jimnoneill/paper-to-field-training huggingface dataset:
TCH-043 Stability Study of Sildenafil Capsules by High Performance Liquid Chromatography

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Background

Sildenafil, a phosphodiesterase V inhibitor, is used in paediatrics to treat pulmonary arterial hypertension. However no paediatric formulation was available until a recent launch announced a powder for oral suspension.

Purpose

To determine the stability of sildenafil capsules for paediatric dilutions. A HPLC assay has been developed for this purpose.

Materials and Methods

The sildenafil dosing method, developed from a previously published method1, is a reverse phase HPLC with UV detection at 240 nm. The column is a C18, the mobile phase composition is acetonitrile/ammonium acetate 0.2 M (50/50) with a flow set at 1 mL/min. Linearity and precision cheques (repeatability and intermediate precision) have been performed to validate the method. Capsules of 1 mg, 5 mg and 10 mg (of sildenafil base) were prepared with sildenafil citrate and corn starch. Samples wer kept at ambient temperature in transparent blister packs sealed with aluminium foil. Uniformity of mass was verified at D0. The visual appearance of the capsules, sildenafil concentrations and chromatographic profiles were checked at D0, D7, D14, D21, D35, D42, D56 and D70.

Results

The method was linear up to 150 mg/mL. Repeatability and intermediate precision were demonstrated (SD < 2%). Uniformity of mass was verified, no change in visual appearance and no additional chromatographic peaks were observed. The percentages of the remaining concentrations of sildenafil in the capsules compared to initial concentrations were higher than 90% at D70.

Conclusions

The method has been validated and used in a stability study which demonstrated the stability of sildenafil capsules up to ten weeks under the storage conditions studied. These results led us to apply a shelf life of eight weeks to sildenafil capsules.

Reference

Daragmeh N. et al,Determination of sildenafil citrate and related substances in the commercial products and tablet dosage form using HPLC. J Pharm Biomed Anal. 2001;25:483–492 No conflict of interest.
Desulfurization of Thioamides into Amides with Dinitrogen Tetroxide

Field: Chemistry (Physical Sciences)

Secondary and tertiary thioamides or diphenylthionocarbonate reacted readily with dinitrogen tetroxide at ca.0°C in acetonitrile to afford the corresponding amides or carbonate in good to excellent yields. The desulfurization appears to proceed via an S-nitroso intermediate by the selective electrophilic attack of nitrosonium cation on the thione sulfur atom.
Real-time and robust grasping detection

Field: Computer Science (Physical Sciences)

Depth-based gesture cameras provide a promising and novel way to interface with computers. Nevertheless, this type of interaction remains challenging due to the complexity of finger interactions and the under large viewpoint variations. Existing middleware such as Intel Perceptual Computing SDK (PCSDK) or SoftKinetic IISU can provide abundant hand tracking and gesture information. However, the data is too noisy (Fig. 1, left) for consistent and reliable use in our application. In this work, we present a filtering approach that combines several features from PCSDK to achieve more stable hand openness and supports grasping interactions in virtual environments. Support vector machine (SVM), a machine learning method, is used to achieve better accuracy in a single frame, and Markov Random Field (MRF), a probability theory, is used to stabilize and smooth the sequential output. Our experimental results verify the effectiveness and the robustness of our method.
SQUARE‐WAVE ANALYSIS OF SKIN IMPEDANCE

Field: Medicine (Health Sciences)

ABSTRACT A method is described for studying skin impedance phenomena, based on analysis of waveforms of current through the skin produced by square voltage pulses. In several experiments, the method is used to provide data relevant to the choice of an appropriate equivalent circuit for skin. Removal of the stratum corneum eliminates the parallel resistive and capacitative elements, and slightly reduces the series or ‘ohmic’ resistance. During healing the source of skin potential recovers before the other electrodermal parameters have returned to normal. The relationship of these parameters to electrode area, current density, and site temperature is studied. It is argued that the capacitance of skin may not vary with the frequency of the measuring current, in contrast to traditional views. The main purpose of the paper is to illustrate and advocate the square‐wave method of analysis.
Regionally different responses of GABAergic interneuron populations to a NMDA receptor antagonist challenge with MK-801 and an antipsychotic “rescue therapy“ in an animal model of psychosis

Field: Neuroscience (Life Sciences)

