Miracle-dz/UniFAR-FTUs huggingface dataset:
Purification of soluble HLA class I complexes from human serum or plasma deliver high quality immuno peptidomes required for biomarker discovery

Soluble human leukocyte antigen class I (sHLA)‐peptide complexes have been suggested to play a role in the modulation of immune responses and in immune evasion of cancer cells. The set of peptides eluted from sHLA molecules could serve as biomarker for the monitoring of patients with cancer or other conditions. Here, we describe an improved sHLA peptidomics methodology resulting in the identification of 1816 to 2761 unique peptide sequences from triplicate analyses of serum or plasma taken from three healthy donors. More than 90% of the identified peptides were 8–11mers and 74% of these sequences were predicted to bind to cognate HLA alleles, confirming the quality of the resulting immunopeptidomes. In comparison to the HLA peptidome of cultured cells, the plasma‐derived peptides were predicted to have a higher stability in complex with the cognate HLA molecules and mainly derived from proteins of the plasma membrane or from the extracellular space. The sHLA peptidomes can efficiently be characterized by using the new methodology, thus serving as potential source of biomarkers in various pathological conditions.
A study of the excretion of organic antimonials using a polarographic procedure.

other mixtures, e.g. of C22H4402 and C24H4802, which have been examined [Chibnall, Piper & Williams, 1936], show too many irregularities to be used for direct comparison. Some estimate of the nature of the impurities present may, however, be made by correlating the X-ray measurements with the general observations made by Chibnall et al. [1936] on the behaviour of fatty acid mixtures. For this purpose measurements had to be made of both the B and C polymorphic modifications, the X-ray photographs usually being taken of samples pressed lightly on to glass slides. A. The original preparation, when recrystallized from acetone, showed X-ray lines corresponding to the C modification alone. On recrystallization from benzene and from acetic acid, preparations were obtained, both of which showed lines due to B and C modifications on the same photograph. Such behaviour was noted by Piper and co-workers [Chibnall et al. 1936] in the binary mixture containing 2.5-10% and 80-90% of the lower constituent. Here the C spaci#g is slightly lower, the B spacing slightly higher than, the best values for pure C22H4402 . Both these types of spacing change may be due to mixture of a small quantity of C20H4002, say 2-5-10%, with C22H4402, but it seems very probable that the fraction still contains traces of other acids, particularly C24H4802. IIIR5. This fraction, when recrystallized from methanolethyl acetate, showed the B spacing alone. While the spacings. both of this, and of the methyl ester, are intermediate between those of C22H4402 and C24H4802, the data do not fit very well with the observations that have been made on mixtures of synthetic C22114402 and C24H4802, so that the mixture is presumably more complex.
Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype

Hereditary hemorrhagic telangiectasia (HHT; Osler‐Weber‐Rendu disease) is an autosomal dominant disease characterized by arteriovenous malformations ranging from cutaneous and mucous membrane telangiectasias to more severe pulmonary, gastrointestinal, and cerebral arteriovenous malformations (AVMs). Acute complications from bleeding or pulmonary shunting may be catastrophic. However, when diagnosed early, the complications can usually be prevented. Mutations in two genes, Endoglin (ENG) and activin receptor‐like kinase 1 (ACVRL1 or ALK1) have been associated with HHT. We describe the results of mutation analysis on a consecutive series of 200 individuals undergoing clinical genetic testing for HHT. The observed sensitivity of mutation detection was similar to that in other series with strict ascertainment criteria. A total of 127 probands were found, with sequence changes consisting of 103 unique alterations, 68 of which were novel. In addition, eight intragenic rearrangements in the ENG gene and two in the ACVRL1 gene were identified in a subset of coding sequence mutation–negative individuals. Most individuals tested could be categorized by the number of HHT diagnostic criteria present. Surprisingly, almost 50% of the cases with a single symptom were found to have a significant sequence alteration; three of these reported only nosebleeds. Genetic testing can confirm the clinical diagnosis in individuals and identify presymptomatic mutation carriers. As many of the complications of HHT disease can be prevented, a confirmed molecular diagnosis provides an opportunity for early detection of AVMs and management of the disease. Hum Mutat 27(7), 667–675, 2006. © 2006 Wiley‐Liss, Inc.
Population Genetic Simulations of Complex Phenotypes with Implications for Rare Variant Association Tests

