gebhart/patrepeval huggingface dataset:
Estimating creatinine clearance in elderly patients with low serum creatinine concentrations (1994)

The accuracy of creatinine clearance (CLcr) estimates generated for elderly patients with a low serum creatinine (SCr) concentration when the SCr concentration was rounded to 1.0 mg/dL was evaluated, and daily aminoglycoside dosages calculated with CLcr estimates based on the actual and the rounded SCr concentrations were compared with the actual dosage required as determined by aminoglycoside concentration measurements. Twenty-four-hour urine collections were obtained from elderly hospitalized patients with stable renal function, and CLcr was measured. SCr concentrations were measured at baseline, during urine collection, and after urine collection. CLcr was calculated twice with each of seven methods, once by using the actual SCr concentration and once by rounding the SCr concentration to 1.0 mg/dL. Rounding the SCr concentration to 1.0 mg/dL resulted in significant underestimation of CLcr by all seven methods. The Cockcroft-Gault equation used with ideal body weight and the rounded SCr concentration resulted in the largest bias. For six of the seven methods, bias was greater and precision less when SCr concentrations of < 0.7 mg/dL were rounded than when SCr concentrations of ≥0.7 mg/dL were rounded. The Bjornsson method used with the actual SCr concentration appeared to offer the best combination of low bias and high precision. The required aminoglycoside dosage was significantly underestimated when the rounded SCr concentration was used. In elderly patients with low SCr concentrations, rounding the SCr concentration to 1.0 mg/dL led to underestimates of both CLcr and the correct aminoglycoside dosage.
Conformational properties of the acetylcholine receptor as revealed by studies with constrained depolarizing ligands (1979)

Conformational aspects of the acetylcholine receptor (AcChoR) of Electrophorus electricus have been examined by studies of its interaction with structurally related, constrained aromatic bis quaternary compounds. Among the compounds synthesized was 3,3'-bis[alpha-(trimethylammonium)-methyl]azobenzene dibromide (3,3'-bisQ). This compound is photochromic and can exist in a cis or trans isomeric form, both of which have now been isolated in pure form. Trans-3,3'-bisQ is the most potent activator known, producing a 60-mV depolarization at 0.2 muM and 50% activity at 0.06 muM. The cis isomer is less than 1% as active. Its high activity and constrained structure suggest that trans-3,3'-bisQ can be considered to be a "template" of the combining site of AcChoR, when the latter is in the activated state. The following conclusions can then be drawn concerning the AcChoR binding site. (i) Depolarization can occur by interaction with reagents that are essentially inflexible. (ii) The binding site has a planar hydrophobic region that interacts with methylene groups of acetylcholine and with hydrophobic areas in general. (iii) In the same plane as the hydrophobic area is a site that interacts with electron-donating functional groups including the carbonyl oxygen of acetylcholine and the azo nitrogens of trans-3,3'-bisQ. (iv) About 1.5 A out of the plane of the hydrophobic and the electron acceptor site is an anionic site; when the AcChoR is in the activated state, this site is separated from the electron acceptor site by 5.2 A and from another anionic site by 11 A. (v) The anionic sites are located within a cleft of limited size, sufficient to accommodate quaternary methyl groups. (vi) Although depolarization can occur with reagents that possess only hydrophobic and cationic groups if their geometric arrangement is proper, the highest activity resides in compounds capable of all of the interactions cited above.
Fine Structural Study of Neurofibrillary Changes in a Family with Amyotrophic Lateral Sclerosis (1984)

Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performed in two brothers from a family ("C" family) previously described by Kurland and Mulder in 1955. The perikaryal hyaline inclusions consisted of accumulations of randomly oriented neurofilaments interspersed with thick linear densities associated with granular material. Some of the accumulations showed a central condensation. Cord-like, swollen neuronal processes were composed, for the most part, of numerous neurofilaments arranged parallel to the long axes. Dense structures were sometimes observed within the large bundles of filaments. They were composed of ill-defined dense, granular and fibrillar material associated with scattered vesicles and mitochondria. These dense areas were sometimes surrounded by various amounts of fine filaments, approximately 5 nm in diameter.
Targeting the N-Terminal Domain of the Androgen Receptor: A New Approach for the Treatment of Advanced Prostate Cancer (2016)

