gebhart/patrepeval huggingface dataset:
Phosphatidylinositol 3-Kinase α–Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study (2018)

Purpose We report the first-in-human phase Ia study to our knowledge ( ClinicalTrials.gov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor. Patients and Methods In the dose-escalation phase, patients with PIK3CA-altered advanced solid tumors received once-daily or twice-daily oral alpelisib on a continuous schedule. In the dose-expansion phase, patients with PIK3CA-altered solid tumors and PIK3CA-wild-type, estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer received alpelisib 400 mg once daily. Results One hundred thirty-four patients received treatment. Alpelisib maximum tolerated doses were established as 400 mg once daily and 150 mg twice daily. Nine patients (13.2%) in the dose-escalation phase had dose-limiting toxicities of hyperglycemia (n = 6), nausea (n = 2), and both hyperglycemia and hypophosphatemia (n = 1). Frequent all-grade, treatment-related adverse events included hyperglycemia (51.5%), nausea (50.0%), decreased appetite (41.8%), diarrhea (40.3%), and vomiting (31.3%). Alpelisib was rapidly absorbed; half-life was 7.6 hours at 400 mg once daily with minimal accumulation. Objective tumor responses were observed at doses ≥ 270 mg once daily; overall response rate was 6.0% (n = 8; one patient with endometrial cancer had a complete response, and seven patients with cervical, breast, endometrial, colon, and rectal cancers had partial responses). Stable disease was achieved in 70 (52.2%) patients and was maintained > 24 weeks in 13 (9.7%) patients; disease control rate (complete and partial responses and stable disease) was 58.2%. In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, median progression-free survival was 5.5 months. Frequently mutated genes (≥ 10% tumors) included TP53 (51.3%), APC (23.7%), KRAS (22.4%), ARID1A (13.2%), and FBXW7 (10.5%). Conclusion Alpelisib demonstrated a tolerable safety profile and encouraging preliminary activity in patients with PIK3CA-altered solid tumors, supporting the rationale for selective PI3Kα inhibition in combination with other agents for the treatment of PIK3CA-mutant tumors.
Validity of adult retrospective reports of adverse childhood experiences: review of the evidence (2004)

Retrospective studies have a worthwhile place in research, but further research is needed to examine possible biases in reporting.
Imaging with99mTc ECDG Targeted at the Multifunctional Glucose Transport System: Feasibility Study with Rodents (2003)

There are similarities between (99m)Tc ECDG uptake and (18)F FDG uptake in tumors, and study findings supported the potential use of (99m)Tc ECDG as a functional imaging agent.
Reduction of infarct size and postischemic inflammation from ATL-146e, a highly selective adenosine A2Areceptor agonist, in reperfused canine myocardium (2004)

Adenosine and adenosine A(2A) receptor agonists have been shown to limit myocardial infarct size when given at vasodilatory doses during reperfusion. This beneficial effect is thought to be due, in part, to stimulation of adenosine A(2A) receptors on inflammatory cells. The specific aims of this study were to determine whether the anti-inflammatory and cardioprotective properties of a novel adenosine A(2A) receptor agonist, ATL-146e (ATL), alone or in combination with the phosphodiesterase IV inhibitor rolipram would occur using very low, nonvasodilating doses. In a canine model of reperfused myocardial infarction, low-dose ATL given alone reduced infarct size by 45% (P < 0.05 vs. control). When ATL was combined with a very low dose of rolipram (0.001 microg.kg(-1).min(-1)), a marked reduction in P-selectin expression and neutrophil infiltration (51% lower; P < 0.001 vs. control) was seen and the infarct size reduction (58% lower; P < 0.01 vs. control) was greater than observed with ATL (45% lower; P < 0.05) or rolipram (33% lower; P < 0.05) alone. In conclusion, a low, nonvasodilating dose of ATL, a highly selective adenosine A(2A) receptor agonist, reduced infarct size after reperfusion. Furthermore, combining ATL and the phosphodiesterase IV inhibitor rolipram reduced infarct size even more than either agent alone. Such combination therapy may be beneficial clinically by potentiating cardioprotection after coronary reperfusion at doses far below those producing vasodilatation or side effects.
Developmental regulation of V(D)J recombination at the TCR a/5 locus (1998)

