Miracle-dz/UniFAR-FTUs huggingface dataset:
Substrate-induced Changes in Domain Interaction of Vacuolar H+-Pyrophosphatase*

Background: H+-PPase is a PPi-dependent proton translocase with 16 transmembrane domains embedded in a lipid bilayer. Results: The domain interaction is observed by single molecule AFM, and the force peaks are changed in the presence of substrate. Conclusion: The domains of PPi-binding sites process the conformational change during substrate binding and hydrolysis. Significance: This investigation provides significant mechanisms of the substrate binding and hydrolysis of H+-PPase. Single molecule atomic force microscopy (smAFM) was employed to unfold transmembrane domain interactions of a unique vacuolar H+-pyrophosphatase (EC 3.6.1.1) from Vigna radiata. H+-Pyrophosphatase is a membrane-embedded homodimeric protein containing a single type of polypeptide and links PPi hydrolysis to proton translocation. Each subunit consists of 16 transmembrane domains with both ends facing the lumen side. In this investigation, H+-pyrophosphatase was reconstituted into the lipid bilayer in the same orientation for efficient fishing out of the membrane by smAFM. The reconstituted H+-pyrophosphatase in the lipid bilayer showed an authentically dimeric structure, and the size of each monomer was ∼4 nm in length, ∼2 nm in width, and ∼1 nm in protrusion height. Upon extracting the H+-pyrophosphatase out of the membrane, force-distance curves containing 10 peaks were obtained and assigned to distinct domains. In the presence of pyrophosphate, phosphate, and imidodiphosphate, the numbers of interaction curves were altered to 7, 8, and 10, respectively, concomitantly with significant modification in force strength. The substrate-binding residues were further replaced to verify these domain changes upon substrate binding. A working model is accordingly proposed to show the interactions between transmembrane domains of H+-pyrophosphatase in the presence and absence of substrate and its analog.
Structure and proposed mechanism of l‐α‐glycerophosphate oxidase from Mycoplasma pneumoniae

The formation of H2O2 by the FAD‐dependent l‐α‐glycerophosphate oxidase (GlpO) is important for the pathogenesis of Streptococcus pneumoniae and Mycoplasma pneumoniae. The structurally known GlpO from Streptococcus sp. (SspGlpO) is similar to the pneumococcal protein (SpGlpO) and provides a guide for drug design against that target. However, M. pneumoniae GlpO (MpGlpO), having < 20% sequence identity with structurally known GlpOs, appears to represent a second type of GlpO that we designate as type II GlpOs. In the present study, the recombinant His‐tagged MpGlpO structure is described at an approximate resolution of 2.5 Å, solved by molecular replacement using, as a search model, the Bordetella pertussis protein 3253 (Bp3253), comprising a protein of unknown function solved by structural genomics efforts. Recombinant MpGlpO is an active oxidase with a turnover number of approximately 580 min−1, whereas Bp3253 showed no GlpO activity. No substantial differences exist between the oxidized and dithionite‐reduced MpGlpO structures. Although, no liganded structures were determined, a comparison with the tartrate‐bound Bp3253 structure and consideration of residue conservation patterns guided the construction of a model for l‐α‐glycerophosphate (Glp) recognition and turnover by MpGlpO. The predicted binding mode also appears relevant for the type I GlpOs (such as SspGlpO) despite differences in substrate recognition residues, and it implicates a histidine conserved in type I and II Glp oxidases and dehydrogenases as the catalytic acid/base. The present study provides a solid foundation for guiding further studies of the mitochondrial Glp dehydrogenases, as well as for continued studies of M. pneumoniae and S. pneumoniae glycerol metabolism and the development of novel therapeutics targeting MpGlpO and SpGlpO.
Learning Goal-Decomposition Rules Using Exercises

