bluuebunny/crossref_metadata_2025 huggingface dataset:
National-moral ideas in Aziza Jafarzadeh’s literary prose
Authors: Huseynova Arzu
Published: July 2022

The literary work of Aziza Jafarzade (1921-2003), one of the famous representatives of Azerbaijani literature, is distinguished by specificity and uniqueness in terms of ideological context. The writer’s novels, tales, and short stories have become the object of comprehensive analysis and have gained deserving recognition from literary critics for their singularity and aesthetic quality. The author gave preference to historical themes. Her works “Baku-1501”, “Before ‘Gulustan’,” “The Tears of the Khazar,” “Zarrintaj-Takhira” and “Woe,” written in different years, have become unique examples of Azerbaijani prose both for the urgency of the problems and specificity of form. Aziza Jafarzade, in her literary activity, addressed topics related to the history of Azerbaijan and skillfully turned the problems of national and moral problems into a literary text. This attitude allowed the author to depict in her work the history of the division of Azerbaijan by the hands of the imperialist states. That is why the split of Azerbaijan in two, the ideas of the unity and integrity of the nation attract attention in her works.
The Contributions of Georgia’s Geopolitics to the Country’s Economy
Authors: Ibrahimli Haleddin , Koç Murat
Published: July 2022

This article investigates the effects of Georgia’s current geopolitical situation on the country’s economic development. Although Georgia lost control of the two strategic regions such as Abkhazia and Ossetia, right after the collapse of the Soviet Union, it maintained its geopolitical importance in the South Caucasus. In this context, the definition of geographical space was clarified in the article, and the recent situation in the South Caucasus, the changes in the region after the collapse of the Soviet Union, and the results of these changes were evaluated. In addition, the advantages of Georgia’s geopolitical position and other additional issues affecting the economic development of this country were taken into account, the reflections on the problems between Azerbaijan and Armenia on Georgia were examined, and finally, comments on the future of the South Caucasus were made.
Artistic Immortality as an Objet Petit a: The Subject of Samuel Taylor Coleridge’s “Kubla Khan”
Authors: Hosseini Sajed , Babaie Payam
Published: July 2022

This study presents a psychoanalytical reading of Coleridge’s “Kubla Khan” having an eye on Žižek’s theory of the subject. “Kubla Khan” contains a host of components providing an illustration of Coleridge’s psychological status. In such a case, Žižekian approach to psychoanalysis could provide a suitable paradigm for an analytical reading of the poem. The works of Žižek conducted disputatious re-articulations of the subject/object, the displacement of an objet petit a (object of desire) with object-cause of desire, and parallax. Žižek, like Hegel, accentuates the one-to-one relationship of the subject and the object while introducing parallax and the ticklish subject, which are later followed by tickling object. It is thus possible to illustrate the psychoanalytical status of Coleridge in the course of writing “Kubla Khan.” The poem pictures a path to immortality while it is in search to immortalize its poet too. In this study, it is demonstrated how Coleridge followed his objet petit a, which is ‘artistic immortality,’ in the lines of “Kubla Khan.”
Culture vs Stereotypical Thinking vs Language Facts
Authors: Lemish Nataliya , Matvieieva Svitlana , Orlova Yuliia , Kononets Juliia
Published: July 2022

The paper considers the topical issue of contemporary Intercultural Communication, Linguoculturology, Psycholinguistics, Psychology, dealing with importance of an individual’s awareness of cultural factors of different nations, specificity of national thinking (stereotypical in particular), ability of different languages to reflect reality differently, as well as establishing their interrelation. The findings prove close (integral and interdependent) relations among culture, stereotypical thinking, and language facts. It is stated that all the cultural universals contain a kind of deep structures of human consciousness which correlate with national peculiarities of each separate culture. Any changes in society always cause changes of vital senses and values fixed in cultural universals. Language is a prerequisite and “a verbal expression” of culture. As a sociocultural factor language helps to gain and organize human experience, and any national culture depends upon the character and specificity of a separate language. The results show that thinking is investigated through language analysis. The authors argue that thinking is influenced by national values and customs of the country where a person is brought up, thus confirming the existence of stereotypical thinking. Such stereotypes are rooted in social conditions and prior experiences; they may be neutral or have a positive / negative impact. People should be aware of explicit / implicit stereotypes existence and of an individual’s ability to think stereotypically. In this connection language facts (in their relation to stereotypical thinking within various cultures) are readily perceived by most representatives of discrete nations / groups and reflect both the encouraged moral values, and beliefs, as well as stigmatised human vices and ridiculed negative phenomena.
Evaluation of Enterococcus faecalis, Lactobacillus acidophilus, and Lactobacillus plantarum in Biopsy Samples of Colorectal Cancer and Polyp Patients Compared to Healthy People
Authors: Dadashi Masoud , Sahebi Abolfazl , Arjmand-Teymouri Reza , Mirzaii Mehdi , Mousavian Mehdi , Yaslianifard Somayeh
Published: July 2022

