gebhart/patrepeval huggingface dataset:
A Synthetic Polyphosphoinositide Headgroup Surrogate in Complex with SHIP2 Provides a Rationale for Drug Discovery (2012)

Phosphoinositides regulate many cellular processes, and cellular levels are controlled by kinases and phosphatases. SHIP2 (SH2 (Src homology 2)-domain-containing inositol-phosphatase-2) plays a critical role in phosphoinositide signaling, cleaving the 5-phosphate from phosphatidylinositol 3,4,5-trisphosphate. SHIP2 is thought to be involved in type-2 diabetes and obesity, conditions that could therefore be open to pharmacological modulation of the enzyme. However, rational design of SHIP2 inhibitors has been limited by the absence of a high-resolution structure. Here, we present a 2.1 Å resolution crystal structure of the phosphatase domain of SHIP2 bound to the synthetic ligand biphenyl 2,3',4,5',6-pentakisphosphate (BiPh(2,3',4,5',6)P(5)). BiPh(2,3',4,5',6)P(5) is not a SHIP2 substrate but inhibits Ins(1,3,4,5)P(4) hydrolysis with an IC(50) of 24.8 ± 3.0 μM, (K(m) for Ins(1,3,4,5)P(4) is 215 ± 28 μM). Molecular dynamics simulations suggest that when BiPh(2,3',4,5',6)P(5) binds to SHIP2, a flexible loop folds over and encloses the ligand. Compounds targeting such a closed conformation might therefore deliver SHIP2-specific drugs.
Initial construct cross-cultural validation of the Short Form 36 for quality of life assessment of systemic lupus erythematosus patients in Singapore. (1997)

The objective of this study was to determine if the Short Form 36 (SF-36) Health Survey Questionnaire measures differences in quality of life between lupus patients and healthy controls in Singapore. A cross-sectional pilot study was conducted on consecutive English-speaking, female Chinese lupus patients seen at a Rheumatology unit. Healthy volunteers were recruited as controls during the same time period. All subjects completed the United Kingdom version of the SF-36. Lupus disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index and converted to a global score. Lupus-related damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACRDI). The main outcomes measured were the mean SF-36 scale scores for lupus patients and healthy controls. Thirty-six lupus patients and 76 controls were included in the study. All subjects were English-speaking, Chinese female between 21 and 53 years of age. The mean age of patients and controls was 31.9 and 29.0 years respectively. Lupus patients had lower mean scale scores than controls for physical functioning (73.0 versus 89.7, P < 0.0027), bodily pain (71.0 versus 81.4, P < 0.027), physical role functioning (55.7 versus 89.5, P < 0.0001) and general health (47.4 versus 51.8, P < 0.05). Mean scale scores for vitality, social and emotional role function and mental health were similar in both groups. Ten patients had active disease (BILAG global scores of 3 to 14) and 13 patients had lupus-related damage (Damage Index scores of 1 to 7). These preliminary data suggest that the SF-36 Health Survey may be able to measure differences in quality of life between lupus patients and healthy controls in Singapore.
Cystic fibrosis–related diabetes onset can be predicted using biomarkers measured at birth (2021)

We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.
12.5Gb/s optical driver and receiver ICs with double threshold AGC for SATA Out-of-Band transmission (2015)

In order to realize reliable OOB (Out-of-Band) transmission which is a major problem in optically connected SATA (Serial ATA) or SAS (Serial Attached SCSI), 12.5 Gb/s driver and receiver ICs with a newly-developed double threshold AGC were fabricated by TSMC 90 nm CMOS process. The double threshold AGC realized the rejection of small noise in a transmission line in an idle condition and the suppression of long decay in the end of a burst, and highly reliable optical OOB transmission was achieved. Optically connected SATA 6 Gb/s system operation was demonstrated for the first time in the world.
High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm (2007)

High-speed, high-resolution optical coherence tomography (OCT) imaging of the human retina is demonstrated using a frequency-swept laser at 850 nm. A compact external cavity semiconductor laser design, optimized for swept-source ophthalmic OCT, is described. The laser enables an effective 16 kHz sweep rate with >10 mm coherence length and a tuning range of approximately 35 nm full width at half-maximum, yielding an axial resolution of <7 micro m in tissue.
Identification of Novel HSP90α/β Isoform Selective Inhibitors Using Structure-Based Drug Design. Demonstration of Potential Utility in Treating CNS Disorders such as Huntington’s Disease (2014)

