Miracle-dz/UniFAR-FTUs huggingface dataset:
Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid β-peptides in human cerebrospinal fluid

The proteolytic processing of human amyloid precursor protein (APP) into shorter aggregating amyloid β (Aβ)-peptides, e.g., Aβ1-42, is considered a critical step in the pathogenesis of Alzheimer’s disease (AD). Although APP is a well-known membrane glycoprotein carrying both N- and O-glycans, nothing is known about the occurrence of released APP/Aβ glycopeptides in cerebrospinal fluid (CSF). We used the 6E10 antibody and immunopurified Aβ peptides and glycopeptides from CSF samples and then liquid chromatography—tandem mass spectrometry for structural analysis using collision-induced dissociation and electron capture dissociation. In addition to 33 unglycosylated APP/Aβ peptides, we identified 37 APP/Aβ glycopeptides with sialylated core 1 like O-glycans attached to Thr(−39, −21, −20, and −13), in a series of APP/AβX-15 glycopeptides, where X was −63, −57, −52, and −45, in relation to Asp1 of the Aβ sequence. Unexpectedly, we also identified a series of 27 glycopeptides, the Aβ1-X series, where X was 20 (DAEFRHDSGYEVHHQKLVFF), 19, 18, 17, 16, and 15, which were all uniquely glycosylated on Tyr10. The Tyr10 linked O-glycans were (Neu5Ac)1-2Hex(Neu5Ac)HexNAc-O- structures with the disialylated terminals occasionally O-acetylated or lactonized, indicating a terminal Neu5Acα2,8Neu5Ac linkage. We could not detect any glycosylation of the Aβ1-38/40/42 isoforms. We observed an increase of up to 2.5 times of Tyr10 glycosylated Aβ peptides in CSF in six AD patients compared to seven non-AD patients. APP/Aβ sialylated O-glycans, including that of a Tyr residue, the first in a mammalian protein, may modulate APP processing, inhibiting the amyloidogenic pathway associated with AD.
Ankle arthroscopy in children.

We read the article by Vasukutty et al with interest, care and appreciation, especially since reports in this field are rare. We have some additional questions for the authors. One of the conclusions is the importance of a thorough physical examination. On that we agree. However, we feel that the approach described by the authors lacks structure. In the results section the authors report a lot of data but patient history, patient complaints and physi cal examination are mentioned interchangeably. In our opinion, it would have been useful to provide a simple diagram indicating history, complaints, physical exami nation, additional diagnostics, the examination under anaesthesia (EUA) and the arthroscopy as the golden standard, for each patient. In this way the combination of history, a good physical examination and additional diagnostics will allow for accurate diagnosis and neither EUA nor diagnostic arthroscopy of the ankle will prove necessary.1 We believe patient feedback on the physical examination is mandatory to differentiate between anterior ankle pain related to anterior ankle impingement and typical deep ankle pain related to a symptomatic osteochondral defect.2 This also goes for the physical examination of a child. We feel that the (long) term results for each patient re main unclear because the authors did not use validated outcome scores nor seemingly easy Likert or visual ana logue scales that are developed for children.3 In order to be able to conclude that ankle arthroscopy ‘is an ef fective way of treating post-traumatic ankle pathology', it would be wise to present intermediate and long-term results with validated outcome scores. Besides this, in 25% of the cases no traumatic event was reported. We do not understand the thinking behind the setup of this research. Why did the authors not use magnetic res onance imaging (MRI) in every patient? Only then can the conclusion about the accuracy of MRI on diagnosing ankle impingement truly be made. What was the argu ment for using MRI? The authors do, however, perform an EUA in every patient - but for what purpose? We feel that the information from the patients’ medical history and the findings on physical examination (eg recognis able or deep ankle pain, or even tenderness on palpation on the anteromedial distal tibial rim) is sufficient. There is therefore no need for EUA. Complication rates in ankle arthroscopy vary widely but rates up to 17% have been reported.4 Several children underwent diagnostic arthroscopy, for which the authors refer to an article published in 1996.5 Nowadays, ankle arthroscopy should be used only as a therapeutic tool since less invasive radiological modalities exist.1,6 How many children suffered from complications following the (diagnostic) ankle arthroscopy in their series? (See also arguments under point 1.)
Rediscovering the Color Line within Work Organizations

