gebhart/patrepeval huggingface dataset:
Review of analytical methods used in the dissolution testing of pharmaceuticals (1994)

The in vitro dissolution test is the most useful quality control test for pharmaceutical dosage forms such as tablets and capsules from the standpoint of bioavailability and physical consistency. Because bioavailability is largely dependent upon having the drug in dissolved state, for poorly soluble drugs the dissolution test can give an indication of poor bioavailability and reduced efficacy. In dissolution testing modern analytical techniques play an important part. This paper provides an overview of the analytical techniques used in dissolution testing and assesses their advantages and disadvantages.
Mechanism of Schottky barrier formation: The role of amphoteric native defects (1987)

A correlation between the Fermi level pinning deduced from Schottky barrier heights and from electrical properties of irradiated III–V semiconductors is found. The correlation indicates that similar defects are responsible for the Fermi level stabilization in both cases. It is proposed that amphoteric native defects, i.e., the defects which change their electrical characteristics depending on the Fermi level position, play a dominant role in the processes leading to a Schottky barrier formation. A detailed analysis of metal–GaAs contacts shows that in this case the amphoteric defects responsible for the barrier heights are VGa (acceptor) and a donor complex AsGa+VAs. It is shown that for thick metal coverages two barriers are formed. A surface barrier determined by the charge associated with a native defect and the bulk barrier controlled by the bulk doping. The sum of the two barrier heights satisfies the Schottky condition for the interface, but it is the bulk barrier that determines the macroscopic electrical properties of the contact. The model explains the evolution of the Fermi level position at the interface observed for metal coverages varying in a broad range of thicknesses. The relationship of the present proposal to previous models of Schottky barriers is discussed.
Switchable Surfactants (2006)

Many industrial applications that rely on emulsions would benefit from an efficient, rapid method of breaking these emulsions at a specific desired stage. We report that long-chain alkyl amidine compounds can be reversibly transformed into charged surfactants by exposure to an atmosphere of carbon dioxide, thereby stabilizing water/alkane emulsions or, for the purpose of microsuspension polymerization, styrene-in-water emulsions. Bubbling nitrogen, argon, or air through the amidinium bicarbonate solutions at 65 degrees C reverses the reaction, releasing carbon dioxide and breaking the emulsion. We also find that the neutral amidines function as switchable demulsifiers of an aqueous crude oil emulsion, enhancing their practical potential.
Vaccination with cytotoxic T lymphocyte epitope‐containing peptide protects against a tumor induced by human papillomavirus type 16‐transformed cells (1993)

Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immunization of mice against lethal virus infection. To study whether this approach can be successful against virus-induced tumors we generated a B6 (H-2b) tumorigenic cell line transformed by human papillomavirus (HPV). This virus is detected in over 90% of all human cervical cancers. To identify vaccine candidates, we generated a set of 240 overlapping peptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. These peptides were tested for their ability to bind H-2Kb and H-2Db MHC class I molecules. Binding peptides were compared with the presently known peptide-binding motifs for H-2Kb and H-2Db and the predictive value of these motifs is shortly discussed. The high-affinity H-2Db-binding peptide and putative CTL epitope E7 49-57 (RAHYNIVTF) was used in vaccination studies against HPV 16-transformed tumor cells. Immunization with peptide E7 49-57 rendered mice insensitive to a subsequent challenge with HPV 16-transformed tumor cells in vivo, and induced a CTL response which lysed the tumor cells in vitro.
The combination of a blood test and Fibroscan improves the non‐invasive diagnosis of liver fibrosis (2009)

The synchronous combination of a blood test plus LSE improves the accuracy of the non-invasive diagnosis of liver fibrosis and, consequently, markedly decreases the biopsy requirement in the diagnostic algorithm, notably to <10% in cirrhosis diagnosis.
Wide bandgap compound semiconductors for superior high-voltage unipolar power devices (1994)

This paper presents a critical evaluation of the performance capabilities of various wide bandgap semiconductors for high power and high frequency unipolar electronic devices. Seven different figures of merit have been analyzed. Theoretical calculations show that besides diamond and SiC, compounds like AlN, GaN, InN, and ZnO, and the intermetallics (Ga/sub x/In/sub 1-x/N, Al/sub x/In/sub 1-x/N, Al/sub x/Ga/sub 1-x/N, and (AlN)/sub x/(SiC)/sub 1-x/) offer several orders of magnitude improvement in the on-resistance and in the potential for successful operation at higher temperatures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Variations of dose and electrode spacing for rat breast cancer electrochemical treatment (2001)

