gebhart/patrepeval huggingface dataset:
REFMAC5 for the refinement of macromolecular crystal structures (2011)

This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part of the CCP4 suite. REFMAC5 utilizes different likelihood functions depending on the diffraction data employed (amplitudes or intensities), the presence of twinning and the availability of SAD/SIRAS experimental diffraction data. To ensure chemical and structural integrity of the refined model, REFMAC5 offers several classes of restraints and choices of model parameterization. Reliable models at resolutions at least as low as 4 Å can be achieved thanks to low-resolution refinement tools such as secondary-structure restraints, restraints to known homologous structures, automatic global and local NCS restraints, `jelly-body' restraints and the use of novel long-range restraints on atomic displacement parameters (ADPs) based on the Kullback-Leibler divergence. REFMAC5 additionally offers TLS parameterization and, when high-resolution data are available, fast refinement of anisotropic ADPs. Refinement in the presence of twinning is performed in a fully automated fashion. REFMAC5 is a flexible and highly optimized refinement package that is ideally suited for refinement across the entire resolution spectrum encountered in macromolecular crystallography.
Inhalation exposure methodology. (1984)

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.).
A method of spatial calibration for camera and radar (2010)

The technique of multi-sensor fusion has already been used widely in intelligent vehicle environment perception. The spatial calibration of the radar and camera is the basis for road detection with information fusion real-timely. So, a method of spatial calibration of radar and the camera has been proposed to implement the spatial calibration of the two sensors. The non-linear distortion of the camera is considered in the paper. Coordinate transformation between the coordinates relevant to the radar and camera is introduced as the constraints. After transforming the feature between the related coordinates of image and the relative coordinates of radar, the calibration parameters are determined with the least square error function. Experiment results indicate that this method is simple and easy to realize, which has the high accuracy that satisfy requirement of the system.
Activation of carbon dioxide: nickel-catalyzed electrochemical carboxylation of diynes (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTActivation of carbon dioxide: nickel-catalyzed electrochemical carboxylation of diynesSylvie Derien, Jean Claude Clinet, Elisabet Dunach, and Jacques PerichonCite this: J. Org. Chem. 1993, 58, 9, 2578–2588Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/jo00061a038https://doi.org/10.1021/jo00061a038research-articleACS PublicationsRequest reuse permissionsArticle Views1136Altmetric-Citations70LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Open‐label study of infliximab treatment for psoriatic arthritis: Clinical and magnetic resonance imaging measurements of reduction of inflammation (2002)

Abstract Objective To evaluate infliximab efficacy and safety in disease‐modifying antirheumatic drug–unresponsive psoriatic arthritis (PsA). Methods In a 54‐week, open‐label, compassionate‐use study, 10 patients received intravenous infliximab (5 mg/kg; weeks 0, 2, 6; individualized dosing after week 10). Patients continued their current therapy (stable dose) until week 10. Assessments were performed at weeks 2, 6, 10, and 54. Magnetic resonance imaging (MRI) objectively measured joint inflammation at weeks 0 and 10. Results Patients achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria (ACR20) in all patients by week 2; 8 patients improved 70% (ACR70) at week 10; 6 patients maintained ACR70 after week 54. Week 10 MRI revealed an 82.5% mean reduction in inflammation from baseline, and psoriasis area and severity index scores were reduced by 71.3% ± 16.7%. There were no significant adverse events, severe infections, or infusion reactions. Conclusion Infliximab was effective, safe, and well tolerated in PsA. Arthritis and psoriasis improved in all patients during the 54‐week evaluation. Further investigation of the use of infliximab for PsA and psoriasis is warranted.
Trisomy 13 detection in the first trimester of pregnancy using a chromosome‐selective cell‐free DNA analysis method (2012)

Chromosome-selective sequencing of cfDNA can detect the majority of cases of trisomy 13 at an FPR of less than 0.1%.
Neofunction of ACVR1 in fibrodysplasia ossificans progressiva (2015)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor point mutations in ACVR1 (also known as ALK2), a type I receptor for bone morphogenetic protein (BMP). Two mechanisms of mutated ACVR1 (FOP-ACVR1) have been proposed: ligand-independent constitutive activity and ligand-dependent hyperactivity in BMP signaling. Here, by using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs), we report a third mechanism, where FOP-ACVR1 abnormally transduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling but not BMP signaling. Activin-A enhanced the chondrogenesis of induced mesenchymal stromal cells derived from FOP-iPSCs (FOP-iMSCs) via aberrant activation of BMP signaling in addition to the normal activation of TGF-β signaling in vitro, and induced endochondral ossification of FOP-iMSCs in vivo. These results uncover a novel mechanism of extraskeletal bone formation in FOP and provide a potential new therapeutic strategy for FOP.
Epithelial to Mesenchymal Transition: Expression of the Regulators Snail, Slug, and Twist in Pancreatic Cancer (2007)

