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Climate change presents a pressing global challenge, necessitating urgent action across all sectors of society. More and more companies are pledging ambitious decarbonization goals. In this context, green bonds have emerged as a significant financial instrument for financing sustainable initiatives, particularly in the corporate sector. This study investigates the relationship between the decarbonization ambitions of private issuers and the "greenium" of corporate green bonds. The greenium refers to the premium or discount associated with these environmentally focused bonds compared to their conventional counterparts. Through a comprehensive literature review, the study examines prior research on climate change urgency, corporate decarbonization efforts, the evolution of the green bond market and how bonds get their green certification. Utilizing a dataset of "Use of Proceed" green bonds issued by private listed companies in the European Union over the past five years, the study employs panel regression analysis to explore the impact of decarbonization targets on the greenium. The findings aim to provide insights for corporate strategies, informing decisions at the nexus of sustainability and financial markets. By contributing empirical evidence to this critical dialogue, the research seeks to advance understanding and facilitate informed action towards a low-carbon future

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M-/-CIITA-/-CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16 weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4 weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40 weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected.

In this work, we present a study of the propagation of low-frequency magneto-acoustic waves into the solar chromosphere within small-scale inclined magnetic fields over a quiet-magnetic network region utilizing near-simultaneous photospheric and chromospheric Dopplergrams obtained from the HMI instrument onboard SDO spacecraft and the Multi-Application Solar Telescope (MAST) operational at the Udaipur Solar Observatory, respectively. Acoustic waves are stochastically excited inside the convection zone of the Sun and intermittently interact with the background magnetic fields resulting into episodic signals. In order to detect these episodic signals, we apply the wavelet transform technique to the photospheric and chromospheric velocity oscillations in magnetic network regions. The wavelet power spectrum over photospheric and chromospheric velocity signals show a one-to-one correspondence between the presence of power in the 2.5-4 mHz band. Further, we notice that power in the 2.5-4 mHz band is not consistently present in the chromospheric wavelet power spectrum despite its presence in the photospheric wavelet power spectrum. This indicates that leakage of photospheric oscillations (2.5-4 mHz band) into the higher atmosphere is not a continuous process. The average phase and coherence spectra estimated from these photospheric and chromospheric velocity oscillations illustrate the propagation of photospheric oscillations (2.5-4 mHz) into the solar chromosphere along the inclined magnetic fields. Additionally, chromospheric power maps estimated from the MAST Dopplergrams also show the presence of high-frequency acoustic halos around relatively high magnetic concentrations, depicting the refraction of high-frequency fast mode waves around vA ~ vs layer in the solar atmosphere., Comment: 16 pages, 7 figures, Accepted for Publication in Journal of Atmospheric and Solar-Terrestrial Physics (Special Issue of STP-15)

Phosphoglycerate kinase-1 (PGK1) deficiency is a rare X-linked disorder caused by pathogenic variants in the PGK1 gene. Complete loss-of-function variants have not been reported in this gene, indicating that residual enzyme function is critical for viability in males. Therefore, copy number variants (CNVs) that include single exon or multiple exon deletions or duplications are generally not expected in individuals with PGK1 deficiency. Here we describe a 64-year-old male presenting with a family history (three additional affected males) and a personal history of childhood-onset metabolic myopathy that involves episodes of muscle pain, stiffness after activity, exercise intolerance, and myoglobinuria after exertion. Biochemical analysis on a muscle biopsy indicated significantly reduced activity (15% compared to normal) for phosphoglycerate kinase (PGK1), a glycolytic enzyme encoded by PGK1. A diagnosis of PGK1 deficiency was established by molecular analysis which detected an approximately 886 kb deletion involving the polyadenylation site in the 3'UTR of the PGK1 gene. RNA analysis showed significantly reduced PGK1 transcript levels (30% compared to normal). This is the first deletion reported in the PGK1 gene and is the first pathogenic variant involving the 3'UTR polyadenylation site of this gene. Our report emphasizes the role of 3'UTR variants in human disorders and underscores the need for exploring noncoding regions of disease-associated genes when seeking a molecular diagnosis.

