Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the Expression of Peptide–Major Histocompatibility Complexes Using High Affinity Soluble Divalent T Cell Receptors

Understanding the regulation of cell surface expression of specific peptide–major histocompatibility complex (MHC) complexes is hindered by the lack of direct quantitative analyses of specific peptide–MHC complexes. We have developed a direct quantitative biochemical approach by engineering soluble divalent T cell receptor analogues (TCR–Ig) that have high affinity for their cognate peptide–MHC ligands. The generality of this approach was demonstrated by specific staining of peptide-pulsed cells with two different TCR–Ig complexes: one specific for the murine alloantigen 2C, and one specific for a viral peptide from human T lymphocyte virus–1 presented by human histocompatibility leukocyte antigens–A2. Further, using 2C TCR– Ig, a more detailed analysis of the interaction with cognate peptide–MHC complexes revealed several interesting findings. Soluble divalent 2C TCR–Ig detected significant changes in the level of specific antigenic–peptide MHC cell surface expression in cells treated with γ-interferon (γ-IFN). Interestingly, the effects of γ-IFN on expression of specific peptide–MHC complexes recognized by 2C TCR–Ig were distinct from its effects on total H-2 Ld expression; thus, lower doses of γ-IFN were required to increase expression of cell surface class I MHC complexes than were required for upregulation of expression of specific peptide–MHC complexes. Analysis of the binding of 2C TCR–Ig for specific peptide–MHC ligands unexpectedly revealed that the affinity of the 2C TCR–Ig for the naturally occurring alloreactive, putatively, negatively selecting, complex, dEV-8–H-2 Kbm3, is very low, weaker than 71 μM. The affinity of the 2C TCR for the other naturally occurring, negatively selecting, alloreactive complex, p2Ca–H-2 Ld, is ∼1000-fold higher. Thus, negatively selecting peptide–MHC complexes do not necessarily have intrinsically high affinity for cognate TCR. These results, uniquely revealed by this analysis, indicate the importance of using high affinity biologically relevant cognates, such as soluble divalent TCR, in furthering our understanding of immune responses.
Protein SIC, a Novel Extracellular Protein of Streptococcus pyogenes Interfering with Complement Function (*)

The human pathogen Streptococcus pyogenes possesses a chromosomal region, the mga regulon, that contains co-regulated genes important to the virulence of these bacteria. A novel gene located in the mga regulon of a S. pyogenes strain of serotype M1 was cloned and sequenced. It translates into a protein of 305 amino acid residues, including a signal sequence of 32 amino acids and a central region consisting of three tandem repeats. The sequence represents a novel structure with no significant homology to any previously published sequence. The protein was purified from the streptococcal culture media where it is present in substantial amounts. Affinity chromatography of human plasma on Sepharose coupled with the protein specifically adsorbed two plasma proteins which were identified as clusterin and histidine-rich glycoprotein (HRG). The interactions between the streptococcal protein and the plasma proteins were further characterized using purified clusterin and HRG. Inhibition experiments indicated that they have affinity for overlapping or closely located sites in the streptococcal protein. Both clusterin and HRG are regulators of the membrane attack complex (C5b-C9) of complement. When the streptococcal protein was added to serum, complement-mediated lysis of sensitized sheep erythrocytes and guinea pig erythrocytes was inhibited. In addition, the streptococcal protein was incorporated into C5b-C9 in serum, indicating the location of its action. The name, protein SIC, streptococcal inhibitor of complement-mediated lysis, is therefore suggested for this novel protein. The occurrence of protein SIC and its gene was investigated in a collection of S. pyogenes strains comprising 55 different M serotypes. Only M1 and M57 strains were positive in this screening, indicating that protein SIC could be a virulence determinant. Thus, during recent years, the M1 serotype has been connected with a world-wide increase of severe and toxic S. pyogenes infections.
Facies, sequence stratigraphy, reservoir and seal potential of the Mafraq Formation, Sultanate of Oman: An integrated outcrop analogue study

