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Antioxidant activity is an essential aspect of oxygen-sensitive merchandise and goods, such as food and corresponding packaging, cosmetics, and biomedicine. Technical lignin has not yet been applied as a natural antioxidant, mainly due to the complex heterogeneous structure and polydispersity of lignin. This report presents antioxidant capacity studies completed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The influence of purification on lignin structure and activity was investigated. The purification procedure showed that double-fold selective extraction is the most efficient (confirmed by ultraviolet-visible (UV/Vis), Fourier transform infrared (FTIR), heteronuclear single quantum coherence (HSQC) and 31P nuclear magnetic resonance spectroscopy, size exclusion chromatography, and X-ray diffraction), resulting in fractions of very narrow polydispersity (3.2⁻1.6), up to four distinct absorption bands in UV/Vis spectroscopy. Due to differential scanning calorimetry measurements, the glass transition temperature increased from 123 to 185 °C for the purest fraction. Antioxidant capacity is discussed regarding the biomass source, pulping process, and degree of purification. Lignin obtained from industrial black liquor are compared with beech wood samples: antioxidant activity (DPPH inhibition) of kraft lignin fractions were 62⁻68%, whereas beech and spruce/pine-mixed lignin showed values of 42% and 64%, respectively. Total phenol content (TPC) of the isolated kraft lignin fractions varied between 26 and 35%, whereas beech and spruce/pine lignin were 33% and 34%, respectively. Storage decreased the TPC values but increased the DPPH inhibition.
Analytical redundancy relations are fundamental in model-based fault detection and isolation. Their numerical evaluation yields a residual that may serve as a fault indicator. Considering switching linear time-invariant system models that use ideal switches, it is shown that analytical redundancy relations can be systematically deduced from a diagnostic bond graph with fixed causalities that hold for all modes of operation. Moreover, as to a faultless system, the presented bond graph–based approach enables to deduce a unique implicit state equation with coefficients that are functions of the discrete switch states. Devices or phenomena with fast state transitions, for example, electronic diodes and transistors, clutches, or hard mechanical stops are often represented by ideal switches which give rise to variable causalities. However, in the presented approach, fixed causalities are assigned only once to a diagnostic bond graph. That is, causal strokes at switch ports in the diagnostic bond graph reflect only the switch-state configuration in a specific system mode. The actual discrete switch states are implicitly taken into account by the discrete values of the switch moduli. The presented approach starts from a diagnostic bond graph with fixed causalities and from a partitioning of the bond graph junction structure and systematically deduces a set of equations that determines the wanted residuals. Elimination steps result in analytical redundancy relations in which the states of the storage elements and the outputs of the ideal switches are unknowns. For the later two unknowns, the approach produces an implicit differential algebraic equations system. For illustration of the general matrix-based approach, an electromechanical system and two small electronic circuits are considered. Their equations are directly derived from a diagnostic bond graph by following causal paths and are reformulated so that they conform with the matrix equations obtained by the formal approach based on a partitioning of the bond graph junction structure. For one of the three mode-switching examples, a fault scenario has been simulated.
Here, we present a miR mechanism which is active in the nucleus and is essential for the production of intron included, C-terminal truncated and biologically active proteins, like e.g. Vim3. We exemplified this mechanism by miRs, miR-15a and miR-498, which are overexpressed in clear cell renal carcinoma or oncocytoma. Both miRs directly interact with DNA in an intronic region, leading to transcriptional stop, and therefore repress the full length version of the pre-mRNA, resulting in intron included truncated proteins (Mxi-2 and Vim3). A computational survey shows that this miR:DNA interactions mechanism may be generally involved in regulating the human transcriptome, with putative interaction sites in intronic regions for over 1000 genes. In this work, an entirely new mechanism is revealed how miRs can repress full length protein translation, resulting in C-terminal truncated proteins.
The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research.
