gebhart/patrepeval huggingface dataset:
Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients (2011)

Efforts to improve efficacy and minimize toxicity have led to pharmacokinetic monitoring of plasma 5-Fluorouracil (5-FU) levels in colorectal cancer patients undergoing chemotherapy. We observed variation in basal 5-FU levels in 21 patients and significant variation during subsequent dose optimization. Tumor KRAS, BRAF mutations and TS mRNA levels were determined. Regimens included FOLFOX6 + Avastin (N = 8), FOLFOX6 (N = 11), FOLFIRI (N = 1) and FOLFOX4 (N = 1). Mutations identified in tumors included G12V KRAS (N = 2), G12A KRAS (N = 1), and V600E BRAF (N = 3). Six-of-eleven patients with normalized tumor TS mRNA levels < 4.0 had a 5-FU AUC of 20 mg.h/L or greater, and 80% of patients (4 of 5) with TS levels > 4.0 had a plasma 5-FU AUC of less than or equal to 20 mg.h/L. Approximately 2/3 of patients achieved therapeutic 5-FU AUC levels with 0-2 dose adjustments while a sub-group of ~1/3 of patients slowly achieved therapeutic levels (> 3-4 dose increases leading to supra-therapeutic 5-FU and subsequent reductions to lesser than original doses). Liver metastases and tumor TS levels did not fully account for variable 5-FU AUC optimization patterns. The 5-FU level during continuous infusion was half-therapeutic in one patient who received FOLFOX4. The observed heterogeneous patterns at baseline and during dose optimization of 5-FU levels suggest variations in 5-FU metabolism among treated patients. Physiological and/or genetic differences underlying heterogeneity in 5-FU levels during dose optimization require further study of patient demographics, single nucleotide polymorphisms in Dihydropyrimidine Dehydrogenase (DPD), TS, or other genes that impact 5-FU metabolism and gene expression changes in liver after 5-FU therapy.
Ultra compact 45 GHz CMOS compatible Germanium waveguide photodiode with low dark current (2011)

We present a compact 1.3 × 4 μm2 Germanium waveguide photodiode, integrated in a CMOS compatible silicon photonics process flow. This photodiode has a best-in-class 3 dB cutoff frequency of 45 GHz, responsivity of 0.8 A/W and dark current of 3 nA. The low intrinsic capacitance of this device may enable the elimination of transimpedance amplifiers in future optical data communication receivers, creating ultra low power consumption optical communications.
Structure determination of membrane proteins by NMR spectroscopy (2002)

Current strategies for determining the structures of membrane proteins in lipid environments by NMR spectroscopy rely on the anisotropy of nuclear spin interactions, which are experimentally accessible through experiments performed on weakly and completely aligned samples. Importantly, the anisotropy of nuclear spin interactions results in a mapping of structure to the resonance frequencies and splittings observed in NMR spectra. Distinctive wheel-like patterns are observed in two-dimensional 1H-15N heteronuclear dipolar/15N chemical shift PISEMA (polarization inversion spin-exchange at the magic angle) spectra of helical membrane proteins in highly aligned lipid bilayer samples. One-dimensional dipolar waves are an extension of two-dimensional PISA (polarity index slant angle) wheels that map protein structures in NMR spectra of both weakly and completely aligned samples. Dipolar waves describe the periodic wave-like variations of the magnitudes of the heteronuclear dipolar couplings as a function of residue number in the absence of chemical shift effects. Since weakly aligned samples of proteins display these same effects, primarily as residual dipolar couplings, in solution NMR spectra, this represents a convergence of solid-state and solution NMR approaches to structure determination.
Origin of human bipedalism: The knuckle-walking hypothesis revisited (2001)

Some of the most long-standing questions in paleoanthropology concern how and why human bipedalism evolved. Over the last century, many hypotheses have been offered on the mode of locomotion from which bipedalism originated. Candidate ancestral adaptations include monkey-like arboreal or terrestrial quadrupedalism, gibbon- or orangutan-like (or other forms of) climbing and suspension, and knuckle-walking. This paper reviews the history of these hypotheses, outlines their predictions, and assesses them in light of current phylogenetic, comparative anatomical, and fossil evidence. The functional significance of characteristics of the shoulder and arm, elbow, wrist, and hand shared by African apes and humans, including their fossil relatives, most strongly supports the knuckle-walking hypothesis, which reconstructs the ancestor as being adapted to knuckle-walking and arboreal climbing. Future fossil discoveries, and a clear understanding of anthropoid locomotor anatomy, are required to ultimately test these hypotheses. If knuckle-walking was an important component of the behavioral repertoire of the prebipedal human ancestor, then we can reject scenarios on the origin of bipedalism that rely on a strictly arboreal ancestor. Moreover, paleoenvironmental data associated with the earliest hominins, and their close relatives, contradict hypotheses that place the agents of selection for bipedality in open savanna habitats. Existing hypotheses must explain why bipedalism would evolve from an ancestor that was already partly terrestrial. Many food acquisition and carrying hypotheses remain tenable in light of current evidence. Yrbk Phys Anthropol 44:70–105, 2001. © 2001 Wiley-Liss, Inc.
Pilot screening programme for small molecule activators of p53 (2005)

