gebhart/patrepeval huggingface dataset:
Phase I trial of taxol in patients with advanced cancer. (1987)

Taxol is a unique plant-derived antineoplastic agent that appears to exert its cytotoxic effect by interfering with microtubule structure and function. In this phase I trial, in which the drug was given as a brief iv infusion every 3 weeks, the dose-limiting toxicity was leukopenia, with thrombocytopenia being seen much less frequently. Sensory neuropathy was frequently seen at the highest dosage, with numbness and paresthesias appearing in a glove-and-stocking distribution. In some cases, this appeared to be a cumulative effect. Total alopecia was common. Other toxic effects observed included nausea and vomiting, mucositis, myalgias, and phlebitis. The frequent occurrence early in the study of acute cardiovascular and pulmonary toxicity suggestive of hypersensitivity reactions was decreased in frequency and severity by prolonging the infusions and premedication with corticosteroids and antihistamines. Two heavily treated patients appeared to respond to this agent, one with non-small cell lung cancer and one with ovarian cancer. Based on these data, we recommend a starting dose in phase II trials of 212 mg/m2 in patients with minimal prior therapy and 170 mg/m2 in heavily treated patients. At least initially, these trials should be carried out in institutions familiar with the use of this drug.
Wall shear stress oscillation and its gradient in the normal left coronary artery tree bifurcations. (2014)

Proximal LCA bifurcation exhibit lower spatial wall shear stress and lower wall shear stress gradient values compared to distal bifurcations. The lateral walls compared to the bifurcation itself are exposed to low WSS and WSSG. With regards to the temporal variation, wall shear stress and its gradient exhibited lower values throughout systole as compared to diastole, suggesting a possible atherogenic effect of both the systolic phase by itself as well as the phasic oscillation of wall shear stress and its gradient from systole to diastole.
Molecular features and expression of DAZAP2 in human multiple myeloma (2007)

DAZAP2 is downregulated in MM samples and it may be a signal molecule in MM cells. DAZAP2 is involved in the pathogenesis of MM and could be used as a genetic marker for MM.
Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease (2001)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
ACRL STANDARDS: Standards for college libraries (2000)

These standards are intended to apply to li braries supporting academic programs at the bachelor's and master's degree levels.Earlier standards for college libraries relied heavily upon resource and program "inputs" such as financial support, space, materials, and staff activities.1These new standards continue to consider "inputs," but they also take into con sideration "outputs" and "outcomes."In or der to create uniformity, the definitions as described in the ACRL "Task Force on Aca demic Library Outcomes Assessment Report" will be used in these standards.Inputs are generally regarded as the raw materials of a library program-the money, space, collection, equipment, and staff out of which a program can arise.Outputs serve to quantify the work done, i.e., number of books circulated, number of reference questions answered.Outcomes are the ways in which library users are changed as a result of their contact with the library's resources and programs.2
Permeation and block of N‐methyl‐D‐aspartic acid receptor channels by divalent cations in mouse cultured central neurones. (1987)