Demographic events and natural selection alter patterns of genetic variation within populations and may play a substantial role in shaping the genetic architecture of complex phenotypes and disease. However, the joint impact of these basic evolutionary forces is often ignored in the assessment of statistical tests of association. Here, we provide a simulation‐based framework for generating DNA sequences that incorporates selection and demography with flexible models for simulating phenotypic variation (sfs_coder). This tool also allows the user to perform locus‐specific simulations by automatically querying annotated genomic functional elements and genetic maps. We demonstrate the effects of evolutionary forces on patterns of genetic variation by simulating recently inferred models of human selection and demography. We use these simulations to show that the demographic model and locus‐specific features, such as the proportion of sites under selection, may have practical implications for estimating the statistical power of sequencing‐based rare variant association tests. In particular, for some phenotype models, there may be higher power to detect rare variant associations in African populations compared to non‐Africans, but power is considerably reduced in regions of the genome with rampant negative selection. Furthermore, we show that existing methods for simulating large samples based on resampling from a small set of observed haplotypes fail to recapitulate the distribution of rare variants in the presence of rapid population growth (as has been observed in several human populations).
HIGH-RESOLUTION 5 μm SPECTROSCOPY OF TRANSITIONAL DISKS

We present high-resolution M-band (∼5 μm) spectra of 14 transitional disks—circumstellar disks with an optically thick outer zone but an inner region significantly depleted of small dust grains—obtained with NIRSPEC on the Keck II telescope. We detect CO emission from nine disks, and show that for the majority of these systems, the emission originates in the depleted inner disk region. We find that the presence of high 5 μm veiling, strong CO emission, and high accretion rates are usually correlated, suggesting that at least two classes of transitional disks exist—those nearly completely cleared, and those only partially depleted, within their transition radius. Cleared inner disks are consistent with the presence of a close stellar companion, or with formation by photoevaporation. Of the cleared transitional disks, at least two (HD 98800 B and CoKu Tau/4) are known to be circumbinary with projected binary separations of several AU or less. Partially depleted inner disks most often have CO that extends to small (≲1 AU) radii, but compared to “classical” disks the CO excitation temperature is lower and the emission radii are larger than that expected for dust sublimation. These disks are consistent with the presence of a giant planet, and inconsistent with having been formed by photoevaporation. Although the inner regions of such disks are vertically optically thin in dust emission, line-of-sight opacities from the star can be large, and the complex physical and chemical processes therein make it difficult to derive a fiducial CO abundance with respect to molecular hydrogen. Thus, CO M-band lines are best suited to providing lower bounds as to the total inner disk gas mass. Amongst the partially depleted sources, veiling measurements and CO emission models demonstrate a great diversity of inner disk gas content and gas/dust ratios, suggesting a variety of planet-forming environments.
Stabilization of the Lower Thoracic and Lumbar Spine with the Internal Spinal Skeletal Fixation System: Indications, Techniques, and First Results of Treatment

Since 1984, 30 patients with burst fractures of the lower thoracic and lumbar spine were treated with AO internal spinal skeletal fixation system. All patients in this series had a minimum follow-up of 12 months. This new instrumentation is a posterior intrapedicular system developed by Dick in 1982. It allows stable fixation that is limited only to adjacent spinal segments. The internal fixator permits reduction in all three planes. Independently, it is possible to add distraction or compression to the involved segments. It also is able to reduce effectively the “middle column” which is thought to be accomplished by “ligamentotaxis. ” In this series there were 16 neurologically intact patients and 14 with partial or complete neurologic injury. There were two minor instrumentation loosenings early in the series. Most patients in this series had a near-anatomic reduction of all three columns in the involved segment. It was also possible to re-establish the normal lordosis of the lumbar spine. The device provided sufficient rigid fixation for rapid postoperative mobilization in a light external orthosis.
Recurrence of nephrotic syndrome in kidney grafts of patients with congenital nephrotic syndrome of the Finnish type: role of nephrin.

BACKGROUND Congenital nephrotic syndrome of the Finnish type (CNF, NPHS1) is caused by mutations in the NPHS1 gene. NPHS1 codes for nephrin, a cell adhesion protein located at the glomerular slit diaphragm. Renal transplantation is the only treatment option for most patients with NPHS1. We have previously described recurrence of severe proteinuria in grafts transplanted to children with NPHS1. Here we studied the pathophysiology of this proteinuria. METHODS Clinical data, light and electron microscopic findings as well as the expression of nephrin in the proteinuric grafts were studied. The patients' sera were screened for antibodies against kidney glomerulus and nephrin molecule using indirect immunofluorescence and ELISA. RESULTS Fifteen episodes of recurrent nephrotic syndrome occurred in 13 (25%) of 51 grafts transplanted to 45 Finnish children with NPHS1. All nine patients with recurrence had a Fin-major/Fin-major genotype, which leads to absence of nephrin in the native kidney. Rescue therapy (cyclophosphamide) was successful in seven episodes, but six kidneys were lost due to this process. Antibodies reacting against glomerulus were found in eight, and high anti-nephrin antibody levels were detected in four of the nine patients. In electron microscopy, the fusion of the foot process and decreases in the detectable slit diaphragms in the podocyte pores were observed. The expression of nephrin mRNA was markedly reduced in two, and granular staining for nephrin was seen in three of five grafts. CONCLUSIONS Circulating anti-nephrin antibodies seem to have a pathogenic role in the development of heavy proteinuria in kidney grafts of NPHS1 patients with Fin-major/Fin-major genotype.
Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis).

