gebhart/patrepeval huggingface dataset:
Targeting the Binding Function 3 (BF3) Site of the Androgen Receptor Through Virtual Screening. 2. Development of 2-((2-phenoxyethyl) thio)-1H-benzimidazole Derivatives (2013)

The human androgen receptor (AR) is a proven therapeutic target in prostate cancer. All current antiandrogens, such as Bicalutamide, Flutamide, Nilutamide, and Enzalutamide, target the buried hydrophobic androgen binding pocket of this protein. However, effective resistance mechanisms against these therapeutics exist such as mutations occurring at the target site. To overcome these limitations, the surface pocket of the AR called binding function 3 (BF3) was characterized as an alternative target for small molecule therapeutics. A number of AR inhibitors directly targeting the BF3 were previously identified by us ( J. Med. Chem. 2011 . 54 , 8563 ). In the current study, based on the prior results, we have developed structure-activity relationships that allowed designing a series of 2-((2-phenoxyethyl)thio)-1H-benzimidazole and 2-((2-phenoxyethyl)thio)-1H-indole as lead BF3 inhibitors. Some of the developed BF3 ligands demonstrated significant antiandrogen potency against LNCaP and Enzalutamide-resistant prostate cancer cell lines.
Using adaptive avatars for visualizing recent music listening history and supporting music discovery (2014)

This paper studies the idea of using adaptive avatars for visualizing recent music listening, supporting music discovery, and encouraging social interaction. In the evaluated prototype the avatar responds to the user's music listening by changing its appearance by gaining new clothing and accessories to parts of the avatar. The gained items and parts match to the listened songs. The parts can be played as playlists and be sent to other users as visual recommendations. In a user study with 22 participants, the concept was found fun, interesting and said to provide new music listening experiences. Users were highly interested in the evolving avatar and seeing/listening to others' avatars. Users had several different avatar creation strategies that are very interesting for new music discovery. Users also listened to new types of music broadly using the avatars. Based on the results, the paper proposes design implications for using avatars in music discovery services.
<title>Interobserver variations on interpretation of multislice CT lung cancer screening studies, and the implications for computer-aided diagnosis</title> (2002)

With low dose multi-slice CT for screening of lung cancer, physicians are now finding and examining increasingly smaller nodules. However as the size of detectable nodules becomes smaller, there may be greater differences among physicians as to what is detected and what constitutes a nodule. In this study, 10 CT screening studies of smokers were individually evaluated by three thoracic radiologists. After consensus to determine a gold standard, the number of nodules detected by individual radiologists ranged from 1.4 to 2.1 detections per patient. Each radiologist detected nodules missed by the other two. Although a total of 26 true nodules were detected by one or more radiologists, only 8 (31%) were detected by all three radiologists. The number of true nodules detected by an integrated automatic detection algorithm was 3.2 per patient after radiologist validation. Including these nodules in the gold standard set reduced the sensitivity of nodule detection by each radiologist to less than half. The sensitivity of nodule detection by the computer was better at 64%, proving especially efficacious for detecting smaller and more central nodules. Use of the automatic detection module would allow individual radiologists to increase the number of detected nodules by 114% to 207%.
Spatial bias in cAMP generation determines biological responses to PTH type 1 receptor activation (2021)

The parathyroid hormone (PTH) type 1 receptor (PTHR) is a class B G protein–coupled receptor (GPCR) that regulates mineral ion, vitamin D, and bone homeostasis. Activation of the PTHR by PTH induces both transient cell surface and sustained endosomal cAMP production. To address whether the spatial (location) or temporal (duration) dimension of PTHR-induced cAMP encodes distinct biological outcomes, we engineered a biased PTHR ligand (PTH<sup>7d</sup>) that elicits cAMP production at the plasma membrane but not at endosomes. PTH<sup>7d</sup> stabilized a unique active PTHR conformation that mediated sustained cAMP signaling at the plasma membrane due to impaired β-arrestin coupling to the receptor. Experiments in cells and mice revealed that sustained cAMP production by cell surface PTHR failed to mimic the pharmacological effects of sustained endosomal cAMP production on the abundance of the rate-limiting hydroxylase catalyzing the formation of active vitamin D, as well as increases in circulating active vitamin D and Ca<sup>2+</sup> and in bone formation in mice. Thus, similar amounts of cAMP generated by PTHR for similar lengths of time in different cellular locations, plasma membrane and endosomes, mediate distinct physiological responses. These results unveil subcellular signaling location as a means to achieve specificity in PTHR-mediated biological outcomes and raise the prospect of rational drug design based upon spatiotemporal manipulation of GPCR signaling.
Association Between Serum Carnosinase Concentration and Activity and Renal Function Impairment in a Type-2 Diabetes Cohort (2022)