Teaching problem-solving through exercises is a widely used pedagogic technique. A human teacher selects certain problems and orders them according to their level of difficulty to form a sequence of exercises. A student starts by solving simple problems first; then, attempts harder problems applying the knowledge gained from solving the earlier problems; and then still harder problems, and so on. Machine learning of problem solving using exercises, apart from following this pedagogic tradition, offers a compromise between supervised speedup learning and unsupervised speedup learning. Supervised speedup learning, although more efficient than the latter, places the burden of providing the solutions to the training problems on the teacher-mostly a human. Unsupervised speedup learning, in contrast, expects the learner to solve the training problems, while unburdening the teacher. However, this is computationally hard for the learner for it lacks control knowledge and, hence, its only recourse is brute-force search. In exercises approach, teacher has the task of providing an exercise set-a sequence of problems ordered by difficulty. The learner has to solve the exercise problems using the bootstrapping method akin to the above-described method followed by a human student. Previously, Natarajan (1989) used exercises approach in speedup learning for learning control rules represented in the form of tree patterns. In this work, we use exercises approach for learning first-order recursive goal-decomposition rules (d-rules). A d-rule is a 3-tuple (g, c, sg) that decomposes a goal g into a sequence of subgoals sg, provided the condition c holds. The input to the system is a sequence of exercises ordered according to their difficulty levels. The difficulty levels correspond to goal-subgoal hierarchies except in the case of recursion-where the number of recursive calls is also used to set the difficulty level of a goal. This approach follows two main steps: For each exercise, (1) exercise-solver solves the exercise by searching in the space of operators and previously learned drules, and outputs the solution (the plan) and the subgoals used; and (2) first-order inductive learner forms a hypothesis d-rule using the initial state as the d-rule
A tropospheric ozone maximum over the Middle East

The GEOS‐CHEM global 3‐D model of tropospheric chemistry predicts a summertime O3 maximum over the Middle East, with mean mixing ratios in the middle and upper troposphere in excess of 80 ppbv. This model feature is consistent with the few observations from commercial aircraft in the region. Its origin in the model reflects a complex interplay of dynamical and chemical factors, and of anthropogenic and natural influences. The anticyclonic circulation in the middle and upper troposphere over the Middle East funnels northern midlatitude pollution transported in the westerly subtropical jet as well as lightning outflow from the Indian monsoon and pollution from eastern Asia transported in an easterly tropical jet. Large‐scale subsidence over the region takes place with continued net production of O3 and little mid‐level outflow. Transport from the stratosphere does not contribute significantly to the O3 maximum. Sensitivity simulations with anthropogenic or lightning emissions shut off indicate decreases of 20–30% and 10–15% respectively in the tropospheric O3 column over the Middle East. More observations in this region are needed to confirm the presence of the O3 maximum.
Active Vibration-induced PM Noise Control in Optical Fibers: Preliminary Studies

Vibration causes mechanical distortions in fiberoptic transmission lines that induce time (phase) fluctuations. RF systems are increasingly using optical fibers in various ways and must occasionally operate in environments with acoustic and structure-born vibration. A scheme is described which enables electronic suppression and cancellation of vibration-induced spurious phase noise in an optical fiber wound on a spool. The scheme is applied to an opto-electronic oscillator (OEO). Close-to-carrier spectral lines often occur due to mechanical vibration of state-of-the-art oscillators. Passive vibration-suppression schemes (shock mounts, isolation chambers, etc.) do not always adequately reduce discrete line spectra that originate from vibration effects. However, vibration can be readily detected and measured by use of accelerometers. One can correct for these low-frequency vibration artifacts by subtracting a digitally-generated version of the artifacts based on their detection. This approach is generically referred to as "active noise control" and is used for selective noise-cancellation, room acoustic and vibration isolation, vibration suppression in video recording, active magnetic shielding, and other situations that require external noise cancellation or suppression. Active noise control can be applied to virtually all systems and applications that are subject to vibration-induced PM noise. We present simulation results in several cases representing typical vibrating oscillator scenarios. We report progress and experiences with operational hardware.
Structural Changes in Human Teeth after Heating up to 1200°C in Argon Atmosphere

The phase transformation of hydroxyapatite (HAP, Ca10(PO4)6(OH)2) to the beta tricalcium phosphate phase (β-TCP, β-Ca3(PO4)2) at 1100°C is well known. However, in the case of human tooth, the HAP phase transformation is still an open area. For example, the CaO phase has sometimes been reported in the set of phases that make up the teeth. In this study, physical changes of human teeth when subjected to heat treatment in inert atmosphere (argon) were studied. The results were compared with those obtained in air atmosphere, from room temperature (25°C) up to 1200°C. Morphological changes were analyzed by light and scanning electron microscopy (SEM). The HAP to β-TCP phase transformation was followed in powder samples by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Heating of teeth results in the removal of organic material and structural water before the HAP to β-TCP phase transformation, the increment in hardness and the induced crystal growth. The percentage of the phases, crystal growth and lattice parameter variations as a function of temperature was quantified by Rietveld analysis. The black color was observed in dentin heated under argon atmosphere. Differences in expansivity produce fractures in dentin at 300°C in argon and at 400°C in air. In dentin, the coexistence of the HAP and β-TCP phases was observed after 800°C in argon and after 600°C in air; in enamel it was observed at 600°C in argon compared with 400°C in air. In general, the role played by the argon atmosphere during the thermal treatment of the teeth is to retard the processes observed in air.
Development and Evaluation of an Ovine Antibody-Based Platform for Treatment of Clostridium difficile Infection