Some behavioral symptoms and neuropathological features also found in genuine schizophrenia, like numerical alterations of GABAergic interneurons, could be emulated in an animal model of psychosis based on prolonged, low-dose exposure to the N-methyl-D-aspartate NMDA-receptor antagonist MK-801. By immunohistochemistry directed against calcium-binding proteins, specific for interneuronal subtypes we examined distinct subpopulations of GABAergic interneurons and their spatial distribution throughout different brain regions, focussing on the limbic system. Compared to saline control, animals having received MK-801 exhibited a markedly decreased density of hippocampal parvalbumin-positive interneurons in the dentate gyrus, whereas the calretinin-immunoreactivity was significantly increased in the dentate gyrus of the hippocampal formation. NeuN-expressing cells representing adult neurons where almost unaffected, as were glial cells expressing GFAP, thus excluding unspecific neurotoxic effects of MK-801. Co-administration of the antipsychotic drug haloperidol mitigated the reduction of parvalbumine-positive interneurons in the hippocampal formation, but led to a marked reduction in the density of prefrontal parvalbumin expressing interneurons, when comparing with MK-801 or haloperidol treatment alone. These data show that a prolonged application of NMDA-receptor antagonist could, in part, mimic some neuropathologic findings in human schizophrenia, thus strengthening the idea that chronic, low-dose NMDA-receptor antagonism in animals is a viable approach in mimicking aspects of schizophrenia. Moreover, this study provides further evidence for regional differences in the response of GABAergic interneurons to NMDA-receptor antagonism and antipsychotic treatment.
Is rye bunt, Tilletia secalis, present in North America?

Field: Agricultural and Biological Sciences (Life Sciences)

A volunteer rye plant ( Secale cereale ) infected by a reticulate spored species of Tilletia was collected in a wheat field in southeastern Idaho in 1993 (WSP 71279). The smut fungus was identified as Tilletia contraversa , the dwarf bunt pathogen of wheat, based on teliospore morphology and stunting of the host. Inoculation studies conducted in the greenhouse confirmed that the rye-infecting bunt was able to infect wheat. A phylogenetic analysis based on the internal transcribed spacer region rDNA, eukaryotic translation elongation factor 1 alpha, and the second largest subunit of RNA polymerase II demonstrated that the rye-infecting bunt was distinct from T. contraversa and the common bunt pathogens of wheat, T. caries and T. laevis . The rye-infecting bunt fits within the species concept of T. secalis , a pathogen of cultivated rye in Europe. The ability of T . contraversa , T. caries and T. laevis to infect rye and of T. secalis to infect wheat has resulted in confusion over the identity of bunts found infecting rye. This study is the first demonstration in North America of a bunt fungus infecting rye that is genetically distinct from the wheat bunt pathogens.
The impact of parental income and education on the schooling of their children

Field: Economics, Econometrics and Finance (Social Sciences)

Abstract We investigate the relationship between early school-leaving and parental education and paternal income using UK Labour Force Survey data. OLS estimation reveals modest effects of income, stronger effects of maternal education relative to paternal, and stronger effects on sons than daughters. Using IV to simultaneously model the endogeneity of parental education and income, the maternal education effect disappears, while paternal education remains significant but only for daughters. In our favourite specification, which proxy for permanent income, paternal income becomes insignificant. Thus policies alleviating income constraints to alter schooling decisions may not be as effective as policies which increase permanent income. JEL codes I20; J62
Effect bulb size and two specie mooseer to yield components bulb percent allicin in weather mashhad

Field: Agricultural and Biological Sciences (Life Sciences)

One of the most important species of medicinal and industrial shallot Iran. Those in the as normal and in elevated areas with very cold climate to semi grow cold. Shallot (Allium altissimum) and Persian shallot (Allium hirtifolium), are represented important species in Iran. To investigate the possibility of domestication and cultivation of these two native cultivars, an experiment with three Bulb sizes (small, medium and large) and two species of mossir (Aligoodarz and Kalat) and inflorescence removing with three replications was conducted in horticulture department of Ferdowsi University of Mashhad. The results showed that the percentage of Bulblet, was affected by treatments. Bulb lowest percentage of Bulblet (24.7 percent) and most of the mass production of shallot Kalat Bulblet (40.4 percent) was related to the Aligoodarz mooseer specie. Largest Bulb size (80.2 gr) and highest Allicin content (4.24 µg/mg) was observed in large size Bulbs of Aligoodarz native species. Stem flower removal showed no significant difference within Bulb weight, but it affected Bulb size and Allicin content significantly.
Context-Aware Semantic Adaptation of Multimedia Presentations

Field: Computer Science (Physical Sciences)

In this paper, we present our work on context aware semantic adaptation of multimedia structured documents. We propose semantic annotation of multimedia scenes, expressing semantic information on each media object, as well as on the dependencies between all the media objects of the scene. We use these annotations in order to perform a semantic adaptation on multimedia presentations. We use our proposed description tools under the framework of MPEG-21, and we show that, in order to preserve the consistency and meaningfulness of the adapted multimedia scene, the adaptation process needs the semantic information of the presentation.
MANIFESTAREA TOLERANȚEI LA INCERTITUDINE ȘI A STIMEI DE SINE A STUDENȚILOR

