gebhart/patrepeval huggingface dataset:
Raman spectroscopy of proteins: a review (2013)

In this work, 26 proteins of different structure, function and properties are investigated by Raman spectroscopy with 488, 532 and 1064 nm laser lines. The excitation lines were chosen in NIR and Vis range as the most common and to show the difference due to normal and resonance effect, sometimes accompanied by the fluorescence. The selected proteins were divided, according to the Structural Classification of Proteins, into four classes according to their secondary structure, i.e. α‐helical (α), β‐sheet (β), mixed structures (α/β, α + β, s) and others. For all compounds, FT‐Raman and two Vis spectra are presented along with the detailed band assignment. To the best of our knowledge, this is the first review showing the potential of Raman spectroscopy for the measurement and analysis of such a large collection of individual proteins. This work can serve as a comprehensive vibrational spectra library, based on our and previous Raman measurements. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Efficient Synthesis of 11-cis-Retinoids (1999)

Synthesis of 11-cis-retinal analogues, of great importance in bioorganic studies of the photoreceptor of the visual transduction pathway, has been hampered by unusual difficulties in establishing the 11-cis geometry. However, a general and mild preparation of 11-cis-retinoids in high yield has been achieved by reduction of 11-yne precursors to 11-cis-enes with Cu/Ag-activated zinc dust (below). The ready availability of the 11-yne precursors makes this strategy applicable for general use.
Interaction of metastatic tumor cells with bovine lens capsule basement membrane. (1984)

The use of bovine lens capsule basement membrane as a model substratum for studies of invasion and extravasation by metastatic tumor cells is described. The abilities of three independently isolated pairs of metastatic variant cell lines to digest the purified substrates, laminin, type IV collagen, and type I collagen, were compared with their abilities to solubilize isotope from 125I-labeled lens capsule basement membrane matrix. The cell lines used were +SA and -SA mouse mammary adenocarcinoma cells, RT7-4bs and RT7-4b-Ls rat hepatocarcinoma cells, and B16-F1 and B16-F10 mouse melanoma cells. In general, imperfect correlations of lytic activity with metastatic ability were found for the purified substrate digestions, but, for each pair of variants, the more metastatic tumor cell line was always able to solubilize more surface-bound isotope from the lens capsule. Visual evidence of tumor cell-associated digestion of lens capsule basement membrane was obtained using transmission electron microscopy. Mouse mammary carcinoma cells attached more rapidly to lens capsule than to endothelial cell monolayers or tissue culture plastic. We next added endothelial cells to the model substrate. Aortic endothelial cells grew well on lens capsules without apparent synthesis of additional basement membrane matrix. In additional studies, the lens capsule was used in a chamber apparatus to demonstrate that cellular invasion of the full thickness of this basement membrane structure could be demonstrated and readily quantitated. Our results indicate that bovine lens capsule is a particularly versatile basement membrane structure useful for studies of tumor cell invasion and extravasation. In addition, the comparison of purified substrate digestions with lens capsule matrix digestion indicates the desirability of also using a matrix digest when correlating lytic abilities of tumor cells with their metastatic abilities.
CURRENT COST DEPRECIATION: A PROGRAMMING PERSPECTIVE (1982)

Professional accounting bodies in the United Kingdom, the United States and Canada are requiring disclosure of current cost of capital equipment and related depreciation. In this paper the ability of a normative programming model of the firm to produce depreciation allocations in accordance with economic depreciation is examined, and the model's depreciation allocations are compared with current professional pronouncements. It is found that if the firm can costlessly adjust capacity period‐by‐period, current cost depreciation is on strong theoretical grounds. Otherwise depreciation should be based on value‐use.
Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress (2005)

Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN) in the endothelium. Evidence suggests that polyphenolic antioxidants contained in the juice derived from the pomegranate can contribute to the reduction of oxidative stress and atherogenesis. The aim of the present study was to evaluate the effects of intervention with pomegranate juice (PJ) on oxidation-sensitive genes and endothelial NO synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Cultured human coronary artery endothelial cells (EC) exposed to high shear stress in vitro and hypercholesterolemic mice were used in this study. PJ concentrate reduced the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased eNOS expression (which was decreased by perturbed shear stress) in cultured EC and in atherosclerosis-prone areas of hypercholesterolemic mice. Moreover, oral administration of PJ to hypercholesterolemic mice at various stages of disease reduced significantly the progression of atherosclerosis. This experimental study indicates that the proatherogenic effects induced by perturbed shear stress can be reversed by chronic administration of PJ. This approach may have implications for the prevention or treatment of atherosclerosis and its clinical manifestations.
Stable antiviral expression in BALB/c 3T3 cells carrying a beta interferon sequence behind a major histocompatibility complex promoter fragment (1991)

