gebhart/patrepeval huggingface dataset:
BAX 855, a PEGylated rFVIII product with prolonged half-life. Development, functional and structural characterisation. (2012)

A longer acting recombinant FVIII is expected to serve patients' demand for a more convenient prophylactic therapy. We have developed BAX 855, a PEGylated form of Baxter's rFVIII product ADVATE™ based on the ADVATE™ manufacturing process. The conjugation process for preparing BAX 855 uses a novel PEG reagent. The production process was adjusted to yield a rFVIII conjugate with a low PEGylation degree of about 2 moles PEG per FVIII molecule. This optimised modification degree resulted in an improved PK profile for rFVIII without compromising its specific activity. PEGylation sites were identified by employing various HPLC- and MS-based methods. These studies not only indicated that about 60% of the PEG chains are localised to the B-domain, which is cleaved off upon physiological activation during the coagulation process, but also demonstrated an excellent lot to lot consistency with regard to PEGylation site distribution. Detailed biochemical characterization further showed that PEGylated FVIII retained all the physiological functions of the FVIII molecule with the exception of binding to the LRP clearance receptor which was reduced for BAX 855 compared to ADVATE™. This might provide an explanation for the prolonged circulation time of BAX 855 as reduced receptor binding might slow-down clearance. Preclinical studies showed improved pharmacokinetic behaviour and clinically relevant prolonged efficacy compared to ADVATE™ without any signs of toxicity or elevated immunogenicity. The comprehensive preclinical data package formed the basis for approval of the phase 1 clinical study by European authorities which started in 2011.
A G-Box-Binding Protein from Soybean Binds to the E1 Auxin-Response Element in the Soybean GH3 Promoter and Contains a Proline-Rich Repression Domain (1997)

The E1 promoter fragment (-249 to -203) is one of three auxin-response elements (AuxREs) in the soybean (Glycine max L.) GH3 promoter (Z.-B. Liu, T. Ulmasov, X. Shi, G. Hagen, T.J. Guilfoyle [1994] Plant Cell 6: 645-657). Results presented here further characterize and delimit the AuxRE within the E1 fragment. The E1 fragment functioned as an AuxRE in transgenic tobacco (Nicotiana tabacum L.) plants, as well as in transfected protoplasts. The AuxRE within E1 contains a G-box, and this G-box was used to clone a G-box-binding factor (GBF) from soybean (SGBF-2). This 45-kD GBF contains an N-terminal proline-rich domain and a C-terminal basic/leucine zipper DNA-binding domain. Gel-mobility shift assays were used to characterize the binding specificity of SGBF-2. Antiserum raised against recombinant SGBF-2 was used to further characterize SGBF-2 and antigenically related GBFs in soybean nuclear extracts. Co-transfection assays with effector and reporter plasmids in carrot (Daucus carota L.) protoplasts indicated that the N-terminal proline-rich domain of SGBF-2 functioned as a repression domain in both basal and auxin-inducible transcription.
Antimicrobial hydrogels for the treatment of infection (2013)

The increasing prevalence of microbial infections, especially those associated with impaired wound healing and biomedical implant failure has spurred the development of new materials having antimicrobial activity. Hydrogels are a class of highly hydrated material finding use in diverse medical applications such as drug delivery, tissue engineering, as wound fillers, and as implant coatings, to name a few. The biocompatible nature of many gels make them a convenient starting platform to develop selectively active antimicrobial materials. Hydrogels with antimicrobial properties can be obtained through the encapsulation or covalent immobilization of known antimicrobial agents, or the material itself can be designed to possess inherent antimicrobial activity. In this review we present an overview of antimicrobial hydrogels that have recently been developed and when possible provide a discussion relevant to their mechanism of action.
Synthesis of therapeutically useful prostaglandin and prostacyclin analogs (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of therapeutically useful prostaglandin and prostacyclin analogsPaul W. Collins and Stevan W. DjuricCite this: Chem. Rev. 1993, 93, 4, 1533–1564Publication Date (Print):June 1, 1993Publication History Published online1 May 2002Published inissue 1 June 1993https://pubs.acs.org/doi/10.1021/cr00020a007https://doi.org/10.1021/cr00020a007research-articleACS PublicationsRequest reuse permissionsArticle Views2432Altmetric-Citations284LEARN 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
An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens (2006)