<b>Introduction:</b> Genetic studies have identified associations of carnosinase 1 (CN1) polymorphisms with diabetic kidney disease (DKD). However, CN1 levels and activities have not been assessed as diagnostic or prognostic markers of DKD in cohorts of patients with type 2 diabetes (T2D). <b>Methods:</b> We established high-throughput, automated CN1 activity and concentration assays using robotic systems. Using these methods, we determined baseline serum CN1 levels and activity in a T2D cohort with 970 patients with no or only mild renal impairment. The patients were followed for a mean of 1.2 years. Baseline serum CN1 concentration and activity were assessed as predictors of renal function impairment and incident albuminuria during follow up. <b>Results:</b> CN1 concentration was significantly associated with age, gender and estimated glomerular filtration rate (eGFR) at baseline. CN1 activity was significantly associated with glycated hemoglobin A1c (HbA1c) and eGFR. Serum CN1 at baseline was associated with eGFR decline and predicted renal function impairment and incident albuminuria during the follow-up. <b>Discussion:</b> Baseline serum CN1 levels were associated with presence and progression of renal function decline in a cohort of T2D patients. Confirmation in larger cohorts with longer follow-up observation periods will be required to fully establish CN1 as a biomarker of DKD.
Hole–Mask Colloidal Lithography (2007)

Hole-mask colloidal lithography (HCL) represents a truly versatile and simple bottom-up nanofabrication method based on colloidal self-assembly lithographic patterning. The HCL technique provides an effective means of patterning vast surface areas with diverse functional nanoarchitectures. Examples include arrays of nanodiscs, oriented elliptical nanostructures, (binary) nanodisc pairs, nanocones on extended surfaces and nanodiscs embedded in a surrounding matrix.
ChemInform Abstract: Sulfamic Acid: An Efficient and Recyclable Solid Acid Catalyst for the Synthesis of 4,5‐Dihydropyrrolo[1,2‐a]quinoxalines. (2015)

Abstract Sulfamic acid catalyzed reaction of substrate (I) with aldehydes provides the title compounds in excellent yields.
Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency (2022)

Multiple sulfatase deficiency (MSD) is a rare recessively inherited Mendelian disorder that manifests with developmental delay, neurodegeneration, skeletal deformities, facial dysmorphism, congenital growth retardation, and other clinical signs. The disorder is caused by mutations in the <i>SUMF1</i> gene, which encodes the formylglycine-generating enzyme (FGE), and responsible for the activation of sulfatases. Mutations in <i>SUMF1</i> result in reduced or absent FGE function with consequent compromised activities of its client sulfatases. This leads to an accumulation of enzyme substrates, such as glycosaminoglycans and sulfolipids, within lysosomes and subsequently impaired lysosome function and cellular pathology. Currently, there are no disease modifying therapeutic options for MSD patients, hence the need for more suitable animal models to investigate the disorder. Here, we describe the characterisation of a <i>sumf1</i> null zebrafish model, which has negligible sulfatase activity. Our <i>sumf1</i> <sup>-/-</sup> zebrafish model successfully recapitulates the pathology of MSD such as cranial malformation, altered bone development, an enlarged population of microglia, and growth retardation during early development but lacks early lethality of mouse <i>Sumf1</i> <sup>-/-</sup> models. Notably, we provide evidence of recovery in MSD pathology during later developmental stages, resulting in homozygous mutants that are viable. Hence, our data suggest the possibility of a unique compensatory mechanism that allows the <i>sumf1</i> <sup>-/-</sup> null zebrafish to survive better than human MSD patients and mouse <i>Sumf1</i> <sup>-/-</sup> models.
Domains 1 and 4 of vascular cell adhesion molecule-1 (CD106) both support very late activation antigen-4 (CD49d/CD29)-dependent monocyte transendothelial migration (1995)

