gebhart/patrepeval huggingface dataset:
Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia (2003)

Abstract Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐ N ‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD 50 in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and &gt;2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro . Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.
A novel ultra‐thin backlight system without optical sheets using a multi‐layered lightguide (2011)

Abstract— A backlight system using a newly developed multi‐layered lightguide (MLL) is described. The MLL can function as a backlight without additional optical sheets such as prism sheets or diffusers. It was developed as a multi‐layered sheet featuring different refractive indexes for different layers. A prototype was built, and the principles were confirmed by comparison with theory. With a thickness of 0.414 mm, the prototype is the thinnest backlight in the world, using only a MLL and a reflector.
InterProScan – an integration platform for the signature-recognition methods in InterPro (2001)

The Perl-based InterProScan implementation is available from the EBI ftp server (ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/) and the SRS-basedInterProScan is available upon request. We provide the public web interface (http://www.ebi.ac.uk/interpro/scan.html) as well as email submission server (interproscan@ebi.ac.uk).
Active multilayered capsules for in vivo bone formation (2010)

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled.
Preparation and Reactions of Masked Allylic Organozinc Reagents (1998)

Allylic zinc reagents have been prepared from sterically hindered homoallylic alcohols 10 and 13, using a novel fragmentation reaction of the corresponding zinc alkoxide, without any homocoupling products. These allylic zinc reagents react with a range of electrophiles in good to excellent yields. Substituted allylic zinc reagents have also been prepared in this manner. alpha-Substituted homoallylic alcohols 37, 46, and 51 give solely alpha-substituted products after the fragmentation-allylation sequence; these products are obtained not only regioselectively but also with extremely high anti diastereoselectivity. Likewise, gamma-substituted homoallylic alcohols 57 and 58, undergo the fragmentation-allylation reaction to give gamma-substituted products. The reaction has also been demonstrated to be catalytic in zinc salts.
Thrombotic Thrombocytopenic Purpura (2006)

A 40-year-old obese black woman has had weakness and epigastric pain for several weeks and diarrhea and vomiting for four days. She does not appear acutely ill; the physical examination is normal except for abdominal tenderness. Her hematocrit is 25 percent. The platelet count is 10,000 per cubic millimeter. The peripheral-blood smear shows occasional fragmented and polychromatophilic red cells. The serum creatinine level is 1.1 mg per deciliter (97.2 μmol per liter), bilirubin 2.5 mg per deciliter (42.8 μmol per liter), and lactate dehydrogenase 722 U per liter (normal, <250). How should this case be managed?
Security services in an open service environment (2002)

Emerging telecommunication services use, store or transmit sensitive personal data to form individual network services. We suggest an add-on approach to realize secure telecommunication services which saves the huge investments in the existing ISDN network infrastructure. This is done by adding trusted runtime environments that contain security functions to the existing service infrastructure. This approach aims at separating sensitive service functions from highly complex functions of public telecommunication networks. We propose an enhancement of existing network service interfaces by standardized security service interfaces to enable the provision of open security services. Separated security control functions of independent service providers, however, might not be trusted by network operators. Therefore, this contribution particularly considers gateway functions implementing access control and ancillary conditions concerning network integrity.
Lower bounds for graph embeddings and combinatorial preconditioners (2004)

Given a general graph G, a fundamental problem is to find a spanning tree H that best approximates G by some measure. Often this measure is some combination of the congestion and dilation of an embedding of G into H. One example is the routing timep(G, H) ≤ O (congestion + dilation), the number of steps necessary to route pairwise demands G on network links H in the store-and-forward packet routing model. Another is the condition numberkf(G, H) ≤ O (congestion · dilation), the square root of which bounds the number of iterations necessary to solve a linear system with coefficient matrix G preconditioned by H using the classical conjugate gradient method. The algorithmic applications of being able to find (efficiently) a good tree approximation H for a graph G are numerous; but what if no good tree exists.In this paper, we seek to identify the class of graphs G which are intrinsically difficult to approximate by a particular measure. It is easily seen that with respect to routing time, G is hardest to approximate by a tree H precisely when it contains either long cycles (which yield high dilation)or large separators (which yield high congestion). We show that with respect to condition number, the existence of long cycles or large separators in G is sufficient but not necessary or it to be hardest to approximate, by demonstrating a nearly-linear lower bound or the case in which G is a square mesh. The proof uses concepts from circuit theory, linear algebra, and geometry, and it generalizes to the case in which H is a spanning subgraph of G of Euler characteristic k. The result has consequences or the design of preconditioners or symmetric M-matrices and perhaps also of communication networks.
A Novel Method for the Estimation of Podocyte Injury: Podocalyxin-Positive Elements in Urine (2008)