We are exploring the use of interferon (IFN) genes for somatic cell gene therapy and have investigated the possibility of transforming cells into low constitutive IFN producers over prolonged periods of time without impeding cell survival or replication. Here we report the possibility of conferring a permanent antiviral state to cells by introducing an IFN-beta gene with a modified transcriptional control. This was achieved by placing the murine IFN-beta-coding sequence behind the IFN-inducible 0.6-kb XhoII-NruI promoter region of the H-2Kb major histocompatibility complex gene. BALB/c 3T3 cells that are normally permissive for virus infection were transformed with this construction, and 14 of the 21 clonal cell lines obtained displayed different levels of enhanced resistance to the replication of vesicular stomatitis virus, encephalomyocarditis virus, and Semliki Forest virus. The permanent antiviral state was dependent on the presence of new IFN-beta fragments in Southern blots and was accompanied by very low constitutive synthesis of IFN-beta, and the presence of construct-derived IFN mRNA could be demonstrated only after polymerase chain reaction amplification of cDNA. The antiviral state was stable over a 9-month period in culture, corresponding to about 250 cell generations, and did not affect cell replication, since the average population doubling time of these cells was not significantly different from that of the control clone. Twenty-nine control clonal cell lines, stably transformed with either the neo gene alone (22 lines) or the neo gene together with a mutated murine IFN-beta gene coding for an inactive protein (7 lines), did not develop stable antiviral expression. We conclude that low constitutive synthesis of autocrine IFN-beta is sufficient to induce a permanent antiviral state, is compatible with cell survival and replication, and therefore merits further exploration for use in somatic cell gene therapy.
Elimination Reaction of Fluoroölefins with Organolithium Compounds (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElimination Reaction of Fluoroölefins with Organolithium CompoundsSTANLEY DIXONCite this: J. Org. Chem. 1956, 21, 4, 400–403Publication Date (Print):April 1, 1956Publication History Published online1 May 2002Published inissue 1 April 1956https://pubs.acs.org/doi/10.1021/jo01110a005https://doi.org/10.1021/jo01110a005research-articleACS PublicationsRequest reuse permissionsArticle Views920Altmetric-Citations122LEARN 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
Statistical principles in experimental design. (1962)

CHAPTER 1: Introduction to Design CHAPTER 2: Principles of Estimation and Inference: Means and Variance CHAPTER 3: Design and Analysis of Single-Factor Experiments: Completely Randomized Design CHAPTER 4: Single-Factor Experiments Having Repeated Measures on the Same Element CHAPTER 5: Design and Analysis of Factorial Experiments: Completely-Randomized Design CHAPTER 6: Factorial Experiments: Computational Procedures and Numerical Example CHAPTER 7: Multifactor Experiments Having Repeated Measures on the Same Element CHAPTER 8: Factorial Experiments in which Some of the Interactions are Confounded CHAPTER 9: Latin Squares and Related Designs CHAPTER 10: Analysis of Covariance
Influence of R-CHOP Therapy on Immune System Restoration in Patients with B-Cell Lymphoma (2016)

The immunosuppressive effect of R-CHOP in newly diagnosed cases of B-cell lymphoma tends to persist for >2 years, although sIgG levels were restored more quickly than CD4+ cell counts.
Linkage disequilibrium in human populations (2003)

Whereas the human linkage map appears on limited evidence to be constant over populations, maps of linkage disequilibrium (LD) vary among populations that differ in gene history. The greatest difference is between populations of sub-Saharan origin and populations remotely derived from Africa after a major bottleneck that reduced their heterozygosity and altered their Malecot parameters, increasing the intercept M that reflects association in founders and decreasing the exponential decline epsilon. Variation among populations within this ethnic dichotomy is much smaller. These observations validate use of a cosmopolitan LD map based on a sizeable sample representing a large population reliably typed for markers at high density. Then an LD map for a region or isolate within an ethnic group may be created by fitting the sample LD to the cosmopolitan map, estimating Malecot parameters simultaneously. The cosmopolitan map scaled by epsilon recovers 95% of the information that a local map at the same density gives and therefore more than the information in a low-resolution local map. Relative to a Eurasian cosmopolitan map the scaling factors are estimated to be 0.82 for isolates of European descent, 1.53 for Yorubans, and 1.74 for African Americans. These observations are consistent with a common bottleneck (perhaps but not necessarily speciation) approximately 173,500 years ago, if the bottleneck associated with migration out of Africa was 100,000 years ago. Eurasian populations (especially isolates with numerous cases) are efficient for genome scans, and populations of recent African origin (such as African Americans) are efficient for identification of causal polymorphisms within a candidate sequence.
The Kinetics and Folding Pathways of Intramolecular G-Quadruplex Nucleic Acids (2012)