We investigated the role of the 6 domain (6D) and 7 domain (7D) forms of human VCAM-1 as counter-receptors for the alpha 4 beta 1 integrin (VLA-4) in monocyte migration induced by C5a. Across Chinese hamster ovary (CHO) cell monolayers transfected with VCAM-6D or VCAM-7D, monocyte migration was not inhibited by treatment of monocytes with mAb to CD18. Addition of mAb to alpha 4 to the CD18 mAb inhibited monocyte migration by 90% across CHO VCAM-6D and CHO VCAM-7D. mAbs to domain 1 (4B9) or domain 4 (GH12) of VCAM-1 each inhibited migration across CHO VCAM-7D partially, when monocytes were also treated with anti-CD18 mAb. When the VCAM-1 mAbs were combined, migration of these monocytes across CHO VCAM-7D was further inhibited to the same degree as with mAbs to alpha 4 plus CD18. IL-1-treated human umbilical vein endothelium (HUVE) supported CD18-independent, VLA-4-mediated monocyte migration to C5a. A mAb to domain 1 of VCAM-1 almost completely inhibited the CD18-independent migration across HUVE activated with IL-1 for 2 h or 20 h, but was less inhibitory when HUVE was treated with IL-1 for 5 h. However, when mAbs to domain 1 and domain 4 were combined, CD18-independent migration was inhibited completely under all conditions tested. These results suggest that either domain 1 or domain 4 of VCAM-1 can mediate VLA-4-dependent monocyte transendothelial migration, that VLA-4 interaction with these two domains can account for all of the VLA-4-mediated migration, and that the expression of VCAM-1 variants on HUVE depends partly on the duration of IL-1 activation.
A complete, multi-level conformational clustering of antibody complementarity-determining regions (2014)

Classification of antibody Complementarity-Determining Region (CDR) conformations is an important step that drives antibody modelling and engineering, prediction from sequence, directed mutagenesis and induced-fit studies, and allows inferences on sequence-to-structure relations. Most of the previous work performed conformational clustering on a reduced set of structures or after application of various structure pre-filtering criteria. In this study, it was judged that a clustering of every available CDR conformation would produce a complete and redundant repertoire, increase the number of sequence examples and allow better decisions on structure validity in the future. In order to cope with the potential increase in data noise, a first-level statistical clustering was performed using structure superposition Root-Mean-Square Deviation (RMSD) as a distance-criterion, coupled with second- and third-level clustering that employed Ramachandran regions for a deeper qualitative classification. The classification of a total of 12712 CDR conformations is thus presented, along with rich annotation and cluster descriptions, and the results are compared to previous major studies. The present repertoire has procured an improved image of our current CDR Knowledge-Base, with a novel nesting of conformational sensitivity and specificity that can serve as a systematic framework for improved prediction from sequence as well as a number of future studies that would aid in knowledge-based antibody engineering such as humanisation.
Contact Electrography &#x2013; A New Electrographic Printing Technology (2001)