ABSTRACT Treatment of Clostridium difficile is a major problem as a hospital-associated infection which can cause severe, recurrent diarrhea. The currently available antibiotics are not effective in all cases and alternative treatments are required. In the present study, an ovine antibody-based platform for passive immunotherapy of C. difficile infection is described. Antibodies with high toxin-neutralizing titers were generated against C. difficile toxins A and B and were shown to neutralize three sequence variants of these toxins (toxinotypes) which are prevalent in human C. difficile infection. Passive immunization of hamsters with a mixture of toxin A and B antibodies protected them from a challenge with C. difficile spores in a dose-dependent manner. Antibodies to both toxins A and B were required for protection. The administration of toxin A and B antibodies up to 24 h postchallenge was found to reduce significantly the onset of C. difficile infection compared to nonimmunized controls. Protection from infection was also demonstrated with key disease isolates (ribotypes 027 and 078), which are members of the hypervirulent C. difficile clade. The ribotype 027 and 078 strains also have the capacity to produce an active binary toxin and these data suggest that neutralization of this toxin is unnecessary for the management of infection induced by these strains. In summary, the data suggest that ovine toxin A and B antibodies may be effective in the treatment of C. difficile infection; their potential use for the management of severe, fulminant cases is discussed.
Diagnosis of large-bowel cancer in the asymptomatic patient.

In a survey of 2,000 physical examinations performed in an internist's office, seven patients with invasive carcinoma of the colon were found. None of the patients in the survey was examined because of large-bowel symptoms. All seven patients had positive tests for occult blood in at least one of three stool specimens. This finding led to the preparation of an easier method for multiple stool examination as a routine office procedure. Recent reports have emphasized the limitations of the sigmoidoscope in cancer detection. If a positive reaction is obtained from a multiple stool occult blood test, the patient should be further examined with barium sulfate enema roentgenograms. This is one of the best methods for detecting large-bowel cancer during routine well-patient examinations.
The POSTGRES Data Model

Abstract : This paper describes the data model for POSTGRES, a next-generation extensible database management system being developed at the University of California StR86. The data model is a relational model that has been extended with abstract data types, data of type procedure, and attribute and procedure inheritance. These mechanisms can be used to simulate a wide variety of semantic and object-oriented data modeling constructs including aggregation and generalization, complex objects with shared subobjects, and attributes that reference tuples in other relations.
Mechanism of Epidermal Growth Factor Regulation of Vav2, a Guanine Nucleotide Exchange Factor for Rac*

Vav2 is a member of the Vav family that serves as a guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Unlike Vav1, whose expression is restricted to cells of hematopoietic origin, Vav2 is broadly expressed. Recently, Vav2 has been identified as a substrate for the epidermal growth factor (EGF) receptor; however, the mechanism by which Vav2 is activated in EGF-treated cells is unclear. By the means of an in vitro protein kinase assay, we show here that purified and activated EGF receptor phosphorylates Vav2 exclusively on its N-terminal domain. Furthermore, EGF receptor phosphorylates Vav2 on all three possible phosphorylation sites, Tyr-142, Tyr-159, and Tyr-172. In intact cells we also show that Vav2 associates with the activated EGF receptor in an Src homology 2 domain-dependent manner, with Vav2 Src homology 2 domain binding preferentially to autophosphorylation sites Tyr-992 and Tyr-1148 of the EGF receptor. Treatment of cells with EGF results in stimulation of exchange activity of Vav2 as measured on Rac; however, the intensity of the exchange activity does not show any correlation with the level of Vav2 tyrosine phosphorylation. Introducing a point mutation into the Vav2 pleckstrin homology domain or treatment of cells with the phosphatidylinositol 3-kinase inhibitor LY294002 prior to EGF stimulation inhibits Vav2 exchange activity. Although phosphorylation mutants of Vav2 can readily induce actin rearrangement in COS7 cells, pleckstrin homology domain mutant does not stimulate membrane ruffling. These results suggest that EGF regulates Vav2 activity basically through phosphatidylinositol 3-kinase activation, whereas tyrosine phosphorylation of Vav2 may rather be necessary for mediating protein-protein interactions.
Relative Clauses*

