gebhart/patrepeval huggingface dataset:
Cyclic Adenosine Monophosphate/Protein Kinase A Mediates Parathyroid Hormone/Parathyroid Hormone‐Related Protein Receptor Regulation of Osteoclastogenesis and Expression of RANKL and Osteoprotegerin mRNAs by Marrow Stromal Cells (2002)

Parathyroid hormone (PTH) is a major regulator of osteoclast formation and activation, effects that are associated with reciprocal up- and down-regulation of RANKL and osteoprotegerin (OPG), respectively. The roles of specific downstream signals generated by the activated PTH/PTH-related protein (PTHrP) receptor (PTH1R), such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phospholipase C/protein kinase C (PLC/PKC), in controlling RANKL and OPG expression and osteoclastogenesis remain uncertain. In MS1 conditionally transformed clonal murine marrow stromal cells, which support PTH-induced osteoclast formation from cocultured normal spleen cells, PTH(1-34) increased RANKL and macrophage colony-stimulating factor (M-CSF) mRNA expression and decreased that of OPG when present continuously for 7-20 days at 37 degrees C in the presence of dexamethasone (Dex). In cells precultured for 7 days and then treated with PTH(1-34), similar reciprocal regulation of RANKL and OPG occurred, maximally at 6-24 h, that was of greater amplitude than the changes induced by chronic (7-10 days) PTH exposure. These acute effects of PTH(1-34) were mimicked by PKA stimulators (8-bromoadenosine [8Br]-cAMP or forskolin [FSK]), blocked by the PKA inhibitor Rp-cAMPs but unaffected by the PKC inhibitor GF109203X. Amino-truncated PTH(1-34) analogs PTH(5-34) and PTH(7-34) neither increased cAMP production in MS1 cells nor regulated RANKL or OPG mRNA. Reciprocal RANKL/OPG mRNA regulation was induced in MS1 cells by PTH(3-34) but only at high concentrations that also increased cAMP. The highly PKA-selective PTH analog [Gly1,Arg19]human PTH(1-28) exerted effects similar to PTH(1-34) on RANKL and OPG mRNAs and on osteoclast formation, both in MS1/spleen cell cocultures and in normal murine bone marrow cultures. The direct PKC stimulator 12-O-tetradecanoylphorbol-13-acetate (PMA) did not induce RANKL mRNA in MS1 cells, but it did up-regulate OPG mRNA and also antagonized osteoclast formation induced by PTH(1-34) in both MS1/spleen cocultures and normal bone marrow cultures. Thus, cAMP/PKA signaling via the PTH1R is the primary mechanism for controlling RANKL-dependent osteoclastogenesis, although direct PKC activation may negatively regulate this effect of PTH by inducing expression of OPG.
Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation (2015)

Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Previous studies demonstrate that T1-diabetes decreases osteoblast activity and viability. Bisphosphonate therapy, commonly used to treat osteoporosis, is demonstrated to inhibit osteoclast activity as well as osteoblast apoptosis. Therefore, we examined the effect of weekly alendronate treatments on T1-diabetes induced osteoblast apoptosis and bone loss. Bone TUNEL assays identified that alendronate therapy prevents the diabetes-induced osteoblast death observed during early stages of diabetes development. Consistent with this, alendronate treatment for 40 days was able to prevent diabetes-induced trabecular bone loss. Alendronate was also able to reduce marrow adiposity in both control diabetic mice compared to untreated mice. Mechanical testing indicated that 40 days of alendronate treatment increased bone stiffness but decreased the work required for fracture in T1-diabetic and alendronate treated mice. Of concern at this later time point, bone formation rate and osteoblast markers, which were already decreased in diabetic mice, were further suppressed in alendronate-treated diabetic mice. Taken together, our results suggest that short-term alendronate treatment can prevent T1-diabetes-induced bone loss in mice, possibly in part by inhibiting diabetes onset associated osteoblast death, while longer treatment enhanced bone density but at the cost of further suppressing bone formation in diabetic mice.
Diastrophic dysplasia gene maps to the distal long arm of chromosome 5. (1990)

We have used polymorphic DNA markers to map the gene for a clinically well-characterized form of osteochondrodysplasia, diastrophic dysplasia (DD), an autosomal recessive disorder of unknown pathogenesis. Linkage was analyzed in 13 families with two or three affected sibs comprising a total of 84 individuals. Positive two-point logarithm-of-odds (lod) scores were obtained between the DD locus and three polymorphic markers on chromosome 5. The highest pairwise lod score estimate of 7.37 with zero recombination to locus D5S72 suggests very tight linkage. There was no evidence of heterogeneity. Multipoint linkage analysis against the published order of the three loci gave the result centromere-D5S84-(DD, D5S72)-D5S61-terminus with a four-point lod score of 9.11. The present findings place the DD locus distal to the gene for adenomatous polyposis coli on the distal part of the long arm of chromosome 5. Our results provide a basis for refining the map position of the DD locus followed by physical localization, isolation, and characterization of the gene.
Supplementary Tables 1-4 from Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity (2023)

