Miracle-dz/UniFAR-FTUs huggingface dataset:
Semiautomatic sequence‐specific assignment of proteins based on the tertiary structure—The program st2nmr

The sequence‐specific assignment of resonances is still the most time‐consuming procedure that is necessary as the first step in high‐resolution NMR studies of proteins. In many cases a reliable three‐dimensional (3D) structure of the protein is available, for example, from X‐ray spectroscopy or homology modeling. Here we introduce the st2nmr program that uses the 3D structure and Nuclear Overhauser Effect spectroscopy (NOESY) peak list(s) to evaluate and optimize trial sequence‐specific assignments of spin systems derived from correlation spectra to residues of the protein. A distance‐dependent target function that scores trial assignments based on the presence of expected NOESY crosspeaks is optimized in a Monte Carlo fashion. The performance of the program st2nmr is tested on real NMR data of an α‐helical (cytochrome c) and β‐sheet (lipocalin) protein using homology models and/or X‐ray structures; it succeeded in completely reproducing the correct sequence‐specific assignments in most cases using 2D and/or 15N/13C Nuclear Overhauser Effect (NOE) data. Additionally to amino acid residues the program can also handle ligands that are bound to the protein, such as heme, and can be used as a complementary tool to fully automated assignment procedures. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 335–340, 2002
Amodiaquine for treating malaria.

BACKGROUND Amodiaquine has been widely used to treat malaria. Due to reports of fatal adverse drug reactions, discontinuation or modification of its use has been suggested. OBJECTIVES The objective of this review was to assess the effects of amodiaquine for treating malaria. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group trials register and Medline. We also contacted researchers in the field and drug companies. SELECTION CRITERIA Randomised and quasi-randomised trials comparing amodiaquine with other treatment for uncomplicated malarial infections in adults and children. DATA COLLECTION AND ANALYSIS Both reviewers independently extracted data and assessed trial quality. MAIN RESULTS Forty trials were included. Allocation was adequately concealed in three trials. Amodiaquine was more effective than chloroquine for parasite clearance. The combined results of parasite clearance at seven days from 24 trials was 83% for amodiaquine and 56% for chloroquine (odds ratio 4.29, 95% confidence interval 3.51 to 5.24). The odds ratio for parasite clearance at 14 days was 6.00, 95% confidence interval 4.38 to 8.21. Amodiaquine and sulfadoxine/pyrimethamine showed similar results for parasite clearance on day seven, but sulfadoxine/pyrimethamine appeared to be more effective on day 14 and 28. No significant difference for adverse events was observed between amodiaquine and chloroquine and sulfadoxine/pyrimethamine. Reported adverse effects were minor or moderate, not life threatening. REVIEWER'S CONCLUSIONS There is some evidence to support the continued use of amodiaquine in the treatment of uncomplicated malaria, although drug resistance should be considered. Monitoring for toxicity should also continue.
Psychiatric comorbidity in adolescent inpatients with substance use disorders.

OBJECTIVE To assess DSM-III-R Axis I and Axis II co-occurrence and comorbidity in adolescent inpatients with substance use disorders (SUD). METHOD A consecutive series of 138 adolescent inpatients were reliably assessed with structured diagnostic interviews for Axis I disorders and Axis II personality disorders. To determine significant co-occurrence of diagnoses, comparisons were between 69 patients with SUD and 69 patients without SUD. RESULTS Disruptive behavior disorders were diagnosed significantly more frequently in patients with SUD than in those without SUD. Conduct disorder was diagnosed more frequently and oppositional defiant disorder was diagnosed less frequently in the SUD patients than in the non-SUD patients. Anxiety disorders were diagnosed less frequently in the SUD group. Cluster B personality disorders and borderline personality disorder were diagnosed more frequently in the SUD group. CONCLUSIONS The findings replicate previous research showing high rates of co-occurrence of other psychiatric disorders in adolescent inpatients with SUD. The use of a relevant psychiatric comparison group allows for finer distinctions regarding significant comorbidity and the psychopathological implications thereof.
Limited Immunogenicity of Human Induced Pluripotent Stem Cell-Derived Cartilages

Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at a considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors. In this study, we examined the immunogenicity of human iPSC-derived cartilages (hiPS-Carts) in vitro to evaluate whether allogeneic hiPS-Carts can be a new cell/tissue source. The cells in hiPS-Carts expressed limited amounts of major histocompatibility complex (MHC) class I (HLA-ABC) and MHC class II (HLA-DRDQDP). Treatment with interferon γ (IFNγ) induced the expression of MHC class I, but not MHC class II in hiPS-Carts. A mixed lymphocyte reaction assay showed that hiPS-Carts stimulated the proliferation of neither T cells nor the activation of NK cells. Furthermore, hiPS-Carts suppressed the proliferation of T cells stimulated with interleukin 2 and phytohemagglutinin (PHA). Together with previously reported findings, these results suggest that hiPS-Carts are no more antigenic than human cartilage. Additionally, in combination with the fact that iPSCs are unlimitedly expandable and thus can supply unlimited amounts of iPS-Carts from even one iPSC line, they suggest that allogeneic hiPS-Carts are a candidate source for transplantation to treat articular cartilage damage.
International management platform for children’s interstitial lung disease (chILD-EU)

Background Children’s interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register. Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. Also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chILD cases. Methods A web-based chILD management platform with a registry and biobank was successfully designed and implemented. Results Over a 3-year period, 575 patients were included for observation spanning a wide spectrum of chILD. In 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the diagnosis reached by the referring team was not confirmed by peer review. Among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%). The ability of nine expert clinicians to subcategorise the final diagnosis into the chILD-EU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the ‘wrong’ answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation. Conclusions We have shown that chILD-EU has generated a platform to help the clinical assessment of chILD. Trial registration number Results, NCT02852928.
Multiple Residues in the Transmembrane Helix and Connecting Peptide of Mouse Tapasin Stabilize the Transporter Associated with the Antigen-processing TAP2 Subunit*

The type I endoplasmic reticulum (ER) glycoprotein tapasin (Tpn) is essential for loading of major histocompatibility complex class I (MHC-I) molecules with an optimal spectrum of antigenic peptides and for stable expression of the heterodimeric, polytopic TAP peptide transporter. In a detailed mutational analysis, the transmembrane domain (TMD) and ER-luminal connecting peptide (CP) of mouse Tpn were analyzed for their capacity to stabilize the TAP2 subunit. Replacement of the TMD of Tpn by TMDs from calnexin or the Tpn-related protein, respectively, completely abolished TAP2 stabilization after transfection of Tpn-deficient cells, whereas TMDs derived from distantly related Tpn molecules (chicken and fish) were functional. A detailed mutational analysis of the TMD and adjacent residues in the ER-luminal CP of mouse Tpn was performed to elucidate amino acids that control the stabilization of TAP2. Single amino acid substitutions, including a conserved Lys residue in the center of the putative TMD, did not affect TAP2 expression levels. Mutation of this Lys plus four additional residues, predicted to be neighbors in an assumed α-helical TMD arrangement, abrogated the TAP2-stabilizing capacity of Tpn. In the presence of a wild-type TMD, also the substitution of a highly conserved Glu residue in the CP of Tpn strongly affected TAP2 stabilization. Defective TAP2 stabilization resulted in impaired cell surface expression of MHC-I molecules. This study thus defines a novel, spatially arranged motif in the TMD of Tpn essential for stable expression of the TAP2 protein and a novel protein interaction mode involving an ER-luminal Glu residue close to the membrane.
Monte Carlo MCNP-4B-based absorbed dose distribution estimates for patient-specific dosimetry.

UNLABELLED This study was intended to verify the capability of the Monte Carlo MCNP-4B code to evaluate spatial dose distribution based on information gathered from CT or SPECT. METHODS A new three-dimensional (3D) dose calculation approach for internal emitter use in radioimmunotherapy (RIT) was developed using the Monte Carlo MCNP-4B code as the photon and electron transport engine. It was shown that the MCNP-4B computer code can be used with voxel-based anatomic and physiologic data to provide 3D dose distributions. RESULTS This study showed that the MCNP-4B code can be used to develop a treatment planning system that will provide such information in a time manner, if dose reporting is suitably optimized. If each organ is divided into small regions where the average energy deposition is calculated with a typical volume of 0.4 cm(3), regional dose distributions can be provided with reasonable central processing unit times (on the order of 12-24 h on a 200-MHz personal computer or modest workstation). Further efforts to provide semiautomated region identification (segmentation) and improvement of marrow dose calculations are needed to supply a complete system for RIT. It is envisioned that all such efforts will continue to develop and that internal dose calculations may soon be brought to a similar level of accuracy, detail, and robustness as is commonly expected in external dose treatment planning. CONCLUSION For this study we developed a code with a user-friendly interface that works on several nuclear medicine imaging platforms and provides timely patient-specific dose information to the physician and medical physicist. Future therapy with internal emitters should use a 3D dose calculation approach, which represents a significant advance over dose information provided by the standard geometric phantoms used for more than 20 y (which permit reporting of only average organ doses for certain standardized individuals)
COS 598 C : Detecting overlapping communities , and theoretical frameworks for learning deep nets and dictionaries Lecturer : Sanjeev Arora Scribe :

