gebhart/patrepeval huggingface dataset:
Exploring Alternative Strategies for the Identification of Potent Compounds Using Support Vector Machine and Regression Modeling (2018)

Support vector regression (SVR) is a premier approach for the prediction of compound potency. Given the conceptual link between support vector machine (SVM) and SVR modeling, SVR is capable of accounting for continuous and discontinuous structure-activity relationships (SARs) in potency prediction, which further extends the classical quantitative SAR (QSAR) paradigm. In the context of virtual compound screening, compound potency prediction can be applied to identify the most potent compounds that are available or enrich database selection sets with potent compounds. To these ends, we have evaluated new potency prediction strategies. Conventional (direct) potency prediction using SVR was compared to two-stage SVM-SVR modeling and potency prediction using SVR models trained in the presence of active and inactive compounds, a previously unconsidered approach. The latter models were found to maximize the recall of potent compounds but were least accurate in predicting high potency values. For this purpose, direct SVR predictions were preferred. However, the best balance between accurate potency predictions and enrichment of potent compounds in database selection sets was achieved by combined SVM-SVR modeling. Taken together, our findings further extend current approaches for compound potency prediction in virtual compound screening.
Nerve growth factor for neuropathic pain (2017)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the analgesic efficacy and adverse effects of nerve growth factor for chronic neuropathic pain.
Movable-Boundary Channel-Access Schemes for Integrated Voice/Data Networks (1990)

Abstract : Channel-access protocols for integrated radio networks must reflect the different communication requirements associated with voice and data, as well as the impact each type of traffic has on the other. In this report we introduce a new class of protocols that we have developed for this application, which are known as the Voice/Data Interleaved-Frame Fixed-Length (VD-IFFL) protocols. As a first step in the discussion of the VD-IFFL protocols, we introduce the IFFL protocols, which are similar to the Interleaved-Frame-Flush-Out (IFFO) protocols (a class of schemes developed for data-only applications) except that they have a fixed frame length, a desirable feature in voice communication. The VD-IFFL protocols use a movable-boundary mechanism to share the channel between voice and data traffic. Voice traffic is handled on a reservation basis, while data traffic is handled using a hybrid IFFL scheme that combines reservation and contention. These protocols are characterized by infinite Markov chains, whose transition probabilities have been evaluated exactly.
Applying Signaling Compression (SigComp) to the Session Initiation Protocol (SIP) (2007)

This document describes some specifics that apply when Signaling
Compression (SigComp) is applied to the Session Initiation Protocol
(SIP), such as default minimum values of SigComp parameters,
compartment and state management, and a few issues on SigComp over
TCP. Any implementation of SigComp for use with SIP must conform to
this document and SigComp, and in addition support the SIP and Session
Description Protocol (SDP) static dictionary.
Rapid Visualization of Chemically Related Compounds Using Kendrick Mass Defect as a Filter in Mass Spectrometry Imaging (2019)

&lt;div&gt; &lt;p&gt;Kendrick mass defect (KMD) analysis is widely used for helping the detection and identification of chemically related compounds based on exact mass measurements. We report here the use of KMD as a criterion for filtering complex mass spectrometry dataset. The method enables an automated, easy and efficient data processing, enabling the reconstruction of 2D distributions of family of homologous compounds from MSI images. We show that the KMD filtering, based on an in-house software, is suitable and robust for high resolution (full width at half-maximum, FWHM, at &lt;i&gt;m/z&lt;/i&gt; 410 of 20 000) and very high-resolution (FWHM, at &lt;i&gt;m/z&lt;/i&gt; 410 of 160 000) MSI data. This method has been successfully applied to two different types of samples, bacteria co-cultures and brain tissue section&lt;/p&gt; &lt;/div&gt;
Transfer of Human α- to β-Hemoglobin via Its Chaperone Protein (2004)