1. Spinal cord and hippocampal neurones in cell culture were voltage clamped using the tight-seal, whole-cell recording technique. The concentration of sodium and a series of divalent cations in the extracellular media was varied to study permeation through excitatory amino acid receptor channels activated by the selective agonists N-methyl-D-aspartic acid (NMDA), kainic acid and quisqualic acid. 2. On raising the extracellular calcium concentration, with [Na+]o held constant at 105 mM, the reversal potential of responses to NMDA shifted in the depolarizing direction. This shift was adequately described by the extended constant-field equation over the range 0.3-50 mM-calcium. Using ionic activity coefficients we calculate a value of PCa/PNa = 10.6. Under the same experimental conditions the reversal potential of responses to kainic and quisqualic acids was much less affected by raising the calcium concentration, such that PCa/PNa = 0.15. A depolarizing shift of the NMDA reversal potential was also recorded during application of 20 mM-barium, strontium or manganese, suggesting permeation of these ions. The permeability sequence was Ca2+ greater than Ba2+ greater than Sr2+ much greater than Mn2+. No depolarizing shift of the NMDA reversal potential occurred during application of 20 mM-cobalt, magnesium or nickel. 3. In experiments in which the extracellular Na+ concentration was varied the extended constant-field equation was adequate in predicting shifts of the NMDA reversal potential recorded on varying [Na+]o over the range 50-150 mM, but failed to accurately predict the reversal potential of responses to NMDA with 10 mM-[Ca2+]o and only 10 or 20 mM-[Na+]o. These results imply an apparent increase in PCa/PNa on lowering [Na+]o and may result from interaction of permeant ions within the channel. 4. Barium and to a lesser extent calcium, but not strontium (all 20 mM), reduced the slope conductance of responses to NMDA recorded within +/- 15 mV of the reversal potential; over this limited range of membrane potential the current-voltage relationship remained linear in the presence of each of these ions. In contrast manganese produced a strong, voltage-dependent block of responses to NMDA, similar to that produced by magnesium, such that even close to the reversal potential the NMDA current-voltage relationship was highly non-linear. Thus manganese both permeates and blocks the NMDA receptor channel. 5. Raising the extracellular calcium concentration, from 0.1 to 5 mM, had two effects on the conductance mechanism activated by NMDA.(ABSTRACT TRUNCATED AT 400 WORDS)
Solution and refinement of drug structures from powder data (1996)

morphous replacement (MIR) phases were determined by matching histograms of electron density. Accurate metal cluster geometries and the associated en-ors in atomic positions can be determined from refinement against anomalous differences using normal scatte1ing phases hom a refined structure. When applied to MAD data collected on SiRHP, these methods confirmed the 4Fe-4S cluster asymmetry initially observed in the refined 1.6 A resolution structure and resulted in a MAD-phased, expe1imental, electron-density map that is of better quality than the combined MAD/ MIR map originally used to solve the structure.
Interferon-tau and interferon-alpha interact with the same receptors in bovine endometrium. Use of a readily iodinatable form of recombinant interferon-tau for binding studies. (1994)

Trophoblasts of ruminant species secrete multiple forms of a novel Type I interferon (IFN-tau) for a few days preceding implantation. These IFN-tau are structurally distinct from IFN-alpha, -beta, and -omega, but it remains unclear whether they have any distinguishing biological properties. It has been of interest, therefore, to study their interaction with Type I IFN receptors. However, a recombinant bovine IFN-tau (boIFN-tau 1) prepared for such use is rapidly inactivated during chemical iodination with 125I, presumably because a critical tyrosine becomes modified. Here we describe the synthesis of a novel IFN-tau 1 in which Leu169 and Leu171 in the carboxyl terminus have been replaced by 2 tyrosine residues. The recombinant product (rboIFN-tau 1Y2) can be readily iodinated without significant loss of antiviral and antiproliferative activities, provided that reaction time with 125I is minimized. Both rboIFN-tau 1Y2 and rboIFN-alpha 1 compete with each other for binding to bovine endometrial cell membranes and Madin-Darby bovine kidney cells. Dissociation constants of both IFN are quite similar (Kd = 3.7 x 10(-10) and 3.5 x 10(-10) M, respectively). Cross-linking studies reveal a single size class of receptor polypeptide on endometrium and Madin-Darby canine kidney cells whose molecular weight is reduced from approximately 130,000 to approximately 70,000 by treatment with N-glycosidase. These studies with a single recombinant form of boIFN-tau avoid the difficulties that arise from use of a mixture of naturally occurring isoforms. They provide further evidence for the presence of a receptor common to both IFN-tau and IFN-alpha in bovine tissues and no indication for a unique IFN-tau-binding polypeptide in endometrium.
A capacitor-less DRAM cell on 75nm gate length, 16nm thin fully depleted SOI device for high density embedded memories (2005)

