The King of Rockingham County and the Original Bridge to Nowhere

This chapter, reveals the story -- the clash of personalities, the economic tensions, and the political significance -- behind Rockingham County v. Luten Bridge Co. Since its publication in 1929, the opinion has proceeded to leave an impression on generations of law students. Luten Bridge, a staple in most contracts casebooks, is known today as the paradigmatic case that demonstrates the duty to mitigate damages in contract law, whereby a nonbreaching party is not compensated for performance that occurs after the other party announces an intention to breach. This chapter takes on three objectives: it identifies the case\u27s original importance, uncovers the opinion\u27s political and jurisprudential significance, and tells a remarkable story, one that arose within a heated tax revolt pitting the county\u27s farmers against its most celebrated industrialist. Much more than a crisp illustration of the duty to mitigate, Rockingham County v. The Luten Bridge Co. offers a window into a southern community\u27s struggles with a divided social order, the introduction of wealth into local politics, and a changing economy

Subjective mental well-being among higher education students in Finland during the first wave of COVID-19

Aims: Increased mental health problems during the COVID-19 pandemic have become a major concern among young adults. Our aim was to understand which COVID-19-related questions predicted mental well-being during the outbreak. Methods: Two cross-sectional datasets were used. The primary dataset was collected in May 2020 (n = 1001), during the initial COVID-19 outbreak, and the secondary in April 2019 (n = 10866), before the pandemic. Mental well-being was assessed with the Short Warwick-Edinburgh Mental Well-Being Scale. Relationships between mental well-being and COVID-19-related questions were investigated with lasso regression. As an exploratory analysis, two-way ANOVAs were used to compare mental well-being before and during the outbreak. Results: Higher levels of mental well-being were associated with lower levels of academic stress and COVID-19-related worry, along with a higher satisfaction with the procedures and information provided by the higher education institutions and the government. COVID-19-related symptoms and infections did not have an impact on students' mental well-being during the outbreak. Small to moderate effect sizes across the time points were detected, indicating an overall decrease in mental well-being across age and gender during the outbreak. Conclusions: COVID-19 had an impact on higher education students' mental well-being. Higher education institutes may play a crucial role in protecting their students' well-being during uncertain times.Peer reviewe

Nuorten avomuotoinen OPI-mielenterveyskuntoutus : Koettu hyöty ja vaikuttavuus sekä kuntoutusmallin soveltuvuus

OPI-hankkeen tarkoituksena oli kehittää avomuotoista kuntoutusmallia ammatillisessa koulutuksessa oleville 16–25-vuotiaille opiskelijoille, joilla oli diagnosoitu masennus- ja/tai ahdistuneisuushäiriö. Kuntoutusmallilla pyrittiin tukemaan nuoria elämänhallinnassa ja opiskelussa, vahvistamaan nuoren toimintakykyä ja hyvinvointia sekä vähentämään mielenterveysongelmiin liittyviä haittoja. Vuosina 2011–2013 toteutettiin yhteensä kahdeksan avomuotoista ryhmäkuntoutuskurssia, joihin kuului myös yksilökäyntejä sekä verkostotapaamisia. Kurssit kestivät seurantoineen noin 1,5 vuotta ja ne toteutettiin lukukausien aikana. OPI-hankkeen yhteydessä toteutettiin arviointitutkimus, jonka tavoite oli selvittää kuntoutusmallin koettua hyötyä ja vaikuttavuutta, sidosryhmäyhteistyötä sekä kuntoutusmallin soveltuvuutta vakiintuneeksi toiminnaksi. Tutkimukseen osallistui 70 kuntoutujaa. Aineistoa kerättiin kyselylomakkeilla sekä eri tahojen haastatteluilla (kuntoutujat, projektiryhmät). Kuntoutuksen ja opiskelujen yhteen nivominen onnistui enimmäkseen hyvin. Ryhmässä saatu vertaistuki koettiin kuntoutuksen suurimmaksi anniksi. Seuranta-aikana nuorten masennusoireet vähenivät, elämänlaatu, itse arvioitu terveydentila sekä opiskelukyky ja kognitiivinen toimintakyky kohentuivat. Nuoret olisivat kuitenkin tarvinneet kuntoutusta jo varhaisemmassa vaiheessa. Noin kolme nuorta neljästä arvioi, että oli saavuttanut kuntoutukselle asettamansa tavoitteet vähintään melko hyvin. Tavoitteiden saavuttaminen ja kuntoutuksen koettu vaikuttavuus olivat yhteydessä kuntoutuksen oikea-aikaisuuteen, yhteistyöhön hoitavan tahon sekä opiskeluterveydenhuollon kanssa sekä vuorovaikutuksen onnistumiseen ohjaajan ja nuoren välillä. Tutkimuksen tulokset antavat varsin rohkaisevan kuvan oppilaitoksen kanssa yhteistyössä toimivan ja opintojen kanssa yhteen sovitetun kuntoutuksen mahdollisuuksista nuorten syrjäytymisen ehkäisemisessä