The alpha-hemoglobin-stabilizing protein (AHSP), a small protein of 102 amino acids, is synthesized in red blood cell precursors. It binds specifically to alpha-hemoglobin (alpha-Hb) subunits acting as a chaperone protein, preventing the formation of alpha-hemoglobin-cytotoxic precipitates. We have engineered recombinant AHSP in a pGEX vector to study the functional consequence of interaction between AHSP and alpha-Hb. By in vitro binding assays, we have isolated the complexes glutathione S-transferase-AHSP.alpha-Hb and AHSP.alpha-Hb. The latter assembles as a heterodimer based on size-exclusion chromatography. These complexes exhibited monophasic CO binding kinetics, as observed for isolated alpha- and beta-subunits of hemoglobin. However, the rate of CO (or oxygen) binding to alpha-hemoglobin bound to its chaperone is three times slower than that observed for isolated alpha-hemoglobin, demonstrating a form that is intermediate to the R- and T-hemoglobin states. The physiologically relevant replacement of the chaperone by beta-hemoglobin chains could be detected by both ligand binding kinetics and tryptophan fluorescence quenching.
Cost-Effectiveness of a National Sugar-Sweetened Beverage Tax to Reduce Cancer Burdens and Disparities in the United States (2020)

A penny-per-ounce national SSB tax is cost-effective for cancer prevention in the United States, with the largest health gains and economic benefits among low-income Americans.
SOX9 Knockout Induces Polyploidy and Changes Sensitivity to Tumor Treatment Strategies in a Chondrosarcoma Cell Line (2020)

As most chemotherapeutic drugs are ineffective in the treatment of chondrosarcoma, we studied the expression pattern and function of SOX9, the master transcription factor for chondrogenesis, in chondrosarcoma, to understand the basic molecular principles needed for engineering new targeted therapies. Our study shows an increase in SOX9 expression in chondrosarcoma compared to normal cartilage, but a decrease when the tumors are finally defined as dedifferentiated chondrosarcoma (DDCS). In DDCS, SOX9 is almost completely absent in the non-chondroid, dedifferentiated compartments. CRISPR/Cas9-mediated knockout of SOX9 in a human chondrosarcoma cell line (HTB94) results in reduced proliferation, clonogenicity and migration, accompanied by an inability to activate MMP13. In contrast, adhesion, apoptosis and polyploidy formation are favored after SOX9 deletion, probably involving BCL2 and survivin. The siRNA-mediated SOX9 knockdown partially confirmed these results, suggesting the need for a certain SOX9 threshold for particular cancer-related events. To increase the efficacy of chondrosarcoma therapies, potential therapeutic approaches were analyzed in SOX9 knockout cells. Here, we found an increased impact of doxorubicin, but a reduced sensitivity for oncolytic virus treatment. Our observations present novel insight into the role of SOX9 in chondrosarcoma biology and could thereby help to overcome the obstacle of drug resistance and limited therapy options.
From Chiral Counterions to Twisted Membranes (2002)

In membranes, the chirality of the amphiphile constituents is sometimes expressed at a supramolecular scale of nanometers or micrometers. We have recently reported that membranes of nonchiral dicationic n-2-n amphiphiles can also be chirally twisted upon interacting with chiral tartrate counterions. Here, we demonstrate that the mechanism of the chiral induction by counterions involves specific anion-cation recognition and the induction of conformationally labile chirality in the cations. Single-crystal X-ray diffraction shows that the amphiphilic cations exist as a mixture of chiral conformers. (1)H NMR data establish a specific recognition between tartrate and n-2-n cations and show that chiral conformers also exist in solution. Circular dichroism (CD) in the UV-vis shows a sharp conformational change of tartrate ions from anti to gauche when bound to the chiral cationic membranes. This is confirmed by CD in the infrared region which also shows concomitant induced CD bands in the vibrations of the n-2-n amphiphiles. These results represent the first example of the so-called Pfeiffer effect in a membrane. They provide a general framework for designing new tunable membrane systems. Our work also includes the first application of vibrational circular dichroism in the study of chiral conformations of amphiphiles in membranes and demonstrates the very high potential of this technique.
Measurement of the<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>I</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn><mml:mo stretchy="false">/</mml:mo><mml:mn>2</mml:mn></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>K</mml:mi><mml:mo>π</mml:mo><mml:mtext> </mml:mtext><mml:mi mathvariant="script">S</mml:mi></mml:math>-wave amplitude from Dalitz plot analyses of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:msub><mml:mi>η</mml:mi><mml:mi>c</mml:mi></mml:msub><mml:mo stretchy="false">→</mml:mo><mml:mi>K</mml:mi><mml:mover accent="true"><mml:mi>K</mml:mi><mml:mo stretchy="false">¯</mml:mo></mml:mover><mml:mi>π</mml:mi></mml:math>in two-photon interactions (2016)

