gebhart/patrepeval huggingface dataset:
Abstract 2457: Ex vivo analysis of novel isoflavanoids (ME-143 and ME-334) in patient derived triple negative breast cancer tumors. (2013)

Abstract There is an unmet need for novel effective therapeutics to treat triple negative (ER, PR and Her2 negative) breast cancer in clinics. Phase I clinical studies of 2 novel isoflavonoid investigational drugs, ME-143 and ME-344 have been shown them to be generally well tolerated in patients with solid tumors. ME-143, a next analogue of the investigational anti-cancer drug Phenoxodiol binds at low nanomolar concentrations to a tumor-specific variant of cell surface associated NADH oxidase (tNOX), resulting in caspase activation and apoptotic tumor cell death. ME-344, a second investigational anti-cancer isoflavonoid, is structurally related to ME-143 but functionally distinct. ME-344 is a mitochondrial targeting agent that interferes with tumor cell energy generation resulting in cell death via mitochondrial membrane destabilization and autophagy induction through the disruption of both mTOR1 and mTOR2 upstream and downstream signal transduction pathways. Pre-clinical studies using in vitro cell lines showed significantly high potency for both compounds either when used as single agents or when combined with cytotoxic and targeted anti-cancer agents. The present study investigated the ex vivo efficacy of ME-143 and ME-344 using patient-derived tumor cells from triple negative breast cancer. Tumor tissue was disintegrated into single cell suspension and expanded in mouse as subcutaneous patient-derived xenograft before harvesting for the studies. Mouse tumor cells were disintegrated into single cells and were grown as spheroids to mimic the tumor micro-environment and single agent as well as combination treatments were performed. Using a high content imaging platform, various endpoints were evaluated to compare the efficacies of the drugs. Both ME-143 and ME-344 as single agents showed efficacy in inhibiting cell proliferation as well as colony formation in patient-derived triple negative breast cancer cells while combination of these agents with Cisplatin and Gemcitabine demonstrated additive or synergistic effects. Use of high content imaging has enabled the identification of patient population that has tumor cells resistant to very high doses of drugs. Follow-up studies are planned to characterize the sub-population of cells that are resistant to high dose of these drugs. Citation Format: Kesavan Nair Praveen, Thomas Broudy, Cyrus Mirsaidi, Ofir Moreno, Daniel Gold. Ex vivo analysis of novel isoflavanoids (ME-143 and ME-334) in patient derived triple negative breast cancer tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2457. doi:10.1158/1538-7445.AM2013-2457
Ion selectivity of gram-negative bacterial porins (1985)

Twelve different porins from the gram-negative bacteria Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Yersinia pestis were reconstituted into lipid bilayer membranes. Most of the porins, except outer membrane protein P, formed large, water-filled, ion-permeable channels with a single-channel conductance between 1.5 and 6 nS in 1 M KCl. The ions used for probing the pore structure had the same relative mobilities while moving through the porin pore as they did while moving in free solution. Thus the single-channel conductances of the individual porins could be used to estimate the effective channel diameters of these porins, yielding values ranging from 1.0 to 2.0 nm. Zero-current potential measurements in the presence of salt gradients across lipid bilayer membranes containing individual porins gave results that were consistent with the conclusions drawn from the single-channel experiments. For all porins except protein P, the channels exhibited a greater cation selectivity for less mobile anions and a greater anion selectivity for less mobile cations, which again indicated that the ions were moving inside the pores in a fashion similar to their movement in the aqueous phase. Three porins, PhoE and NmpC of E. coli and protein P of P. aeruginosa, formed anion-selective pores. PhoE and NmpC were only weakly anion selective, and their selectivity was dependent on the mobility of the ions. In contrast, cations were unable to enter the selectivity filter of the protein P channel. This resulted in a high anion selectivity for all salts tested in this study. The other porins examined, including all of the known constitutive porins of the four gram-negative bacteria studied, were cation selective with a 3- to 40-fold preference for K+ ions over Cl- ions.
Comparative Study of the Hemostatic Efficacy of a New Human Fibrin Sealant: Is an Antifibrinolytic Agent Necessary? (2002)