Algorithms for grading acute graft-versus-host disease (GVHD) are inaccurate in assessing mortality risk. We developed a method to predict mortality by using data from 386 patients with acute GVHD. From the onset of GVHD to day 100, GVHD manifestations were scored for the skin, liver, and upper and lower gastrointestinal tract, and data were recorded for immunosuppressive treatment, performance, and fever. Logistic regression models predicting nonrelapse mortality (NRM) at day 200 were developed with data from 193 randomly selected patients and then validated in the remaining 193 patients. Clinical parameters were grouped to optimize predictive accuracy measured as the area under a receiver-operator characteristic (ROC) curve. The optimal model included the total serum bilirubin concentration, oral intake, need for treatment with prednisone, and performance score. When the overall burden of GVHD was measured by using average Acute GVHD Activity Index (aGVHDAI) scores for each patient in training and validation data sets, areas under ROC curves were 0.87 and 0.85, respectively. Contour lines were generated to reflect the predicted NRM at day 200 as a function of current aGVHDAI scores. These results demonstrate that clinical manifestations of GVHD severity can be used to accurately predict the risk of NRM in real time.
Sequence‐Specific DNA Detection Using High‐Affinity LNA‐Functionalized Gold Nanoparticles (2007)

Lock and load: The functionalization of gold nanoparticles with locked nucleic acid (LNA; see image) is reported. These nanoconjugate probes offer immense stability and selectivity towards complementary DNA, allowing the detection of specific DNA sequences.
Closure and Repropagation of Healed Cracks in Silicate Glass (1985)

Cracks in soda‐lime‐silica and vitreous silica glass close against a finite load at humidities between 0.01 % and 100%. The force associated with crack closure (0.15 J/m 2 ) can be predicted by a model which involves hydrogen‐bonded linkages of surface‐adsorbed water molecules. The fracture energy to reopen healed cracks in vitreous silica is also in the range of hydrogen‐bonding interactions. In the driest environments used, healed cracks in soda‐lime‐silica glass required 1.7 ± 0.2 J/m 2 to reopen. This bonding energy can be attributed to the formation of either cationic bridges or siloxane bonds between fracture surfaces. Since crack healing was observed to be independent of the number of cycles, a cationic bridging model is favored to explain healing effects at room temperature.
The 5' and 3' non-coding sequences of the c-myc gene, required in vitro for its post-transcriptional regulation, are dispensable in vivo. (1993)

We have previously shown that in vivo the steady-state level of c-myc mRNA in different quiescent organs and its induction in the early stages of hepatic regeneration and after inhibition of protein synthesis are mainly controlled by post-transcriptional mechanisms. In order to localize the target sequences for these mechanisms, transgenic lines expressing various versions of the human c-myc proto-oncogene have been constructed. To avoid all possible transcriptional controls due to the c-myc 5' regulatory region, the c-myc genomic sequences were fused to MHC H-2Kb class I regulatory sequences, which have previously been shown to be able to drive reporter gene expression in most adult tissues. The transgenes contained either all human c-myc genomic sequences or were deleted for one of the sequences which have been shown in in vitro experiments to play a role in c-myc mRNA stabilization, in particular exon 1, intron 1 and the 3' non-coding region. Several independent transgenic lines were derived for each construct. Using S1 nuclease protection analysis, we have monitored H-2K, mouse c-myc and transgene mRNA expression in several quiescent adult organs, at the start of liver regeneration and after inhibition of protein synthesis in each transgenic line. Our results indicate that the 5' non-coding sequences, including exon 1 and intron 1, and the 3' untranslated region are all dispensable in the different aspects of c-myc post-transcriptional regulation.
Energy-efficient Autonomous Four-rotor Flying Robot Controlled at 1 kHz (2007)

