gebhart/patrepeval huggingface dataset:
Steady-state fluorescence and time-resolved fluorescence monitor changes in tryptophan environment in arginase from Saccharomyces cerevisiae upon removal of catalytic and structural metal ions (1990)

Yeast arginase is a trimeric protein of identical subunits, each containing three tryptophans. Time-resolved fluorescence and steady-state fluorescence were employed to monitor the effects of removing the weakly bound catalytic Mn2+ as well as the tightly bound structural Zn2+/Mn2+. Resolution of the total native emission spectrum into decay-associated spectra (DAS) yielded components with lifetimes of 0.1, 1.2, and 4.0 ns. Upon removal of the catalytic metal, the intensities increased approximately 20% while the lifetimes increased less than 10%, and the DAS were unchanged except in intensity. The two major components are well resolved, but the 0.1-ns term is small and dominated by scattered excitation. In contrast, removal of the structural metal increased decay times to 0.2, 1.8, and 5.3 ns. More important, both native DAS red-shifted and became indistinguishable. These data suggest that removal of the catalytic metal does little to change the microenvironments of the individual tryptophans while removal of the structural metal causes partial unfolding of the protein. The excitation spectra for the active and inactive trimers were resolved into their excitation DAS (IEDAS), suggesting ground-state heterogeneity of the fluorescent species. In contrast, the excitation spectra of arginase without the structural metal could not be resolved due to the indistinguishable DAS. The tryptophans are quenched by acrylamide but not by cesium or iodide. Global analysis of the acrylamide quenching data resulted in two quenching decay-associated spectra (QDAS) which correlated well with the DAS. Since the apoenzyme does not exhibit tryptophan accessibility to either positive or negative ionic quenchers, one must assume that the "unfolded" monomeric protein retains considerable tertiary structure.
β-Lactams: A New Class of Conformationally-Rigid Inhibitors of γ-Aminobutyric Acid Aminotransferase (1992)

A structural similarity of several monobactams (2-4), 3-aminonocardicinic acid (6), 6-aminopenicillanic acid (7), 7-aminocephalosporanic acid (8), and 7-aminodesacetoxycephalosporanic acids (9, 10) to gamma-aminobutyric acid (GABA) and to known inhibitors and substrates of GABA aminotransferase is described. Because of this, the above-mentioned compounds were tested as competitive inhibitors and as inactivators of pig brain GABA aminotransferase. All of the compounds were competitive inhibitors of GABA aminotransferase. On the basis of the inhibitory potency of these conformationally-rigid GABA analogues it is hypothesized that GABA is bound at the active site with its amino and carboxylate groups in a syn orientation. None of the compounds inactivates GABA aminotransferase. These beta-lactam analogues represent the first examples of a new class of inhibitors of GABA aminotransferase.
Antibacterial and antifungal LDPE films for active packaging (2014)

Active antimicrobial packaging is a promising form of active packaging that can kill or inhibit microorganism growth in order to maintain product quality and safety. One of the most common approaches is based on the release of volatile antimicrobial agents from the packaging material such as essential oils. Due to their highly volatile nature, the challenge is to preserve the essential oils during the high‐temperature melt processing of the polymer, while maintaining high antimicrobial activity for a desired shelf life. This study suggests a new approach in order to achieve this goal. Antimicrobial active films are developed based on low‐density polyethylene (LDPE), organo‐modified montmorillonite clays (MMT) and carvacrol (used as an essential oil model). In order to minimize carvacrol loss throughout the polymer compounding, a pre‐compounding step is developed in which clay/carvacrol hybrids are produced. The hybrids exhibit a significant increase in the d‐spacing of clay and enhanced thermal stability. The resulting LDPE/(clay/carvacrol) films exhibit superior and prolonged antibacterial activity against Escherichia coli and Listeria innocua , while polymer compounded with pure carvacrol loses the antibacterial properties within days. The films also present an excellent antifungal activity against Alternaria alternata , used as a model plant pathogenic fungus. Furthermore, infrared spectroscopy analysis of the LDPE/(clay/carvacrol) system displayed significantly higher carvacrol content in the film as well as a slower out‐diffusion of the carvacrol molecules in comparison to LDPE/carvacrol films. Thus, these new films have a high potential for antimicrobial food packaging applications due to their long‐lasting and broad‐spectrum antimicrobial efficacy. Copyright © 2014 John Wiley &amp; Sons, Ltd.
Data from Maytansine and Cellular Metabolites of Antibody-Maytansinoid Conjugates Strongly Suppress Microtubule Dynamics by Binding to Microtubules (2023)

