gebhart/patrepeval huggingface dataset:
Rational Design of a Multiepitope Vaccine Encoding T-Lymphocyte Epitopes for Treatment of Chronic Hepatitis B Virus Infections (2007)

Protein sequences from multiple hepatitis B virus (HBV) isolates were analyzed for the presence of amino acid motifs characteristic of cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes with the goal of identifying conserved epitopes suitable for use in a therapeutic vaccine. Specifically, sequences bearing HLA-A1, -A2, -A3, -A24, -B7, and -DR supertype binding motifs were identified, synthesized as peptides, and tested for binding to soluble HLA. The immunogenicity of peptides that bound with moderate to high affinity subsequently was assessed using HLA transgenic mice (CTL) and HLA cross-reacting H-2(bxd) (BALB/c x C57BL/6J) mice (HTL). Through this process, 30 CTL and 16 HTL epitopes were selected as a set that would be the most useful for vaccine design, based on epitope conservation among HBV sequences and HLA-based predicted population coverage in diverse ethnic groups. A plasmid DNA-based vaccine encoding the epitopes as a single gene product, with each epitope separated by spacer residues to enhance appropriate epitope processing, was designed. Immunogenicity testing in mice demonstrated the induction of multiple CTL and HTL responses. Furthermore, as a complementary approach, mass spectrometry allowed the identification of correctly processed and major histocompatibility complex-presented epitopes from human cells transfected with the DNA plasmid. A heterologous prime-boost immunization with the plasmid DNA and a recombinant MVA gave further enhancement of the immune responses. Thus, a multiepitope therapeutic vaccine candidate capable of stimulating those cellular immune responses thought to be essential for controlling and clearing HBV infection was successfully designed and evaluated in vitro and in HLA transgenic mice.
Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation (2013)

Australian NZ Clinical Trials Registry (ACTRN12610000866000).
A molecular and genetic outline of cardiac morphogenesis (2013)

Perturbations in cardiac development result in congenital heart disease, the leading cause of birth defect-related infant morbidity and mortality. Advances in cardiac developmental biology have significantly augmented our understanding of signalling pathways and transcriptional networks underlying heart formation. Cardiogenesis is initiated with the formation of mesodermal multipotent cardiac progenitor cells and is governed by cross-talk between developmental cues emanating from endodermal, mesodermal and ectodermal cells. The molecular and transcriptional machineries that direct the specification and differentiation of these cardiac precursors are part of an evolutionarily conserved programme that includes the Nkx-, Gata-, Hand-, T-box- and Mef2 family of transcription factors. Unravelling the hierarchical networks governing the fate and differentiation of cardiac precursors is crucial for our understanding of congenital heart disease and future stem cell-based and gene therapies. Recent molecular and genetic lineage analyses have revealed that subpopulations of cardiac progenitor cells follow distinctive specification and differentiation paths, which determine their final contribution to the heart. In the last decade, progenitor cells that contribute to the arterial pole and right ventricle have received much attention, as abnormal development of these cells frequently results in congenital defects of the aortic and pulmonary outlets, representing the most commonly occurring congenital cardiac defects. In this review, we provide an overview of the building plan of the vertebrate four-chambered heart, with a special focus on cardiac progenitor cell specification, differentiation and deployment during arterial pole development.
Mechanical Properties and Biocompatibility of in Situ Enzymatically Cross-Linked Gelatin Hydrogels (2017)

Overall, transglutaminase cross-linked gelatin hydrogels might be suitable as injectable hydrogels for the engineering of musculoskeletal and other types of connective tissues.
Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma. (1998)

Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.
Giant cell arteritis: Current treatment and management (2015)

Glucocorticoids remain the cornerstone of medical therapy in giant cell arteritis (GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Imaging techniques (e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with large-vessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.
Interim results from ASCENT: A double-blinded randomized study of DN-101 (high-dose calcitriol) plus docetaxel vs. placebo plus docetaxel in androgen-independent prostate cancer (AIPC) (2005)

