gebhart/patrepeval huggingface dataset:
Targeting proteins for ubiquitination and degradation in the treatment of human disease (2004)

Protein degradation is one of the tactics employed by the cell for irreversibly inactivating proteins. In eukaryotes, ATP-dependent protein degradation in the cytoplasm and nucleus is carried out by the 26S proteasome. Most proteins are targeted to the 26S proteasome by covalent attachment of a multiubiquitin chain. A key component of the enzyme cascade that results in attachment of the multiubiquitin chain to the target or labile protein is the ubiquitin ligase that controls the specificity of the ubiquitination reaction. Defects in ubiquitin-dependent proteolysis have been shown to result in a variety of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders.

The SCF (Skp1-Cullin-F-box-Hrt1) complex is a heteromeric ubiquitin ligase that multiubiquitinates proteins important for signal transduction and cell cycle progression. A technology was developed known as Protac (Proteolysis Targeting Chimeric Molecule), that acts as a bridge, bringing together the SCF ubiquitin ligase with a protein target, resulting in its ubiquitination and degradation. The Protac contains a peptide moiety at one end that is recognized by SCF that is chemically linked to the binding partner or ligand of the target protein. The first demonstration of the efficacy of Protac technology was the successful recruitment, ubiquitination, and degradation of the protein Methionine Aminopeptidase-2 (MetAP-2) through a covalent interaction between MetAP-2 and Protac. Subsequently, we demonstrated that Protacs could effectively ubiquitinate and degrade cancer-promoting proteins (estrogen and androgen receptors) through non-covalent interactions in vitro and in cells. Finally, cell-permeable Protacs can also promote the degradation of proteins in cells. Biologically, this work signifies the amazing versatility and flexibility of the ubiquitin-proteasome system. Technologically, this work represents the development of a novel ?chemical genetics? approach to selectively target proteins for degradation. Practically, this work is ?Proof of Concept? that exploiting the cell?s natural proteolytic machinery is a potential avenue for the treatment of human disease.
The diastereomers of -fluoroglutamate: complementary structural analogues. (1971)

The racemates of the diastereomers of γ-fluoroglutamate have been separated by ion-exchange chromatography, and the relative configuration of the 2 asymmetrical carbon atoms has been established by an unambiguous chemical method. The two diastereomers of L-γ-fluoroglutamate were prepared enzymatically, and both (on their appropriate derivatives) are substrates for the following enzymes: glutamate dehydrogenase (EC 1.4.1.3), glutamine synthetase (EC 6.3.1.2), glutamate decarboxylase (EC 4.1.1.15), carboxypeptidase G(EC 3.4.2.6), and leucine aminopeptidase (EC 3.4.1.1). The reactions of these enzymes and D-glutamate cyclase (EC 4.2.1.54) confirm the tentative assignment of configurations at the α-carbon of γ-fluoroglutamate that was proposed previously. Preliminary kinetic studies with several of these enzymes normally reactive with glutamate indicate that the threo tends to be more reactive than the erythro diastereomer. Possible biological and biochemical applications of these glutamate analogues are discussed.
Radio Frequency Interactions with Air Cargo Container Materials for Real-Time Cold Chain Monitoring (2011)

Transportation is an important part of the supply chain as goods are being transported over thousands of kilometers from their production sites to consumers thanks to increasing globalization. Many perishable items, most of which are temperature sensitive, need to be transported by air due to their short shelf life. Today's regulations do not allow RFID (radio frequency identification) to be utilized inside aircrafts during flight, but the need for real time cold chain management is pushing the air cargo industry to investigate the capabilities of this technology. Since, environmental conditions highly influence the RFID system's outcome, it is mandatory to understand the RF behavior around air cargo materials.
Sensing Acetylcholine and Anticholinesterase Compounds (2014)

