gebhart/patrepeval huggingface dataset:
Nudix hydrolase 18 catalyzes the hydrolysis of active triphosphate metabolites of the antivirals remdesivir, ribavirin, and molnupiravir (2022)

Remdesivir and molnupiravir have gained considerable interest because of their demonstrated activity against SARS-CoV-2. These antivirals are converted intracellularly to their active triphosphate forms remdesivir-TP and molnupiravir-TP. Cellular hydrolysis of these active metabolites would consequently decrease the efficiency of these drugs; however, whether endogenous enzymes that can catalyze this hydrolysis exist is unknown. Here, we tested remdesivir-TP as a substrate against a panel of human hydrolases and found that only Nudix hydrolase (NUDT) 18 catalyzed the hydrolysis of remdesivir-TP with notable activity. The k<sub>cat</sub>/K<sub>m</sub> value of NUDT18 for remdesivir-TP was determined to be 17,700 s<sup>-1</sup>M<sup>-1</sup>, suggesting that NUDT18-catalyzed hydrolysis of remdesivir-TP may occur in cells. Moreover, we demonstrate that the triphosphates of the antivirals ribavirin and molnupiravir are also hydrolyzed by NUDT18, albeit with lower efficiency than Remdesivir-TP. Low activity was also observed with the triphosphate forms of sofosbuvir and aciclovir. This is the first report showing that NUDT18 hydrolyzes triphosphates of nucleoside analogs of exogenous origin, suggesting that NUDT18 can act as a cellular sanitizer of modified nucleotides and may influence the antiviral efficacy of remdesivir, molnupiravir, and ribavirin. As NUDT18 is expressed in respiratory epithelial cells, it may limit the antiviral efficacy of remdesivir and molnupiravir against SARS-CoV-2 replication by decreasing the intracellular concentration of their active metabolites at their intended site of action.
Social ownership and the reform of the nationalised industries: The Labour Party's plans (1986)

People on all parts of the political spectrum have criticised the traditional form of public ownership ‐ the nationalised corporation. If that is not to be replaced, as the present Government would have it, through privatisation, what are the alternatives? The Labour Party has been attempting to define some, and in so doing to replace the concept of the Morrisonian corporation by what it considers the more democratic and accountable one of social ownership.
A true fiber optic refractometer (2017)

Abstract The best instrument to measure the refractive index of liquids is the Abbe refractometer which can only provide accuracies of the order of 10 −5 at visible wavelengths and 10 −4 in the near infrared. Here we present a technique by which the exact wavelength positions in the near infrared frequency comb of a tilted grating inscribed in the core of an optical fiber can be used to measure the absolute value of the refractive index of a liquid in which the fiber is inserted, with an accuracy of ±5×10 −5 . This is in contrast to typical fiber optic‐based “refractometry” where only refractive index variations can be measured accurately, hence the appellation of “true” fiber optic refractometer here. In addition to the increased accuracy, the fiber refractometer proposed here offers the additional advantages associated with in situ measurements. The performance of this refractometer is demonstrated by measurements in water from room temperature down to near freezing at wavelengths in the 1550 nm window. image
Crystal Structure and Site Preference of Ba-Doped α-Tricalcium Phosphate (Ca1-xBax)3(PO4)2through High-Resolution Synchrotron Powder Diffraction (x= 0.05 to 0.15) (2007)

The single phase of barium-substituted alpha tricalcium phosphate (Ba-α-TCP) (Ca1-xBax)3(PO4)2 (x = 0.05, 0.10, and 0.15) has been prepared by solid-state reactions. The crystal structure of the Ba-α-TCP powders has been investigated by high-resolution synchrotron powder diffraction and the Rietveld method. Diffraction data were successfully analyzed by the single phase Ba-α-TCP (space group P21/a). Unit-cell parameters a, b, c, and β increase with increasing Ba content. Most of the Ba atoms are located at three crystallographic sites among the eighteen cation sites in the α-(Ca1-xBax)3(PO4)2 (x = 0.05, 0.10, and 0.15). The refined positional parameters and occupancy factors of the preference sites for Ba substitutions were Ca17: (0.0909(6), 0.4167(2), 0.7823(5)) g(Ba) = 0.72(2); Ca11: (0.4068(6), 0.2506(2), 0.2199(5)) g(Ba) = 0.67(1); Ca5: (0.0983(6), 0.0837(2), 0.7857(5)) g(Ba) = 0.65(1) in the α-(Ca0.85Ba0.15)3(PO4)2. Here, g(Ba) is the occupancy factor of Ba atoms. These sites have relatively smaller bond valence sums, indicating the preference sites for the larger-sized Ba substitutions.
Control of Flame-Holding in Supersonic Airflow by Secondary Air Injection (1998)