We describe an efficient, reliable, and robust four-rotor flying platform for indoor and outdoor navigation. Currently, similar platforms are controlled at low frequencies due to hardware and software limitations. This causes uncertainty in position control and unstable behavior during fast maneuvers. Our flying platform offers a 1 kHz control frequency and motor update rate, in combination with powerful brushless DC motors in a light-weight package. Following a minimalistic design approach this system is based on a small number of low-cost components. Its robust performance is achieved by using simple but reliable highly optimized algorithms. The robot is small, light, and can carry payloads of up to 350g
Representation of Uncertainty in Computer Vision Using Fuzzy Sets (1986)

Uncertainty in computer vision can arise at various levels. It can occur in the low level in the raw sensor input, and extends all the way through intermediate and higher levels. Ideally, at any level where decisions are being made on the basis of previous processing steps, a computer vision system must have sufficient flexibility for representation of uncertainty in any of these levels.
Pharmacokinetics and first clinical experiences with an antihypertensive dopamine (DA2) agonist (1992)

The pharmacokinetic properties and first clinical experiences with the antihypertensive dopamine (DA2) agonist, carmoxirole, are summarized. In man carmoxirole was rapidly absorbed. On oral administration the maximum plasma concentration was reached after 2-3 h. The drug was metabolized, mainly to an ester-type glucuronide, and was excreted (unchanged carmoxirole plus glucuronide) largely by the kidneys. The plasma half-life of the parent compound was 5.5 h. For the dose range tested (0.5 to 1.5 mg) the pharmacokinetics were linear. The drug was rapidly distributed in animals but only very small amounts penetrated the blood-brain barrier. Carmoxirole did not affect supine blood pressure in healthy subjects, but under the conditions of the Schellong's test some orthostatic reactions occurred with high doses. In patients the blood pressure was reduced for at least 8 h after single oral doses. On repeated administration for several weeks a relevant antihypertensive effect was still measurable 12 and 24 h after dose. The most frequently reported adverse events have been headache, dizziness, tiredness, nausea, and gastric disorders. These symptoms are considered to be mainly due to blood pressure reduction, as is frequently observed at the beginning of antihypertensive therapy. In patients the incidence of orthostatic reactions is appreciably lower than in healthy subjects, and in both change of position was sufficient to relieve the symptoms.
Ribozyme Oligonucleotides Against Transforming Growth Factor-β Inhibited Neointimal Formation After Vascular Injury in Rat Model (2000)

Overall, this study provides the first evidence that selective blockade of TGF-beta resulted in inhibition of neointimal formation, accompanied by a reduction in collagen synthesis and DNA synthesis in a rat model. We anticipate that modification of ribozyme ON pharmacokinetics will facilitate the potential clinical utility of the ribozyme strategy.
Commercialization of microfluidic point-of-care diagnostic devices (2012)

A large part of the excitement behind microfluidics is in its potential for producing practical devices, but surprisingly few lab-on-a-chip based technologies have been successfully introduced into the market. Here, we review current work in commercializing microfluidic technologies, with a focus on point-of-care diagnostics applications. We will also identify challenges to commercialization, including lessons drawn from our experience in Claros Diagnostics. Moving forward, we discuss the need to strike a balance between achieving real-world impact with integrated devices versus design of novel single microfluidic components.
Considerations in the assessment of heart rate variability in biobehavioral research (2014)

Heart rate variability (HRV) refers to various methods of assessing the beat-to-beat variation in the heart over time, in order to draw inference on the outflow of the autonomic nervous system. Easy access to measuring HRV has led to a plethora of studies within emotion science and psychology assessing autonomic regulation, but significant caveats exist due to the complicated nature of HRV. Firstly, both breathing and blood pressure regulation have their own relationship to social, emotional, and cognitive experiments - if this is the case are we observing heart rate (HR) changes as a consequence of breathing changes? Secondly, experiments often have poor internal and external controls. In this review we highlight the interrelationships between HR and respiration, as well as presenting recommendations for researchers to use when collecting data for HRV assessment. Namely, we highlight the superior utility of within-subjects designs along with the importance of establishing an appropriate baseline and monitoring respiration.
Effects of the Adenosine A1-Receptor Antagonist on Defecation, Small Intestinal Propulsion and Gastric Emptying in Rats (1995)