The T-cell receptor (TCR) alpha/delta locus includes a large number of V, D, J and C gene segments that are used to produce functional TCR delta and TCR alpha chains expressed by distinct subsets of T lymphocytes. V(D)J recombination events within the locus are regulated as a function of developmental stage and cell lineage during T-lymphocyte differentiation in the thymus. The process of V(D)J recombination is regulated by cis-acting elements that modulate the accessibility of chromosomal substrates to the recombinase. Here we evaluate how the assembly of transcription factor complexes onto enhancers, promoters and other regulatory elements within the TCR alpha/delta locus imparts developmental control to VDJ delta and VJ alpha rearrangement events. Furthermore, we develop the notion that within a complex locus such as the TCR alpha/delta locus, highly localized and region-specific control is likely to require an interplay between positive regulatory elements and blocking or boundary elements that restrict the influence of the positive elements to defined regions of the locus.
Spatial and Temporal Expression of a Maize Lipid Transfer Protein Gene (1991)

Lucienne Sossountzov, Luis Ruiz-Avila, Florence Vignols, Alain Jolliot, Vincent Arondel, , , , Emile Miginiac, Michel Delseny, , Jean-Claude Kader, Spatial and Temporal Expression of a Maize Lipid Transfer Protein Gene, The Plant Cell, Vol. 3, No. 9 (Sep., 1991), pp. 923-933
Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes (1996)

A mAb J43 has been produced against the product of the mouse PD-1 gene, a member of the Ig gene superfamily, which was previously isolated from an apoptosis-induced T cell hybridoma (2B4.11) by using subtractive hybridization. Analyses by flow cytometry and immunoprecipitation using the J43 mAb revealed that the PD-1 gene product is a 50-55 kDa membrane protein expressed on the cell surface of several PD-1 cDNA transfectants and 2B4.11 cells. Since the molecular weight calculated from the amino acid sequence is 29, 310, the PD-1 protein appears to be heavily glycosylated. Normal murine lymphoid tissues such as thymus, spleen, lymph node and bone marrow contained very small numbers of PD-1(+) cells. However, a significant PD-1(+) population appeared in the thymocytes as well as T cells in spleen and lymph nodes by the in vivo anti-CD3 mAb treatment. Furthermore, the PD-1 antigen expression was strongly induced in distinct subsets of thymocytes and spleen T cells by in vitro stimulation with either anti-CD3 mAb or concanavalin A (Con A) which could lead T cells to both activation and cell death. Similarly, PD-1 expression was induced on spleen B cells by in vitro stimulation with anti-IgM antibody. By contrast, PD-1 was not significantly expressed on lymphocytes by treatment with growth factor deprivation, dexamethasone or lipopolysaccharide. These results suggest that the expression of the PD-1 antigen is tightly regulated and induced by signal transduction through the antigen receptor and do not exclude the possibility that the PD-1 antigen may play a role in clonal selection of lymphocytes although PD-1 expression is not required for the common pathway of apoptosis.
Simply Complex: The Efficient Synthesis of an Intricate Molecular Acceptor for High-Performance Air-Processed and Air-Tested Fullerene-Free Organic Solar Cells (2017)

A perylene diimide (PDI) flanked diketopyrrolopyrrole (DPP) π-conjugated small molecule has been synthesized through an efficient and sustainable direct heteroarylation protocol. When paired with the donor polymer PTB7-Th, air-processed and tested bulk-heterojunction (BHJ) organic solar cells (OSCs) achieved a high power conversion efficiency (PCE) of 5.6%. The new acceptor showed favorable morphological changes upon solvent vapor annealing leading to a near 3-fold increase in PCE. This result is among the best reported utilizing DPP-based acceptors in air-processed and tested OSCs. All solar cells exhibited good air and light stability over a 35-day evaluation period.
Review of magnesium-based biomaterials and their applications (2018)