Active control tests were performed to improve e ame-holding in a e xed-geometry rectangular scramjet combustor at an off-design point and to improve self-ignition in the combustor. With a e xed-geometry combustor, the pressure oscillation originated from unstable e ame-holding, and/or blowoff were measured at an off-design point. Eight air injectors were installed in the combustor wall, and secondary air was injected into the boundary layer, which developed downstream of a step that controlled the effective cross-sectional area of the combustor. Signals from pressure transducers on the combustor wall were used as feedback signals for the control. This control system was simple to install in a e xed-geometry combustor. The control system was effective in improving combustion oscillation and/or blowoff at an off-design point and was responsive to a rapid condition change. It was also valid for improving the selfignition limit.
Proteasome Inhibition Upregulates the Cell Surface Expression of Receptors for IFN-?? and TNF-?? on Murine Neuroblastoma Cells and Enhances The Proapoptotic And Overall Antitumor Activity Of Systemic Cytokine Therapy In Murine Neuroblastoma Tumors (2005)

s: Abstracts for the 20th Annual Scientific Meeting of the International Society for Biological Therapy of Cancer (Primary Authors are Italicized): NEW AGENTS IN DEVELOPMENT
PROCESSING AND MECHANICAL PROPERTIES OF Si3N4/SiC NANOCOMPOSITES USING Si NITRIDED Si3N4 POWDER (1999)

The pressureless sintering was investigated to fabricate dense Si3N4/SiC nanocomposites from commercially available Si nitrided Si3N4 powder. MgAl2O4+ZrO2 (totally 10 and 15wt%) or Y2O3+Al2O3 (totally 10.5 and 14wt%) and 5-30vol% SiC were used as sintering additives and second phase dispersions, respectively. With increasing SiC content, the density of the composite containing less amount of sintering additives decreased linearly, while the large amount of sintering additives decreased gradually the density or kept it constant. The composites with higher SiC content presented a relatively smaller Si3N4 grain size, because the Si3N4 grain growth was inhibited by SiC particles that pinned the grain boundary movement. While decrease in strength was observed for the composites with less amount of sintering additives, an improvement of the strength was found for the composites with high amount of sintering additives. The strength change of the composites was consistent with their densification behavior and microstructural observation. Composite with 20vol% SiC exhibited high strength up to 1GPa. With increasing SiC content, hardness increased but toughness decreased. It is concluded that the results of this study provide an economic way to fabricate the Si3N4/SiC nanocomposite with high performance.
Direct Observation and Real-Time Tracking of an Extraordinarily Stable Folding Intermediate in Mitotic Arrest Deficient Protein 2 Folding by Single-Molecule Fluorescence Resonance Energy Transfer (2023)

Although ensemble experiments have suggested that mitotic arrest deficient protein 2 (Mad2), a metamorphic protein, has folding intermediates, direct evidence and characterization are not available. It remains an outstanding challenge to capture the folding intermediates in real time, which is crucial to elucidate the folding mechanism, but the folding intermediates are normally unstable and only exist transiently. By combining confocal-microscopy-based and total internal reflection fluorescence (TIRF)-microscopy-based single-molecule Förster resonance energy transfer (sm-FRET) techniques, we have investigated the folding/unfolding process of Mad2 and captured its folding intermediate at the single-molecule level. This provides direct evidence for the existence of an intermediate along the folding pathway of Mad2. The folding intermediate proved to be extraordinarily stable, with an extremely long average dwell time of 2.3 s under the conditions of 3 M GdmCl at ambient temperature. The folding trajectories obtained from TIRF experiments further suggest that the intermediate is on-pathway to native Mad2.
Review of Migration, Research Methods, and Passage for Downstream Migrant Fishes in the Northeast USA (2003)

