Miracle-dz/UniFAR-FTUs huggingface dataset:
GTP Binding and Signaling by Gh/Transglutaminase II Involves Distinct Residues in a Unique GTP-binding Pocket*

Gh is a dual function protein. It has receptor signaling activity that requires GTP binding and Ca2+-activated transglutaminase (TGase) activity that is inhibited by GTP binding. Gh shows no homology with other GTP-binding proteins, and its GTP-binding site has not been defined. Based on sequence analysis of [α-32P]GTP-photolabeled and proteolytically released internal peptide fragments, we report localization of GTP binding to a 15-residue segment (159YVLTQQGFIYQGSVK173) of the Ghcore domain. This was confirmed by site-directed mutagenesis; a Gh/fXIIIA chimera (in which residues 162–179 of Gh were substituted with the equivalent but nonhomologous region of the non-GTP-binding TGase factor XIIIA) and a Ghpoint mutant, S171E, retained TGase activity but failed to bind and hydrolyze GTP and did not support α1B-adrenergic receptor signaling. Slight impairment of GTP binding (1.5-fold) and hydrolysis (10-fold) in the absence of altered TGase activity did not affect signaling by the mutant K173N. However, greater impairment of GTP binding (6-fold) and hydrolysis (50-fold) abolished signaling by the mutant K173L. Mutant S171C exhibited enhanced GTP binding and signaling. Thus, residues Ser171 and Lys173 are critical for both GTP binding and signaling but not TGase activity. Mutagenesis of residues N-terminal to Gly170 impaired both GTP binding and TGase activity. From computer modeling of Gh, it is evident that the GTP-binding region identified here is distinct from, but interacts with, the TGase active site. Together with structural considerations of Gh versus other GTP-binding proteins, these findings indicate that Gh has a unique GTP-binding pocket and provide for the first time a mechanism for GTP-mediated regulation of the TGase activity of Gh.
Amelioration of Behavioral Abnormalities in BH4-deficient Mice by Dietary Supplementation of Tyrosine

This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4)-deficient Spr −/− mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH4-deficient Spr −/− mice. We found that Spr −/− mice display variable ‘open-field’ behaviors, impaired motor functions on the ‘rotating rod’, and dystonic ‘hind-limb clasping’. In this study, we report that these aberrant motor deficits displayed by Spr −/− mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of Spr −/− mice may not be the biological feature of aberrant motor behaviors associated with BH4 deficiency. Brain levels of dopamine (DA) and its metabolites in Spr −/− mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of Spr −/− mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH4-deficiency.
Geological controls on the formation of alluvial meanders and floodplain wetlands: the example of the Klip River, eastern Free State, South Africa

Floodplain wetlands are common features of rivers in southern Africa, but they have been little studied from a geological or geomorphological perspective. Study of the upper Klip River, eastern Free State, South Africa, indicates strong geological controls on the formation of alluvial meanders and associated floodplain wetlands. Along this river, pronounced and abrupt changes in valley width are strongly linked to lithological variations. Where weakly cemented sandstone crops out, the Klip has laterally eroded bedrock and carved valleys up to 1500 m wide. In these valleys, the river meanders (sinuosity up to ∼1·75) on moderate gradients (<0·001) within extensive floodplains marked by numerous oxbow lakes, backswamps and abandoned channels, many of which host substantial wetlands. In contrast, where highly resistant dolerite crops out, lateral erosion of bedrock is restricted, with the Klip tending instead to erode vertically along joints or fractures. Here, valleys are narrower (<200 m), channel‐bed gradients are steeper (>0·003), the river follows a much straighter course (sinuosity ∼1·10–1·34), and floodplains are restricted in width.
Trends in antidepressant use among U.S. cancer survivors, 1999-2012.

One in three patients with cancer experiences some type of mental disorder (1). Antidepressants are effective in treating depressive symptoms among cancer survivors (2). However, little is knownabout the prevalence and trends of antidepressant use in this group. This study tracked trends in antidepressant use from 1999 to 2012 among cancer survivors age $20 by using data from the National Health and Nutrition Examination Survey. Diagnosis was ascertained on the basis of the question, “Have you ever been told by a doctor or other health professional that you had cancer or a malignancy of any kind? ” Cancer survivorship was defined as a cancer diagnosis (most recent, excluding nonmelanoma skin cancer) three years or more before the survey. Current use of prescription medications was recorded by interviewers on the basis of bottles provided by participants, and they were classified according to Lexicon Plus (www.multum.com/Lexicon. htm). Antidepressants were identified by second-level Multum codes (code 249). To facilitate comparison, sexand age-adjusted rates of antidepressant use were estimated for adults without a cancer history. From 1999 to 2012, the average rate of antidepressant use among cancer survivorswas 18.3% (95%CI516.09%220.62%), compared with 12.3% among adults without a cancer history. Prevalence of use among survivors increased rapidly and nearly doubled (p5.04), from 10.6% (CI56.3%217.3%) in 1999–2000 to 20.8% (CI514.0%229.8%) in 2011–2012 (Figure 1). Over the same period, a smaller increase (7.2 percentage points) was observed among adults without a cancer history. The trend in use showed some nonlinearity. Among survivors, the rate temporarily declined, from 21.2% (CI514.8%229.4%) in 2003–2004 to 18.6% (CI514.4%223.7%) in 2005–2006, but resumed increasing thereafter. Antidepressant use among cancer survivors increased notably over the past decade. Future studies should examine benefits of antidepressants and risks of side effects in treating depression among cancer survivors.
Automatic Image Annotation Using Modified Keywords Transfer Mechanism Base on Image-Keyword Graph