Abstract Acetylcholine is a key neurotransmitter, and anticholinesterase agents are essential compounds used as medical drugs, pesticides, and chemical warfare agents. A semisynthetic fluorescence‐based probe for the direct, real‐time detection of acetylcholine and anticholinesterase compounds is introduced. The probe possesses good sensitivity, tunable detection range, and can be selectively targeted to cell surfaces, thereby making it an attractive tool for applications in analytical chemistry and quantitative biology.
Gas Chromatographic Analysis of Gaseous Hydrocarbons with Capillary Column (1964)

毛管を用いたガスクロマトグラフィーによるC1～C4のパラフィン類,モノオレフィン類,ジオレフィン類,アセチレン類および脂環類の炭化水素21成分の分析について研究した。毛管では含まれる固定相の量が少ないので,軽質成分を分離するためには低温で操作することが必要である。炭化水素成分の分配係数への温度効果を知るために,成分の固定相液への溶解熱を計算して比較考察した。マレイン酸ジブチル(DBM)およびβ,β-オキシジプロピオニトリル(ODPN)を固定相液とした場合には,一般に不飽和度の高い炭化水素は溶解熱が高く,アセチレン類がもっとも高い値をもっている。-30℃においてDBM-ODPN混合液を固定相として炭化水素の分離を調べたところ,(a)DBM95wt%-ODPN5wt%,(b)DBM62wt%-ODPN38wt%,(c)DBM37wt%-ODPN63wt%でかなり良好な結果が得られた。すなわち(a),(b)ではC3,C4の全成分にわたってよい分離が得られるが,エチレンおよびエタンは分離できなかった。(c)ではC3,C4はもとより,試料にn-ペンタンおよびイソペンタンが共存しても,他の成分から完全に分離することができ,かつエチレンおよびエタンも不完全であるが分離することが認められた。
ChemInform Abstract: Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Structure, Raman scattering, and transport properties of boron-doped graphite (2001)

Boron-doped highly oriented graphite films (B-HOGF's) with an atomic fraction of boron from 0.4 up to 2.2 at. % have been prepared from well-crystallized, highly oriented graphite. The effect of boron doping on crystal structure has been investigated in terms of texture observation with a field-emission gun-type scanning electron microscope and by measurements of the x-ray diffraction and Raman scattering. The results indicate that in B-HOGF's, boron atoms substituted in the graphite lattice and induced disorder, which caused the Raman bands related to the disorder in graphite layer planes to appear. For each of the B-HOGF's, the temperature dependence of the resistivity in a range 1.8--300 K has been measured. The Hall coefficient and transverse magnetoresistance have also been measured at 3.0 K in a magnetic field range up to 4 T. The Hall coefficient data indicate that each of the B-HOGF's is a mixed crystal of graphite grains with and without boron atoms. The temperature dependence of the resistivity and field dependence of the transverse magnetoresistance for B-HOGF's show a characteristic that is possibly explained by a three-dimensional weak localization theory proposed by Sugihara Hishiyama, and Kaburagi.
Vacuum-ultraviolet laser spectroscopy: Radiative lifetimes of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi>A</mml:mi></mml:mrow><mml:mrow><mml:mn>1</mml:mn><mml:mi>u</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math>states of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Ar</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Kr</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Xe</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>, and dependence on internuclear distance (1988)

