gebhart/patrepeval huggingface dataset:
Effect of Difference in Fatty Acid Chain Lengths of Medium- Chain Lipids on Lipid/Surfactant/Water Phase Diagrams and Drug Solubility (2016)

Lipids consisting of medium chain fatty acids are commonly used in the development of lipid-based selfemulsifying and self-microemulsifying drug delivery systems. However, no systematic approach to selecting one lipid over another has been reported in the literature. In this study, propylene glycol (PG) monoester (PG monocaprylate, Capmul PG-8®) and PG diester (PG dicaprylocaprate, Captex 200P®) of C8-fatty acids were compared with PG monoester (PG monolaurate, Capmul PG-12®) and PG diester (PG dilaurate, Capmul PG-2L®) of C12-fatty acids with respect to their phase diagrams, and especially for their ability to form microemulsions in the presence of a common surfactant, Cremophor EL®, and water. The solubility of two model drugs, danazol and probucol, in the lipids and lipid/surfactant mixtures were also compared. The effect of the chain length of medium-chain fatty acids (C8 versus C12) on the phase diagrams of the lipids was minimal. Both shorter and longer chain lipids formed essentially similar microemulsion and emulsion regions in the presence of Cremophor EL® and water, although the C12-fatty acid esters formed larger gel regions in the phase diagrams than the C8-fatty acid esters. When monoesters were mixed with their respective diesters at 1:1 ratios, larger microemulsion regions with lower lipid particle sizes were observed compared to those obtained with individual lipids alone. While the solubility of both danazol and probucol increased greatly in all lipids studied, compared to their aqueous solubility, the solubility in C12-fatty acid esters was found to be lower than in C8-fatty acid esters when the lipids were used alone. This difference in solubility due to the difference in fatty acid chain length, practically disappeared when the lipids were combined with the surfactant.
Potential antitumor applications of a monoclonal antibody specifically targeting human papilloma virus 16 E749–57 peptide (2012)

Our study aims to evaluate whether the approach of TCRm mAb has therapeutic potential against HPV-induced tumors. In the present study, we generated a murine IgG2a mAb 6C10 specifically recognizing HPV-16-E7(49-57) epitope (RAHYNIVTF) in the polypeptides and in complex with a MHC class I molecule. Analysis of the primary structure shows that the 6C10 Ab displays a novel sequence in the CDR of the heavy chain, compared to the sequences in the Kabat database, which suggests the Ab has completed its affinity maturation. The 6C10 Ab can specifically recognize E7 and Trx-E7(30-67) protein in ELISA, and can also specifically bind to T2 cell carrying HPV-16-E7(49-57) peptide. In the TC-1 cell tumor-bearing mouse model, 6C10 exhibits tumor suppression activity when compared to the isotype control Ab. 6C10 Ab has showed tumor-inhibition potency in a mouse model and this Ab may have the prospect of cancer therapy.
Size estimation of chemical space: how big is it? (2011)

The values here are much smaller than previously reported. However, the numbers are large but not astronomical. A clear rationale on how we reach these numbers is given, which hopefully will lead to more refined predictions.
Comparison of Single‐ and Repeated‐Dose Pharmacokinetics of Diazepam (1998)

Repeat dosing of DZP leads to substantial accumulation, and high, persistent serum and CSF concentrations, which may explain the toxic effects of repeat DZP dosing. Repeat dosing of DZP using a tapering protocol, however, may increase the effectiveness of DZP in treating SE by preventing relapses without substantially increasing toxicity.
A novel member of the subtilisin-like protease family from Bacillus subtilis (1999)

aprX is a 1326 bp gene of Bacillus subtilis strain 168 that encodes a serine protease, probably intracellular, characterized by significant similarity with subtilisins, thermitases and pyrolysins. Transcription analysis, performed by RT-PCR and primer extension, allowed the localization of the active promoter and showed that aprX is expressed in stationary phase. The pattern of expression of aprX and its dependence on various transition state regulatory genes (degU, degQ, hpr, abrB, sinR), monitored by lacZ transcriptional fusions, are distinctive from those of subtilisin and other degradative enzymes. aprX is not essential for either growth or sporulation.
The ProTide Prodrug Technology: From the Concept to the Clinic (2017)

The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavor that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery, and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery, and its role in the improvement of drug delivery and efficacy.
Chromosome assignment by polymerase chain reaction techniques: assignment of the oncogene FGF-5 to human chromosome 4. (1990)