A capacitor-less DRAM cell on very thin film (Tsi=16nm) and short gate length (Lg=75nm) fully depleted (FD) device is demonstrated for the first time. Memory operations mechanisms are presented and retention time compatible to eDRAM requirements is measured at 85/spl deg/C. Nondestructive reading is demonstrated at 25/spl deg/C and disturb margins are deeply investigated, showing the possibility of matrix integration. This study is then extended to another type of FD device: the very promising double gate architecture.
Notch Signaling: Cell Fate Control and Signal Integration in Development (1999)

Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development. Signals exchanged between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus, Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis.
Algorithms for weighted multi-tape automata (2004)

This report defines various operations for weighted multi-tape automata (WMTAs) and describes algorithms that have been implemented for those operations in the WFSC toolkit. Some algorithms are new, others are known or similar to known algorithms. The latter will be recalled to make this report more complete and self-standing. We present a new approach to multi-tape intersection, meaning the intersection of a number of tapes of one WMTA with the same number of tapes of another WMTA. In our approach, multi-tape intersection is not considered as an atomic operation but rather as a sequence of more elementary ones, which facilitates its implementation. We show an example of multi-tape intersection, actually transducer intersection, that can be compiled with our approach but not with several other methods that we analysed. To show the practical relavance of our work, we include an example of application: the preservation of intermediate results in transduction cascades.
Sequence features of viral and human Internal Ribosome Entry Sites predictive of their activity (2017)

Translation of mRNAs through Internal Ribosome Entry Sites (IRESs) has emerged as a prominent mechanism of cellular and viral initiation. It supports cap-independent translation of select cellular genes under normal conditions, and in conditions when cap-dependent translation is inhibited. IRES structure and sequence are believed to be involved in this process. However due to the small number of IRESs known, there have been no systematic investigations of the determinants of IRES activity. With the recent discovery of thousands of novel IRESs in human and viruses, the next challenge is to decipher the sequence determinants of IRES activity. We present the first in-depth computational analysis of a large body of IRESs, exploring RNA sequence features predictive of IRES activity. We identified predictive k-mer features resembling IRES trans-acting factor (ITAF) binding motifs across human and viral IRESs, and found that their effect on expression depends on their sequence, number and position. Our results also suggest that the architecture of retroviral IRESs differs from that of other viruses, presumably due to their exposure to the nuclear environment. Finally, we measured IRES activity of synthetically designed sequences to confirm our prediction of increasing activity as a function of the number of short IRES elements.
Teriparatide Increases Strength of the Peripheral Skeleton in Premenopausal Women With Idiopathic Osteoporosis: A Pilot HR-pQCT Study (2014)

In premenopausal women with IOP, 18 months of teriparatide was associated with increases in trabecular volumetric BMD, improved trabecular microarchitecture, and estimated bone strength at both the radius and tibia.
Molecular Evolution of Shark C-type Natriuretic Peptides (1994)

C-type natriuretic peptides (CNP) of varying length were isolated from the atrium or ventricle of a shark, Lamna ditropis and their amino acid sequences were determined. Although the sequence of Lamna CNP was highly homologous to those of other CNPs sequenced to date, the Lamna CNP-41, the longest CNP identified in this study, has one amino acid replacement from those of Triakis scyllia and Scyliorhinus canicula, and three amino acid replacements from that of Squalus acanthias. The degree of similarity of CNP molecules coincides well with their systematic positions in the cladogram of elasmobranchs; Lamna, Triakis and Scyliorhinus belong to the same order, but Lamna and Squalus belong to different orders. The facts that Lamna and Triakis are in different suborders but Triakis and Scyliorhinus are in the same suborder and have identical CNP-41, also support this evolutionary implication.
Negative Regulation of Cytokine Signaling Pathways (2000)

