gebhart/patrepeval huggingface dataset:
Mutanome engineered RNA immuno-therapy (MERIT) for patients with triple negative breast cancer (TNBC) (2018)

Background: Treatment of triple negative breast cancer (TNBC) is hampered by lack of established therapeutic targets like hormone receptors or HER-2. Surgery, chemotherapy and radiotherapy are the standard of care yet cure rates in patients with TNBC remain inferior compared to other BC subtypes. Approaches tailored to the patient’s individual tumor signature may lead to improvement. The “Mutanome Engineered RNA Immuno-Therapy (MERIT)” consortium is validating an innovative individualized mRNA-based vaccine for TNBC treatment. MERIT is a collaboration of 5 European partners (academia and industry) dedicated to realize a personalized approach for TNBC treatment. The consortium set up a clinical workflow covering drug development from target discovery and validation to GMP manufacturing and drug release for each individual patient (MUTANOME). Moreover, the consortium established a pre-synthesized mRNA vaccine warehouse containing the most frequently shared tumor-associated antigens (TAA) in TNBC for drug supply (WAREHOUSE). Trial design: A phase I trial in 2 European countries assesses the feasibility, safety and biological efficacy of this personalized immunotherapy. TNBC patients (pT1cN0M0 – TxNxM0) after surgery and (neo-)adjuvant chemotherapy will be allocated to one of two study arms. Patients in ARM1 receive 8 WAREHOUSE vaccinations with personalized TAA combinations corresponding to the patient tumor’s antigen-expression profile. Patients in ARM2 are first treated with the WAREHOUSE approach followed by 8 vaccination cycles of an on-demand manufactured MUTANOME vaccine encoding the unique mutation signature of the individual patient identified by NGS. The mRNAs are administered intravenously as a RNA-lipoplex formulation which protects RNA from degradation, activates innate immunity, transfects APCs and consequently induces highly potent antigen-specific T-cell responses. Three clinical sites are open for recruitment; >12 patients were screened and vaccinations with WAREHOUSE or MUTANOME RNAs have started. We give insights into features of the established process and present first stratification data. MERIT was funded by the EU Commission’s FP7 and is led by BioNTech AG. Clinical trial identification: EudraCT: 2014-002274-37. Legal entity responsible for the study: BioNTech AG. Funding: European Commission’s FP7; BioNTech AG. Disclosure: L. Heesen, K. Frenzel, S. Bolte, V. Bukur, E. Derhovanessian, S. Kreiter, A. Kuhn: Employment: BioNTech. M. Diken: Patent ownership, patent applications, employment: BioNTech AG. K. Kühlcke: Employment: BioNTech IMFS. T. Sjöblom: Founder, board member, shareholder: ExScale Biopecimen Solutions. A. Ö. Türeci: Co-founder: Ganymed Pharmaceuticals GmbH. U. Sahin: Patent ownership, patent applications, stock owner, management board member, co-founder: BioNTech AG; Co-founder, chair: TRON gGmbH; Membership on advisory board, co-founder: Ganymed Pharmaceuticals GmbH. All other authors have declared no conflicts of interest.
Standardized fluorescent staining method for fast and affordable microplastics monitoring and its application for a long-term monitoring of microplastics in the effluent of a German wastewater treatment plant. (2022)