Background: Colorectal cancer (CRC) is one of the leading causes of death in both men and women worldwide. According to different studies, infectious agents or microbiota dysbiosis can play a role in CRC progression. Objective: This study aimed to evaluate the prevalence of Enterococcus faecalis, Lactobacillus acidophilus, and Lactobacillus plantarum in people with polyps or CRC compared to healthy individuals. Methods: In this study, 60 biopsy samples were collected from three groups, including patients with CRC, polyps, and healthy people. The genomic DNA was extracted from the collected samples and amplified by polymerase chain reaction (PCR) to detect E. faecalis, L. acidophilus, and L. plantarum. In the next step, quantitative real-time PCR was used to evaluate the copy number of the bacteria in the studied groups. Results: There was no statistically significant difference between the studied groups regarding age and gender (P > 0.05). The mean number of E. faecalis was higher in patients with CRC than in patients with polyps and healthy individuals (P < 0.05). Also, the mean numbers of L. acidophilus and L. plantarum were higher in healthy individuals than in patients with polyps and CRC (P < 0.05). Conclusions: Our findings indicate that L. acidophilus and L. plantarum in people with a family history of CRC and patients with polyps may effectively prevent or reduce CRC progression.
Are There Any Differences Between the Effect of Resistance and Aerobic Training on Spatial Learning and Memory in the Rat Model of AD?
Authors: Ebrahimi Khadijeh , Baghaiee Behrouz
Published: July 2022

Background: Physical training, especially endurance training as a non-pharmacological prevention strategy, can attenuate the consequences of memory loss in Alzheimer's disease (AD) without side effects. However, the role of resistance training and the difference between these two types of training have not been well established in this field. Objectives: The aim of this study was to determine and compare the effect of both trainings on spatial learning and memory in the amyloid-beta(Aβ)-induced rat model of AD using the Morris Water Maze test (MWM). Methods: Rats were randomly divided into six groups: Control; treadmill; resistance; Aβ + normal saline; Aβ + treadmill and; Aβ + Resistance (n = 6 group). Alzheimer's disease rats were induced by intracerebroventricular (i.c.v.) infusion of Aβ25-35 peptides. After performing aerobic (by treadmill) and resistance training (by vertical ladder with weights attached to the animals' tails) for eight weeks, the rats underwent the MWM. Results: The results showed that the mean escape latency significantly increased and the time in the target quadrant significantly decreased in the AD rats compared to the Control group (P < 0.05). However, there was no significant difference in the mean escape latency and time in the target quadrant between the Control, Treadmill, and Resistance groups (P < 0.05). Also, both AD-training groups had significantly less escape latency and more time in the target quadrant compared to the AD group (P < 0.005) without any significant differences between them (P < 0.05). Conclusions: Finally, we conclude that both trainings could improve spatial memory and learning without any superiority over each other in the AD animals and may subsequently prevent the progression of AD.
Evaluation of False Negative Among SARS-COV-2 Patients with Negative Real-time PCR Result Using Nested-RT PCR
Authors: Alinezhadi Mastaneh , Neisi Niloofar , Rasti Mojtaba , Arshadi Maniya , Parsanahad Mehdi , Cheraghian Bahman
Published: July 2022

Background: Fast and precise detection of SARS-CoV-2 RNA in clinical samples and subsequent quarantine are two critical factors in preventing virus transmission and distribution through the community. The false-negative result is a major problem in the SARS-CoV-2 detection because of the kind of sample (swab sample), sampling error, and sensitivity of PCR test, which can be reduced by a much more sensitive test such as nested PCR. Objectives: This study aimed to evaluate the false-negative rate among samples that were negative by a real-time PCR test using RT-nested PCR. Methods: One hundred eighty-four negative samples were included in the study, and nucleic acid was extracted using a commercial kit based on a silica filter column and then subjected to RT-nested PCR using three sets of primers targeting Orf1ab, N, and RdRp regions. Results: Among 184 negative swab samples for SARS-CoV-2, 27 (14.6%) cases were positive for the Orf1ab gene using RT-nested PCR. The samples were tested using N and RdRp primer sets. Also, seven (3.8%) cases were positive for the N gene, and four (2.1%) cases were positive for the RdRp gene. Conclusions: The results indicated that RT-nested PCR could be more sensitive than real-time PCR and reduce the false-negative rate.
Changes of Gene Expression in Candida albicans Isolates from Vaginal Infections by Effects of Zinc Oxide Nanoparticles and Fluconazole
Authors: Abedzadeh Hajar Azadeh , Dakhili Mohammad , Saghazadeh Mojgan , Aghaei Soheil , Nazari Razieh
Published: July 2022

Background: There are serious challenges of drug resistance in Candida albicans infection. Therefore, it is essential to identify new antifungal agents against resistant species to effectively treat patients affected by these species. Objectives: The present study aimed to study how zinc oxide nanoparticles (ZnO-NPs) and fluconazole affected the genes encoding resistance to fluconazole (i.e., CDR2 and ERG11) and those encoding adhesins (i.e., ALS1 and HWP1) in C. albicans isolates. Methods: In this descriptive-analytic study, samples of 120 patients with vaginitis were obtained using sterile swabs. After the identification of C. albicans strains, the fluconazole-resistant candida isolates were treated with various sub-minimum inhibitory concentrations of ZnO-NPs, fluconazole, and a combination of ZnO-NPs and fluconazole. Then, the effects of ZnO-NPs and fluconazole on the expression levels of ALS1, HWP1, CDR2, and ERG11 genes were evaluated by real-time polymerase chain reaction. Results: In this study, 50 out (41.6%) of 120 species with C. albicans were isolated, and 13 (26%) of 50 species were resistant to fluconazole. The expression analysis of fluconazole-resistant C. albicans strains showed that the expression of HWP1 and ALS1 genes was decreased by 2.84 and 1.62 times (P < 0.05), respectively. Nevertheless, the expression of CDR2 increased 1.42 - fold after the treatment with fluconazole. The expression of ERG11, CDR2, HWP1, and ALS1 in isolates treated with the combination of ZnO-NPs and fluconazole was downregulated by 2.1, 5.9, 3, and 5.5 times, respectively, compared to that of the control group. Conclusions: Based on the results, ZnO-NPs are helpful for the treatment of vaginitis-related C. albicans isolates in combination with fluconazole.
Career Development of Nursing Preceptors in Iran: A Descriptive Study
Authors: Habibzadeh Sajjad , Haririan Hamidreza , Hassankhani Hadi , Wytenbroek Lydia
Published: July 2022

