Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypertriglyceridemia and Hyperinsulinemia Are Potent Inducers of Endothelin-1 Release in Humans

The purpose of the study was to evaluate fasting endothelin-1 levels in subjects with syndrome X, in subjects with insulinoma, and in normal subjects. The single and synergistic contributions of insulin and triglyceride levels to endothelin-1 release were studied in normal subjects. This was achieved by the evaluation of endothelin-1 levels in response to an insulin bolus combined with a euglycemic clamp (protocol A) and during intralipid (test 1) or saline (test 2) infusions lasting 360 min (protocol B). In protocol B, a euglycemic two-step hyperinsulinemic (25 and 125 mU · kg−1 · h−1) clamp was started at 120 min. Subjects with syndrome × showed significantly higher endothelin-1 levels than normal subjects and subjects with insulinoma (7.22 ± 0.89 vs. 2.61 ± 0.38 and 2.49 ± 0.24 pg/ml, P < 0.01). After an insulin bolus, endothelin-1 levels peaked at 10 min (3.71 ± 0.96 pg/ml). The incremental area of endothelin-1 was significantly higher after insulin than after a saline bolus. In test 1, an acute increase in triglyceride levels significantly enhanced endothelin-1 levels, with were further increased by the synergistic contribution of high insulin and triglyceride levels. In test 2, endothelin-1 release was achieved at high insulin levels but remained significantly lower than in test 1. In conclusion, subjects with syndrome × showed higher endothelin-1 levels than normal subjects and subjects with insulinoma. These levels were reproduced in normal subjects by a simultaneous increase in insulin and triglyceride levels.
Limitations of a morphological criterion of adaptive inference in the fossil record

Experimental analyses directly inform how an anatomical feature or complex functions during an organism's lifetime, which serves to increase the efficacy of comparative studies of living and fossil taxa. In the mammalian skull, food material properties and feeding behaviour have a pronounced influence on the development of the masticatory apparatus. Diet‐related variation in loading magnitude and frequency induce a cascade of changes at the gross, tissue, cellular, protein and genetic levels, with such modelling and remodelling maintaining the integrity of oral structures vis‐à‐vis routine masticatory stresses. Ongoing integrative research using rabbit and rat models of long‐term masticatory plasticity offers unique insight into the limitations of functional interpretations of fossilised remains. Given the general restriction of the palaeontological record to bony elements, we argue that failure to account for the disparity in the hierarchical network of responses of hard versus soft tissues may overestimate the magnitude of the adaptive divergence that is inferred from phenotypic differences. Second, we note that the developmental onset and duration of a loading stimulus associated with a given feeding behaviour can impart large effects on patterns of intraspecific variation that can mirror differences observed among taxa. Indeed, plasticity data are relevant to understanding evolutionary transformations because rabbits raised on different diets exhibit levels of morphological disparity comparable to those found between closely related primate species that vary in diet. Lastly, pronounced variation in joint form, and even joint function, can also characterise adult conspecifics that differ solely in age. In sum, our analyses emphasise the importance of a multi‐site and hierarchical approach to understanding determinants of morphological variation, one which incorporates critical data on performance.
Tethering of proteins to RNAs by bacteriophage proteins

Many steps in the control of gene expression are dependent on RNA‐binding proteins, most of which are bi‐functional, in as much as they both bind to RNA and interact with other protein partners in a functional complex. A powerful approach to study the functional properties of these proteins in vivo, independently of their RNA‐binding ability, is to attach or tether them to specifically engineered reporter mRNAs whose fate can be easily followed. Two tethering systems have been mainly used in eukaryotic cells, namely the MS2 coat protein system and the lambda N—B box system. In this review, we firstly describe several studies in which these tethering systems have been used and provide an overview of these applications. We next describe the major features of these two systems, and, finally, we highlight a number of points that should be considered when designing experiments using this approach.
Cerebrospinal fluid oligoclonal bands and progression of disability of multiple sclerosis