Automatic image annotation is widely considered to be an important yet open problem due to the well-known semantic gap. Recent works show that nearest-neighbor-based annotation approaches are simple and effective. In this paper we use a modified keywords transfer mechanism base on image-keyword unidirectional graph to derive a great annotator. The unidirectional graph describes the relationships between images and keywords, and can be derived from images with human annotations. On that basis, a modified keywords transfer mechanism base on visual neighbors is used to annotate new images. Our method achieves better annotation performance than two of the most advanced annotation methods in terms of precision, recall and F1 metrics on the open benchmark database.
Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL*

In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the β-clamp-interacting motif (β motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with β-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until β clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the β motif. For example, the region corresponding to the β motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the β motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 Å-resolution crystal structure of A. aeolicus MutL CTD, which lacks the β motif but retains the metal-binding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of β motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of β-clamp and that β-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a β motif-containing MutL, required β-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on β-clamp.
Mapping the internal structure of sand dunes with GPR : A case history from the Jafurah sand sea of eastern Saudi Arabia

The study of the geometry and internal structure of modern aeolian deposits (sand dunes) can give a better understanding of sandstone hydrocarbon reservoirs like the A and B members of Unayzah Formation in Saudi Arabia. These members have been shown to contain depositional facies like aeolian dunes, aeolian sand sheets, and interdunes (Melvin and Heine, 2004).
Polyglutamine homopolymers having 8–45 residues form slablike β‐crystallite assemblies

At least nine inherited neurodegenerative diseases, including Huntington's, are caused by poly(L‐glutamine) (polyGln, polyQ) expansions > 35–40 repeats in widely or ubiquitously expressed proteins. Except for their expansions, these proteins have no sequence homologies, and their functions mostly remain unknown. Although each disease is characterized by a distinct pathology specific to a subset of neuronal cells, the formation of neuronal intranuclear aggregates containing protein with an expanded polyQ is the hallmark and common feature to most polyQ disorders. The neurodegeneration is thought to be caused by a toxic gain of function that occurs at the protein level and depends on the length of the expansion: Longer repeats cause earlier age of onset and more severe symptoms. To address whether there is a structural difference between polyQ having < 40 versus > 40 residues, we undertook an X‐ray fiber diffraction study of synthetic polyQ peptides having varying numbers of residues: Ac‐Q8‐NH2, D2Q15K2, K2Q28K2, and K2Q45K2. These particular lengths bracket both the range of normalcy (9–36 repeats) and the pathological (45 repeats), and therefore could be indicative of the structural changes expected in expanded polyQ domains. Contrary to expectations of different length‐dependent morphologies, we accounted for all the X‐ray patterns by slablike, β‐sheet structures, ∼20 Å thick in the β‐chain direction, all having similar monoclinic lattices. Moreover, the slab thickness indicates that K2Q45K2, rather than forming a water‐filled nanotube, must form multiple reverse turns. Proteins 2005. © 2005 Wiley‐Liss, Inc.
CAMA Centre for Applied Macroeconomic Analysis The Stochastic Volatility in Mean Model with Time-Varying Parameters : An Application to Inflation Modeling CAMA Working Paper 7 / 2015 March 2015

This paper generalizes the popular stochastic volatility in mean model of Koopman and Hol Uspensky (2002) to allow for time-varying parameters in the conditional mean. The estimation of this extension is nontrival since the volatility appears in both the conditional mean and the conditional variance, and its coefficient in the former is time-varying. We develop an efficient Markov chain Monte Carlo algorithm based on band and sparse matrix algorithms instead of the Kalman filter to estimate this more general variant. We illustrate the methodology with an application that involves US, UK and Germany inflation. The estimation results show substantial time-variation in the coefficient associated with the volatility, high-lighting the empirical relevance of the proposed extension. Moreover, in a pseudo out-of-sample forecasting exercise, the proposed variant also forecasts better than various standard benchmarks. T H E A U S T R A L I A N N A T I O N A L U N I V E R S I T Y
Evaluation of local arterial stiffness using ultrafast imaging: A comparative study using local arterial pulse wave velocity estimation and shear wave imaging

