gebhart/patrepeval huggingface dataset:
The KGBR viewpoint–lighting ambiguity (2003)

We address the visual ambiguities that arise in estimating object and scene structure from a set of images when the viewpoint and lighting are unknown. We obtain a novel viewpoint-lighting ambiguity called the KGBR that corresponds to a group of three-dimensional affine transformations on the object or scene geometry combined with transformations on the object or scene albedo. Our analysis assumes orthographic projection with an affine camera model. We include photometric cues, such as shadowing and shading, that we model using Lambertian reflectance functions with shadows (cast and attached) and multiple light sources (but no interreflections). We relate the KGBR to affine ambiguities in estimating shape and to the generalized bas-relief (GBR) ambiguity.
Jewish religion and risk of breast cancer (1996)

These results are consistent with data suggesting that certain groups of Jewish women have a higher than expected rate of mutation in the breast-cancer gene BRCA1.
Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site (2018)

During protein synthesis, ribosomes discriminate chirality of amino acids and prevent incorporation of D-amino acids into nascent proteins by slowing down the rate of peptide bond formation. Despite this phenomenon being known for nearly forty years, no structures have ever been reported that would explain the poor reactivity of D-amino acids. Here we report a 3.7Å-resolution crystal structure of a bacterial ribosome in complex with a D-aminoacyl-tRNA analog bound to the A site. Although at this resolution we could not observe individual chemical groups, we could unambiguously define the positions of the D-amino acid side chain and the amino group based on chemical restraints. The structure reveals that similarly to L-amino acids, the D-amino acid binds the ribosome by inserting its side chain into the ribosomal A-site cleft. This binding mode does not allow optimal nucleophilic attack of the peptidyl-tRNA by the reactive α-amino group of a D-amino acid. Also, our structure suggests that the D-amino acid cannot participate in hydrogen-bonding with the P-site tRNA that is required for the efficient proton transfer during peptide bond formation. Overall, our work provides the first mechanistic insight into the ancient mechanism that helps living cells ensure the stereochemistry of protein synthesis.
Data from Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice.&lt;/p&gt;Experimental Design:&lt;p&gt;This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected.&lt;/p&gt;Results:&lt;p&gt;The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated &lt;i&gt;IGHV&lt;/i&gt;, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose.&lt;/p&gt;Conclusions:&lt;p&gt;These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.&lt;/p&gt;&lt;/div&gt;
Characterization of Multiblock Copolymers by Chromatographic Techniques (2011)

Multiblock copolymers (MBC) composed of blocks of poly(1,4-dioxanone) (PPDO) and poly(e-caprolactone) (PCL) were investigated in order to gain information on the extend of chemical heterogeneity of the samples. A gradient chromatographic method was established allowing separation of purely PPDO- from purely PCL-containing chains. Application of the gradient to MBC made of PPDO- and PCL-diols connected by trimethylhexamethylene diisocyanate (TMDI) resulted in two well separated peaks which were analyzed by means of FTIR, 1H-NMR and pyrolysis GC-MS. It was shown that the first peak was composed to a large extent of PPDO and only lower amounts of PCL were incorporated. Conversely, the second peak consisted predominantly of PCL with only a minor fraction of PPDO. Thus, the MBCs having PPDO and PCL segments show an unexpected broad chemical heterogeneity.
Homogeneous and Heterogeneous Polymerization ofɛ-Caprolactone by Neodymium Alkoxides Prepared In Situ (2001)

The synthesis of lanthanide(III) alkoxides has been described as a series of reactions for which the control of product purity is difficult. The possibility of using amide complexes, in the presence of alcohol, to produce alkoxides was investigated in homogeneous and heterogeneous media. The polymerization of ε-caprolactone with alkoxides formed in situ was performed with and without excess alcohol. The latter system was efficient since the polymers were obtained in a short time period, with a well-controlled molecular weight and low polydispersity. The alcohol functionalized all the polymer chains.
Treating viral hepatitis C: efficacy, side effects, and complications (2006)

The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. However, the current standard therapy--pegylated interferon alpha and ribavirin--has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.
Keystone Symposium on Multiple Sclerosis (2009)

The First Keystone Symposium on Multiple Sclerosis, sponsored by the National Multiple Sclerosis Society, was held in Santa Fe, New Mexico, USA. This meeting brought together scientists and physicians studying the genetics, epidemiology, immunology and neurobiology of multiple sclerosis for a 5-day conference consisting of 28 lectures from world-renowned experts in the field, 23 short talks summarizing experimental data and three poster sessions.
Creation of Novel Cores for β-Secretase (BACE-1) Inhibitors: A Multiparameter Lead Generation Strategy (2014)

