gebhart/patrepeval huggingface dataset:
Human serum megakaryocyte colony-stimulating activity increases in response to intensive cytotoxic chemotherapy. (1984)

Sera from patients with aplastic anemia and amegakaryocytic thrombocytopenia contain an activity that stimulates megakaryocyte colony formation in vitro. We have assayed this megakaryocyte colony-stimulating activity (Meg-CSA) in sera of four patients receiving intensive antileukemic chemotherapy to determine whether the appearance of Meg-CSA is a physiologic response to the suppression of megakaryocytopoiesis. Three of the four patients were receiving consolidation or late intensification therapy for acute myoblastic leukemia (AML) in remission. The fourth was receiving induction therapy for de novo AML. During all or part of four chemotherapeutic cycles, serial Meg-CSA levels were assessed and correlated with the corresponding peripheral platelet counts. All courses of cytotoxic chemotherapy resulted in increases in serum Meg-CSA comparable to activity levels present in sera from patients with aplastic anemia. Two of the three patients studied during the early postchemotherapy interval manifested initial serum Meg-CSA elevations seven days before their thrombocytopenic nadirs when platelet counts were still between 100,000/mm3 and 140,000/mm3. Bone marrow recovery from chemotherapy was characterized by a decrease in serum Meg-CSA to pretherapy levels that occurred concurrently with the rise in platelet count to normal. These observations support the hypothesis that Meg-CSA is a physiologic humoral regulator of megakaryocytopoiesis elaborated in response to the depletion of either bone marrow megakaryocytes or megakaryocyte progenitor cells.
Frequent epigenetic inactivation of RASSF10 in thyroid cancer (2009)

The Ras association domain family (RASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of a novel RASSF member termed RASSF10 in thyroid carcinogenesis. The RASSF10 CpG island promoter was intensively methylated in nine thyroid cancer cell lines and in 66% of primary thyroid carcinomas. RASSF10 methylation was significantly increased in primary thyroid carcinoma compared to normal thyroid and follicular adenoma (0 and 10%, respectively; p < 0.004). Patients with cancerous lymph nodes were significantly hypermethylated for RASSF10 in primary thyroid tumors compared to those with non-affected lymph nodes (79 vs. 36%; p = 0.047). RASSF10 promoter hypermethylation correlated with a reduced expression and treatment with a DNA methylation inhibitor reactivated RASSF10 transcription. In summary, our data show frequent epigenetic inactivation of RASSF10 in thyroid cancer. These results suggest that RASSF10 may encode a novel epigenetically inactivated candidate tumor suppressor gene in thyroid carcinogenesis.
Localization of Phosphoglucose Isomerase in Escherichia coli and Its Relation to the Induction of the Hexose Phosphate Transport System (1972)

The localization of phosphoglucose isomerase (PGI) was studied in relation to the induction of hexose phosphate uptake in Escherichia coli. The uptake system is induced only by extracellular glucose-6-phosphate (G6P); there is no induction by intracellular G6P. Fructose-6-phosphate (F6P) is an indirect inducer, and isomerization of F6P to G6P must occur before induction. PGI has been considered to be an internal enzyme; therefore, uptake of F6P by noninduced cells and leakage of the G6P formed would be required for induction. In this study, it was concluded that part of the PGI activity is located in the cell surface because: (i) uninduced, intact cells are able to convert F6P to G6P, whereas the activity of G6P dehydrogenase is not detectable; (ii) when cells are subjected to osmotic shock, about 10% of the PGI activity is found in the shock fluid; and (iii) sorbitol-6-phosphate (S6P) inhibits both PGI activity of whole cells and the induction of hexose phosphate transport system by F6P. S6P was not taken by intact cells. The data indicate that the isomerization of F6P to G6P can take place on the cell surface, and this explains the indirect induction of hexose phosphate transport by F6P.
Evaluation of Field-Effect Mobility and Contact Resistance of Transistors That Use Solution-Processed Single-Walled Carbon Nanotubes (2012)