Supplementary Tables 1-4 from Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity
Patch selection by bumble bees navigating discontinuous landscapes (2021)

Pollen and nectar resources are unevenly distributed over space and bees must make routing decisions when navigating patchy resources. Determining the patch selection process used by bees is crucial to understanding bee foraging over discontinuous landscapes. To elucidate this process, we developed four distinct probability models of bee movement where the size and the distance to the patch determined the attractiveness of a patch. A field experiment with a center patch and four peripheral patches of two distinct sizes and distances from the center was set up in two configurations. Empirical transition probabilities from the center to each peripheral patch were obtained at two sites and two years. The best model was identified by comparing observed and predicted transition probabilities, where predicted values were obtained by incorporating the spatial dimensions of the field experiment into each model's mathematical expression. Bumble bees used both patch size and isolation distance when selecting a patch and could assess the total amount of resources available in a patch. Bumble bees prefer large, nearby patches. This information will facilitate the development of a predictive framework to the study of bee movement and of models that predict the movement of genetically engineered pollen in bee-pollinated crops.
Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas (2009)

Low BRCA1 expression in primary sporadic ovarian carcinoma is associated with prolonged survival. Recurrent ovarian carcinomas commonly have increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which could mediate resistance to platinum based therapies. However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations.
Restructuring of Mechanically Deboned Chicken and Nonmeat Binders in a Twin‐screw Extruder (1990)

ABSTRACT A twin‐screw cooking extruder was used to restructure mechanically deboned chicken (MDC) in combination with three nonmeat binders, corn starch (CS), soy protein isolate (SPI) and wheat gluten (WG), at concentrations of 10–30%. Extrudates were evaluated by apparent tensile stress (ATS), Warner Bratzler shear stress (WBSS), proximate composition and reheat yield. SPI and WG were less effective than starch for increasing the ATS and WBSS of extruded MDC. The effects of die temperatures between 71–115°C on chemical and textural properties of extrudates containing 10% and 15% starch were investigated. The ATS and WBSS increased as a function of temperature up to 104°C. Fat content and lipid oxidation decreased as extrusion temperatures increased.
Community modulated recursive trees and population dependent branching processes (2021)

Abstract We consider random recursive trees that are grown via community modulated schemes that involve random attachment or degree based attachment. The aim of this article is to derive general techniques based on continuous time embedding to study such models. The associated continuous time embeddings are not branching processes: individual reproductive rates at each time t depend on the composition of the entire population at that time, and hence vertices do not reproduce independently. Using stochastic analytic techniques we show that various key macroscopic statistics of the continuous time embedding stabilize, allowing asymptotics for a host of functionals of the original models to be derived.
Complement C1q in plasma induces nonspecific binding of poly(acrylic acid)-coated upconverting nanoparticle antibody conjugates (2022)

Upconverting nanoparticles are attractive reporters for immunoassays, because their high specific activity and lack of autofluorescence background enable their detection at extremely low concentrations. However, the sensitivity achieved with heterogeneous sandwich immunoassays using nanoparticle reporters is generally limited by the nonspecific binding of nanoparticle antibody conjugates to solid supports. In this study, we characterized plasma components associated with elevated nonspecific binding of poly(acrylic acid)-coated upconverting nanoparticles in heterogeneous two-step sandwich immunoassays. Plasma was consecutively fractionated using various chromatographic methods by selecting after each step the fractions producing the highest nonspecific binding of upconverting nanoparticle conjugates in an immunoassay for cardiac troponin I. Finally, the proteins in the fractions associated with highest amount of nonspecific binding were separated by gel electrophoresis and identified with mass spectrometry. The results indicated that complement component C1q was present in the fractions associated with the highest signal from nonspecific binding. The interference was not limited to only poly(acrylic acid)-coated nanoparticles or certain antibody combination, but occurred more generally. The interference was removed by increasing the ionic strength of the assay buffer in the sample incubation step or by adding a negatively charged blocker to bind on positively charged C1q, suggesting that the interaction is mostly electrostatic. Hence, we assume that the interference is likely to affect various negatively charged nanoparticles. The identification of complement component C1q as the major interfering protein allows for more rational design of countermeasures in future immunoassay development utilizing nanoparticle reporters.
Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms (2017)

Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms. At the systemic level, the iron-regulatory hormone hepcidin is released from the liver in response to these cues, binds to ferroportin and triggers its degradation. The relative importance of individual ferroportin control mechanisms and their interplay at the systemic level is incompletely understood. Here, we built a mathematical model of systemic iron regulation. It incorporates the dynamics of organ iron pools as well as regulation by the hepcidin/ferroportin system. We calibrated and validated the model with time-resolved measurements of iron responses in mice challenged with dietary iron overload and/or inflammation. The model demonstrates that inflammation mainly reduces the amount of iron in the blood stream by reducing intracellular ferroportin transcription, and not by hepcidin-dependent ferroportin protein destabilization. In contrast, ferroportin regulation by hepcidin is the predominant mechanism of iron homeostasis in response to changing iron diets for a big range of dietary iron contents. The model further reveals that additional homeostasis mechanisms must be taken into account at very high dietary iron levels, including the saturation of intestinal uptake of nutritional iron and the uptake of circulating, non-transferrin-bound iron, into liver. Taken together, our model quantitatively describes systemic iron metabolism and generated experimentally testable predictions for additional ferroportin-independent homeostasis mechanisms.
Extensible Provisioning Protocol (EPP) Unhandled Namespaces (2021)

The Extensible Provisioning Protocol (EPP), as defined in RFC 5730,
includes a method for the client and server to determine the objects
to be managed during a session and the object extensions to be used
during a session. The services are identified using namespace URIs.
How should the server handle service data that needs to be returned in
the response when the client does not support the required service
namespace URI, which is referred to as an unhandled namespace? An
unhandled namespace is a significant issue for the processing of RFC
5730 poll messages, since poll messages are inserted by the server
prior to knowing the supported client services, and the client needs
to be capable of processing all poll messages. This document defines
an operational practice that enables the server to return information
associated with unhandled namespace URIs that is compliant with the
negotiated services defined in RFC 5730.
Abstract 1675: Analytical validation of MSI High detection with GuardantOMNI (2019)

Background: Late stage therapy selection is advancing beyond the detection of classical driver alterations (SNV, Indel, CNV, Fusion) to the use of aggregate biomarkers comprising combinations of SNVs, Indels, and fusions, that reflect the underlying mutational process, indicate the cellular dysfunction, and suggest the neoantigen signature. GuardantOMNI (OMNI), is a highly sensitive 500-gene cfDNA sequencing test designed to detect primary somatic mutations as well as aggregate biomarkers including TMB and DDR pathway defects. The newest version of OMNI introduces MSI biomarker detection, which is an indication for the first FDA-approved pan-cancer therapy. Here we present the first analytical validation study of OMNI MSI-H detection.Methods: Probabilistic models for MSI detection were designed to interrogate instability across >1300 loci, differentiating PCR and sequencing induced artifacts from true biological signals using molecular barcoding as implemented in the Guardant digital sequencing platform. Cut-offs were selected based on the analysis of the training healthy donor cohort and locked prior to validation. Analytical performance was assessed using pre-characterized cell lines, cancer-free donor-samples, and clinical patient samples. Qualitative and quantitative orthogonal confirmation was provided by next-generation sequencing (NGS) and published information.Results: 350 samples were processed for this study, using both 5ng and 30ng cfDNA input levels, and all samples passed sequencing QC metrics established prior to testing. Cell line-based dilution studies performed in triplicate spanning 5ng and 30ng input range as well as in silico simulation demonstrated 95% limit of detection (LoD) at 0.1% Analysis of 121 healthy donor and 16 MSS advanced cancer patient samples identified no false positives (FP). In 240 patient samples with orthogonal confirmation of MSI status from tissue or panel NGS, GuardantOMNI demonstrated 100% analytic sensitivity (3/3) and 100% analytic specificity (237/237) with a PPV of 1 and and NPV 1. Retrospective analysis of 2000+ clinical samples detected MSI high in 16% of colorectal cancers, 4% of prostate cancers, and 0.6% of non-small cell lung cancers.Conclusions: Here we have demonstrated the performance of MSI-H detection with GuardantOMNI (OMNI), which has the potential to accelerate clinical trial enrollment, research and discovery with a single, non-invasive blood sample.Citation Format: Jing Zhao, Alexander Artyomenko, Carlo Artieri, John Latham, Stephen R. Fairclough, Catalin Barbacioru, Elena Helman, John Strickler, Darya Chudova, Richard Lanman, AmirAli Talasaz. Analytical validation of MSI High detection with GuardantOMNI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1675.
Pelvic discontinuity (2013)