Although American sociology has long been concerned with racial and ethnic inequality within work organizations, this traditional strength has languished in recent years. Few ethnographic studies have managed to capture what E. C. Hughes once called “the knitting of racial groups” at work. This article critically reviews the literature on race and work organizations and offers a set of propositions that target neglected aspects of racial boundaries at work. These center on the spatial dimension of race and organizations, the relevance of racial boundaries for the acquisition of skill and expertise, the bearing of status hierarchies on the reproduction of racial boundaries, and the character of corporate and judicial responses to racial inequalities at work. This article offers a tentative strategy for research in the field that might reclaim the lost tradition of E. C. Hughes.
Modulation of CD11C+ splenic dendritic cell functions in murine visceral leishmaniasis: correlation with parasite replication in the spleen

BALB/c mice resolve Leishmania donovani infection in the liver over an 8–12‐week period. However, after an initial phase of 2–4 weeks where increases in parasite load are not readily detectable, parasite numbers in the spleen begin to increase reaching maximum levels at 16 weeks post‐infection. Thereafter, parasite replication in the spleen is controlled and BALB/c mice maintain this residual parasite load in the spleen for many months, without further increase. We evaluated functions of CD11C+ splenic dendritic cells throughout the course of L. donovani infection in the spleen of BALB/c mice. Unlike the dendritic cell (DC)‐specific antigen DEC‐205, CD11C was not up‐regulated on macrophages during visceral leishmaniasis. No appreciable impairment of splenic DC functions was observed when this antigen‐presenting cell subset was purified from 30‐day post‐infected mice. Significant impairment in inducing allogeneic mixed lymphocyte reaction (MLR) and presenting L. donovani antigens or keyhole limpet haemocyanin (KLH) to specific T cells was observed with CD11C+ splenic DC purified from 60‐day post‐infected mice. Functional impairment of splenic DC at 60 days post‐infection correlated with their reduced surface expression of major histocompatibility complex (MHC) class II molecules, impairment of interleukin‐12 (IL‐12) production and to their ability to suppress interferon‐γ (IFN‐γ) production by Leishmania antigen‐primed T cells. Of interest, the impairment of splenic DC in presenting Leishmania antigens or KLH to specific T cells was corrected at 120 days post‐infection, and correlated with their up‐regulation of MHC class II expression, IL‐12 production, induction of IFN‐γ by Leishmania antigen‐primed T cells and the onset of control over splenic parasite replication in vivo. These results indicate that functional integrity of DC may be important in controlling L. donovani infection.
Culicoides Midge Bites Modulate the Host Response and Impact on Bluetongue Virus Infection in Sheep

Many haematophagous insects produce factors that help their blood meal and coincidently favor pathogen transmission. However nothing is known about the ability of Culicoides midges to interfere with the infectivity of the viruses they transmit. Among these, Bluetongue Virus (BTV) induces a hemorrhagic fever- type disease and its recent emergence in Europe had a major economical impact. We observed that needle inoculation of BTV8 in the site of uninfected C. nubeculosus feeding reduced viraemia and clinical disease intensity compared to plain needle inoculation. The sheep that developed the highest local inflammatory reaction had the lowest viral load, suggesting that the inflammatory response to midge bites may participate in the individual sensitivity to BTV viraemia development. Conversely compared to needle inoculation, inoculation of BTV8 by infected C. nubeculosus bites promoted viraemia and clinical symptom expression, in association with delayed IFN- induced gene expression and retarded neutralizing antibody responses. The effects of uninfected and infected midge bites on BTV viraemia and on the host response indicate that BTV transmission by infected midges is the most reliable experimental method to study the physio-pathological events relevant to a natural infection and to pertinent vaccine evaluation in the target species. It also leads the way to identify the promoting viral infectivity factors of infected Culicoides in order to possibly develop new control strategies against BTV and other Culicoides transmitted viruses.
Products of Vitamin D3 or 7-Dehydrocholesterol Metabolism by Cytochrome P450scc Show Anti-Leukemia Effects, Having Low or Absent Calcemic Activity