A structure-based drug design strategy was used to optimize a novel benzolactam series of HSP90α/β inhibitors to achieve >1000-fold selectivity versus the HSP90 endoplasmic reticulum and mitochondrial isoforms (GRP94 and TRAP1, respectively). Selective HSP90α/β inhibitors were found to be equipotent to pan-HSP90 inhibitors in promoting the clearance of mutant huntingtin protein (mHtt) in vitro, however with less cellular toxicity. Improved tolerability profiles may enable the use of HSP90α/β selective inhibitors in treating chronic neurodegenerative indications such as Huntington's disease (HD). A potent, selective, orally available HSP90α/β inhibitor was identified (compound 31) that crosses the blood-brain barrier. Compound 31 demonstrated proof of concept by successfully reducing brain Htt levels following oral dosing in rats.
Relationship between charge transfer state electroluminescence and the degradation of organic photovoltaics (2021)

The degradation of archetype organic photovoltaics comprising both vacuum and solution-deposited bulk heterojunction active regions is investigated and quantified using a theory based on detailed balance, which relates the open-circuit voltage to the efficiency of charge transfer state emission. To describe this relationship, we account for the difference between electroluminescent external quantum efficiency and the charge transfer emission efficiency. An empirical factor, m, is introduced to distinguish between nonradiative defect sites both within, m = 1, and outside, m &amp;gt;1, of the photoactive heterojunction. The m-factor is used to determine the primary sources of degradation for archetype solution- and vacuum-processed material systems. We conclude that degradation occurs primarily within the donor–acceptor heterojunction for the vacuum-processed devices (where m = 1.020 ± 0.002) and outside of the photoactive heterojunction for the solution-processed devices studied, both with and without an anode buffer layer (where m = 2.93 ± 0.09 and m = 1.90 ± 0.01, respectively).
Laparoscopic extirpation of renal cell cancer: Feasibility, questions, and concerns (1996)

Laparoscopic nephrectomy for benign disease has become an increasingly popular alternative to open surgery as more urologists gain confidence in their laparoscopic skills. However, the idea of laparoscopic extirpation of renal cell cancer caused significant concerns over the adequacy of surgical resection margins, trocar site seeding, and potential tumor spillage. The present chapter is the result of 5 year's experience with laparoscopic nephrectomy for renal tumor. To date, total and radical nephrectomies have been performed at Washington University in 20 patients; in each case, the appropriate surgical margins were obtained. Moreover, there have been, as yet, no instances of tumor spillage or delayed trocar seeding in our or others' experience. Furthermore, the immediate effectiveness of the procedure equals that of open radical nephrectomy; yet the hospital stay, patient discomfort, and convalescence are all markedly decreased. Only two drawbacks to the laparoscopic approach remain: 1) lengthy operative time, and 2) the increased cost associated with the prolonged operating room time. These problems will only be overcome by increased surgeon experience and further technological advances. Lastly, given the newness of the procedure, follow-up of these patients is still brief; however, results to date substantiate the hypothesis that laparoscopic radical nephrectomy is an effective, minimally invasive, long-term therapy for patients with localized renal cell cancer.
Real Time Vibrational Spectroscopy Using Raman Induced Phase Conjugation In Liquids And Solids (1989)

A real time technique to measure phonon dynamics using the Raman induced phase conjugation technique in combination with streak-camera technology is described. The technique is used to carry out spectral measurements of the third order nonlinear susceptibility and to determine vibrational and optical phonon dephasing kinetics in liquids and solids
Postfilament supercontinuum on 100  m path in air (2021)

Pulses at 744 nm with 90 fs duration, 6 mJ energy, and a weakly divergent wavefront propagate for more than 100 m and generate a filament followed by an unprecedently long high intensity (≥1<i>T</i><i>W</i>/<i>c</i><i>m</i><sup>2</sup>) light channel. Over a 20 m long sub-section of this channel, the pulse energy is transferred continuously to the infrared wing, forming spectral humps that extend up to 850 nm. From 3D+time carrier-resolved simulations of 100 m pulse propagation, we show that spectral humps indicate the formation of a train of femtosecond pulses appearing at a predictable position in the propagation path.
Overexpression of ANAC046 Promotes Suberin Biosynthesis in Roots of Arabidopsis thaliana (2019)