Background: The career development of nursing preceptors is key to improving the quality of clinical education. However, there is a lack of sufficient and specific information about the career development of nursing preceptors in Iran. Objectives: This study aimed to investigate the nursing preceptors’ career development status. Methods: A descriptive cross-sectional study was carried out with the participation of 92 nursing preceptors. Participants were selected by census sampling method from 5 hospitals in Tabriz, Iran. Demographic and 6-dimension career development questionnaires were used to collect data. The collected data were analyzed using SPSS version 22, and the significance level for all statistical tests was determined to be less than 0.05. Results: Participants received the highest career development on ethical, cultural, and individual dimensions with mean scores of 3.55 ± 0.471, 3.41 ± 0.525, and 3.38 ± 0.540, respectively. However, they obtained the lowest career development on the organizational, research, and educational dimensions with mean scores of 2.68 ± 0.580, 2.28 ± 0.672, and 2.20 ± 0.690, respectively. Moreover, a comparison of career development based on demographic information showed that female preceptors, preceptors with more than 20 years of work experience, preceptors with master’s degrees, and contract employees had the highest mean scores for career development. Conclusions: Given the preceptors’ cooperation with nursing faculty as clinical nursing educators and their role in nursing education, officials of nursing faculties should develop specific career development programs (especially in organizational, research, and educational dimensions) and establish an effective relationship between preceptors and professors to enhance nursing students education.
Hiding in Plain Sight: Surprising Pharma and Biotech Connections to NIH’s National Cancer Institute
Authors: Uygur Berna , Ferguson Steven , Pollack Michael
Published: July 2022

The National Institutes of Health (NIH), and especially its largest and oldest institute, the National Cancer Institute (NCI), have long been among the best - but perhaps not the most well-known supporters - for the life sciences and pharmaceutical industries, providing non-dilutive funding, scientific guidance, education for potential future employees, and importantly, collaboration opportunities including clinical trials and technology licensing partnerships. In this study, various databases were used, including the NCI Technology Transfer Center (TTC) internal agreement database, NIH technology licensing database, Global Data, Pitchbook, and NIH RePORTER, to explore and analyze collaborations and licensing partnerships between NCI TTC and life science and pharmaceutical companies. For early-stage companies receiving funding or taking part in collaborations and licensing, there is a significant relationship between these NIH agreements and successful financial exits. NCI support not only reaches these early-stage firms but also extends to the Top 20 pharmaceutical companies. These two findings highlight the importance of NCI collaborations for both early-stage and established life science and pharmaceutical companies.
“WHY STARTUPS FAIL: NEW ROADMAP FOR ENTREPRENEURIAL SUCCESS” BY TOM EISENMANN CURRENCY, AN IMPRINT OF RANDOM HOUSE (2021)
Authors: Arthur A. Boni
Published: July 2022

The recently published book “Why Startups Fail: New Roadmap for Entrepreneurial Success” authored by Tom Eisenmann summarizes research on a much debated topic- what is the reason or reasons whey startups fail? The book is based on an extensive, multi- year study led by Eisenmann with assistance from his students at the Harvard Business School (HBS). Their study examined failure modes in 470 technology companies with an objective of answering more definitively why startup companies fail. Therefore, the Eisenman book provides a “deep dive” of what we can learn about the failure modes of startups in the technology industry. We recommend this book for anyone who seeks an answer to why companies fail. But, can we extrapolate their findings to the biopharma industry? While there are definitely differences across startups in different industries, e. g. “tech to biopharma/med tech/digital health” It is our opinion that cross-industry benchmarking can be a very useful methodology that may instruct entrepreneurs on how to minimize “errors of both omission and commission”, and how to start and grow successful companies – across industries, including health related organizations; biopharma, MedTech, and the emerging field of digital health. Our concluding section, focuses on special issues pertinent to the unique challenges for biopharma companies. This comparison is supported by a­­ short summary of a recent overview article by Boni and Abremski . This article identified best practices for starting and growing successful companies in digital health based on our respective experiences at Carnegie Mellon University, and UC San Diego. Evidence from both tech and biotech seem to support an overall conclusion that the most important predictor for startup company success is the extended team.
Keys for Building and Leading Teams for Innovation in Organizations: Three Book Reviews and Author Commentaries
Authors: Arthur A. Boni
Published: July 2022