In order to find optimal core structures as starting points for lead optimization, a multiparameter lead generation workflow was designed with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. De novo design of core fragments was connected with three predictive in silico models addressing target affinity, permeability, and hERG activity, in order to guide synthesis. Taking advantage of an additive SAR, the prioritized cores were decorated with a few, well-characterized substituents from known BACE-1 inhibitors in order to allow for core-to-core comparisons. Prediction methods and analyses of how physicochemical properties of the core structures correlate to in vitro data are described. The syntheses and in vitro data of the test compounds are reported in a separate paper by Ginman et al. [J. Med. Chem. 2013, 56, 4181-4205]. The affinity predictions are described in detail by Roos et al. [J. Chem. Inf. 2014, DOI: 10.1021/ci400374z].
Needle stylet with integrated optical fibers for spectroscopic contrast during peripheral nerve blocks (2011)

The effectiveness of peripheral nerve blocks is highly dependent on the accuracy at which the needle tip is navigated to the target injection site. Even when electrical stimulation is utilized in combination with ultrasound guidance, determining the proximity of the needle tip to the target region close to the nerve can be challenging. Optical reflectance spectroscopy could provide additional information about tissues that is complementary to these navigation methods. We demonstrate a novel needle stylet for acquiring spectra from tissue at the tip of a commercial 20-gauge needle. The stylet has integrated optical fibers that deliver broadband light to tissue and receive scattered light. Two spectrometers resolve the light that is received from tissue across the wavelength range of 500-1600 nm. In our pilot study, measurements are acquired from a postmortem dissection of the brachial plexus of a swine. Clear differences are observed between spectra acquired from nerves and those acquired from adjacent tissue structures. We conclude that spectra acquired with the stylet have the potential to increase the accuracy with which peripheral nerve blocks are performed.
The Effects of Hydroxyl Radical Attack on Dopa, Dopamine, 6‐Hydroxydopa, and 6‐Hydroxydopamine (1995)

High pressure liquid chromatography with electrochemical detection (HPLC-ED) was employed in conjugation with a sensitive and specific salicylate hydroxylation assay to evaluate the immediate effects of hydroxyl radical (.OH) attack on four catechol intermediates of eumelanin, dopamine (3,4-dihydroxyphenylethylamine), its precursor dopa (3,4-dihydroxyphenylalanine), and their respective neurotoxic trihydroxyphenyl derivatives, 6-hydroxydopamine (2,4,5-trihydroxyphenylethylamine,6-OHDA) and 6-hydroxydopa(2,4,5-trihydroxyphenylalanine, TOPA). Semiquinone and quinone species were identified as the initial products of the oxidation of these four catechol substrates. The enhanced oxidations of the catechols when exposed to .OH attack was accompanied by marked decreases in the level of each semiquinone species. Quinone levels were elevated in reactions involving .OH attack on dopamine and 6-OHDA, but absent in reactions involving radical attack on dopa or TOPA, suggesting that dopaquinone (DOQ) and TOPA p-quinone (TOPA p-Q) are oxidized more rapidly by .OH than are the quinones of dopamine and 6-OHDA. The formation of 6-OHDA p-quinone (6-OHDA p-Q) in incubations involving DA and .OH suggest that the .OH-mediated hydroxylation of DA may be a mechanism for generating this potentially cytotoxic trihydroxyphenyl. The results of this study demonstrate for the first time that semiquinone and quinone intermediates of eumelanin are the initial products derived from the .OH-mediated oxidations of dopa, DA, TOPA, and 6-OHDA. These observations suggest that if .OH is generated beyond the capabilities of cytoprotective mechanisms, the radical can rapidly oxidize catechol precursors, augment melanogenesis, and generate additional cytotoxic quinoid intermediates of eumelanin.
Manganese-Porphyrin-Catalyzed C-H Fluorination: Hydrocarbons, But Not Drugs? (2022)