One of the biggest challenges in microplastics (MP) research is the lack of standardized, fast, and affordable MP monitoring. There are a variety of methods used for sampling, sample processing and detection, which makes it almost impossible to compare data among different studies. Additionally, commonly used methods for MP detection are time consuming and require expensive measuring devices and well-trained staff. Fluorescent staining of MP in environmental samples is a promising approach for fast and inexpensive MP detection. To receive better fluorescence properties of MP and reduce the risks of false positives, the fluorescent properties of 23 chemically modified Nile red derivates were investigated. It is demonstrated how to modify a standard microscope or camera with a low budget into a fluorescent imaging tool. Subsequently, a standard protocol for MP sampling, sample preparation and detection was developed. For standardized detection, an automated particle counting software is applied to analyze the fluorescent images. Methods to avoid and control contamination of the samples with MP are presented. Depending on the imaging tool used and the number of samples taken, the average processing time per sample was 25-60 minutes including sampling, sample processing and detection. The developed method was applied for the long-term monitoring of MP in the effluent of a German wastewater treatment plant (WWTP) over a period of 10 months. The results show high temporal fluctuations of the MP contamination ranging from 1-145 MP/l. This demonstrates that a larger number of samples is needed to properly evaluate the MP outputs of WWTP, for which the developed method is well suited. The investigated WWTP was equipped with granulated activated carbon and an advanced oxidation process (H2O2 + UV-C), which showed no effect on the MP concentrations, as they are designed to remove dissolved organic trace substances, but not suspended micropollutants as MP. Also see: https://micro2022.sciencesconf.org/426798/document
Two-Fold Reduction of Dibenzo[a,e]cyclooctatetraene with Group 1 Metals: From Lithium to Cesium (2020)

Chemical reduction of sym-dibenzo[a,e]cyclooctatetraene (DBCOT, 1) has been investigated using group 1 metals ranging from Li to Cs as the reducing agents. With all alkali metals, DBCOT readily undergoes a 2-fold reduction to afford the doubly reduced DBCOT2– (12–) anion. Seven products of 12– with different alkali-metal counterions have been isolated and fully characterized. Their X-ray diffraction structural analyses reveal the ligand core planarization upon addition of two electrons as well as the versatility of 12– in alkali-metal coordination. The negative charge localization at the central eight-membered ring of 12– identified by theoretical calculations is fully consistent with the X-ray crystallographic and NMR spectroscopic results. A broad range of solid-state structural arrangements of the resulting products stems from different metal binding patterns and secondary interactions involving coordinating agents used for crystallization (THF vs 18-crown-6 and [2.2.2]cryptand). This family of alkali-metal salts of 12– provides useful reagents for ligand metathesis reactions that can be used in the preparation of various transition-metal or lanthanide-based organometallic complexes.
Mental Health Problems/Additional “Psychiatric Disorders” (2014)

Abstract ADHD/DAMP/ESSENCE should be seen as a deviation from normal psychomotor development that does not, however, inevitably bring about psychiatric problems. Psychiatric problems of different kinds, including depression, anxiety, conduct disorder, tics and autistic traits are nevertheless very common. Doctors and psychologists who are responsible for adequate measures being implemented in ADHD/DAMP and other ESSENCE must be well versed in these additional psychiatric problems. Also, doctors, child and adult specialists alike, need to be up-to-date and experienced in ADHD/DAMP when dealing with people with mental health problems of any type. ADHD/DAMP and other ESSENCE are clearly extremely common underlying conditions in a wide variety of mental health disorders.
Development and validation of a low-cost polymer selective laser sintering machine (2020)

Due to manufacturer implemented processing parameter restrictions and the cost prohibitive nature of selective laser sintering (SLS) machines, researchers have limited opportunities to explore the processing of new materials using this additive manufacturing (3D printing) process. Accordingly, this article aimed to overcome these limitations by describing the build and operation of a customizable low-cost polymer SLS machine. The machine boasts a three piston powder bed with the center build piston heated by PID controlled ceramic heaters. Thermal energy for powder consolidation was provided via a 2.44 W solid state diode laser which was mechanically traversed using stepper motor driven belt drives. New layers of powder were deposited by a counter-rotating roller system. The SLS machine was controlled by executing G-code in Mach3 allowing full customization of processing parameters. The machine demonstrated the production of parts from polyamide-12 reaching densities of 918 ± 9 kg/m<sup>3</sup> while achieving an elastic modulus of 358.36 ± 3.04 MPa and elongation at break of 11.13 ± 0.02%. With part properties similar to those achievable with a commercial machine, this low-cost SLS machine could be a vital tool in assisting researchers to explore the processing of new materials.
Human breast cancer susceptibility to paclitaxel therapy is independent of Bcl-2 expression. (2000)