Background Cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,23(OH)2D3, as well as 1-hydroxyvitamin D3 to 1α,20-dihydroxyvitamin D3 (1,20(OH)2D3). It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed to 20(OH)7DHP. UVB induces transformation of the steroidal 5,7-dienes to pregnacalciferol (pD) and a lumisterol-like compounds (pL). Methods and Findings To define the biological significance of these P450scc-initiated pathways, we tested the effects of their 5,7-diene precursors and secosteroidal products on leukemia cell differentiation and proliferation in comparison to 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). These secosteroids inhibited proliferation and induced erythroid differentiation of K562 human chronic myeloid and MEL mouse leukemia cells with 20(OH)D3 and 20,23(OH)2D3 being either equipotent or slightly less potent than 1,25(OH)2D3, while 1,20(OH)2D3, pD and pL compounds were slightly or moderately less potent. The compounds also inhibited proliferation and induced monocytic differentiation of HL-60 promyelocytic and U937 promonocytic human leukemia cells. Among them 1,25(OH)2D3 was the most potent, 20(OH)D3, 20,23(OH)2D3 and 1,20(OH)2D3 were less active, and pD and pL compounds were the least potent. Since it had been previously proven that secosteroids without the side chain (pD) have no effect on systemic calcium levels we performed additional testing in rats and found that 20(OH)D3 had no calcemic activity at concentration as high as 1 µg/kg, whereas, 1,20(OH)2D3 was slightly to moderately calcemic and 1,25(OH)2D3 had strong calcemic activity. Conclusions We identified novel secosteroids that are excellent candidates for anti-leukemia therapy with 20(OH)D3 deserving special attention because of its relatively high potency and lack of calcemic activity.
Do Interests and Cognitive Abilities Help Explain College Major Choice Equally Well for Women and Men?

The present study examines whether vocational interests, measured by Holland’s RIASEC model, and objectively assessed cognitive abilities, were useful in discriminating among various major categories for a sample of 1990 German university students. Interests and specific abilities, in combination, significantly discriminated among major categories and furthermore, ability measures added incremental validity to prediction based on interest measures alone. Logistic regression analyses revealed significant differences in predictor importance between women and men. Furthermore, overall gender differences in interests and cognitive abilities were identifiable within major categories as well. Implications for career counseling are discussed.
Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

Aim: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. Methods: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. Results: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. Conclusion: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.
Soil C, N, P and Its Stratification Ratio Affected by Artificial Vegetation in Subsoil, Loess Plateau China

Artificial vegetation restoration can induce variations in accumulation and distribution of soil carbon (C), nitrogen (N) and phosphorus (P). However, little is known about variations in soil C, N and P nutrient fraction stratification following artificial vegetation in Loess Plateau China. Based on the hypothesis that re-vegetated can improve soil quality and stratification ratios (SR) can be used as an indicator to evaluate soil quality. This study measured contents and storages of soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP) and their SRs in topsoil (0–20 cm) and subsoil (20–60 cm) in three 30-year re-vegetated lands that had been converted from arable land (Robinia pseudoacacia L., Caragana Korshinskii Kom. and abandoned cropland with low interferences and few management measures) and one slope cropland (SC) as a control for three soil profiles(0–20 cm, 20–40 cm and 40–60 cm) from June 2009 to June 2013. The results showed that the contents and storages of SOC, TN and TP in re-vegetated land were significantly higher than those in the SC in both topsoil and subsoil. The storages of SOC, TN and TP in the topsoil (0–20 cm) of the re-vegetated lands increased by 16.2%-26.4%, 12.7%-28.4% and 16.5%-20.9%, respectively, and increased by smaller but significant amounts in subsoil from 2009 to 2013. The SRs for SOC, TN and TP in the re-vegetated lands were mostly >2 (either for 0–20:20–40 cm or 0–20:40–60 cm) and greater than that in the SC. The SRs showed an increasing trend with increasing restoration age. The results also showed that the land use type and soil depth were the most influential factors for the SRs and storages, and the SRs of SOC and TN had significantly positive correlations with their storages. The SRs were concluded to be a good indicator for evaluating the soil quality, which can be significantly enhanced through vegetation restoration. Moreover, vegetation restoration can significantly enhance SOC, TN and TP accumulation in both topsoil and subsoil.
Type I Interferon in the Pathogenesis of Lupus

Investigations of patients with systemic lupus erythematosus have applied insights from studies of the innate immune response to define IFN-I, with IFN-α as the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I–signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFN-I–induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained antivirus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients.
Targeted overexpression of transforming growth factor alpha in the epidermis of transgenic mice elicits hyperplasia, hyperkeratosis, and spontaneous, squamous papillomas.