The transcription factors Snail and Slug are expressed in pancreatic cancer but not in normal tissue, suggesting a role in the progression of human pancreatic tumors. Twist, activated by hypoxia, may play an important role in the invasive behavior of pancreatic tumors.
Engineering host cell lines to reduce terminal sialylation of secreted antibodies (2010)

Covalently-linked glycans on proteins have many functional roles, some of which are still not completely understood. Antibodies have a very specific glycan modification in the Fc region that is required for mediating immune effector functions. These Fc glycans are typically highly heterogeneous in structure, and this heterogeneity is influenced by many factors, such as type of cellular host and rate of Ab secretion. Glycan heterogeneity can affect the Fc-dependent activities of antibodies. It has been shown recently that increased Fc sialylation can result in decreased binding to immobilized antigens and some Fcγ receptors, as well as decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activity. In contrast, increased Fc sialylation enhances the anti-inflammatory activity of antibodies. To produce antibodies with increased effector functions, we developed host cell lines that would limit the degree of sialylation of recombinantly-expressed antibodies. Towards this end, the catalytic domain of the Arthrobacter ureafaciens sialidase (sialidase A) was engineered for secreted expression in mammalian cell lines. Expression of this sialidase A gene in mammalian cells resulted in secreted expression of soluble enzyme that was capable of removing sialic acid from antibodies secreted into the medium. Purified antibodies secreted from these cells were found to possess very low levels of sialylation compared with the same antibodies purified from unmodified host cells. The low sialylated antibodies exhibited similar binding affinity to soluble antigens, improved ADCC activity, and they possessed pharmacokinetic properties comparable to their more sialylated counterparts. Further, it was observed that the amount of sialidase A expressed was sufficient to thoroughly remove sialic acid from Abs made in high-producing cell lines. Thus, engineering host cells to express sialidase A enzyme can be used to produce recombinant antibodies with very low levels of sialylation.
Stabilization of Inorganic Nanocrystals by Organic Dendrons (2002)

A series of hydrophilic organic dendron ligands was designed and synthesized for stabilizing high-quality semiconductor and noble metal nanocrystals. The focal point of the dendron ligands is chosen to be a thiol group which is a universal coordinating site for compound semiconductor and noble metal nanocrystals. The methods for binding these dendron ligands onto the surface of the nanocrystals are simple and straightforward. The thin, about 1-2 nm, but closely packed and tangled ligand shell provides sufficient stability for the "dendron-protected nanocrystals" to withstand the rigors of the coupling chemistry and the standard separation/purification techniques. The chemistry presented can be immediately applied for the development of a new generation of biomedical labeling reagents based on high-quality semiconductor nanocrystals. It also provides an alternative path to apply noble metal nanocrystals for developing sensitive detection schemes for chemical and biochemical purposes. The concept may further provide an optimal solution for many other problems encountered in nanocrystal-related research and development, for which the stability of the nanocrystals is a critical issue. Furthermore, the experimental results confirmed that the photochemical stability of colloidal semiconductor and noble metal nanocrystals is the key for developing reliable and reproducible processing chemistry for these nanocrystals.
Poly(ADP-ribose) synthesis in blocked and damaged cells and its relation to carcinogenesis. (1992)

There is compelling evidence showing that repair of DNA damage depends on the synthesis of poly(ADP-ribose) molecules at specific sites on histones and other proteins in nuclei of injured cells. In the present study, we have studied the effect of long-term exposure of mouse cells to nicotinamide and various cell cycle blockers on the ability of the cells to increase their levels of poly(ADP-ribose) in response to DNA methylation damage with dimethylsulfate (DMS). Of the cell cycle blockers used, hydroxyurea (HU) and cytosine arabinofuranoside (ara-C) inhibit DNA elongation at the replication fork and cause the appearance of small DNA molecules, whereas butyrate and colcemid block cells without interfering with DNA synthesis. In addition, cells were treated with nicotinamide, an inhibitor of poly(ADP-ribose) polymerase but also a precursor in NAD+ biosynthesis. Long-term exposure of cultured cells to these agents was followed with a short-term damage with DMS. The size-class distribution and concentration of poly(ADP-ribose) molecules were determined using high resolution polyacrylamide gel electrophoresis and were found to contain 1 to more than 30 ADP-ribosyl groups. On the contrary, histones from blocked cell nuclei were found to be mono- and oligo(ADP-ribosyl)ated. Thus, the large molecules of poly(ADP-ribose) were associated with nonhistone proteins and most likely with the enzyme pADP-R polymerase. DMS damage caused an increase in the levels of poly(ADP-ribose) that was synthesized in lysates from cells treated with any one drug alone. On the other hand, a dramatic decrease in total protein poly(ADP-ribosyl)ation resulted from DMS damage of cells treated with nicotinamide + HU or nicotinamide + ara-C. This decrease was not observed in combinations of nicotinamide with cell-cycle blockers that do not directly interfere with DNA synthesis (butyrate and colcemid). We suggest that nicotinamide + ara-C or nicotinamide + HU might be used as effective antineoplastic treatments by virtue of their ability simultaneously to damage DNA and reduce poly(ADP-ribosyl)ation and presumably DNA repair. A model for the facilitation of DNA repair by poly(ADP-ribosyl)ation of histones and of poly(ADP-ribose) polymerase is presented.
Dual-threshold voltage techniques for low-power digital circuits (2000)