Received 6 December 2007 Accepted 11 December 2007 Dear Sirs, I read with great interest the paper of Koch et al. [1] on cerebrospinal fluid (CSF) oligoclonal bands (OCB) and progression of disability in multiple sclerosis (MS). Their data confirm the findings of the placebo subgroup of the large phase III trial of interferon b-1a (Avonex ) [2], which revealed that the presence and number of OCB does not determine the disease course as measured by EDSS score in relapsing MS. It would however been of greater interest to know the CSF WBC status of their patients at the time of analysis. In particular, data from the interferon b-1a study [2] revealed that 28% of all patients with relapsing MS had abnormal CSF WBC counts (‡6 cells/ mm) at baseline. Furthermore, a significant relationship was observed between baseline CSF WBC and subsequent disease activity in these placebo-treated patients. Those patients with abnormal WBC counts at baseline turned out to have higher relapse rates during the following years, and were significantly less likely to remain relapse free. This important issue could have been considered in the discussion.
Tranexamic acid reduces blood transfusions in elderly patients undergoing combined aortic valve and coronary artery bypass graft surgery: a randomized controlled trial.

OBJECTIVE To evaluate the effects of tranexamic acid on postoperative blood loss and transfusion requirements in elderly patients undergoing combined aortic valve replacement and coronary artery bypass graft surgery (CABG). DESIGN A prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. SETTING A university hospital (single institution). PARTICIPANTS Sixty-four patients 70 years or older undergoing combined aortic valve replacement and CABG surgery were included. One patient was withdrawn from the study after randomization by the attending surgeon because of a change in the surgical procedure. The remaining 63 patients were analyzed as intention to treat. INTERVENTIONS The included patients were randomized to treatment with either tranexamic acid, 10 mg/kg, as a bolus injection before surgery followed by 1 mg/kg/h as an infusion during surgery, or a corresponding volume of 0.9% sodium chloride. MEASUREMENTS AND MAIN RESULTS Postoperative blood loss was recorded for 16 hours. The transfusion of blood products was recorded during the entire hospital stay. The number of packed red cell transfusions given to the patients was significantly lower in the tranexamic acid group compared with the placebo group (median, 3.0 [interquartile range, 2-5] v 5.0 [3-7], p = 0.049). CONCLUSION Tranexamic acid reduced the number of packed red cell transfusions given to patients 70 years or older undergoing combined aortic valve replacement and CABG surgery.
Up-regulation of Fas (APO-1/CD95) ligand and down-regulation of Fas expression in human esophageal cancer.

Fas (APO-1/CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. In this study, we analyzed Fas and FasL expression in normal esophageal mucosa and esophageal squamous cell carcinomas. Reverse transcriptase-PCR revealed that Fas, soluble Fas, and FasL were expressed in all eight esophageal squamous carcinoma cell lines analyzed. Furthermore, it was demonstrated that FasL expressed in esophageal carcinoma cells is functional because coculture experiments using FasL-expressing TE-15 esophageal carcinoma cells resulted in apoptosis of Jurkat T leukemia cells, which are sensitive to Fas-mediated apoptosis. Immunohistochemistry of Fas and FasL showed that they are constitutively expressed in normal esophageal mucosa, FasL being predominantly in the basal and suprabasal layers, whereas Fas is in more differentiated layers, i.e., rows of polyhedral cells of the intermediate layers and squamous cells forming the outer layers. In 18 of 19 invasive esophageal squamous cell carcinomas, FasL expression was found in >50% of tumor cells. In contrast, most tumors (15 of 19, 79%) either showed no Fas expression or showed expression in <5% of tumor cells. These alterations were already detected in dysplasia and carcinoma in situ. These results suggest that up-regulation of FasL and down-regulation of Fas expression are early and frequent events associated with the evolution of esophageal squamous cell carcinomas.
A gender–dependent genetic predisposition to produce high levels of IL‐6 is detrimental for longevity

