gebhart/patrepeval huggingface dataset:
Substituted Aryl Benzylamines as Potent and Selective Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 3 (2021)

17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed at high levels in testes and seminal vesicles; it is also present in prostate tissue and involved in gonadal and non-gonadal testosterone biosynthesis. The enzyme is membrane-bound, and a crystal structure is not yet available. Selective aryl benzylamine-based inhibitors were designed and synthesised as potential agents for prostate cancer therapeutics through structure-based design, using a previously built homology model with docking studies. Potent, selective, low nanomolar IC<sub>50</sub> 17β-HSD3 inhibitors were discovered using <i>N</i>-(2-([2-(4-chlorophenoxy)phenylamino]methyl)phenyl)acetamide (<b>1</b>). The most potent compounds have IC<sub>50</sub> values of approximately 75 nM. Compound <b>29</b>, <i>N</i>-[2-(1-Acetylpiperidin-4-ylamino)benzyl]-<i>N</i>-[2-(4-chlorophenoxy)phenyl]acetamide, has an IC<sub>50</sub> of 76 nM, while compound <b>30</b>, <i>N</i>-(2-(1-[2-(4-chlorophenoxy)-phenylamino]ethyl)phenyl)acetamide, has an IC<sub>50</sub> of 74 nM. Racemic <i>C</i>-allyl derivative <b>26</b> (IC<sub>50</sub> of 520 nM) was easily formed from <b>1</b> in good yield and, to determine binding directionality, its enantiomers were separated by chiral chromatography. Absolute configuration was determined using single crystal X-ray crystallography. Only the <i>S</i>-(+)-enantiomer (<b>32</b>) was active with an IC<sub>50</sub> of 370 nM. Binding directionality was predictable through our in silico docking studies, giving confidence to our model. Importantly, all novel inhibitors are selective over the type 2 isozyme of 17β-HSD2 and show <20% inhibition when tested at 10 µM. Lead compounds from this series are worthy of further optimisation and development as inhibitors of testosterone production by 17β-HSD3 and as inhibitors of prostate cancer cell growth.
Constitutive Vagus Nerve Activation Modulates Immune Suppression in Sepsis Survivors (2018)

Patients surviving a septic episode exhibit persistent immune impairment and increased mortality due to enhanced vulnerability to infections. In the present study, using the cecal ligation and puncture (CLP) model of polymicrobial sepsis, we addressed the hypothesis that altered vagus nerve activity contributes to immune impairment in sepsis survivors. CLP-surviving mice exhibited less TNFα in serum following administration of LPS, a surrogate for an infectious challenge, than control-operated (control) mice. To evaluate the role of the vagus nerve in the diminished response to LPS, mice were subjected to bilateral subdiaphragmatic vagotomy at 2 weeks post-CLP. CLP-surviving vagotomized mice exhibited increased serum and tissue TNFα levels in response to LPS-challenge compared to CLP-surviving, non-vagotomized mice. Moreover, vagus nerve stimulation in control mice diminished the LPS-induced TNFα responses while having no effect in CLP mice, suggesting constitutive activation of vagus nerve signaling in CLP-survivors. The percentage of splenic CD4<sup>+</sup> ChAT-EGFP<sup>+</sup> T cells that relay vagus signals to macrophages was increased in CLP-survivors compared to control mice, and vagotomy in CLP-survivors resulted in a reduced percentage of ChAT-EGFP<sup>+</sup> cells. Moreover, CD4 knockout CLP-surviving mice exhibited an enhanced LPS-induced TNFα response compared to wild-type mice, supporting a functional role for CD4<sup>+</sup> ChAT<sup>+</sup> T cells in mediating inhibition of LPS-induced TNFα responses in CLP-survivors. Blockade of the cholinergic anti-inflammatory pathway with methyllcaconitine, an α7 nicotinic acetylcholine receptor antagonist, restored LPS-induced TNFα responses in CLP-survivors. Our study demonstrates that the vagus nerve is constitutively active in CLP-survivors and contributes to the immune impairment.
Supplementary Figure 1 from Effects of Dasatinib on Src Kinase Activity and Downstream Intracellular Signaling in Primitive Chronic Myelogenous Leukemia Hematopoietic Cells (2023)