Solution-processed single-walled carbon nanotubes (SWNTs) offer many unique processing advantages over nanotubes grown by the chemical vapor deposition (CVD) method, including capabilities of separating the nanotubes by electronic type and depositing them onto various substrates in the form of ultradensely aligned arrays at low temperature. However, long-channel transistors that use solution-processed SWNTs generally demonstrate inferior device performance, which poses concerns over the feasibility of using these nanotubes in high-performance logic applications. This paper presents the first systematic study of contact resistance, intrinsic field-effect mobility (μ(FE)), and conductivity (σ(m)) of solution-processed SWNTs based on both the transmission line method and the Y function method. The results indicate that, compared to CVD nanotubes, although solution-processed SWNTs have much lower μ(FE) for semiconducting nanotubes and lower σ(m) for metallic nanotubes due to the presence of a higher level of structural defects, such defects do not affect the quality of electric contacts between the nanotube and metal source/drain electrodes. Therefore, solution-processed SWNTs are expected to offer performance comparable to that of CVD nanotubes in ultimately scaled field-effect transistors, where contacts will dominate electron transport instead of electron scattering in the channel region. These results show promise for using solution-processed SWNTs for high-performance nanoelectronic devices.
Plasma Delivery of Retinoic Acid to Tissues in the Rat (1995)

All-trans-retinoic acid (RA) activates ligand-dependent transcription factors that regulate retinoid-responsive gene expression. It is assumed that all-trans-RA is formed within cells through in situ oxidation of retinol derived from the circulation. However, the circulation contains low levels of all-trans-RA (approximately 0.2-0.7% of that of plasma retinol). Our studies investigated the extent to which plasma all-trans-RA contributes to tissue pools of this retinoid and explored factors responsible for regulating its uptake by tissues and cells. Rats were continuously infused, to steady state, with all-trans-[3H]RA. From measures of specific activities of all-trans-[3H]RA at steady state, we determined that the preponderance of all-trans-RA in brain and liver was derived from the circulation. For six other tissues, approximately 10-30% of the retinoid was derived from the circulation, but pancreas and testis derived very little from the circulating pool. In other studies, we showed that retinoid nutritional status influences clearance of a bolus dose of all-trans-RA and that neither the rate of cellular all-trans-RA uptake nor its intracellular half-life is influenced by cellular lipid levels. Taken together, our data indicate that plasma all-trans-RA contributes to tissue pools of this retinoid and that specific and physiologically responsive cellular processes mediate its uptake.
New Method for the Direct Determination of Dissolved Fe(III) Concentration in Acid Mine Waters (1999)

A new method for direct determination of dissolved Fe(III) in acid mine water has been developed. In most present methods, Fe(III) is determined by computing the difference between total dissolved Fe and dissolved Fe(II). For acid mine waters, frequently Fe(II) ≫ Fe(III); thus, accuracy and precision are considerably improved by determining Fe(III) concentration directly. The new method utilizes two selective ligands to stabilize Fe(III) and Fe(II), thereby preventing changes in Fe reduction−oxidation distribution. Complexed Fe(II) is cleanly removed using a silica-based, reversed-phase adsorbent, yielding excellent isolation of the Fe(III) complex. Iron(III) concentration is measured colorimetrically or by graphite furnace atomic absorption spectrometry (GFAAS). The method requires inexpensive commercial reagents and simple procedures that can be used in the field. Calcium(II), Ni(II), Pb(II), Al(III), Zn(II), and Cd(II) cause insignificant colorimetric interferences for most acid mine waters. Waters containing >20 mg of Cu/L could cause a colorimetric interference and should be measured by GFAAS. Cobalt(II) and Cr(III) interfere if their molar ratios to Fe(III) exceed 24 and 5, respectively. Iron(II) interferes when its concentration exceeds the capacity of the complexing ligand (14 mg/L). Because of the GFAAS elemental specificity, only Fe(II) is a potential interferent in the GFAAS technique. The method detection limit is 2 μg/L (40 nM) using GFAAS and 20 μg/L (0.4 μM) by colorimetry.
Culturing nerve cells (1998)