We study the processes $\ensuremath{\gamma}\ensuremath{\gamma}\ensuremath{\rightarrow}{K}_{S}^{0}{K}^{\ifmmode\pm\else\textpm\fi{}}{\ensuremath{\pi}}^{\ensuremath{\mp}}$ and $\ensuremath{\gamma}\ensuremath{\gamma}\ensuremath{\rightarrow}{K}^{+}{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{0}$ using a data sample of $519\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ recorded with the BABAR detector operating at the SLAC PEP-II asymmetric-energy ${e}^{+}{e}^{\ensuremath{-}}$ collider at center-of-mass energies at and near the $\mathrm{\ensuremath{\Upsilon}}(nS)$ ($n=2$, 3, 4) resonances. We observe ${\ensuremath{\eta}}_{c}$ decays to both final states and perform Dalitz plot analyses using a model-independent partial wave analysis technique. This allows a model-independent measurement of the mass-dependence of the $I=1/2$ $K\ensuremath{\pi}\text{ }\mathcal{S}$-wave amplitude and phase. A comparison between the present measurement and those from previous experiments indicates similar behavior for the phase up to a mass of $1.5\text{ }\text{ }\mathrm{GeV}/{c}^{2}$. In contrast, the amplitudes show very marked differences. The data require the presence of a new ${a}_{0}(1950)$ resonance with parameters $m=1931\ifmmode\pm\else\textpm\fi{}14\ifmmode\pm\else\textpm\fi{}22\text{ }\text{ }\mathrm{MeV}/{c}^{2}$ and $\mathrm{\ensuremath{\Gamma}}=271\ifmmode\pm\else\textpm\fi{}22\ifmmode\pm\else\textpm\fi{}29\text{ }\text{ }\mathrm{MeV}$.
Cell fractionation with affinity ligands conjugated to agarose-polyacrolein microsphere beads (1983)

A new effective insoluble support useful for cell fractionation based on agarose-polyacrolein microsphere beads (APAMB) of diameters 150--250 micrometers has been developed. The synthesized polyacrolein (PA) microspheres, of average diameter 0.2 micrometer, are provided with reactive aldehyde groups through which various ligands containing primary amino groups are bound covalently in a single step at physiological pH. Antibodies coupled to the microspheres are very effective for labelling of cell surface receptors on human red blood cells and mouse lymphoid cells. APAMB were obtained by encapsulating the PA microspheres with agarose. Antibodies and lectins bound to the APAMB serve to construct affinity columns for the separation of red blood cells and murine lymphocyte subpopulations. Anti-human red blood cell antibodies coupled to anti-immunoglobulin APAMB are effective in separating human from turkey red blood cells, whereas either anti-Thy 1.2 anti-immunoglobulin antibodies or soybean agglutinin coupled to APAMB have proved useful for the separation of T and B cells from heterogeneous population of spleen cells. The separation procedure is simple, rapid and effective. The viability of the fractionated cells is unaffected by the procedure and the recovery of the cells is high: between 80% and 100%.
Microresonators in CMOS Compatible Substrate (2010)

We report our recent progress in designing and developing traveling-wave microresonators on CMOS compatible substrate, with a focus on ultra-compact Si-based microring and microdisk resonators in the visible and near infrared wavelengths with ultra-high Q and small mode volume, suitable for strong light-matter interaction. The performance of these resonators is discussed, and the design and fabrication challenges and solutions to achieve efficient coupling from the bus-waveguide to the resonator is mentioned. Coupled-resonator architectures for the design of filters are analyzed and theoretical and experimental results for the flat-band filters with wide bandwidth and large free spectral range are presented. Furthermore, by using a detailed thermal model we demonstrate optimized microresonator structures on semiconductor substrates with improved thermal conductivity that can sustain a high circulating optical intensity at the resonance wavelength, which is particularly useful for nonlinear optics and optical signal processing applications. Finally, we address some of the applications and future prospects of such microresonators in CMOS-compatible substrate technology, including portable multi-purpose bio/chemical sensing systems, reconfigurable optical signal processing modules and chip-scale optical amplifiers and lasers.
Identification of an insect-produced olfactory cue that primes plant defenses (2017)