The Janus family of protein tyrosine kinases (JAKs) and STAT transcription factors regulate cellular processes involved in cell growth, differentiation, and transformation through their association with cytokine receptors. The CIS family of proteins (also referred to as the SOCS or SSI family) has been implicated in the regulation of signal transduction by a variety of cytokines. Most of them appear to be induced after stimulation with several different cytokines, and at least three of them (CIS1, CIS3/SOCS3, and JAB/SOCS1) negatively regulate cytokine signal transduction by various means: CIS1 inhibits STAT5 activation by binding to cytokine receptors that recruit STAT5, whereas JAB/SOCS-1 and CIS3/SOCS-3 directly bind to the kinase domain of JAKs, thereby inhibiting tyrosine-kinase activity. Therefore, these CIS family members seem to function in a classical negative feedback loop of cytokine signaling. Biochemical characterization as well as gene disruption studies indicate that JAB/SOCS1/SSI-1 is an important negative regulator of interferon gamma signaling. The mechanisms by which these inhibitors of cytokine signal transduction exert their effects have been extensively studied and will provide useful information for regulating tyrosine-kinase activity.
Development of a recombinant baculovirus expressing a modified juvenile hormone esterase with potential for insect control (1995)

Abstract Baculovirus insecticides are receiving renewed attention as insect pest control agents following the development of fast‐acting recombinant baculoviruses. Here we report on the construction and biological activity of a recombinant baculovirus derived from the nuclear polyhedrosis virus of Autographa californica which expresses a modified form of juvenile hormone esterase (JHE). The serine at the catalytic site of the JHE has been mutated to a glycine residue so that the protein does not degrade JH. The recombinant baculovirus expressing this modified form of JHE, named AcJHE‐SG, has enhanced activity against lepidopteran larvae. Lethal times of the recombinant are 20 to 30% lower than for the wild type virus, and a 66% reduction in feeding damage caused by infected larvae is observed. This result is comparable to the best recombinant baculovirus developed to date, AcAaIT, which expresses an insect‐selective scorpion toxin. The potential of these recombinant viruses for commercialization as insecticides is discussed. Bioassays of AcJHE‐SG in conjunction with anti‐JH agents indicate that the virus is not killing by an anti‐JH mechanism. Larvae apparently die from contraction‐paralysis, or disruption of the normal sequence of events at the molt. © 1995 Wiley‐Liss, Inc.
Continuous interleukin‐6 application in vivo via macroencapsulation of interleukin‐6–expressing COS‐7 cells induces massive gliosis (2001)

The inflammatory cytokine interleukin-6 (IL-6) was found in senile plaques of Alzheimer's patients and might be involved in the pathology of Parkinson's disease and multiple sclerosis. Interestingly, an astocytosis is also found in these neurodegenerative disorders. To evaluate the direct effects of IL-6 in vivo on glial cells, we created a new in vivo model. IL-6 and mock-transfected (control group) COS-7 cells were encapsulated in a poly-acryl-nitril membrane for implantation into the rat striatum. Afterward, the host immune reaction to the membrane without encapsulated cells and the biological action of IL-6-producing capsules was evaluated. Animals with an implanted membrane without cells showed a moderate astrocytosis 5 days after the operation. Furthermore, microglia and T-cells could be detected and after 30 days the astrocytosis decreased to a small layer around the membrane. In comparison to the control group, which received a sham operation, our results demonstrate that the response of glial cells is caused by the mechanical damage of the surgical procedure itself rather than due to the introduced membrane material. In contrast, we found a massive proliferation and activation of astrocytes and microglia after 10 days by IL-6-secreting capsules, indicating that IL-6 is involved in the induction of gliosis. Control animals that received encapsulated mock-transfected COS-7 cells showed only a weak response. These data point to an involvement of IL-6 in the proliferation and activation of glial cells as seen in neurodegenerative disorders.
On the dependence of the elastic properties of a porous rock on the compressibility of the pore fluid (1975)