Podocytes form an outer aspect of the glomerular capillary wall and play a decisive role in its permeability for macromolecules. The main podocyte surface antigen podocalyxin, a highly electronegative sialoglycoprotein, prevents the podocyte foot processes from collapsing. Podocyte damage in glomerular disease is supposed to be accompanied by podocyte detachment, and shed podocytes and their fragments (marked by podocalyxin) may be identified in the urine. Using anti-podocalyxin monoclonal antibody, PCX+EL were counted by FACS in 38 patients with various types of active glomerulonephritis, 15 patients with chronic glomerulonephritis in long-term remission and 44 healthy controls. Urinary levels of PCX+EL were significantly higher in patients with active glomerulonephritis compared to patients with chronic glomerulonephritis in longterm remission (93 +/- 100 vs. 6.3 +/- 3.2/microl of urine, P < 0.000001) and healthy controls (4.4 +/- 2.6/microl of urine, P < 0.000001 compared to active glomerulonephritis, n.s. compared to chronic glomerulonephritis in longterm remission). These preliminary data suggest the potential of this simple method to monitor the activity of glomerular disease. Further prospective studies of larger cohorts of patients with individual glomerular diseases are clearly warranted.
Monocyte activation: rapid induction of α1/β1 (VLA‐1) integrin expression by lipopolysaccharide and interferon‐γ (1995)

Monocytes play a key role in inflammation, tissue injury and remodelling and wound healing, and most monocyte effector functions are dependent on adhesive interactions. We have analyzed the changes in the pattern of beta 1 integrin expression that take place during monocyte activation and demonstrated that lipopolysaccharide (LPS) and interferon (IFN)-gamma specifically induce the expression of the alpha 1/beta 1 integrin, which was detectable on the monocyte membrane as early as 12 h after monocyte activation. The up-regulated alpha 1/beta 1 expression was not dependent on monocyte adherence to solid surfaces, and Northern blot analysis revealed that LPS and IFN-gamma induce the alpha 1 mRNA de novo. Monocyte deactivating cytokines such as interleukin (IL)-4 or IL-10, could only minimally inhibit the LPS- or IFN-gamma mediated up-regulation of alpha 1/beta 1, suggesting that cytokine release subsequent to monocyte activation does not play a major role in the integrin induction. Interestingly, the LPS-induced expression of alpha 1/beta 1 was found to be dependent on the redox state of the cell, since it was inhibited by antioxidants which also altered the morphological changes that take place during monocyte culture in vitro. The rapid induction of alpha 1 in LPS-activated monocytes suggests that alpha 1/beta 1 might be involved not only in monocyte/extracellular matrix interactions during inflammatory reactions, but also in contributing to further monocyte activation and cytokine production during septic shock syndrome.
Calophyllum products. III. Structure of blancoic acids (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCalophyllum products. III. Structure of blancoic acidsGeorge H. Stout and Karl D. SearsCite this: J. Org. Chem. 1968, 33, 11, 4185–4190Publication Date (Print):November 1, 1968Publication History Published online1 May 2002Published inissue 1 November 1968https://pubs.acs.org/doi/10.1021/jo01275a038https://doi.org/10.1021/jo01275a038research-articleACS PublicationsRequest reuse permissionsArticle Views130Altmetric-Citations18LEARN 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
Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease. (2001)

