gebhart/patrepeval huggingface dataset:
Functional Outcomes of Bone Graft Substitutes for Benign Bone Tumors (2004)

Benign bone tumors are frequently treated surgically by intralesional excision with grafting. Due to the significant morbidity associated with autogenous graft, there is interest in bone graft substitutes. Ninety-eight consecutive patients with benign bone tumors treated by intralesional excision with bone graft substitutes were retrospectively reviewed. Functional scores using the International Symposium of Limb Salvage (ISOLS) system were obtained at most recent follow-up. The mean functional score was 28.3 out of 30 (94%). Three patients suffered fractures that ultimately healed with management. There were no local recurrences. Based on results of this study, bone graft substitutes are a reasonable alternative to autogenous grafting with a successful functional outcome.
Role of PI3K-Akt in crosstalk between Notch and CD28-CD80/86 pathways in dendritic cell “backsignaling” (162.2) (2012)

Abstract Survival of myeloma cells is characterized by their interaction with bone marrow stromal cells, which produce critical soluble factors including IL-6 and IDO. Targeting pathways involved in production of factors which are important in myeloma cell biology, provides novel therapeutic targets for a disease which otherwise remains incurable. At the cellular level, dendritic cells (DC) in the bone marrow microenvironment and at the molecular level the CD28-CD80/86 and Notch-Jagged pathways were separately implicated by us in myeloma induced IL-6 production. While Notch signaling leading to IL-6 production in DC is well understood, the mechanism of “backsignaling” via CD80/86- ligands with short cytoplasmic tails, remains largely uncharacterized. We demonstrate that inhibiting Notch signaling leads to a significant decrease in CD28 mediated IL-6 and IDO production by DC, suggesting crosstalk between Notch and CD28-CD80/86 pathways. IL-6 production by dendritic cells, upon ligation of CD80/86 by CD28-Ig, involves the PI3K-Akt-FoxO3a axis, which has not been previously established. Furthermore, we demonstrate a novel crosstalk between Notch and CD80/86 signaling involving regulation of the PI3K-Akt pathway by casein kinase and PTEN, which in turn are regulated by Notch signaling. Targeting pathways involved in IL-6 and IDO prompts not only clinical evaluation to improve MM patient outcome but also extends to advancing knowledge in T-cells and normal plasma cell biology.
Novel 3D Pharmacophore of α-MSH/γ-MSH Hybrids Leads to Selective Human MC1R and MC3R Analogues (2004)

To further evaluate elements that could contribute to the 3D topographical structure of gamma-MSH, we have systematically designed a group of linear gamma-MSH analogues and evaluated their biological activities: without a N-terminal acetyl, with and without a C-terminal amide, with Nle(3), with l- or d-Phe(6) or d-Nal(2')(6), and with d-Trp(8) or d-Nal(2')(8). It was found that changing the C-terminal acid in gamma-MSH to an amide and replacing Met with Nle leads to increased binding affinities at all four subtypes of melanocortin receptors (10-100 fold). Substitution of Trp(8) with d-Nal(2')(8) and Phe(6) with d-Phe(6) in gamma-MSH-NH(2) forms a selective antagonist for the hMC3R, whereas, substitution of Phe(6) with d-Nal(2')(6) and replacing Trp(8) with d-Trp(8) at gamma-MSH-NH(2) yields a selective partial agonist for the hMC1R. Finally, substitution of His(5) with Pro(5) and Trp(8) with d-Nal(2')(8) in gamma-MSH-NH(2) leads to a highly potent and selective agonist for the hMC1R. Molecular modeling showed that, at the C-terminal of Nle(3)-gamma-MSH-NH(2), there is a reverse-turn-like structure, suggesting that there might be a secondary binding site involved in ligand-receptor interaction for gamma-MSH analogues that may explain the enhanced binding affinities of the Nle(3)-gamma-MSH-NH(2) analogues. Our results indicate that increasing the hydrophobicity and replacing Phe(6) and Trp(8) with bulkier aromatic amino acid residues is very important for selectivity of alpha-MSH/gamma-MSH hybrids for hMCRs.
SNL-NUMO collaborative : development of a deterministic site characterization tool using multi-model ranking and inference. (2008)