Time-resolved fluorescence studies of ${\mathrm{Ar}}_{2}$, ${\mathrm{Kr}}_{2}$, and ${\mathrm{Xe}}_{2}$ formed by supersonic jet expansion and excited by monochromatic, tunable, vacuum-ultraviolet radiation have been used to measure the radiative lifetimes of selected, high vibronic levels of the lowest excimer (${A}_{1u}$) states. For ${\mathrm{Ar}}_{2}$, lifetimes of levels v'=24--30 were found to have an average value of 160\ifmmode\pm\else\textpm\fi{}10 ns; for ${\mathrm{Kr}}_{2}$, levels v'=32--38 had average lifetimes of 56\ifmmode\pm\else\textpm\fi{}5 ns; and for ${\mathrm{Xe}}_{2}$, levels v'=36--43 had average lifetimes of 45\ifmmode\pm\else\textpm\fi{}6 ns. These lifetimes for ${\mathrm{Ar}}_{2}$, ${\mathrm{Kr}}_{2}$, and ${\mathrm{Xe}}_{2}$ differ by factors of approximately 20, 5, and 2, respectively, from values for the v'\ensuremath{\sim}0 levels obtained earlier with high gas pressures and excitation by charged particles or synchrotron radiation. It is shown that these large variations in radiative lifetimes with vibrational level arise from increases in electronic transition moments as internuclear distances increase from equilibrium values to those corresponding to the high vibrational levels. The agreement between all measured lifetimes and calculated values (with spin-orbit coupling included) is well within the accuracy permitted by the presently known spectroscopic constants of ${\mathrm{Ar}}_{2}$, ${\mathrm{Kr}}_{2}$, and ${\mathrm{Xe}}_{2}$.
Prediction of early distant relapses on tamoxifen in early-stage breast cancer (BC): A potential tool for adjuvant aromatase inhibitor (AI) tailoring (2005)

509 Background: The majority of early-stage BC express estrogen receptors (ER) and receive tamoxifen in the adjuvant setting. Yet up to 40% of these patients will relapse on tamoxifen and develop incurable metastatic disease. Recent evidence from three large randomised controlled trials exploring the role of AI in the adjuvant setting shows a benefit from the novel strategy, however the optimal sequence and duration of AI/tamoxifen treatment is unknown. Therefore, it is vital that we learn to identify those women at higher risk of tamoxifen resistance. Our aim was to identify genes that could predict for this subset of women. Methods: We determined the gene expression profiles from 105 tamoxifen-only treated ER positive early stage BC (training set) using Affymetrix U133 A and B chips. Within this group, 30 (29%) patients developed distant recurrence at a median time to relapse of 3.8 years (yrs) and 75 (71%) remained disease free at a median of 5.7 yrs of follow-up. The independent validation set consisted of 64 ER+ tamoxifen only treated BC patients (17 recurrences) from a different institution (Karolinska, Sweden). Results: Cox proportional hazards regression analysis identified 50 genes that were significantly associated with distant relapse on tamoxifen. The probability of selecting these genes by chance was estimated to be p=0.001 after 1000 random permutations. These genes were powerful predictors of clinical outcome in the independent validation set, dividing the cohort into 2 statistically different prognostic groups (p=0.02) in the poor prognostic group (tamoxifen resistant) the median time to distant relapse was 2.4yrs compared with 7yrs in the good prognostic one (tamoxifen sensitive). We are currently validating this signature in another independent dataset (Guys hospital, UK). Conclusions: These results suggest that a group of genes can identify BC patients at risk of early distant relapse on tamoxifen. These patients could be the ideal candidates for upfront AIs, while the others would be considered for sequential tamoxifen/AI. This hypothesis will be tested in an upcoming prospective clinical trial “MINDACT”.
Neural networks for electrical impedance tomography image characterisation (1992)

The Southampton electrical impedance tomography (EIT) system used a Sheffield data acquisition unit and a PC based 'Harlequin' transputer card to reconstruct and display images of the distribution of internal conductivity within the thorax. The system produces real-time images relating to both cardiac and pulmonary function. As a first step towards diagnosis using these images neural nets have been applied to the identification of regions of interest in the EIT images for which some activity with time, such as ventricular ejection, is sought. This paper addresses the use of a back-projection network to identify characteristic regions within the images. The network facilitates the production of automated real-time activity plots by defining their effective extent in the images of specific organs. The application is novel within the medical imaging field as the aim is to use neural networks for real-time image analysis.
Paradoxical Lateralization of Parasagittal Sharp Waves in a Patient with Epilepsia Partialis Continua (1982)