&lt;div&gt;Abstract&lt;p&gt;Maytansine is a potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at subnanomolar concentrations. However, its side effects and lack of tumor specificity have prevented successful clinical use. Recently, antibody-conjugated maytansine derivatives have been developed to overcome these drawbacks. Several conjugates show promising early clinical results. We evaluated the effects on microtubule polymerization and dynamic instability of maytansine and two cellular metabolites (&lt;i&gt;S&lt;/i&gt;-methyl-DM1 and &lt;i&gt;S&lt;/i&gt;-methyl-DM4) of antibody-maytansinoid conjugates that are potent in cells at picomolar levels and that are active in tumor-bearing mice. Although &lt;i&gt;S&lt;/i&gt;-methyl-DM1 and &lt;i&gt;S&lt;/i&gt;-methyl-DM4 inhibited polymerization more weakly than maytansine, at 100 nmol/L they suppressed dynamic instability more strongly than maytansine (by 84% and 73%, respectively, compared with 45% for maytansine). However, unlike maytansine, &lt;i&gt;S&lt;/i&gt;-methyl-DM1 and &lt;i&gt;S&lt;/i&gt;-methyl-DM4 induced tubulin aggregates detectable by electron microscopy at concentrations ≥2 μmol/L, with &lt;i&gt;S&lt;/i&gt;-methyl-DM4 showing more extensive aggregate formation than &lt;i&gt;S&lt;/i&gt;-methyl-DM1. Both maytansine and &lt;i&gt;S&lt;/i&gt;-methyl-DM1 bound to tubulin with similar &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;D&lt;/sub&gt; values (0.86 ± 0.2 and 0.93 ± 0.2 μmol/L, respectively). Tritiated &lt;i&gt;S&lt;/i&gt;-methyl-DM1 bound to 37 high-affinity sites per microtubule (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;D&lt;/sub&gt;, 0.1 ± 0.05 μmol/L). Thus, &lt;i&gt;S&lt;/i&gt;-methyl-DM1 binds to high-affinity sites on microtubules 20-fold more strongly than vinblastine. The high-affinity binding is likely at microtubule ends and is responsible for suppression of microtubule dynamic instability. Also, at higher concentrations, &lt;i&gt;S&lt;/i&gt;-methyl-DM1 showed low-affinity binding either to a larger number of sites on microtubules or to sedimentable tubulin aggregates. Overall, the maytansine derivatives that result from cellular metabolism of the antibody conjugates are themselves potent microtubule poisons, interacting with microtubules as effectively as or more effectively than the parent molecule. Mol Cancer Ther; 9(10); 2689–99. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;
ChemInform Abstract: A Dioxane Template for Highly Selective Epoxy Alcohol Cyclizations. (2013)

Abstract This is presented with a view to preparing ladder polyether compounds.
Investigations into the Effects of Thermal and Compositional Stratification on HCCI Combustion – Part II: Optical Engine Results (2009)

&lt;div class="htmlview paragraph"&gt;The effect that thermally and compositionally stratified flowfields have on the spatial progression of iso-octane-fueled homogeneous charge compression ignition (HCCI) combustion were directly observed using highspeed chemiluminescence imaging. The stratified in-cylinder conditions were produced by independently feeding the intake valves of a four-valve engine with thermally and compositionally different mixtures of air, vaporized fuel, and argon.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Results obtained under homogeneous conditions, acquired for comparison to stratified operation, showed a small natural progression of the combustion from the intake side to the exhaust side of the engine, a presumed result of natural thermal stratification created from heat transfer between the in-cylinder gases and the cylinder walls. Large differences in the spatial progression of the HCCI combustion were observed under stratified operating conditions. Qualitative observations of the manner in which the combustion proceeded indicated that ±20 °C temperature stratification, ±15% fuel concentration stratification, and ±5 air-fuel ratio stratification all similarly affected the combustion progression, with the combustion proceeding, in general, from high to low temperature, high to low fuel concentration, or high to low air-fuel ratio. Concurrent and opposite stratification of these parameters were often present and mitigated the effects that the stratified flowfields had on the manner in which the combustion progressed spatially.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The possibility of using the thermal and compositional stratification studied herein for HCCI combustion control was evaluated in a hypothetical recompression-type engine. The magnitude of stratification that could be maintained until combustion commenced was estimated to be small, and competing effects were often present, likely limiting the effects the stratification could have on the combustion.&lt;/div&gt;
Leveraging Semi-Supervised Learning in Video Sequences for Urban Scene Segmentation. (2020)