Field: Psychology (Social Sciences)

THE MANIFESTATION OF STUDENTS ‘TOLERANCE TO UNCERTAINTY AND THEIR SELF-ESTEEM. The research of tolerance to uncertainty and self-esteem as an individual predisposition to report to complex social and professional situations is particularly current and important in the context of the pandemic that revealed several psychological problems. The psycho-emotional well-being of the population is interpreted as the way the person perceives himself, evaluates his life, the way he feels and activates on a personal and social level. This interpretation has changed during the pandemic crisis. Young people mention that in moments of uncertainty their safety is affected, which leads them to make impulsive, anxiety-filled choices. Respectively, self-esteem undergoes changes with the confrontation of situations full of uncertainty. A high level of self-esteem allows people to act effectively, to cope with the difficulties of existence.
Elites and Professional Ideology: Self-Discipline and Self-Administration by the Anwaltskammer Celle

Field: Social Sciences (Social Sciences)

In the same way that the Imperial Justice Laws changed the circumstances in which individuals had to make decisions about entering the private legal profession, structuring their careers, and leading their lives, lawyers in the newly created lawyers' chambers faced corporate decisions about how to structure professional life. The lawyers' chamber, a juridical person under public law, with its seat in the city in which the court of appeal lay, was the principal organ for the new self-government. The provisions of the Lawyers' Statute (RAO) provided lawyers laconic guidance and a bare framework for self-government, leaving it to their own initiative how to flesh out the direction and governance of their professional and even their private lives.
Cancer-testis antigen specific chimeric antigen receptor T cells for cancer immunotherapy

Field: Medicine (Health Sciences)

Adoptive chimeric antigen receptor (CAR) T cell therapy has shown promising results in early phase clinical trials, in particular when treating hematological malignancies. In this novel immunotherapeutic approach, isolated autologous T cells are ex vivo engineered to express a CAR, expanded to obtain sufficient cell numbers and finally infused back to the patient. Such CAR T cells are redirected to a predefined target antigen by an antibody derived binding domain and have been shown to substantially reduce the tumor burden as long as the cancer cells present the target antigen. However, solid tumors do not express exclusive target antigens, thereby hampering therapeutic safety due to potential on-target/off-tumor toxicity. In this project, we developed CARs that contain phage display selected fully human antibody binding domains specific for the tumor associated antigens AKAP4, SP17 and SPAG9. In healthy tissues, the expression of these so called cancer-testis antigens is restricted to spermatocytes, however, it has been shown that their expression can be upregulated in certain tumor entities most probably due to deregulated epigenetic events. We successfully selected AKAP4, SP17 and SPAG9 antibody fragments (scFvs) from human B cell repertoires that were further characterized as soluble scFv-hFc fusion proteins. We demonstrated antigen specificity by ELISA and SPR spectroscopy as well as surface binding to several tumor cell lines representing colorectal, ovarian, plasma cell and B cell cancers. Importantly, we also observed binding of the scFv-hFc fusion proteins to primary plasma cells isolated from multiple myeloma patients, but neither to plasma cells from two 2 out of 3 patients showing unremarkable bone marrow morphology, nor to peripheral blood mononuclear cells derived from healthy donors. SP17 and SPAG9 specific scFv lead candidates were fused as antigen binding domain to five different CAR backbones that contained either CD8α or hFc extracellular spacer domains and intracellular second or third generation stimulatory domains. The second generation CAR constructs showed superior characteristics compared to the third generation CARs as indicated by higher transduction efficiencies of the T cells and a higher surface expression of the CAR molecule. In addition, T cells expressing the second generation CARs showed less signs of T cell exhaustion, preferentially differentiated toward the central memory phenotype and showed specific cytotoxicity towards ovarian cancer and multiple myeloma cell lines. We here provide the basis for a novel cellular therapy by redirecting CAR T cells to tumor specific cancer-testis antigens to safely treat various cancer entities.
Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma

Field: Medicine (Health Sciences)