In order to improve the quality of text and graphic printers in electrophotographic powder marking technologies, the resolution of the imaging subsystem has been increased and the diameter of toner particles has been decreased. We present a new electrographic printing technology called contact electrography, which has the potential for a high image quality without the need for further improvements in toner particle size or image resolution.Contact electrography works for example with square metal pads on 50 &#x3BC;m centers (500 dpi) fabricated on an insulating layer of a metal cylinder (image cylinder). A write head with a row of electrodes (metal fingers) is in contact with a row of the metal pads of the image cylinder. Voltages are applied to the metal fingers so that the metal pads are charged and an electrostatic latent image is formed during the rotation of the image cylinder. The following steps (development, transfer, fusing, and cleaning) are very similar to conventional electrophotography.Laboratory systems using this technology have been built and tested. These systems have demonstrated the ability to print for the first time, to our knowledge, in any powder marking system based on electrophotography, both black and white single pixels at 500 dpi, using conventional 9 &#x3BC;m diameter toner. The reasons for this improved image quality have been investigated and an explanation for this result is presented.
Supplementary Data Table S4 from Selective Vulnerability to Pyrimidine Starvation in Hematologic Malignancies Revealed by AG-636, a Novel Clinical-Stage Inhibitor of Dihydroorotate Dehydrogenase (2023)

&lt;p&gt;X-ray data collection and refinement statistics for DHODHâ€¢FMNâ€¢OROâ€¢AG-636&lt;/p&gt;
Referencing of markerless CT data sets with cone beam subvolume including registration markers to ease computer‐assisted surgery ‐ A clinical and technical research (2012)

Regarding the advantages of the new method which allows performing CAS by enhancing the initial markerless data set with a marked subvolume gained by cone beam (CBCT) scan, this technique will play a major part in navigation-assisted surgery and will address widespread general methodological solutions that are of great interest in multidisciplinary treatment.
Guided Lithium Deposition by Surface Micro‐Patterning of Lithium‐Metal Electrodes (2018)

Abstract Uncontrolled lithium (Li) deposition has hampered the evolution of Li‐metal electrode‐based Li‐batteries. In this work, we report the differences of a guided Li deposition with a size change of the square hole micro‐patterns carved on the Li‐metal surface with two different dimensions using a simple stamping method. Li deposition is preferentially initiated on the top edge for the smaller pattern and on the bottom for the larger pattern. Although the two patterns lead to a more uniform utilization of the Li, the larger pattern shows a higher cycling stability within a LiFePO 4 /Li cell than that of the smaller one indicating that initiating the Li deposition from the bottom of the hole is more efficient in confining the deposited Li. Based on the impedance analysis of the compressed Li electrodes, we suggest that the guided Li deposition on the bottom of the hole is attributed to a large contrast in the resistance of native surface passivation layer between the top and hole surfaces. This improved understanding can further advance guided Li deposition induced by surface patterns for high performance Li‐metal batteries.
Proof of concept studies for tissue-protective agents in multiple sclerosis (2009)

The next step would be to perform one or more studies of potential tissue-protective agents with these designs in mind, creating the longitudinal data necessary to refine endpoint selection, eligibility criteria, and sample size estimates for future trials.
Decomposition and virtualization of eigenface for face recognition under various lighting conditions (2004)

It is intended in this paper to construct a recognition method that is more robust against changes of lighting conditions than the conventional method. The method applies orthogonal decomposition and virtualization to the eigenface within the framework of the subspace method. The eigenface is derived by applying principal component analysis (eigenvalue decomposition) to the set of face images for each person under various lighting conditions. In the proposed method, the standard face eigenspace (canonical space) is used, and the face image is orthogonally decomposed into the projection component, which is affected mostly by the lighting variation, and the residual component, which contains other aspects of personality and noise. By analyzing the residual component, the noise component in the input image is eliminated. By the above approach, the eigenspace (eigen-projection) containing the standard face information, and the eigenspace (eigen-residual) containing the individuality, are constructed. To the eigen-projection, the concept of the virtual subspace is applied, and the virtual eigen-projection is constructed. With this procedure, stable recognition is realized using the subspace method, even if only a small number of images (as few as one) are registered. © 2004 Wiley Periodicals, Inc. Syst Comp Jpn, 36(1): 25–34, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10638
Pre-mRNA splicing in plants: characterization of Ser/Arg splicing factors. (1996)