We examined the effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and (R)-7,8-dihydro-8-ethyl-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1 -i]purin- 5(4H)-one (KF20274), selective adenosine A1-receptor antagonists, on the gastrointestinal propulsion in rats, as compared with those of the laxative bisacodyl. DPCPX and KF20274 (p.o.) dose-dependently increased the fecal pellet output, whereas these drugs at the dose that increased defecation did not affect small intestinal propulsion or gastric emptying. Bisacodyl increased defecation and slowed gastric emptying without any influence on small intestinal propulsion. Bisacodyl, but not DPCPX or KF20274, induced diarrhea at the dose inducing defecation. The present results suggest that the adenosine A1-receptor antagonist selectively enhances the lower gastrointestinal propulsion, resulting in defecation without diarrhea.
The Notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell‐derived embryoid bodies independently of sonic hedgehog signaling (2007)

During development of the neural tube, inhibition of the Notch response as well as the activation of the Sonic Hedgehog (Shh) response results in the formation of neuronal cell types. To determine whether Shh and Notch act independently, we tested the effects of the Notch inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) on neuralized, embryonic stem (ES) cell-derived embryoid bodies (EBs), while varying the levels of Shh pathway activation. Shh-resistant EBs were derived from Smo null ES cells, while EBs with constitutive high level of Shh pathway activation were derived from Ptc1 null ES cells. Intermediate levels of Shh pathway activation was achieved by the addition of ShhN to the EB culture medium. It was found that DAPT-mediated inhibition of the Notch response resulted in enhanced neuronal differentiation. In the absence of Shh, more interneurons were detected, while the main effect of DAPT on EBs with an activated Shh response was the precocious loss of ventral neuronal precursor-specific markers.
The impact of nutritional supplementation on quality of life in patients infected with hepatitis C virus (2013)

Nutritional therapy with either soybean or casein supplementation improved quality of life in patients infected with HCV. Quality of life was influenced by anthropometric, biochemical, clinical and sociodemographic factors in patients with HCV before nutritional supplementation.
Priming for a Cytotoxic Response to Minor Histocompatibility Antigens: Antigen Specificity and Failure to Demonstrate a Carrier Effect (1977)

Spleen cells from normal mice do not give a detectable in vitro cytotoxic T cell (CTL) response to minor H antigens. Spleen cells from animals primed in vivo with minor H antigens give a strong CTL response when boosted in culture with the appropriate stimulating cells. Here I have studied the requirements for priming a CTL response to minor H antigens. It is shown that priming is just as antigen specific as is cytolytic effector function. That is, priming cells have to carry the same minor antigens as the challenge cells. Inducing a graft-vs-host reaction in vivo does not nonspecifically allow spleen cells to respond to minor H antigens in vitro. Using minor H congenic mice (congenic for H-Y and/or H-7) I have also tried, and failed, to demonstrate a carrier effect in priming. Female mice primed to H-Y were challenged in culture with cells bearing H-Y and H-7 antigens in the hope that a helper response to H-Y would augment a CTL response to H-7. This did not happen, however. Such primed and boosted cells gave a strong secondary CTL response to H-Y but none to H-7. It is concluded that in order to prime for a detectable in vitro response to minor antigens it is necessary to expose the CTL precursors to antigen in vivo. This either expands the size of the pool of precursors by cell division or changes them in some qualitative way.
Ultrahigh-Water-Content Supramolecular Hydrogels Exhibiting Multistimuli Responsiveness (2012)