Today we present some ideas for provable learning of deep nets and dictionaries, two important (and related) models. The common thread is a simple algorithm for detecting overlapping communities in networks. While community detection is typically thought of as a way to discover structure in, say, large social networks, here we use as a general purpose algorithmic tool to understand structure of latent variable models. The algorithm for learning deep nets and dictionaries starts by identifying correlations among variables, and represent these pairwise correlations using a graph. Then it uses community-finding to uncover the underlying connection structure.
Hyperglycemia-induced Intracellular Depletion of Ascorbic Acid in Human Mononuclear Leukocytes

It has recently been reported that glucose and its analogues inhibit in vitro ascorbic acid transport across the cell membrane of polymorphonuclear leukocytes and fibroblasts. We have studied the effect of in vivo hyperglycemia on the intracellular ascorbic acid level of mononuclear leukocytes in normal and diabetic human subjects. Administration of an intravenous glucose load resulted in a prompt decrease of mononuclear leukocyte ascorbic acid level in the normal subjects. The rate of its decline correlated closely with the rate of change of plasma glucose. Among the NIDDM subjects in the fasting state, the plasma glucose was high and the leukocyte ascorbic acid level was low when compared with that of the normal subjects. The decrease in the leukocyte ascorbic acid level during disposition of the i.v. glucose load was not statistically significant in the diabetics. The hyperglycemia-induced intracellular depletion of ascorbic acid could be clinically important and requires further evaluation.
Climate Change Impacts on Biodiversity—The Setting of a Lingering Global Crisis

Climate change has created potential major threats to global biodiversity. The multiple components of climate change are projected to affect all pillars of biodiversity, from genes over species to biome level. Of particular concerns are “tipping points” where the exceedance of ecosystem thresholds will possibly lead to irreversible shifts of ecosystems and their functioning. As biodiversity underlies all goods and services provided by ecosystems that are crucial for human survival and wellbeing, this paper presents potential effects of climate change on biodiversity, its plausible impacts on human society as well as the setting in addressing a global crisis. Species affected by climate change may respond in three ways: change, move or die. Local species extinctions or a rapidly affected ecosystem as a whole respectively might move toward its particular “tipping point”, thereby probably depriving its services to human society and ending up in a global crisis. Urgent and appropriate actions within various scenarios of climate change impacts on biodiversity, especially in tropical regions, are needed to be considered. Foremost a multisectoral approach on biodiversity issues with broader policies, stringent strategies and programs at international, national and local levels is essential to meet the challenges of climate change impacts on biodiversity.
Enhanced brain small‐worldness after sleep deprivation: a compensatory effect

Sleep deprivation has a variable impact on extrinsic activities during multiple cognitive tasks, especially on mood and emotion processing. There is also a trait‐like individual vulnerability or compensatory effect in cognition. Previous studies have elucidated the altered functional connectivity after sleep deprivation. However, it remains unclear whether the small‐world properties of resting‐state network are sensitive to sleep deprivation. A small‐world network is a type of graph that combines a high local connectivity as well as a few long‐range connections, which ensures a higher information‐processing efficiency at a low cost. The complex network of the brain can be described as a small‐world network, in which a node is a brain region and an edge is present when there is a functional correlation between two nodes. Here, we investigated the topological properties of the human brain networks of 22 healthy subjects under sufficient sleep and sleep‐deprived conditions. Specifically, small‐worldness is utilized to quantify the small‐world property, by comparing the clustering coefficient and path length of a given network to an equivalent random network with same degree distribution. After sufficient sleep, the brain networks showed the property of small‐worldness. Compared with the resting state under sufficient sleep, the small‐world property was significantly enhanced in the sleep deprivation condition, suggesting a possible compensatory adaptation of the human brain. Specifically, the altered measurements were correlated with the neuroticism of subjects, indicating that individuals with low‐levels of neuroticism are more resilient to sleep deprivation.
Bis(dimethylformamide-κO){4,4′,6,6′-tetrachloro-2,2-[butane-1,4-diyl(nitrilomethanylylidene)]diphenolato-κ4 O,N,N′,O′}nickel(II)