ObjectiveLimb-girdle muscular dystrophies (LGMDs), one of the most heterogeneous neuromuscular disorders (NMDs), involves predominantly proximal-muscle weakness with >30 genes associated with different subtypes. The clinical-genetic overlap among subtypes and with other NMDs complicate disease-subtype identification lengthening diagnostic process, increases overall costs hindering treatment/clinical-trial recruitment. Currently seven LGMD clinical trials are active but still no gene-therapy-related treatment is available. Till-date no nation-wide large-scale LGMD sequencing program was performed. Our objectives were to understand LGMD genetic basis, different subtypes' relative prevalence across US and investigate underlying disease mechanisms.MethodsA total of 4656 patients with clinically suspected-LGMD across US were recruited to conduct next-generation sequencing (NGS)-based gene-panel testing during June-2015 to June-2017 in CLIA-CAP-certified Emory-Genetics-Laboratory. Thirty-five LGMD-subtypes-associated or LGMD-like other NMD-associated genes were investigated. Main outcomes were diagnostic yield, gene-variant spectrum, and LGMD subtypes' prevalence in a large US LGMD-suspected population.ResultsMolecular diagnosis was established in 27% (1259 cases; 95% CI, 26-29%) of the patients with major contributing genes to LGMD phenotypes being: CAPN3(17%), DYSF(16%), FKRP(9%) and ANO5(7%). We observed an increased prevalence of genetically confirmed late-onset Pompe disease, DNAJB6-associated LGMD subtype1E and CAPN3-associated autosomal-dominant LGMDs. Interestingly, we identified a high prevalence of patients with pathogenic variants in more than one LGMD gene suggesting possible synergistic heterozygosity/digenic/multigenic contribution to disease presentation/progression that needs consideration as a part of diagnostic modality.InterpretationOverall, this study has improved our understanding of the relative prevalence of different LGMD subtypes, their respect

ObjectiveLimb-girdle muscular dystrophies (LGMDs), one of the most heterogeneous neuromuscular disorders (NMDs), involves predominantly proximal-muscle weakness with >30 genes associated with different subtypes. The clinical-genetic overlap among subtypes and with other NMDs complicate disease-subtype identification lengthening diagnostic process, increases overall costs hindering treatment/clinical-trial recruitment. Currently seven LGMD clinical trials are active but still no gene-therapy-related treatment is available. Till-date no nation-wide large-scale LGMD sequencing program was performed. Our objectives were to understand LGMD genetic basis, different subtypes' relative prevalence across US and investigate underlying disease mechanisms.MethodsA total of 4656 patients with clinically suspected-LGMD across US were recruited to conduct next-generation sequencing (NGS)-based gene-panel testing during June-2015 to June-2017 in CLIA-CAP-certified Emory-Genetics-Laboratory. Thirty-five LGMD-subtypes-associated or LGMD-like other NMD-associated genes were investigated. Main outcomes were diagnostic yield, gene-variant spectrum, and LGMD subtypes' prevalence in a large US LGMD-suspected population.ResultsMolecular diagnosis was established in 27% (1259 cases; 95% CI, 26-29%) of the patients with major contributing genes to LGMD phenotypes being: CAPN3(17%), DYSF(16%), FKRP(9%) and ANO5(7%). We observed an increased prevalence of genetically confirmed late-onset Pompe disease, DNAJB6-associated LGMD subtype1E and CAPN3-associated autosomal-dominant LGMDs. Interestingly, we identified a high prevalence of patients with pathogenic variants in more than one LGMD gene suggesting possible synergistic heterozygosity/digenic/multigenic contribution to disease presentation/progression that needs consideration as a part of diagnostic modality.InterpretationOverall, this study has improved our understanding of the relative prevalence of different LGMD subtypes, their respect

We present properties of intensity oscillations of a sunspot in the photosphere and chromosphere using G~band and CaIIH filtergrams from Hinode. Intensity power maps as function of magnetic field strength and frequency reveal reduction of power in Gband with increase in photospheric magnetic field strength at all frequencies. In CaIIH, however, stronger fields exhibit more power at high frequencies particularly in the 4.5 mHz-8.0 mHz band. Power distribution in different locations of the active region show that the oscillations in CaIIH exhibit more power in comparison to that of Gband. We also relate the power in intensity oscillations with different components of the photospheric vector magnetic field using near simultaneous spectro-polarimetric observations of the sunspot from the Hinode spectropolarimeter. The photospheric umbral power is strongly anti-correlated with the magnetic field strength and its the line-of-sight component while there is a good correlation with the transverse component. A reversal of this trend is observed in the chromosphere with the exception at low frequencies ($\nu\le$ 1.5 mHz). The power in sunspot penumbrae is anti-correlated with the magnetic field parameters at all frequencies (1.0 $\le\nu\le$ 8.0 mHz) in both the photosphere and chromosphere, except that the chromospheric power shows a strong correlation in the frequency range 3-3.5 mHz., Comment: Accepted for publication in the journal "Research in Astronomy and Astrophysics (RAA)"