In biomedical applications, the conventionally used metallic materials, including stainless steel, Co-based alloys and Ti alloys, often times exhibit unsatisfactory results such as stress shielding and metal ion releases. Secondary surgical operation(s) usually become inevitable to prevent long term exposure of body with the toxic implant contents. The metallic biomaterials are being revolutionized with the development of biodegradable materials including several metals, alloys, and metallic glasses. As such, the nature of metallic biomaterials are transformed from the bioinert to bioactive and multi-biofunctional (anti-bacterial, anti-proliferation, anti-cancer, etc.). Magnesium-based biomaterials are candidates to be used as new generation biodegradable metals. Magnesium (Mg) can dissolve in body fluid that means the implanted Mg can degrade during healing process, and if the degradation is controlled it would leave no debris after the completion of healing. Hence, the need for secondary surgical operation(s) for the implant removal could be eliminated. Besides its biocompatibility, the inherent mechanical properties of Mg are very similar to those of human bone. Researchers have been working on synthesis and characterization of Mg-based biomaterials with a variety of composition in order to control the degradation rate of Mg since uncontrolled degradation could result in loss of mechanical integrity, metal contamination in the body and intolerable hydrogen evolution by tissue. It was observed that the applied methods of synthesis and the choice of components affect the characteristics and performance of the Mg-based biomaterials. Researchers have synthesized many Mg-based materials through several synthesis routes and investigated their mechanical properties, biocompatibility and degradation behavior through in vitro, in vivo and in silico studies. This paper is a comprehensive review that compiles, analyses and critically discusses the recent literature on the important aspects of Mg-based biomaterials.
Genome-Wide Methylation Changes in the Brains of Suicide Completers (2013)

These results suggest broad reprogramming of promoter DNA methylation patterns in the hippocampus of suicide completers. This may help explain gene expression alterations associated with suicide and possibly behavioral changes increasing suicide risk.
Light-induced luminescence quenching in precursor-route poly(p-phenylene vinylene) (1989)

The authors report the observation in partially converted precursor-route poly(p-phenylene vinylene) (PPV) of a strong light-induced luminescence fatigue. Increasing the conversion towards the fully conjugated polymer results in a loss of the quenching effect. They discuss exciton annihilation at photoexcited charged polaronic states as a possible mechanism for this phenomenon.
Progress in Drug Delivery to the Central Nervous System by the Prodrug Approach (2008)

This review describes specific strategies for targeting to the central nervous system (CNS). Systemically administered drugs can reach the brain by crossing one of two physiological barriers resistant to free diffusion of most molecules from blood to CNS: the endothelial blood-brain barrier or the epithelial blood-cerebrospinal fluid barrier. These tissues constitute both transport and enzymatic barriers. The most common strategy for designing effective prodrugs relies on the increase of parent drug lipophilicity. However, increasing lipophilicity without a concomitant increase in rate and selectivity of prodrug bioconversion in the brain will result in failure. In these regards, consideration of the enzymes present in brain tissue and in the barriers is essential for a successful approach. Nasal administration of lipophilic prodrugs can be a promising alternative non-invasive route to improve brain targeting of the parent drugs due to fast absorption and rapid onset of drug action. The carrier-mediated absorption of drugs and prodrugs across epithelial and endothelial barriers is emerging as another novel trend in biotherapeutics. Several specific transporters have been identified in boundary tissues between blood and CNS compartments. Some of them are involved in the active supply of nutrients and have been used to explore prodrug approaches with improved brain delivery. The feasibility of CNS uptake of appropriately designed prodrugs via these transporters is described in detail.
A Study on the Application and Residues of Plant Growth Regulators in the Fruit Sugarcane Grown in the Sub-Suitable Region (2010)

In this paper, we used plant growth regulators, such as gibberellin and ethephon to treat fruit sugarcane Qiantang5 respectively. The results show that the spraying of gibberellin on the plants with its concentration of30g/year.667m2 has positive effects on most agronomic characters, such as growth speed, plant height, validstalks, brix, sucrose content and yield. The residue of gibberellin is 0.05mg/kg. However, ethephon has nopositive effects on agronomic characters except the growth speed.
RETRACTED: Selection of cyclic peptide aptamers to HCV IRES RNA using mRNA display (2008)