We present a patient with epilepsia partialis continua involving the right leg who demonstrated sharp waves paradoxically distributed over the vertex and right hemisphere. Posterior tibial nerve evoked potentials also showed a similar paradoxical lateralization. We postulate that generators situated on the mesial surface of the left hemisphere projected their activity obliquely, leading to paradoxical lateralization of the recorded electrical activity.
Carbon-13 nuclear magnetic resonance examination of naphthalene derivatives. Assignments and analysis of substituent chemical shifts (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon-13 nuclear magnetic resonance examination of naphthalene derivatives. Assignments and analysis of substituent chemical shiftsWilliam Kitching, Maxwell Bullpitt, David Gartshore, William Adcock, T. C. Khor, David Doddrell, and Ian D. RaeCite this: J. Org. Chem. 1977, 42, 14, 2411–2418Publication Date (Print):July 1, 1977Publication History Published online1 May 2002Published inissue 1 July 1977https://pubs.acs.org/doi/10.1021/jo00434a014https://doi.org/10.1021/jo00434a014research-articleACS PublicationsRequest reuse permissionsArticle Views867Altmetric-Citations72LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Determining chemical compositions by the method of multi-energy radiography (2002)

A theoretical model of multi-energy radiography is proposed and two approaches—“synthesis” and “analysis”—to studying the structure of objects by this method are considered. It is theoretically proved that the atomic numbers of elements and the other parameters of chemical composition of a sample can be restored from the multichannel absorption data. The multi-energy radiography approach and possible generalizations open wide prospects for both basic experimental investigations and nondestructive testing applications.
449 (2013)

Introduction: Statin use following aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. The benefit of acute statin treatment in patients previously treated with statins is unknown. We tested the hypothesis that pre-admission statin use would improve functional outcomes and delayed cerebral ischemic events among patients acutely treated with pravastatin. Methods: We prospectively identified patients with aSAH treated with pravastatin according to our hospital protocol. Functional outcomes were assessed using the modified Ranking scale (mRS) at 14 days, 28 days and 3 months. Delayed cerebral ischemia was assessed using clinical evaluation and cerebral angiography. Results: Patients on statins prior to admission were more likely to have a history of diabetes, hypertension, coronary artery disease and stroke. There was no difference in the percentage of patients with a positive neurologic outcome (mRS 0–3) at 3 months between the pre-admission statin group compared to non-users (56. 3% vs. 72.4%, p = 0.095). In multivariate logistic regression, pre-admission statin use was not predictive or a positive neurologic outcome (relative risk 1.177, 95% CI 0.440–3.146, p = 0.746). Conclusions: Pre-admission statin use was not protective in patients with aSAH. It is likely that acute therapy with pravastatin following aneurysm rupture provides neuroprotective effects.
Numerical analysis of silicon carbide Schottky diodes and power MOSFETs (2002)

A silicon carbide (SiC) device simulator has been developed to exactly evaluate the electrical characteristics of SiC power devices. Avalanche breakdown voltages were predicted based on the ionization integral method for high-resistivity n-type diodes (<1.0*10/sup 16/ cm/sup -3/ donor concentration). The calculated value for concentrations of 2.0*10/sup 15/ cm/sup -3/ was 40% lower than a previous prediction. It was predicted that 4500-V platinum-SiC diodes would have a forward voltage drop of 3.3 V for 100 A/cm/sup 2/ and that 4500-V MOSFETs would have a specific on-resistance of 0.023 Omega -cm/sup 2/. The breakdown voltages of Schottky diodes with low-barrier-height metals such as titanium are determined by large leakage currents and not by avalanche breakdown. The reverse recovery time of a Schottky diode can be less than 10 ns even for the fast switching case.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Mutational analysis of the avian pneumovirus conserved transcriptional gene start sequence identifying critical residues (2005)

