gebhart/patrepeval huggingface dataset:
Precision Measurement of the Casimir Force from 0.1 to0.9μm (1998)

We have used an atomic force microscope to make precision measurements of the Casimir force between a metallized sphere of diameter 196 \ensuremath{\mu}m and flat plate. The force was measured for plate-sphere surface separations from 0.1 to 0.9 \ensuremath{\mu}m. The experimental results are consistent with present theoretical calculations including the finite conductivity, roughness, and temperature corrections. The root mean square average deviation of 1.6 pN between theory and experiment corresponds to a $1%$ deviation at the smallest separation.
Antibody therapy for breast cancer. (2005)

Targeted therapies against tumor biological properties are an essential part of individualized therapy concepts in breast cancer. Next to risk-adapted strategies using conventional chemo- and/or endocrine therapies, antibody therapy has become an additional option. The humanized monoclonal antibody trastuzumab (Herceptin) is the first novel targeted therapy approved for routine clinical application in advanced breast cancer. Patients with HER2/neu protein overexpression as assessed by immunohistochemistry (IHC) and/or gene amplification as assessed by fluorescence in-situ hybridization (FISH) in their tumors respond well to palliative trastuzumab therapy, either as single agent or in combination with chemotherapy. New combinations with endocrine therapy are currently being evaluated in clinical trials. Trastuzumab therapy is generally well-tolerated. So far, considerable cardiotoxicity was seen only in combination with doxorubicin. Thus, extensive cardiomonitoring is now performed in trials assessing further chemotherapeutic partners. Clinical trials looking at early trastuzumab therapy in the adjuvant (e.g. HERA, BOND 006) or neoadjuvant (e.g. TECHNO) setting are still open for recruitment in Germany. Since only about those 25 % of breast cancers which are HER2/neu-positive are eligible for trastuzumab, novel targeted therapeutics for the remaining HER2/neu-negative tumors are needed. Another therapeutic antibody, 2C4 (Pertuzumab, Omnitarg), is currently under clinical evaluation. It binds to a different epitope on HER2/neu than trastuzumab and inhibits heterodimerization with other HER receptors. Phase I data showed that 2C4 is well tolerated and clinically active.
The pore structure of macroreticular ion exchange resins (1967)

Abstract A series of new cation and anion exchange resins differing entirely from conventional homogeneous (microreticular) gels and having a rigid macroporous structure similar to those of conventional adsorbents are characterized. These ion exchangers have been designated as macroreticular ion exchange resins . A detailed analysis is made of the pore structure of the resins including pore size distribution, surface area, and electron micrographs. From these data a model of the physical structure is presented. The relationship between the physical structure and utility of these ion exchange resins is developed for various areas of application, including catalysis, adsorption from nonpolar solvents, and the adsorption of large molecules such as peptides and proteins. The effect of hydration upon the pore structure of several of the macroreticular ion exchange resins is critically evaluated also. During the course of hydration, the gel portion hydrates first and this is followed by the filling of the macroreticular pores. From these data one is able to ascertain the pore structure not only in the anhydrous state but also in aqueous media.
The breast tumor-associated epitope defined by monoclonal antibody 3E1.2 is an O-linked mucin carbohydrate containing N-glycolylneuraminic acid. (1991)

