gebhart/patrepeval huggingface dataset:
Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study (1990)

Among 3,638 children with acute lymphoblastic leukemia (ALL) entered on Pediatric Oncology Group (POG) protocols between June 1981 and April 1989, successful cytogenetic studies were available for 2,519, 58 (2.3%) of which had the Philadelphia (Ph) chromosome detected. Features associated with the presence of the Ph chromosome were high leukocyte count (median, 33 x 10(9)/L), older age median, 9.6 years), a higher proportion of French-American-British L2 morphology, and a lower frequency of mediastinal mass. Immunologic marker studies at diagnosis in 56 Ph+ cases identified early pre-B ALL in 42 cases (75%), pre-B-cell in 9 (16%), and T-cell in 5 (9%). This distribution is similar to that found in Ph+ ALL. Intensive multiagent chemotherapy induced complete remissions in only 78% of eligible Ph+ patients compared with 96% of those without an identified Ph chromosome (P less than .001). Of 44 eligible Ph+ patients treated on POG frontline protocols for children with non-T, non-B-cell ALL, 27 have failed therapy, compared with 520 of 1,892 without an identified Ph chromosome (logrank P less than .001). Ph+ ALL is an aggressive form of acute leukemia that frequently presents in older children with a high leukocyte count, FAB L2 morphology, and a pseudodiploid karyotype, and becomes multidrug-resistant early. Thus, Ph+ cases require early identification to permit treatment with intensive induction regimens and experimental approaches such as bone marrow transplantation.
Correlation between the induction of heat shock protein 70 and enhanced viral reactivation in mammalian cells treated with ultraviolet light and heat shock. (1989)

Enhanced viral reactivation (EVR) is considered to be one manifestation of an inducible response to DNA damage in mammalian cells analogous to the SOS response in Escherichia coli. EVR is characterized by the increased survival of ultraviolet (UV)-irradiated virus in cells which have been pretreated with DNA-damaging agents or by another type of cellular stress, heat shock (HS). In this study, we have analyzed the induction of nuclear proteins from Vero cells treated with either UV or HS, with the goal of identifying the protein(s) which mediate the EVR response. Results of 2-dimensional protein gel electrophoresis and fluorographic analysis of [35S]methionine-labeled nuclear proteins showed that UV-irradiation caused the increased synthesis of five proteins at 4-9 h after treatment. At 19-24 h, one of these proteins was still being synthesized at a higher level in UV-irradiated cells, and there were nine additional proteins whose syntheses were enhanced over control levels. In contrast, HS induced only one Mr 72,000 nuclear protein whose synthesis was maximal during the 4-9-h labeling period and corresponded to one of the proteins induced by UV at 19-24 h. Subsequent Western and Northern blot analyses have confirmed that this protein is a member of the heat shock protein (hsp) 70 family. Elevated nuclear levels of this protein correlated temporally with the maximum EVR response induced by each treatment (4 h after HS and 24 h after UV). Since the kinetics of EVR is different following UV and HS and parallels the difference in the induction of nuclear levels of hsp70 following each treatment, the results suggest that hsp70 may be involved in mediating the EVR response. In addition, this protein may also play a role in the recovery of DNA synthesis in UV-irradiated cells.
A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity (2006)

A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC(50) of r7-kla (3.54 +/- 0.11 micromol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within minutes, the morphologic changes in cells and mitochondrial leakage were apparent by microscopy and was consistent with rapid apoptosis. Our results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems.
Top Value-Added Chemicals from Biomass - Volume II—Results of Screening for Potential Candidates from Biorefinery Lignin (2007)