Scaling and power reduction trends in future technologies will cause subthreshold leakage currents to become an increasingly large component of total power dissipation. This paper presents several dual-threshold voltage techniques for reducing standby power dissipation while still maintaining high performance in static and dynamic combinational logic blocks. MTCMOS sleep transistor sizing issues are addressed, and a hierarchical sizing methodology based on mutual exclusive discharge patterns is presented. A dual-V/sub t/ domino logic style that provides the performance equivalent of a purely low-V/sub t/ design with the standby leakage characteristic of a purely high-V/sub t/ implementation is also proposed.
Troponin I Encompasses an Extended Troponin C in the Ca2+-Bound Complex: A Small-Angle X-ray and Neutron Scattering Study (1994)

We have studied the solution structure of skeletal muscle troponin C complexed with troponin I in the presence of calcium using small-angle X-ray and neutron scattering. 4Ca2+.troponin C in the complex has an extended dumbbell shape with a radius of gyration of 23.9 +/- 0.5 A and a maximum linear dimension of approximately 72 A, similar to the values obtained from the crystal structure coordinates of troponin C (Herzberg & James, 1985). Troponin I is even more extended than troponin C with a radius of gyration of 41 +/- 2 A and a maximum linear dimension of approximately 118 A. The centers-of-mass for each component of the complex are approximately coincident (< 10-A separation) as are their long axes, and the troponin I component encompasses the 4Ca2+.troponin C. These data provide new insights into the nature of the conformational arrangement of this important Ca(2+)-sensitive molecular switch.
Successful treatment of resistant SAPHO syndrome with anti-TNF therapy (2013)

A 42-year-old Caucasian woman with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) refractory to non-steroidal anti-inflammatory drugs, sulfasalzine, methotrexate, bisphosphonates and steroids was successfully treated with antitumour necrosis factor therapy (infliximab). This case was a diagnostic challenge leading to extensive investigations for infection and malignancy and delayed diagnosis for several years. We report the significant improvement in clinical, radiological and laboratory markers of disease activity on infliximab and the steroid sparing effect of such therapy.
Glycine Antagonist in Neuroprotection for Patients With Acute Stroke (2001)

In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.
A Single Heteroclitic Epitope Determines Cancer Immunity After Xenogeneic DNA Immunization Against a Tumor Differentiation Antigen (2003)

Successful active immunization against cancer requires induction of immunity against self or mutated self Ags. However, immunization against self Ags is difficult. Xenogeneic immunization with orthologous Ags induces cancer immunity. The present study evaluated the basis for immunity induced by active immunization against a melanoma differentiation Ag, gp100. Tumor rejection of melanoma was assessed after immunization with human gp100 (hgp100) DNA compared with mouse gp100 (mgp100). C57BL/6 mice immunized with xenogeneic full-length hgp100 DNA were protected against syngeneic melanoma challenge. In contrast, mice immunized with hgp100 DNA and given i.p. tolerizing doses of the hgp100 D(b)-restricted peptide, hgp100(25-33), were incapable of rejecting tumors. Furthermore, mice immunized with DNA constructs of hgp100 in which the hgp100(25-27) epitope was substituted with the weaker D(b)-binding epitope from mgp100 (mgp100(25-27)) or a mutated epitope unable to bind D(b) did not reject B16 melanoma. Mice immunized with a minigene construct of hgp100(25-33) rejected B16 melanoma, whereas mice immunized with the mgp100(25-33) minigene did not develop protective tumor immunity. In this model of xenogeneic DNA immunization, the presence of an hgp100 heteroclitic epitope with a higher affinity for MHC created by three amino acid (25 to 27) substitutions at predicted minor anchor residues was necessary and sufficient to induce protective tumor immunity in H-2(b) mice with melanoma.
The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer (2013)