The breast cancer-associated epitope (mammary serum antigen or MSA) defined by monoclonal antibody (Mab) 3E1.2 is a neuraminidase-sensitive carbohydrate expressed on MUC-1-encoded molecules. However, the reactivity of Mab 3E1.2 is also reduced by protease treatment of the mucin, which suggests that 3E1.2 binds to multimers of the sialylated carbohydrate in a protein conformation-dependent manner. The common N-acetyl derivative of neuraminic acid (5-acetylneuraminic acid) is not involved in the epitope, since lectins specific for 5-acetylneuraminic acid (linked to GalNAc or Gal) are nonreactive with MSA-positive molecules. However, the N-glycolyl derivative, 5-glycolylneuraminic acid (Neu5Gc), forms a major part of the epitope since both free Neu5Gc and porcine stomach mucin (greater than 90% neuraminic acid as Neu5Gc) inhibit the binding of Mab 3E1.2, while bovine or ovine submaxillary mucins, fetuin, bovine gangliosides, and other carbohydrates do not. Indeed, the presence of Neu5Gc on human tumor mucin was confirmed by electrospray mass spectrometry. Neu5Gc is attached to an O-linked carbohydrate, since the expression of MSA by MCF-7 breast cancer cells is inhibited by the O-glycosylation inhibitor phenyl-N-acetyl-alpha-D-galactosaminide, but not by the N-glycosylation inhibitor tunicamycin, and the epitope is removed by treatment with O-glycanase but not N-glycanase F, endoglycosidase F, or endoglycosidase H, which are specific for N-linked glycans. This is likely to be a core glycan since 3E1.2 reacts after treatment of the mucin with trifluoromethanesulfonic acid, which removes most backbone and peripheral carbohydrates. Treatment with galactosidase or N-acetyl glucosaminidase enhances the binding of Mab 3E1.2, indicating that the Neu5Gc is not attached to galactose or N-acetyl galactosamine. Furthermore, the susceptibility of MSA to treatment with Arthrobacter urea-faciens neuraminidase [which is specific for alpha (2-6)-linked NeuNAc] and the loss in reactivity of GalNAc-specific lectins after periodate oxidation [alpha (2-3)-linked but not alpha (2-6)-linked NeuNAc protects GalNAc from periodate oxidation] indicate that the Neu5Gc may be attached alpha (2-6) to peptide-linked GalNAc. These results show that MSA is a Neu5Gc-containing O-linked core glycan, which represents a unique tumor-associated epitope not previously identified on human mucins.
Evidence for specific recognition sites mediating clearance of lysosomal enzymes in vivo. (1976)

A study of the clearance of liver lysosomal enzymes was carried out in the rat. Purified rat liver lysosomal beta-D-glucuronidase (EC 3.2.1.31), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), alpha-L-fucosidase (EC 3.2.1.51), and alpha-D-mannosidase (EC 3.2.1.24), as well as rat preputial gland beta-glucuronidase, were infused intravenously into anesthetized rats. All of the enzymes were rapidly cleared from the circulation. Sodium periodate oxidation of lysosomal beta-glucuronidase resulted in a near abolition of rapid clearance, a reduction in concanavilin-A-Sepharose binding, and a reduction in neutral sugar content, accompanied by alteration in isoelectric focusing properties. Similarly, periodate oxidation of lysosomal N-acetyl-beta-D-glucosaminidase resulted in a loss of the rapid clearance property. These results suggest that specific recognition sites occur on lysosomal hydrolases which mediate clearance following intravenous injection, and that these sites involve the carbohydrate portions of the enzymes.
Computational and in Vitro Analysis of Destabilized DNA Regions in the Interferon Gene Cluster:  Potential of Predicting Functional Gene Domains (2002)

Recent evidence adds support to a traditional concept according to which the eukaryotic nucleus is organized into functional domains by scaffold or matrix attachment regions (S/MARs). These regions have previously been predicted to have a high potential for stress-induced duplex destabilization (SIDD). Here we report the parallel results of binding (reassociation) and computational SIDD analyses for regions within the human interferon gene cluster on the short arm of chromosome 9 (9p22). To verify and further refine the biomathematical methods, we focus on a 10 kb region in the cluster with the pseudogene IFNWP18 and the interferon α genes IFNA10 and IFNA7. In a series of S/MAR binding assays, we investigate the promoter and termination regions and additional attachment sequences that were detected in the SIDD profile. The promoters of the IFNA10 and the IFNA7 genes have a moderate ∼20% binding affinity to the nuclear matrix; the termination sequences show stronger association (70−80%) under our standardized conditions. No comparable destabilized elements were detected flanking the IFNWP18 pseudogene, suggesting that selective pressure acts on the physicochemical properties detected here. In extended, noncoding regions a striking periodicity is found of rather restricted SIDD minima with scaffold binding potential. By various criteria, the underlying sequences represent a new class of S/MARs, thought to be involved in a higher level organization of the genome. Together, these data emphasize the relevance of SIDD calculations as a valid approach for the localization of structural, regulatory, and coding regions in the eukaryotic genome.
Modulating CRISPR gene drive activity through nucleocytoplasmic localization of Cas9 in S. cerevisiae (2019)