Part 1 A user's guide: getting started, Gary Banker, Kimberly Goslin. Part 2 General principles: types of nerve cell cultures, their advantages and limitations, Gary Banker, Kimberly Goslin primary dissociated cell cultures, Dennis Higgins, Gary Banker transfecting cultured neurons, Ann Marie Craig characterizing and studying neuronal cultures, Ginger S. Withers, Gary Banker. Part 3 Culture of specific cell types - choosing the right system: culture and experimental use of the PC12 rat pheochromocytoma cell line, Lloyd A. Greene et al neuronlike cells derived in culture from P19 embryonal carcinoma and embryonic stem cells, Gerard Bain et al culturing the large neurons of aplasia, Daniel J. Goldberg, Samuel Schacher culturing spinal neurons and muscle cells from xenopus embryos, Nacira Tabti et el cultures from chick peripheral ganglia, Carolyn L. Smith culturing mammalian sympathoadrenal derivatives, Nagesh K. Mahanthappa, Paul H. Patterson mass cultures and microislands of neurons from postnatal rat brain, Michael M. Segal et al rat hippocampal neurons in low-density culture, Kimberley Goslin et al rat striatal neurons in low-density, serum-free culture, Roseann Ventimiglia, Ronald M. Lindsay cell culture of cholinergic and cholinoceptive neurons from the medial habenulae, Raul Krauss, Gerald D. Fischbach the cerebellum - purification and coculture of identified cell populations, Mary Beth Hatten et al organotypic slice cultures of neural tissue, Beat H. Gahwiler et al culture of astrocytes, oligodendrocytes, and O-2A progenitor cells, Mark Noble, Margot Mayer-Proschel tissue culture methods for the study of myelination, Naomi Kleitman et al.
Counting the cost of fast access: using discrete choice experiments to elicit preferences in general practice. (2006)

In publicly provided healthcare systems, when limited resources are coupled with unlimited demand, decisions have to be made about the efficient allocation of scarce resources. This raises questions of how services should be provided (for example, should breast cancer patients be prescribed Trastuzumab®? Should there be an increased role for pharmacists in prescribing?) through to the optimal provision and financing of health care (for example, how can we encourage doctors to provide out-of-hours care or work in remote and rural areas?). Trade-offs inevitably have to be made. A technique gaining popularity in health economics to identify trade-offs is the discrete choice experiment approach,1 used by Longo et al 2 in this Journal to consider patients' preferences for shared decision-making. Within general practice the technique has been used to elicit patient and community preferences,2–6 as well as to explore GP preferences for job characteristics.7–9

Discrete choice experiments are based on the assumptions that interventions, services or policies can be described by characteristics, and that value depends on the levels of these characteristics. Responders are presented with a number of choices that involve different levels of attributes. For each choice they are asked which option they would choose. Making choices involves trade-offs between attribute levels. Responses are analysed using regression techniques and from this it is possible to estimate the relative importance of attributes, as well as the trade-offs between attributes; for example, how much longer individuals are willing to …
A phase 1 study of MM-111, a bispecific HER2/HER3 antibody fusion protein, combined with multiple treatment regimens in patients with advanced HER2-positive solid tumors. (2014)

651 Background: MM-111 (111) inhibits ligand activated HER3 signaling in HER2+ tumors. This study evaluated the safety of 111 combined with standard of care (SOC) HER2-targeting regimens (Rx): capecitabine (X) + cisplatin (C) + trastuzumab (T) (Arm 1); lapatinib (L) +/- trastuzumab (Arm 2); paclitaxel (P) + trastuzumab (Arm 3); lapatinib + paclitaxel + trastuzumab (Arm 4); docetaxel (D) + trastuzumab (Arm 5). Methods: This was a multi-arm Phase 1, dose escalation study of 111 in combination with SOC regimens to evaluate safety, pharmacokinetics (PK), and anti-tumor activity. Patients were required to have documented advanced HER2-positive cancer and adequate organ function. Each arm was designed to run as a separate Phase 1 study to address safety and tolerability and utilized a “3 + 3” design with standard dosing of the SOC regimen. 111 was dosed weekly at 10 mg/kg and escalated up to 20 mg/kg where possible. For Arm 5, 111 was dosed q3w starting at 30mg/kg and escalated up to 40mg/kg. Results: A total of 86 patients (11 bladder, 46 breast, 15 gastro-esophageal, 14 other cancers) were enrolled and treated across all five arms. Dose-limiting toxicities (DLTs) included anemia, acute renal failure (assessed as cisplatin-related), chest pain, decreased appetite, diarrhea, febrile neutropenia, hyperuricemia, hypokalemia, hyponatremia, hypophosphatemia, mucosal inflammation, nausea, neutropenia, stomatitis, thrombocytopenia, and vomiting. An MTD was not reached in Arms 2-5; Arm 1 required a capecitabine dose reduction. Conclusions: Treatment with 111 and SOC HER2-directed regimens was feasible. The Recommended 111 Phase 2 doses are 20mg/kg QW and 40mg/Q3W. Additional safety, PK and preliminary activity data will be provided. Clinical trial information: NCT01304784.Patient outcomes summary. Arm Rx (Dose) Units 111 and T (mg/kg) X, D, C and P (mg/m2) Arm 1 X (1000) C (80) T (4/2) 111 (5-10) Arm 2 T (4/2) L (1000) 111 (10-20) Arm 3 P (80) T (4/2) 111 (10-20) Arm 4 P (80) L (750) T (4/2) 111 (10-20) Arm 5 D (75) T (8/6) 111 (30-40) N (safety population) 17 31* 23 9 6 DLT 6 4 1 1 0 SAE 5 12 6 4 1 N (evaluable population) 14 24 21 9 6 CR; PR; SD 1 CR;3 PR;6 SD 4 PR;10 SD 6 PR;7 SD 4 PR; 3 SD 1 PR; 2 SD *10 patients did not receive T.
Minimal Effect of Gene Clustering on Expression inEscherichia coli (2012)