Pre-spawning adults of most northeast diadromous species migrate from the Atlantic Ocean into rivers in March-June. Many adults survive spawning and return downstream to salt water. Thus, for species passed upstream of dams to spawn, both post-spawned adults and early life stages (typically, juveniles) need safe passage when moving downstream past dams and water withdrawals. Many northeast potamodromous fishes (=riverine fish species here) have evolved up- and downstream migrations that occur from March to November. Migrations of the riverine Connecticut River shortnose sturgeon, Acipenser brevirostrum, show the river is a busy highway of up- and downstream movement of various life stages during March-November. These migrations may be typical of long-lived riverine fishes that have evolved in a large open river. Researchers study downstream fish migrations using traps, nets, telemetry, and hydroacoustic techniques. When field studies are not possible, scientists study migration of early life stages in artificial streams. Fish passage in the northeast US is directed by agencies at a few diadromous sport fish species that are the subject of restoration programs, and not at the diverse diadromous and riverine migratory fish community. Target species and life stages are typically adult and juvenile alosids (American shad, Alosa sapidissima, and blueback herring, A. aestivalis), and Atlantic salmon, Salmo salar, smolts. These fish are in the upper part of the water column; so surface bypass systems are effective. At Holyoke Dam, Connecticut River, MA efforts are underway to protect two new diadromous target species that are benthic, i.e., the federally endangered shortnose sturgeon and American eel, Anguilla rostrata, whose populations have declined. To date, no bypass system for benthic species has been developed. Screens are commonly used in the western US to protect fish with mixed success, but are uncommon in the Northeast because agencies protect surface migrants mainly using bar racks with 25-mm clear spacing that extend from the surface to 3 m deep. While this effort has been successful for a few surface-oriented species, it does not protect small fish of any species or benthic species. Many northeast rivers have been dammed and the riverine fish populations
Virtual prototyping AADL architectures in a polychronous model of computation (2008)

While synchrony and asynchrony are two distinct concepts of concurrency theory, effective and formally defined embedded system design methodologies usually mix the best from both synchronous and asynchronous worlds by considering locally synchronous processes composed in a globally asynchronous way to form so called GALS architectures. In the avionics domain, for instance, the Architecture Analysis and Design Language (AADL) may be used to describe both the hardware and software architecture of an application at system-level. Yet, a synchronous design formalism might be preferred to model and validate each of the critical components of the architecture in isolation. In this paper, we illustrate the use of the polychronous (multi-clocked synchronous) paradigm to model partially asynchronous applications. The specification formalism Signal is used to describe real-world avionic applications using concepts of Integrated Modular Avionics (IMA). We show how an AADL architecture can be automatically translated into a synchronous model in SIGNAL using these modeling concepts. We present a case study on the design of generic system architecture. The approach is being implemented in the framework of the ANR project TopCased.
<title>Finishing and proof testing of windows for manned space craft</title> (1993)

The development of the Space Shuttle Orbiter in the early 1970s marked the first time that a fracture mechanics approach was taken to the design of the window systems of a manned space craft. Earlier vehicles were never subjected to repeated launch and re-entry and therefore fatigue or slow crack growth were not major concerns. The design and proof test methodology evolved at that time continues to be applied in the development of the window systems for the Space Station Freedom. A combination of fixed abrasive grinding, lapping, and chemical machining is employed on the fused silica window panes to insure that sub- surface damage is carefully controlled and minimized. All panes are proof tested under controlled atmospheric conditions which preclude crack growth during the test. This paper also covers some of the history of space craft window design, the rationale for the material choices as well as a review of the finishing and test methods employed.
Construction of Random Input-Output Codes With Moderate Block Lengths (2016)