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma (FNHL) based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer’s scope restricts the intervention to rituximab in combination with CVP (cyclophosphamide, vincristine and prednisolone) (R-CVP); the only comparator used was CVP alone. The evidence from the one included randomised controlled trial (RCT) suggests that the addition of rituximab to a CVP chemotherapy regimen has a positive effect on the outcomes of time to treatment failure, disease progression, overall tumour response, duration of response and time to new lymphoma treatment in patients with stage III/IV FNHL compared with CVP alone. Adverse events were comparable between the two arms. This study was confirmed as the only relevant RCT. The economic analyses provided by the manufacturer were modelled using a three-state Markov model with with the health states being defined as progression-free survival (PFS), progressed (in which patients have relapsed) and death (which is an absorbing state). The model generated results for a cohort of patients with an initial age of 53 and makes no distinction between men and women. The model is basic in design, with several serious design flaws and key parameter values that are probably incompatible. Attempting to rectify the identified errors and limitations of the model did not increase the incremental cost-effectiveness ratio (ICER) above £30,000. Although the cost-effectiveness results obtained appear to be compelling in support of R-CVP compared with CVP for the trial population the results may not be so convincing for a more representative population. The results of the ERG analysis on the impact of age suggest that ICERs increase steadily with age, as the proportion of PFS that can be converted to overall survival (OS) is diminished by rising mortality rates in the general population. For the most extreme scenario (no OS gain) the ICER appears to remain below £30,000 per QALY gained. On balance the evidence indicates that R-CVP is more cost-effective than CVP. The guidance issued by NICE in July 2006 as a result of the STA states that rituximab within its licensed indication (in combination with cyclophosphamide, vincristine and prednisolone) is recommended as an option for the treatment of symptomatic stage III/IV follicular non-Hodgkin’s lymphoma in previously untreated patients.
Characterization of VP1 gene of coxsackievirus A16 prevalent among hand foot mouth disease suffered children in Taizhou, P. R. China, between 2010 and 2013

Field: Medicine (Health Sciences)

A total of 453 strains of Coxsackievirus A16 (CV‐A16) were screened out of 1,509 hand‐foot‐mouth disease (HFMD) samples collected in Taizhou during the period from 2010 to 2013. And between first quarter of 2011 and first quarter of 2013, an outbreak of CV‐A16 was found among the HFMD sufferers in Taizhou. Phylogenic analysis of VP1 sequences indicated a major CV‐A16 sub‐group in Taizhou, whose change pattern of effective population sizes was found to be similar to the pattern of the actual percentage changes of CV‐A16 during the outbreak over the same period. More importantly, the sub‐group all displayed a Leu (L) to Met (M) mutation at site‐23 of capsid VP1 which might be correlated with the outbreak of CV‐A16 in Taizhou. J. Med. Virol. 88:202–210, 2016 . © 2015 Wiley Periodicals, Inc.
Pregnancy establishment and maintenance in cattle1

Field: Veterinary (Health Sciences)

A single ovulation, reciprocal embryo transfer study was used to investigate effects of oocyte competence and maternal environment on pregnancy establishment and maintenance in beef cows. Estrous cycles were synchronized in suckled beef cows and embryo donors were inseminated on d 0 (n = 810). Cows were classified on d 0 as having a small (<12.5 mm) or large (≥12.5 mm) ovulatory follicle and randomly chosen as donors or recipients to remove confounding effects of ovulatory follicle size on fertility. Embryos (n = 393) or oocytes (n = 44) were recovered on d 7, and all viable embryos were transferred into recipients (n = 354). All statistical analyses were conducted using the GLM procedure of SAS. Path analysis (with significance set at P < 0.10) was used to examine potential cause-effect relationships among the measured variables. Greater donor cow BW, circulating estradiol concentration at insemination, postpartum interval, and ovulatory follicle size directly increased (P < 0.10) fertilization success. Greater donor cow age was the only factor that directly decreased (P < 0.10) fertilization success. Viability of d-7 embryos was directly inhibited (P < 0.10) by rapid follicular growth rate from d -2 to 0 and heavier BW. Direct beneficial effects to embryo viability were increased serum progesterone concentration on d -2 and ovulatory follicle size. Pregnancy maintenance from d 7 to 27 was enhanced (P < 0.10) by increased serum estradiol concentration on d 0 and progesterone concentration on d 7 in the recipient cow. Increased follicular diameter in the recipient cow on d 0 was detrimental to pregnancy maintenance from d 7 to 27. This manuscript defines the complex interplay and relative contributions of endocrine and physical factors both prior and subsequent to fertilization that influence both oocyte competence and maternal environment and their roles in establishment and maintenance of pregnancy.
The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180gag-fms encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180gag-fms) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120v-fms, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. Both constructs were biologically active when transfected into NIH 3T3 cells and produced morphologically transformed foci at equivalent efficiencies. When transfected into a cell line (psi 2) expressing complementary viral gene functions, G418-resistant (Neor) cells containing either of these vector DNAs produced high titers of transforming viruses. Analysis of proteins produced in cells containing the vector lacking gag gene sequences showed that gP180gag-fms was not synthesized, whereas normal levels of both immature gp120v-fms and mature gp140v-fms were detected. The glycoprotein was efficiently transported to the cell surface, and it retained wild-type tyrosine kinase activity. We conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180gag-fms is mediated by signal peptidase and that the amino termini of gp140v-fms and the c-fms gene product are identical.