This “From the Boardroom” introductory article and the subsequent book reviews builds on a recent book review by this Editor that focused on “Why Startups Fail: New Roadmap for Entrepreneurial Success” (by Harvard professor Tom Eisenmann, also published in this edition of JCB. Eisenman’s excellent book was based on a multi-company study of early-stage companies that succeeded vs. those that failed. He found that the extended team and its leadership are the most important predictors of success of an entrepreneurial venture. This finding, highlighted that leadership based on teams, partnerships, alliances and networks are important success factors in all industries. They are a means to create and sustain a competitive advantage to commercialize and bring innovations to market and fulfill unmet needs. Reading Eisenmann’s book prompted me to now take a “deeper dive” into the essential components needed for success to build, grow, lead and sustain innovative organizations of any size – from startups through their emergent growth stages, and to maturity. This encouraged me to find other materials to complement Eisenmann’s book
The last decade of the Chudov Monastery history: from the October Revolution to demolition.
Authors: Mironenko Maxim
Published: July 2022

The article examines the last stage of the existence of the Chudov Monastery of the Moscow Kremlin in its last decades. This period is one of the least studied in the history of the monastery, and yet, it is at this time that both the personal dramas of the inhabitants of the monastery before the closure of the monastery and the procedure for transferring valuables to the Armory that began immediately are exposed. Using the example of the monastery, we see how the new government forms a position regarding valuable monuments. It is noteworthy that the inhabitants of the monastery believed to the last that they would be able to find a compromise solution and leave at least a few monks to guard the monastery and perform divine services, but, unfortunately, the plans of the new government were completely different. In parallel with the process of evicting the monks, there is a struggle for the preservation of the complex exclusively as a monument of architecture and culture, where the main role is played by the Department for Museums and the protection of monuments of Art and antiquity, in those years it was headed first by I. Grobar, and a little later it was replaced by N.Sedova-Trotskaya, which led to the strengthening of the department - this allowed us to do a lot for the preservation of monuments. The work introduces new sources that describe in detail the plot of the relationship between the monastery and the new government, the scrupulousness of preparing for the restoration of the monastery and the feat that scientists performed to save the monument from further destruction as a result of shelling. But all the efforts of scientists for the restoration were in vain, in a great hurry, on the night of December 16-17, 1929, the Cathedral of the Miracle of Archangel Michael was blown up. The restorers did not have time to finish the work on measurements, photo fixation, and even save the frescoes already removed from the walls, which were prepared for museumification.
The comparative method in Guido Panciroli's treatise "Two books about memorable things, now lost and, on the contrary, recently ingeniously invented"
Authors: Galkova Daria Aleksandrovna
Published: July 2022

This article is devoted to the problem of understanding the phenomena and objects inherent in antiquity and modern times in Guido Panciroli's treatise "Two books about memorable things", published for the first time in 1599 in Amberg. Of particular interest in Panciroli's work is his approach to the search and comparison of phenomena that fell out of use due to the fall of the Roman Empire or came into use in the updated tradition already in the Middle Ages. The formulation of the problem and the logic of the reasoning of the author of the treatise fully reveal his ideas about the replenishment and loss of knowledge available to people in a historical perspective. The main merit of Panchiroli is an attempt to reconstruct the circle of forgotten and new technologies by comparing different historical periods. At the same time, the author strives for the impartiality of his judgments and does not try to reveal the superiority of one era over another. Through an appeal to the "forgotten" and "lost" ancient knowledge, Panchiroli gives it publicity, draws attention to it, which together leaves hope for the possibility of revival. The "new" inventions, which somehow became part of the European tradition, personified the increment of knowledge. Their discovery became another confirmation that reality is plastic and subject not only to oblivion, but to renewal.
Development of HOTS Integrated Problem Based Learning (PBL) Chemistry Learning Module on Buffer Solution Material at SMA Negeri 1 Purba
Authors: Panggabean Freddy Tua Musa , Sari Munthe Grestina Winda , Silitonga Pasar Maulim , Juniar Anna , Selly Rini
Published: July 2022

This research was conducted to design a Problem Based Learning (PBL) based learning module with the ADDIE model. The problems studied are 1) How is the feasibility (validity) and learning effectiveness of the Problem Based Learning (PBL)-based module developed on the buffer solution material to measure students' Higher Order Thinking Skills (HOTS) and 2) What are the students' chemistry learning outcomes using the module-based Problem Based Learning (PBL) is higher than the KKM score. The subjects of this study were 3 expert validators (expert lecturers), and 1 high school chemistry teacher to evaluate the learning to be developed and class XI MIA students of SMA Negeri 1 Purba who were determined by random sampling using an experimental class totaling 30 students. The results of the study showed that 1) the problem-based learning module for chemistry-based learning buffer solution material that was developed was feasible to be used for learning materials to improve students' critical thinking skills. The module is declared effective as seen from the increase in student learning outcomes, namely the average pretest value of 33.5 and posttest 80.13 in the experimental class, 2) The learning outcomes of chemistry using Problem Based Learning (PBL)-based modules developed on buffer solution material are higher than the value KKM (75) with an average score of 80.13.
Genetic Analysis of Heterosis of F1 Seed Yield and Quality Attributes in Fenugreek (Trigonella foenum graecum L.)
Authors: Kumar Dijendra , Ram C. N. , Yadav G. C. , Nath Shiva , Rai Mritunjay
Published: July 2022