The mixed carbonate-siliciclastic Lower to Middle Jurassic Mafraq Formation unconformably overlies the Triassic Mahil Formation in outcrops of the Oman Mountains (pre-Mafraq Unconformity, known as pre-Marrat unconformity in other regions of Arabia). Together with the overlying Dhruma Formation, it is part of the Sahtan Group. This study provides: (1) a detailed facies analysis based on sedimentological logging of 12 outcrops. Twenty-four facies types were established and grouped into five facies associations, which can also be recognized in subsurface core intervals; (2) a detailed sequence-stratigraphic framework of the Mafraq Formation. Facies stacking and log patterns reveal cycle hierarchies on four scales from m-scale cycles, to several m-thick cycle sets, to tens of m-thick, high-frequency sequences, to 100 m-thick composite sequences; and (3) a documentation of potential reservoir and seal units. The study follows an approach from 1-D (outcrop sections) to 2-D (correlations and potential reservoir dimensions). The Mafraq outcrop type section, located in Wadi Sahtan is documented in an integrated way (facies, litho-, bio-, chemo- and sequence stratigraphy), together with additional outcrops of the Mafraq Formation throughout North Oman. 2-D correlation of the Mafraq Formation throughout North Oman is essentially based on cycle sets and provides key information about the lateral paleogeographic development of the formation. A general proximal-distal trend, from south to north, has been proposed by Ziegler (2001); outcrop data from the Oman Mountains confirms this trend and adds an EW-deepening component. The mixed carbonate-clastic Lower Mafraq Member (Sequence) with a coastal/estuarine to shallow-marine environment forms onlaps onto the pre-Mafraq Unconformity below, and thins out completely after some 10s of kilometers towards the southeast. The Upper Mafraq Member (Sequence) seems to be continuous over 10s of kilometers with less thickness decrease. Instead, a transition from a more distal carbonate shoal - backshoal environment in the northwest to a proximal clastic coastal/estuarine/terrestrial environment in the southeast can be observed. On a 100s km-scale significant thinning and a change towards terrestrial clastic facies can be observed southeast of the Oman Mountains area. Combined results from lateral/vertical logging, paleoenvironmental interpretations and correlation provided 3-D information about the dimensions of potential reservoir and seal units. Several potential reservoir/seal intervals and their dimensions in dip direction could be identified: (1) Lower Mafraq Sequence: various types of sandbodies, most of them with a lateral extent ca. 5 km, sealed by shales. (2) Upper Mafraq Sequence, northwestern part: oolitic grainstones, laterally correlative over 10–20 km, sealed by shales. (3) Upper Mafraq Sequence, southeastern part: channelized sandstones units, lateral extent up to km, sealed by shales.
A molecular census of 26S proteasomes in intact neurons

A detailed look at proteasomes in situ The 26S proteasome is a protein machine that degrades intracellular proteins in the cytosol. The proteasome is critical for protein quality control and for the regulation of numerous cellular processes in eukaryotic cells. The structure of isolated proteasomes is well established, but how intact proteasomes look within the cell is less clear. Asano et al. used an improved approach to electron cryotomography to look at proteasomes in intact hippocampal neurons. Their analysis suggests that these cells only use about 20% of their proteasomes in an unstressed state, which leaves significant spare capacity to deal with proteotoxic stress. Science, this issue p. 439 Only 20% of proteasomes are being used in unstressed hippocampal neurons. The 26S proteasome is a key player in eukaryotic protein quality control and in the regulation of numerous cellular processes. Here, we describe quantitative in situ structural studies of this highly dynamic molecular machine in intact hippocampal neurons. We used electron cryotomography with the Volta phase plate, which allowed high fidelity and nanometer precision localization of 26S proteasomes. We undertook a molecular census of single- and double-capped proteasomes and assessed the conformational states of individual complexes. Under the conditions of the experiment—that is, in the absence of proteotoxic stress—only 20% of the 26S proteasomes were engaged in substrate processing. The remainder was in the substrate-accepting ground state. These findings suggest that in the absence of stress, the capacity of the proteasome system is not fully used.
Satisfaction with participation in multiple sclerosis and spinal cord injury