In the title Schiff base complex, [Ni(C18H14Cl4N2O2)(C3H7NO)2], the geometry around the NiII atom is distorted octahedral. It is coordinated by the N2O2 donor atoms of the tetradentate Schiff base ligand and the O atoms of two dimethylformamide molecules, which are cis to one another. The benzene rings are almost normal to each other [dihedral angle = 88.60 (14)°]. The various intramolecular C—H⋯O hydrogen bonds make S(5) and S(6) ring motifs. In the crystal, molecules are linked by pairs of weak C—H⋯Cl interactions, forming inversion dimers.
Biomarkers in primary open angle glaucoma

Abstract Glaucoma, a leading cause of blindness worldwide, is currently defined as a disturbance of the structural or functional integrity of the optic nerve that causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. This disturbance usually can be arrested or diminished by adequate lowering of intraocular pressure (IOP). Glaucoma can be divided roughly into two main categories, ‘open angle’ and ‘closed angle’ glaucoma. Open angle, chronic glaucoma tends to progress at a slower rate and patients may not notice loss of vision until the disease has progressed significantly. Primary open angle glaucoma (POAG) is described distinctly as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibers. Such loss develops in the presence of open anterior chamber angles, characteristic visual field abnormalities, and IOP that is too high for the healthy eye. It manifests by cupping and atrophy of the optic disc, in the absence of other known causes of glaucomatous disease. Several biological markers have been implicated with the disease. The purpose of this study was to summarize the current knowledge regarding the non-genetic molecular markers which have been predicted to have an association with POAG but have not yet been validated.
Role of Progesterone in HIV and Parasitic Infections

Progesterone (P4) plays different physiological roles, including reproductive and non-reproductive actions. Most of P4 effects are mediated by its interaction with its nuclear receptor (PR). Among the non-reproductive functions of P4, the regulation of the immune response, particularly during pregnancy, is remarkably important. P4 is able to modulate the immune response during normal physiological processes, as well as in infectious diseases, including parasitic and viral infections. During parasitic infections, P4 not only exerts its action upon the immune system, but also directly acts on the parasite, as it has been shown for helminthes and protozoans. Variations of P4 levels during the menstrual cycle could be involved in changes in susceptibility to infection, such as that caused by the human immunodeficiency virus (HIV). P4 could be involved in the acquisition and development of HIV disease, regulating infection susceptibility. Further investi- gations could open new application fields, where the differential effects of P4 upon the immune response represent the keystone of a successful hormonal therapy as well as the design of new drugs with more specific actions on parasites and virus.
Discriminatively Trained And-Or Tree Models for Object Detection

This paper presents a method of learning reconfigurable And-Or Tree (AOT) models discriminatively from weakly annotated data for object detection. To explore the appearance and geometry space of latent structures effectively, we first quantize the image lattice using an over complete set of shape primitives, and then organize them into a directed a cyclic And-Or Graph (AOG) by exploiting their compositional relations. We allow overlaps between child nodes when combining them into a parent node, which is equivalent to introducing an appearance Or-node implicitly for the overlapped portion. The learning of an AOT model consists of three components: (i) Unsupervised sub-category learning (i.e., branches of an object Or-node) with the latent structures in AOG being integrated out. (ii) Weakly supervised part configuration learning (i.e., seeking the globally optimal parse trees in AOG for each sub-category). To search the globally optimal parse tree in AOG efficiently, we propose a dynamic programming (DP) algorithm. (iii) Joint appearance and structural parameters training under latent structural SVM framework. In experiments, our method is tested on PASCAL VOC 2007 and 2010 detection benchmarks of 20 object classes and outperforms comparable state-of-the-art methods.
The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells

Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.