In laboratory studies, ectopic overexpression of the antiapoptotic protein Bcl-2 has been shown to result in resistance to the cytotoxic effects of many chemotherapeutic drugs. Furthermore, posttranslational modification of moderately expressed endogenous Bcl-2 has been correlated with susceptibility to paclitaxel treatment in vitro. To determine whether tumor expression of Bcl-2 protein correlates with response and ultimate outcome in vivo, we quantified Bcl-2 expression by immunohistochemical analysis of archived biopsy specimens from metastatic breast cancer patients treated with single-agent paclitaxel. The statistical association between the degree of Bcl-2 expression, objective tumor response, and clinical outcome was then determined. In patients (n = 39) whose tumors had low (< or = 10% cells positive) Bcl-2 levels by immunohistochemical analysis, the overall response (complete response + partial response) rate was 21% versus an overall response rate of 22% in patients (n = 36) with high (>10% cells positive) Bcl-2 expression (P = 0.92). In patients with low Bcl-2 expression, the median time to progression was 126 days [95% confidence interval (CI), 63-160 days]. This was not significantly different than the 105 days for patients with high tumor Bcl-2 expression (95% CI, 84-214 days). The median survival time from initiation of paclitaxel therapy for patients with low Bcl-2 expression was 663 days (95% CI, 456-1119 days) and was not significantly different than the 450 days (95% CI, 239-1058 days) observed for patients with high Bcl-2 expression. In conclusion, we found that in metastatic breast cancer, there is no significant association between tumor Bcl-2 expression and response to paclitaxel, median time to progression, or survival, suggesting that the main mechanism of paclitaxelinduced cytotoxicity in breast tumors is independent of Bcl-2 expression.
Termination of translation in eukaryotes is mediated by the quaternary eRF1•eRF3•GTP•Mg2+ complex. The biological roles of eRF3 and prokaryotic RF3 are profoundly distinct (2006)

GTP hydrolysis catalyzed in the ribosome by a complex of two polypeptide release factors, eRF1 and eRF3, is required for fast and efficient termination of translation in eukaryotes. Here, isothermal titration calorimetry is used for the quantitative thermodynamic characterization of eRF3 interactions with guanine nucleotides, eRF1 and Mg2+. We show that (i) eRF3 binds GDP (K(d) = 1.9 microM) and this interaction depends only minimally on the Mg(2+) concentration; (ii) GTP binds to eRF3 (K(d) = 0.5 microM) only in the presence of eRF1 and this interaction depends on the Mg2+ concentration; (iii) GTP displaces GDP from the eRF1*eRF3*GDP complex, and vice versa; (iv) eRF3 in the GDP-bound form improves its ability to bind eRF1; (v) the eRF1*eRF3 complex binds GDP as efficiently as free eRF3; (vi) the eRF1*eRF3 complex is efficiently formed in the absence of GDP/GTP but requires the presence of the C-terminus of eRF1 for complex formation. Our results show that eRF1 mediates GDP/GTP displacement on eRF3. We suggest that after formation of eRF1*eRF3*GTP*Mg2+, this quaternary complex binds to the ribosomal pretermination complex containing P-site-bound peptidyl-tRNA and the A-site-bound stop codon. The guanine nucleotide binding properties of eRF3 and of the eRF3*eRF1 complex profoundly differ from those of prokaryotic RF3.
Waste-aware dilution and mixing of biochemical samples with digital microfluidic biochips (2011)