Supervised learning in large discriminative models is a mainstay for modern computer vision. Such an approach necessitates investing in large-scale human-annotated datasets for achieving state-of-the-art results. In turn, the efficacy of supervised learning may be limited by the size of the human annotated dataset. This limitation is particularly notable for image segmentation tasks, where the expense of human annotation is especially large, yet large amounts of unlabeled data may exist. In this work, we ask if we may leverage semi-supervised learning in unlabeled video sequences and extra images to improve the performance on urban scene segmentation, simultaneously tackling semantic, instance, and panoptic segmentation. The goal of this work is to avoid the construction of sophisticated, learned architectures specific to label propagation (e.g., patch matching and optical flow). Instead, we simply predict pseudo-labels for the unlabeled data and train subsequent models with both human-annotated and pseudo-labeled data. The procedure is iterated for several times. As a result, our Naive-Student model, trained with such simple yet effective iterative semi-supervised learning, attains state-of-the-art results at all three Cityscapes benchmarks, reaching the performance of 67.8% PQ, 42.6% AP, and 85.2% mIOU on the test set. We view this work as a notable step towards building a simple procedure to harness unlabeled video sequences and extra images to surpass state-of-the-art performance on core computer vision tasks.
Neurocognitive function in bipolar disorder: a comparison between bipolar I and II disorder and matched controls (2013)

The present study suggests that the type and degree of cognitive dysfunction is similar in bipolar I and II patients. Notably, treatment with antipsychotics - but not a history of psychosis - was associated with more severe cognitive impairment. Given that patients with bipolar I disorder are more likely to be on antipsychotic drugs, this might explain why some previous studies have found that patients with type I bipolar disorder are more cognitively impaired than those with type II.
OC20.07: Fetal exome sequencing: yield and limitations observed in a single tertiary centre (2018)

To explore the indications and diagnostic outcomes of fetal exome sequencing analyses performed in a single referral centre. 77 unrelated fetal samples underwent exome sequencing between 2012 and 2017. Indications, turnaround time, diagnostic rates, and pregnancy outcomes were analysed. The pregnant women were assessed at average gestational age of 23.6 ± 2.9 (range 14-36) weeks. Average time from sample submission to initial result decreased with time, and in 2017 averaged 25.8 ± 7.2 days. The most common indication for fetal exome sequencing was multiple malformations (21/77, 27%), followed by isolated brain malformations (15/77, 19%). Twelve fetuses (15%) were referred for isolated increased nuchal translucency (IINT). Exome analysis was diagnostic for 16 fetuses. A comparison of cases of fetal malformations vs. IINT showed that exome analysis did not reveal any known or probable pathogenic variants in IINT cases, whereas among fetuses with anatomic malformation, a molecular diagnosis was reached in 16/65 (25%). Proband-only cases received a diagnosis more often than trio exomes. Exome sequencing has the potential to provide molecular diagnoses in cases where conventional prenatal cytogenetic testing is negative. A referral bias of consanguineous cases could account for the high diagnostic rate for proband-only sequencing. Syndrome-specific prognostic information enables parents to make informed decisions, whereas challenges include time limitations and variant interpretation in the setting of non-specific fetal findings. As we report only established disease-gene associations, further segregation and functional studies in a research setting are expected to significantly increase the diagnostic yield.
Equivalence of MammaPrint array types in clinical trials and diagnostics (2016)