Current literature indicates that elevated IL‐6 serum levels are associated with diseases, disability and mortality in the elderly. In this paper, we studied the IL‐6 promoter genetic variability at –174 C/G locus and its effect on IL‐6 serum levels in a total of 700 people from 60 to 110 years of age, including 323 centenarians. We found that the proportion of homozygotes for the G allele at –174 locus decreases in centenarian males, but not in centenarian females. Moreover, we found that, only among males, homozygotes for the G allele at –174 locus have higher IL‐6 serum levels in comparison with carriers of the C allele. On the whole, our data suggest that those individuals who are genetically predisposed to produce high levels of IL‐6 during aging, i.e. –174 locus GG homozygous men, are disadvantaged for longevity.
Molecular bases of dominant negative and loss of function mutations at the murine c‐kit/white spotting locus: W37, Wv, W41 and W.

The proto‐oncogene c‐kit encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand and is allelic with the murine white‐spotting locus (W). Mutations at the W locus affect various aspects of hematopoiesis, the proliferation and migration of primordial germ cells and melanoblasts during development. The original W mutation and W37 are severe lethal mutations when homozygous. In the heterozygous state the W mutation has a weak phenotype while W37 has dominant characteristics. Wv and W41 are weak W mutations with dominant characteristics. We have characterized the molecular basis of these four W mutations and determined their effects on mast cell differentiation by using a fibroblast/mast cell co‐culture assay. We show that W37, Wv and W41 are the result of missense mutations in the kinase domain of the c‐kit coding sequence (W37 E‐‐‐‐K at position 582; Wv T‐‐‐‐M position 660 and W41 V‐‐‐‐M position 831), which affect the c‐kit associated tyrosine kinase to varying degrees. The c‐kit protein products in homozygous mutant mast cells are expressed normally, although the 160 kd cell membrane form of the c‐kitW37 protein displays accelerated turnover characteristics. The W mutation is the result of a 78 amino acid deletion which includes the transmembrane domain of the c‐kit protein. A 125 kd c‐kit protein was detected in homozygous W/W mast cells which lacks kinase activity and is not expressed on the cell surface. (ABSTRACT TRUNCATED AT 250 WORDS)
Editorial: Special issue on "cross-national perspectives on ownership and governance in family firms"

T special issue is devoted to studies of ownership and governance of family firms in a comparative institutional framework. Family firms as an ownership form dominate both emerging and advanced economies and account for the majority of firms worldwide (Astrachan & Shanker, 2003; Claessens, Djankov, & Lang, 2000; La Porta, Lopez-de-Silanes, & Shleifer, 1999). They are estimated to create more than 70 percent of global gross domestic product and comprise about 80 percent of all business enterprises in the US (Astrachan & Shanker, 2003). While they are mostly small-to-medium in size (Faccio & Lang, 2002), family firms are also well represented among publicly listed and large-sized organizations (Anderson & Reeb, 2003; Masulis, Pham, & Zein, 2011; Morck, Wolfenzon, & Yeung, 2005). For instance, family firms constitute over 35 percent of the S&P 500 Industrials (Anderson & Reeb, 2003) and one-third of total shareholdings in Germany are family shareholdings (Franks & Mayer, 2001). Family businesses differ from non-family firms, particularly with respect to their governance arrangements. In a family-owned business, family members tend to control and directly influence the firm. However, this ownership and involvement of the family can take various forms as these firms may also be listed on stock exchanges (Masulis et al., 2011), include nonfamily owners (Villalonga & Amit, 2006), and count with the engagement of independent board members (Anderson & Reeb, 2004) and professional top executives (Patel & Cooper, 2014). Therefore, family business research tends to be a study of a specific ownership type and governance form. Ownership and governance in family firms have attracted broad scholarly attention, not just in management, but also in economics, finance, accounting, psychology, and sociology as family involvement has the potential to influence key firm outcomes, such as employee retention, goal setting, strategic and operational behavior, as well as social and financial performance. Researchers have drawn on various theoretical perspectives – including agency (Schulze, Lubatkin, & Dino,
miRNA and piRNA expression profiles of breeder cock testes detected by next‐generation sequencing