Random I/O (RIO) codes, recently introduced by Sharon and Alrod, is a coding scheme to improve the random input/output performance of flash memories. Multilevel flash memories require, on the average, more than a single read threshold in order to read a single logicalpage. This number is important to be optimized since it sets the read latency of flash memories. An (n, M, t) RIO code assumes that t pages are stored in n cells with t + 1 levels. The first page is read by applying a read threshold between levels t and t + 1. Similarly, the second page is read by applying a read threshold between levels t - 1 and t, and so on. As a consequence, if a cell reads as bit 1 for a page (say page m), the cell also reads as bit 1 for all the successive pages (m + 1, m + 2⋯). Therefore, Sharon and Alrod showed that the design of RIO codes is equivalent to the design of WOM codes. The latter family of codes attracted substantial attention in recent years in order to improve the lifetime of flash memories by allowing writing multiple messages to the memory without the need for an erase operation. In this paper, we notice two important distinctions between RIO codes and WOM codes. While in WOM codes, the messages are received one after the other and thus are not known all in advance, in RIO codes the information of all logical pages can be known in advance when programming the cells. Even though this knowledge does not improve the maximum sumrate of RIO codes, it allows the design of efficient high-rate codes with a moderate block length, which do not exist for WOM codes. We also study another family of RIO codes, called here partial RIO codes, that allow to find even more efficient codes while allowing to sense more than a single threshold to read some pages.
Safety, tolerability and pharmacokinetics of PL 14736, a novel agent for treatment of ulcerative colitis, in healthy male volunteers. (2002)

PL 14736, a novel 15 amino acid peptide, has shown benefical activity in experimental models of gastrointestinal damage. Seven-day intracolonic administration of PL 14736 to rats has significantly reduced the extent TNBS-induced colonic damage and hastened healing. These results have encuraged the development of the compound for the treatment of patients with ulcerative colitis. In this first study in man, rectal administration of PL 14736 to healthy male volunteers was safe and well tolerated. Based on these data, a randomized, double-blind, placebo-controlled study was started in order to investigate the tolerabillity and efficacy of Pl 14736 enemas in patients with acute mild to moderate ulcerative colitis
A comparison of test requirements, methods, and results for seven MCM products (2002)

This paper presents seven MCM designs, compares and contrasts the test approaches used in each design, and lists test solutions and recommendations that can be extended to future MCM technology. Important topics covered include design-for-testability, logic simulation, and fault diagnosis. Unique to this discussion are details concerning the refinement of test practices required to support product transition from prototype design to volume manufacturing.
Isolation, expression analysis, and functional characterization of the first antidiuretic hormone receptor in insects (2010)

Diuresis following blood-gorging in Rhodnius prolixus is the major process leading to the transmission of Chagas' disease. We have cloned the cDNA of the first receptor known to be involved in an antidiuretic strategy in insects, a strategy that prevents diuresis. This receptor belongs to the insect CAPA receptor family known in other insects to be activated by peptides encoded within the capability gene. We characterize the expression profile in fifth-instars and find expression is localized to the alimentary canal. Highest transcript levels are found in Malpighian tubules and the anterior midgut, which are known targets of the antidiuretic hormone, RhoprCAPA-alpha2. Two transcripts were identified, capa-r1 and capa-r2; however, the latter encodes an atypical G protein-coupled receptor lacking a region ranging between the first and second transmembrane domain. Our heterologous expression assay revealed the expressed capa-r1 receptor is activated by RhoprCAPA-alpha2 (EC(50) = 385nM) but not by RhoprCAPA-alpha1. Structural analogs of the inactive RhoprCAPA-alpha1 were capable of activating the expressed capa-r1 receptor, confirming the importance of the C-terminal consensus sequence common to CAPA-related peptides. In addition, this receptor has some sensitivity to the pyrokinin-related peptide, RhoprCAPA-alphaPK1, but with an efficacy approximately 40-fold less than RhoprCAPA-alpha2. Other peptides belonging to the PRXamide superfamily were inactive on the capa-r1 receptor. Taken together, the neuroendocrinological relevance of this receptor in facilitating the antidiuretic strategy in R. prolixus may make this receptor a useful target for development of agonists or antagonists that could help influence the transmission of Chagas' disease that occurs during diuresis in this medically important insect-disease vector.
Hybrid BIST Based on Repeating Sequences and Cluster Analysis 1 (2008)