4516 Background: High doses of calcitriol enhance the antitumor activity of multiple classes of chemotherapy in preclinical models and showed encouraging Phase 2 results in combination with docetaxel for AIPC. DN-101 is a new high-dose oral formulation designed to conveniently and reliably deliver the high calcitriol concentrations required for cancer therapy. Methods: Patients (pts) had metastatic AIPC, testosterone < 50 ng/ml, adequate organ function, clinical or PSA progression after anti-androgen withdrawal. Pts received weekly docetaxel 36 mg/m2 iv for 3 weeks of a 4-week cycle with standard dexamethasone and either 45 μg DN-101 or placebo orally 1 day prior to docetaxel. The study was powered at 85% to detect a 20% improvement in the fraction of patients with a ≥ 50% decline in serum PSA confirmed at least 4 weeks later (PSA response rate). Results: An interim analysis with a data cut-off of 6 months (June 2004) and median follow-up of 8 months is presented. 250 pts were randomized 1:1 at 48 sites in the US and Canada. Baseline characteristics were similar for both arms. PSA responses within 6 months (the primary endpoint) occurred more frequently in pts receiving DN-101 (58%) than placebo (49%), however this trend did not reach statistical significance (Cochran-Mantel-Haenszel chi square p=0.16). 102 patients had measurable disease. Objective response rate was 28% (3 CR, 10 PR of 46) vs. 20% (1 CR, 10 PR of 56) for DN-101 vs. placebo-treated patients. Most common grade 3/4 toxicities in the DN-101 and placebo-treated arms were neutropenia (8% vs. 8%), fatigue (7% vs. 15%), and hyperglycemia (6% vs. 11%). Serious adverse events occurred less frequently in DN-101 treated pts (24% vs. 36%, p=0.038). A similar trend was observed for AEs resulting in discontinuation of docetaxel (14% vs. 22% p=0.07). Conclusions: Early results show trends that favor DN-101 with respect to PSA and measurable tumor response rate and toxicity but do not reach statistical significance. Recommendations regarding further studies of DN-101 and docetaxel in AIPC will be made when the secondary endpoints of overall and progression-free survival are mature. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novacea Aventis, Novacea Aventis, Aventis Speakers Bureau, Novacea Novacea
Glycosyl Trifluoroacetimidates. 2. Synthesis of Dioscin and Xiebai Saponin I (2002)

Two trisaccharide steroidal saponins, dioscin (1) and Xiebai saponin I (2) with various bioactivities, were efficiently synthesized using the newly developed glycosyl N-phenyl trifluoroacetimidates (10-13) as glycosylation donors. Thus, dioscin was synthesized in five steps and a 33% overall yield from diosgenin and glycosyl trifluoroacetimidates (10 and 11). Xiebai saponin I was synthesized in eight steps and a 32% overall yield from laxogenin and glycosyl trifluoroacetimidates (10, 12, and 13), whereupon, the rare steroid laxogenin was prepared from diosgenin in four steps and an overall 69% yield. All the glycosylation reactions involved in the present syntheses demonstrated that glycosyl trifluoroacetimidates were successful donors comparable to the corresponding glycosyl trichloroacetimidates.
A Probiotic Strain of L. Acidophilus Reduces DMH-Induced Large Intestinal Tumors in Male Sprague-Dawley Rats (1999)

Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p < 0.05). Other treatments showed no statistically significant change from control for these indexes of tumorigenesis. For rats fed L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.
Premature centromere division: A mechanism of non‐disjunction causing X chromosome aneuploidy in somatic cells of man (1975)

Apparent acentric fragments which replaced a C-group chromosome in cultured blood lymphocytes from a woman patient were shown by autoradiography, G-banding and C-banding to be complete X chromosomes in which the centromere had divided prematurely in relation to the centromeres of other chromosomes in the same metaphase. Metaphases with multiple 'fragments' suggested that non-disjunction of the 'fragments' had occurred. This anomaly of the X chromosome was associated with increased aneuploidy of a C-group chromosome, presumed to be X. Premature centromere division of the X chromosome (PCD, X) appeared to be a mechanism of non-disjunction which caused significant monosomy and trisomy of the X chromosome in blood cells and skin fibroblasts. The frequency of cells with multiple fragments and the extent of the aneuploidy in 48 hr. blood cultures indicated that this mechanism of non-disjunction operated during mitosis both in vivo and in vitro. Premature centromere division occurred at a lower frequency in normal women donors, and was age-related, being four times more frequent in women 60 years and older than in women under 40. Associated with the higher frequency of PCD, the older women also showed evidence of increased X chromosome aneuploidy. Premature centromere division of the X chromosome is considered to be the mechanism of non-disjunction, causing the well-documented increased number of 45, -C metaphases in ageing women. Premature centromere division was rare in men, but an age effect was again suggested.
Molecular cloning and expression of the Saccharomyces cerevisiae RFC3 gene, an essential component of replication factor C. (1994)