These findings have implications for control of traditional nuclease-dependent editing and use of gene drive systems within other organisms. For instance, initiation of a nuclear export mechanism to Cas9 could serve as a molecular safeguard within an active gene drive to reduce or eliminate editing.
Single Etch Patterning of Stacked Silver and Molybdenum Alloy Layers on Glass Using Microcontact Wave Printing (2005)

Stacked thin layers of silver alloy (AgPdCu) and MoCr layers on 10 x 15 cm2 glass substrates were patterned by microcontact wave printing and etching. Patterns of etch-resistant octadecanethiol self-assembled monolayers (SAMs) were wave printed with regular backplane stabilized PDMS stamps. Pattern development was achieved by etching both metal layers in a single step, employing a nitric acid-based etching bath. Trifluoroacetic acid and a nitrite salt were identified as essential bath components for a homogeneous etching process. Etch defects could be eliminated by the addition of a decanesulfonate, which stabilizes the SAM resist via a defect healing mechanism.
Scoring of atopic dermatitis by SCORAD using a training atlas by investigators from different disciplines (1997)

The ETAC (Early Treatment of the Atopic Child) study, a multi-national double-blind placebo-controlled randomized trials, has been in progress since 1994. Fifty-six centers in Europe and Canada participate in this study. A total of 817 children with atopic dermatitis [AD] were recruited. The severity of AD was scored using the SCORAD (objective criteria). Ninety-eight investigators (mostly pediatricians) were trained by three members of the European Task Force on Atopic Dermatitis [ETFAD] to standardize their objective SCORAD scoring (system developed by the ETFAD). The experts selected photographs and prepared a training atlas. The percentages of photographs assessed by the 98 non-expert investigators below, within and above the range of evaluations by the three experts were calculated. Taking over and underscoring together, edema/papulation was the easiest intensity item to score (82% within the range by the experts). The global symptom score, as well as lichenification, edema/papulation, oozing and excoriation registered by physicians with dermatological experience were not statistically significantly different from those by other. Erythema was statistically significantly better scored by those with dermatological experience. The results of the Euclidean Distance method showed that the item excoriations gave the largest distance. Erythema and excoriations were scored better by dermatologically experienced physicians (t-test, p = 0.042 and p = 0.063 respectively), but lichenification was better scored by non-dermatologically experienced physicians (p = 0.013). The extent of surface area involved in the disease was calculated on 3 sets of photographs. Most evaluations by the 98 nonexpert investigators were within the range of the experts. Dermatologically experienced physicians scored significantly better than the others (t-test, p = 0.006). This training program is useful for standardizing the scoring in AD and indicates that SCORAD can be used by investigators from different disciplines.
Mechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesicles (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesiclesPeter J. Sims, Alan S. Waggoner, Chao-Huei Wang, and Joseph F. HoffmanCite this: Biochemistry 1974, 13, 16, 3315–3330Publication Date (Print):July 1, 1974Publication History Published online1 May 2002Published inissue 1 July 1974https://pubs.acs.org/doi/10.1021/bi00713a022https://doi.org/10.1021/bi00713a022research-articleACS PublicationsRequest reuse permissionsArticle Views2708Altmetric-Citations746LEARN 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
Effect of A-Ring Modifications on the DNA-Binding Behavior and Cytotoxicity of Pyrrolo[2,1-c][1,4]benzodiazepines (1999)