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P </= 0.001). Electrodes spacing was not an important factor within a given range. At 5, 10, and 15 mm spacing, the fraction showing the necrosis were 54.1, 60.4, and 59.2%, respectively (P = 0.552). The overlap rate of necroses was similar in the 5 and 10 mm groups (82.5 and 85%) and lower in the 15 mm group (65%). We conclude that the tumor responses to EChT, local control, survival rates, and necrosis percentages were significantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not significantly affect the tumor responses to EChT within the same dose. For a diameter of 2.0-2.5 cm rat breast cancer, EChT should be applied with 5-10 mm spacing and a minimum dosage of 80 C.
Dissecting the Electrostatic Interactions and pH-Dependent Activity of a Family 11 Glycosidase, (2001)

Previous studies of the low molecular mass family 11 xylanase from Bacillus circulans show that the ionization state of the nucleophile (Glu78, pK(a) 4.6) and the acid/base catalyst (Glu172, pK(a) 6.7) gives rise to its pH-dependent activity profile. Inspection of the crystal structure of BCX reveals that Glu78 and Glu172 are in very similar environments and are surrounded by several chemically equivalent and highly conserved active site residues. Hence, there are no obvious reasons why their apparent pK(a) values are different. To address this question, a mutagenic approach was implemented to determine what features establish the pK(a) values (measured directly by (13)C NMR and indirectly by pH-dependent activity profiles) of these two catalytic carboxylic acids. Analysis of several BCX variants indicates that the ionized form of Glu78 is preferentially stabilized over that of Glu172 in part by stronger hydrogen bonds contributed by two well-ordered residues, namely, Tyr69 and Gln127. In addition, theoretical pK(a) calculations show that Glu78 has a lower pK(a) value than Glu172 due to a smaller desolvation energy and more favorable background interactions with permanent partial charges and ionizable groups within the protein. The pK(a) value of Glu172 is in turn elevated due to electrostatic repulsion from the negatively charged glutamate at position 78. The results also indicate that all of the conserved active site residues act concertedly in establishing the pK(a) values of Glu78 and Glu172, with no particular residue being singly more important than any of the others. In general, residues that contribute positive charges and hydrogen bonds serve to lower the pK(a) values of Glu78 and Glu172. The degree to which a hydrogen bond lowers a pK(a) value is largely dependent on the length of the hydrogen bond (shorter bonds lower pK(a) values more) and the chemical nature of the donor (COOH > OH > CONH(2)). In contrast, neighboring carboxyl groups can either lower or raise the pK(a) values of the catalytic glutamic acids depending upon the electrostatic linkage of the ionization constants of the residues involved in the interaction. While the pH optimum of BCX can be shifted from -1.1 to +0.6 pH units by mutating neighboring residues within the active site, activity is usually compromised due to the loss of important ground and/or transition state interactions. These results suggest that the pH optima of an enzyme might be best engineered by making strategic amino acid substitutions, at positions outside of the "core" active site, that electrostatically influence catalytic residues without perturbing their immediate structural environment.
Measurement of plant leaf area using CAD image processing techiques (2003)

A rapid method for measuring individual leaf area of plant was developed by means of AutoCAD 2000, digital picture of plant leaf and referring ruler to measure area and perimeter of plant. Meanwhile, the method was compared with the values from grid-counting method, leaf-copy and weighing method, instrumental scanning method, etc. The results showed that there are close relationships between CAD image processing method and the other traditional methods. The dominant advantage was rapid, accurate, suitable to measure leaf area of plant, especially it wasn抰 necessary to pick the leaf.
Female hypoactive sexual desire disorder due to androgen deficiency: clinical and psychometric issues. (1997)

Menopause, surgical or naturally occurring, with reduced or deficient ovarian functioning has a major impact on morbidity and mortality in mid to late life. In particular, a growing body of literature is focusing on the role of androgens in maintaining women's health and emotional well-being. Further study is needed in the administration of physiologic levels of testosterone replacement therapy as an adjustment to estrogen replacement. The Sexual Energy Scale was developed to provide an objective means of measuring the change in a patient's subjective experience of vitality/sexual energy with androgen replacement therapy. The scale also provides a clinical indication for androgen replacement dosage adjustment. Advantages in using low doses of methyltestosterone in women with hypoactive sexual desire disorder are discussed.
Notes (1953)

G. R. Clemo, R. J. W. Holt, D. G. Bew, R. N. Chakravarti, A. T. Shulgin, E. M. Gal, R. J. W. Le Fèvre, I. Youhotsky, C. C. Addison, J. Lewis, M. D. Potter and E. P. Taylor, J. Chem. Soc., 1953, 1313 DOI: 10.1039/JR9530001313
AN OVERVIEW OF TECHNIQUES FOR REDUCING PEAK TO AVERAGE POWER RATIO AND ITS SELECTION CRITERIA FOR ORTHOGONAL FREQUENCY DIVISION MULTIPLEXING RADIO SYSTEMS (2009)