NAC (NAM (no apical meristem), ATAF1/2, and CUC2 (cup-shaped cotyledon)) proteins are one of the largest families of plant-specific transcription factors, and this family is present in a wide range of land plants. Here, we have investigated the role of <i>ANAC046</i> in the regulation of suberin biosynthesis and deposition in <i>Arabidopsis</i>. Subcellular localization and transcriptional activity assays showed that <i>ANAC046</i> localizes in the nucleus, where it functions as a transcription activator. Analysis of the P<sub>ANAC046</sub>:GUS lines revealed that <i>ANAC046</i> is mainly expressed in the root endodermis and periderm, and is also induced in leaves by wounding. The transgenic lines overexpressing <i>ANAC046</i> exhibited defective surfaces on the aerial plant parts compared to the wild-type (WT) as characterized by increased permeability for Toluidine blue stain and greater chlorophyll leaching. Quantitative RT-PCR analysis showed that the expression of suberin biosynthesis genes was significantly higher in the roots and leaves of overexpression lines compared to the WT. The biochemical analysis of leaf cuticular waxes showed that the overexpression lines accumulated 30% more waxes than the WT. Concurrently, overexpression lines also deposited almost twice the amount of suberin content in their roots compared with the WT. Taken together, these results showed that <i>ANAC046</i> is an important transcription factor that promotes suberin biosynthesis in <i>Arabidopsis thaliana</i> roots.
European Microscopy Congress 2016: Proceedings (2016)

Linear crystal defects called dislocations are one of the most fascinating concepts in materials science that govern mechanical and optoelectronic properties of many materials across a broad range of application. Three-dimensional (3-D) study of dislocation network is in principle accessible by conventional tomographic and stereoscopic techniques in Transmission Electron Microscopy (TEM). In these techniques in general the need to tilt the specimen for acquiring image series over large tilt ranges remain however an intricate problem, in particular when diffraction contrast or sensitivity to electron beam are involved. Here, a novel method in scanning TEM (STEM) is presented that provides a reliable and fast assessment of the 3-D configuration of dislocations using data acquired from just one sample tilt. This technique acquires a stereoscopic pair of images by selecting different ray paths of a convergent illumination in STEM mode. The resulting images are then treated with a dedicated stereovision reconstruction algorithm, yielding a full 3-D reconstruction of dislocations arrangement. The success of this method is demonstrated by measurement of dislocation arrangements in two experimental cases.
Review of the application of ionic liquids as solvents for chitin (2012)

Abstract Chitin is one of the most abundant biopolymers, but due to its high crystallinity, it is completely insoluble in most organic and inorganic solvents. Chitin is soluble only in solvents that can destroy intersheet and intrasheet H-bonds, and many of these solvents are toxic, corrosive, nondegradable, or mutagenic. Because of these drawbacks, there is a search for more environmentally friendly solvents for chitin. It has been shown that ionic liquids (ILs) can dissolve chitin at elevated temperatures (80°–110°C) or with application of microwave irradiation. The highest solubility of chitin in an IL was about 20% (1-ethyl-3-methylimidazolium acetate), whereas chitin was shown to be insoluble in 1-allyl-3-methylimidazolium chloride and 1-butyl-3-methylimidazolium formate. Dissolved chitin can be regenerated by mixing with water or methanol, where the polymer precipitates from the solution. X-ray diffraction patterns of native polymer and precipitates have been compared and only small changes in crystallinity have been observed. In addition, Fourier transform infrared spectra remained similar for both forms of chitin, native and regenerated. Presented data hold great promise for the improvement of the chemistry of chitin and open new routes for chemical and enzymatic modifications of this polymer.
Quantitative Measurement of P- and E-Selectin Adhesion Molecules in Acute Pancreatitis (2000)