A diallel set of 10 parents and their 45 F1 hybrids developed through diallel mating design (excluding reciprocals) were analysed to estimate the magnitude of heterosis for seed yield and its component in fenugreek. The present study was conducted at Main Experimental Station, Department of Vegetable Science, Acharya Narendra Deva University of Agriculture and Technology, Narendra Nagar (Kumarganj), Ayodhya (UP), India, during Rabi, 2020-21 (Y1) and 2021–22 (Y2). Appreciable heterosis were found over better parent and standard variety for all the traits under study in desirable direction. For early maturity traits i.e., days to 50% flowering, days to maturity negative heterosis is desirable, for these traits cross combinations P1× P2, P2×P5, P1×P10 and P5×P9 exhibited highest significant heterosis over better parent and standard variety. Seed yield per plant being a compound trait and is a multiplicative product of several basic component characters of yield. The top three hybrids based on seed yield per plant, best hybrids were P5 × P9, P7 × P10 and P3 × P9.
Purification from pig kidney of a microsomal cytochrome P450 catalyzing 1α‐hydroxylation of 25‐hydroxyvitamin D3
Authors: Axén Eva
Published: July 2002

A cytochrome P450 catalyzing 1α‐hydroxylation of 25‐hydroxyvitamin D3 was purified from pig kidney microsomes. The enzyme preparation showed one protein band on gel electrophoresis with apparent M
r of 52,500 and a specific cytochrome P450 content of 10.7 nmol/mg of protein. The 25‐hydroxyvitamin D3 1α‐hydroxylase copurified with the vitamin D3 25‐hydroxylase during purification. A cytochrome P450 catalyzing 1α‐hydroxylation was purified also from liver microsomes. The apparently homogeneous enzyme showed the same catalytic properties and apparent M
r as the kidney enzyme. The results of the present communication demonstrate the presence in kidney of a previously unknown microsomal 1α‐hydroxylase in addition to the assumed specific mitochondrial 1α‐hydroxylase. The possibility that microsomal 1α‐hydroxylation in pig kidney and liver is catalyzed by the previously described porcine microsomal vitamin D 25‐hydroxylase(s) is discussed.
A recombinant polypeptide, composed of the α‐helical neck region and the carbohydrate recogniton domain of conglutinin, self‐associates to give a functionally intact homotrimer
Authors: Wang Jiu-Yao , Kishore Uday , Reid Kenneth B.M.
Published: July 2002

A recombinant polypeptide composed of the α‐helical neck region and carbohydrate recognition domain (CRD) of bovine conglutinin was expressed in Escherichia coli. The recombinant protein formed inclusion bodies but could be solubilised using a denaturation‐renaturation cycle based on urea and then purified by affinity chromatography on a TSK‐N‐acetylglucosamine column. The purified product behaved as a homotrimer in nondissociating conditions, with three CRDs held together by the α‐helical neck regions. The trimer, although lacking the N‐terminal and collagen regions of the native conglutinin, showed the same binding carbohydrate specificities as the native molecule, for the complement fragment C3b and for lipopolysaccharides derived from Gram‐negative bacteria.
Postdate antenatal testing
Authors: Ohel G. , Yaacobi N. , Linder N. , Younis J.
Published: July 2002

Objective: To test the effect on pregnancy outcome of a policy of very early commencement of postdate surveillance testing, and induction of labor at 42 weeks. Methods: Retrospective analysis of 2776 consecutive cephalic deliveries at 38–42 weeks of gestation. Management of the postdate pregnancies included twice‐weekly antenatal testing beginning at 40 completed weeks and elective induction of labor at 42 completed weeks. Pregnancy outcome parameters were compared between the groups delivered at 38–40 weeks and at 41–42 weeks. Results: There were 2138 pregnancies delivered at 38–40 weeks and 638 at 41–42 weeks. The latter group had a statistically significant increase in the rate of cesarean section, mainly accounted for by an increased rate of fetal distress and failure to progress in labor. Similarly the rate of instrumental vaginal delivery, meconium in labor and macrosomia had a statistically significantly higher incidence in the postdate group. These differences in outcome were already apparent at 41 weeks of gestation. Conclusion: Despite early initiation of fetal surveillance, starting at 40 completed weeks, postdate pregnancies are associated with an increased rate of emergency cesarean section, macrosomia and meconium in labor.
Stathmin gene expression in mammary gland and in Nb2 cells
Authors: Puissant Claudine , Mitev Vanio , Lemnaouar Mustapha , Manceau Valérie , Sobel André , Houdebine Louis‐Marie
Published: July 2002

Summary— Mammary gland growth occurs essentially during pregnancy and induction of milk synthesis is triggered at parturition. Prolactin is mammogenic in vivo but only marginally in vitro. Prolactin induces milk synthesis in vivo and in cultured mammary cells. Prolactin is also strictly required for the multiplication of the rat lymphoid Nb2 cells. Stathmin is an ubiquitous and highly conserved phosphoprotein which seems to be involved in the intracellular mechanisms which trigger cell multiplication and differentiation. In the present study, the concentration of stathmin mRNA has been evaluated during the pregnancy‐lactation‐weaning cycle in mouse and rabbit. Stathmin mRNA appeared at its highest level during pregnancy and it was almost undetectable during lactation. Prolactin injected into mid‐pregnant rabbits induced milk synthesis and this effect was not accompanied by any modification of stathmin mRNA concentration. In cultured primary rabbit mammary cells, prolactin induced casein gene expression without any alteration of stathmin mRNA concentration. In Nb2 cells, prolactin induced a progressive increase of stathmin mRNA concentration. This effect was not significant until after 4 h of prolactin action. These data suggest that stathmin is involved in mammary and Nb2 cell multiplication but may not be necessary for mammary cell differentiation.
Study of human erythrocyte membrane protein interactions by selective solubilization of Triton‐skeletons
Authors: Navarro‐Prigent Marie‐José , Séguin Isabelle , Boivin Pierre , Dhermy Didier
Published: July 2002