The hepatitis C virus (HCV) is a positive strand RNA flavivirus that is a major causative agent of serious liver disease, making new treatment modalities an urgent priority. Because HCV translation initiation occurs by a mechanism that is fundamentally distinct from that of host mRNAs, it is an attractive target for drug discovery. The translation of HCV mRNA is initiated from an internal ribosomal entry site (IRES), independent of cap and poly(A) recognition and bypassing eIF4F complex formation. We used mRNA display selection technology combined with a simple and robust cyclization procedure to screen a peptide library of >10(13) different sequences and isolate cyclic peptides that bind with high affinity and specificity to HCV IRES RNA. The best peptide binds the IRES with subnanomolar affinity, and a specificity of at least 100-fold relative to binding to several other RNAs of similar length. The peptide specifically inhibits HCV IRES-initiated translation in vitro with no detectable effect on normal cap-dependent translation initiation. An 8-aa cyclic peptide retains most of the activity of the full-length 27-aa bicyclic peptide. These peptides may be useful tools for the study of HCV translation and may have potential for further development as an anti-HCV drug.
How do atrial pacing algorithms prevent atrial arrhythmias? (2004)

With an ageing population, atrial fibrillation has become an increasing cause of hospital admission and morbidity. Pacemaker implantation may prevent atrial tachyarrhythmias by preventing bradycardia and pauses. Implantable devices are now available with specific atrial pacing algorithms designed to prevent atrial arrhythmias. These algorithms work by increasing the atrial pacing rate to achieve continuous overdrive pacing or by responding to triggers such as premature atrial complexes. This article examines how the algorithms work by describing the functions of one of the new generation of pacemakers in detail. Early studies have indicated that the use of preventative pacing can reduce atrial arrhythmia burden and symptomatic atrial fibrillation in selected patients. There are clearly some patients who benefit from implantation of these devices but what remains unclear is how to identify this patient group.
Detection and identification of activated oncogenes in human skin cancers occurring on sun-exposed body sites. (1988)

High-molecular-weight DNA isolated from eight fresh human skin cancers occurring on sun-exposed body sites were assayed for their ability to transform NIH 3T3 cells. A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select cells that had taken up the transfected DNA. About 2 weeks after transfection, G418-resistant colonies were pooled and injected s.c. into athymic nude mice. The NIH 3T3 cells transfected with DNA from six of the human skin cancers induced tumors in nude mice. DNAs from all six tumor cell lines contained human alu sequences. Southern blot hybridization with ras-specific probes revealed that DNAs from the four alu-rich tumors contained the human Ha-ras oncogene, in addition to that of the NIH 3T3 controls. In contrast, DNAs from the other two tumors did not contain any of the known oncogenes tested, except those endogenous to NIH 3T3 cells. DNAs from three of four first cycle tumorigenic transformants gave rise to morphologically transformed foci when assayed in a second cycle of transfection. DNAs from all three secondary transformants contained discrete human alu sequences, and in addition, contained Ha-ras sequences similar to those present in their respective primary transformants. Interestingly, DNA from both primary and secondary transformants of one particular human squamous cell carcinoma contained highly amplified copies of the Ha-ras oncogene. These results suggest that activation of the Ha-ras oncogene may be common in human skin cancers originating on sun-exposed body sites. Further characterization of the Ha-ras oncogenes present in these human skin cancers may provide information on the molecular mechanisms by which UV radiation of the sun induces human neoplasms on exposed body sites.
Preclinical biology of interleukin 11: A multifunctional hematopoietic cytokine with potent thrombopoietic activity (1995)