Purpose: To validate a single item self-report of satisfaction with participation in two groups with differing patterns of symptoms and disease progress, multiple sclerosis (MS) and spinal cord injury (SCI). Method: Community-dwelling adults with MS (N = 1,271) or SCI (N = 620) completed a battery of self-report questionnaires covering demographic information, disease specific measures, symptoms, psychological distress, social-environmental issues, and overall well-being. They were also asked to rate satisfaction with participation: How satisfied are you with your ability to take part in activities that are important to you: not satisfied, somewhat satisfied, satisfied, or very satisfied. Kendall’s tau rank correlation coefficient and χ2 tests were used to examine the strength and direction of associations between demographic and symptom variables and responses to the participation item. Results: Although the demographics of the MS and SCI differed in predictable ways, younger participants and those employed report more satisfaction with participation. Ratings of satisfaction with participation were also consistently associated with a number of variables including less fatigue, pain, depression, stress, anxiety, as well as higher overall measures of well-being across the two populations. Conclusions: More research is needed to better understand the multiple dimensions that comprise participation and to develop robust and sensitive measurement tools. A global rating of satisfaction with participation using one item has a number of potentially useful applications including description of case mix in clinical trials. Implications for Rehabilitation Restrictions in participation are faced by many adults with disability including those with multiple sclerosis or spinal cord injury. These restrictions are associated with an array of biopsychosocial variables. A psychometrically sound indicator of satisfaction with participation could be used to describe the severity of condition, to adjust case mix in clinical trials, or to track global change disability status.
The Influence of Crude Oils on Well Tubing Corrosion Rates

A model is proposed to describe the corrosion caused by CO 2 dissolved in a fluid containing crude oil and water. To this end three types of phase behaviour of water/oil mixtures has been taken as a starting point to describe the effect of the presence of oil on the resulting corrosion rate of carbon steel. An equation is postulated expressing the likelihood of each of these suggested modes of phase behaviour occurring, which relates directly to their influence upon the corrosivity of the oil/water mixture. An extrapolation of this model to heavier types of crude oil is proposed, which links the API gravity to the water-in-oil-emulsion stability, which, in turn, is linked to the effect of oil wetting of the metal. For very light oil the model defaults to a model derived for an oil field studied previously. The resulting formula, combining the watercut, fluid velocity, angle of deviation of the tubing and API gravity of the oil is also shown to reproduce the typical behaviour for the corrosion of steel in oil/water emulsions observed by others.
The Hachinski ischemic scale and cognition: the influence of ethnicity.

OBJECTIVE cardiovascular burden is considered a risk factor for the development of cognitive dysfunction and dementia. While this link is well established in the literature, implementing this work in primary care settings remains a challenge. The goal of this study is to examine the utility of the Hachinski Ischemic Scale (HIS) in identifying cognitive dysfunction and diagnosis of mild cognitive impairment (MCI) in an ethnically diverse sample. METHODS data were analysed on 517 participants (211 Mexican Americans and 306 non-Hispanic Whites) recruited from Project FRONTIER, a study of rural health. Neuropsychological measures were utilised to assess for cognitive functioning. RESULTS among non-Hispanic Whites, HIS scores were significantly related to poorer performance on tasks of global cognition [B (SE) = -0.13 (0.06), P = 0.02], immediate memory [B (SE) = -0.85 (0.26), P < 0.001], attention [B (SE) = -1.6 (0.36), P < 0.001] and executive functioning [B (SE) = 0.46 (0.12), P < 0.001], and significantly predicted diagnosis of MCI [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.2-1.6]. For Mexican Americans, HIS scores were significantly related to immediate memory [B (SE) = -0.78 (0.28), P = 0.01], attention [B (SE) = -0.74 (0.36), P = 0.04] and executive functioning [B (SE) = 0.37 (0.14), P = 0.01]; however, HIS scores were not significantly related to diagnosis of MCI in Mexican Americans (OR = 1.2, 95% CI = 0.96-1.4, P = 0.116). CONCLUSION HIS scores were related to cognitive functioning; however, these results differed by ethnicity. It is possible that these findings indicate that vascular factors may increase risk for MCI among non-Hispanic Whites but not for Mexican Americans. These findings are consistent with past research that suggests risk factors for MCI may differ by ethnicity.
Effects of Blood Pressure Lowering on Cerebral White Matter Hyperintensities in Patients With Stroke: The PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy

Background—The prevalence of white matter hyperintensities (WMHs) detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. We report here the results of an MRI substudy of PROGRESS (Perindopril Protection Against Recurrent Stroke Study), a randomized trial of blood pressure lowering in subjects with cerebrovascular disease. Methods and Results—The substudy comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months (SD=6.0 months). At the first MRI, WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH). Participants were assigned to a combination of perindopril plus indapamide (or their placebos; 58%) or to single therapy with perindopril (or placebo). At the time of the second MRI, the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure. Twenty-four subjects (12.5%) developed new WMHs at follow-up. The risk of new WMH was reduced by 43% (95% CI −7% to 89%) in the active treatment group compared with the placebo group (P=0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group (0.4 mm3 [SE=0.8]) compared with the placebo group (2.0 mm3 [SE=0.7]; P=0.012). This difference was greatest for patients with severe WMH at entry, 0.0 mm3 (SE=0) in the active treatment group versus 7.6 mm3 (SE=1.0) in the placebo group (P<0.0001). Conclusions—These results indicate that an active blood pressure–lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease.
On the complexity of XPath containment in the presence of disjunction, DTDs, and variables

XPath is a simple language for navigating an XML-tree and returning a set of answer nodes. The focus in this paper is on the complexity of the containment problem for various fragments of XPath. We restrict attention to the most common XPath expressions which navigate along the child and/or descendant axis. In addition to basic expressions using only node tests and simple predicates, we also consider disjunction and variables (ranging over nodes). Further, we investigate the containment problem relative to a given DTD. With respect to variables we study two semantics, (1) the original semantics of XPath, where the values of variables are given by an outer context, and (2) an existential semantics introduced by Deutsch and Tannen, in which the values of variables are existentially quantified. In this framework, we establish an exact classification of the complexity of the containment problem for many XPath fragments.
Combined Action Observation and Motor Imagery Neurofeedback for Modulation of Brain Activity

Motor imagery (MI) and action observation have proven to be efficacious adjuncts to traditional physiotherapy for enhancing motor recovery following stroke. Recently, researchers have used a combined approach called imagined imitation (II), where an individual watches a motor task being performed, while simultaneously imagining they are performing the movement. While neurofeedback (NFB) has been used extensively with MI to improve patients' ability to modulate sensorimotor activity and enhance motor recovery, the effectiveness of using NFB with II to modulate brain activity is unknown. This project tested the ability of participants to modulate sensorimotor activity during electroencephalography-based II-NFB of a complex, multi-part unilateral handshake, and whether this ability transferred to a subsequent bout of MI. Moreover, given the goal of translating findings from NFB research into practical applications, such as rehabilitation, the II-NFB system was designed with several user interface and user experience features, in an attempt to both drive user engagement and match the level of challenge to the abilities of the subjects. In particular, at easy difficulty levels the II-NFB system incentivized contralateral sensorimotor up-regulation (via event related desynchronization of the mu rhythm), while at higher difficulty levels the II-NFB system incentivized sensorimotor lateralization (i.e., both contralateral up-regulation and ipsilateral down-regulation). Thirty-two subjects, receiving real or sham NFB attended four sessions where they engaged in II-NFB training and subsequent MI. Results showed the NFB group demonstrated more bilateral sensorimotor activity during sessions 2–4 during II-NFB and subsequent MI, indicating mixed success for the implementation of this particular II-NFB system. Here we discuss our findings in the context of the design features included in the II-NFB system, highlighting limitations that should be considered in future designs.
Characterization of the effect of LPS on dendritic cell subset discrimination in spleen