Several A-ring-modified analogues of the DNA-binding antitumor agent DC-81 (5) have been synthesized in order to study structure-reactivity/cytotoxicity relationships. For two molecules (23 and 30) the modifications required the addition of a fourth ring to give the novel dioxolo[4,5-h]- and dioxano[5,6-h]pyrrolo[2,1-c][1, 4]benzodiazepin-11-one (PBD) ring systems, respectively. Another three analogues (34, 38, and 48) have the native benzenoid A-ring replaced with pyridine, diazine, or pyrimidine rings to give the novel pyrrolo[2,1-c][1,4]pyridodiazepine, pyrrolo[2,1-c][1, 4]diazinodiazepine, and pyrrolo[2,1-c][1,4]pyrimidinodiazepine systems, respectively. The other new analogues (16a,b) have extended chains at the C8-position of the DC-81 structure. During the synthesis of these compounds, a novel tin-mediated regiospecific cleavage reaction of the dioxole intermediate 18 was discovered, leading to the previously unknown iso-DC-81 (20). In addition, an unusual simultaneous nitration-oxidation reaction of 4-(3-hydroxypropoxy)-3-methoxybenzoic acid (8) was found to produce 3-(4-carboxy-2-methoxy-5-nitrophenoxy)propanoic acid (9), a key intermediate, in high yield. In general, the results of cytotoxicity and DNA-binding studies indicated that none of the changes made to the A-ring of the PBD system significantly improved either binding affinity or cytotoxicity in comparison to DC-81. This result suggests that the superior potency of natural products such as anthramycin (1), tomaymycin (2), and sibiromycin (3) is due entirely to differences in C-ring structure, and in particular exo or endo unsaturation at the C2-position and C2-substituents containing unsaturation. This study also provided information regarding the influence of A-ring substitution pattern on the relative stability of the interconvertible N10-C11 carbinolamine, carbinolamine methyl ether, and imine forms of PBDs.
Colorectal disorders: A dietary management perspective (2000)

Dietary lifestyle is relevant for prevention and treatment of various colorectal conditions. Colorectal disorders have significant morbidity and mortality in a western-style community, particularly irritable bowel syndrome (IBS), colorectal cancer, haemorrhoids, constipation and diverticular disease. This review addresses how bowel health can be maintained, what foods and dietary lifestyles are associated with risk for disease and what foods are of real value in management. Bowel health is that state where the individual is satisfied with defaecation, the diet does not create undue risk for disease and lumenal contents maintain an intact and functional mucosa. Bowel health depends on a healthy dietary lifestyle, but in particular on an adequate intake of non-digestable dietary polysaccharide. Diet influences biology in part by altering the lumenal environment. Effects such as high butyrate levels, lowered pH, a predominance of 'healthy'over 'unhealthy' bacteria, rapid intestinal transit, high faecal bulk, a non-leaky epithelial barrier, adsorption of dietary carcinogens by fibre, low bile salt concentrations, reduced generation of toxic bile salts or protein derivatives and provision of certain bioactive substances are seen as beneficial. Diet influences future risk for colorectal cancer (vegetables, animal fats, polysaccharides amongst others) and for diverticular disease (fibre). Adequate fibre and resistant starch can improve constipation and anorectal conditions such as fissure and haemorrhoids. The role of diet in managing patients with IBS is complex. Fibre may worsen symptoms in severe cases of IBS, diverticular disease and inflammatory bowel disease. Certain carbohydrates of limited digestibility/absorbability, such as lactose, fructose and sorbitol, can precipitate IBS symptoms. Low fat, high fibre diets may reduce recurrence of colorectal adenomas. Diet has a significant role to play in colorectal disorders.
Evaluation in vitro of adriamycin immunoconjugates synthesized using an acid-sensitive hydrazone linker. (1990)