Supplementary Figure 1 from Effects of Dasatinib on Src Kinase Activity and Downstream Intracellular Signaling in Primitive Chronic Myelogenous Leukemia Hematopoietic Cells
206 GENERATION OF HUMAN INDUCED PLURIPOTENT STEM CELLS FROM DENTAL PULP-DERIVED MESENCHYMAL STEM CELLS (2011)

Induced pluripotent stem (iPS) cells are somatic cells that have been reprogrammed to a pluripotent state and a great source for regenerative medicine. Several types of human somatic and adult stem cells have been reprogrammed into iPS cells, including mesenchymal stem cells (MSC). Recently, human dental pulp has been considered as a valuable alternative source of MSC (hDP-MSC) with excellent proliferation capacity and multilineage differentiation potential. In this study, our objective was to establish iPS cells from hDP-MSC and evaluate the expression of transcriptional factors and in vitro differentiation potential into mesenchymal lineages. The hMSC were isolated from the dental pulp of male donor (~18 years old) were cultured in advanced-DMEM supplemented with 10% fetal bovine serum at 37°C, 5% CO2 in a humidified atmosphere. The hDP-MSC at passage 3 were analysed for the expression of MSC-specific surface markers (CD44 and CD90) using flow cytometry and transcriptional factors (Oct4, Nanog and Sox2) by immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR). Differentiation into adipocytes and osteocytes of hDP-MSC was carried out under specific conditions for 2 and 4 weeks, respectively and assessed by cytochemical staining (Oil red O, von Kossa and Alizarin Red S, respectively). iPS cells were generated from hDP-MSC at passage 3 by using pMXs retroviral vector (Addgene, Cambridge, MA, USA) containing cDNA of c-Myc, Klf4, Nanog and Sox2. The iPS cells were evaluated for alkaline phosphatase (AP) activity, expression of human embryonic stem cells (hESC) markers (Rex1, Nanog, Oct4, SSEA-1 and TRA-160) by immunostaining. Isolated hDP-MSC expressed surface markers, such as CD44 and CD90 (86% and 93%, respectively) by flow cytometry and positively stained for transcriptional factors (Oct4, Nanog and Sox2) by immunofluorescence. Further, the cells were capable of differentiating in vitro into adipocytes and osteocytes as demonstrated by Oil red O and von Kossa and Alizarin red S staining, respectively. The iPS cells generated from hDP-MSC were positive for AP staining and clearly expressed the markers specific to hESC, including Rex1, Nanog, Oct4, SSEA-1 and TRA-160. In conclusion, hMSC derived from dental pulp could be successfully reprogrammed into iPS cells by retroviral vector systems and the generated iPS cells shared the similar characteristics of hESC. Therefore, hDP-MSC might be an ideal alternative cell source to derive autologous iPS cells for therapeutic applications. This work was supported by Grant No. 2007031034040 from Bio-organ and Grant No. 200908FHT010204005 from Biogreen21.
Streptococci as the new dominant aetiological factors of mastitis in dairy cows in north-eastern Poland: analysis of the results obtained in 2013–2019 (2021)