Summary— The membrane skeleton, responsible for shape and mechanical properties of the red cell, was purified by the Triton extraction procedure in presence of 5 mM, 150 mM or 600 mM NaCl. The proportion of spectrin, protein 4.1 and actin present in erythrocyte skeletons does not depend on the molarity of NaCl used. In contrast ankyrin, protein band 3 and protein 4.2 are removed from skeletons as the ionic strength increased. Solubilization assays of membrane skeletons were used to study protein interactions inside the skeleton. Solubilization was performed by Tris, a non‐selective disruptive reagent, or by p‐mercuribenzene sulfonic acid (PMBS), which principally release spectrin and actin. Tris action was assessed by calculation of the percentage of solubilized proteins, which increased proportionally with Tris molarity. PMBS action was kinetically determined as the decrease in skeleton turbidity. With these two reagents, we observed a lower dissociation of skeletons prepared with high ionic strength buffer. Erythrocyte pretreatment with okadaic acid, an inhibitor of serine‐threonine phosphatases, revealed a phosphorylation‐induced skeleton gelation and a better resistance to Tris‐solubilization.
Cytochrome c oxidase rapidly metabolises nitric oxide to nitrite
Authors: Torres Jaume , Sharpe Martyn A , Rosquist Aasa , Cooper Chris E , Wilson Mike T
Published: July 2002

Previous studies have shown that the addition of nitric oxide to cytochrome c oxidase rapidly generates spectral changes compatible with the formation of nitrite at the binuclear haem:copper centre. Here we directly demonstrate nitrite release following nitric oxide addition to the enzyme. The nitrite complex is kinetically inactive and the off rate for nitrite was found to be slow (0.024 min−1). However, the presence of reductants enhances the off rate and enables cytochrome oxidase to catalyse the rapid oxidation of nitric oxide to nitrite free in solution. This may play a major role in the mitochondrial metabolism of nitric oxide.
Changes in the activity of type 2A protein phosphatases during meiotic maturation and the first mitotic cell cycle in mouse oocytes
Authors: Winston Nicola J. , Maro Bernard
Published: July 2002

We have established an assay to measure protein phosphatase activity in mouse oocytes using [32P]‐radiolabeled phosphorylase a as the substrate. Removal of the radiolabel from the substrate in vitro was linear with time and could be inhibited totally by the addition of okadaic acid (inhibitor of type 1 and type 2 protein phosphatases), or partially by protein inhibitor 2 (inhibitor of type 1 protein phosphatases). We performed a detailed study of the activity of type 2A protein phosphatases in mouse oocytes undergoing meiotic maturation and after parthenogenetic activation of mature oocytes arrested in metaphase II. Significant changes in the activity of type 2A protein phosphatases were observed during the first meiotic and the first mitotic cell cycles. These alterations in type 2A protein phosphatase activity occurred in the absence of changes in the quantity of the catalytic subunit and can be correlated with changes in the activity of protein kinases and rearrangement of the cellular cytoskeleton. Our observations support a role for type 2A protein phosphatases in cell cycle regulation and demonstrate that, like the protein kinases, the type 2A phosphatases also undergo changes in their activity during early mammalian development.
Differential alterations of NF‐κB to oxidative stress in primary basal forebrain cultures
Authors: Gu Zezong , Cain Lisa , Werrbach‐Perez K. , Perez‐Polo J.Regino
Published: July 2002

Oxidative stress has been linked to neuronal cell death resulting from either acute insults due to ischemia, trauma, excitotoxicity, or chronic neurodegenerative diseases. Cholinergic basal forebrain neurons (CBFNs) compete for nerve growth factor (NGF) synthesized in the hippocampus and cortex via retrograde transport. NGF affects CBFN survival and cholinergic function via activation of the NF‐κB transcription factor and this signaling pathway appears to be impaired in aged rats. Here, we demonstrate that activation of NF‐κB in basal forebrain primary culture via treatment with hydrogen peroxide or TNF‐alpha is predominantly restricted to CBFNs, and that NF‐κB activation appears to mostly affect p65 translocation to the nucleus, but not the p50 subunit. These results are consistent with NF‐κB activation being a part of recovery processes after acute oxidative stress. Since p50 or p49 (also called p52) binding to promoter sites does not stimulate transcription — both p50 and p49 lack an activating domain — and p65 does contain an activating domain and thus can act as a transcription enhancer, differential translocation of different NF‐κB dimers can act as repressors of constitutive activity or enhancers. These results are in agreement with the hypothesis that p50/p65 is the active trans‐activating species of NF‐κB, as compared to p50/p50 homodimers which bind to NF‐κB binding sites but do not trans‐activate promoters. Our results also suggest that selective activation of different NF‐κB dimer species may have regulatory significance in neuronal responses to acute or chronic insults to CNS. Thus, increased p65 translocation could have enhancing effects while increased p50 translocation could have a repressor role. Manipulation of the types of NF‐κB species being translocated could provide a basis for therapeutic strategies.
Characterization of Polycationic Amino Acids Fusion Systems for Ion‐Exchange Purification of Cyclodextrin Glycosyltransferase from Recombinant Escherichiacoli
Authors: Kweon Dae‐Hyuk , Lee Dae‐Hee , Han Nam‐Soo , Rha Chan‐Su , Seo Jin‐Ho
Published: July 2002