This report evaluates lignin’s role as a renewable raw material resource. Opportunities that arise from utilizing lignin fit into one of three categories: 1)power, fuel and syngas (generally near-term opportunities) 2) macromolecules (generally medium-term opportunities) 3) aromatics and miscellaneous monomers (long-term opportunities). Biorefineries will receive and process massive amounts of lignin. For this reason, how lignin can be best used to support the economic health of the biorefinery must be defined. An approach that only considers process heat would be shortsighted. Higher value products present economic opportunities and the potential to significantly increase the amount of liquid transportation fuel available from biomass. In this analysis a list of potential uses of lignin was compiled and sorted into “product types” which are broad classifications (listed above as power—fuel—syngas; macromolecules; and aromatics). In the first “product type” (power—fuel—gasification) lignin is used purely as a carbon source and aggressive means are employed to break down its polymeric structure. In the second “product type” (macromolecules) the opposite extreme is considered and advantage of the macromolecular structure imparted by nature is retained in high-molecular weight applications. The third “product type” (aromatics) lies somewhere between the two extremes and employs technologies that would break up lignin’s macromolecular structure but maintain the aromatic nature of the building block molecules. The individual opportunities were evaluated based on their technical difficulty, market, market risk, building block utility, and whether a pure material or a mixture would be produced. Unlike the “Sugars Top 10” report it was difficult to identify the ten best opportunities, however, the potential opportunities fell nicely into near-, medium- and long-term opportunities. Furthermore, the near-, medium- and long-term opportunities roughly align with the three “product types.” From this analysis a list of technical barriers was developed which can be used to identify research needs. Lignin presents many challenges for use in the biorefinery. Chemically it differs from sugars having a complex aromatic substructure. Unlike cellulose, which has a relatively simple substructure of glucose subunits, lignin has a high degree of variability in its structure which differs both from biomass source and from the recovery process used. In addition to its variability lignin is also reactive and to some degree less stable thermally and oxidatively to other biomass streams. What this means is that integrating a lignin process stream within the biorefinery will require identifying the best method to separate lignin from biomass cost-effectively.
Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A (2008)

A beneficial side effect of first-trimester combined screening for trisomy 21 is the detection of a high proportion of fetuses with trisomy 18. If an algorithm for trisomy 18 in addition to the one for trisomy 21 is used, more than 95% of trisomy 18 fetuses can be detected with a minor increase of 0.1% in the overall FPR.
Applications of O.R. in China (1986)

This paper gives a brief description of recent O.R. activity in China. It consists of four parts: mathematical programming; queueing theory and Markov decision processes; reliability theory; simulation. Emphasis is placed on the current situation of practical O.R.
Drug Conjugates Such as Antibody Drug Conjugates (ADCs), Immunotoxins and Immunoliposomes Challenge Daily Clinical Practice (2012)

Drug conjugates have been studied extensively in preclinical in vitro and in vivo models but to date only a few compounds have progressed to the clinical setting. This situation is now changing with the publication of studies demonstrating a significant impact on clinical practice and highlighting the potential of this new class of targeted therapies. This review summarizes the pharmacological and molecular background of the main drug conjugation systems, namely antibody drug conjugates (ADCs), immunotoxins and immunoliposomes. All these compounds combine the specific targeting moiety of an antibody or similar construct with the efficacy of a toxic drug. The aim of this strategy is to target tumor cells specifically while sparing normal tissue, thus resulting in high efficacy and low toxicity. Recently, several strategies have been investigated in phase I clinical trials and some have entered phase III clinical development. This review provides a detailed overview of various strategies and critically discusses the most relevant achievements. Examples of the most advanced compounds include T-DM1 and brentuximab vedotin. However, additional promising strategies such as immunotoxins and immunoliposmes are already in clinical development. In summary, targeted drug delivery by drug conjugates is a new emerging class of anti-cancer therapy that may play a major role in the future.
The Clinical Utility of DCISionRT® on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery (2021)

DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.
“I” and “Me” (2016)

Abstract The distinction between “I” and “me” as dimensions of human self‐consciousness was first set forth by William James in his classic The Principles of Psychology . Somewhat more than a decade later, George Herbert Mead began to employ this distinction in his early essays on functional and social psychology. But when a set of his course lectures on social psychology at the University of Chicago was published posthumously as Mind, Self, and Society , Mead's readers were confronted with passages that seemed to embrace not only the Jamesian version of the “I” and “me” distinction but another version as well. As a result, a good deal of confusion and controversy has resulted among those who have attempted to make use of this distinction as a tool for sociological analysis.
The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro (2010)