Yeast replication factor C (RF-C) is a multi-polypeptide complex required for processive DNA replication by DNA polymerases delta and epsilon. The gene encoding the 40-kDa subunit of the Saccharomyces cerevisiae RF-C (RFC3) has been cloned. The RFC3 gene is required for yeast cell growth and has been mapped to the left arm of chromosome XIV. The deduced amino acid sequence of the RFC3 gene shows a high homology to the 36-, 37-, and 40-kDa subunits of human RF-C (also called activator 1), with the highest homology to the 36-kDa subunit. Among the conserved regions are the A motif of ATP binding proteins; the "DEAD box," common to DNA helicases and other ATPases; and the "RFC box," an approximately 15-amino acid domain virtually identical in the yeast and human RF-C subunits. Limited homology to the functional homologs of the Escherichia coli replication apparatus was also observed. The steady-state mRNA levels of RFC3 do not change significantly during the mitotic cell cycle of yeast. The intact form of the RFC3 gene product (Rfc3p) has been overproduced in E. coli and purified to homogeneity. Purified Rfc3p has an ATPase activity that is markedly stimulated by single-stranded DNA but not by double-stranded DNA or RNA.
Crimean-Congo Hemorrhagic Fever Virus Glycoprotein Processing by the Endoprotease SKI-1/S1P Is Critical for Virus Infectivity (2007)

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe human disease. The CCHFV medium RNA encodes a polyprotein which is proteolytically processed to yield the glycoprotein precursors PreGn and PreGc, followed by structural glycoproteins Gn and Gc. Subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P) plays a central role in Gn processing. Here we show that CCHFV-infected cells deficient in SKI-1/S1P produce no infectious virus, although PreGn and PreGc accumulated normally in the Golgi apparatus, the site of virus assembly. Only nucleoprotein-containing particles which lacked virus glycoproteins (Gn/Gc or PreGn/PreGc) were secreted. Complementation of SKI-1/S1P-deficient cells with a SKI-1/S1P expression vector restored release of infectious virus (>10(6) PFU/ml), confirming that SKI-1/S1P processing is required for incorporation of viral glycoproteins. SKI-1/S1P may represent a promising antiviral target.
A Convenient Synthesis of Primary Amines Using Sodium Diformylamide as A Modified Gabriel Reagent (1990)

Sodium diformylamide (1) was used as a convenient substitute for phthalimide in the Gabriel synthesis of primary amines. Reagent 1 undergoes smooth N-alkylation with alkyl halides or p-toluenesulfonates 2 in acetonitrile or dimethylformamide to give the corresponding N,N-diformylalkylamines 3 in good yields, except with alkylating agents which are susceptible to base-catalyzed elimination. The formyl group of 3 can be easily removed by hydrochloric acid to give the corresponding alkylamine hydrochlorides 5 or free alkylamines 4.
The Intracisternal A-Particle Proximal Enhancer-Binding Protein Activates Transcription and Is Identical to the RNA- and DNA-Binding Protein p54 nrb /NonO (1997)

The long terminal repeats of murine intracisternal A particles (IAPs) contain an IAP proximal enhancer (IPE) element that is inactive in murine F9 embryonal carcinoma cells and active in the parietal endoderm cell line PYS-2. The element binds efficiently to a 60-kDa IPE-binding protein (IPEB) present in PYS-2 cells but poorly to F9 proteins, suggesting a role for IPEB in regulating IAP expression. We have purified calf thymus IPEB, which binds to the IPE and transactivates a reporter gene in HeLa cell extracts. Based on the peptide sequence of the purified calf IPEB, we have cloned a 420-bp cDNA and showed that the encoded protein is the homolog of human p54nrb and mouse NonO, which are characterized by the presence of two RNA recognition motifs. We show that p54nrb is an IPE-binding transcription activator with its DNA-binding and activation domains in the N- and C-terminal halves, respectively. The activation domain of p54nrb is active in HeLa, PYS-2, and F9 cells, whereas p54nrb as a whole molecule is active in HeLa and PYS-2 cells but not in F9 cells. Thus, the lack of activity of p54nrb in F9 cells is due to an ineffective DNA-binding domain. We demonstrate that p54nrb also binds to a pre-mRNA. Based on the close sequence relatedness of this protein to PSF, which is required for pre-mRNA splicing in vitro, we discuss the possibility that p54nrb has dual roles in transcription and splicing.
Amino-steroids. Part III. 2- and 3-Amino-5α-androstanes (1968)