The Gram‐negative bacterial endotoxin lipopolysaccharide (LPS) is a potent inflammatory mediator and a leading cause of bacterial sepsis. While LPS is known to activate antigen‐presenting cells, here we find that LPS down‐regulates expression of CD11c and CD11b on splenic dendritic cell subsets, thus confounding the ability to identify these subsets following treatment. This has implications with regard to tracking the response to LPS in terms of the cell subsets involved, and should be considered whenever such studies are undertaken.
High-level synthesis system (HLDESA) for processor arrays

An approach to high-level synthesis of processor arrays is presented. In particular we describe methods and tools of the system HLDESA for processor array design which include resource constraints. Two major groups of resource constraints are considered: implementation constraints such as area and performance constraints to meet desired properties of the array as well as interface constraints such as communication constraints to ensure that the array can be embedded in a given environment. For integrating these two constraint types in the design process of processor arrays several optimization problems are described, and the method of iterative co-partitioning is presented.
NBER WORKING PAPER SERIES OPTIMAL FISCAL AND MONETARY POLICY UNDER STICKY PRICES

This paper studies optimal . scal and monetary policy under sticky product prices. The theoretical framework is a stochastic production economy without capital. The government finances an exogenous stream of purchases by levying distortionary income taxes, printing money, and issuing one-period nominally risk-free bonds. The main findings of the paper are: First, for a miniscule degree of price stickiness (i.e., many times below available empirical estimates)the optimal volatility of in.ation is near zero. This result stands in stark contrast with the high volatility of inflation implied by the Ramsey allocation when prices are flexible. The finding is in line with a recent body of work on optimal monetary policy under nominal rigidities that ignores the role of optimal fiscal policy. Second, even small deviations from full price flexibility induce near random walk behavior in government debt and tax rates, as in economies with real non-state-contingent debt only. Finally, sluggish price adjustment raises the average nominal interest rate above the one called for by the Friedman rule. Stephanie Schmitt-Grohé Martín Uribe Department of Economics Department of Economics Rutgers University University of Pennsylvania New Brunswick, NJ 08901 3718 Locust Walk and NBER, CEPR Philadelphia, PA 19104 grohe@econ.rutgers. edu and NBER uribe@econ.upenn. edu
Acute and Chronic Effects of IL-22 on Acetaminophen-Induced Liver Injury

Acetaminophen (APAP)-induced liver injury (AILI) accounts for half of the acute liver failure cases in the United States. A better understanding of the underlying mechanisms of AILI is necessary for the development of novel antidotes. We found that pretreatment with IL-22 protected mice from APAP-mediated hepatotoxicity. The protection was dependent on STAT3, as IL-22 failed to reduce APAP hepatotoxicity in liver-specific STAT3 knockout mice. In contrast to the acute exposure to IL-22, the endogenous chronic overexpression of IL-22 in IL-22 transgenic (TG) mice or IL-22 adenovirus treatment for 6 wk resulted in a markedly increased susceptibility to AILI. Furthermore, the hepatic expression levels of cytochrome 2E1 (Cyp2E1) and Cyp1A2 were much higher in IL-22TG mice. Ablation of Cyp2E1 but not hepatic STAT3 abolished AILI and protein-adduct formation in IL-22TG mice. Finally, hepatic expression of HNF-1α, a transcriptional factor that is known to control Cyp2E1 expression, was elevated in IL-22TG mice compared with wild-type mice. Upregulation of hepatic Cyp2E1 was only observed in mice with constitutive overexpression of IL-22 but not with short-term treatment with one dose of IL-22 or multiple doses of IL-22 for 2 wk. In conclusion, short-term acute IL-22 exposure protects mice against AILI through STAT3 activation; however, chronic constitutive overexpression of IL-22 exacerbates AILI by increasing Cyp2E1 and toxic reactive APAP metabolite production. These findings may not only enhance our understanding of the effects of chronic inflammation on AILI in patients with liver disease, but are also helpful to identify novel therapeutic targets for the treatment of AILI.