The objective of our study was to evaluate prevalence of selected bacterial and fungal pathogens of mastitis in dairy cattle in north-eastern Poland. Our study was conducted from 2013 to 2019 in 1,665 clinically and sub-clinically infected quarter milk samples (2013, n = 368; 2014, n = 350; 2015, n = 290; 2016, n = 170; 2017, n = 173; 2018, n = 224; and 2019, n = 90). The isolation and identification of the pathogens were performed in keeping with generally accepted microbiological procedures. In 2013, mastitis was most commonly caused by Staphylococcus aureus (24%), Streptococcus spp. (22%), Streptococcus agalactiae (12%) and coagulase-negative staphylococci (11%). In 2014, the most common pathogens were Streptococcus spp. (25%), Staphylococcus aureus (18%) and coagulase-negative staphylococci (10%); in 2015, 2016, 2017, 2018 and 2019, Streptococcus spp. (from 39-49%) were the most frequent strains isolated from the quarter milk samples. Other pathogens were isolated occasionally (below 15% in all years). In conclusion, the role of environmental bacteria has been gradually increasing in the Warmia Province. The importance of infectious pathogens has been decreasing, indicating the efficacy of the applied preventive programmes and a need for the development of new programmes targeting environmental pathogens.
New route to biologically active 3,8-dioxabicyclo[3.2.1]octane derivatives related to zoapatanol (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew route to biologically active 3,8-dioxabicyclo[3.2.1]octane derivatives related to zoapatanolDavid M. Walba and George S. StoudtCite this: J. Org. Chem. 1983, 48, 26, 5404–5406Publication Date (Print):December 1, 1983Publication History Published online1 May 2002Published inissue 1 December 1983https://pubs.acs.org/doi/10.1021/jo00174a063https://doi.org/10.1021/jo00174a063research-articleACS PublicationsRequest reuse permissionsArticle Views278Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
AAV‐mediated knockdown of phospholamban leads to improved contractility and calcium handling in cardiomyocytes (2007)

Our results suggest that AAV-delivered shRNAs mediated physiologically significant suppression of phospholamban that may be useful in combating the effects of chronic heart failure.
Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling (2017)

Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3. Our results demonstrate that S1P disrupts Hippo signaling by reducing YAP phosphorylation and increasing the expression of CCN1 and CCN2 in both ovarian cancer cells. Furthermore, the increase in CCN1/CCN2 expression contributes to the S1P-induced increase in cancer cell proliferation.
Indirect immunofluorescence for the diagnosis of Lassa fever infection. (1975)

The indirect immunofluorescent technique is a rapid method for identification of Lassa virus and Lassa virus antibody. In the study reported here, Lassa virus antigen was detected by this method in Vero cell cultures within 24 hours of their inoculation with an infected human blood specimen. A diagnosis could be made from field-collected specimens within 3 days of their receipt.Fluorescent antibodies against Lassa virus were detected in human serum as early as 7 to 10 days after onset of illness, and were detected as long as 61 months after infection. Complement fixing antibodies were not as long lasting.No antigenic differences were noted by the indirect immunofluorescence technique between several Lassa virus strains isolated from Nigeria, Liberia, and Sierra Leone over a 6-year period.
Analysis of Phosphorus Balance of Farmland in Beijing——a Case Study of Miyun County and Fangshan District (2010)

By applying methodology of phosphorus balance of farmland ecological system,taking Miyuan County and Fangshan County,Beijing as examples,the soil nutrient balance of phosphorus were studied. Results showed that in 2006,total phosphorus surplus in Miyuan and Fangshan were 4,084.11t and 10,851.19t respectively,and phosphorus surplus intensity were 110.81kg/hm2 and 386.48kg/hm2. Phosphorus fertilizer is the most important source of phosphorus inputs in Miyun and Fangshan. Use of phosphate fertilizer was one of the factors affecting variation of phosphorus balance in arable land,and there was a good relationship between them. Different geographical fertilizer inputs result in total amount of phosphorus balance and intensity in distribution of serious imbalance. The amount of phosphorus balance increased from northwest to southeast in Fangshan District while phosphorus surplus intensity was less in western and more in eastern part of Miyun County,and greater phosphorus surplus intensity was in south of Fangshan District. Through comparative study and analysis of basic tend of loss and surplus of phosphorus nutrient,potential cause of pollution was found and controlling measures and corresponding measures about the promotion of farm phosphorus balance and reduction of nutrient load of phosphorus were proposed.
Thermal Relaxation Spectra for Evaluating Luminescence Quantum Efficiency of CASN:Eu2+ Measured by Balanced-Detection Sagnac-Interferometer Photothermal Deflection Spectroscopy (2020)