The folding kinetics of G-quadruplex forming sequences is critical to their capacity to influence biological function. While G-quadruplex structure and stability have been relatively well studied, little is known about the kinetics of their folding. We employed a stopped-flow mixing technique to systematically investigate the potassium-dependent folding kinetics of telomeric RNA and DNA G-quadruplexes and RNA G-quadruplexes containing only two G-quartets formed from sequences r[(GGA)(3)GG] and r[(GGUUA)(3)GG]. Our findings suggest a folding mechanism that involves two kinetic steps with initial binding of a single K(+), irrespective of the number of G-quartets involved or whether the G-quadruplex is formed from RNA or DNA. The folding rates for telomeric RNA and DNA G-quadruplexes are comparable at near physiological [K(+)] (90 mM) (τ = ~60 ms). The folding of a 2-quartet RNA G-quadruplex with single nucleotide A loops is considerably slower (τ = ~700 ms), and we found that the time required to fold a UUA looped variant (τ > 100 s, 500 mM K(+)) exceeds the lifetimes of some regulatory RNAs. We discuss the implications of these findings with respect to the fundamental properties of G-quadruplexes and their potential functions in biology.
Nanosecond electric pulses modulate skeletal muscle calcium dynamics and contraction (2017)

Irreversible electroporation therapy is utilized to remove cancerous tissues thru the delivery of rapid (250Hz) and high voltage (V) (1,500V/cm) electric pulses across microsecond durations. Clinical research demonstrated that bipolar (BP) high voltage microsecond pulses opposed to monophasic waveforms relieve muscle contraction during electroporation treatment. Our group along with others discovered that nanosecond electric pulses (nsEP) can activate second messenger cascades, induce cytoskeletal rearrangement, and depending on the nsEP duration and frequency, initiate apoptotic pathways. Of high interest across in vivo and in vitro applications, is how nsEP affects muscle physiology, and if nuances exist in comparison to longer duration electroporation applications. To this end, we exposed mature skeletal muscle cells to monopolar (MP) and BP nsEP stimulation across a wide range of electric field amplitudes (1-20 kV/cm). From live confocal microscopy, we simultaneously monitored intracellular calcium dynamics along with nsEP-induced muscle movement on a single cell level. In addition, we also evaluated membrane permeability with Yo-PRO-1 and Propidium Iodide (PI) across various nsEP parameters. The results from our findings suggest that skeletal muscle calcium dynamics, and nsEP-induced contraction exhibit exclusive responses to both MP and BP nsEP exposure. Overall the results suggest in vivo nsEP application may elicit unique physiology and field applications compared to longer pulse duration electroporation.
Abstract 4611: A 3D in vitro culture-based method to visualize and quantify effects of immuno-modulatory drugs (2017)

Abstract BACKGROUNDUnleashing the full potential of cancer immunotherapy is hampered by a lack of effective in vitro testing methods. 2D cultured cells poorly reflect the in vivo situation and lack the tumour microenvironment whereas humanized animal models are slow, have low throughput and are expensive. 3D cultures, on the other hand, more faithfully reproduce the organization of a tissue, recapitulating the cell-cell connections and cellular heterogeneity found in the tumour and allow for a cost-efficient testing of drug candidates. To address the unmet need of immunotherapy cancer drug developers for robust assays that incorporate the human immune system, with functional read-outs in a high throughput (384well plate) format, we developed an in vitro platform based on 3D co-cultures of cancer tumoroids and immune cells. This assay is designed to test the capacity of small molecules, bi-specific antibodies, checkpoint modulators, vaccines and combinations of thereof to enhance anti-cancer immune responses. METHODSCancer cells of different sources were grown in a hydrogel to form tumoroids and then HLA-matched PBMCs pre-conditioned via different protocols to achieve activated or exhausted T cells, were added in the presence or absence of immune-modulatory drugs. T cell infiltration and subsequent tumoroid killing was quantified using 3D high-content imaging. After ‘optical sectioning’ 3D image stacks were reconstituted and morphometric analysis was performed with OMiner software. RESULTS AND CONCLUSIONS Addition of immune checkpoint inhibitors, pembrolizumab and ipilimumab, led to enhanced T cell infiltration and cytotoxicity of exhausted T cells. These results showed that automated 3D image and data analysis enables discrimination of immune-tumour cell interactions depending on activation status of T cells and permits the visualization of T cell re-gain of function in the presence of checkpoint modulators. A 3D environment allows the different cell types to engage in a more realistic setting than when cells are grow in a monolayer and enables the quantification of spatially resolved information, which is of an utmost importance when studying tumor-immune cell relationships. This new and innovative platform empowers immunotherapy drug developers with a powerful tool to evaluate drug performance. Furthermore, drug combinations can be studied to determine synergistic effects with other checkpoint inhibitors of standard of care compounds in an efficient manner. Citation Format: Lidia Daszkiewicz, Kuan Yan, Maarten Klop, Leo Price. A 3D in vitro culture-based method to visualize and quantify effects of immuno-modulatory drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4611. doi:10.1158/1538-7445.AM2017-4611
Use of lyoprotectants in the freeze-drying of a model protein, ribonuclease A. (1989)