A Method for the Sustainable Documentation of Operations Processes in Parcel Distribution Centers
(2018)
There is often no common understanding on operational processes in logistics companies as they are not properly documented. Hence, people execute the same process differently and training is conducted by experienced operators on an ad-hoc basis. Furthermore, continuous process improvement is hampered as neither the ideal process nor current issues in as-is processes are visible. A major reason for the missing documentation is the complexity of existing business process modelling languages. Modelling experts are required for initially describing the processes and also for updating the models after process changes. Furthermore, operations people are usually not used to read complex process models in EPCs or BPMN diagrams. In order to overcome these limitations, a domain-specific modelling language which facilitates maintaining up-to-date process models has been designed with a large logistics company in Germany. The paper at hand briefly describes this language and illustrates the method on how to apply it in operations environments.
Argentina substantially contributes to the global organic agriculture and food sector due to its large areas of organically managed agricultural land. However, most of the organic production is intended for export. Overall, food supply for the domestic organic market is hardly tapped. Based on this, we investigate the current importance of organic agriculture and food production as well as consumption attitudes and behavior within the country. The novelty of the study also lies in the observation, documentation and analysis of latest stakeholder‐driven developments towards organic agriculture and food. Furthermore, the publication allows the Argentinean organic market to be significantly more visible for the international audience.
Females are influenced more than males by visual cues during many spatial orientation tasks; but females rely more heavily on gravitational cues during visual-vestibular conflict. Are there gender biases in the relative contributions of vision, gravity and the internal representation of the body to the perception of upright? And might any such biases be affected by low gravity? 16 participants (8 female) viewed a highly polarized visual scene tilted ±112° while lying supine on the European Space Agency's short-arm human centrifuge. The centrifuge was rotated to simulate 24 logarithmically spaced g-levels along the long axis of the body (0.04-0.5g at ear-level). The perception of upright was measured using the Oriented Character Recognition Test (OCHART). OCHART uses the ambiguous symbol "p" shown in different orientations. Participants decided whether it was a "p" or a "d" from which the perceptual upright (PU) can be calculated for each visual/gravity combination. The relative contribution of vision, gravity and the internal representation of the body were then calculated. Experiments were repeated while upright. The relative contribution of vision on the PU was less in females compared to males (t=-18.48, p≤0.01). Females placed more emphasis on the gravity cue instead (f:28.4%, m:24.9%) while body weightings were constant (f:63.0%, m:63.2%). When upright (1g) in this and other studies (e.g., Barnett-Cowan et al. 2010, EJN, 31,1899) females placed more emphasis on vision in this task than males. The reduction in weight allocated by females to vision when in simulated low-gravity conditions compared to when upright under normal gravity may be related to similar female behaviour in response to other instances of visual-vestibular conflict. Why this is the case and at which point the perceptual change happens requires further research.
Bei Thymian (Thymus vulgaris) handelt es sich um eine sehr varietätenreiche Art, die aufgrund ihres Gehaltes an therapeutisch wirksamen Inhaltsstoffen als Arzneipflanze monographiert ist. Insbesondere das ätherische Öl mit dem Hauptbestandteil Thymol (ca. 50%) hat eine hohe antioxidative Wirkung. Ziel ist es, dieses Potential als nachhaltig produzierte Additive zu nutzen. Hierfür eignen sich antioxidativ bzw. antimikrobiell wirksame sowie UV-absorbierende Substanzen, die das Produkt bei Zusatz vor oxidativem Stress, mikrobiellem Abbau und Qualitätsverlust schützen.
Hierzu werden zunächst sechs Varianten auf verschiedene Parameter analysiert, um die potenteste Variante auszuwählen. Auf diese Variante wird sich die weitere Forschung konzentrieren.
Daher wird das ätherische Öl durch azeotrope Destillation extrahiert und mittels GCMS analysiert. In Extrakten werden zudem das AP und Absorptionsverhalten bestimmt. Auch die chemische Zusammensetzung des Extrakts sowie die flüchtigen Stoffe des Thymians werden untersucht. Generell gibt es wenig qualitative, teilweise jedoch quantitative Unterschiede: Eine Variante weist u.a. einen deutlich höheren Thymolgehalt im Öl (ca. 65 %) und ein hohes hydrophiles AP auf. Somit ist eine vielversprechende Variante für die weitere Entwicklung und Optimierung bioaktiver Additive gefunden.