Activation of the p53 tumour suppressor is predicted to have therapeutically beneficial effects. Many current anti-cancer therapies activate the p53 response via DNA damage. Non-genotoxic activation of the p53 pathway would open the way to long-term and possibly prophylactic treatments. We have established a simple protocol to screen small compound libraries for activators of p53-dependent transcription, and to select and characterise the most interesting hits, which include non-genotoxic activators. These compounds or their derivatives are of potential clinical interest. This approach may also lead to the identification of novel p53-activating compound families and possibly to the description of novel molecular pathways regulating p53 activity.
A segment vocoder at 150 b/s (2005)

In this paper we investigate several methods for reducing the bit rate of a segment vocoder [1] by 35% to 150 b/s. In the original vocoder we used a random sample of vectors as a set of templates for vector quantization. We demonstrate in this paper that this random quantizer is near-optimal by comparing it with quantizers that use clustering algorithms for quantizing speech segments. The reduction of the bit rate of the segment vocoder was achieved primarily by using a segment network, i.e., not all segment templates are allowed to follow a given segment template. The spectral continuity of speech is used to determine the subset of templates, that can be used to quantize an input segment. To achieve the low rate of 150 b/s, we also reduced the bit rate for coding pitch, gain, and segment duration. Finally, we present the bit allocation used for transmitting speech at 150 b/s as a single speaker segment vocoder.
Differences in cell-to-cell spread of pathogenic and apathogenic rabies virus in vivo and in vitro (1985)

Pathogenic parental rabies virus and apathogenic variant virus were shown to differ in their ability to infect neurons in vivo and neuroblastoma cells in vitro. After intracerebral inoculation, the distribution of infected neurons in the brain was similar for both viruses, but the rate of spread throughout the brain, the number of infected neurons, and the degree of cellular necrosis were much lower in the case of apathogenic virus. After adsorption to mouse neuroblastoma cells, apathogenic virus was less rapidly internalized than pathogenic virus, and cell-to-cell spread of apathogenic variant virus was completely prevented by the addition of rabies virus-neutralizing antibody, whereas the spread of pathogenic virus was not affected.
Lua—An Extensible Extension Language (1996)

This paper describes Lua, a language for extending applications. Lua combines procedural features with powerful data description facilities, by using a simple, yet powerful, mechanism of tables . This mechanism implements the concepts of records, arrays and recursive data types (pointers), and adds some object-oriented facilities, such as methods with dynamic dispatching. Lua presents a mechanism of fallbacks that allows programmers to extend the semantics of the language in some unconventional ways. As a noteworthy example, fallbacks allow the user to add different kinds of inheritance to the language. Currently, Lua is being extensively used in production for several tasks, including user configuration, general-purpose data-entry, description of user interfaces, storage of structured graphical metafiles, and generic attribute configuration for finite element meshes.
Dissolvable Metal Supports for 3D Direct Metal Printing (2016)

Additive manufacturing (AM) offers the ability to fabricate complex metallic structures and shapes in a layer-by-layer process. However, overhanging surfaces often require support structures to be fabricated and minimize thermally induced distortion. Unlike polymer AM processes, soluble sacrificial support materials have not been identified and characterized for metallic materials, and, as a result, support structures in 3D printed metals must be removed using additional machining operations. In this work, we demonstrate that sacrificial metal supports can be fabricated by taking advantage of differences in the chemical and electrochemical stability between different metals. As a demonstration, a stainless steel bridged structure with a 90° overhang was fabricated using a carbon steel sacrificial support that was later removed through electrochemical etching in 41 wt.% nitric acid with bubbling O2. Open circuit potentials and potentiodynamic polarization curves were gathered to verify etch selectivity. No machining, grinding, or finishing operations were required to remove the metallic supports using this approach. This novel approach introduces new capabilities to AM that could drastically reduce the postprocessing needed for 3D printed metal components.
Study of resolution limits due to intrinsic bias in chemically amplified photoresists (1999)