Highly sensitive broadband photothermal spectroscopy with a white-light lamp as the excitation source was developed by combining a Sagnac interferometer and balanced detection with a photothermal deflection method. A probe beam was split by a birefringent crystal CaCO3 into signal and reference beams with a balanced intensity. This balanced detection enabled the measurement of photoexcited thermal relaxation spectra of materials in the air over the whole visible range in the weak excitation limit 50 µW/cm2. The photothermal excitation spectrum of Eu2+-doped CaAlSiN3 phosphors (CASN:Eu2+) with a high luminescent quantum efficiency was measured to be distinctly different from the photoluminescence excitation spectrum which reflects the absorption spectrum, revealing the thermal relaxation mechanism of the phosphor. Assuming a typical non-radiative relaxation from the higher excited states to the lowest excited state and successively to the ground state, it is demonstrated that the photoluminescence efficiency of the phosphors is readily evaluated simply by comparing the photothermal and photoluminescence excitation spectra.
Noise Reduction for Interpolations based on Pilot-Block Averaging in DVB-T Receivers (2006)

This paper proposes a noise-reduction method to improve the channel-estimation performance in DVB-T receivers. Pilot-insertion type approximation and pilot-block averaging are employed to reduce noise effect. Computer simulation shows that the proposed method improves the estimation performance by more than 1 dB in terms of the SER after equalization.
Effect of Etched Sidewall Tilt on the Reflection Loss of Silicon-on-Insulator (SOI) or III-V Etched Facet Reflector (2008)

The effect of etching’s verticality on the reflection loss of strongly-guiding SOI or weakly-guiding III-V etched facet reflector (EFR) is studied. High tolerance on tilt makes SOI EFR much more resilient to etching deviation.
Mass spectral analysis of mouse serum proteome to predict tumor clearance (2015)

Meeting abstracts A novel transposon tumor induction model was used to induce cholangiocarcinoma tumors in C57BL/6 mice. In this system, it is possible to drive immune related activities that will lead to 1) large tumors, no clearance or response by tumor-directed CD8+ T cells, 2) large tumors, no
17-LB: A Multicenter Study of the Burden of Hypoglycemia across Trimesters in Pregnancies Complicated by Type 1 Diabetes (LOIS-P Study) (2020)

Pregnancies in type 1 diabetes (T1D) are high-risk, and data in the U.S. are limited regarding clinical and CGM based hypoglycemia throughout pregnancy while on sensor augmented insulin pump (SAP). Pregnant women with T1D on insulin pump ≤ 16 wks gestation were enrolled at 3 U.S. centers and used study Dexcom G6. We analyzed episodes of severe hypoglycemia (SH) and days with &amp;gt; 20 hrs of CGM for biochemical hypoglycemia (BH) based on international consensus guidelines (&amp;lt;63 and &amp;lt;54 mg/dl) and frequency/duration of prolonged hypoglycemia (PH, ≥120 mins &amp;lt; 54 mg/dl) Twenty pregnant subjects, age 31 ± 4.5 yrs, 14 ± 8 yrs of T1D, baseline weight 77 ± 16 kg, BMI 28 ± 6.2 kg/m2, HbA1c 6.5 ± 0.7%, were studied. Gestational age at enrollment and delivery was 11.4 ± 4 and 37.7 ± 1.5 wks respectively. One subject experienced a single episode of SH with an overall incidence 7/100 patient years. Percentage of hypoglycemia and BH events per trimester are described in Table 1. BH was common in each trimester, but most frequent in the first. Eighteen events of PH occurred in four subjects (20%) lasting 120-410 mins with two events each in two, three events in one and 11 events in one subject respectively with 15 (83%) events occurring between 12am-6am. Our study shows pregnant women with T1D on SAP frequently experience level 1 hypoglycemia, and 20% experience prolonged hypoglycemia predominantly overnight. Disclosure R. Kaur: None. B.H. Smith: None. J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. B. Ozaslan: None. G. O’Malley: Research Support; Self; Abbott, Dexcom, Inc. M. Trinidad: None. D. Desjardins: None. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. C. Levister: None. C. Reid: None. S.K. McCrady-Spitzer: None. S.J. Ogyaadu: None. M. Church: None. M. Piper: None. W.K. Kremers: Research Support; Self; AstraZeneca. B. Rosenn: None. C.J. Levy: Consultant; Self; Dexcom, Inc. Employee; Spouse/Partner; Allergan plc. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott. Funding National Institutes of Health (122358); Dexcom, Inc. (AP-2018-016)
Dengue Virus Evolution under a Host-Targeted Antiviral (2015)