Pelvic discontinuity represents a rare but challenging problem for orthopaedic surgeons. It is most commonly encountered during revision total hip replacement, but can also result from an iatrogentic acetabular fracture during hip replacement. The general principles in management of pelvic discontinuity include restoration of the continuity between the ilium and the ischium, typically with some form of plating. Bone grafting is frequently required to restore pelvic bone stock. The acetabular component is then impacted, typically using an uncemented, trabecular metal component. Fixation with multiple supplemental screws is performed. For larger defects, a so-called 'cup-cage' reconstruction, or a custom triflange implant may be required. Pre-operative CT scanning can greatly assist in planning and evaluating the remaining bone stock available for bony ingrowth. Generally, good results have been reported for constructs that restore stability to the pelvis and allow some form of biologic ingrowth.
Successful treatment of psychosis in a patient with Kufor-Rakeb syndrome with low dose aripiprazole: a case report (2019)

We present a case of a 32-year-old male with Kufor-Rakeb syndrome (KRS), a form of juvenile parkinsonism due to mutations of the ATP13A2 gene at PARK9 locus. The patient was seen for daily behavioral outbursts and psychotic symptoms. At first assessment, CGI scale was estimated at 5; "Markedly ill". Aripiprazole was started at 2 mg and then increased to 3 mg. Two years later, psychotic symptoms were judged to be "much improved" (CGI-C = 2). This significant improvement without drug-induced motor side effects suggests that aripiprazole at low doses (2-5 mg) is effective and tolerated in patients with KRS.
ChemInform Abstract: SYNTHESIS OF 8‐METHOXY‐ AND 8‐METHOXY‐6‐METHYLHOMOPHTHALIC ANHYDRIDES, KEY INTERMEDIATES FOR THE SYNTHESIS OF ANTHRACYCLINONES AND PERI‐HYDROXYLATED POLYCYCLIC AROMATIC COMPOUNDS (1985)

Abstract Aus dem Oxocyclohexenyldicarbonsäuredimethylester (I) wird durch Oxidation mit DDQ oder mit Schwefelblume der 3‐Hydroxyhomo‐ phthalsäureester (II) gewonnen; dieser wird O‐methyliert und nach alkalischer Hydrolyse zum Homophthalsäureanhydrid (IV) cyclisiert.
Acoustic nonlinearities in earth solids (1998)

Nonlinear elastic response in earth solids is a robust and representative physical characteristic. In this lecture the evidence leading to this conclusion is presented by providing an overview of theoretical and experimental developments in the domain. Illustrated measurements include those of nonlinear response in rock from a variety of dynamical wave experiments. The evidence leads to a pattern of unifying behavior. Nonlinear elasticity in earth solids is large relative to most materials; hysteresis and ‘‘discrete’’ memory play an important role in nonlinear properties of earth solids; nonlinear response is evident over a large frequency interval (dc to several MHz at least); and nonlinear response is significant, as is commonly appreciated, at large static and dynamic strain levels, but also at small strains where this behavior and the manifestations of this behavior are commonly disregarded. Recently, the methodology for extracting the nonlinear coefficients for a material have been proposed. Some theoretical models of structural nonlinearity of solid media and of wave propagation in such media are also described.
Concentration effect on gain of Pr/sup 3+/-doped fluoride fiber for 1.3 mu m amplification (1992)

The concentration quenching mechanism in Pr/sup 3+/-doped fluoride fiber operating at the 1.3- mu m band is investigated. It is confirmed that the cooperative upconversion process causes signal gain saturation with pump power and degrades the gain characteristics of Pr/sup 3+/-doped fluoride fiber at a concentration of 1000 p.p.m. The reduction in gain coefficient due to cooperative upconversion is almost suppressed at a concentration of 500 p.p.m. A Pr/sup 3+/ concentration of 500 p.p.m. is a practical concentration for the fabrication of efficient Pr/sup 3+/-doped fluoride fiber amplifiers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Increasing College Students’ Awareness on Mindset Practices while Teaching (2019)

Teachers often encourage students to succeed and reward students’ accomplishments by offering supportive, esteem-boosting messages. However, teachers may not always be aware of how the messages they send to their students may affect a student’s mindset. Research shows that when teachers praise a student for their intelligence rather than for a student’s effort, the student will develop a fixed mindset of which the child will believe their basic qualities are fixed traits, later leading to poor academic achievement. To address teachers’ awareness on developing mindsets, I created a recorded presentation about fixed and growth mindsets and delivered it to CSUMB service learning students interning at the Central Coast Citizenship Project.