Fusion proteins with charged polycationic amino acid tails were constructed for the purpose of simple ion‐exchange purification with high purity. A number of positively charged lysine and arginine tails were fused to the C‐terminus of cyclodextrin glycosyltransferase (CGTase) derived from Bacillus macerans and expressed in Escherichia coli. The ionic binding forces provided by the tails allowed the selective recovery of CGTase from recombinant E. coli cell extracts, while CGTase by itself could not bind to the cation exchanger at neutral pH. The type of amino acids used and the length of the tail directly affected the purification factors. Most intracellular proteins of E. coli adsorbed on the cation exchanger could be removed by washing with 400 mM NaCl solution at pH 7.4, suggesting that a fusion partner suitable for purification purpose should be provided with high binding strength and the maintenance of adsorption by washing with NaCl solution. Among the fusion CGTases constructed, the CGTK10ase containing 10 lysine residues provided sufficiently high binding strength to allow purification to its homogeneity through simple ion‐exchange chromatography.
Biological Verification of Fluid‐to‐Particle Interfacial Heat Transfer Coefficients in a Pilot Scale Holding Tube Simulator
Authors: Ramaswamy H. S. , Awuah G. B. , Simpson B. K.
Published: July 2002

Inactivation kinetics of immobilized bovine pancreas trypsin (type III) was used in conjunction with a finite difference model to verify fluid‐to‐particle heat transfer coefficients to particulates in a holding tube of a pilot scale aseptic processing simulator operated at temperatures ranging from 90 and 110 °C. The enzyme was sealed in a stainless steel capsule, which was pretested to be suitable for high‐temperature, short‐time applications, and embedded at the center of a finite cylindrical particle. The percentage retention of the enzyme activity was calculated by using transient temperatures and their respective D values in a finite difference program. Heat transfer coefficients estimated for the potato particles under similar experimental conditions were used as input data. Excellent comparison was observed between predicted and measured percentage retention of enzyme activity.
Protein Adsorption Characteristics of a Sulfonic‐Acid‐Group‐Containing Nonwoven Fabric
Authors: Kim Min , Sasaki Masami , Saito Kyoichi , Sugita Kazuyuki , Sugo Takanobu
Published: July 2002

A sulfonic acid (SO3H)‐group‐containing nonwoven fabric was prepared by radiation‐induced graft polymerizaton of an epoxy‐group‐containing monomer, glycidyl methacrylate, onto a nonwoven fabric and subsequent sulfonation. The nonwoven fabric containing SO3H groups at different densities was equilibrated with lysozyme in a buffer (pH 6.0). The equilibrium binding capacity (EBC) of lysozyme increased linearly with increasing SO3H group density. The SO3H‐group‐containing polymer chains extended from the pore surface due to mutual electrostatic repulsion and held lysozyme in multilayers. The maximum EBC was 0.7 kg/kg at a SO3H group density of 1.7 mol/kg.
Continuous infusion of FVIII and FIX concentrates:in vitroanalysis of clinically relevant parameters
Authors: Thomas K. B. , Urbancik W. , Turecek P. L. , Gritsch H. , Schreiber J. , Weber A. , Schönhofer W. , Strauss M. , Linnau Y. , Schoppmann A.
Published: July 2002

A high purity factor VIII/von Willebrand Factor (FVIII/vWF)concentrate (IMMUNATE*[STIM plus†])(n = 6 batches), and a high purityfactor IX (FIX) concentrate (IMMUNINE*[STIMplus]) (n = 7 batches), wereassessedin vitrofor their applicability to continuousinfusion. Parameters pertinent to continuous infusion wereinvestigated and included stability, sterility and, in the caseof FIX, the generation of potentially thrombogenic components.Four stationary or transportable mini infusion pumps, equippedwith polyethylene, polypropylene or polyvinylchloride plasticcomponents were used. The concentrates were reconstitutedwithout extra filling volume and perfused at12.5 mL h−1and1 mL h−1; sampling was carriedout at the start of the experiment and for up to 48 h.The FVIII procoagulant activity (FVIII:C) was assayed byamidolytic, 1‐stage and 2‐stage assays; vWF was examined forristocetin cofactor activity, antigen and multimers. The FIXcoagulation activity (FIX:C) was determined by a 1‐stagecoagulation assay; thrombogenicity potential was assessedinvivo(Wessler stasis model in rabbits) andinvitro(FIXa and nonactivated thromboplastin time).Reconstituted concentrate incubated under the same conditionsserved as a control. Both concentrates remained sterilethroughout the testing period. The perfused and control samplesremained stable, retaining over 95% of activity for FVIII:C andover 90% for FIX:C for up to 48 h. Intermittent decreaseof FVIII:C or FIX:C was not observed, suggesting no adsorptionof FVIII or FIX onto plastic surfaces during either short orlong‐term exposure. No thrombogenic components were detected inthe high purity FIX concentrate. Thus, under theinvitroconditions used, FVIII/vWF and FIX were found to besuitable for administration by continuous infusion.
Immunogenicity of malaria transmission‐blocking vaccine candidate, y230.CA14 following crosslinking in the presence of tetanus toxoid
Authors: Vincent Arokia A. , Fanning Sarah , Caira Francesco C. , Williamson Kim C.
Published: July 2002