We describe a new chromosomal assignment method based on the polymerase chain reaction mediated amplification of target sequences in DNAs from somatic cell hybrids. The new method is faster, much more sensitive and less labor intensive than the standard method of chromosome assignment by Southern hybridization analysis of somatic cell hybrid DNAs. The feasibility of the new approach was demonstrated by verifying the assignment of the previously mapped acidic fibroblast growth factor gene to human chromosome 5. The method was employed to assign the related oncogene, FGF-5, to human chromosome 4.
Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): A trial coordinated by the Eastern Cooperative Oncology Group (2007)

LBA8025 Background: We compared lenalidomide plus high (standard) dose Dex (R+HighD) versus lenalidomide plus low dose Dex (R+LowD) in newly diagnosed MM. Methods: Pts with untreated, symptomatic MM were eligible. Pts in both arms received lenalidomide 25 mg/day PO days 1–21 every 28 days. In addition, pts in the R+HighD arm received Dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the R+LowD arm received Dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The primary null hypothesis was that response rates at 4 months on the 2 arms are equivalent. Planned sample size was 196 eligible pts per arm with one-sided 0.10 Type I and 0.05 Type II error rate. Pre-planned interim analysis is performed by an independent DMC when full information is available on 25%, 50% and 75% of accrual. All analysis were intent to treat. Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to R+HighD, 222 to R+LowD. Arms were well balanced for age, gender, stage, bone lesions, hemoglobin, beta-2 microglobulin, performance status, bone marrow plasma cells, and M protein levels at baseline. Major grade 3 or higher toxicities included thromboembolism (22.1% with R+HighD vs 6.1% in R+LowD), infection/pneumonia (15.7% vs 7.5%) and hyperglycemia (9.7% vs 6.6%). Grade 3 or higher non-hematologic toxicities occurred in 65.9% (R+HighD) versus 54.9% (R+LowD) respectively; corresponding grade 4 or higher rates were 20.3% vs 13.1% respectively. Overall survival (OS) at first interim analysis was significantly superior with R+LowD, P&lt;0.001; one year survival 96.5% (R+LowD) versus 86% (Rev+HighD). OS differences in favor of R+LowD were seen in pts &lt;65 (P=0.015; one year rate 98% vs 90%) and pts 65 and older (P=0.004; one year rate 95% vs 83%), respectively. DMC recommended release of survival results, and recommended switching all pts to R+LowD. DMC also recommended closure of an expansion phase trial of R+HighD investigating optimal thromboprophylaxis. Conclusions: Lenalidomide plus low-dose dexamethasone is associated with superior OS compared to lenalidomide plus high-dose dexamethasone. This study has major implications for future use of high-dose dexamethasone in the treatment of MM. No significant financial relationships to disclose.
Identification and functional validation of PNAs that inhibit murine CD40 expression by redirection of splicing (2004)

Cognate recognition between the CD40 receptor and its ligand, CD154, is thought to play a central role in the initiation and propagation of immune responses. We describe the specific down regulation of cell surface associated CD40 protein expression by use of a peptide nucleic acid (PNA) antisense inhibitor, ISIS 208529, that is designed to bind to the 3' end of the exon 6 splice junction within the primary CD40 transcript. Binding of ISIS 208529 was found to alter constitutive splicing, leading to the accumulation of a transcript lacking exon 6. The resulting protein product lacks the transmembrane domain. ISIS 208529-mediated CD40 protein depletion was found to be sequence specific and dose dependent, and was dependent on the length of the PNA oligomer. CD40-dependent induction of IL-12 in primary murine macrophages was attenuated in cells treated with ISIS 208529. Oligolysine conjugation to the PNA inhibitor produced an inhibitor, ISIS 278647, which maintained its specificity and displayed efficacy in BCL1 cells and in primary murine macrophages in the absence of delivery agents. These results demonstrate that PNA oligomers can be effective inhibitors of CD40 expression and hence may be useful as novel immuno-modulatory agents.
Public policies in the pharmaceutical sector : a case study of Brazil (2000)

This discussion paper provides an overview of pharmaceutical sector trends in Brazil. It focuses on three key areas in the pharmaceutical sector: supply and distribution, financing, and institutional capacity. The report concludes that focusing on: a) strengthening the enforcement of drug regulations and b) building public procurement capacity could improve the availability of cost-effective and appropriate quality drug supplies for the poorest members of the population. Public-private partnerships in pharmaceuticals could contribute to greater effectiveness in both sectors. This report was based on consultations with stakeholders in Brazil and Washington from September 1998-March 1999, as well as on policy documents and legislation relevant to the pharmaceutical sector.
Rateless Codes for MIMO Channels (2008)