In AP, the production of inflammatory cytokines precedes up-regulation of P- and E-selectin, whose expression coincided with the increased infiltration of CD18-positive cells and neutrophil sequestration in lung tissue. Temporally, these events correlate with evidence of histologic pulmonary injury and underscore the role of adhesion molecules as mediators of pathophysiologic events. This mechanistic pathway may afford novel therapeutic interventions in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.
Abstract 3847: High-throughput 3D screening reveals differences in drug sensitivities between culture models of JIMT1 breast cancer cells . (2013)

Abstract The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional (2D) monolayers on plastic. However, many cellular features are impaired in these unnatural conditions and big alterations in gene expression in comparison to tumors have been reported. Three-dimensional (3D) cell culture models have become increasingly popular and are suggested to be better models than 2D monolayers due to improved cell-to-cell contacts and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput 3D drug screening method and to compare drug responses in JIMT1 breast cancer cells when grown in 2D, in polyHEMA coated anchorage independent 3D models and in Matrigel on-top 3D cell culture models. We screened 102 compounds with multiple concentrations and biological replicates for their effects on cell proliferation. The cells were either treated immediately upon plating or they were allowed to grow in 3D for four days prior to the drug treatment. Big variations in drug responses were observed between the models indicating that comparisons of culture model influenced drug sensitivities cannot be made based on effects of a single drug. However, we show with the 63 most prominent drugs that, in general, JIMT1 cells grown on Matrigel were significantly more sensitive to drugs than cells grown in 2D cultures, while responses of cells grown in polyHEMA resembled those of 2D. Furthermore, comparison of gene expression profiles of the cell culture models to xenograft tumors indicated that cells cultured in Matrigel and as xenografts most closely resembled each other. In this study we also suggest that 3D cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives for traditional 2D screens towards better comparability to in vivo state. Citation Format: Vesa J. Hongisto, Sandra Nyberg, Vidal Fey, John-Patrick Mpindi, Olli Kallioniemi, Merja Perälä. High-throughput 3D screening reveals differences in drug sensitivities between culture models of JIMT1 breast cancer cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3847. doi:10.1158/1538-7445.AM2013-3847
Elucidation of the Na2/3FePO4 and Li2/3FePO4 Intermediate Superstructure Revealing a Pseudouniform Ordering in 2D (2014)

Based on TEM, synchrotron X-ray diffraction, DFT calculations, and Mössbauer spectroscopy, a unified understanding of the Na and Li intercalation process in FePO4 is proposed. The key to this lies in solving the highly sought-after intermediate A(2/3)FePO4 (A = Na, Li) superstructures that are characterized by alkali ions as well as Fe(II)/Fe(III) charge orderings in a monoclinic three-fold supercell. Formation energies and electrochemical potential calculations confirm that Na(2/3)FePO4 and Li(2/3)FePO4 are stable and metastable, respectively, and that they yield insertion potentials in fair agreement with experimental values. The 2/3 Na(Li) and 1/3 vacancy sublattice of the intermediate phases forms a dense (101)(Pnma) plane in which the atom/vacancy ordering is very similar to that predicted for the most uniform distribution of 1/3 of vacancies in a 2D square lattice. Structural analysis strongly suggests that the key role of this dense plane is to constrain the intercalation in the diffusion channels to operate by cooperative filling of (bc)(Pnma). From a practical point of view, this generalized mechanism highlights the fact that an interesting strategy for obtaining high-rate FePO4 materials would consist in designing grains with an enhanced (101) surface area, thereby offering potential for substantial improvements with respect to the performance of rechargeable Li and Na batteries.
Modulating the optoelectronic properties of hybrid Mo-thiolate thin films (2021)

Hybrid MoS2-based molybdenum thiolate thin films with selected organic motifs are grown using molecular layer deposition (MLD), allowing for tunable optoelectronic film properties. The thin films are deposited at 170 °C using the metal precursor molybdenum hexacarbonyl and one of the three organic precursors: 1,2-ethanedithiol, 1,4-butanedithiol, and 1,4-benzenedithiol. The resulting Mo-ethanethiolate, Mo-butanethiolate, and Mo-benzenethiolate films show saturating growth with a growth per cycle of 1.2, 1.0, and 1.5 Å/cycle, respectively. Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, x-ray absorption spectroscopy, and x-ray diffraction are used to characterize the as-deposited films. Results show that by changing the organic precursor, the film composition as well as the optical and electronic properties can be tuned. The Mo-thiolate films grown with benzenedithiol exhibit the lowest resistivity, which at 12 mΩ cm is ∼400 times more conductive than Mo-thiolates grown with aliphatic organic linkers. All three backbone chemistries of the Mo-thiolates show an optical bandgap between 2.3 and 2.4 eV and mild photoconductivity response. The MLD of these Mo-thiolate films demonstrates the synthesis of transition metal-organosulfur thin films with tunable properties.
Generation of CEP-stable 2-cycle 0.65-mJ infrared pulses by OPCPA (2008)