We have previously proposed a novel method for measuring arterial stiffness using shear wave imaging (SWI). In this study, we evaluate the performance of this method on a healthy population (N=30) and we compare it to local measurement of the arterial pulse wave velocity (PWV) achieved at the same arterial site using ultrafast imaging. Ultrafast imaging was used to track shear wave induced remotely by acoustic radiation force at the carotid site at a frame rate of 10000 images/second with a 8 MHz ultrasound probe. SWI was acquired with a repetition rate of 7 Hz in order to measure stiffness variation over the cardiac cycle. The axial-velocity field in the imaging plane was obtained using conventional Doppler algorithm. As shown in a previous study, acoustic radiation force applied normally to the arterial wall induces mainly a flexural guided mode (FO) which propagates between 100 to 1500 Hz. The dispersion curve of this mode is extracted from the 2D-FFT of the shear wave spatio-temporal velocity field within and along the arterial wall. The shear modulus is then estimated by a theoretical fit of the experimental dispersion curve. Ultrafast imaging was also used to measure the tissue velocity of the arterial wall at the same site at a frame rate of 1000 images/s during 1 second. PWV was estimated by tracking the pulse wave along the arterial wall based on spatio-temporal velocity field at early and end-systole. Each ultrasound measurement was repeated 3 times on each carotid to estimate the reproducibility of the technique. Lower reproducibility was found on systolic PWV measurements. Thanks to its higher frequency content, the PWV at end-systole was measured more accurately and was found to be more reliable, but was not visible in all volunteers. In contrast, SWI offered high reproducibility. Moreover, arterial stiffness was achieved 6 times per seconds contrary to one time per second for PWV, giving access to the arterial stiffness time variation during the cardiac cycle.
Stimulation of Natural Killer T Cells by Glycolipids

Natural killer T (NKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive research by chemists and immunologists to understand how glycolipids are recognized, possible responses by NKT cells, and the structural features of glycolipids necessary for stimulatory activity. The presence of this cell type in humans and most mammals suggests that it plays critical roles in antigen recognition and the interface between innate and adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells have been identified, and it is likely that glycolipid antigens remain to be discovered. Multiple series of structurally varied glycolipids have been synthesized and tested for stimulatory activity. The structural features of glycolipids necessary for NKT cell stimulation are moderately well understood, and designed compounds have proven to be much more potent antigens than their natural counterparts. Nevertheless, control over NKT cell responses by designed glycolipids has not been optimized, and further research will be required to fully reveal the therapeutic potential of this cell type.
Diabetes and risk of bladder cancer

Diabetes is an emerging public health issue in the US, affecting 11% of Americans over the age of 20, with long‐term complications that include cardiovascular disease, retinopathy, neuropathy, and nephropathy. A recent meta‐analysis found that bladder cancer incidence was approximately 40% higher in individuals with diabetes; however, few studies considered duration or type of therapy and had limited adjustment for potentially confounding factors.
18F-FLT PET Does Not Discriminate Between Reactive and Metastatic Lymph Nodes in Primary Head and Neck Cancer Patients

Repopulation of clonogenic tumor cells is inversely correlated with radiation treatment outcome in head and neck squamous cell carcinomas. A functional imaging tool to assess the proliferative activity of tumors could improve patient selection for treatment modifications and could be used for evaluation of early treatment response. The PET tracer 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) can image tumor cell proliferation before and during radiotherapy, and it may provide biologic tumor information useful in radiotherapy planning. In the present study, the value of 18F-FLT PET in determining the lymph node status in squamous cell carcinoma of the head and neck was assessed, with pathology as the gold standard. Methods: Ten patients with newly diagnosed stage II–IV squamous cell carcinoma of the head and neck underwent 18F-FLT PET before surgical tumor resection with lymph node dissection. Emission 18F-FLT PET and CT images of the head and neck were recorded and fused, and standardized uptake values (SUVs) were calculated. From all 18 18F-FLT PET-positive lymph node levels and from 8 18F-FLT PET-negative controls, paraffin-embedded lymph node sections were stained and analyzed for the endogenous proliferation marker Ki-67 and for the preoperatively administered proliferation marker iododeoxyuridine. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for 18F-FLT PET. Results: Primary tumor sites were oral cavity (n = 7), larynx (n = 2), and maxillary sinus (n = 1). Nine of the 10 patients examined had 18F-FLT PET-positive lymph nodes (SUVmean: median, 1.2; range, 0.8–2.9), but only 3 of these patients had histologically proven metastases. All metastatic lymph nodes showed Ki-67 and iododeoxyuridine staining in tumor cells. In the remaining 7 patients, there was abundant Ki-67 and iododeoxyuridine staining of B-lymphocytes in germinal centers in PET-positive lymph nodes, explaining the high rate of false-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value of 18F-FLT PET were 100%, 16.7%, 37.5%, and 100%, respectively. Conclusion: In head and neck cancer patients, 18F-FLT PET showed uptake in metastatic as well as in nonmetastatic reactive lymph nodes, the latter due to reactive B-lymphocyte proliferation. Because of the low specificity, 18F-FLT PET is not suitable for assessment of pretreatment lymph node status. This observation may also negatively influence the utility of 18F-FLT PET for early treatment response evaluation of small metastatic nodes.
Functional organization of human supplementary motor cortex studied by electrical stimulation