Because of emerging resistance mechanisms that involve the ligand-binding domain of the androgen receptor (AR), there is currently no effective treatment addressing tumor escape mechanisms related to current AR-targeted therapies. Many patients still demonstrate limited clinical response to current hormonal agents, and castration-resistant prostate cancer remains a lethal disease. Intense research efforts are under way to develop therapies to target resistance mechanisms, including those directed at other parts of the AR molecule. A novel small-molecule agent, EPI-506, represents a new pharmaceutical class, AR N-terminal domain inhibitors, and shows preclinical promise to overcome many known resistance mechanisms related to novel hormonal therapies.
PLASMA GELSOLIN IS REDUCED IN TRAUMA PATIENTS (1999)

Tissue injury results in the release of the intracellular protein actin which is cleared from the circulation by the plasma proteins gelsolin and Gc-globulin, constituting the Extracellular Actin Scavenger System (EASS). Experimental studies have shown that excessive amounts of actin in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P < 0.0001. There was no correlation between admission levels of gelsolin and ISS or survival. This study illustrates that the plasma concentration of gelsolin is significantly diminished immediately after traumatic injury. Further studies are necessary to establish a role for gelsolin or EASS in the development of MODS in trauma patients. The level of serum or plasma gelsolin can be determined rapidly and accurately using a nephelometric assay.
Design, Synthesis, and Evaluation of the Multidrug Resistance-Reversing Activity of d-Glucose Mimetics of Hapalosin (1998)

When five substituents of hapalosin were placed on D-glucose, molecular modeling revealed that the substituents on mimetics 2 and 3 occupy similar spatial positions as the corresponding substituents on hapalosin. Mimetic 3 and all the glucopyranoside intermediates generated in its synthesis were assessed for their ability to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) or the multidrug resistance-associated protein (MRP). None of the sugar compounds were as effective as hapalosin in inhibiting P-gp in cytotoxicity and drug accumulation assays using MCF-7/ADR cells. By contrast, four D-glucose compounds exhibited similar efficacy as hapalosin in antagonizing MRP in cytotoxicity assays with HL-60/ADR cells.
Effects of ovariectomy on bone morphology in maxillae of mature rats (1999)

Postmenopausal oestrogen deficiency results in bone loss (osteoporosis) in humans and experimental animals. The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of post-menopausal osteoporosis. At 5 months after ovariectomy of 3-month-old female rats, the mid and distal femurs and maxillae were dissected and processed for quantitative backscattered electron microscopic examinations. Histomorphometric analysis of femurs in OVX rats showed significant loss in metaphyseal trabecular bone areas compared with sham-operated controls; no significant bone loss was observed in the cortical bone areas of mid-diaphyses in OVX rats. Net bone areas in the maxillae of OVX rats was similar to that of sham-operated controls. Bone structure of maxillae in OVX rats was also similar to that in controls. Our results suggest that, in this animal model of osteoporosis, prominent bone loss occurs mainly in the bone areas formed by endochondral ossification such as distal femurs, but those areas formed by intramembranous ossification such as mid-femurs and maxillae sustained less effects by OVX.
콘크리트 표면 차수벽형 사력댐의 구조적 안정성 평가 및 GPS 다짐 시공관리 (2010)

To determine the effect of draining for the drainage layer in CFGD(Concrete Faced Gravel Dam) body, centrifuge model tests were performed. Also, soil compaction works are essential to construction of dams in order to avoid unexpected settlement of superstructures. Taking advantage of oscillating accelerometer, this research was made to complement existing methods for assessment of soil stiffness. In order to examine the validity of compaction-degree suggested in the study, tests on vibration characteristics using accelerometers was also performed.
LC3, an Autophagosome Marker, Can be Incorporated into Protein Aggregates Independent of Autophagy: Caution in the Interpretation of LC3 Localization (2007)

Autophagy is an intracellular bulk degradation system, through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Microtuble-associated protein light chain 3 (LC3), a mammalian homolog of yeast Atg8, has been used as a specific marker to monitor autophagy. Upon induction of autophagy, LC3 is conjugated to phosphatidylethanolamine and targeted to autophagic membranes. Therefore, changes in LC3 localization have been used to measure autophagy. However, this method has some limitations. In this report, we show that LC3 protein tends to aggregate in an autophagy-independent manner when it is transiently overexpressed by transfection. In addition, LC3 is easily incorporated into intracellular protein aggregates, such as inclusion bodies induced by polyQ expression or formed in autophagy-deficient hepatocytes, neurons, or senescent fibroblasts. These findings demonstrate that punctate dots containing LC3 do not always represent autophagic structures. Therefore, LC3 localization should be carefully interpreted, particularly if LC3 is overexpressed by transient transfection or if aggregates are formed within cells.
Cloning, purification and crystallization of full-length human annexin 2 (2002)