Abstract An equation is derived for the dependence of the elastic properties of a porous material on the compressibility of the pore fluid. More generally, the elastic properties of a container of arbitrary shape are related to the compressibility of the fluid filling a cavity in the container. If the pore system or cavity under consideration is filled with a fluid of compressibility kappa F , the compressibility kappa of the closed container is given byEquationHere kappa A is the compressibility of the container with the fluid pressure held constant in the interconnected pore system or cavity. Fluids in other pores or cavities not connected with the one in question contribute to the value of kappa A . phi is the porosity, i.e., the volume fraction corresponding to the pore system or cavity in question. The equation contains two distinct effective compressibilities, kappa M and kappa (sub phi ) , of the material exclusive of the pore fluid. When this material is homogeneous, one has kappa M = kappa (sub phi ) , and the equation reduces to a well-known relation by Gassmann. For the other elastic properties, we also obtain expressions which generalize Gassmann's work and which also differ from it only in the appearance of kappa (sub phi ) instead of kappa M in one term. Our result is intimately related to the reciprocity theorem of elasticity. Special cases are discussed.
Functional Proteomics of the Active Cysteine Protease Content in Drosophila S2 Cells (2003)

The fruit fly genome is characterized by an evolutionary expansion of proteases and immunity-related genes. In order to characterize the proteases that are active in a phagocytic Drosophila model cell line (S2 cells), we have applied a functional proteomics approach that allows simultaneous detection and identification of multiple protease species. DCG-04, a biotinylated, mechanism-based probe that covalently targets mammalian cysteine proteases of the papain family was found to detect Drosophila polypeptides in an activity-dependent manner. Chemical tagging combined with tandem mass spectrometry permitted retrieval and identification of these polypeptides. Among them was thiol-ester motif-containing protein (TEP) 4 which is involved in insect innate immunity and shares structural and functional similarities with the mammalian complement system factor C3 and the pan-protease inhibitor alpha2-macroglobulin. We also found four cysteine proteases with homologies to lysosomal cathepsin (CTS) L, K, B, and F, which have been implicated in mammalian adaptive immunity. The Drosophila CTS equivalents were most active at a pH of 4.5. This suggests that Drosophila CTS are, similar to their mammalian counterparts, predominantly active in lysosomal compartments. In support of this concept, we found CTS activity in phagosomes of Drosophila S2 cells. These results underscore the utility of activity profiling to address the functional role of insect proteases in immunity.
Evoking durable anti-cancer responses with blocking antibodies to PD-1 and PD-L1 (2012)

Inhibitory immune checkpoints play a critical role in regulating the strength and duration of immune responses in order to maintain self-tolerance and prevent autoimmunity (1). Such regulatory mechanisms are typically exploited by tumors as an immune escape mechanism and thereby pose a major obstacle to the induction of clinically relevant anti-cancer immune responses capable of controlling and/or eradicating disease (2).
Ultrathin Carbon Molecular Sieve Films and Room-Temperature Oxygen Functionalization for Gas-Sieving (2019)

Inorganic membranes based on carbon molecular sieve (CMS) films hosting slit-like pores can yield high molecular selectivity with a sub-angstrom resolution in molecular differentiation and therefore are highly attractive for energy-efficient separations. However, the selective layer thickness of the state-of-the-art CMS membranes for gas separation is more than 1 μm, yielding low gas permeance. Also, there is no room-temperature functionalization route for the modification of the pore-size-distribution of CMS to increase the molecular selectivity. In this context, we report two novel fabrication routes, namely, transfer and masking techniques, leading to CMS films with thicknesses as small as 100 nm, yielding attractive gas-sieving performances with H<sub>2</sub> permeance reaching up to 3060 gas permeation unit (GPU). Further, a rapid and highly tunable room-temperature ozone treatment-based postsynthetic modification is reported, shrinking the electron density gap in the nanopores by a fraction of an angstrom and improving gas selectivities by several folds. The optimized membranes yielded H<sub>2</sub> permeance of 507 GPU and H<sub>2</sub>/CH<sub>4</sub> selectivity of 50.7.