It is increasingly clear that plants perceive and respond to olfactory cues. Yet, knowledge about the specificity and sensitivity of such perception remains limited. We previously documented priming of anti-herbivore defenses in tall goldenrod plants (Solidago altissima) by volatile emissions from a specialist herbivore, the goldenrod gall fly (Eurosta solidaginis). Here, we explore the specific chemical cues mediating this interaction. We report that E,S-conophthorin, the most abundant component of the emission of male flies, elicits a priming response equivalent to that observed for the overall blend. Furthermore, while the strength of priming is dose dependent, plants respond even to very low concentrations of E,S-conophthorin relative to typical fly emissions. Evaluation of other blend components yields results consistent with the hypothesis that priming in this interaction is mediated by a single compound. These findings provide insights into the perceptual capabilities underlying plant defense priming in response to olfactory cues.Plants are able to prime anti-herbivore defenses in response to olfactory cues of insect pests. Here, Helms et al. identify the insect pheromone E,S-conophthorin produced by the goldenrod gall fly as the specific chemical component that elicits this priming response in goldenrod plants.
ChemInform Abstract: Enantioselective Copper‐Catalyzed 1,3‐Dipolar Cycloadditions (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.
CD4+ T Cell Help Has an Epitope-Dependent Impact on CD8+ T Cell Memory Inflation during Murine Cytomegalovirus Infection (2009)

Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8(+) T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4(+) T cells have been implicated in maintaining the function and/or number of CD8(+) T cells in other chronic infections. Moreover, CD4(+) T cells are essential for complete control of MCMV. Thus, we wondered whether CD4(+) T cell deficiency would result in impaired MCMV-specific CD8(+) T cell responses. Here we show that CD4(+) T cell deficiency had an epitope-specific impact on CD8(+) T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8(+) T cells was substantially impaired in CD4(+) T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8(+) T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4(+) T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8(+) T cells.
28-day oral toxicity study with soft corticosteroid BNP-166 in rats and dogs, followed by a 14-day recovery period. (2002)

The aim of the present study was to evaluate the soft corticosteroid BNP-166 in rats and dogs treated orally with 0.2, 2.0, and 20.0 mg/kg for 28 days and the reversibility of any abnormalities during a 14-day post-dosing period. The test substance, BNP-166, was well tolerated during the 28-day treatment period. The observed changes were all characteristic for the pharmacological actions of a glucocorticoid. Treatment related changes occurred in the adrenals and thymus, and, to a lesser extent, in the lymph nodes, spleen and liver. There were no statistically significant reductions in the cortisol levels of all groups in the 0.2 and 2 mg/kg treatments. Significant reductions were observed in the high-dose group (20 mg/kg), but levels returned to normal by the end of the 14-day recovery period. Based on the results, the No Observable Adverse Effect Level (NOAEL) of BNP-166 soft corticosteroid in rat and dog after 28-day oral administration is 2 mg/kg. This value is approximately 40 times higher than that of budesonide. Pharmacodynamic and receptor binding studies have shown BNP-166 to have a similar potency to budesonide; therefore, BNP-166 can be considered safer when administered orally than other corticosteroids such as prednisolone or budesonide.
Serendipity in the Quest for New Organic Materials (2016)

Presented on September 14, 2016 at 4:00 p.m. in the Engineered Biosystems Building, Room 1005
Correction: Author Correction: Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals (2018)

This corrects the article DOI: 10.1038/ncomms15587.
Tumor collection/processing under physioxia uncovers highly relevant signaling networks and drug sensitivity (2022)