The presence of somatotopic organization in the human supplementary motor area (SMA) remains a controversial issue. In this study, subdural electrode grids were placed on the medial surface of the cerebral hemispheres in 13 patients with intractable epilepsy undergoing evaluation for surgical treatment. Electrical stimulation mapping with currents below the threshold of afterdischarges showed somatotopic organization of supplementary motor cortex with the lower extremities represented posteriorly, head and face most anteriorly, and the upper extremities between these two regions. Electrical stimulation often elicited synergistic and complex movements involving more than one joint. In transitional areas between neighboring somatotopic representations, stimulation evoked combined movements involving the body parts represented in these adjacent regions. Anterior to the supplementary motor representation of the face, vocalization and speech arrest or slowing of speech were evoked. Various sensations were elicited by electrical stimulation of SMA. In some cases a preliminary sensation of “urge” to perform a movement or anticipation that a movement was about to occur were evoked. Most responses were contralateral to the stimulated hemisphere. Ipsilateral and bilateral responses were elicited almost exclusively from the right (nondominant) hemisphere. These data suggest the presence of combined somatotopic organization and left-right specialization in human supplementary motor cortex.
Geochemistry of amphibolites from Mt. Sylarna, Central Scandinavian Caledonides

Abstract A geochemical study of the low-grade Seve amphibolites from Mt. Sylarna indicates that they have an affinity to abyssal, tholeiitic magma. The spilitic character of the amphibolites is emphasized in the interpretation of their magma-tectonic implications. A proposed pre-orogenic relationship between, the underlying Sarv tholeiitic dykes and the Seve amphibolites in the Sylarna-Helags area is discussed. It is concluded that a magma-genetic relation may exist, which, however, does not place constraints on the translation distance of the Seve Nappe. A hypothetical model for a comagmatic origin of the Sarv dolerites and the Mt. Sylarna amphibolites is proposed, involving early basaltic volcanism in the Iapetus Ocean.
Prediction of Audible Magnetic Noise Radiated by Adjustable-Speed Drive Induction Machines

This paper presents a fully analytical model of the electromagnetic and vibro-acoustic behavior of variable-speed squirrel-cage induction machines. This model is integrated in a fast simulation tool that can be used to design motors with low magnetic noise levels on their whole speed range. Some simulation results at variable speed are favorably compared with experiments at both vibratory (spectrograms) and acoustic levels (sonagrams) on several motors, on a wide power range (from 700 W to 250 kW). These extensive tests show that the model correctly predicts the main exciting forces, motor natural frequencies, and resonances during adjustable-speed drive. The simulation tool, called Diva, has been successfully applied to design a new low-noise ALSTOM motor.
Representing Verbs with Rich Contexts: an Evaluation on Verb Similarity

Several studies on sentence processing suggest that the mental lexicon keeps track of the mutual expectations between words. Current DSMs, however, represent context words as separate features, thereby loosing important information for word expectations, such as word interrelations. In this paper, we present a DSM that addresses this issue by defining verb contexts as joint syntactic dependencies. We test our representation in a verb similarity task on two datasets, showing that joint contexts achieve performances comparable to single dependencies or even better. Moreover, they are able to overcome the data sparsity problem of joint feature spaces, in spite of the limited size of our training corpus.
Lapatinib and renal cell carcinoma

Introduction: Major progress in treatment of renal cell carcinoma (RCC) has occurred in the past decade. Areas covered: This review reports the background on the potential implication of the EGF/EGFR pathway in RCC, the different data on EGFR positivity in RCC and results from prospective Phase II and III trials on lapatinib in RCC, along with other EGF/EGFR inhibitors. Expert opinion: Despite important progress and the real revolution of the past decade in treatment of RCC, treatment still remains palliative most of the time. To improve treatment, it is necessary to understand whether a specific population could be selected on a molecular feature of the tumor. Until there is better knowledge of the biology, further development of drugs such as lapatinib cannot be supported.