The lack of a sensitive immunoassay for quantitating serum prostate-specific membrane antigen (PSMA) hinders its clinical utility as a diagnostic/prognostic biomarker. An innovative protein biochip immunoassay was used to quantitate and compare serum PSMA levels in healthy men and patients with either benign or malignant prostate disease. PSMA was captured from serum by anti-PSMA antibody bound to ProteinChip arrays, the captured PSMA detected by surface-enhanced laser desorption/ionization mass spectrometry, and quantitated by comparing the mass signal integrals to a standard curve established using purified recombinant PSMA. The average serum PSMA value for prostate cancer (623.1 ng/ml) was significantly different (P < 0.001) from that for benign prostate hyperplasia (117.1 ng/ml) and the normal groups (age <50, 272.9 ng/ml; age >50, 359.4 ng/ml). These initial results suggest that serum PSMA may be a more effective biomarker than prostate-specific antigen for differentiating benign from malignant prostate disease and warrants additional evaluation of the surface-enhanced laser desorption/ionization PSMA immunoassay to determine its diagnostic utility.
Structure–property relationship in heat‐set poly(ethylene terephthalate) fibers. IV. Recovery behavior (1984)

Abstract This study describes the recovery behavior from tensile strains of up to 0.15, of oriented poly(ethylene terephthalate) (PET) fibers, which were heat‐set at different temperatures while free to relax and when held taut at constant length at room temperature. The taut annealed samples showed superior recovery behavior over the strain range studied. From structural studies on these samples, and also from FTIR studies of structural changes during deformation on similar shapes, it is concluded that, while the recovery behavior in the free‐annealed samples is dominated by the amporphous phase, both the crystalline and the amorphous phases influence the recovery behavior of the taut‐annealed samples.
Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor α chain gene rearrangement (1998)

Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to autoimmune T lymphocyte-mediated destruction of pancreatic beta cells. Although both major histocompatibility complex class I-restricted CD8(+) and class II-restricted CD4(+) T cell subsets are required, the specific role each subset plays in the pathogenic process is still unclear. Here we show that class I-dependent T cells are required for all but the terminal stages of autoimmune diabetes development. To characterize the diabetogenic CD8(+) T cells responsible, we isolated and propagated in vitro CD8(+) T cells from the earliest insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted to H-2Kd, and showed a diverse T cell receptor beta chain repertoire. In contrast, their alpha chain repertoire was more restricted, with a recurrent amino acid sequence motif in the complementarity-determining region 3 loop and a prevalence of Valpha17 family members frequently joined to the Jalpha42 gene segment. These results suggest that a number of the CD8(+) T cells participating in the initial phase of autoimmune beta cell destruction recognize a common structural component of Kd/peptide complexes on pancreatic beta cells, possibly a single peptide.
Aspects on pathophysiological mechanisms in COPD (2007)

Chronic obstructive pulmonary disease (COPD) is a condition which is characterized by irreversible airway obstruction due to narrowing of small airways, bronchiolitis, and destruction of the lung parenchyma, emphysema. It is the fourth most common cause of mortality in the world and is expected to be the third most common cause of death by 2020. The main cause of COPD is smoking but other exposures may be of importance. Exposure leads to airway inflammation in which a variety of cells are involved. Besides neutrophil granulocytes, macrophages and lymphocytes, airway epithelial cells are also of particular importance in the inflammatory process and in the development of emphysema. Cell trafficking orchestrated by chemokines and other chamoattractants, the proteinase-antiproteinase system, oxidative stress and airway remodelling are central processes associated with the development of COPD. Recently systemic effects of COPD have attracted attention and the importance of systemic inflammation has been recognized. This seems to have direct therapeutic implications as treatment with inhaled glucocorticosteroids has been shown to influence mortality. The increasing body of knowledge regarding the inflammatory mechanism in COPD will most likely have implications for future therapy and new drugs, specifically aimed at interaction with the inflammatory processes, are currently being developed.
Arginine-Binding RNAs Resembling TAR Identified by in Vitro Selection (1996)