Seven of the eight genes in the avian pneumovirus (APV) genome contain a conserved 9 nt transcriptional start sequence with the virus large (L) polymerase gene differing from the consensus at three positions. The sequence requirements of the APV transcriptional gene start sequence were investigated by generating a series of mutations in which each of the nine conserved bases was mutated to each of the other three possible nucleotides in a minigenome containing two reporter genes. The effect of each mutation was assessed by measuring the relative levels of expression from the altered and unaltered gene start sequences. Mutations at positions 2, 7 and 9 significantly reduced transcription levels while alterations to position 5 had little effect. The L gene start sequence directed transcription at levels approximately 50 % below that of the consensus gene start sequence. These data suggest that there are common features in pneumovirus transcriptional control sequences.
Superluminale Eigenschaften von Wellenpaketen (1994)

Abstract In einer ganzen Reihe von Arbeiten wurden in den letzten Jahren superluminale Effekte vorausgesagt und beobachtet. Der Beitrag zeigt, daß die in den verschiedenen Experimenten beobachteten Phänomene nicht dem Kausalitätsprinzip widersprechen. Oft existiert sogar eine anschauliche Begründung, weshalb die „Überlichtgeschwindigkeiten”︁ Scheingeschwindigkeiten darstellen, die sich auf Paare von Raum‐Zeit‐Punkten ohne kausalen Zusammenhang beziehen.
A Model of Binocular Gaze Estimation (2007)

Binocular image-pairs contain information about the three-dimensional structure of the visible scene, which can be recovered by the identification of corresponding points. However, the resulting disparity field also depends on the orientation of the eyes. If it is assumed that the exact eye-positions cannot be obtained from oculomotor feedback, then the gaze parameters must also be recovered from the images, in order to properly interpret the retinal disparity field. Existing models of biological stereopsis have addressed this issue independently of the binocular-correspondence problem. It has been correctly assumed that if the correspondence problem can be solved, then the disparity field can be decomposed into gaze and structure components, as described above. In this work we take a different approach; we emphasize that although the complete point-wise disparity field is sufficient for gaze estimation, it is not in fact necessary. We show that the gaze parameters can be recovered directly from the images, independently of the point-wise correspondences. The relationship between binocular vergence and the resulting epipolar geometry is derived. Our algorithm is then based on the simultaneous representation of all epipolar geometries that are feasible with respect to a fixating oculomotor system. This is done in an essentially two-dimensional space, parameterized by azimuth and viewing-distance. We define a cost function that measures the compatibility of each geometry
Evidence that Low-Level Viremias during Effective Highly Active Antiretroviral Therapy Result from Two Processes: Expression of Archival Virus and Replication of Virus (2005)

Episodes of low-level viremia (LLV), with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels ranging from 50 to 400 copies (c)/ml, occur commonly during highly active antiretroviral therapy (HAART). LLV has been associated with virologic failure of HAART in some studies, while in others LLV did not appear to affect the clinical outcome. To understand the processes leading to LLV, genetic analyses were used to determine whether plasma virions emanated from archived or from newly evolved viral genomes. Episodes of LLV (plasma HIV-1 RNA, 50 to 379 [median, 77] c/ml) were detected in 21/37 (57%) HIV-1-infected children with median plasma HIV-1 RNA levels of <50 c/ml during 79 patient years of HAART. Viral sequences were derived by direct sequencing of PCR products from 21 plasma specimens diluted to end point. In phylogenetic analysis, LLV viral sequences grouped with virus from early in the course of infection in 8/11 subjects. Six specimens had multiple identical viral sequences, suggesting origin from clonally expanded infected cells. LLV plasma virus evolved over time, indicating viral replication, in 3/11 subjects. Two of these had frequent LLV, including the selection of drug-resistant mutants. In summary, plasma virus from episodes of LLV during effective HAART appeared to originate from two distinct processes, (i) clonal outgrowth from long-lived HIV-1-infected cells, presumably following activation and proliferation of these cells, and (ii) ongoing viral replication that included the selection of new drug-resistant mutants. These observations provide a plausible explanation for the divergent clinical outcomes previously associated with LLV.