Annexin 2, a Ca(2+)/phospholipid-binding protein, is involved in many biological processes, including membrane aggregation and the modulation of fibrinolytic activity. Here, the expression and purification of recombinant full-length human annexin 2 is reported, as well as crystals obtained by sitting-drop and hanging-drop vapor diffusion at 277 K. A condition consisting of 18% PEG 8000, 0.1 M sodium cacodylate pH 6.5, 0.2 M calcium acetate yielded long needles that diffracted to 3.20 A. Another condition, consisting of 2.5 M NaCl, 0.1 M acetate pH 4.5, 0.2 M Li(2)SO(4), gave crystals with unit-cell parameters a = 48.36, b = 62.86, c = 119.11 A that diffracted to 1.52 A. Both crystals belong to the orthorhombic P2(1)2(1)2(1) space group. The high-resolution 1.52 A data set was collected at ALS beamline 5.0.2 and is 93.0% complete, with an R(sym) of 4.5%. The structure of full-length annexin 2 will provide insight into how its N-terminal domain contributes to its functional role in a variety of biological processes.
Alkenylphenols Related to the Poison Ivy Principle. An Improved Method of Synthesis Involving the Na-Butanol Cleavage of Benzyl Ethers (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkenylphenols Related to the Poison Ivy Principle. An Improved Method of Synthesis Involving the Na-Butanol Cleavage of Benzyl EthersBernard Loev and Charles R. DawsonCite this: J. Am. Chem. Soc. 1956, 78, 23, 6095–6098Publication Date (Print):December 1, 1956Publication History Published online1 May 2002Published inissue 1 December 1956https://pubs.acs.org/doi/10.1021/ja01604a039https://doi.org/10.1021/ja01604a039research-articleACS PublicationsRequest reuse permissionsArticle Views468Altmetric-Citations25LEARN 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-Alertsclose Get e-Alerts
RAPID ISOLATION OF HUMAN CD34 HEMATOPOIETIC STEM CELLS—PURGING OF HUMAN TUMOR CELLS (1992)

Human CD34+ hematopoietic stem cells were purified using a new technology in which monoclonal antibodies are covalently immobilized on polystyrene surfaces. The CD34+ cell isolation scheme involved three sequential processes: (1) purification of bone marrow mononuclear cells; (2) enrichment of CD34+ cells using covalently immobilized soybean agglutinin; and (3) positive selection of CD34+ cells using polystyrene surfaces coated with the anti-CD34 monoclonal antibody ICH3. CD34+ cells purified by this process have both low-to-medium forward light scatter and low 90 degrees light-scatter properties. Moreover, the purified CD34+ cells are greater than 85% viable, express appropriate characteristic surface antigens, and are 10-50-fold enriched in short- and long-term hematopoietic activity. CD34+ cells collected in this manner from bone marrow samples contaminated with radiolabeled breast carcinoma, neuroblastoma, acute myelogenous leukemia, or small cell lung carcinoma cells were 99.9% depleted of the tumor cells. The CD34+ cell selection devices are sterile and are easily scaled-up to process clinical scale bone marrow samples.
Phase II Study of Efficacy, Safety, and Pharmacokinetics of Trastuzumab Monotherapy Administered on a 3-Weekly Schedule (2005)

Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration.
Text-based editing of talking-head video (2019)

Editing talking-head video to change the speech content or to remove filler words is challenging. We propose a novel method to edit talking-head video based on its transcript to produce a realistic output video in which the dialogue of the speaker has been modified, while maintaining a seamless audio-visual flow (i.e. no jump cuts). Our method automatically annotates an input talking-head video with phonemes, visemes, 3D face pose and geometry, reflectance, expression and scene illumination per frame. To edit a video, the user has to only edit the transcript, and an optimization strategy then chooses segments of the input corpus as base material. The annotated parameters corresponding to the selected segments are seamlessly stitched together and used to produce an intermediate video representation in which the lower half of the face is rendered with a parametric face model. Finally, a recurrent video generation network transforms this representation to a photorealistic video that matches the edited transcript. We demonstrate a large variety of edits, such as the addition, removal, and alteration of words, as well as convincing language translation and full sentence synthesis.
Dynamic Contrast-Enhanced and Diffusion MRI Show Rapid and Dramatic Changes in Tumor Microenvironment in Response to Inhibition of HIF-1α Using PX-478 (2005)