A key challenge in design automation of digital microfluidic biochips is to carry out on-chip dilution/mixing of biochemical samples/reagents for achieving a desired concentration factor (CF). In a bioassay, reducing the waste is crucial because the waste droplet handling is cumbersome and the number of waste reservoirs on-chip needs to be minimized to use limited volume of sample and expensive reagents and hence to reduce the cost of a biochip. The existing dilution algorithms attempt to reduce the number of mix/split steps required in the process but focus little on minimization of sample requirement or waste droplets. In this work, we characterize the underlying combinatorial properties of waste generation and identify the inherent limitations of two earlier mixing algorithms (BS algorithm by Thies et al., Natural Computing 2008; DMRW algorithm by Roy et al., IEEE TCAD 2010) in addressing this issue. Based on these properties, we design an improved dilution/mixing algorithm (IDMA) that optimizes the usage of intermediate droplets generated during the dilution process, which in turn, reduces the demand of sample/reagent and production of waste. The algorithm terminates in O(n) steps for producing a target CF with a precision of 1/2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</sup> . Based on simulation results for all CF values ranging from 1/1024 to 1023/1024 using a sample (100% concentration) and a buffer solution (0% concentration), we present an integrated scheme of choosing the best waste-aware dilution algorithm among BS, DMRW, and IDMA for any given value of CF. Finally, an architectural layout of a DMF biochip that supports the proposed scheme is designed.
The Design of Wireless Fingerprint Attendance System (2006)

In this paper, a wireless fingerprint attendance management system is designed and implemented .This system based biometrics and wireless technique solves the problem of spurious attendance and the trouble of laying the corresponding network. It can make the users' attendances more easily and effectively.
A data reduction scheme for improving the accuracy of oxygen saturation calculations from spectrometricin vivomeasurements (1998)

A developing tool in ophthalmological research and practice is the study of the oxygen saturation in retinal vessels because this measurement contains important diagnostic information about the metabolism at the human ocular fundus. Imaging spectrometry enables locally resolved measurements of the oxygen saturation simultaneously in arteries and veins. The vessel reflex, imaging errors of the detection system and the noise of the signal result in substantial uncertainties in the calculated data. We present a data processing method for the improvement of the primary information leading to a reduction of the uncertainties of the derived oxygen saturation.
104: Multi-Regional Injections of Low Dose Botulinum Toxin a for Men with Chronic Pelvic Pain Syndrome (2006)

You have accessJournal of UrologyModerated Poster, Saturday, May 20, 2006, 3:30 - 5:30 pm1 Apr 2006104: Multi-Regional Injections of Low Dose Botulinum Toxin a for Men with Chronic Pelvic Pain Syndrome Seung Mok Shin, and Dong Soo Park Seung Mok ShinSeung Mok Shin More articles by this author , and Dong Soo ParkDong Soo Park More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)32371-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "104: Multi-Regional Injections of Low Dose Botulinum Toxin a for Men with Chronic Pelvic Pain Syndrome." The Journal of Urology, 175(4S), p. 34 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 34 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Seung Mok Shin More articles by this author Dong Soo Park More articles by this author Expand All Advertisement Loading ...
The Effect of Acute and Chronic Stress on GrowthA Presentation from the European Society for Paediatric Endocrinology (ESPE) New Inroads to Child Health (NICHe) Conference on Stress Response and Child Health in Heraklion, Crete, Greece, 18 to 20 May 2012. (2012)

Impaired bone growth is observed in many children exposed to stress, but whether the underlying cause is psychological or secondary to a variety of chronic disorders is unclear. The growth plate is specifically targeted by stress through many different mechanisms, including increased serum concentrations of proinflammatory cytokines and cortisol, as well as impaired actions of the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis. Both glucocorticoids, such as cortisol, and proinflammatory cytokines adversely affect several aspects of chondrogenesis in the growth plate, and these effects can be ameliorated by raising local IGF-1 concentrations. However, this intervention does not completely normalize growth. In children with stress related to chronic inflammation, the cornerstone of improving stress-impaired growth remains the judicious use of glucocorticoids while ensuring effective control of the disease process. Specific immunomodulatory therapy that targets the actions of tumor necrosis factor-α (TNFα) is at least partially effective at rescuing linear growth in many children with juvenile idiopathic arthritis (JIA). Patients who do not respond to anti-TNF treatment may be candidates for therapeutic agents that target other proinflammatory cytokines and for GH intervention. Although GH treatment rescues linear growth in some patients with JIA, it is unknown whether GH can rescue growth in those patients who do not respond to anticytokine therapy. Further experimental and clinical studies are needed to explore these and other new potential treatment strategies that could improve bone growth in patients who do not respond to conventional therapy.
Enhanced Performance of HgCdTe Midwavelength Infrared Electron Avalanche Photodetectors With Guard Ring Designs (2020)