Preclinical studies of primary cancer cells are typically done after tumors are removed from patients or animals at ambient atmospheric oxygen (O<sub>2</sub>, ~21%). However, O<sub>2</sub> concentrations in organs are in the ~3 to 10% range, with most tumors in a hypoxic or 1 to 2% O<sub>2</sub> environment in vivo. Although effects of O<sub>2</sub> tension on tumor cell characteristics in vitro have been studied, these studies are done only after tumors are first collected and processed in ambient air. Similarly, sensitivity of primary cancer cells to anticancer agents is routinely examined at ambient O<sub>2</sub>. Here, we demonstrate that tumors collected, processed, and propagated at physiologic O<sub>2</sub> compared to ambient air display distinct differences in key signaling networks including LGR5/WNT, YAP, and NRF2/KEAP1, nuclear reactive oxygen species, alternative splicing, and sensitivity to targeted therapies. Therefore, evaluating cancer cells under physioxia could more closely recapitulate their physiopathologic status in the in vivo microenvironment.
Effects of Substrate Misorientation and Zn Doping Characteristics on the Performance of AlGaInP Visible Light-Emitting Diodes (1994)

Effects of substrate misorientation and Zn doping characteristics on the device performance of AlGaInP double-heterostructure light-emitting diodes are described. The light output power is found to be strongly dependent on the Zn concentration. The degradation of light output, which was caused by the increase in the number of Zn atoms, is investigated by photoluminescence and electroluminescence measurements. The emission properties can be improved by optimizing the growth of AlGaInP on an intentionally misoriented substrate and the Zn-doping level in the p-cladding layer. The external quantum efficiency of 3.5% at 618 nm can be obtained from the optimized LEDs with a 7.5-µm-thick GaP window layer.
Immunization of Rabbits with a Quadrivalent<i>Shigella</i>Bioconjugate Vaccine Induces Functional Antibodies Reactive with<i>Shigella</i>Isolates from Kenya (2022)

Diarrheal diseases are a leading cause of global morbidity and mortality, disproportionately affecting children in resource-limited settings. Although improvements in hygiene and access to clean water are helpful, vaccines are considered essential due to the low infectious dose of <i>Shigella</i> species and increasing antibiotic resistance. Building on achievements with conjugate vaccines, a safe and immunogenic novel bioconjugate vaccine linking <i>Shigella</i> O-antigen to Pseudomonas aeruginosa exoprotein A has been developed to induce immunity against Shigella flexneri 2a, 3a, and 6 and S. sonnei. This study evaluated the breadth of reactivity and functionality of pooled serum from rabbits immunized with monovalent and quadrivalent <i>Shigella</i> bioconjugates formulated with or without an adjuvant against <i>Shigella</i> serotypes isolated in Kenya. Rabbit sera were assayed by colony blot for reactivity with 67 isolates of <i>Shigella</i> serotypes targeted by the vaccine, S. flexneri (2a, 3a, and 6) and S. sonnei, and 42 isolates of <i>Shigella</i> serotypes not targeted by the vaccine, S. flexneri (1b, 2b, 4a, and 4b), S. boydii, and S. dysenteriae. <i>Shigella</i> isolates testing positive in the colony blot assay were then used to assess functional activity using a bactericidal assay. Of the 41 <i>Shigella</i> isolates targeted by the vaccine, 22 were reactive with the adjuvanted quadrivalent and the respective monovalent rabbit sera. The S. flexneri 2a and 3a monovalent rabbit serum cross-reacted with S. flexneri 3a, 2b, and 2a, respectively. Immunization with the adjuvanted quadrivalent vaccine also induced cross-reactivity with isolates of S. flexneri 2b, 4a, and 4b. Collectively, these results suggest that the <i>Shigella</i> quadrivalent vaccine may be more broadly protective than designed, offering a promising solution to <i>Shigella</i> infections. <b>IMPORTANCE</b> Diarrheal diseases are the third leading cause of death globally, disproportionally affecting low- to middle-income countries like Kenya, with <i>Shigella</i> species being the leading cause of bacterial diarrhea, especially in children. The low infectious dose and high antibiotic resistance levels complicate treatment, leading to long-term sequelae that necessitate control measures such as vaccines to reduce morbidity and mortality rates, especially among children under 5 years of age. A quadrivalent bioconjugate <i>Shigella</i> vaccine was recently developed to safely and effectively induce immunity against four important <i>Shigella</i> spp. This study demonstrates the breadth of reactivity and functionality of the parenterally administered bioconjugate vaccine by evaluating the ability of rabbit sera to bind and kill <i>Shigella</i> isolates recently collected in Kenya. These results suggest that the <i>Shigella</i> quadrivalent vaccine may be more broadly protective than designed and may offer a promising solution to the morbidity and mortality associated with <i>Shigella</i> infections.