Hydrogels are three-dimensional networked materials that are similar to soft biological tissues and have highly variable mechanical properties, making them increasingly important in a variety of biomedical and industrial applications. Herein we report the preparation of extremely high water content hydrogels (up to 99.7% water by weight) driven by strong host-guest complexation with cucurbit[8]uril (CB[8]). Cellulosic derivatives and commodity polymers such as poly(vinyl alcohol) were modified with strongly binding guests for CB[8] ternary complex formation (K(eq) = 10(12) M(-2)). When these polymers were mixed in the presence of CB[8], whereby the overall solid content was 90% cellulosic, a lightly colored, transparent hydrogel was formed instantaneously. The supramolecular nature of these hydrogels affords them with highly tunable mechanical properties, and the dynamics of the CB[8] ternary complex cross-links allows for rapid self-healing of the materials after damage caused by deformation. Moreover, these hydrogels display responsivity to a multitude of external stimuli, including temperature, chemical potential, and competing guests. These materials are easily processed, and the simplicity of their preparation, their availability from inexpensive renewable resources, and the tunability of their properties are distinguishing features for many important water-based applications.
Prevalence and Comorbidity of Sexual Dysfunctions in a Portuguese Clinical Sample (2006)

We investigated the prevalence and comorbidity of sexual dysfunction in a clinical Portuguese sample. A total of 96 participants (47 females and 49 males with a diagnosis of sexual dysfunction (DSM-IV; American Psychological Association, 1994) assigned by a group of trained sex therapists) answered the Female Sexual Function Index (FSFI; Rosen et al., 2000) and the International Index of Erectile Function (IIEF; Rosen et al., 1997). Results indicated erectile dysfunction (70%) and female hypoactive sexual desire disorders (40.4%) as the most prevalent complaints, with premature ejaculation (22.4%), vaginismus (25.5%), and female orgasmic disorder (21.3%) also showing relevant prevalences. Comorbidity studies indicated higher levels of overlapping among female sexual difficulties with strong associations between desire, subjective arousal, and orgasmic disorders, as well as between dyspareunia and vaginismus.
The entire nucleotide sequence and classification of a hepatitis C virus isolate of a novel genotype from an Indonesian patient with chronic liver disease (1994)

Three hepatitis C virus (HCV) isolates were obtained from patients with chronic liver diseases in Indonesia which were not classifiable into any of the genotypes I/1a, II/1b, III/2a, IV/2b or V/3a reported previously. The entire nucleotide sequence was determined for one HCV isolate (HC-G9); the remaining two isolates were of the same genotype based on a > 95% similarity within their partial sequences spanning 2927 nucleotides (nt). The HC-G9 genome consisted of 9440 nt including the 5' untranslated region of 341 nt, an open reading frame of 9033 nt coding for a polyprotein of 3011 amino acids and the 3' untranslated region of 66 nt (U stretch of 17 to 47 nt at the extreme 3' terminus excluded). It differed by 20 to 33% in nucleotide sequence from any of 14 HCV genomes of genotypes I/1a to IV/2b whose full-length sequences are known. By the unweighted pair-group method with arithmetic mean, HC-G9 was on a major branch (group 1) of the phylogenetic tree of HCV to which genotypes I/1a and II/1b belong. It is proposed, therefore, that the novel genotype for HC-G9 should be called 1c. A method was developed to identify genotype 1c by PCR with a primer deduced from the core gene that was specific to it. Since genotype 1c was detected in seven (15%) of 48 HCV RNA samples from Indonesian patients with chronic liver disease, but not in any of 1097 from other districts of the world, it appears to have evolved and remained in Indonesia. In addition to its epidemiological importance, the association of genotype 1c HCV with the severity of liver disease and its response to interferons deserve to be evaluated.
Synthesis of sulfonyl and sulfenyl derivatives of pyridine and 1,2,4-triazole (2006)

The corresponding sulfonamides and sulfenamides were synthesized from 5-methyl-4-phenyl-4H-1,2,4-triazole-3-thiol and 6-tert-butyl-3-cyano-4-phenylpyridine-2-thiol.
Randomized Clinical Trial of Therapeutic Exercise in Subacute Stroke (2003)

This structured, progressive program of therapeutic exercise in persons who had completed acute rehabilitation services produced gains in endurance, balance, and mobility beyond those attributable to spontaneous recovery and usual care.