OBJECTIVE This study, known as STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis), evaluated the safety and efficacy of adalimumab (Humira), a fully human monoclonal tumor necrosis factor-alpha (TNF-a) antibody, when given with standard antirheumatic therapy in patients with active rheumatoid arthritis (RA) not adequately responding to such therapies. Standard antirheumatic therapy included traditional disease modifying antirheumatic drugs (DMARD), low dose corticosteroids, nonsteroidal antiinflammatory drugs (NSAID), and/or analgesics. METHODS In this 24-week, double-blind, placebo-controlled study, 636 patients with RA were randomly assigned to receive adalimumab 40 mg subcutaneously (sc) every other week (n = 318) or placebo (n = 318) while continuing standard antirheumatic therapy. The frequencies of adverse events, serious adverse events, severe or life-threatening adverse events, adverse events leading to withdrawal, infection, or serious infection were the primary endpoints. Secondary endpoints were determined by American College of Rheumatology (ACR) response criteria. RESULTS During the study, the majority of patients received concomitant traditional DMARD (83.5%) and/or corticosteroids, NSAID, and/or analgesics (97.3%). Overall, 56.0% of patients continued treatment with one, 23.6% with 2, and 3.9% with > or = 3 traditional DMARD. At 24 weeks, there were no statistically significant differences between the adalimumab and placebo groups in their respective rates of adverse events (86.5% vs 82.7%), serious adverse events (5.3% vs 6.9%), severe or life-threatening adverse events (11.9% vs 15.4%), or those leading to withdrawal (2.8% vs 2.2%). There were also no statistically significant differences in the rates of infections (52.2% vs 49.4%) or serious infections (1.3% vs 1.9%) between the groups. The incidence and types of adverse events did not vary between adalimumab- and placebo-treated patients by the number of concomitant traditional DMARD (0, 1, or 2). Adalimumab-treated patients compared with placebo-treated patients achieved statistically superior ACR20 (52.8% vs 34.9%), ACR50 (28.9% vs 11.3%), and ACR70 (14.8% vs 3.5%) response rates at Week 24 (p < or = 0.001). CONCLUSION This study demonstrated that addition of adalimumab 40 mg given sc every other week to concomitant standard antirheumatic therapy is well tolerated and provides significant improvements in signs and symptoms of RA. The data indicate that adalimumab is a safe and effective therapeutic option in patients with active RA who have an inadequate response to standard antirheumatic therapy, including one or more traditional DMARD, corticosteroids, NSAID, and analgesics.
Depletion of CD8+ T cells suppresses growth of Trypanosoma brucei brucei and interferon‐gamma) production in infected rats

Sprague‐Dawley rats infected with Trypanosoma brucei brucei showed a strong and rapid induction of splenocyte IFN‐γ (within 12 h post‐infection) as measured by a single cell assay for IFN‐γ secretion. Depiction of CD8+ cells in infected rats abrogated the IFN‐γ production, suppressed parasite growth and increased survival of the animals. Induction of MHC class I antigens in the paraventricular and supra‐optic hypothalamic nuclei caused by the trypanosome infection was also inhibited by the CD8+ cell depletion. It is suggested that the CD8+ cells are involved directly or indirectly in growth regulation of the parasite and that IFN‐γ induced by the parasite may be one of the factors that trigger MHC expression and immunosuppression.
Do CEOS in Mergers Trade Power for Premium? Evidence from 'Mergers of Equals'

I analyze chief executive officer (CEO) incentives to negotiate shared control in the postmerger governance of the surviving firm. In order to do this, I study abnormal returns in a sample of "mergers of equals" (MOEs) transactions in which the two firms are approximately equal in postmerger board representation. These transactions are friendly mergers generally characterized by premerger negotiations that result in both greater shared control (board and management) and more equal sharing of merger gains between the two firms. On average, the value created measured by combined event returns is no different between MOEs and a matched sample of transactions. However, target shareholders capture less of the gains measured by event returns in transactions with shared governance. Moreover, target shareholders' share of the gains is systematically related to variables representing postmerger control rights, and shared governance is more likely in transactions in which CEOs face greater incentives for control. The evidence suggests that CEOs trade power for premium by negotiating shared control in the merged firm in exchange for lower shareholder premiums. Copyright 2004, Oxford University Press.
Diet and risk of gastric cancer. A population‐based case‐control study in Sweden