We present properties of intensity oscillations of a sunspot in the photosphere and chromosphere using G~band and CaIIH filtergrams from Hinode. Intensity power maps as function of magnetic field strength and frequency reveal reduction of power in Gband with increase in photospheric magnetic field strength at all frequencies. In CaIIH, however, stronger fields exhibit more power at high frequencies particularly in the 4.5 mHz-8.0 mHz band. Power distribution in different locations of the active region show that the oscillations in CaIIH exhibit more power in comparison to that of Gband. We also relate the power in intensity oscillations with different components of the photospheric vector magnetic field using near simultaneous spectro-polarimetric observations of the sunspot from the Hinode spectropolarimeter. The photospheric umbral power is strongly anti-correlated with the magnetic field strength and its the line-of-sight component while there is a good correlation with the transverse component. A reversal of this trend is observed in the chromosphere with the exception at low frequencies ($\nu\le$ 1.5 mHz). The power in sunspot penumbrae is anti-correlated with the magnetic field parameters at all frequencies (1.0 $\le\nu\le$ 8.0 mHz) in both the photosphere and chromosphere, except that the chromospheric power shows a strong correlation in the frequency range 3-3.5 mHz., Comment: Accepted for publication in the journal "Research in Astronomy and Astrophysics (RAA)"

Muscular dystrophies have historically been characterised according to clinical criteria, however in the genomic age the muscular dystrophies are now subdivided into groups according to the primary gene defect. Currently identified are 29 different loci and encoded proteins, giving rise to 34 distinct forms of muscular dystrophy (Dalkilic & Kunkel 2003;Hsu 2004). The majority of these types of muscular dystrophy are caused by perturbations of different components of the dystrophin-glycoprotein complex (DGC) an integral component of the cellular cytoskeleton (see below). Dystrophin is the largest component of the DGC and is absent in Duchenne muscular dystrophy (DMD), and severely truncated with decreased levels in Becker muscular dystrophy (BMD) (Hoffman & Kunkel 1989). DMD and the allelic BMD are the most common forms of muscular dystrophy in humans and together they are termed dystrophinopathies (Kingston et al. 1984; Shaw & Dreifuss1969). DMD alone accounts for approximately 80% of all the myopathies in the muscular dystrophy group (Culligan et al. 1998).The dystrophin gene is the second largest described to date, totalling 1.5% of the X chromosome, 0.1% of the entire genome. The DMD gene is 99% introns, with a coding sequence of 86 exons (including the promoters) and remains the only known human metagene (Blake et al. 2002; Burmeister et al. 1988; Hamed & Hoffmann 2006; Kenwrick et al. 1987; Koenig et al. 1987; Kunkel et al. 1986; Muntoni et al. 2003; Roberts et al. 1993; Smith et al. 2006; Van Ommen et al. 1987; Wallis et al. 2004). Dystrophin wasdemonstrated to be localised at the sarcolemma in human skeletal muscle after its’ genetic characterisation (Arahata et al. 1988; Sugita et al. 1988; Zubrzycka-Gaarn et al. 1988). This discovery was followed by a report of dystrophin messenger RNA in brain, with the protein being specifically localised at postsynaptic densities (PSD) in the CNS, in particular in the hippocampus, cerebral cortex and in cerebellar Purkin

Branched fibers are a well-documented phenomenon of regenerating dystrophic skeletal muscle. They are found in the muscles of boys with Duchenne muscular dystrophy (DMD) and in the muscles of mdx “aged” mice, an animal model of DMD. However, only a handful of studies have investigated how the contractile properties of these morphologically deformed fibers differ from those of normal fibers in aged muscle. These studies have found an association between the extent of fiber branching and susceptibility to damage from eccentric contractions. They have also found that branched muscle fibers cannot sustain maximal contractions and that branch points are sites of increased mechanical stress. Newimaging techniques like second harmonic imaging have revealed that the sub-cellular myofibrillar structure is greatly disturbed at branch points. These findings have important implications for understanding the function of dystrophin. It is commonly thought that dystrophin’s role is to mechanically stabilise the sarcolemma, as numerous studies haveshown that eccentric contractions damage dystrophic muscle more than normal muscle. However, the finding that branched fibers are mechanically weakened raises the question: Is it the lack of dystrophin, or is it the fiber branching, that leads to the vulnerability of dystrophic muscle to contractile damage? The other question is how the presence of these branched fibers alters the contractile properties of “aged” dystrophic muscle. Throughout this chapter I will use the term branched to describe the malformed fibers. Most earlier studies use the terminology “split fiber”, but because it conjures up images of a Y-shapedbifurcation, with one adult fiber giving rise to two daughter fibers it is somewhat misleading as we now know many fibers, if not most display a complex syncytia of interconnecting branches. Some branches do not originate from the main fiber but are results of incomplete regeneration with myotubes fusing to repair the damage