Maintaining orientation in an environment with non-Earth gravity (1 g) is critical for an astronaut's operational performance. Such environments present a number of complexities for balance and motion. For example, when an astronaut tilts due to ascending or descending an inclined plane on the moon, the gravity vector will be tilted correctly, but the magnitude will be different from on earth. If this results in a mis-perceived tilt, then that may lead to postural and perceptual errors, such as mis-perceiving the orientation of oneself or the ground plane and corresponding errors in task judgment.
The elucidation of conformations and relative potential energies (rPEs) of small molecules has a long history across a diverse range of fields. Periodically, it is helpful to revisit what conformations have been investigated and to provide a consistent theoretical framework for which clear comparisons can be made. In this paper, we compute the minima, first- and second-order saddle points, and torsion-coupled surfaces for methanol, ethanol, propan-2-ol, and propanol using consistent high-level MP2 and CCSD(T) methods. While for certain molecules more rigorous methods were employed, the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pV5Z theory level was used throughout to provide relative energies of all minima and first-order saddle points. The rPE surfaces were uniformly computed at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVTZ level. To the best of our knowledge, this represents the most extensive study for alcohols of this kind, revealing some new aspects. Especially for propanol, we report several new conformations that were previously not investigated. Moreover, two metrics are included in our analysis that quantify how the selected surfaces are similar to one another and hence improve our understanding of the relationship between these alcohols.
Polyurethane (PU) coatings were successfully produced using unmodified kraft lignin (KL) as an environmentally benign component in contents of up to 80 wt%. Lignin samples were precipitated from industrial black liquor in aqueous solution working at room temperature and different pH levels (pH 2 to pH 5). Lignins were characterized by UV-Vis, FTIR, pyrolysis-GC/MS, SEC and 31P-NMR. Results show a correlation between pH level, OH number and molecular weight Mw of isolated lignins. Lignin-based polyurethane coatings were prepared in an efficient one step synthesis dissolving lignin in THF and PEG425 in an ultrasonic bath followed by addition of 4,4-diphenylmethanediisocyanate (MDI) and triethylamine (TEA). Crosslinking was achieved under very mild conditions (1 hour at room temperature followed by 3 hours at 35 °C). The resulting coatings were characterized regarding their physical properties including ATR-IR, TGA, optical contact angle, light microscopy, REM-EDX and AFM data. Transparent homogeneous films of high flexibility resulted from lignins isolated at pH 4, possessing a temperature resistance up to 160 °C. Swelling tests revealed a resistance against water. Swelling in DMSO depends on index, pH of precipitation and catalyst utilization for PU preparation. According to AFM studies, surface roughness is between 10 and 28 nm.
Amino acids perform multiple essential physiological roles in humans, and accordingly, their importance to health has been the subject of extensive attention. In this special issue of the Journal of Nutrition and Metabolism, we focus on the various inborn errors of amino acid metabolism, their diagnostic challenges, new treatment approaches, and recent advances in patient monitoring as well as clinical outcomes.
Triple-negative breast cancer (TNBC) lacks targeted therapies and has a worse prognosis than other breast cancer subtypes, underscoring an urgent need for new therapeutic targets and strategies. IRE1 is an endoplasmic reticulum (ER) stress sensor, whose activation is predominantly linked to the resolution of ER stress and, in the case of severe stress, to cell death. Here we demonstrate that constitutive IRE1 RNase activity contributes to basal production of pro-tumorigenic factors IL-6, IL-8, CXCL1, GM-CSF, and TGFβ2 in TNBC cells. We further show that the chemotherapeutic drug, paclitaxel, enhances IRE1 RNase activity and this contributes to paclitaxel-mediated expansion of tumor-initiating cells. In a xenograft mouse model of TNBC, inhibition of IRE1 RNase activity increases paclitaxel-mediated tumor suppression and delays tumor relapse post therapy. We therefore conclude that inclusion of IRE1 RNase inhibition in therapeutic strategies can enhance the effectiveness of current chemotherapeutics.