Uncertainty in site characterization arises from a lack of data and knowledge about a site and includes uncertainty in the boundary conditions, uncertainty in the characteristics, location, and behavior of major features within an investigation area (e.g., major faults as barriers or conduits), uncertainty in the geologic structure, as well as differences in numerical implementation (e.g., 2-D versus 3-D, finite difference versus finite element, grid resolution, deterministic versus stochastic, etc.). Since the true condition at a site can never be known, selection of the best conceptual model is very difficult. In addition, limiting the understanding to a single conceptualization too early in the process, or before data can support that conceptualization, may lead to confidence in a characterization that is unwarranted as well as to data collection efforts and field investigations that are misdirected and/or redundant. Using a series of numerical modeling experiments, this project examined the application and use of information criteria within the site characterization process. The numerical experiments are based on models of varying complexity that were developed to represent one of two synthetically developed groundwater sites; (1) a fully hypothetical site that represented a complex, multi-layer, multi-faulted site, and (2) a site that was based on the Horonobe site in northern Japan. Each of the synthetic sites were modeled in detail to provide increasingly informative 'field' data over successive iterations to the representing numerical models. The representing numerical models were calibrated to the synthetic site data and then ranked and compared using several different information criteria approaches. Results show, that for the early phases of site characterization, low-parameterized models ranked highest while more complex models generally ranked lowest. In addition, predictive capabilities were also better with the low-parameterized models. For the latter iterations, when more data were available, the information criteria rankings tended to converge on the higher parameterized models. Analysis of the numerical experiments suggest that information criteria rankings can be extremely useful for site characterization, but only when the rankings are placed in context and when the contribution of each bias term is understood.
Stereotactic radiosurgery alone for multiple brain metastases? A review of clinical and technical issues (2017)

Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases.
Information aggregation in exponential family markets (2014)

We consider the design of prediction market mechanisms known as automated market makers. We show that we can design these mechanisms via the mold of exponential family distributions, a popular and well-studied probability distribution template used in statistics. We give a full development of this relationship and explore a range of benefits. We draw connections between the information aggregation of market prices and the belief aggregation of learning agents that rely on exponential family distributions. We develop a natural analysis of the market behavior as well as the price equilibrium under the assumption that the traders exhibit risk aversion according to exponential utility. We also consider similar aspects under alternative models, such as budget-constrained traders.
Supplementary File 5 from Mass Spectrometry–Based Proteomics Reveals Potential Roles of NEK9 and MAP2K4 in Resistance to PI3K Inhibition in Triple-Negative Breast Cancers (2023)

&lt;p&gt;Response markers (pathways)&lt;/p&gt;
Structural and Mechanistic Analysis of Sialic Acid Synthase NeuB from Neisseria meningitidis in Complex with Mn2+, Phosphoenolpyruvate, and N-Acetylmannosaminitol (2004)

In Neisseria meningitidis and related bacterial pathogens, sialic acids play critical roles in mammalian cell immunity evasion and are synthesized by a conserved enzymatic pathway that includes sialic acid synthase (NeuB, SiaC, or SynC). NeuB catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine, directly forming N-acetylneuraminic acid (or sialic acid). In this paper we report the development of a coupled assay to monitor NeuB reaction kinetics and an 18O-labeling study that demonstrates the synthase operates via a C-O bond cleavage mechanism. We also report the first structure of a sialic acid synthase, that of NeuB, revealing a unique domain-swapped homodimer architecture consisting of a (beta/alpha)8 barrel (TIM barrel)-type fold at the N-terminal end and a domain with high sequence identity and structural similarity to the ice binding type III antifreeze proteins at the C-terminal end of the enzyme. We have determined the structures of NeuB in the malate-bound form and with bound PEP and the substrate analog N-acetylmannosaminitol to 1.9 and 2.2 A resolution, respectively. Typical of other TIM barrel proteins, the active site of NeuB is located in a cavity at the C-terminal end of the barrel; however, the positioning of the swapped antifreeze-like domain from the adjacent monomer provides key residues for hydrogen bonding with substrates in the active site of NeuB, a structural feature that leads to distinct modes of substrate binding from other PEP-utilizing enzymes that lack an analogous antifreeze-like domain. Our observation of a direct interaction between a highly ordered manganese and the N-acetylmannosaminitol in the NeuB active site also suggests an essential role for the ion as an electrophilic catalyst that activates the N-acetylmannosamine carbonyl to the addition of PEP.
Understanding the Role of Polymer Surface Nanoscale Topography on Inhibiting Bacteria Adhesion and Growth (2015)