Retention of poorly deformable red blood cells (RBCs) by the human spleen has been recognized as a critical determinant of pathogenesis in hereditary spherocytosis, malaria, and other RBC disorders. Using an ex vivo perfusion system, we had previously shown that retention of Plasmodium falciparum-infected RBCs (Pf-RBCs) occur in the splenic red pulp, upstream from the sinus wall. To experimentally replicate the mechanical sensing of RBCs by the splenic microcirculation, we designed a sorting device where a mixture of 5- to 25-μm-diameter microbeads mimics the geometry of narrow and short interendothelial splenic slits. Heated RBCs, Pf-RBCs, and RBCs from patients with hereditary spherocytosis were retained in the microbead layer, without hemolysis. The retention rates of Pf-RBCs were similar in microbeads and in isolated perfused human spleens. These in vitro results directly confirm the importance of the mechanical sensing of RBCs by the human spleen. In addition, rigid and deformable RBC subpopulations could be separated and characterized at the molecular level, and the device was used to deplete a stored RBC population from its subpopulation of rigid RBCs. This experimental approach may contribute to a better understanding of the role of the spleen in the pathogenesis of inherited and acquired RBC disorders.
CURRENT STATUS OF THE HORMONAL TREATMENT OF ENDOMETRIOSIS (1966)

From the Department of Obstetrics and Gynecology, Harvard Medical School, Boston, and the Free Hospital for Women, Brookline, Massachusetts
Telomerase Activity in Candidate Stem Cells From Fetal Liver and Adult Bone Marrow (1998)

Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric repeats onto the 3′ ends of eukaryotic chromosomes. Activation of telomerase may prevent telomeric shortening and correlates with cell immortality in the germline and certain tumor cells. Candidate hematopoietic stem cells (HSC) from adult bone marrow express low levels of telomerase, which is upregulated with proliferation and/or differentiation. To address this issue, we stimulated purified candidate HSC from human adult bone marrow with stem cell factor (SCF), interleukin-3 (IL-3), and Flt3-ligand (FL). After 5 days in culture, activity was detected in total cell extracts from IL-3–, SCF + FL–, SCF + IL-3–, FL + IL-3–, and SCF + IL-3 + FL–stimulated cultures, but not from cells cultured in SCF or FL alone. Within the CD34+fraction of the cultured cells, significant activity was found in the CD34+CD71+ fraction. In addition, PKH26 staining confirmed that detectable telomerase activity was present in dividing PKH26lo cells, whereas nondividing PKH26hi cells were telomerase negative. Because in these experiments no distinction could be made between cycling “candidate” stem cells that had retained or had lost self-renewal properties, fetal liver cells with a CD34+CD38− phenotype, highly enriched for cycling stem cells, were also examined and found to express readily detectable levels of telomerase activity. Given the replication-dependent loss of telomeric DNA in hematopoietic cells, these observations suggest that the observed telomerase activity in candidate stem cells is either expressed in a minor subset of stem cells or, more likely, is not sufficient to prevent telomere shortening.
Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. (1998)

Increasing metalloproteinase activity, by adding purified metalloproteinases or by inducing their expression by IL-1alpha treatment, increased outflow facility. Inhibition of endogenous trabecular metalloproteinase activity using TIMP or several families of synthetic metalloproteinase inhibitors reduced outflow rates. The elevation and the reduction of outflow rates were reversible, with changes requiring 1 to 3 days. Kinetic enzyme inhibition analysis produced 50% inhibitory concentration values for these inhibitors that were compatible with the concentration ranges for outflow inhibition. CONCLUSIONS. The ability of several specific matrix metalloproteinase inhibitors to reduce outflow facility implies that endogenous extracellular matrix turnover by these enzymes was required for the maintenance of trabecular outflow resistance, at least in this human culture model. These observations provide support for the hypothesis that controlled extracellular matrix turnover is important in the regulation of aqueous humor outflow facility.
Analysis of lamb wave propagation characteristics in rotated Y‐cut X‐propagation LiNbO3 plates (1986)