Background Sustained hemostasis by fibrin sealant (FS) is critically important when it is used in trauma surgery. To purportedly delay fibrin degradation and prevent premature hemostatic failure, some FS products added an antifibrinolytic agent (e.g., bovine aprotinin). The purpose of this study was to compare the overall hemostatic efficacy of a new inhibitor-free FS obtained from the American Red Cross (ARC-FS) to a clinically available aprotinin-containing FS preparation (Tisseel). The need for addition of an antifibrinolytic agent was assessed under normal and high-fibrinolytic conditions. Methods The abdominal aortas of anesthetized rabbits were transected and anastomosed, end-to end, using only four interrupted sutures. The suture line was covered with ∼2 mL of either type of FS and blood flow was restored. Blood loss was absorbed by gauze and measured. All rabbits were recovered and underwent histologic examination 4 weeks after operation. The efficacy of FS was also tested under a high-fibrinolytic state by treating the rabbits with human recombinant tissue plasminogen activator (0.15 mg/kg, 3-hour infusion). The investigators were blinded to the treatment groups. Results The majority (11 of 12) of deaths occurred because of bleeding at the suture line within 7 days of surgery. Sustained hemostasis by FS (>1 week) was required for normal tissue healing and long-term survival of animals. Application of ARC-FS to the suture line produced immediate hemostasis in 43% of animals (three of seven), with mean blood loss of 4.8 ± 1.8 mL, and 86% long-term survival. Tisseel application produced immediate hemostasis in 13% of animals (one of eight), with mean blood loss of 26.9 ± 7.0 mL (p < 0.05 vs. ARC-FS) and survival rate of 37% (three of eight). Under high-fibrinolytic conditions, ARC-FS produced immediate and complete hemostasis in seven of eight animals (88%), whereas the Tisseel demonstrated complete hemostasis in one of seven (p < 0.01). The ARC-FS rabbits had a blood loss of 1.9 ± 1.9 mL and survival rate of 75% (six of eight), whereas the Tisseel animals had a mean blood loss of 30 ± 6.0 mL and survival rate of 43% (three of seven) (p < 0.01). No detrimental effect on healing was noted with either product. Conclusion ARC-FS provides effective and secure hemostasis against high-pressure arterial bleeding under both normal and high-fibrinolytic conditions. Addition of an antifibrinolytic agent such as aprotinin is not required to sustain the hemostatic function of this fibrin sealant.
Supplementary Methods from A New Class of Antibody–Drug Conjugates with Potent DNA Alkylating Activity (2023)

&lt;p&gt;Synthesis of IGNs&lt;/p&gt;
X‐ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: Implications for inhibitor selectivity (1999)

Effective inhibitors of matrix metalloproteinases (MMPs), a family of connective tissue-degrading enzymes, could be useful for the treatment of diseases such as cancer, multiple sclerosis, and arthritis. Many of the known MMP inhibitors are derived from peptide substrates, with high potency in vitro but little selectivity among MMPs and poor bioavailability. We have discovered nonpeptidic MMP inhibitors with improved properties, and report here the crystal structures of human stromelysin-1 catalytic domain (SCD) complexed with four of these inhibitors. The structures were determined and refined at resolutions ranging from 1.64 to 2.0 A. Each inhibitor binds in the active site of SCD such that a bulky diphenyl piperidine moiety penetrates a deep, predominantly hydrophobic S'1 pocket. The active site structure of the SCD is similar in all four inhibitor complexes, but differs substantially from the peptide hydroxamate complex, which has a smaller side chain bound in the S'1 pocket. The largest differences occur in the loop forming the "top" of this pocket. The occupation of these nonpeptidic inhibitors in the S'1 pocket provides a structural basis to explain their selectivity among MMPs. An analysis of the unique binding mode predicts structural modifications to design improved MMP inhibitors.
Perspective-Based Development of Modular Product Architectures (2009)