In this article, the performance of midwavelength infrared (MWIR) HgCdTe electron avalanche photodiodes (e-APDs) with variable annealing processes and guard ring design is investigated. Carrier distribution in the device is performed by simulation methods to better understand the mercury interstitial dynamic transport mechanism. It is found that the device with suitable annealing time can effectively reduce the dark current while maintaining the bandwidth at a high level. Surface leakage current and the effect of guard ring design in ion implanted-type HgCdTe e-APDs are clarified by the electric-field distribution. The simulated results show that the dark current, excess noise factor, and mean square noise can be decreased with a guard ring design. In addition, the temperature-dependent performance of HgCdTe e-APD with guard ring is simulated, indicating optimization operating window. This article demonstrates the significance of guard ring designs for HgCdTe APDs, and the simulation method will provide an effective way to determine the source of the current generation mechanism.
TOPOGRAPHIC MAPPING THROUGH MEASUREMENT OF VEHICLE ATTITUDE AND ELEVATION (2004)

A self-propelled agricultural sprayer was equipped with four RTK DGPS receivers and an inertial measurementunit (IMU) to measure vehicle attitude and field elevation as the vehicle was driven across a field. Data were collected ina stop-and-go fashion at 3.05 m (10 ft) intervals, as well as in a continuous fashion at three different speed levels on a 2.3 hafield area with varying topography. Pitch and roll offset angles were estimated to within 95% confidence intervals that rangedfrom 0.01 to 0.10. Using ordinary kriging, digital elevation models (DEMs) were interpolated using only elevationmeasurements, as well as a combination of elevation and vehicle attitude measurements. The resulting DEMs were comparedwith each other to evaluate the effect of including attitude measurement on DEM accuracy. At the widest measurement swathwidth, the DEMs generated with attitude measurements had RMSE values of 10 to 11 cm, which was significantly lower thanthe RMSE of 15 cm associated with the DEMs generated without attitude measurements. Vehicle speed affected DEM error,but no discernable trends were detected. These results provide evidence supporting the feasibility of using vehicle-basedmeasurements collected during typical field operation for accurate DEM development.
Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors (2013)

A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.
Abatement of an Azo Dye on Structured C-Nafion/Fe-Ion Surfaces by Photo-Fenton Reactions Leading to Carboxylate Intermediates with a Remarkable Biodegradability Increase of the Treated Solution (2003)

A novel C-Nafion/Fe-ion structured fabric capable of mediating Orange II decomposition in Fenton-immobilized photoassisted reactions is presented. The catalyst preparation requires the right balance between the amount of the Nafion necessary to protect the C-surface and the minimum encapsulation of the Fe-cluster catalytic sites inside the Nafion to allow the photocatalysis to proceed. The C-Nafion/Fe fabric can be used up to pH 10 under light to photocatalyze the disappearance of Orange II in the presence of H2O2. The photocatalysis mediated by the C-Nafion/Fe-ion fabric increased with the applied light intensity and reaction temperature in the reaction needing an activation energy of 9.8 kcal/mol. This indicates that ion− and radical−molecule reactions take place during Orange II disappearance. The build up and decomposition of intermediate iron complexes under light involves the recycling of Fe2+ and was detected by infrared spectroscopy (FTIR). This observation, along with other experimental results, allows us to suggest a surface mechanism for the dye degradation on the C-Nafion/Fe-ion fabrics. The C-Nafion/Fe-ion fabric in the presence of H2O2 under solar simulated light transforms the totally nonbiodegradable Orange II into a biocompatible material with a very high BOD5/COD value. X-ray photoelectron spectroscopy (XPS) and sputtering by Ar+-ions of the upper surface layer of the C-Nafion/Fe-ion fabric allow us to describe the intervention of the photocatalyst down to the molecular level. Most of the Fe clusters examined by transmission electron microscopy (TEM) showed particle sizes close to 4 nm due to their encapsulation into the Gierke cages of the Nafion thin film observed by scanning electron microscopy (SEM) and optical microscopy (OM).