Transformation of C-H to C-F bonds in organic compounds can be used in drug design to easily diversify molecular series under exploration. A particularly attractive fluorination reaction is the recently discovered aliphatic C-H bonds fluorination catalyzed by manganese(Mn)-containing porphyrins, which proceeds under mild conditions and with high yields. However, this fluorination technique has been applied so far only to a narrow range of carbon rich organic substrates. In this preliminary study, based on quantum chemical modeling of several key stages in the presumed mechanism of this reaction, we put forward a hypothesis to explain difficulties of extending the Mn-porphyrin-catalyzed fluorination to nitrogen rich drug-like molecules, namely, a significant growth of the height of the activation barrier for drug-like substrates. Specifically, we demonstrate that reaction energies are comparable for various substrates, including those for which Mn-porphyrin-catalyzed fluorination occurs and those for which it does not occur, and hence, thermodynamic factors are unlikely to control the observed differences in the reactivity. Next, we carry out a first-pass modeling of fluorination reaction paths for two substrates, cyclohexane versus piperidine, as a representative of the type of nitrogen rich compound that can and cannot be fluorinated under recommended conditions, and found a significant difference in activation energies (~7 kcal/mol vs ~40 kcal/mol), which might point at the reason for the difference in the reactivity. Further computational modeling is required to reveal the limitations of the Mn-porphyrin-catalyzed fluorination, and, if possible, possible ways to overcome such limitations.
Truncated D-Optimal Designs for Screening Experiments (2008)

SYNOPTIC ABSTRACTD-optimal designs have proved useful in analyzing common factorial experiments involving multilevel categorical factors. When analyzed by ANOVA, they allow the estimation of coefficients in a regression equation and the contributions to the variance by the main effects and interactions. If the measurement of contribution to variance is necessary but the estimation of all interaction coefficients in the regression equation is not, it is possible to reduce the number of experimental runs below a minimum D-optimal design, using what we call truncated D-optimal screening designs. D-efficiency calculations are not available due to the singularity of the design matrix; another method must be used to pare down the matrix while maintaining reasonable estimation of the original full factorial data. Covering arrays are adapted to guide this reduction. Combining properties of D-optimal designs and covering arrays produces designs that perform well at estimating full factorial results. A method is then developed to target specific interactions prior to the design of the experiment when process specific knowledge is available to indicate which interactions are least important.
Adaptive synchronization for non-coherent UWB receivers (2004)

Ultra-wideband (UWB) radio transmits data using sub-nanosecond pulses with a very low duty-cycle. It is a promising candidate for short-range communications in dense multipath environments. However, UWB systems have to cope with great design challenges, including difficulties on synchronization, template signal design, and multipath energy combining. The UWB differential scheme with a non-coherent receiver offers a way to solve these problems, but may experience performance degradation due to inadequate synchronization knowledge. In this paper a novel adaptive synchronization algorithm for UWB non-coherent receivers is proposed, which adaptively improves on partial synchronization information until frame-level synchronization is achieved. The algorithm requires only tens of symbol durations, which is orders of magnitude less than that of the coherent receiver. Performance enhancement is observed through both theoretical analysis and simulations.
The Early Information Society: Information Management in Britain before the Computer (2007)

Contents: Preface Part I Overview: The information society before the computer, Alistair Black and Dave Muddiman. Part II Infrastructure, Networks and the State: Science, industry and the state: scientific and technical information in early 20th-century Britain, Dave Muddiman The history and development of ASLIB, 1924-1960, Dave Muddiman. Part III The Management of Information in the Early Information Economy: A pre-history of the learning organisation: information and knowledge management before the digital age, Alistair Black Enterprise and intelligence: the early company library in context, Alistair Black. Part IV The Information Workforce: Education for the early information professions in Britain, c1918-1961, Helen Plant Women's employment in industrial libraries and information bureaux in Britain c1918-1960, Helen Plant. Part V Conclusion: Reconsidering the chronology of the information age, Alistair Black and Dave Muddiman Appendices Bibliography Index.
Lineage‐specific evolution and gene flow in <scp> <i>Listeria monocytogenes</i> </scp> are independent of bacteriophages (2020)

Listeria monocytogenes is a foodborne pathogen causing systemic infection with high mortality. To allow efficient tracking of outbreaks a clear definition of the genomic signature of a cluster of related isolates is required, but lineage-specific characteristics call for a more detailed understanding of evolution. In our work, we used core genome MLST (cgMLST) to identify new outbreaks combined to core genome SNP analysis to characterize the population structure and gene flow between lineages. Whilst analysing differences between the four lineages of L. monocytogenes we have detected differences in the recombination rate, and interestingly also divergence in the SNP differences between sub-lineages. In addition, the exchange of core genome variation between the lineages exhibited a distinct pattern, with lineage III being the best donor for horizontal gene transfer. Whilst attempting to link bacteriophage-mediated transduction to observed gene transfer, we found an inverse correlation between phage presence in a lineage and the extent of recombination. Irrespective of the profound differences in recombination rates observed between sub-lineages and lineages, we found that the previously proposed cut-off of 10 allelic differences in cgMLST can be still considered valid for the definition of a foodborne outbreak cluster of L. monocytogenes.
Development of a Highly Accurate Person Tracking System for Home Service Robots (2023)

