The fractional bubble coverage is the leading quantity required for information on the actual current density of gas-evolving electrodes at a given nominal current density I/A. As confirmed by ...experiments, the bubble coverage increases with increasing current density, provided the values are sufficiently small. At large values of the bubble coverage, both variables develop in opposite directions: The nominal current density decreases as the bubble coverage increases. However, the current density is not the single quantity acting on the bubble coverage. Additionally numerous other quantities impact. They are traced up and their interferences are discussed. Particularly their impact on the interrelation of bubble coverage and current density is studied. The outcome is significant particularly for understanding real processes occurring at elevate electrode potentials likewise in laboratory and in industrial electrochemical reactors.
All investigations of electrochemical reactors with gas-evolving electrodes must take account of the fact that the actual current density controlling cell operation commonly differs substantially ...from the nominal current density used for practical purposes. Both quantities are interrelated by the fractional bubble coverage. This parameter is shown to be affected by a large number of operational quantities. However, available relationships of the bubble coverage take account only of the nominal current density. A further essential insufficiency is their inconsistency with reality for very large values of the bubble coverage being of relevance for operation conditions leading to anode effects. An improved relationship applicable to the total range is proposed.
In Part I of this paper 1 relationships for the gas-evolution efficiency were derived theoretically on the basis of a mathematical model. Now a numerical analysis is carried out referring to the ...conditions of a realistic electrolysis system. The results are compared with experimental data.
Applying the model equations shows that the gas-evolution efficiency is significantly smaller than unity in the total range of current density applied in laboratory as well as in nearly all industrial reactors. The impact of the bubble coverage as observed from experimental data is confirmed. Moreover, mass transfer of dissolved gas from the electrode to liquid bulk has decisive influence. The over-all mass transfer rate results from the combined action of several competing mass transfer mechanisms. At low values of the current density, free convective mass transfer mechanisms of various origins dominate. In this case, the electrode height is an important parameter explaining the enormous scatter of experimental data. The dominating impact steadily shifts to microconvective mass transfer as the current density is increased.
Making use of an analogy between heat transfer in boiling and mass transfer in gas evolution at electrodes may be a helpful tool. Over decades, science in both fields has developed independently – ...except for a few tentative attempts. The problem is that one of the fields is mainly of interest in process engineering, whereas the other field is traditionally attributed to electrochemistry, although it is a purely physical domain. In fact, both fields exhibit many aspects in common. However, there are numerous particularities definitely limiting an analogy some of which have not been discerned so far. The important Nukiyama curve of boiling was set in analogy to a current–potential curve of gas-evolving electrodes. The formal resemblance of both curves obscures some essential distinctions. Congruities in analogy and their distinct limits are analyzed.
At gas-evolving electrodes, the product of an electrochemical reaction, e.g. H
2 or O
2, does initially not exist as a gas but in dissolved form in the electrolyte liquid. Its appearance in the form ...of gas bubbles results from subsequent desorption. However, the process of desorption from the liquid phase into the gaseous phase is commonly not complete in the vicinity of the electrode or at all in the interelectrode space. The fraction of the product transferred into the gaseous phase of gas bubbles adhering to the electrode surface is termed the
gas-evolution efficiency. This quantity is one of the controlling parameters in estimating the rate of microconvective mass transfer, the industrially most important mechanism. A theoretical investigation shows the impact of the bubble coverage – previously only derived from an analysis of experimental data in combination with an unsubstantiated perception – and gives information on further controlling quantities: the mass transfer coefficients of two competing mechanisms.
Various types of uncontrolled potential increase must be distinguished at gas-evolving electrodes. A theoretical analysis on the basis of fundamental relationships shows that the increase in ...potential – commonly associated with the so-called anode effect at cells with constant or varied current – is caused in some cases by limitation of mass transfer. In other cases it is the result of reaching a summit current value created by the presence of gas bubbles in contact with the electrode surface. Which of the causes is the controlling one depends on the bulk concentration of the reacting substance and on the state of the electrode surface, particularly on material and roughness directly acting on the wettability. It is not sufficient to attribute any uncontrolled potential increase solely to mass transfer control as hitherto done. Several types must be taken into consideration.
As distinct from electrodes without gas evolution, the current dependence on the potential at gas-evolving electrodes exhibits a substantial variety of behaviour patterns. In potential-controlled ...cells, the current may smoothly increase up to a limiting value induced by mass transfer of the reactant. Alternatively, the current may attain a maximum followed by a usually substantial decrease to low values. This decrease may proceed smoothly or abruptly. The diversity of the shapes of the current/potential curves was found to depend mainly on the cell design and the operating conditions by a joint action of overpotential and ohmic potential drop. Elementary electrochemical relationships together with a few empirical auxiliary functions suffice to verify the distinct shapes of the current-potential curves and to explain the causes.
Translational control is a major level of gene expression regulation in the male germ line. DDX3Y located in the AZFa region of the human Y chromosome encodes a conserved RNA helicase important for ...translational control at the G1-S phase of the cell cycle. In human, DDX3Y protein is expressed only in premeiotic male germ cells. In primates, DDX3Y evolved a second promoter producing novel testis-specific transcripts. Here, we show primate species-specific use of alternative polyadenylation (APA) sites for these testis-specific DDX3Y transcript variants. They have evolved subsequently in the 3´UTRs of the primates´ DDX3Y transcripts. Whereas a distal APA site (PAS4) is still used for polyadenylation of most DDX3Y testis transcripts in Callithrix jacchus; two proximal APAs (PAS1; PAS2) are used predominantly in Macaca mulatta, in Pan trogloydates and in human. This shift corresponds with a significant increase of DDX3Y protein expression in the macaque testis tissue. In chimpanzee and human, shift to predominant use of the most proximal APA site (PAS1) is associated with translation of these DDX3Y transcripts in only premeiotic male germ cells. We therefore assume evolution of a positive selection process for functional DDX3Y testis transcripts in these primates which increase their stability and translation efficiency to promote its cell cycle balancing function in the human male germ line.
Abstract
STUDY QUESTION
Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue?
SUMMARY ANSWER
...Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease.
WHAT IS KNOWN ALREADY
Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered.
STUDY DESIGN, SIZE, DURATION
We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 ± 3.8 mean ± SD years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 ± 5.0 mean ± SD years) from an internal biobank.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes >10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a non-malignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis.
MAIN RESULTS AND THE ROLE OF CHANCE
The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 ± 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 ± 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 ± 1.0, n = 8 and 4.1 ± 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to non-alkylating agents were within recently published normative reference values.
LIMITATIONS, REASONS FOR CAUTION
Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available.
WIDER IMPLICATIONS OF THE FINDINGS
This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Förening För Barnasjukvård/ Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Väre Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
At all gas-evolving electrodes, the fraction of the electrode surface area covered by adhering bubbles, the so-called bubble coverage, is of substantial effect on the cell operation. A simple ...empirical relationship is presented to correlate the bubble coverage with the current density. For better understanding the processes, a general relationship is derived showing that numerous further parameters are involved, particularly temperature, pressure and diffusion coefficient, further some parameters which are interrelated with the current density such as supersaturation, gas evolution efficiency and bubble break-off diameter. Experimental investigation is applied to the variation of the break-off diameter and the time-variant change of the bubble coverage.
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