miRNAs are small non-coding regulatory RNAs that play key roles in diverse biological processes. In this study, we used the Solexa sequencing technique to profile miRNAs in breeder cock testes to illustrate their functions. A total of 663 co-expressed miRNAs and 3,180 co-expressed piRNAs were detected in three libraries. Based on Mir-X™ miRNA qRT-PCR, three miRNAs representing low, medium and high expression levels according to the sequencing results were selected randomly to validate the miRNAs' expression profiles. Results suggested that the miRNA expression profiles data could represent actual miRNA expression levels. Moreover, target genes prediction of the co-expressed miRNAs and further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, which revealed that some candidate miRNAs were involved in the regulation of the spermatogenesis process, spermatozoa function and testicular metabolism. In conclusion, we provided a useful resource for further elucidation of the miRNAs' regulatory role in spermatogenesis, contributing to a preliminary database for functional and molecular mechanistic studies in testicular metabolism, spermatogenesis and other testes functions.
Automorphism Groups of Higher-Weight Dowling Geometries

The weight k Dowling geometry M(Ek, n) is the restriction of the projective geometry PG(n ? 1, q) to the projective points having k or fewer nonzero coordinate entries. These matroids arise when examining the Fundamental Problem of Linear Coding Theory in the context of the Critical Problem of Matroid Theory. In this paper, we study the group of automorphisms of M(Ek, n) for all weights k ? 2. For fixed q ? 2, the automorphism groups of the Dowling geometries M(E3, n), M(E4, n), . , M(En ? 1, n) are isomorphic. If q = 2 and k ? n ? 2, then the automorphism group is either the symmetric group on n elements or the symmetric group on n + 1 elements according to whether k is odd or even. We conclude with remarks on the automorphism groups of weight 2 Dowling geometries M(E2, n).
Subdivisions and neuron types of the nucleus of the solitary tract that project to the parabrachial nucleus in the hamster

The solitary nuclear complex (NST) consists of a number of subdivisions that differ in their cytoarchitectonic features as well as in the amounts of inputs they receive from lingual afferent axons. In this study horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) of the hamster to determine which of these subdivisions contain cells that project to the pons. In the rostral, gustatory division of the NST, the rostral central subdivision contains the greatest number of labelled pontine‐projection neurons. The rostral lateral subdivision contains moderate numbers of labelled cells; progressively fewer labelled cells are in the ventral, medial, and dorsal subdivisions. In the caudal, general viscerosensory division of the NST, the caudal central subdivision contains the majority of labelled cells, although fewer than its rostral counterpart. Progressively fewer cells are labelled in the medial, laminar, ventrolateral, and lateral subdivisions; none in the dorsolateral subdivision. Small horseradish peroxidase injections into the pons revealed that cells of the rostral central and rostral lateral subdivisions of the NST project to the medial subdivision of the PBN, predominantly to caudal and ventral parts of the subdivision. Cells of the caudal central and medial subdivisions of the NST project to the central lateral subdivision of the PBN, predominantly to intermediate and rostral‐dorsal parts of the subdivision. Outside the NST, cells in the spinal trigeminal nucleus and parvicellular reticular formation were also labelled after PBN injections.
In Silico Identification and Characterization of mRNA-Like Noncoding Transcripts in Medicago truncatula

Accumulating evidence suggests that that non-coding RNAs (ncRNAs) play key roles in gene regulation and may form the basis of an inter-gene communication system. Many ncRNAs are synthesized similar to mRNAs and can be detected through screening of polyA-rich EST or cDNA libraries. We developed a computational pipeline to screen EST and genomic sequence data for those transcribed genes with limited protein coding potential and applied this pipeline to the model legume Medicago truncatula. This process identified a set of 503 mRNA-like transcripts that appear not to encode proteins. Further computational analysis showed that many of these ncRNA candidates share structural similarities to known ncRNAs and that they clearly differ from protein coding genes and non-transcribed regions in their base and oligonucleotide compositions, as well as in aspects of secondary structure. By using a machine learning approach, we show that the distinctive ncRNA features presented in this study can be used to discriminate most ncRNAs and may thus be useful for improving ncRNA prediction. Computational analysis of EST isolation frequencies in various plant tissues showed that the expression levels and expression profiles of the putative ncRNAs and mRNAs differ - most interestingly, the putative ncRNAs are highly expressed relative to mRNAs in the root nodule tissue and conserved only in closely related plants. The work presented here constitutes the first large-scale prediction and characterization of ncRNAs in legumes, and provides a basis for further research on elucidating ncRNA function in legume genomics.
[Reconstruction of the ossicular chain with titanium implants. Results of a multicenter study].