PX-478 is a new agent known to inhibit the hypoxia-responsive transcription factor, HIF-1alpha, in experimental tumors. The current study was undertaken in preparation for clinical trials to determine which noninvasive imaging endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were used to monitor acute effects on tumor hemodynamics and cellularity, respectively. Mice bearing human xenografts were treated either with PX-478 or vehicle, and imaged over time. DW imaging was performed at three b values to generate apparent diffusion coefficient of water (ADCw) maps. For DCE-MRI, a macromolecular contrast reagent, BSA-Gd-DTPA, was used to determine vascular permeability and vascular volume fractions. PX-478 induced a dramatic reduction in tumor blood vessel permeability within 2 hours after treatment, which returned to baseline by 48 hours. The anti-VEGF antibody, Avastin, reduced both the permeability and vascular volume. PX-478 had no effect on the perfusion behavior of a drug-resistant tumor system, A-549. Tumor cellularity, estimated from ADCw, was significantly decreased 24 and 36 hours after treatment. This is the earliest significant response of ADC to therapy yet reported. Based on these preclinical findings, both of these imaging endpoints will be included in the clinical trial of PX-478.
Absorption of Danazol After Administration to Different Sites of the Gastrointestinal Tract and the Relationship to Single‐ and Double‐Peak Phenomena in the Plasma Profiles (1993)

The absorption of danazol (100 mg) after oral or intraintestinal administration to the proximal jejunum or proximal ileum has been studied in healthy female subjects. The extent of danazol absorption after administration as a solubilized glycerol mono-oleate emulsion formulation was approximately twofold and fourfold greater after oral dosing when compared with jejunal or ileal administration, respectively. Although not statistically significant in this study, the extent of absorption after jejunal administration was generally greater than after ileal administration. After oral dosing, qualitative assessment identified the presence of double peaks or major shouldering characteristics in 14 of the 16 individual danazol plasma concentration-time profiles, whereas only single peaks were present after intraintestinal administration. These data are consistent with the double peaking phenomena after oral administration of the emulsion formulation being stomach-related. The double peaking effect may be explained in terms of a probable combination of gastric emptying regulated absorption (due to the presence of the lipid in the emulsion formulation) and the dependence of danazol solubility on bile salt solubilization within the upper small intestine.
Differential Serum Levels of Eosinophilic Eotaxins in Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis, and Autoimmune Hepatitis (2013)

To investigate pathogenic mechanisms of primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and autoimmune hepatitis (AIH), serum levels of 26 chemokines and cytokines were determined and compared with patients with chronic hepatitis C or in healthy controls. The chemokine eotaxin-3 (E3; CCL26), which recruits eosinophils to sites of inflammation, was found to be highly elevated in all PSC, PBC, and AIH patients compared with HCV patients and healthy controls. Eotaxin-1 (E1; CCL11), another eosinophil-specific chemokine, was elevated in PSC but reduced in PBC and AIH, while the macrophage-derived chemokine (MDC; CCL22) was lower in all PSC, PBC, and AIH patients compared with HCV patients and controls. By incorporating levels of the interleukin (IL)-15 into a diagnostic algorithm, PSC, PBC, and AIH patients could each be differentiated with good sensitivity and specificity. These findings represent the first study to compare the level of serum cytokine/chemokine levels among these related autoimmune-like liver diseases. Furthermore, our data indicate that the measurement of serum E3, E1, CCL22, and IL-15 levels can aid in the diagnosis of these clinically challenging diseases and shed light on the potential pathogenic mechanisms underlying these diseases. By suggesting a potential role for an allergic phenomenon involving eosinophils, which may define them as liver-specific allergic diseases, this may open up potential new therapeutic avenues by abrogating the action of these disease-associated immune modulators.
Formation of Tubules by a Polymerizable Surfactant (1984)

Abstract The 1, 2-bis(10, 12-tricosadiynoyl)-sn-glycero-3-phosphocholine, in which both fatty acyl chains contain polymerizable diacetylenic units, has been studied with regard to its behavior in aqueous dispersion before and after polymerization. The monomeric lipid may be dispersed in distilled water above its chain melting transition temperature, but, contrary to previous reports, it does not stay in liposomal form on subsequent reduction of the temperature. Microscopic observation shows formation of structures resembling so-called cochleate cylinders, except that these cylinders are water-filled. These "tubules" reversibly convert to liposomal form on heating above the monomer chain melting temperature. However, on polymerization with ultraviolet light, the cylinders are “locked in” and no morphological changes are observed on heating. These unique structures may represent a new class of orientable polymers.