This article presents experimental results that suggest that classical Fickian diffusion cannot account for any significant fraction of the critical dimension bias observed in chemically amplified photoresists. A transport mechanism based on reaction front propagation is proposed as a possible explanation for the experimental observations.
Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model (2007)

This report shows that interleukin (IL) 17-producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor beta and IL-6 additionally need IL-1 and neutralization of interferon (IFN) gamma and IL-4 for CCR6 expression. Forced expression of RORgamma t, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1beta, IL-17, or tumor necrosis factor alpha, and is suppressed by IFN-gamma or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.
Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells (1981)

Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.
Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision (2006)

Nanotechnology is often associated with materials fabrication, microelectronics, and microfluidics. Until now, the use of nanotechnology and molecular self assembly in biomedicine to repair injured brain structures has not been explored. To achieve axonal regeneration after injury in the CNS, several formidable barriers must be overcome, such as scar tissue formation after tissue injury, gaps in nervous tissue formed during phagocytosis of dying cells after injury, and the failure of many adult neurons to initiate axonal extension. Using the mammalian visual system as a model, we report that a designed self-assembling peptide nanofiber scaffold creates a permissive environment for axons not only to regenerate through the site of an acute injury but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we show that regenerated axons reconnect to target tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behavior. The peptide nanofiber scaffold not only represents a previously undiscovered nanobiomedical technology for tissue repair and restoration but also raises the possibility of effective treatment of CNS and other tissue or organ trauma.
Folate Conjugated Doxorubicin-Loaded Membrane Vesicles for Improved Cancer Therapy (2003)

The new concept developed in this study is the preparation of a new derivative of erythrocyte ghosts, i.e., membrane vesicles loaded with doxorubicin (Dox) HCl and coupled to folic acid to improve cancer chemotherapy. N-hydroxysuccinimide (NHS) folate was then conjugated to membrane vesicles. These membrane vesicles were extensively characterized for in vitro and in vivo performance. The vesicle size obtained was in the range of 1.2-1.5 microm and in vitro release profile showed 51.8 and 38.7% of drug release in case of Dox-V and Dox-FV, respectively, in 16 hr. The stability studies were performed at 4 degrees C by assessing the effect on vesicle size and leakage after 7, 15, and 21 days. The stability study showed negligible leakage and no appreciable change in the vesicle size after storage for several days in both formulations. The cytostatic activity was assessed and found that IC50 was decreased 3.2 and 2.1 times for Dox-FV compared with free drug and Dox-V, respectively. The cytotoxic activity showed similar profile among the formulations: order of toxicity was Dox-FV > Dox-V > free drug. The mean survival time was found in order of Dox-FV > Dox-V > free drug > control (FV). The increase in life for Dox-FV was 212.9%. Overall, this folic acid conjugated vesicle system proved to be a potential delivery system for improved cancer therapy.
Investigation of Bioterrorism-Related Anthrax, United States, 2001: Epidemiologic Findings (2002)

In October 2001, the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify additional cases and determine possible exposures to Bacillus anthracis. Surveillance was enhanced through health-care facilities, laboratories, and other means to identify cases, which were defined as clinically compatible illness with laboratory-confirmed B. anthracis infection. From October 4 to November 20, 2001, 22 cases of anthrax (11 inhalational, 11 cutaneous) were identified; 5 of the inhalational cases were fatal. Twenty (91%) case-patients were either mail handlers or were exposed to worksites where contaminated mail was processed or received. B. anthracis isolates from four powder-containing envelopes, 17 specimens from patients, and 106 environmental samples were indistinguishable by molecular subtyping. Illness and death occurred not only at targeted worksites, but also along the path of mail and in other settings. Continued vigilance for cases is needed among health-care providers and members of the public health and law enforcement communities.
Electronic computer solution for the MPN equation used in the determination of bacterial populations (1960)

Abstract The utility and the practical precision of the Most Probable Number method for determining bacterial populations is currently restricted by a lack of adequate tables of solved examples or alternatively by an easy and quick solution to individual problems. Where an electronic computer is available, these restrictions need not apply. A computer programme and example solution for tabulated data and individual problems are presented in this paper.
Characterization of receptor-mediated and store-regulated Ca2+ influx in human neutrophils (1994)