The fact that animal introns are not spliced out in plants suggests that recognition of pre-mRNA splice sites differs between the two kingdoms. In plants, little is known about proteins required for splicing, as no plant in vitro splicing system is available. Several essential splicing factors from animals, such as SF2/ASF and SC-35, belong to a family of highly conserved proteins consisting of one or two RNA binding domain(s) (RRM) and a C-terminal Ser/Arg-rich (SR or RS) domain. These animal SR proteins are required for splice site recognition and spliceosome assembly. We have screened for similar proteins in plants by using monoclonal antibodies specific for a phosphoserine epitope of the SR proteins (mAb1O4) or for SF2/ASF. These experiments demonstrate that plants do possess SR proteins, including SF2/ASF-like proteins. Similar to the animal SR proteins, this group of proteins can be isolated by two salt precipitations. However, compared to the animal SR proteins, which are highly conserved in size and number, SR proteins from Arabidopsis, carrot, and tobacco exhibit a complex pattern of intra- and interspecific variants. These plant SR proteins are able to complement inactive HeLa cell cytoplasmic S1OO extracts that are deficient in SR proteins, yielding functional splicing extracts. In addition, plant SR proteins were active in a heterologous alternative splicing assay. Thus, these plant SR proteins are authentic plant splicing factors.
Data from Optimizing Precision Medicine for Breast Cancer Brain Metastases with Functional Drug Response Assessment (2023)

&lt;div&gt;&lt;p&gt;The development of novel therapies for brain metastases is an unmet need. Brain metastases may have unique molecular features that could be explored as therapeutic targets. A better understanding of the drug sensitivity of live cells coupled to molecular analyses will lead to a rational prioritization of therapeutic candidates. We evaluated the molecular profiles of 12 breast cancer brain metastases (BCBM) and matched primary breast tumors to identify potential therapeutic targets. We established six novel patient-derived xenograft (PDX) from BCBM from patients undergoing clinically indicated surgical resection of BCBM and used the PDXs as a drug screening platform to interrogate potential molecular targets. Many of the alterations were conserved in brain metastases compared with the matched primary. We observed differential expressions in the immune-related and metabolism pathways. The PDXs from BCBM captured the potentially targetable molecular alterations in the source brain metastases tumor. The alterations in the PI3K pathway were the most predictive for drug efficacy in the PDXs. The PDXs were also treated with a panel of over 350 drugs and demonstrated high sensitivity to histone deacetylase and proteasome inhibitors. Our study revealed significant differences between the paired BCBM and primary breast tumors with the pathways involved in metabolisms and immune functions. While molecular targeted drug therapy based on genomic profiling of tumors is currently evaluated in clinical trials for patients with brain metastases, a functional precision medicine strategy may complement such an approach by expanding potential therapeutic options, even for BCBM without known targetable molecular alterations.&lt;/p&gt;Significance:&lt;p&gt;Examining genomic alterations and differentially expressed pathways in brain metastases may inform future therapeutic strategies. This study supports genomically-guided therapy for BCBM and further investigation into incorporating real-time functional evaluation will increase confidence in efficacy estimations during drug development and predictive biomarker assessment for BCBM.&lt;/p&gt;&lt;/div&gt;
Improvement of Monte Carlo Code A3MCNP for Large-Scale Shielding Problems (2004)

A3MCNP (Automatic Adjoint Accelerated MCNP) is a revised version of the MCNP Monte Carlo code, that automatically prepares variance reduction parameters for the CADIS (Consistent Adjoint Driven Importance Sampling) methodology. Using a deterministic “importance” (or adjoint) function, CADIS performs source and transport biasing within the weight-window technique. The current version of A3MCNP uses the 3-D Sn transport TORT code to determine a 3-D importance function distribution. Based on simulation of several real-life problems, it is demonstrated that A3MCNP provides precise calculation results with a remarkably short computation time by using the proper and objective variance reduction parameters. However, since the first version of A3MCNP provided only a point source configuration option for large-scale shielding problems, such as spent-fuel transport casks, a large amount of memory may be necessary to store enough points to properly represent the source. Hence, we have developed an improved version of A3MCNP (referred to as A3MCNPV) which has a volumetric source configuration option. This paper describes the successful use of A3MCNPV for a concrete cask streaming problem and a PWR dosimetry problem.