Genes that interact or function together are often clustered in bacterial genomes, and it has been proposed that this clustering may affect gene expression. In this study, we directly compared gene expression in nonclustered arrangements and in three common clustered arrangements (codirectional, divergent, and operon) using synthetic circuits in Escherichia coli. We found that gene clustering had minimal effects on gene expression. Specifically, gene clustering did not alter constitutive expression levels or stochastic fluctuations in expression ("expression noise"). Remarkably, the expression of two genes that share the same chromosome position with the same promoter (operon) or with separate promoters (codirectional and divergent arrangements) was not significantly more correlated than genes at different chromosome positions (nonclustered arrangements). The only observed effect of clustering was increased transcription factor binding in codirectional and divergent gene arrangements due to DNA looping, but this is not a specific feature of clustering. In summary, we demonstrate that gene clustering is not a general modulator of gene expression, and therefore any effects of clustering are likely to occur only with specific genes or under certain conditions.
The role of p38 mitogen‐activated protein kinase in IL‐6 and IL‐8 production from the TNF‐α‐ or IL‐1β‐stimulated rheumatoid synovial fibroblasts (1999)

We examined the role of p38 mitogen-activated protein (MAP) kinase in the tumor necrosis factor alpha (TNF-alpha)- or interleukin-1beta (IL-1beta)-induced production of interleukin-6 (IL-6) and interleukin-8 (IL-8) in fresh rheumatoid synovial fibroblast (RSF) cultures concomitantly with the induction of p38 MAP kinase activity. Pretreatment of RSF with a specific p38 MAP kinase inhibitor, SB203580, blocked the induction of IL-6 and IL-8 without affecting nuclear translocation of nuclear factor kappaB (NF-kappaB) or IL-6 and IL-8 mRNA levels. These findings suggest that p38 MAP kinase inhibitor may have synergistic, rather than additive, effect for the treatment of rheumatoid arthritis.
Anti-inflammatory therapies in sepsis and septic shock (2000)

Despite advances in supportive care, the morbidity and mortality rate resulting from sepsis and septic shock remain high (30 - 50%). A central hypothesis driving sepsis research in recent years is that this syndrome is the result of excessive inflammation. Therapies designed to inhibit the inflammatory response were first shown to be markedly beneficial in animal models of sepsis and then tested in numerous clinical trials involving thousands of patients. Three broad anti-inflammatory strategies have been investigated. First, glucocorticoids in high doses administered at the onset of sepsis were studied. This approach proved unsuccessful. More recently, however, glucocorticoids in lower doses have been found to have a beneficial effect in patients with septic shock. Whether the mechanism of this treatment benefit is through inhibition of inflammation, or by counteracting a relative steroid refractoriness occurring during sepsis, remains unknown. The next focus of research were agents active against the endotoxin molecule. However, as with the experience with glucocorticoids, this approach lacked a consistent pattern of efficacy. It is unclear if this lack of efficacy is the result of endotoxin being a poor therapeutic target, or from testing agents which lacked the appropriate biological activity. Most recently, clinical trials in sepsis have focused on inhibiting specific host pro-inflammatory mediators (e.g., TNF, interleukins). While individual trials of inhibitors of these pro-inflammatory mediators failed to show a convincing benefit, pooling the results of these trials suggest that this approach has a marginal effect, supporting a role for excessive inflammation in sepsis. An unanswered question is reconcilling the very favourable effects obtained with anti-inflammatory treatments in animal models with the marginal results in humans. Further clinical and laboratory research is needed and may provide insight into more effective ways to use the anti-inflammatory agents already tested, or to investigate other potentially more effective anti-inflammatory agents in this syndrome.
Splice Variants of the Drosophila PS2 Integrins Differentially Interact with RGD-containing Fragments of the Extracellular Proteins Tiggrin, Ten-m, and D-Laminin α2 (1998)