The concept of Orthogonal Frequency Division Multiplexing (OFDM) has been known since 1966, but it only reached sufficient maturity for deployment in standard systems during 1990s. OFDM is an attractive modulation technique for transmitting large amounts of digital data over radio waves. One major disadvantage of OFDM is that the time domain OFDM signal which is a sum of several sinusoids leads to high peak to average power ratio (PAPR). Number of techniques have been proposed in the literature for reducing the PAPR in OFDM systems. In this paper the various techniques proposed for reducing the PAPR and the selection criteria for choosing these techniques have been discussed. The goal is to convey the fundamental ideas and intuitive understanding of the concept introduced. This is done primarily to give an overview of the various techniques known today for PAPR reduction.
Network and data security design for telemedicine applications (1997)

The maturing of telecommunication technologies has ushered in a whole new era of applications and services in the health care environment. Teleworking, teleconsultation, mutlimedia conferencing and medical data distribution are rapidly becoming commonplace in clinical practice. As a result, a set of problems arises, concerning data confidentiality and integrity. Public computer networks, such as the emerging ISDN technology, are vulnerable to eavesdropping. Therefore it is important for telemedicine applications to employ end-to-end encryption mechanisms securing the data channel from unauthorized access of modification. We propose a network access and encryption system that is both economical and easily implemented for integration in developing or existing applications, using well-known and thoroughly tested encryption algorithms. Public-key cryptography is used for session-key exchange, while symmetric algorithms are used for bulk encryption. Mechanisms for session-key generation and exchange are also provided.
Managing Money (1994)

When I am asked what I do at a party, I tend to tell them what my job title is and they look blank, and I laugh, and that is the end of the conversation. People do not follow through with, ‘Oh, how fascinating, do tell me more.’
Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis II. Skin morphogenesis (1989)

Expression and the role of E- and P-cadherin in the histogenesis of the surface epidermis and hair follicles were examined using the upper lip skin of the mouse. P-cadherin is expressed exclusively in the proliferating region of these tissues, that is in the germinative layer of the surface epidermis, the outer root sheath and the hair matrix. E-cadherin is coexpressed in these layers but this molecule was also detected in non-proliferating regions such as the intermediate layer of the surface epidermis and the immature regions of the inner root sheath. Neither P- nor E-cadherin was detected in fully keratinized layers such as the horny layer of the surface epidermis, the outermost layer of the outer root sheath and the mature hair fibres. These two cadherins were not detected in dermal cells. We cultured pieces of the upper lip skin in vitro in the absence or presence of a monoclonal antibody to E-cadherin (ECCD-1) or to P-cadherin (PCD-1). In control cultures, skin morphogenesis normally occurred in a pattern whereby the hair follicles grew and dermal cells were condensed to form the dermal sheath. A mixture of ECCD-1 and PCD-1, however, induced abnormal morphogenesis in the skin in several respects. (1) The cuboidal or columnar arrangement of basal epithelial cells was distorted. (2) Hair follicles were deformed. (3) Condensation of dermal cells was suppressed, causing a homogeneous distribution of these cells. These results suggest that cadherins present in epidermal cells are involved not only in maintaining the arrangement of these cells but also in inducing dermal condensation.
Molecular‐targeted agents combination therapy for cancer: Developments and potentials (2013)

Although chemotherapy has advanced into the era of targeted drugs, the antitumor efficacies of current therapies are limited, most likely because of the high degree of cancer clonal heterogeneity, intratumor genetic heterogeneity and cell signal complexity. As shutdown of a single target does not necessarily eradicate the cancer, the use of combinations of molecular-targeted agents (MATs) has been proposed, and some pioneering research has been conducted to examine the efficacy of this strategy. In this article, the clinical and preclinical studies that are underway in an attempt to improve the anticancer efficacy of chemotherapies through combination strategies are summarized. Studies of combining cytotoxic agents with MATs, coinhibiting two or more targets in a single pathway or coinhibiting parallel or compensatory pathways as well as specific combinations will be introduced, and the antitumor potentials of each combination strategy will be evaluated.
Regulation of Casein Kinase Iϵ Activity by Wnt Signaling (2004)