MammaPrint is an FDA-cleared microarray-based test that uses expression levels of the 70 MammaPrint genes to assess distant recurrence risk in early-stage breast cancer. The prospective RASTER study proved that MammaPrint Low Risk patients can safely forgo chemotherapy, which is further subject of the prospective randomized MINDACT trial. While MammaPrint diagnostic results are obtained from mini-arrays, clinical trials may be performed on whole-genome arrays. Here we demonstrate the equivalence and reproducibility of the MammaPrint test. MammaPrint indices were collected for breast cancer samples: (i) on both customized certified array types (n = 1,897 sample pairs), (ii) with matched fresh and FFPE tissues (n = 552 sample pairs), iii) for control samples replicated over a period of 10 years (n = 11,333), and iv) repeated measurements (n = 280). The array type indicated a near perfect Pearson correlation of 0.99 (95 % CI: 0.989-0.991). Paired fresh and FFPE samples showed an excellent Pearson correlation of 0.93 (95 % CI 0.92-0.94), in spite of the variability introduced by intratumoral tissue heterogeneity. Control samples showed high consistency over 10 year's time (overall reproducibility of 97.4 %). Precision and repeatability are overall 98.2 and 98.3 %, respectively. Results confirm that the combination of the near perfect correlation between array types, excellent equivalence between tissue types, and a very high stability, precision, and repeatability demonstrate that results from clinical trials (such as MINDACT and I-SPY 2) are equivalent to current MammaPrint FFPE and fresh diagnostics, and can be used interchangeably.
THE POSTGANGLIONIC EXCITATORY INNERVATION OF THE MOUSE URINARY BLADDER AND ITS MODULATION BY PREJUNCTIONAL GABABRECEPTORS (1986)

Field stimulation produced reproducible contractions of the mouse isolated urinary bladder whose amplitude was frequency-related. These contractions were partially sensitive to atropine (3 microM), unaffected by hexamethonium (10 microM) and almost abolished by tetrodotoxin (0.5 microM). Atropine (3 microM) suppressed contractions produced by exogenous acetylcholine thereby indicating atropine-resistance of the nerve-mediated contractions. Nerve-mediated contractions of the mouse urinary bladder were enhanced by physostigmine (0.1-0.5 microM) and inhibited by hemicholinium-3 (0.5 mM) thus confirming the presence of a cholinergic component in the excitatory postganglionic innervation. Atropine (3 microM) inhibition of the nerve-mediated contractions increased with increasing duration and strength of the train of stimulation. The nerve-mediated contractions of the mouse bladder were unaffected by phentolamine (0.2 microM), propranolol (0.3 microM) or indomethacin (5 microM). ATP (1mM) the major candidate for the role of nonadrenergic-noncholinegic (NANC) excitatory neurotransmitter in the mammalian urinary bladder produced a contraction of the mouse isolated bladder. Exposure to the stable ATP analogue alpha, beta-methylene ATP (APCPP) or beta, gamma-methylene ATP (APPCP) produced a partial desensitization of the nerve-mediated response which, for APCPP, was greater in the presence than in the absence of atropine (3 microM). In the presence of atropine (3 microM) and after APCPP desensitization the amplitude of the response to field stimulation amounted to about 20% of the original response and was sensitive to tetrodotoxin, indicating that it is nerve-mediated. GABA (0.001-0.3 mM) inhibited the amplitude of field stimulation induced contractions of mouse urinary bladder. This effect was mimicked by the selective GABAB receptor agonist, (+/-)-baclofen, but not by the selective GABAA receptor agonist, homotaurine. GABA and (+/-)-baclofen exhibited cross-desensitization. The GABA-or (+/-)-baclofen-induced inhibition of the nerve-mediated contractions were reduced by previous exposure to homotaurine (1 mM) or to 5-aminovaleric acid (2 mM), two GABAB receptor antagonists. On the other hand the inhibitory effects of GABA or (+/-)-baclofen were unaffected by picrotoxin (0.1 mM), a selective GABAA receptor antagonist. The inhibitory effect of GABA on nerve-mediated contractions was reduced in the presence of atropine or hemicholinium-3 as well as following desensitization of P2-purinoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Applications of the SMS method to the design of compact optics (2010)

New ultra-thin optical designs are presented that comprise discontinuous optical sections (called channels) working in parallel (multichanneling) to provide the desired optical function. Aplanatic (a particular case of SMS-design) multichannel designs are also shown and used to explain more easily the design procedure. Typically, these multichannel devices are at least formed by three optical surfaces: one of them has discontinuities in the shape, a second one may have discontinuities in its derivative while the third one is smooth. The number of discontinuities is the same in the two first surfaces: Each channel is defined by the smooth surfaces in between the discontinuities, so that the surfaces forming each separate channel are all smooth. No diffractive effects are considered.
Variable step size dichotomous coordinate descent affine projection algorithm (2009)