A case‐control study to evaluate risk factors of gastric cancer was carried out in areas with contrasting incidence rates in Sweden. Face‐to‐face interviews were conducted with 338 of 456 eligible histologically confirmed gastric‐cancer cases and 669 of 880 eligible control subjects, sampled from population registers and frequency‐matched by age and gender. We focused on 2 periods, adolescence and 20 years prior to interview. The association of gastric‐cancer risk with dietary habits during adolescence were similar to that found for the period 20 years before interview; high consumption of wholemeal bread, fruit and vegetables was associated with reduced gastric‐cancer risk. In addition, cheese, fish and tea had a protective effect during adolescence. Increased gastric‐cancer risk was related to whole‐milk consumption, but this association decreased substantially in a multivariate analysis including vegetables. There was a positive relationship between gastric‐cancer risk and the age at which the interviewees started using refrigerators. This population‐based study confirmed the protective effect of a high consumption of vegetables and fruit in the development of gastric cancer, but failed to find any association between intake of meat, sausage, cold cuts, liver, salt, coffee, the habit of frying, smoking or grilling foods, and risk of gastric cancer.
Both endogenous and environmental factors affect embryo proliferation in the polyembryonic wasp Copidosoma floridanum

Summary Copidosoma floridanum is a polyembryonic, parasitic wasp of the moth Trichoplusia ni. Following oviposition into a host, the C. floridanum egg initially undergoes complete (holoblastic) cleavage to form a single morula stage embryo. This embryo then undergoes a proliferation phase in which multiple, secondary morulae develop. C. floridanum has also evolved a caste system whereby some secondary morulae develop into soldier larvae whose function is defense whereas others develop into reproductive larvae that become adult wasps. In the current study, we conducted manipulative and candidate gene studies to identify factors affecting the proliferation phase of C. floridanum development. Transplantation of morulae of different ages into different host stages indicated that both embryo age and host environment affected the total number of offspring produced per morula. Morula age and brood size also significantly affected whether offspring of one or both castes were produced in a brood. In contrast, the host environment did not significantly affect caste formation. A putative homolog of the gene hedgehog (Cf‐hh) was partially cloned from C. floridanum. In situ hybridization studies indicated that Cf‐hh was expressed in secondary morulae during the proliferation phase of development, suggesting a possible role for the Hh signaling pathway in the evolution of polyembryony.
Multimodal Imaging in Birdshot Retinochoroiditis

ABSTRACT Purpose: To describe retinal vascular changes in Birdshot Retinochoroiditis (BSRC) with multimodal imaging techniques and functional values. Methods: In this single-center study, 64 eyes of 32 subjects with BSRC were classified according to disease activity and duration and underwent imaging with spectral domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and optical coherence tomography angiography (OCTA). Results: Mean age of the patients was 60 years (range, 38–74). OCTA revealed capillary loops (58%), telangiectatic vessels (44%), increased intercapillary spaces (52%), altered vascular architecture (53%), and rarefication of C-scans (63%) in retinal layers. Increased rarefications of C-scans (p = 0.0056; p = 0.0046) and altered vascular architecture (p = 0.0120; p = 0.0243) in superficial and deep capillary layers were significantly correlated with disease activity. Conclusion: OCTA adds new insights in a multimodal imaging approach of retinal vascular layer visualization in BSRC and may contribute to existing methods for diagnosing severity and potentially progression of the disease.
Smoking and polymorphisms of the interleukin-1 gene cluster (IL-1alpha, IL-1beta, and IL-1RN) in patients with periodontal disease.

BACKGROUND Polymorphisms within the interleukin-1 cluster are known to be associated with adult periodontal disease. However, interactions of genetic with other risk factors, especially smoking, remain questionable. The aim of this cross-sectional study was to evaluate the genetic influence on periodontal variables in relation to environmental factors. METHODS One-hundred fifty-four (154) Caucasian subjects were clinically and radiographically assessed for their periodontal status, their smoking history recorded, and their allelic pattern of IL-1alpha, IL-1beta, and IL-1RN polymorphisms determined by genotyping. RESULTS In assessing periodontitis with mean probing depth, mean attachment loss, or mean bone loss, no differences were found in allele frequencies or combined allotypes between subjects with mild or moderate versus those with severe signs of periodontitis. However, the extent of attachment loss defined as percentage of sites >4 mm was significantly associated with the composite genotype of IL-1alpha/1beta in smokers (odds ratio [OR] = 4.00; 95% confidence interval [CI] 1.03 to 16.70; P= 0.02). No differences were found in genotype negative subjects irrespective of their smoking status. They had nearly identical attachment loss as genotype positive non-smokers. Similar non-significant results were found with respect to extent of bone loss. An increased risk of more extended attachment loss was observed also in individuals carrying mutations of the combined genotype IL-1alpha/IL-1RN, again showing enhanced risk only in genotype-positive and smoking subjects. CONCLUSIONS The results provide evidence that the composite genotypes studied show interaction with smoking, the main exposition-related risk factor of periodontal disease. Non-smoking subjects are not at increased risk, even if they are genotype-positive.