We report the latest development of an OPCPA system, generating carrier-envelope-phase-stable 650-muJ 15-fs pulses around 2.1 mum. A novel seed-spectral-shaping method is used to resolve the non-trivial problem of ascertaining the true amplified signal energy.
Fully automatic cross-associations (2004)

Large, sparse binary matrices arise in numerous data mining applications, such as the analysis of market baskets, web graphs, social networks, co-citations, as well as information retrieval, collaborative filtering, sparse matrix reordering, etc. Virtually all popular methods for the analysis of such matrices---e.g., k-means clustering, METIS graph partitioning, SVD/PCA and frequent itemset mining---require the user to specify various parameters, such as the number of clusters, number of principal components, number of partitions, and "support." Choosing suitable values for such parameters is a challenging problem.Cross-association is a joint decomposition of a binary matrix into disjoint row and column groups such that the rectangular intersections of groups are homogeneous. Starting from first principles, we furnish a clear, information-theoretic criterion to choose a good cross-association as well as its parameters, namely, the number of row and column groups. We provide scalable algorithms to approach the optimal. Our algorithm is parameter-free, and requires no user intervention. In practice it scales linearly with the problem size, and is thus applicable to very large matrices. Finally, we present experiments on multiple synthetic and real-life datasets, where our method gives high-quality, intuitive results.
Oxidative Addition of Aryl Sulfonates to Palladium(0) Complexes of Mono- and Bidentate Phosphines. Mild Addition of Aryl Tosylates and the Effects of Anions on Rate and Mechanism (2003)

Oxidative additions of aryl halides to palladium complexes have been studied extensively in recent years, but studies on the oxidative addition of aryl sulfonates to palladium complexes are less common. Here, oxidative additions of aryl triflates to palladium(0) complexes of hindered mono- and bis(phosphines) and the rare oxidative addition of aryl tosylates to palladium(0) complexes of hindered bis(phosphines) are reported. Pd[P(o-tolyl)3]2 reacted with PhOTf in the presence of added halide salts to produce the corresponding {Pd[P(o-tolyl)3](Ar)(μ-X)}2 complexes (X = halide). The rate of oxidative addition was accelerated by the addition of coordinating anions but was not affected by the addition of weakly coordinating anions. This result suggests that the oxidative addition of aryl triflates occurs to an anionic palladium complex ligated by halide. The addition of phenyl triflate to Pd(PPF-t-Bu)[P(o-tolyl)3] in the presence of added bromide produced [(PPF-t-Bu)Pd(Ph)(Br)]. The rate of this oxidative addition was accelerated by added bromide but was more greatly accelerated by the addition of PF6-, a typically noncoordinating anion. This result indicates that a medium effect, not coordination of bromide prior to oxidative addition, accounts for the acceleration of the rate of addition of aryl triflates to Pd(PPF-t-Bu)[P(o-tolyl)3]. The oxidative addition of phenyl tosylate to Pd(PPF-t-Bu)[P(o-tolyl)3] and to Pd(CyPF-t-Bu)[P(o-tolyl)3] also occurred at room temperature to produce the corresponding phenylpalladium tosylate complexes. In the presence of added bromide, arylpalladium bromide complexes were formed. Like the addition of phenyl triflate to Pd(PPF-t-Bu)[P(o-tolyl)3], the rate of oxidative addition was accelerated by addition of either strongly or weakly coordinating anions. The additions of aryl tosylates were also faster in more polar solvents. Thus, the effect of halide on the rate of addition of aryl tosylates to Pd(PPF-t-Bu)[P(o-tolyl)3] is also more likely to result from a medium effect, rather than from coordination of anion to palladium prior to oxidative addition.