Abstract Lamb wave propagation characteristics in rotated Y‐cut X‐propagation LiNbO 3 plates are analyzed theoretically as a parameter of the rotation angle of the crystal to elucidate velocity dispersion characteristics, mechanical displacement and electric potential, and electromechanical coupling constants. Calculation results show Lamb wave propagation characteristics in the 90° rotated Z‐cut plate and the 128° rotated Y‐cut plate. The zero‐order symmetrical mode at a 0° rotation angle (Y‐cut) has a high coupling constant over 20 percent. The zero‐order symmetrical and antisymmetrical modes degenerate with a plate thickness more than three wavelengths and become the Rayleigh wave range in substance. In measurement of the central frequency of the Lamb wave filter, the experimental results agree well with the theoretical analysis and the analytical results by this method are useful in constructing Lamb wave devices using interdigital transducers.
Voltage-gated Na+channels in neuropathic pain (2007)

Neuropathic pain occurs as a result of some form of injury to the nervous system. Although the basis of the disease remains to be fully elucidated, numerous studies have suggested a major role for ion channels in the pathogenesis of neuropathic pain. As Na+ channels play a fundamental role in not only the generation but also in the conduction of an action potential, they have received considerable attention in the aetiology of pain sensation and have become important pharmacological targets. In this review, the authors discuss the importance of specific Na+ channel isoforms in the pathophysiology of neuropathic pain and the present use of Na+ channel antagonists in the treatment of neuropathic pain.
Antisense RNA control of gene expression in bacteriophage P22. I. Structures of sar RNA and its target, ant mRNA. (1997)

Sar RNA is an antisense RNA that is partly responsible for the negative regulation of antirepressor synthesis during development of bacteriophage P22 (Liao SM et al., 1987, Genes & Dev 1:197-203; Wu Th, Liao SM, McClure WR, Susskind MM, Genes & Dev 1:204-212). The structures of sar RNA and its target, ant mRNA, were probed using limited RNase digestion as a function of Mg2+ concentration. Sar RNA forms two hairpins that are present at all Mg2+ concentrations (Mg2+-independent hairpins). One of the hairpins contains three tandem U x U base pairs. Ant RNA forms three Mg2+-independent hairpins and one Mg2+-dependent hairpin. In addition, many nucleotides in sar RNA and ant RNA appear to be involved in tertiary interactions. The effects of RNA structure on the pairing reaction are considered in the accompanying paper (Schaefer KL, McClure WR, 1997, RNA 3:157-174).
Newly developed microcarrier culturing systems--an overview. (1985)

Microcarrier (MC) culturing systems are widely employed for the production of biological products required for human and veterinary uses and serve as a tool for basic research in cell biology. Three types of MCs were developed by our group: cellulose, polyacrylamide and polystyrene based MCs. These newly developed MCs were used for the propagation of primary cells, cells from a human diploid cell strain and cells from established cell lines, for the production of biological products (various viruses, mouse interferon and carcinoembryonic antigen) as well as for studying cell differentiation. Basic questions regarding the effect of the chemical nature of MCs on cell attachment, spreading and growth were investigated throughout the development of these MCs.
Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity (2007)