Purified ribonuclease A (RNase), when freeze-dried in 0.1 M sodium phosphate buffer at pH 3.0, 6.4, and 10.0 was found to lose specific activity as a function of time when stored in the solid state at 45°C. The specific activity loss was a result of the formation of covalently bonded aggregates of RNase. The covalent linkages in the aggregates were not due to disulfide bond interchange. Sucrose, Ficoll 70, and polyvinylpyrrolidone offered lyoprotection by preserving the enzymatic activity of the freeze-dried RNase. (Lyoprotection was defined as the stabilization and prevention of the degradation of a macromolecule both during freeze-drying and afterwards, during storage.) Ficoll 70, a polymer containing sucrose residues, demonstrated the widest range of pH stability and conveyed equivalent lyoprotection at the three pH values tested (3.0,6.4, and 10.0). Sucrose was found to be an effective lyoprotectant only at neutral and alkaline pH, and polyvinylpyrrolidone (PVP) was most effective as a lyoprotectant in an acidic environment. Freeze-dried cakes containing RNase and one of the three lyoprotectants were found to be amorphous and not crystalline solids. Lyoprotectant to RNase mass ratios of at least 6:1 were required to achieve maximum preservation of RNase enzymatic activity for both polymers and sucrose at their respective optimal pH conditions.
The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors (2008)

Overexpression and enhanced activity of insulin-like growth factor-I receptor (IGF-IR) in diverse tumor types make it an attractive target for cancer therapy. BMS-536924 is a potent small molecule inhibitor of IGF-IR, which shows antitumor activity in multiple tumor models, including sarcoma. To facilitate the development of IGF-IR inhibitors as cancer therapy, identification of biomarkers for selecting patients most likely to derive clinical benefit is needed. To do so, 28 sarcoma and neuroblastoma cell lines were screened for in vitro response to BMS-536924 to identify sensitive and resistant cell lines. Notably, Ewing's sarcoma, rhabdomyosarcoma, and neuroblastoma are more responsive to BMS-536924, suggesting these specific subtypes may represent potential targeted patient subpopulations for the IGF-IR inhibitor. Gene expression and protein profiling were performed on these cell lines, and candidate biomarkers correlating with intrinsic and/or acquired resistance to BMS-536924 were identified. IGF-I, IGF-II, and IGF-IR were highly expressed in sensitive cell lines, whereas IGFBP-3 and IGFBP-6 were highly expressed in resistant lines. Overexpression of epidermal growth factor receptor (EGFR) and its ligands in resistant cell lines may represent one possible resistance mechanism by the adaptation of IGF-IR-independent growth using alternative signaling pathways. Based on cross-talk between IGF-IR and EGFR pathways, combination studies to target both pathways were performed, and enhanced inhibitory activities were observed. These results provide a strategy for testing combinations of IGF-IR inhibitors with other targeted therapies in clinical studies to achieve improved patient outcomes. Further exploration of mechanisms for intrinsic and acquired drug resistance by these preclinical studies may lead to more rationally designed drugs that target multiple pathways for enhanced antitumor efficacy.
Infrared Spectroscopic Imaging: The Next Generation (2012)

Infrared (IR) spectroscopic imaging seemingly matured as a technology in the mid-2000s, with commercially successful instrumentation and reports in numerous applications. Recent developments, however, have transformed our understanding of the recorded data, provided capability for new instrumentation, and greatly enhanced the ability to extract more useful information in less time. These developments are summarized here in three broad areas--data recording, interpretation of recorded data, and information extraction--and their critical review is employed to project emerging trends. Overall, the convergence of selected components from hardware, theory, algorithms, and applications is one trend. Instead of similar, general-purpose instrumentation, another trend is likely to be diverse and application-targeted designs of instrumentation driven by emerging component technologies. The recent renaissance in both fundamental science and instrumentation will likely spur investigations at the confluence of conventional spectroscopic analyses and optical physics for improved data interpretation. While chemometrics has dominated data processing, a trend will likely lie in the development of signal processing algorithms to optimally extract spectral and spatial information prior to conventional chemometric analyses. Finally, the sum of these recent advances is likely to provide unprecedented capability in measurement and scientific insight, which will present new opportunities for the applied spectroscopist.