Two rateless code constructions are developed for efficient communication over multi-input multi-output (MIMO) Gaussian channels. The key ingredients in both architectures are layering, dithering, and repetition. Both employ successive cancellation decoding along with minimum mean-square error (MMSE) combining and convert the MIMO channel into a scalar channel to which classical Gaussian base codes can be applied. The first construction based on simple layering induces an additive white Gaussian noise (AWGN) scalar channel and with perfect base codes achieves a substantial efficiency gain over a baseline repetition scheme. At typical spectral efficiencies, this scheme can achieve better than 85% of capacity for a rateless construction with two effective rates. The second construction which uses a diagonal layering (DL) structure is capacity achieving at any SNR and induces a particular time-varying scalar channel. This holds even if the MIMO channel is block constant but time-varying.
Histone Deacetylase Inhibitors: From Bench to Clinic (2008)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Histone Deacetylase Inhibitors: From Bench to ClinicMarielle Paris, Marina Porcelloni, Monica Binaschi, and Daniela Fattori*View Author Information Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia, Rome, Italy* To whom correspondence should be addressed. Phone: +39 06 91184522 . Fax: +39 06 9106137. E-mail: [email protected]Cite this: J. Med. Chem. 2008, 51, 6, 1505–1529Publication Date (Web):February 5, 2008Publication History Received12 September 2007Published online5 February 2008Published inissue 1 March 2008https://pubs.acs.org/doi/10.1021/jm7011408https://doi.org/10.1021/jm7011408review-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views5436Altmetric-Citations332LEARN 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 SUBJECTS:Cells,Inhibition,Inhibitors,Peptides and proteins,Reaction products Get e-Alerts
The effect of ambulatory lumbar traction combined with treadmill on patients with chronic low back pain (2006)

A prospective randomized study was conducted comparing vertical ambulatory traction in 41 patients (group 1) to 35 patients treated by the same traction device combined with daily walking for 12 days and than 8 more sessions on alternating days (grou
Plant behavioural ecology: dynamic plasticity in secondary metabolites (2008)

Behaviour is in part the ability to respond rapidly and reversibly in response to environmental stimuli during the lifetime of an individual. Plants and animals both exhibit behaviour, but plant behaviour is most often examined in the context of morphologically plastic growth. Rapid and reversible secondary metabolite production and release is also a key mechanism by which plants behave. Here, we review plant biochemical plasticity as plant behaviour, and explicitly focus on evidence for responses that display rapid induction, reversibility and ecological relevance. Rapid induction and attenuation of plant secondary metabolites occur as chemically mediated root foraging, plant defence, allelochemistry and to regulate mutualistic relationships. We describe a wealth of information on the induction of various plant biochemical responses to environmental stimuli but found a limited body of literature on the reversibility of induced biochemical responses. Understanding the full cycle of dynamic plasticity in secondary metabolites is an important niche for future research. Biochemical behaviours extend beyond the plant kingdom; however, they clearly illustrate the capacity for plants to behave in ways that closely mirror the classic definitions and research approaches applied to behaviour in animals.
Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. (1996)

The restriction of phosphatidylserine (PtdSer) to the inner surface of the plasma membrane bilayer is lost early during apoptosis. Since PtdSer is a potent surface procoagulant, and since there is an increased incidence of coagulation events in patients with systemic lupus erythematosus (SLE) who have anti-phospholipid antibodies, we addressed whether apoptotic cells are procoagulant and whether anti-phospholipid antibodies influence this. Apoptotic HeLa cells, human endothelial cells, and a murine pre-B-cell line were markedly procoagulant in a modified Russell viper venom assay. This procoagulant effect was entirely abolished by addition of the PtdSer-binding protein, annexin V, confirming that it was PtdSer-dependent. The procoagulant effect was also abolished by addition of IgG purified from the plasma of three patients with anti-phospholipid antibody syndrome, but not IgG from normal controls. Confocal microscopy of apoptotic cells stained with fluorescein-isothiocyanate-conjugated-annexin V demonstrated (Ca2+)-dependent binding to the surface of membrane blebs o apoptotic cells, but not to intracellular membranes. Recent data indicate that the surface blebs of apoptotic cells constitute an important immunogenic particle in SLE. We propose that the PtdSer exposed on the outside of these blebs can induce the production of anti-phospholipid antibodies, which might also enhance the immunogenicity of the bleb contents. When apoptosis occurs in a microenvironment in direct contact with circulating plasma, the unique procoagulant consequences of the apoptotic surface may additionally be expressed. This might explain the increased incidence of pathological intravascular coagulation events that occur in some lupus patients who have anti-phospholipid antibodies.
Positive and negative cis-acting regulatory elements mediate expression of the mouse vascular smooth muscle alpha-actin gene. (1992)