A novel method for linking Adriamycin (ADM) to monoclonal antibodies is described in which the 13-keto position of the anthracycline is used as the attachment site to the linker arm. A new ADM acylhydrazone derivative, Adriamycin 13-[3-(2-pyridyldithio)propionyl]hydrazone hydrochloride, which contains a pyridyl-protected disulfide, was synthesized and used for conjugation to monoclonal antibodies (MAbs) that were thiolated with N-succinimidyl 3-(pyridyldithiol)propionate or 2-iminothiolane. This resulted in formation of a linker between MAb and drug that contained a disulfide bond. Conjugation conditions were optimized to yield conjugates with high ADM:MAb molar ratios. The final immunoconjugate yields were found to decrease as the ADM:MAb molar ratio of the conjugates increased. Stability studies indicated that ADM was released from the immunoconjugates at mildly acidic pHs ranging from 4.5-6.5. Treatment of immunoconjugates with mild reducing agent dithiothreitol resulted in release of an acylhydrazone derivative of ADM. Flow-cytometric studies showed that the binding activity of various MAbs following conjugation to ADM was preserved at ADM:MAb molar ratios up to 10. Antibody-directed cytotoxicity was demonstrated under several assay conditions using combinations of antigen-positive and antigen-negative cells and binding and nonbinding immunoconjugates. In several experiments, ADM immunoconjugates were more potent than equivalent amounts of unconjugated ADM.
hERG Channel Trafficking (2005)

Mutations in the cardiac potassium channel hERG/IKr cause inherited long QT syndrome with increased susceptibility to ventricular arrhythmias. Several mutations in hERG produce trafficking-deficient channels that are retained in the endoplasmic reticulum (ER). Surface expression of certain mutations (i.e. hERG G601S) can be restored by specific channel blockers. Although hERG currents have been studied extensively, little is known about proteins in the processing pathway. Using biochemical and electrophysiological assays we show that the cytosolic chaperones Hsp70 and Hsp90 interact transiently with wild-type hERG. Inhibition of Hsp90 prevents maturation and reduces hERG/IKr currents. Trafficking-deficient mutants remain tightly associated with chaperones in the ER until trafficking is restored, e.g. by channel blockers. hERG/chaperone complexes represent novel targets for therapeutic compounds with cardiac liability such as arsenic, which is used in the treatment of leukaemias. Arsenic interferes with the formation of hERG/chaperone complexes and inhibits hERG maturation causing ECG abnormalities. We conclude that Hsp90 and Hsp70 are crucial for productive folding of wild-type hERG. Therapeutic compounds that inhibit chaperone function produce a novel form of acquired long QT syndrome not by direct channel block but by reduced surface expression due to an acquired trafficking defect of hERG.
Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. (1989)

Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL. Second, both the intact apo B and some of the apo B fragments of lesion LDL reacted in Western blots with antisera that recognize malondialdehyde-conjugated lysine and 4-hydroxynonenal lysine adducts, both of which are found in oxidized LDL; plasma LDL and LDL from normal human intima showed no such reactivity. Third, lesion LDL shared biological properties with oxidized LDL: compared with plasma LDL, lesion LDL produced much greater stimulation of cholesterol esterification and was degraded more rapidly by macrophages. Degradation of radiolabeled lesion LDL was competitively inhibited by unlabeled lesion LDL, by LDL oxidized with copper, by polyinosinic acid and by malondialdehyde-LDL, but not by native LDL, indicating uptake by the scavenger receptor(s). Finally, lesion LDL (but not normal intimal LDL or plasma LDL) was chemotactic for monocytes, as is oxidized LDL. These studies provide strong evidence that atherosclerotic lesions, both in man and in rabbit, contain oxidatively modified LDL.
The in-vitro inhibition of rat alloantigen presentation by immunotoxins--implications for allografting. (1989)

The removal of graft interstitial dendritic cells (IDC) prior to transplantation into a recipient has been shown to improve graft survival in a number of experimental studies. We report the in-vitro properties of two immunotoxins (IT) which could be used to deplete graft IDC when administered ex vivo by hypothermic perfusion in an experimental rat transplantation model. Ricin A chain (RAC) IT targeted at either class II major histocompatibility complex (MHC) molecules or leukocyte common antigens (LCA) were prepared. These IT had similar equilibrium constants, binding kinetics and inhibiting activity of cell-free protein synthesis. IT cytotoxicity was assessed by inhibition of alloantigen presentation by targeted low density spleen cells (LDSC) in a one way mixed lymphocyte culture (MLC). When LDSC were hypothermically incubated for 2 h with IT only the anti class II MHC IT inhibited the MLC and the maximum inhibition depended on the cell allotypes. The inhibition was increased to almost 100% when chloroquine was incorporated throughout the culture period.