Specific binding of the human immunodeficiency virus Tat protein to its RNA site (TAR) is mediated largely by a single arginine residue located within a basic region of the protein. Many essential features of the interaction can be mimicked by the free amino acid arginine, and an NMR model has been proposed in which the arginine guanidinium group binds to a guanine base in the major groove and to two phosphates adjacent to a bulge, with the RNA structure stabilized by a base triple between a U in the bulge and an adjacent A:U base pair. To compare the TAR structure to other arginine-binding RNAs, we performed in vitro selection experiments and identified RNAs with arginine-binding affinities similar to TAR. About 40% of the selected RNAs contained the same motif found in TAR: two stems separated by a bulge of at least two nucleotides, a U at the 5' position of the bulge, and G:C and A:U base pairs above the bulge. In many cases, the upper stems contained only the G:C and A:U pairs, located next to small loops. Chemical modification experiments demonstrated that these "TAR-like" RNAs bound arginine in a manner similar to TAR, and in some cases identified nucleotides outside the binding site that contributed to binding. To explore how small loops might help stabilize the structures of adjacent arginine-binding sites, we measured arginine-binding affinities of TAR-like RNAs having all possible three-nucleotide loops. An RNA with a UAG loop bound with highest affinity, and chemical modification and RNase mapping experiments suggested that the RNA changes conformation upon arginine binding, converting a large unstructured loop into a bulge conformation related to that of TAR. The results suggest that the arginine-binding site in TAR is structurally versatile and demonstrate how binding can be modulated by the surrounding RNA context.
Promoter influence on baculovirus-mediated gene expression in permissive and nonpermissive insect cell lines (1992)

The activities of viral and insect promoters were examined in a range of insect cell lines permissive and nonpermissive for the replication of the baculovirus Autographa californica nuclear polyhedrosis virus. Recombinant baculoviruses were constructed to place the bacterial chloramphenicol acetyltransferase gene under the control of promoters strongly active in the early, late, or very late stages of virus replication. In fully permissive cells, expression from a very late promoter was 2- to 3-fold higher than expression from a late promoter and 10- to 20-fold higher than expression from an early promoter or from a virus-borne insect promoter. In cell lines that do not support the efficient production of viral progeny, late-promoter-driven expression was similar to or surpassed very late promoter-driven expression. In nonpermissive insect cell lines, expression driven by an insect promoter derived from Drosophila melanogaster was higher than expression from the three viral promoters and was especially high in the Drosophila cell line tested. Surprisingly, late-promoter-driven expression, which is dependent on DNA replication, was higher than early-promoter-driven expression in three of four nonpermissive lines. In contrast, very late promoter-driven expression was quite limited in nonpermissive cell lines. The results indicate that the promoter used to drive foreign-gene expression strongly influences the range of insect cells which can efficiently support the production of the foreign protein during infection with recombinant baculoviruses.
Strategies for Wheel Cactus (Opuntia Robusta) - a Significant Non-WoNS for South Australian Rangelands (2009)

The article discusses weed management in South Australia, especially that of wheel cactus, which infests extensive areas of semi-arid environments. The challenges posed to the Weed Management Society of South Australia in tacking the menace of wheel cactus is highlighted. Opuntia species management in South Australia is clustered under the banner of the leading invasive; wheel cactus (Opuntia robusta). This formidable invasive degrades semi-arid ecosystems and has become well established over significant areas within SA. A cross-regional taskforce has formed to raise the profile of Opuntias and coordinate a strategy to prevent further expansion. Communities have formed local groups to raise their concern and coordinate control.
Properties and sequence of the coenzyme B12-dependent glycerol dehydratase ofClostridium pasteurianum (1998)

The genes encoding coenzyme B12-dependent glycerol dehydratase of Clostridium pasteurianum were subcloned and expressed in Escherichia coli. The native molecular mass of the enzyme is 190,000 Da. The enzyme converts glycerol, 1,2-propanediol and 1,2-ethanediol to 3-hydroxypropionaldehyde, propionaldehyde and acetaldehyde, respectively, but glycerol is the preferred substrate. The nucleotide sequences of the dhaBCE genes encoding the three subunits of glycerol dehydratase and of orfZ whose function is unknown were determined. The deduced products of the dhaBCE genes with calculated molecular masses of 60,813, 19,549 and 16,722 Da, respectively, revealed high similarity to amino acid sequences of subunits of coenzyme B12-dependent glycerol and diol dehydratases from other organisms.