayo (mMayo) score in which the PGA subscore is omitted (a subjective measure, and a recognized Mayo score limitation) as an endpoint measure for UC clinical trials.3 In this post hoc analysis, we assessed the efficacy of tofacitinib using endpoint definitions based on mMayo score. Methods In OCTAVE Induction 1 &amp; 2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 wks; clinical responders were re-randomized into OCTAVE Sustain for 52 wks and received placebo, tofacitinib 5 or 10 mg BID. Trial endpoints included remission, symptomatic remission, and clinical remission (Table), assessed at Wk 8 in OCTAVE Induction 1 &amp; 2 and Wk 52 in OCTAVE Sustain. Treatment effects (ie difference from placebo) using mMayo and Mayo scores were evaluated and compared. Results In OCTAVE Induction 1 &amp; 2, numerically more patients achieved remission using the mMayo score (7.7% placebo; 24.8% tofacitinib 10 mg BID) compared with the Mayo score (6.0% placebo; 17.6% tofacitinib 10 mg BID), with a greater difference from placebo with mMayo scores (Table). Likewise, the proportion of patients achieving clinical remission was numerically greater with mMayo scores (7.7% placebo; 25.0% tofacitinib 10 mg BID) compared with Mayo scores (6.0% placebo; 17.7% tofacitinib 10 mg BID), whereas the same proportion of patients achieved symptomatic remission with both scores. The same trends were noted in OCTAVE Sustain, with numerically more patients in placebo and tofacitinib groups achieving remission and clinical remission using mMayo scores compared with Mayo scores (Table), and symptomatic remission achieved by the same proportion of patients with both scores. Conclusion In this post hoc analysis, a statistically significant effect of tofacitinib treatment vs placebo was demonstrated across endpoints based on the mMayo score, agreeing with previously reported data based on the Mayo score.1 Treatment effect sizes for endpoints based on the mMayo score without PGA were the same or numerically greater than corresponding endpoints based on the Mayo score. References
Hexa-Acylated Lipid A Is Required for Host Inflammatory Response to Neisseria gonorrhoeae in Experimental Gonorrhea (2020)

ABSTRACT Neisseria gonorrhoeae causes gonorrhea, a sexually transmitted infection characterized by inflammation of the cervix or urethra. However, a significant subset of patients with N. gonorrhoeae remain asymptomatic, without evidence of localized inflammation. Inflammatory responses to N. gonorrhoeae are generated by host innate immune recognition of N. gonorrhoeae by several innate immune signaling pathways, including lipooligosaccharide (LOS) and other pathogen-derived molecules through activation of innate immune signaling systems, including toll-like receptor 4 (TLR4) and the interleukin-1β (IL-1β) processing complex known as the inflammasome. The lipooligosaccharide of N. gonorrhoeae has a hexa-acylated lipid A. N. gonorrhoeae strains that carry an inactivated msbB (also known as lpxL1 ) gene produce a penta-acylated lipid A and exhibit reduced biofilm formation, survival in epithelial cells, and induction of epithelial cell inflammatory signaling. We now show that msbB -deficient N. gonorrhoeae induces less inflammatory signaling in human monocytic cell lines and murine macrophages than the parent organism. The penta-acylated LOS exhibits reduced toll-like receptor 4 signaling but does not affect N. gonorrhoeae -mediated activation of the inflammasome. We demonstrate that N. gonorrhoeae msbB is dispensable for initiating and maintaining infection in a murine model of gonorrhea. Interestingly, infection with msbB -deficient N. gonorrhoeae is associated with less localized inflammation. Combined, these data suggest that TLR4-mediated recognition of N. gonorrhoeae LOS plays an important role in the pathogenesis of symptomatic gonorrhea infection and that alterations in lipid A biosynthesis may play a role in determining symptomatic and asymptomatic infections.
Design of a Flexible On-Axis Interferometric Null Test for Off-Axis Parabolic and Toroidal Mirrors (2019)

A simulated flexible null test with a high-definition spatial light modulator (SLM) as a reconfigurable nulling element is reported. On-axis testing and the ability to display fiducials on the SLM decouples misalignment and form errors.
Positive epistasis between disease-causing missense mutations and silent polymorphism with effect on mRNA translation velocity (2021)

Significance The same mutation can have different effects among individuals, and one reason for this is the presence of additional mutations, a relationship known as epistasis. Epistatic effects are difficult to predict. We report a rare example of positive epistasis between a silent mutation (that changes nucleotide but not the encoded amino acid) and missense mutation(s) (that change amino acid and cause cystic fibrosis disease). Individually, each mutation has a detrimental effect, but they are beneficial when present together. The underlying molecular effect is in their ability to markedly modulate the ribosomal speed on mRNA in a synergistic fashion. In a broader setting of human diseases, our results suggest that epistasis with silent mutation broadens the spectrum of disease outcome.