Catheter-associated infections, most of which are caused by microbial biofilms, are still a serious issue in healthcare and are associated with significant morbidity, mortality, and excessive medical costs. Currently, the use of nanostructured materials, especially materials with nanofeatured topographies, which have more surface area, altered surface energy, enhanced select protein adsorption, and selectively increased desirable cell functions while simultaneously decreasing competitive cell functions, seem to be among the most promising ways for reducing initial bacteria attachment, biofilm formation, and infections. In this study, polydimethylsiloxane (PDMS), a commonly used polymeric catheter material, was formulated to mimic the nanopatterned topography of natural tissue by using a template method with nanotubular anodized titanium. Results showed that increased PDMS surface nanoscale roughness alone can inhibit both Gram-negative (<i>Escherichia coli</i>) and Gram-positive (<i>Staphylococcus aureus</i>) bacteria adhesion and growth for up to 2 days, the time length of the current study. Additionally, increased fibroblast and endothelial cell adhesion on nano-PDMS indicated that this nanoscale topography had no toxic effects toward mammalian cells. Mechanistically, this study also developed a model for the first time to correlate bacteria responses to nanoscale roughness with initial protein and biomolecule adsorption (specifically, casein protein and glucose, which are unique biomolecules that mediate bacteria functions). Data revealed that the increase in nanoscale roughness and associated energy contributed to greater select casein adsorption during the first several minutes of culture, which is critical for decreasing bacteria attachment and growth. In contrast, no significant differences for glucose adsorption between samples before and after nanofabrication were identified. These results together indicated that the present biomimetic nanopatterned PDMS surface without any chemical or antibiotic modification has the potential to combat catheter-associated infections and should be further investigated.
ChemInform Abstract: Solution and Solid Phase p‐Alkoxybenzylation of Alcohols under Neutral Conditions. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Phenotypic Variation in Combined Granular-Lattice (Avellino) Corneal Dystrophy (1993)

Combined granular and lattice corneal dystrophy may present with substantial phenotypic variation. The disease can be found in individuals who trace their ancestry to both Italy and Germany, a wider geographic distribution than previously proposed.
TRIM33 gene somatic mutations identified by next generation sequencing in neoplasms of patients with anti-TIF1γ positive cancer-associated dermatomyositis (2021)

These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.
Safety Evaluation of River Water and Tap Water in the Shinano River Downstream Region by Ames Mutagenicity Assay. (2004)

信濃川下流域における6箇所の浄水場の水道水と各浄水場付近の河川水 (水道原水) を用いて, 2002年の1年間, 毎月1回TA100-S9条件でAmes変異原性試験を実施した。水道水の変異原性の年平均値は500～990netrev./lであり, 新潟市では1993年よりも低下していた。年平均値のリスクレベルは, 発がんリスクと関連させた評価からは低いと判断された。しかし, 冬期は高めであり, この時期の特に下流地点については留意する必要があると考えられた。水道原水については変異原性生成能 (MFP) を測定した。MFPの年平均値は600～1, 000net rev./lであり, 水道水と同様に冬期に高い傾向を示した。水道水の変異原性と水道原水のMFPには正の相関が見られたことから, 水道水の変異原性の低減を図る上でMFPが水道原水の有用な水質評価指標になる可能性が示唆された。
Are resuscitation fluids harmful? (2000)

Copyright © by 2000 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Observation of Erythrocyte Dynamics in the Retinal Capillaries and Choriocapillaris Using ICG-Loaded Erythrocyte Ghost Cells (2008)

Reinjected ICG-loaded erythrocytes permit routine visualization of retinal capillary and choriocapillaris hemodynamics of the intact eye. It is speculated that erythrocyte-pausing in both microcirculations facilitates metabolic exchange across capillary walls. In retinal capillaries, pausing is presumed to result from vasomotion-which has been postulated as necessary for the inhibition of retinal edema-and in choriocapillaries, to result from the shifting distributions of local perfusion pressures within the network of capillary vessel segments that comprise each lobular area of the choriocapillaris vascular plexus.
<title>Progress in the development of far-ultraviolet etalons</title> (1997)

We report on a continuing program to develop and test reflecting coatings suitable for use in Fabry-Perot etalons operating in the far ultraviolet region of the spectrum. UV etalons are of particular interest for solar studies as they have the potential to enable one to make wide-field high resolution diagnostic images such as spectroheliograms, dopplergrams, and density maps in isolated spectral lines formed in the upper chromosphere, transition region and lower corona. The performance of the high-efficiency coatings required by a UV etalon is limited both by the availability of suitable materials, and by the uniformity and accuracy of the deposition process. The lack of UV transmitting materials with a wide range of refractive index is especially troublesome. The latter problem may be partially overcome by using a vacuum-spaced etalon design. A vacuum-spaced etalon with cultured quartz plates was successfully operated at 160 nm in a previous study. In this study, we investigated a family of coating designs based on the fluoride salts of magnesium and lanthanum, finding that usable etalon performance may be achievable at wavelengths as short as 120 nm. Results of theoretical predictions and the performance of test coatings are presented. This work was supported by NASA under contract NASW-5007.
Transplantation of Marrow to Extramedullary Sites (1968)

Autologous fragments of transplanted marrow have survived in various extramedullary sites in the rat, rabbit, and dog. Survival of the fragments occurs with a complete reconstitution of the hemopoietic and adventitial structures. The process originates from a network of surviving reticular cells which proliferate and differentiate into osteoblasts and give rise to trabecular bone. Later, the reticular cells reconstruct the marrow's microcirculation. Hemopoietic repopulation of the marrow implant takes place only after its sinusoidal microcirculation has been established.
The Importance of 1,5‐Oxygen⋅⋅⋅Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis (2019)