Two new potential ligands of the Drosophila PS2 integrins have been characterized by functional interaction in cell culture. These potential ligands are a new Drosophila laminin alpha2 chain encoded by the wing blister locus and Ten-m, an extracellular protein known to be involved in embryonic pattern formation. As with previously identified PS2 ligands, both contain RGD sequences, and RGD-containing fragments of these two proteins (DLAM-RGD and TENM-RGD) can support PS2 integrin-mediated cell spreading. In all cases, this spreading is inhibited specifically by short RGD-containing peptides. As previously found for the PS2 ligand tiggrin (and the tiggrin fragment TIG-RGD), TENM-RGD induces maximal spreading of cells expressing integrin containing the alphaPS2C splice variant. This is in contrast to DLAM-RGD, which is the first Drosophila polypeptide shown to interact preferentially with cells expressing the alphaPS2 m8 splice variant. The betaPS integrin subunit also varies in the presumed ligand binding region as a result of alternative splicing. For TIG-RGD and TENM-RGD, the beta splice variant has little effect, but for DLAM-RGD, maximal cell spreading is supported only by the betaPS4A form of the protein. Thus, the diversity in PS2 integrins due to splicing variations, in combination with diversity of matrix ligands, can greatly enhance the functional complexity of PS2-ligand interactions in the developing animal. The data also suggest that the splice variants may alter regions of the subunits that are directly involved in ligand interactions, and this is discussed with respect to models of integrin structure.
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis (2003)

The synthesis and excretion of bile acids comprise the major pathway of cholesterol catabolism in mammals. Synthesis provides a direct means of converting cholesterol, which is both hydrophobic and insoluble, into a water-soluble and readily excreted molecule, the bile acid. The biosynthetic steps that accomplish this transformation also confer detergent properties to the bile acid, which are exploited by the body to facilitate the secretion of cholesterol from the liver. This role in the elimination of cholesterol is counterbalanced by the ability of bile acids to solubilize dietary cholesterol and essential nutrients and to promote their delivery to the liver. The synthesis of a full complement of bile acids requires 17 enzymes. The expression of selected enzymes in the pathway is tightly regulated by nuclear hormone receptors and other transcription factors, which ensure a constant supply of bile acids in an ever changing metabolic environment. Inherited mutations that impair bile acid synthesis cause a spectrum of human disease; this ranges from liver failure in early childhood to progressive neuropathy in adults.
<title>Optical power limiting in solution via two-photon absorption: new aromatic heterocyclic dyes with greatly improved performance</title> (1997)

Organic compounds which exhibit optical power limiting exclusively via a two-photon absorption (TPA) mechanism have shown only little promise for providing the limiting activity necessary for the practical protection of eyes and sensors. Unfortunately, there have been few systematic studies of the molecular structure I two-photon absorption property relationships for organics documented in the literature. In order to enable the design and synthesis of new molecules with much larger two-photon absorption cross-sections and improved limiting properties, the synthetic chemist must have access to well defined structure Iproperty data. In an attempt to fill this void, work in our laboratory has centered on the design and synthesis of several new families of aromatic heterocyclic chromophores with systematic variations in their molecular structures. Careful characterization of these new materials in solution at the Photonics Research Laboratory, SUNY Buffalo has produced some well-defined structure Itwo-photon property relationships at 800 nm. In this presentation we will discuss the design and synthesis of these materials with special emphasis of how the flexibility of the synthetic scheme employed enables the incorporation of these chromophores into a wide variety of materials forms. The characterization of the twophoton properties of these materials and the relationship of these results to their optical limiting behavior in solution will also be reviewed.