The use of wearable devices or “wearables” in the physical activity domain has been increasing in the last years. These devices are used as training tools providing the user with detailed information about individual physiological responses and feedback to the physical training process. Advantages in sensor technology, miniaturization, energy consumption and processing power increased the usability of these wearables. Furthermore, available sensor technologies must be reliable, valid, and usable. Considering the variety of the existing sensors not all of them are suitable to be integrated in wearables. The application and development of wearables has to consider the characteristics of the physical training process to improve the effectiveness and efficiency as training tools. During physical training, it is essential to elicit individual optimal strain to evoke the desired adjustments to training. One important goal is to neither overstrain nor under challenge the user. Many wearables use heart rate as indicator for this individual strain. However, due to a variety of internal and external influencing factors, heart rate kinetics are highly variable making it difficult to control the stress eliciting individually optimal strain. For optimal training control it is essential to model and predict individual responses and adapt the external stress if necessary. Basis for this modeling is the valid and reliable recording of these individual responses. Depending on the heart rate kinetics and the obtained physiological data, different models and techniques are available that can be used for strain or training control. Aim of this review is to give an overview of measurement, prediction, and control of individual heart rate responses. Therefore, available sensor technologies measuring the individual heart rate responses are analyzed and approaches to model and predict these individual responses discussed. Additionally, the feasibility for wearables is analyzed.
In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast cancer, UPR signalling promotes a malignant phenotype and can confer tumours with resistance to widely used therapies. Here, we review several roles for UPR signalling in breast cancer, highlighting UPR-mediated therapy resistance and the potential for targeting the UPR alone or in combination with existing therapies.
Small Molecules Enhance Scaffold-Based Bone Grafts via Purinergic Receptor Signaling in Stem Cells
(2018)
The need for bone grafts is high, due to age-related diseases, such as tumor resections, but also accidents, risky sports, and military conflicts. The gold standard for bone grafting is the use of autografts from the iliac crest, but the limited amount of accessible material demands new sources of bone replacement. The use of mesenchymal stem cells or their descendant cells, namely osteoblast, the bone-building cells and endothelial cells for angiogenesis, combined with artificial scaffolds, is a new approach. Mesenchymal stem cells (MSCs) can be obtained from the patient themselves, or from donors, as they barely cause an immune response in the recipient. However, MSCs never fully differentiate in vitro which might lead to unwanted effects in vivo. Interestingly, purinergic receptors can positively influence the differentiation of both osteoblasts and endothelial cells, using specific artificial ligands. An overview is given on purinergic receptor signaling in the most-needed cell types involved in bone metabolism-namely osteoblasts, osteoclasts, and endothelial cells. Furthermore, different types of scaffolds and their production methods will be elucidated. Finally, recent patents on scaffold materials, as wells as purinergic receptor-influencing molecules which might impact bone grafting, are discussed.
Innovations in the mobility industry such as automated and connected cars could significantly reduce congestion and emissions by allowing the traffic to flow more freely and reducing the number of vehicles according to some researchers. However, the effectiveness of these sustainable product and service innovations is often limited by unexpected changes in consumption: some researchers thus hypothesize that the higher comfort and improved quality of time in driverless cars could lead to an increase in demand for driving with autonomous vehicles. So far, there is a lack of empirical evidence supporting either one or other of these hypotheses. To analyze the influence of autonomous driving on mobility behavior and to uncover user preferences, which serve as indicators for future travel mode choices, we conducted an online survey with a paired comparison of current and future travel modes with 302 participants in Germany. The results do not confirm the hypothesis that ownership will become an outdated model in the future. Instead they suggest that private cars, whether conventional or fully automated, will remain the preferred travel mode. At the same time, carsharing will benefit from full automation more than private cars. However, the findings indicate that the growth of carsharing will mainly be at the expense of public transport, showing that more emphasis should be placed in making public transport more attractive if sustainable mobility is to be developed.
We present the performance of the upGREAT heterodyne array receivers on the SOFIA telescope after several years of operations. This instrument is a multi-pixel high resolution (R≳107) spectrometer for the Stratospheric Observatory for Far-Infrared Astronomy (SOFIA). The receivers use 7-pixel subarrays configured in a hexagonal layout around a central pixel. The low frequency array receiver (LFA) has 2×7 pixels (dual polarization), and presently covers the 1.83–2.07THz frequency range, which allows to observe the [CII] and [OI] lines at 158μm and 145μm wavelengths. The high frequency array (HFA) covers the [OI] line at 63μm and is equipped with one polarization at the moment (7 pixels, which can be upgraded in the near future with a second polarization array). The 4.7THz array has successfully flown using two separate quantum-cascade laser local oscillators from two different groups. NASA completed the development, integration and testing of a dual-channel closed-cycle cryocooler system, with two independently operable He compressors, aboard SOFIA in early 2017 and since then, both arrays can be operated in parallel using a frequency separating dichroic mirror. This configuration is now the prime GREAT configuration and has been added to SOFIA’s instrument suite since observing cycle 6.