To assess the effects of transforming growth factor alpha (TGF-alpha) on mammalian skin in vivo, we have targeted its expression to the epidermis of transgenic mice using a vector based on the human K1 (HK1) gene. Neonatal mice expressing the HK1.TGF-alpha transgene were often smaller than normal littermates and had precocious eyelid opening and wrinkled, scaly skin with diffuse alopecia. Juvenile transgenic mouse epidermis was uniformly hyperkeratotic, but this pattern was generally less pronounced in adult transgenic mice unless they expressed high levels of the HK1.TGF-alpha transgene. Spontaneous, squamous papillomas occurred at sites of wounding in adult mice expressing high levels of HK1.TGF-alpha; however, most were prone to regression. Immunoreactive TGF-alpha was 2-6 times higher in the epidermis of these HK1.TGF-alpha lines. Immunoreactive epidermal growth factor receptor had a normal pattern of expression in nonphenotypic adult epidermis, but a marked reduction in the receptor population was detected in hyperplastic newborn epidermis and phenotypic adult epidermis. Autoradiographic localization of 125I-epidermal growth factor showed a similar pattern of distribution, suggesting that the sites of increased TGF-alpha expression induced epidermal growth factor receptor down-regulation. These data demonstrate the in vivo effect of deregulated TGF-alpha expression on epidermal proliferation and differentiation and suggest a potential role for TGF-alpha in carcinogenesis and other hyperproliferative epidermal disorders.
The Influence of Work Motivation on Emotional Intelligence and Team Effectiveness Relationship

Empirical evidence on the role of Emotional Intelligence (EI) in service providers' team role effectiveness is inconclusive despite the obvious conceptual link. The purpose of this paper is to look into the moderating effect of work motivation on the relationship between EI factors (Self Emotional Appraisal, Others' Emotion Appraisal, Regulation of Emotion, and Use of Emotion) and team role effectiveness. Analyses of 167 responses from service providers and their superiors revealed that the interactions between work motivation and Self Emotional Appraisal (SEA) and between work motivation and Others' Emotional Appraisal (OEA) have significant affect on service providers' team role effectiveness. The effect of SEA on team role effectiveness is positive for those with low work motivation while for the high work motivation group, the effect is initially positive but turns negative at high SEA levels. The effect of OEA on team role effectiveness is higher for low work motivation group and for both low and high motivation groups, the moderation effect is positive at the low to moderate levels of OEA but becomes negative at high levels of OEA. The findings indicate that the effect of SEA and OEA on service provider's team role effectiveness is moderated by work motivation, the effect is complex and counter-intuitive. Implications for managerial practices and future research are discussed.
Concurrent general composition of secure protocols in the timing model

In the setting of secure multiparty computation, a set of mutually distrustful parties wish to jointly compute some function of their input (i.e., they wish to securely carry out some distributed task). %The joint computation should be such that even In the stand-alone case, it has been shown that every efficient function can be securely computed. However, in the setting of concurrent composition, broad impossibility results have been proven for the case where there is no honest majority (or trusted setup). In this paper, we investigate the feasibility of obtaining secure multiparty protocols in a network where certain time bounds are assumed. Specifically, the security of our protocols rely on the very reasonable assumption that local clocks do not "drift" too much (i.e., it is assumed that they proceed at approximately the same rate). We show that under this mild timing assumption, it is possible to securely compute any functionality under concurrent general composition (as long as messages from the arbitrary other protocols are delayed for a specified amount of time).
Inclusive education in Malaysia: policy and practice

Malaysia's move towards inclusion was given impetus by its participation in workshops and conferences set up under the auspices of the United Nations (UNESCO 1990; UN 1993; UNESCO 1994). Inclusive education was introduced in the Education Act 1996 as part of the continuum of services available for children with special needs. The purpose of this paper is to discuss the interpretation of policy pertaining to inclusion, its contradictions and its translation into practice within the Malaysian context; and to share experiences on how the national context explains and constrains inclusive practices. This paper examines the problematic issues associated with the interpretation and implementation of inclusive practices at community and school levels. Barriers to inclusion are also discussed from the perspective of conceptualisation and meaning of ‘special educational needs’ and competing priorities of the school system.
HIV Prevention Rationalities and Serostatus in the Risk Narratives of Gay Men

This article examines the rationalistic aspects of HIV prevention discourse. Self-protection, altruistic and egalitarian rationalities are examined from the perspectives of self-regulation, surveillance medicine and risk identity. These themes are examined through 16 in-depth interviews with HIV-positive and HIV-negative gay men in relation to the (dis)order produced in risk administration. The analysis exposes some contradictions, the unequal relations of HIV-positive and HIV-negative gay men and links with notions of risky sex such as `barebacking'. Some implications are identified, including the need for critical reflexivity in HIV prevention and an engagement with practices of resistance.