We found that the expression of RAS, RB, LAMB3 and Ki-67 changed in the different stages of prostate cancer. Furthermore, we confirmed the overexpression of the miRNAs let7c, 100 and 218 in localized prostate cancer but failed to show the control of protein expression by the putative controller miRNAs using immunohistochemistry.
Recent advances in the angiotensin‐converting enzyme 2–angiotensin(1–7)–Mas axis (2008)

In the past few years, the classical concept of the renin-angiotensin system (RAS) has experienced substantial conceptual changes. The identification of: the renin/prorenin receptor; the angiotensin-converting enzyme homologue, ACE2, as an angiotensin peptide-processing enzyme and a virus receptor for severe acute respiratory syndrome, the Mas as a receptor for angiotensin (1-7) [Ang(1-7)], and the possibility of signaling through ACE have contributed to switch our understanding of the RAS from the classical limited-proteolysis linear cascade to a cascade with multiple mediators, multiple receptors and multifunctional enzymes. With regard to Ang(1-7), the identification of ACE2 and of Mas as a receptor implicated in its actions contributed to decisively establish this heptapeptide as a biologically active member of the RAS cascade. In this review, we will focus on the recent findings related to the ACE2-Ang(1-7)-Mas axis and, in particular, on its putative role as an ACE-Ang II-AT(1) receptor counter-regulatory axis within the RAS.
Nerve supply to the posterior longitudinal ligament and the intervertebral disc of the rat vertebral column as studied by acetylcholinesterase histochemistry. II. Regional differences in the distribution of the nerve fibres and their origins. (1990)

Regional differences of the distribution and the origin of the nerve fibres of the posterior longitudinal ligament (PLL) and the intervertebral disc (IVD) were investigated by acetylcholinesterase (AchE) enzyme histochemistry in the rat. The deeper nerve network was well-developed at the lower thoracic and the upper lumbar vertebral levels, but it was hardly seen at the mid-thoracic level. This difference can be correlated with the extensibility of the PLL. The experimental study revealed that the AchE-positive nerve fibres in the PLL and the IVD were mostly derived from the spinal ganglia, that the superficial nerve network was supplied by the spinal ganglia bilaterally and polysegmentally, and that the deeper nerve network was supplied bilaterally but unisegmentally.
Thrashing (1968)

A particularly troublesome phenomenon, thrashing, may seriously interfere with the performance of paged memory systems, reducing computing giants (Multics, IBM System 360, and others not necessarily excepted) to computing dwarfs. The term thrashing denotes excessive overhead and severe performance degradation or collapse caused by too much paging. Thrashing inevitably turns a shortage of memory space into a surplus of processor time.
Specific receptor detection by a functional keratinocyte growth factor-immunoglobulin chimera. (1995)

Fibroblast growth factor receptors (FGFRs) are encoded by at least four distinct highly conserved genes, and alternative splicing generates multiple gene products. The close relationship among different FGFRs has greatly increased the difficulty in generating specific immunochemical probes. As an alternative strategy, we constructed a fusion protein comprising keratinocyte growth factor (KGF) and an IgG1 Fc domain (HFc). The chimeric molecule was efficiently secreted from transfectants as a disulfide-linked dimer that bound KGFRs with high affinity. Moreover, the KGF-HFc, like native KGF, induced DNA synthesis by epithelial cells implying normal functional receptor activation. Because it retained the convenient detection properties of an immunoglobulin, it was possible to use the KGF-HFc in ligand-mediated histochemical analysis of KGFRs. Flow cytometry revealed KGF-HFc chimera detection of the KGFR, an alternative FGFR2 product, but not FGFR1 (flg) or FGFR2 (bek). Histochemical analysis of normal skin demonstrated the specific localization of KGFRs within the spinous layer, a zone of epithelial cell differentiation. KGFRs were also localized to epithelial cells within a specific region of the hair follicle, and they were not detectable in cells of the sweat gland. Tissue sections of soft palate and tonsil, two examples of nonkeratinizing epithelium, revealed staining of stratum spinosum and some staining of the basal cell layer as well. Neither salivary gland epithelium nor lymphoid cells were positive. The ciliated epithelium of the trachea exhibited KGFR expression in intermediate and basal cell layers. In striking contrast to the normal pattern of staining in the adjacent epithelium, a squamous cell carcinoma of skin lacked detectable KGFRs. Our present findings suggest that growth factor-Ig fusion proteins may be generally applicable in ligand-mediated histochemical detection and localization of growth factor receptors.