In this paper, we propose a highly accurate specific person tracking system for home service robots. This study focuses on Selected Online Ada-Boosting (SOAB) and Kernelized Correlation Filters (KCF). It proposes the Selected KCF (SKCF), which combines features of fast adaptation to a specific person and robustness for occlusion. We also propose a system that combines You Only Look Once (YOLO), a real-time object detection algorithm, with SKCF to initialize and recover the tracking system. The proposed system runs at 17 [fps] in an experimental environment with an Intel Core i7-8700K CPU and an NVIDIA GTX 1080 GPU. We also show that the tracking accuracy of the proposed system on public datasets for tracking specific persons is better than that of conventional methods.
NOS2polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: contribution to the transcriptional activity (2006)

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. One of several complications of SSc, pulmonary arterial hypertension (PAH) can be refractory to treatment, both novel and established. In the present study we investigated the ratio of circulating nitric oxide to endothelin-1 in patients with both SSc and PAH, and determined whether polymorphisms in NOS2 (the nitric oxide synthase 2 gene) are associated with susceptibility to PAH. Endothelin-1 in plasma and nitric oxide metabolites (nitrate and nitrite) in serum were measured. The nitric oxide/endothelin-1 ratio was significantly lower in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. We confirmed the presence of two single nucleotide polymorphisms at positions -1,026 and -277 and a pentanucleotide repeat (CCTTT) at -2.5 kilobases. There were significant differences in single nucleotide polymorphisms between patients with SSc who had PAH and those who did not, and between patients with both SSc and PAH and healthy control individuals. The CCTTT repeat was significantly shorter in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. Transcriptional activity were analyzed using the luciferase reporter assay. The transcriptional activity of NOS2 was much greater in fibroblasts transfected by a vector with a long allele of the CCTTT repeat than in those transfected by a vector with a short allele. Polymorphisms in the NOS2 gene are associated with transcriptional activity of the NOS2 gene and with susceptibility to SSc-related PAH.
The electrical characteristics of a conical horn-reflector antenna employing a corrugated horn (1993)

The electrical properties of a conical horn-reflector antenna of 2-3 degrees beamwidth have been investigated over the frequency range of 12-18 GHz. It is shown that the employment of a corrugated horn reduces the characteristic spillover side lobe of the conical horn-reflector antenna by 15 dB and yields excellent main beam circularity over the full Ku band. This results from the taper of the field amplitude toward the edges of the horn aperture in both the E-plane and the H-plane illumination. The performance of the antenna makes it suitable for use in closely packed interferometers for radio astronomy.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling (2013)

NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis of immune disorders and cancer. Its regulation involves a variety of steps, including the controlled degradation of inhibitory IκB proteins. In addition, the inactivation of DNA-bound NF-κB is essential for its regulation. This step requires a factor known as copper metabolism Murr1 domain-containing 1 (COMMD1), the prototype member of a conserved gene family. While COMMD proteins have been linked to the ubiquitination pathway, little else is known about other family members. Here we demonstrate that all COMMD proteins bind to CCDC22, a factor recently implicated in X-linked intellectual disability (XLID). We showed that an XLID-associated CCDC22 mutation decreased CCDC22 protein expression and impaired its binding to COMMD proteins. Moreover, some affected individuals displayed ectodermal dysplasia, a congenital condition that can result from developmental NF-κB blockade. Indeed, patient-derived cells demonstrated impaired NF-κB activation due to decreased IκB ubiquitination and degradation. In addition, we found that COMMD8 acted in conjunction with CCDC22 to direct the degradation of IκB proteins. Taken together, our results indicate that CCDC22 participates in NF-κB activation and that its deficiency leads to decreased IκB turnover in humans, highlighting an important regulatory component of this pathway.
Measuring Activity of Old People in Residential Care (1980)

A handbook was written to instruct researchers and health and social services staff how to carry out sensitive yet quick, simple, and inexpensive measures of engagement in activity by old people in residential care. The handbook was tested experimentally to demonstrate that researchers and staff could observe engagement reliably, using only the written instructions. High levels of the interobserver agreement were attained by subjects with little or no previous experience in direct observation, showing that the handbook was sufficient for training researchers and staff in the use of the measure. Some limitations of the handbook are discussed.