Interleukin 11 (IL-11) is a multifunctional hematopoietic cytokine which was originally identified as a factor produced by an IL-1-stimulated primate stromal cell line. The in vitro biological activities of recombinant human (rHu)IL-11 result predominantly from synergistic interactions with other growth factors. In combination with other cytokines, rHuIL-11 has been shown to support the formation of primitive hematopoietic and lymphohematopoietic progenitor colonies from bone marrow, to promote erythroid burst formation and to stimulate both early and late stages of megakaryocyte proliferation and differentiation. rHuIL-11 is biologically active in mice, rats, dogs and primates when administered as a single agent in vivo. The predominant effect of rHuIL-11 in naive mice was on cells of the megakaryocytic lineage, increasing the number of bone marrow megakaryocyte progenitors, stimulating megakaryocyte endoreplication and increasing peripheral platelet counts in a dose-dependent fashion. Similar megakaryocytic stimulatory activity was seen in nonhuman primates treated with rHuIL-11 where platelet counts were increased by as much as 300%. In several models of severe myelosuppression induced by chemotherapy and/or irradiation and in bone marrow transplant models, there were multilineage hematopoietic stimulation following rHuIL-11 treatment. In these models, accelerated recovery of platelets was a consistent observation, while some models show enhanced neutrophil and red blood cell recovery as well. These results from preclinical studies confirm the broad spectrum of biological activities exhibited by rHuIL-11 in vitro, and suggest that this cytokine may be an effective agent in the treatment of myelosuppression and thrombocytopenia associated with cancer chemotherapy and bone marrow transplantation.
Trends in hydraulic fracturing distributions and treatment fluids, additives, proppants, and water volumes applied to wells drilled in the United States from 1947 through 2010: data analysis and comparison to the literature (2015)

Hydraulic fracturing is presently the primary stimulation technique for oil and gas production in low-permeability, unconventional reservoirs. Comprehensive, published, and publicly available information regarding the extent, location, and character of hydraulic fracturing in the United States is scarce. This national spatial and temporal analysis of data on nearly 1 million hydraulically fractured wells and 1.8 million fracturing treatment records from 1947 through 2010 (aggregated in Data Series 868) is used to identify hydraulic fracturing trends in drilling methods and use of proppants, treatment fluids, additives, and water in the United States. These trends are compared to the literature in an effort to establish a common understanding of the differences in drilling methods, treatment fluids, and chemical additives and of how the newer technology has affected the water use volumes and areal distribution of hydraulic fracturing. Historically, Texas has had the highest number of records of hydraulic fracturing treatments and associated wells in the United States documented in the datasets described herein. Water-intensive horizontal/directional drilling has also increased from 6 percent of new hydraulically fractured wells drilled in the United States in 2000 to 42 percent of new wells drilled in 2010. Increases in horizontal drilling also coincided with the emergence of water-based "slick water" fracturing fluids. As such, the most current hydraulic fracturing materials and methods are notably different from those used in previous decades and have contributed to the development of previously inaccessible unconventional oil and gas production target areas, namely in shale and tight-sand reservoirs. Publicly available derivative datasets and locations developed from these analyses are described.
Neural stem cells and neurodegeneration. (2002)

Neurodegenerative diseases, such as Parkinson's disease, are characterized by a continuous loss of specific populations of neurons. Possible regenerative interventions include transplanting developing neural tissue or neural stem cells into the host brain, and inducing proliferation of endogenous stem cells by pharmacological manipulations. Neural stem cells (NSC), with the capacity to self-renew and produce the major cell types of the brain, exist in the developing and adult central nervous system (CNS). These cells can be grown in vitro while retaining the potential to differentiate into nervous tissue. This review focuses on regenerative therapy in neurodegenerative diseases using NSC.
A dual-mode textile for human body radiative heating and cooling (2017)

Maintaining human body temperature is one of the most basic needs for living, which often consumes a huge amount of energy to keep the ambient temperature constant. To expand the ambient temperature range while maintaining human thermal comfort, the concept of personal thermal management has been recently demonstrated in heating and cooling textiles separately through human body infrared radiation control. Realizing these two opposite functions within the same textile would represent an exciting scientific challenge and a significant technological advancement. We demonstrate a dual-mode textile that can perform both passive radiative heating and cooling using the same piece of textile without any energy input. The dual-mode textile is composed of a bilayer emitter embedded inside an infrared-transparent nanoporous polyethylene (nanoPE) layer. We demonstrate that the asymmetrical characteristics of both emissivity and nanoPE thickness can result in two different heat transfer coefficients and achieve heating when the low-emissivity layer is facing outside and cooling by wearing the textile inside out when the high-emissivity layer is facing outside. This can expand the thermal comfort zone by 6.5°C. Numerical fitting of the data further predicts 14.7°C of comfort zone expansion for dual-mode textiles with large emissivity contrast.