A new affine projection (AP) algorithm based on dichotomous coordinate descent (DCD) iterations has been recently proposed for acoustic echo cancellation (AEC). It uses a constant step size parameter and, therefore, has to compromise between fast convergence and tracking on the one hand, and low misadjustment and robustness to the presence and variations of a near-end signal on the other hand. In this paper we propose a variable step-size (VSS) version of the DCD-AP algorithm (VSS-DCD-AP) that does not require any a priori information about the acoustic environment. It is shown that the new algorithm is robust against near-end signal variations, including double-talk (DT).
ChemInform Abstract: Au(I)‐ and Pt(II)‐Catalyzed Cycloetherification of ω‐Hydroxy Propargylic Esters. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Clinical Implications and Economic Impact of Accuracy Differences among Commercially Available Blood Glucose Monitoring Systems (2013)

Our analysis shows that error patterns over the operating range of BGM meter may lead to relevant clinical and economic outcome differences that may not be reflected in a common accuracy metric or standard. Further research is necessary to validate the findings of this model-based approach.
A feed-forward technique for reconstitution of dropped optical carriers in WDM networks (2003)

We have demonstrated a method by which a network operator can permit direct optical access to his ring without compromising the network integrity due to inadvertent wavelength inaccuracies of remote user equipment. The method imposes only a modest penalty for using a single carrier for both dropping data from the ring and adding it to the ring. Several embodiments are possible. The approach trades off additional terminal complexity for advantages in wavelength control and management.
A Zeolitic Structure (ITQ-34) with Connected 9- and 10-Ring Channels Obtained with Phosphonium Cations as Structure Directing Agents (2008)

Zeolites are materials with a large applied interest. Here we present ITQ-34 a new zeolitic material, obtained combining the use of the highly stable tetraalkylphosphonium cations as structure directing agents with the incorporation of Ge atoms in the structure.
Targeting PI3K Remains Complex in Cancer Therapy (2018)

Dr. Lewis Cantley discusses targeting the PI3K pathway in breast cancer and the importance of managing ambient insulin levels during therapy.
Data from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune-checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T-cell infiltration in PDAC.&lt;/p&gt;Experimental Design:&lt;p&gt;Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from The Cancer Genome Atlas and 92 PDACs from the Australian International Cancer Genome Consortium. We explored associations between immune cell counts by immunohistochemistry, chemokine expression, and transcriptional hallmarks of antitumor immunity by RNA sequencing (RNA-seq), and mutational burden by whole-genome sequencing.&lt;/p&gt;Results:&lt;p&gt;Among all known human chemokines, a coregulated set of four (&lt;i&gt;CCL4, CCL5, CXCL9&lt;/i&gt;, and &lt;i&gt;CXCL10&lt;/i&gt;) was strongly associated with CD8&lt;sup&gt;+&lt;/sup&gt; T-cell infiltration (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Expression of this “4-chemokine signature” positively correlated with transcriptional metrics of T-cell activation (&lt;i&gt;ZAP70, ITK&lt;/i&gt;, and &lt;i&gt;IL2RB&lt;/i&gt;), cytolytic activity (&lt;i&gt;GZMA&lt;/i&gt; and &lt;i&gt;PRF1&lt;/i&gt;), and immunosuppression (&lt;i&gt;PDL1, PD1, CTLA4, TIM3, TIGIT, LAG3, FASLG&lt;/i&gt;, and &lt;i&gt;IDO1&lt;/i&gt;). Furthermore, the 4-chemokine signature marked tumors with increased T-cell activation scores (MHC I presentation, T-cell/APC costimulation) and elevated expression of innate immune sensing pathways involved in T-cell priming (STING and NLRP3 inflammasome pathways, BATF3-driven dendritic cells). Importantly, expression of this 4-chemokine signature was consistently indicative of a T-cell–inflamed phenotype across primary PDAC and PDAC liver metastases.&lt;/p&gt;Conclusions:&lt;p&gt;A conserved 4-chemokine signature marks resectable and metastatic PDAC tumors with an active antitumor phenotype. This could have implications for the appropriate selection of PDAC patients in immunotherapy trials.&lt;/p&gt;&lt;/div&gt;