The importance of 1,5-O⋅⋅⋅chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch=O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O⋅⋅⋅Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density functional theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.
Cervical spinal cord atrophy (2018)

This study provides Class III evidence that MRI cervical spinal cord atrophy distinguishes patients at the onset of progressive MS from those with RIS and RRMS.
Phosphatidylglycerol-specific Phospholipase C from Amycolatopsis Sp. NT115: Biochemical Characterization and Heterologous Expression (2022)

In recent years, phosphatidylglycerol (PG) has been attracting attention in the field of cell physiology such as photosynthesis and germ cells, or clinical diagnosis. Most of phospholipids containing PG are analyzed using HPLC and LC-MS; however, it has been desired to develop an enzymatic assay method for determination of PG concentration in a simple, easy, and high-through put.In our presentation, biochemical characterization of a PG-specific phospholipase C (PG-PLC) from Amycolatopsis sp. NT115 will be reported. PG-PLC (molecular mass, 55 kDa) showed maximal activity at pH 6.0 and 55°C. PG-PLC showed almost no activity on other diacylphospholipids, dipalmitoylPG, lysoPG and glycerol 3-phosphate, demonstrating PG-PLC can recognize not only the substrate headgroup but also the acyl chains. PG-PLC was inhibited by Zn2+; however, it was hardly inhibited by EDTA and non-ionic surfactants such as Triton X-100, Tween 80, Briji 35 and Nonidet P-40. PG-PLC activity was enhanced by 1 mM Mn2+, Al3+, 0.1% sodium deoxycholate by 1.3-2.5 folds. Recombinant PG-PLC (rPG-PLC) was extracellularly produced using Streptomyces lividans/pUC702 expression system. However, unexpectedly it was produced with the N-terminal region deleted by ca. 230 amino acids. As a result, the stability of the deletion mutant (Δ230aa) was markedly decreased. In 96 h culture, rPG-PLC with His6-tag was produced with 0.188 U/mL and 3.36×10-2 U/mg-protein in the culture supernatant. Moreover, 1.52 mg-protein of the purified Δ220aa (2.5 U/mL, 16.4 U/mg-protein) was yielded from 0.9 L of the culture supernatant by His-tag affinity chromatography. Using the purified Δ220aa, kinetic parameters were determined to be Km=0.368 mM, 99.2 µM/min (6.51 mmol/min/mg-protein), kcat=5.29×10-2 s-1, kcat/Km=0.256 mM-1s-1 for POPG.
Explant Developmental State and Shoot Formation in Pinus radiata Cotyledons (1985)

Adventitious shoots from the epidermal and subepidermal layers of Pinus radiata cotyledons were induced in culture. Cotyledons of different ages were examined with light and electron microscopy. The developmental state of the cotyledons at the time of excision influenced their shoot-forming ability in culture. Epidermal layers of cotyledons predisposed to form shoots have less-developed stomatal complexes, thinner cell walls, no epicuticular wax, partially depleted protein reserves, and unhydrolyzed lipid reserves, whereas those of cotyledons that did not form shoots have more-developed stomatal complexes, thicker cell walls, epicuticular wax, depleted protein reserves, and nearly depleted lipid reserves.
Modulation of Microenvironment Acidity Reverses Anergy in Human and Murine Tumor-Infiltrating T Lymphocytes (2012)

Stimulating the effector functions of tumor-infiltrating T lymphocytes (TIL) in primary and metastatic tumors could improve active and adoptive T-cell therapies for cancer. Abnormal glycolysis, high lactic acid production, proton accumulation, and a reversed intra-extracellular pH gradient are thought to help render tumor microenvironments hostile to roving immune cells. However, there is little knowledge about how acidic microenvironments affect T-cell immunity. Here, we report that lowering the environmental pH to values that characterize tumor masses (pH 6-6.5) was sufficient to establish an anergic state in human and mouse tumor-specific CD8(+) T lymphocytes. This state was characterized by impairment of cytolytic activity and cytokine secretion, reduced expression of IL-2Rα (CD25) and T-cell receptors (TCR), and diminished activation of STAT5 and extracellular signal-regulated kinase (ERK) after TCR activation. In contrast, buffering pH at physiologic values completely restored all these metrics of T-cell function. Systemic treatment of B16-OVA-bearing mice with proton pump inhibitors (PPI) significantly increased the therapeutic efficacy of both active and adoptive immunotherapy. Our findings show that acidification of the tumor microenvironment acts as mechanism of immune escape. Furthermore, they illustrate the potential of PPIs to safely correct T-cell dysfunction and improve the efficacy of T-cell-based cancer treatments.