Defining modular product structures requires taking into account various requirements from different perspectives. One problem, however, is that different perspectives on modularization may lead to different optimal product structures, depending on the special requirements the perspectives may have. For this reason, modular product architectures often need to strike a compromise. The approach we present in this paper is based on a differentiated consideration of the product-planning, purchase, assembly and after-sales perspective. While the method shows up the conflicts which are liable to arise between given perspective, certain general concepts are derived from it.
Extension of the Polyanionic Cosalane Pharmacophore as a Strategy for Increasing Anti-HIV Potency (1999)

The anti-HIV agent cosalane inhibits both the binding of gp120 to CD4 as well as an undefined postattachment event prior to reverse transcription. Several cosalane analogues having an extended polyanionic "pharmacophore" were designed based on a hypothetical model of the binding of cosalane to CD4. The analogues were synthesized, and a number of them displayed anti-HIV activity. One of the new analogues was found to possess enhanced potency as an anti-HIV agent relative to cosalane itself. Although the new analogues inhibited both HIV-1 and HIV-2, they were more potent as inhibitors of HIV-1 than HIV-2. Mechanism of action studies indicated that the most potent of the new analogues inhibited fusion of the viral envelope with the cell membrane at lower concentrations than it inhibited attachment, suggesting inhibition of fusion as the primary mechanism of action.
Effects of dimension reduction of hyperspectral images in skin gross pathology (2023)

Investigation of more complex reduction and segmentation schemes with emphasis on the nature of HSI and optical properties of the skin is necessary. Insights on dimension reduction for skin tissue could facilitate the development of HSI-based systems for cancer margin detection at gross level.
Lipopolysaccharide in systemic circulation induces activation of inflammatory response and oxidative stress in cardiorenal syndrome type 1 (2019)

CRS type 1 patients presented an increased level of LPS, pro-inflammatory cytokines, and MPO. Furthermore, there is a direct correlation between LPS and pro-inflammatory cytokines and stress oxidative marker. LPS may play a role in the pathophysiology of CRS type 1 inducing inflammation, oxidative stress and finally kidney damage.
Imaging Radiation Dose and Molecules in Human Radiation Therapy for Cancer (2017)

For the first time in history it is possible to image radiation dose delivered to patients in radiation therapy for cancer, by capturing the Cherenkov light emissions coming from their tissue. These light signals can also be used to excite molecular probes to assay tissue function and potentially response to therapy.
Clean Fractionation Pretreatment Reduces Enzyme Loadings for Biomass Saccharification and Reveals the Mechanism of Free and Cellulosomal Enzyme Synergy (2014)

Enzymatic depolymerization of polysaccharides is often a key step in the production of fuels and chemicals from lignocellulosic biomass. Historically, model cellulose substrates have been utilized to reveal insights into enzymatic saccharification mechanisms. However, translating findings from model substrates to realistic biomass substrates is critical for evaluating enzyme performance. Here, we employ a commercial fungal enzyme cocktail, purified cellulosomes, and combinations of these two enzymatic systems to investigate saccharification mechanisms on corn stover deconstructed either via clean fractionation (CF) or deacetylated dilute sulfuric acid pretreatments. CF is an organosolv pretreatment method utilizing water, MIBK, and either acetone or ethanol with catalytic amounts of sulfuric acid to fractionate biomass components. The insoluble cellulose-enriched fraction (CEF) from CF contains mainly cellulose, with minor amounts of residual hemicellulose and lignin. Enzymatic digestions at both low and high solid loadings demonstrate that CF reduces the amount of enzyme required to depolymerize polysaccharides relative to deacetylated dilute acid-pretreated corn stover. Transmission and scanning electron microscopy of the digested biomass provides evidence for the different mechanisms of enzymatic deconstruction between free and cellulosomal enzyme systems and reveals the basis for the synergistic relationship between the two enzyme paradigms on a process-relevant substrate. These results also demonstrate that the presence of lignin is more detrimental to cellulosome action than to free fungal cellulases. As enzyme costs are a major driver for biorefineries, this study provides key inputs for evaluation of CF as a pretreatment method and synergistic mixed enzyme systems as a saccharification strategy for biomass conversion.
Front Cover: Total Asymmetric Synthesis of Quinine, Quinidine, and Analogues via Catalytic Enantioselective Cascade Transformations (Eur. J. Org. Chem. 35/2019) (2019)