Segments of the 5'-flanking region of the mouse vascular smooth muscle alpha-actin gene were assayed for promoter activity in transfected mouse BC3H1 myogenic cells and AKR-2B embryonic fibroblasts. The region between -150 and -191 that functions as a positive transcriptional element in myogenic and fibroblastic cells contains a mammalian-specific inverted CC(A/T)6GG-type consensus sequence. Expression was restricted to fully differentiated myogenic cells when an additional sequence spanning -191 to -224 was included in reporter gene constructs. This 33-base pair (bp) negative regulatory element is 70% conserved between the mouse and human genes and contains a 10-bp motif at its 3' end that only partially resembles a CC(A/T)6GG element. Retention of a GGGA motif at the 3' boundary of the 33-bp region is sufficient to maintain full transcriptional repression in fibroblasts and is partly responsible for repression in undifferentiated myoblasts. Complete muscle tissue-restrictive expression requires an additional 8 bp from the CC(A/T)6GG-like element immediately 5' to the GGGA motif, since replacement of this region with an unrelated 10-bp sequence completely eliminated restrictive transcriptional behavior in undifferentiated myoblasts. The distal portion of the 5'-flanking region between -224 and -1074 contains six E-box motifs (CANNTG) and mediates high level transcription only in postconfluent BC3H1 myoblasts. Analysis of reporter gene constructs including either the proximal E-box at -240 or all six E-boxes indicate that the five distal E-boxes are not required for high level transcription. A 724-bp segment of the 5'-flanking region consisting of the proximal E-box flanked upstream by a mammalian-specific 352-bp region was sufficient for maximal transcriptional activation in postconfluent BC3H1 myoblasts. Deletion of the 352-bp region restricts the early transcriptional response to high cell density in temporal studies of promoter activity during BC3H1 myogenic cell differentiation.
Generation of Polymerosomes from Double-Emulsions (2005)

Diblock copolymers are known to spontaneously organize into polymer vesicles. Typically, this is achieved through the techniques of film rehydration or electroformation. We present a new method for generating polymer vesicles from double emulsions. We generate precision water-in-oil-in-water double emulsions from the breakup of concentric fluid streams; the hydrophobic fluid is a volatile mixture of organic solvent that contains dissolved diblock copolymers. We collect the double emulsions and slowly evaporate the organic solvent, which ultimately directs the self-assembly of the dissolved diblock copolymers into vesicular structures. Independent control over all three fluid streams enables precision assembly of polymer vesicles and provides for highly efficient encapsulation of active ingredients within the polymerosomes. We also use double emulsions with several internal drops to form new polymerosome structures.
Large electrodeless plasmas at atmospheric pressure sustained by a microwave waveguide (2002)

A 1.5-kW 2.45-GHz magnetron source has been used to reliably sustain large electrodeless plasmas at atmospheric pressure in a shorted waveguide without a resonator. Working gases have been air, nitrogen, and heated off gases of sulfur containing ores and coal in nitrogen. Various colorful plasmas of value to environmental monitoring and processing applications are generated depending on the composition of the working gas.
Simultaneous Suppression of Multiple Genes by Single Transgenes. Down-Regulation of Three Unrelated Lignin Biosynthetic Genes in Tobacco (2002)

Many reports now describe the manipulation of plant metabolism by suppressing the expression of single genes. The potential of such work could be greatly expanded if multiple genes could be coordinately suppressed. In the work presented here, we test a novel method for achieving this by using single chimeric constructs incorporating partial sense sequences for multiple genes to target suppression of two or three lignin biosynthetic enzymes. We compare this method with a more conventional approach to achieving the same end by crossing plants harboring different antisense transgenes. Our results indicate that crossing antisense plants is less straightforward and predictable in outcome than anticipated. Most progeny had higher levels of target enzyme activity than predicted and had lost the expected modifications to lignin structure. In comparison, plants transformed with the chimeric partial sense constructs had more consistent high level suppression of target enzymes and had significant changes to lignin content, structure, and composition. It was possible to suppress three target genes coordinately using a single chimeric construct. Our results indicate that chimeric silencing constructs offer great potential for the rapid and coordinate suppression of multiple genes on diverse biochemical pathways and that the technique therefore deserves to be adopted by other researchers.