The Wnt/beta-catenin signaling pathway is important in both development and cancer. Casein kinase Iepsilon (CKIepsilon) is a positive regulator of the canonical Wnt pathway. CKIepsilon itself can be regulated in vitro by inhibitory autophosphorylation, and recent data suggest that in vivo kinase activity can be regulated by extracellular stimuli. We show here that the phosphorylation state and kinase activity of CKIepsilon are directly regulated by Wnt signaling. Coexpression of XWnt-8 or addition of soluble Wnt-3a ligand led to a significant and rapid increase in the activity of endogenous CKIepsilon. The increase in CKIepsilon activity is the result of decreased inhibitory autophosphorylation because it is abolished by preincubation of immunoprecipitated kinase with ATP. Furthermore, mutation of CKIepsilon inhibitory autophosphorylation sites creates a kinase termed CKIepsilon(MM2) that is significantly more active than CKIepsilon and is not activated further upon Wnt stimulation. Autoinhibition of CKIepsilon is biologically relevant because CKIepsilon(MM2) is more effective than CKIepsilon at activating transcription from a Lef1-dependent promoter. Finally, CKIepsilon(MM2) expression in Xenopus embryos induces both axis duplication and additional developmental abnormalities. The data suggest that Wnt signaling activates CKIepsilon by causing transient dephosphorylation of critical inhibitory sites present in the carboxyl-terminal domain of the kinase. Activation of the Wnt pathway may therefore stimulate a cellular phosphatase to dephosphorylate and activate CKIepsilon
Short Course of Ofloxacin for Treatment of Multidrug-Resistant Typhoid (1995)

In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3-day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever.
Imatinib mesylate blocks a non‐Smad TGF‐β pathway and reduces renal fibrogenesis in vivo (2005)

Transforming growth factor-beta (TGF-beta) is the single most important cytokine promoting renal fibrogenesis. p21-activated kinase-2 (PAK2) and activation of abelson nonreceptor tyrosine kinase (c-abl) have been shown recently to be smad-independent, fibroblast-specific targets downstream of the activated TGF-beta receptor. In the current study we show that in cultured NRK49F-renal fibroblasts (but not in tubular or mesangial cells) TGF-beta similarly activates PAK2 as well as c-abl and induces cell proliferation. Inhibition of the c-abl kinase with imatinib mesylate prevents increased proliferation after TGF-beta addition without affecting PAK2. These in vitro findings were extended to rats with unilateral obstructive nephropathy, a disease model of TGF-beta-driven renal fibrogenesis. In obstructed kidneys, PAK2 and c-abl activity were increased but only c-abl activation was blocked by imatinib. Treatment with imatinib did not prevent renal interstitial infiltration of macrophages or phosphorylation and nuclear translocation of smad2/3 in obstructed kidneys. In contrast, imatinib substantially inhibited an increase in the number of interstitial fibroblasts and myofibroblasts and reduced the expression and interstitial accumulation of collagen type III, collagen type IV and fibronectin. These findings indicate that TGF-beta-induced activation of the nonreceptor c-abl tyrosine kinase regulates fibroblast proliferation and, by this means, is a costimulatory signal in TGF-beta-dependent renal fibrogenesis. Inhibition of c-abl activity with imatinib mesylate ameliorates experimental renal fibrosis in rats.
Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic sites. (1990)

The repair of 2,6-diamino-4-hydroxy-5-N-methyl-formamidopyrimidine (Fapy) residues in DNA is performed by a Fapy-DNA glycosylase activity which is encoded for by the fpg gene in Escherichia coli. Besides DNA glycosylase activity, this protein, the FPG protein, is endowed with an EDTA-resistant activity nicking DNA at apurinic/apyrimidinic (AP) sites. To overproduce the FPG protein, the fpg gene was placed under the control of the tac promoter in the expression vector pKK223-3 yielding the pFPG230 plasmid. The production of the FPG protein in cells harboring the pFPG230 plasmid was 800-fold higher than that of the wild type strain after induction by isopropyl-beta-D-thio-galactopyranoside. From these cells, the FPG protein was purified to homogeneity in sufficient quantity to study its physical and catalytic properties. In its active form, the FPG protein is a globular monomer of 31 kDa and has an experimentally measured isoelectric point of 8.5. When the FPG protein is heat-denatured in the presence of EDTA the two activities are more rapidly inactivated than when heated in the absence of EDTA, suggesting that the FPG protein possesses a tightly bound metal ion. Atomic absorption spectrophotometric analysis shows that there is one zinc/FPG protein molecule. The FPG protein is different from previously described DNA glycosylases and AP-nicking enzymes in E. coli. The contribution of the AP-nicking activity associated with the FPG protein represents 10-20% of the total EDTA-resistant AP-nicking activities in E. coli.
Precise Cas9 targeting enables genomic mutation prevention (2018)

Here, we present a generalized method of guide RNA "tuning" that enables Cas9 to discriminate between two target sites that differ by a single-nucleotide polymorphism. We employ our methodology to generate an in vivo mutation prevention system in which Cas9 actively restricts the occurrence of undesired gain-of-function mutations within a population of engineered organisms. We further demonstrate that the system is scalable to a multitude of targets and that the general tuning and prevention concepts are portable across engineered Cas9 variants and Cas9 orthologs. Finally, we show that the mutation prevention system maintains robust activity even when placed within the complex environment of the mouse gastrointestinal tract.