Asmase Regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage nonalcoholic steatohepatitis

Background & Aims: Acid sphingomyelinase (ASMase) is activated in nonalcoholic steatohepatitis (NASH). However, ASMase's contribution to NASH is poorly understood and limited to hepatic steatosis and glucose metabolism. Here we examined ASMase's role in high fat diet (HFD)-induced NASH. Methods: Autophagy, endoplasmic reticulum (ER) stress and lysosomal membrane permeabilization (LMP) were determined in ASMase-/- mice fed HFD. The impact of pharmacological ASMase inhibition on NASH was analyzed in wild type mice fed HFD. Results: ASMase deficiency determined resistance to HFD or methionine and choline deficient diet-mediated hepatic steatosis. ASMase-/- mice were resistant to HFD-induced hepatic ER stress, but sensitive to tunicamycin-mediated ER stress and steatosis, indicating selectivity in the resistance of ASMase-/- mice to ER stress. Autophagic flux determined in the presence of rapamycin and/or chloroquine was lower in primary mouse hepatocytes (PMH) from ASMase-/- mice and accompanied by increased p62 levels, suggesting autophagic impairment. Moreover, autophagy suppression by chloroquine and brefeldinA caused ER stress in PMH from ASMase+/+ mice but not ASMase-/- mice. ASMase-/- PMH exhibited increased lysosomal cholesterol loading, decreased LMP and apoptosis resistance induced by O-methyl-serine dodecylamide hydrochloride or palmitic acid, effects that were reversed by decreasing cholesterol levels by the oxysterol 25-hydroxycholesterol. In vivo pharmacological ASMase inhibition by amitriptyline, a widely used tricyclic antidepressant, protected wild type mice against HFD- induced hepatic steatosis, fibrosis, and liver damage, effects indicative of early-stage NASH. Conclusions: These findings underscore a critical role for ASMase in diet-induced NASH and suggest the potential of amitriptyline as a treatment for patients with NASH

QTL for phytosterol and sinapate ester content in Brassica napus L. collocate with the two erucic acid genes

Improving oil and protein quality for food and feed purposes is an important goal in rapeseed (Brassica napus L.) breeding programs. Rapeseed contains phytosterols, used to enrich food products, and sinapate esters, which are limiting the utilization of rapeseed proteins in the feed industry. Increasing the phytosterol content of oil and lowering sinapate ester content of meal could increase the value of the oilseed rape crop. The objective of the present study was to identify quantitative trait loci (QTL) for phytosterol and sinapate ester content in a winter rapeseed population of 148 doubled haploid lines, previously found to have a large variation for these two traits. This population also segregated for the two erucic acid genes. A close negative correlation was found between erucic acid and phytosterol content (Spearman’s rank correlation, rs = −0.80**). For total phytosterol content, three QTL were detected, explaining 60% of the genetic variance. The two QTL with the strongest additive effects were mapped on linkage groups N8 and N13 within the confidence intervals of the two erucic acid genes. For sinapate ester content four QTL were detected, explaining 53% of the genetic variance. Again, a close negative correlation was found between erucic acid and sinapate ester content (rs = −0.66**) and the QTL with the strongest additive effects mapped on linkage groups N8 and N13 within the confidence intervals of the two erucic acid genes. The results suggests, that there is a pleiotropic effect of the two erucic acid genes on phytosterol and sinapate ester content; the effect of the alleles for low erucic acid content is to increase phytosterol and sinapate ester content. Possible reasons for this are discussed based on known biosynthetic pathways

Interplay between Structure and Dynamics in Chitosan Films Investigated with Solid-State NMR, Dynamic Mechanical Analysis, and X-ray Diffraction

Modern solid-state NMR techniques, combined with X-ray diffraction, revealed the molecular origin of the difference in mechanical properties of self-associated chitosan films. Films cast from acidic aqueous solutions were compared before and after neutralization, and the role of the counterion (acetate vs Cl⁻) was investigated. There is a competition between local structure and long-range order. Hydrogen bonding gives good mechanical strength to neutralized films, which lack long-range organization. The long-range structure is better defined in films cast from acidic solutions in which strong electrostatic interactions cause rotational distortion around the chitosan chains. Plasticization by acetate counterions enhances long-range molecular organization and film flexibility. In contrast, Cl⁻ counterions act as a defect and impair the long-range organization by immobilizing hydration water. Molecular motion and proton exchange are restricted, resulting in brittle films despite the high moisture content