Proteolytically processed 310 kDa form of Plasmodium falciparum gamete surface antigen, Pfs230, is the target of malaria transmission‐blocking monoclonal antibodies. To design a recombinant malaria transmission‐blocking subunit vaccine, the amino terminus of the 310 kDa surface‐exposed form of Pfs230 was mapped to amino acids (aa) 522 and 584 using a series of peptides and recombinant proteins encoding distinct regions of Pfs230. Antiserum generated against an Escherichia coli‐produced recombinant protein, spanning the Pfs230 processing site and extending into the cysteine domains, r230/MBP.C (aa 443–1132), reduced parasite infectivity by 71.2–89.8%. To determine if the region spanning the cleavage site blocked malaria transmission when produced as a secreted protein by Saccharomyces cerevisiae, y230.CA14 (aa 467–584) was generated, purified, emulsified in adjuvant and used to vaccinate mice. In contrast to E. coli‐produced r230/MBP.C, the immune response generated against y230.CA14 was very weak. To enhance the response, y230.CA14 was mixed with tetanus toxoid, chemically crosslinked, repurifed, and its immunogenicty compared with unconjugated y230.CA14. Conjugated‐y230.CA14/TT required fewer booster injections to induce an immune response against Pfs230 and the antibodies generated reacted with the surface of intact gametes and immunoprecipitated radiolabelled Pfs230 extracted from 125I surface‐labelled gametes to a greater extent. After seven injections, all y230.CA14 vaccinated mice developed anti‐Pfs230 antibodies and the isotype profile was the same. In addition to enhancing the initial immune response generated against y230.CA14, conjugation focuses the immune response toward epitopes within the region of Pfs230 present on the surface of the gamete.
Mucosal mast cell responses are not required for protection against infection with the murine nematode parasite Trichuris muris
Authors: Koyama Koichi , Ito Yoichi
Published: July 2002

Infective forms of Trypanosoma cruzi, the parasite that causes Chagas’ disease, express on their surface an enzyme denominated trans‐sialidase (TS). The present study was designed to evaluate the naturally acquired immune responses to a bacterial recombinant protein representing the catalytic domain of TS in chronically infected chagasic individuals. The cellular immune response was measured by in‐vitro T‐cell proliferation and by interferon (INF)‐g, interleukin (IL)‐4 and IL‐10 production in response to a whole‐parasite homogenate and the recombinant protein. The peripheral blood mononuclear cells of 78·6% of 28 chagasic patients responded to the recombinant protein as estimated by T‐cell proliferation. With respect to cytokine production, 88% of the cells of the chagasic individuals produced IFN‐g on stimulation with the recombinant protein. In contrast, IL‐4 or IL‐10 were minimally produced in response to TS. The cellular immune response was specific because most healthy individuals never exposed to T. cruzi failed to react with this recombinant protein. The plasma of 71·4% or 100% of chagasic patients had IgG antibodies as determined by ELISA or by the presence of TS inhibitory antibodies, respectively. We conclude that the catalytic domain of TS is recognized by IFN‐g producing type 1 cells and antibodies in a large proportion of patients infected with T. cruzi.
ADULT SOFT TISSUE SARCOMA
Authors: Bruce Mann G. , Lewis Jonathan J. , Brennan Murray F.
Published: July 2002

Background: Soft tissue sarcomas (STS) are a group of anatomically and histologically diverse tumours. They account for about 1% of adult malignancies, and about 50% of patients diagnosed with sarcoma eventually die of the disease. These tumours are grouped together because of shared biological characteristics and treatment responses.

Methods: A review of the key literature on STS was undertaken, complemented by data taken from the prospectively accumulated database of 3442 patients treated for STS at Memorial Sloan‐Kettering Cancer Center (MSKCC) from July 1982 to December 1997.

Results: Despite advances in knowledge of the molecular genetics of STS, the aetiology in most cases remains elusive. Management has been gradually refined over the last two decades. Core biopsy usually provides enough material for diagnosis. Computed tomography and magnetic resonance imaging provide a similar amount of information, which is usually adequate for surgical planning. Amputation as standard treatment for extremity lesions has been replaced by limb‐sparing surgery in about 90% of patients. The role of adjuvant radiation has been further defined: it has been shown to be unnecessary for completely excised tumours less than 5 cm in diameter, but effective in decreasing local recurrence for others. Adjuvant chemotherapy has been controversial for many years. Recent meta‐analysis of randomized trial results has found a small reduction in local and distant relapse, and a trend to better overall survival. Recurrent or metastatic disease should be completely excised if possible.

Conclusions: Soft tissue sarcoma requires multidisciplinary care tailored to the individual patient and tumour for optimal results.
Dose perturbation by air cavities in megavoltage photon beams: Implications for cavity surface doses
Authors: Ebert Martin A , Spry Nigel A
Published: July 2002

Gas‐filled cavities in the body are known to perturb megavoltage photon beams in radiation therapy. The bowel represents one such cavity where cavity dimensions can vary throughout a treatment course. This has implications for doses to the surface of the bowel. Doses to the first 0.1 mm and 1.0 mm of cavity surfaces were calculated for 6 MV and 18 MV photon beams for a range of cavity sizes. It is found that relatively minor variations in cavity surface doses result over the typical range of rectal cavity size (2–3 cm). However, the variations in surface dose should be considered whenever bowel reactions must be considered, or when the target cells of interest line the bowel itself.