1. It is not known to what extent the emptying of intracellular Ca2+ stores participates in the mediation of chemoattractant-induced Ca2+ influx in human neutrophils. To study this question, we compared the properties of bivalent-cation influx in response to the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenyl-alanine (f-MLP) and to the microsomal Ca(2+)-ATPase inhibitor thapsigargin. 2. The influx pathway activated by f-MLP and thapsigargin had identical properties of permeation. Mn2+ influx became saturated at around 1 mM extracellular Mn2+, whereas Ca2+ influx did not become saturated up to concentrations of 10 mM. 3. The influx of the two bivalent cations, Mn2+ and Ca2+, was activated to a similar extent and with identical kinetics of activation. 4. The Mn2+ influx activated by f-MLP and thapsigargin was blocked, with identical dose-inhibition curves, by four imidazole analogues. 5. The same relationship between the emptying of Ca2+ stores and bivalent-cation influx was observed for f-MLP and thapsigargin, with a half-maximal activation of the influx at 40% emptying of intracellular stores. 6. In conclusion, neutrophils possess a single type of Ca(2+)-influx pathway that is activated by receptor agonists and by store depletion. Receptor agonists activate this influx pathway to a large extent, if not completely, through the depletion of intracellular Ca2+ stores.
Comparative tumorigenicity of benzo[a]pyrene, 1-nitropyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administered by gavage to female CD rats (1995)

Agents that are ubiquitous in the environment and are known inducers of mammary cancer in rodents can be regarded as potential causes of human cancer and need to be evaluated more completely. Therefore, the purpose of this study was to determine under identical conditions the relative carcinogenic potency in the mammary glands of rats of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Thirty-day-old female CD rats were gavaged once weekly for 8 weeks with B[a]P, 1-NP or PhIP. Each compound was given at 50 mumol/rat/week in 0.5 ml trioctanoin for a total dose of 400 mumol/rat. Forty-one weeks after the last carcinogen administration, rats were killed. In the 1-NP-treated rats, treatment elicited primarily benign tumors. In contrast, the B[a]P- and PhIP-treated rats developed both malignant and benign tumors. The incidence of adenocarcinomas in rats treated with B[a]P or PhIP was comparable and significantly higher than that in animals receiving trioctanoin only. The incidence of benign tumors (fibroadenomas, desmoplastic adenomas and adenomas) observed in animals treated with B[a]P or 1-NP was comparable and significantly higher than that in animals given PhIP or trioctanoin. This is the first report describing the carcinogenic activity of PhIP, given by gavage, in the mammary gland of CD rats and ranking the carcinogenic potency observed under identical conditions, of three agents (B[a]P congruent to PhIP > 1-NP) that are prevalent in the human environment.
GB virus B and hepatitis C virus NS3 serine proteases share substrate specificity (1997)

GB virus B (GBV-B) is a recently discovered virus responsible for hepatitis in tamarins (Saguinus species). GBV-B belongs to the Flaviviridae family and is closely related to the human pathogen hepatitis C virus (HCV). Nonstructural protein 3 (NS3) of HCV has been shown to encompass a serine protease domain required for viral maturation. GBV-B and HCV share only about 30% of the amino acid sequence within the NS3 protease domain. The catalytic triad is conserved, and the residue Phe-154, presumed to be a crucial amino acid for determining the S1 specificity pocket of the HCV NS3 protease, is also conserved. We have expressed a synthetic gene encoding the GBV-B NS3 protease domain in Escherichia coli and have characterized the purified recombinant protein for its activity on HCV substrates. We have shown that the NS3 region of the GBV-B genome actually encodes a serine protease that, despite the low sequence homology, shares substrate specificity with the HCV NS3 protease.
RNase inhibition of human immunodeficiency virus infection of H9 cells. (1994)

Onconase and bovine seminal RNase, two members of the RNase A superfamily, inhibit human immunodeficiency virus type 1 replication in H9 leukemia cells 90-99.9% over a 4-day incubation at concentrations not toxic to uninfected H9 cells. Two other members of the same protein family, bovine pancreatic RNase A and human eosinophil-derived neurotoxin, have no detectable antiviral activity, demonstrating a strikingly selective antiviral activity among homologous ribonucleases. The antiviral RNases do not appear to affect viral particles directly but inhibit replication in host cell cultures. Onconase, already in clinical trials for cancer therapy, and bovine seminal RNase have potential as antiviral therapeutics.