The risk of angiosarcoma following primary breast cancer

Lymphangiosarcoma of the upper extremity is a rare and aggressive tumour reported to occur following post-mastectomy lymphoedema (Stewart–Treves syndrome). Haemangiosarcoma, a related rare tumour, has occasionally been reported to occur in the breast following irradiation. We conducted a case-control study using the University of Southern California-Cancer Surveillance Program, the population-based cancer registry for Los Angeles County, to evaluate the relationship between invasive female breast cancer and subsequent upper extremity or chest lymphangiosarcoma and haemangiosarcoma together referred to as angiosarcoma. Cases were females diagnosed between 1972 and 1995 with angiosarcoma of the upper extremity (n = 20) or chest (n = 48) who were 25 years of age or older and residing in Los Angeles County when diagnosed. Other sarcomas at the same anatomic sites were also studied. Controls were females diagnosed with cancers other than sarcoma during the same time period (n = 266 444). Cases and controls were then compared with respect to history of a prior invasive epithelial breast cancer. A history of breast cancer increased the risk of upper extremity angiosarcoma by more than 59-fold (odds ratio [OR] = 59.3, 95% confidence interval [95% CI] = 21.9–152.8). A strong increase in risk after breast cancer was also observed for angiosarcoma of the chest and breast (OR = 11.6, 95% CI = 4.3–26.1) and for other sarcomas of the chest and breast (OR = 3.3, 95% CI = 1.1–1.7). © 1999 Cancer Research Campaig

Up-regulated expression of LAMP2 and autophagy activity during neuroendocrine differentiation of prostate cancer LNCaP cells

Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells. Using cDNA microarrays, we compared gene expression profiles of NE cells and non-differentiated LNCaP cells. We identified up-regulation of 155 genes, among them LAMP2, a lysosomal membrane protein involved in lysosomal stability and autophagy. We then confirmed up-regulation of LAMP2 in NE cells by qRT-PCR, Western blot and confocal microscopy assays, showing that mRNA up-regulation correlated with increased levels of LAMP2 protein. Subsequently, we determined autophagy activity in NE cells by assessing the protein levels of SQSTM/p62 and LC3 by Western blot and LC3 and Atg5 mRNAs content by qRT-PCR. The decreased levels of SQSTM/p62 was accompanied by an enhanced expression of LC3 and ATG5, suggesting activation of autophagy in NE cells. Blockage of autophagy with 1μM AKT inhibitor IV, or by silencing Beclin 1 and Atg5, prevented NE cell differentiation, as revealed by decreased levels of the NE markers. In addition, AKT inhibitor IV as well as Beclin1 and Atg5 kwockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these results suggest that LAMP2 overexpression assists NE differentiation of LNCaP cells induced by serum deprivation and facilitates autophagy activity in order to attain the NE phenotype and cell survival. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer

Characterization of different FAD-dependent glucose dehydrogenases for possible use in glucose-based biosensors and biofuel cells

In this study, different flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenases (FADGDHs) were characterized electrochemically after “wiring” them with an osmium redox polymer [Os(4,4′-dimethyl-2,2′-bipyridine)2(PVI)10Cl]+ on graphite electrodes. One tested FADGDH was that recently discovered in Glomerella cingulata (GcGDH), another was the recombinant form expressed in Pichia pastoris (rGcGDH), and the third was a commercially available glycosylated enzyme from Aspergillus sp. (AspGDH). The performance of the Os-polymer “wired” GDHs on graphite electrodes was tested with glucose as the substrate. Optimal operational conditions and analytical characteristics like sensitivity, linear ranges and current density of the different FADGDHs were determined. The performance of all three types of FADGDHs was studied at physiological conditions (pH 7.4). The current densities measured at a 20 mM glucose concentration were 494 ± 17, 370 ± 24, and 389 ± 19 μA cm−2 for GcGDH, rGcGDH, and AspGDH, respectively. The sensitivities towards glucose were 2.16, 1.90, and 1.42 μA mM−1 for GcGDH, rGcGDH, and AspGDH, respectively. Additionally, deglycosylated rGcGDH (dgrGcGDH) was investigated to see whether the reduced glycosylation would have an effect, e.g., a higher current density, which was indeed found. GcGDH/Os-polymer modified electrodes were also used and investigated for their selectivity for a number of different sugars