BACKGROUND For decades, oto-surgeons have been trying to find suitable alloplastic materials for replacing ossicles in the case of morphological and functional disorders in the middle ear. The focus of attention has been on tissue tolerance and functionality. PATIENTS A retrospective analysis of the implantation of titanium prostheses is presented (Type "Duesseldorf", Heinz Kurz GmbH, Dusslingen, Germany) in 528 patients operated in 14 ENT hospitals. The hospitals involved are ENT hospitals with different fields of specialization presenting a representative cross-section of surgical ENT treatment. Evaluated were healing results, hearing gain and surgical handling of the implants. RESULTS Despite pathological middle ear conditions, the tissue-implant healing rate was very high. In 4.4% of the patients the implants were rejected. In the case of partial ossicular reconstruction, an average hearing gain between 10 and 20 dB was achieved. Total reconstruction of the ossicular chain showed even better audiological results (15 to 20 dB on average). CONCLUSION Due to the good morphological and functional results achieved, titanium implants have proven their worth for middle ear micro-surgery. Their advantages are their light weight and delicate structure, facilitating very good micro-surgical handling. It is advisable to place a thin layer of cartilage between the prosthesis headplate and the tympanic membrane. In this manner, the number of material extrusions can be safely reduced, however, extrusions cannot completely be avoided.
Failings of the Option Pricing

In this paper we present drawbacks of the Black-Scholes option pricing theory. Shorter version of this paper were announced in [8]. Black-Scholes option theory represents unified construction of no arbitrage pricing. It is common to think that in the theory Black-Scholes price represents the perfect hedging of the stock-bond portfolio. A primary goal of this paper is to highlight drawbacks of the benchmark interpretation of the derivatives pricing concept. In addition we present the critical point on the local volatility adjustment of the Black-Scholes' pricing theory. The essence of the option pricing failings is mathematical errors admitted by their authors. Drawbacks Black-Scholes derivations of the option price we announced first in [5]. More general point of view on derivatives pricing were presented in [6,7].
The Challenge of Inhibiting Alloreactive T‐Cell Memory

Memory T cells specific for donor antigens present a unique challenge in transplantation. In addition to expressing rapid and robust immune responses to a transplanted organ, memory T cells may be resistant to the effects of currently used graft‐prolonging therapies. The increasing recognition that alloreactive memory T cells participate in transplant rejection is driving new lines of research focusing on understanding the immunobiology of alloreactive memory T cells and on designing novel therapies to specifically target memory T cells. The purpose of this review is to summarize the effects of existing immunosuppressive drugs and costimulatory blockade on functions of alloreactive memory T cells that undermine allograft survival.
Subacute proximal diabetic neuropathy

The results of clinical, electrophysiologic, and histologic studies in three patients with a type of diabetic peripheral neuropathy, subacute proximal diabetic neuropathy (diabetic amyotrophy), are presented. On the basis of our findings, we suggest that diabetic amyotrophy is a clinical and pathologic entity separate from mononeuritis multiplex. These patients have a generalized neuropathy, and it is postulated that disordered neuron-axonal metabolism forms the basis for the pathologic and clinical changes. Histochemical changes in the muscle biopsy showed type I predominance. We suggest that this phenomenon represents a conversion of surviving fibers, of whatever type, to a type I oxidative metabolism because of the change in use of these fibers.