Condensation of 2α,3α- and 2β,3β-epoxy-5α-androstanes with secondary cyclic amines gives 2β-amino-3α-ols and 3α-amino-2β-ols respectively; reaction of a 2β-bromo-3α-hydroxy-5α-androstane with the same cyclic amines gives the 2α,3α-epoxide in contrast to the 3α-bromo-2β-hydroxy-isomer, which undergoes substitution without inversion to give the corresponding 3α-amino-2β-ol. The mechanisms of these reactions are discussed. The preparation of 2-morpholino-5α-androst-1-ene-3,17-dione is also described.
piggyBac internal sequences are necessary for efficient transformation of target genomes (2005)

A previously reported piggyBac minimal sequence cartridge, which is capable of efficient transposition in embryo interplasmid transposition assays, failed to produce transformants at a significant frequency in Drosophila melanogaster compared with full-length or less extensive internal deletion constructs. We have re-examined the importance of these internal domain (ID) sequences for germline transformation using a PCR strategy that effectively adds increasing lengths of ID sequences to each terminus. A series of these piggyBac ID synthetic deletion plasmids containing the 3xP3-ECFP marker gene are compared for germline transformation of D. melanogaster. Our analyses identify a minimal sequence configuration that is sufficient for movement of piggyBac vectored sequences from plasmids into the insect genome. Southern hybridizations confirm the presence of the piggyBac transposon sequences, and insertion site analyses confirm these integrations target TTAA sites. The results verify that ID sequences adjacent to the 5' and 3' terminal repeat domains are crucial for effective germline transformation with piggyBac even though they are not required for excision or interplasmid transposition. Using this information we reconstructed an inverted repeat cartridge, ITR1.1k, and a minimal piggyBac transposon vector, pXL-BacII-ECFP, each of which contains these identified ID sequences in addition to the terminal repeat configuration previously described as essential for mobility. We confirm in independent experiments that these new minimal constructs yield transformation frequencies similar to the control piggyBac vector. Sequencing analyses of our constructs verify the position and the source of a point mutation within the 3' internal repeat sequence of our vectors that has no apparent effect on transformation efficiency.
Prediction of electrical power quality disturbances using state estimation techniques (2005)

An actual example of the performance of the proposed method is introduced. The example makes use of the records that took place on the medium voltage distribution network feeding a large industrial city in the west of the city of Alexandria. The results show that the methodology of the proposed method is suitable for the prediction and the analysis of disturbance events so that the approaches to the corrective strategies could be addressed.
Expression of RNase Rh from Rhizopus niveus in Yeast and Characterization of the Secreted Proteins (1991)

The full-length cDNA encoding RNase Rh, which is secreted extracellularly by Rhizopus niveus, was isolated and its nucleotide sequence was determined. It was placed under control of the promoter of the glyceraldehyde 3-phosphate dehydrogenase gene of Saccharomyces cerevisiae in a high expression vector in yeast. Since yeast cells transformed by this plasmid poorly secreted RNase into the medium, the plasmid pYE RNAP-Rh was constructed, in which the signal sequence of RNase Rh was replaced by the prepro-sequence of aspartic proteinase-I, one of the extracellular enzymes secreted by R. niveus. Yeast cells harboring pYE RNAP-Rh produced RNase efficiently (ca. 40 micrograms/ml) into the medium. The product was a mixture of six enzymes (RNase RNAP-Rhs) having 3, 5, 9, 13, 14, and 16 additional amino acid residues attached to the amino terminus of the mature RNase Rh. The major product was the RNase with three additional amino acids at the amino terminus. Limited digestion of RNase RNAP-Rhs with staphylococcal V8 protease succeeded in shortening the various lengths of extra amino acid residues attached to the amino terminus of RNase Rh, yielding an RNase that has 3 additional amino acids at the amino terminus. It has been named RNase RNAP-Rh. The RNase RNAP-Rh showed the same specific activity and CD spectra as those of RNase Rh, suggesting that the two have similar conformations to each other around aromatic amino acid residues and the peptide backbone.
Mutations of the Epidermal Growth Factor Receptor Gene Predict Prolonged Survival After Gefitinib Treatment in Patients With Non–Small-Cell Lung Cancer With Postoperative Recurrence (2005)

EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.