Although hundreds of millions of people are infected with DENV every year, there is currently no approved vaccine or antiviral therapy. UV-4B has demonstrated antiviral activity against DENV and is expected to enter clinical trials soon. Therefore, it is important to understand the mechanisms of DENV resistance to UV-4B. Host-targeted antivirals are thought to have a higher genetic barrier to escape mutants than directly acting antivirals, yet there are very few published studies of viral evolution under host-targeted antivirals. No study to date has described flavivirus evolution in vivo under selective pressure by a host-based antiviral drug. We present the first in vivo study of the sequential progression of viral evolution under selective pressure by a host-targeted antiviral compound. This study bolsters support for the clinical development of UV-4B as an antiviral drug against DENV, and it provides a framework to compare how treatment with other host-targeted antiflaviviral drugs in humans and different animal models influence viral genetic diversity.
On evil twin networks and the value of limited randomized routing (2000)

A dynamic two-stage Delta network (N inputs and outputs) is introduced and analyzed for permutation routing. The notion of evil twins is introduced and a deterministic procedure is given to route any permutation in no more than 2/sup 4//spl radic/N network cycles. Two limited randomized routing schemes are then analyzed. The first called Single Randomization yields on average at most N!+1 (N!=O(logN/loglogN)/sup 1/ and is the greatest integer such that (N!)!/spl les/N) network cycles and the second called Multiple Randomization yields on average at most upper bound [log(logN+1)]+2+1/N network cycles for any input permutation. The probability of any permutation requiring at least c network cycles more than the above average bounds is then shown to be at most 1/(c+1) for Single Randomization and 1/N/sup r/ for Multiple Randomization, respectively. It is then shown how the dynamic two-stage network can be physically realized as a three-stage network. Both the evil twin and Multiple Randomization algorithms have been integrated into an off-the-shelf ASIC from PMC-Sierra, Inc. (PM-73488) which has been designed as a building block for such a three-stage implementation. These routing schemes are also adapted to run on a recirculating network. Recirculation is used to effect a reshuffling of data as in the dynamic network, but with a considerable reduction in network cost.
Individual lipid encapsulated microbubble radial oscillations: Effects of fluid viscosity (2016)

Ultrasound-stimulated microbubble dynamics have been shown to be dependent on intrinsic bubble properties, including size and shell characteristics. The effect of the surrounding environment on microbubble response, however, has been less investigated. In particular, microbubble optimization studies are generally conducted in water/saline, characterized by a 1 cP viscosity, for application in the vasculature (i.e., 4 cP). In this study, ultra-high speed microscopy was employed to investigate fluid viscosity effects on phospholipid encapsulated microbubble oscillations at 1 MHz, using a single, eight-cycle pulse at peak negative pressures of 100 and 250 kPa. Microbubble oscillations were shown to be affected by fluid viscosity in a size- and pressure-dependent manner. In general, the oscillation amplitudes exhibited by microbubbles between 3 and 6 μm in 1 cP fluid were larger than in 4 cP fluid, reaching a maximum of 1.7-fold at 100 kPa for microbubbles 3.8 μm in diameter and 1.35-fold at 250 kPa for microbubbles 4.8 μm in diameter. Simulation results were in broad agreement at 250 kPa, however generally underestimated the effect of fluid viscosity at 100 kPa. This is the first experimental demonstration documenting the effects of surrounding fluid viscosity on microbubble oscillations, resulting in behavior not entirely predicted by current microbubble models.