We present a hybrid BIST approach that extracts the most frequently occurring sequences from deterministic test patterns; these extracted sequences are stored on-chip. We use cluster analysis for sequence extraction, and encode deterministic patterns on the basis of the stored sequences. Experimental results for the ISCAS-89 benchmark circuits show that the proposed approach often requires less on-chip storage and test data volume than other recent BIST methods. 1
One-step DNA melting in the RNA polymerase cleft opens the initiation bubble to form an unstable open complex (2010)

Though opening of the start site (+1) region of promoter DNA is required for transcription by RNA polymerase (RNAP), surprisingly little is known about how and when this occurs in the mechanism. Early events at the lambdaP(R) promoter load this region of duplex DNA into the active site cleft of Escherichia coli RNAP, forming the closed, permanganate-unreactive intermediate I(1). Conversion to the subsequent intermediate I(2) overcomes a large enthalpic barrier. Is I(2) open? Here we create a burst of I(2) by rapidly destabilizing open complexes (RP(o)) with 1.1 M NaCl. Fast footprinting reveals that thymines at positions from -11 to +2 in I(2) are permanganate-reactive, demonstrating that RNAP opens the entire initiation bubble in the cleft in a single step. Rates of decay of all observed thymine reactivities are the same as the I(2) to I(1) conversion rate determined by filter binding. In I(2), permanganate reactivity of the +1 thymine on the template (t) strand is the same as the RP(o) control, whereas nontemplate (nt) thymines are significantly less reactive than in RP(o). We propose that: (i) the +1(t) thymine is in the active site in I(2); (ii) conversion of I(2) to RP(o) repositions the nt strand in the cleft; and (iii) movements of the nt strand are coupled to the assembly and DNA binding of the downstream clamp and jaw that occurs after DNA opening and stabilizes RP(o). We hypothesize that unstable open intermediates at the lambdaP(R) promoter resemble the unstable, transcriptionally competent open complexes formed at ribosomal promoters.
Improved Molecular Detection ofAngiostrongylus cantonensisin Mollusks and Other Environmental Samples with a Species-Specific Internal Transcribed Spacer 1-Based TaqMan Assay (2010)

Angiostrongylus cantonensis is the most common cause of human eosinophilic meningitis. Humans become infected by ingesting food items contaminated with third-stage larvae that develop in mollusks. We report the development of a real-time PCR assay for the species-specific identification of A. cantonensis in mollusk tissue.
Identification of a Lysosomal Pathway Regulating Degradation of the Bone Morphogenetic Protein Receptor Type II (2010)

Bone morphogenetic proteins (BMPs) are critically involved in early development and cell differentiation. In humans, dysfunction of the bone morphogenetic protein type II receptor (BMPR-II) is associated with pulmonary arterial hypertension (PAH) and neoplasia. The ability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma and primary effusion lymphoma, to down-regulate cell surface receptor expression is well documented. Here we show that KSHV infection reduces cell surface BMPR-II. We propose that this occurs through the expression of the viral lytic gene, K5, a ubiquitin E3 ligase. Ectopic expression of K5 leads to BMPR-II ubiquitination and lysosomal degradation with a consequent decrease in BMP signaling. The down-regulation by K5 is dependent on both its RING domain and a membrane-proximal lysine in the cytoplasmic domain of BMPR-II. We demonstrate that expression of BMPR-II protein is constitutively regulated by lysosomal degradation in vascular cells and provide preliminary evidence for the involvement of the mammalian E3 ligase, Itch, in the constitutive degradation of BMPR-II. Disruption of BMP signaling may therefore play a role in the pathobiology of diseases caused by KSHV infection, as well as KSHV-associated tumorigenesis and vascular disease.
Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency (2004)

Adult patients with pituitary disease and partial ACTH deficiency have a cortisol secretory pattern comparable to that of healthy controls. Conventional full-dose replacement with 10 mg twice daily of hydrocortisone produces hypercortisolaemia, whereas half-dose produces a CDC that is not statistically different from that of healthy controls. The results suggest that current conventional glucocorticoid replacement overtreats patients with partial ACTH deficiency under normal unstressed physiological conditions.