Endothelial progenitor cells (EPCs) have been isolated postnatally from bone marrow, blood, and both the intima and adventitia of conduit vessels. However, it is unknown whether EPCs can be isolated from the lung microcirculation. Thus we sought to determine whether the microvasculature possesses EPCs capable of de novo vasculogenesis. Rat pulmonary artery (PAEC) and microvascular (PMVEC) endothelial cells were isolated and selected by using a single-cell clonogenic assay. Whereas the majority of PAECs (approximately 60%) were fully differentiated, the majority of PMVECs (approximately 75%) divided, with approximately 50% of the single cells giving rise to large colonies (>2,000 cells/colony). These highly proliferative cells exhibited the capacity to reconstitute the entire proliferative hierarchy of PMVECs, unveiling the existence of resident microvascular endothelial progenitor cells (RMEPCs). RMEPCs expressed endothelial cell markers (CD31, CD144, endothelial nitric oxide synthase, and von Willenbrand factor) and progenitor cell antigens (CD34 and CD309) but did not express the leukocyte marker CD45. Consistent with their origin, RMEPCs interacted with Griffonia simplicifolia and displayed restrictive barrier properties. In vitro and in vivo Matrigel assays revealed that RMEPCs possess vasculogenic capacity, forming ultrastructurally normal de novo vessels. Thus the pulmonary microcirculation is enriched with EPCs that display vasculogenic competence while maintaining functional endothelial microvascular specificity.
Update on Therapeutic Vascularization Strategies (2008)

The ability to exploit angiogenesis and vascularization as a therapeutic strategy will be of enormous benefit to a wide range of medical and tissue-engineering applications. Angiogenic growth factor and cell-based therapies have thus far failed to produce a robust healing response in clinical trials for a variety of ischemic diseases, while engineered tissue substitutes are still size-limited by a lack of vascularization. The purpose of this review is to investigate current research advances in therapeutic vascularization strategies applied to ischemic disease states, tissue engineering and regenerative medicine. Recent advances are discussed that focus on better regulation of growth factor delivery and attempts to better mimic natural processes by delivering combinations of multiple growth factors, cells and bioactive materials in the right spatial and temporal setting. Some unconventional approaches and novel therapeutic targets that hold significant potential are also discussed.
A 320 MHz, 1.5 mW@1.35 V CMOS PLL for microprocessor clock generation (1996)

This paper describes a low-power microprocessor clock generator based upon a phase-locked loop (PLL). This PLL is fully integrated onto a 2.2-million transistors microprocessor in a 0.35-/spl mu/m triple-metal CMOS process without the need for external components. It operates from a supply voltage down to 1 V at a VCO frequency of 320 MHz. The PLL power consumption is lower than 1.2 mW at 1.35 V for the same frequency. The maximum measured cycle-to-cycle jitter is /spl plusmn/150 ps with a square wave superposed to the supply voltage with a peak-to-peak amplitude of 200 mV and rise/fall time of about 30 ps. The input frequency is 3.68 MHz and the PLL internal frequency ranges from 176 MHz up to 574 MHz, which correspond to a multiplication factor of about 100.
Rapid Quantification of Gene Expression by Competitive RT-PCR and Ion-Pair Reversed-Phase HPLC (1996)

Competitive reverse-transcription PCR (RT-PCR) techniques for quantification of gene expression employ titrations in which the products of multiple PCRs must be separated, analyzed and quantified to compute gene expression in a single sample. We have employed a novel, ion-pair reversed-phase HPLC (IP-RP-HPLC) system to analyze and quantify RT-PCRs performed with mutant RNA internal standards. PCR products could be separated and quantified in 6 minutes per reaction using the absorbance signal from an on-line UV detector. Crude PCR products can be analyzed without further processing and without the addition of radioactive or fluorescent markers to reactions. Analysis of titration regression and slope values approached mathematical ideals indicating that amplification of native and competitor RNA occurred with equal efficiency. Further, serial dilution of input RNA over three orders of magnitude did not affect the calculated level of gene expression or the slope of the titration. IP-RP-HPLC appears to offer important advantages to quantitative measurements of gene expression. These include rapid sample analysis and column re-equilibration, reduced sample handling and opportunity for introduction of quantification error, avoidance of fluorescent or radioactive tracers, high detector sensitivity and linearity and excellent quantitative reliability.