Pozzolanic properties of Pennisetum purpureum grass ash were tested on Portland cement. Results show that the ash can be blended with cements without compromising binding strength of the cement. It was found that Portland cement could be blended with Pennisetum purpureum up to a ratio of 3:2 compromising compressive strength of mortar.Mortar with lower cement replacement took longer to set as evidenced by lower compressive strength within the 28-day aging time. Mortar with higher cement replacement had lower water absorption capacity, an indication that the test pozzolan was of smaller particulate size. XRF analysis and the FTIR spectrum showed that the ash has a higher content of silica. The XRD pattern of the ash showed that the ash was predominantly amorphous. SEM images showed that the ash produced at 600 o C had residual carbon material.
3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HMGCL, HMGCL) deficiency is a rare inborn error of ketogenesis. Even if the ketogenic enzyme is fully disrupted, an elevated signal for the ketone body acetoacetic acid is a frequent observation in the analysis of urinary organic acids, at least if derivatization is performed by methylation. We provide an explanation for this phenomenon and trace it back to degradation of the derivatized 3-hydroxy-3-methylglutaric acid and high temperature of the injector of the gas chromatograph.
Major progress occurred in understanding inborn errors of ketone body transport and metabolism between the International Congresses on Inborn Errors of Metabolism in Barcelona (2013) and Rio de Janeiro (2017). These conditions impair either ketogenesis (presenting as episodes of hypoketotic hypoglycemia) or ketolysis (presenting as ketoacidotic episodes); for both groups, immediate intravenous glucose administration is the most critical and (mHGGCS, HMGCS2) effective treatment measure.
Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.
Through the “Act to Strengthen the Non-financial Reporting by Corporations in their Management and Group Management Reports” (Gesetz zur Stärkung der nichtfinanziellen Berichterstattung der Unternehmen in ihren Lage- und Konzernlageberichten) (CSR Directive Transposition Act, „CSR-RUG“) of 11 April 2017[1], the German Bundestag implemented Directive 2014/95/EU (“CSR Directive”)[2] into German law. Following the European impetus, the CSR-RUG enriches the traditional repertoire of forms of action under environmental law by a further instrument. Already the regulatory context gives an idea of its atypical nature: The centrepiece of the CSR-RUG is the amendment of and addition to the Third Book of the German Commercial Code (Handelsgesetzbuch, “HGB”), which deals with the “trading books” of undertakings, i.e., accounting and reporting requirements. Since the reporting year 2017, large capital market-oriented corporations must report extensively within the framework of their annual management reports on their activities and effects in certain areas of “Corporate Social Responsibility”. This also includes environmental matters. The transparency and publicity this entails is intended to generate positive stimuli for more responsible, sustained and not least of all environmentally friendly entrepreneurial action.
Following a brief presentation of the European legal bases and their implementation in Germany (I.), we will classify the provisions within the underlying concept of Corporate Social Responsibility (II.) and analyse and systemise the governance effects of non-financial reporting (III.). A few remarks on selected aspects of the chosen approach and its implementation (IV.) as well as an outlook summarising our conclusions (V.) will complete this article. By detailing the German approach to transposing the CSR Directive, this paper intends to provide an example of the challenges member state legislators face when complying with modern governance concepts such as Corporate Social Responsibility by way of non-financial reporting obligations.
[1] Federal Law Gazette, Part I 2017, 802 et seq.
[2] Directive 2014/95/EU of the European Parliament and of the Council 22 October 2014 amending Directive 2013/34/EU as regards disclosure of non-financial and diversity information by certain large undertakings and groups, OJ EU No. L 330, p. 1.
Renewable resources are gaining increasing interest as a source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on its resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as a renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, the literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014⁻2018). Special focus is placed on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.