The Front Cover shows a versatile catalytic asymmetric strategy for the total synthesis of quinuclidine natural products, which includes the completed enantioselective synthesis of the classical targets quinine and quinidine More information can be found in the Communication by A. Córdova et al.
Adsorption of Metal Ions onto Hydrophilic Silicon Surfaces from Aqueous Solution: Effect of pH (1998)

This work examines the pH and time dependence of metal deposition onto hydrophilic silicon surfaces. We find that the surface concentration of metal species is proportional to the pH. Time dependence is seen for only a few metals, notably Cr and Fe in this study, especially at high pH. Si surfaces with wet chemical oxides were exposed to a dilute solution of ten metals: Al, Ba, Ca, Cr, Cu, Fe, K, Ni, Sr, and Zn, in dilute nitric acid solution, from pH 3 to 5.6, for different periods of time, from about 1 to 1000 s. At equilibrium the surface concentration of metals is approximately proportional to the ratio of ionic charge to ionic radius of the metal ions for many of the metal ions which exist as hydrated cations at that particular pH. We observe this proportionality over the pH range under study, although the surface concentration varies over several orders of magnitude. Cations which form amphoteric species, such as which forms and at high pH, and several other cations that do not exist as simple cations at some pHs (e.g., , and at high pH), do not show this dependence on ionic charge and radius.
Machiavelli’s Turn to Xenophon (2022)

Machiavelli's treatment of Cyrus, king and founder of the Persian Empire, followed in the tradition of scholars who later came to be known as the Italian Renaissance humanists, who had laboured from the beginning of the fifteenth century to restore the direct knowledge of classical antiquity. In doing so, they made Xenophon part of the common intellectual heritage of sixteenth-century Italians. Machiavelli enrolled in this movement when he listed Cyrus among the chief examples of those who became princes by their own virtue and not by fortune, when he compared him to no less a figure than Moses, and when he exhorted his readers to consult Xenophon's account of Cyrus's life, the only book so honoured in The Prince. Machiavelli was unable, however, simply to follow in the path of others. A sign of the difference between them is that whereas the humanists also took great interest in Plato and Aristotle, Machiavelli harboured doubts, much as Hobbes would later, as to the wisdom of reinstating these figures as intellectual authorities. Indeed, for Machiavelli, Xenophon's particular understanding of politics and philosophy and his manner of writing on these subjects are important elements of the remedy or antidote to the ills he thought produced, in part, by other philosophers from the classical tradition.
Joint CD and PMD compensation for direct-detected optical OFDM using polarization-time coding approach (2009)

We demonstrate a polarization-time coding method for direct-detected OFDM, which provides the signal with immunity against both fibre CD and PMD effects. Further dynamic PTC method is introduced for trading the PMD tolerance with receiving sensitivity.
Monocytes from circulating blood fuse in vitro with purified osteoclasts in primary culture (1984)

The origin of osteoclasts from mononuclear phagocytes and the addition of new nuclei to already differentiated osteoclasts have already been documented by several authors, but the factors controlling these events have not yet been elucidated. With the aim of investigating this problem, monocytes, isolated from circulating blood of laying hens and cultured previously for 5 days, were added to osteoclasts isolated from the medullary bone of the same hen and cultured at low density. The cultures were either fixed and observed under phase contrast at 24-h intervals for 5 days or filmed by time-lapse cinemicrography. With both techniques the formation of extensive areas of membrane contacts, generally followed by fusion between some monocytes and osteoclasts, was observed. The absence of added resorbing factors and the possible mechanisms by which osteoclast precursors are recruited in vivo are discussed.
Power dependence of defect formation in SiO2 glass by F2 laser irradiation (2002)

The dependence of defect formation in a high-purity synthetic SiO2 glass on F2 laser power was studied. Above the threshold value of ∼10 mJ cm−2 pulse−1 (∼0.5 MW cm−2), the concentration of the laser-induced E′ center created by the dissociation of Si–O–Si bond increased as a function of the F2 laser power squared. The quantum yield of the E′ center formed by the high-power F2 laser irradiation was ∼3 orders of magnitude larger than that formed via two-photon absorption processes of KrF or ArF laser pulses. This strongly suggests that irradiating with the high-power F2 laser creates the E′ center via two-step absorption processes.
Processable, Electroactive, and Aqueous Compatible Poly(3,4-alkylenedioxypyrrole)s through a Functionally Tolerant Deiodination Condensation Polymerization (2008)

We present a method for the synthesis of soluble and processable 3,4-alkylenedioxypyrrole (XDOP)-based conjugated polymers via an iododecarboxylation−deiodination polymerization methodology. Polymerization to the respected PXDOP derivatives of suitably high molecular weight (3.8−14.2 kDa vs polystyrene as measured by GPC) was achieved by either heating the neat monomers for a few hours or allowing them to remain at room temperature for several days. A family of four polymers was synthesized and characterized optically and electrochemically. Polymer solutions were transparent in the visible in their neutral states, red in their partially oxidized states, and grayish-green in their heavily oxidized states. Electrochemical measurements of cast films show that all redox processes occur at low potentials (ca. 0 V vs the Fc/Fc+), similar to electrodeposited films. Polymers spray-cast as films onto ITO exhibited high band gaps above 3.0 eV along with stable UV and near-IR electrochromism in organic solvents with almost no change in the visible. An amphiphilic polymer functionalized with oligoethoxy substituents exhibited enhanced electrochemistry in aqueous electrolyte and high-contrast electrochromism with respect to the nonpolar functionalized polymers in the visible and near-IR.
Demand Access Protocol Design and Validation with SPIN (2008)

In order for distributed systems to communicate reliably engineers standardize on communication rules (or protocols). Unforeseen behavior in communication protocols can push faults up to applications resulting in uncontrollable systems and should not be tolerated. However, while most modern protocols undergo extensive testing, rigorous formal methods, such as model checking, are rarely used due to complexity and intractable state spaces. Nevertheless, starting formal validation early in the development cycle provides less-complexity, significantly smaller state spaces and can allow for full validation. As a side benefit early error detection and correction costs significantly less than redesigns later in a system's life-cycle.This paper discusses the preliminary design and validation of the Demand Access Protocol (DAP) using the SPIN model checker. Using English language specifications and flow charts, the author developed a PROMELA (the language used by SPIN) specification and tested basic safety properties. Used correctly, a model checker can thoroughly validate complex systems and guarantee absence of fault conditions.
Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib (2013)

Clinicaltrials.gov, Identifier: NCT00568841.
Optical parametric wideband frequency modulation (2022)

Various types of photonic applications, such as sensing and communication, require the generation of wideband optical frequency-modulated (FM) signals. However, generating a wideband FM signal beyond the electrical bandwidth limitation of optical modulators is difficult. Here, we propose a method to increase the bandwidths of optical FM signals by using the cascaded four-wave-mixing (FWM) process and show its potential in two applications. We first demonstrate 11-fold bandwidth expansion of frequency-modulated continuous-wave signals (from 5 to 55 GHz), beyond the optical modulator bandwidth. Next, we demonstrate the signal-to-noise ratio (SNR) enhancement for analog communication. The SNR of an analog signal can be increased by ∼12.8 dB using the proposed method. These results show the potential of the proposed method for sensing and communication applications. In addition, the proposed concept opens new possibilities in parametric FWM applications.