In (a), Srel is contained within NPmat, and constrains the referent of this NP to be something which I bought, whereas in (b), S rel occurs at the end of the sentence, and constrains the referent of NP mat (the subject of the whole sentence) to be the owner of a CD-burner. In order to describe a situational role for the referent of NP mat, Srel needs to have a grammatical function associated with that role, which we c an all the NPrel function. There may or may not be an overt NP in the RC that expresses NP rel function; in (2b) there is (the ‘relative pronoun’ who in subject position of the RC), and in (2a) there isn’t. In the latter case we can say that the RC contains a ‘gap ’ for the NPrel function (direct object, in this case). Confusing the grammatical an d semantic functions of NP rel
Process patterns and conceptual changes in knowledge representations during information seeking and sensemaking: A qualitative user study

The construction of knowledge representations during sensemaking resembles meaningful learning in which conceptual changes to knowledge structure take place in various forms. Guided by a cognitive process model of sensemaking expanding prior models with ideas from learning and cognitive psychology, we conducted a qualitative user study of 15 participants with news writing and business analysis tasks to investigate the evolvement of their knowledge structures. We collected and analysed think-aloud protocols along with recorded screen activities, intermediate work products including notes and concept maps, and the final reports. Findings suggested that: (a) the sensemaking process can be viewed as composed of several iterations that fall into nine slightly varied common patterns, which make up the components of sensemaking; (b) conceptual changes fall into three broad classes – accretion, tuning and restructuring; and (c) changes in forms of representation seem to assist in sensemaking. These findings provide insights for system design that assists in sensemaking and intelligent use of information.
Age differences in the association of obstructive sleep apnea risk with cognition and quality of life

Using a sample of 2925 stroke‐free participants drawn from a national population‐based study, we examined cross‐sectional associations of obstructive sleep apnea (OSA) risk with cognition and quality of life and whether these vary with age, while controlling for demographics and comorbidities. Included participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were aged 47–93 years. OSA risk was categorized as high or low based on responses to the Berlin Sleep Questionnaire. Cognitive function was assessed with standardized fluency and recall measures. Depressive symptoms were assessed with the four‐item Center for Epidemiologic Studies Depression Scale. Health‐related quality of life (HRQoL) was assessed with the Medical Outcomes Study Short Form‐12 (SF‐12). Multivariate analyses of covariance (mancova) statistics were applied separately to the cognitive and quality of life dependent variables while accounting for potential confounders (demographics, comorbidities). In fully adjusted models, those at high risk for OSA had significantly lower cognitive scores (Wilks’ lambda = 0.996, F3,2786 = 3.31, P < 0.05) and lower quality of life [depressive symptoms and HRQoL] (Wilks’ lambda = 0.989, F3,2786 = 10.02, P < 0.0001). However, some of the associations were age‐dependent. Differences in cognition and quality of life between those at high and low obstructive sleep apnea risk were most pronounced during middle age, with attenuated effects after age 70 years.
PAEDIATRIC ENDOCRINE DISORDERS AT THE UNIVERSITY COLLEGE HOSPITAL, IBADAN: 2002 – 2009

Background: Until recently, most published research focus more on infectious diseases and malnutrition giving the impression that endocrine disorders are uncommon. Reports on endocrine disorders in children in developing countries are few compared to developed countries reflecting the different level of prevalence in the different geographical locations and or level of awareness and availability of facilities for proper diagnosis. Objective: This study aims at defining the burden of paediatric endocrine disorders in Ibadan. Subjects/Methods: A review of records of children who presented at University College Hospital, Ibadan with paediatric endocrine disorders from 2002 to 2009 was carried out. Results: During the eight-year period, a total of 110 children presented with various endocrine disorders but only 94 had complete data for this study. There were 47(50%) males and 37(39.4%) females, and in 10(10.6%) of them, had genital ambiguity at presentation. Patients’ ages ranged from 2 weeks to 15 years with a median of 3 years. Many (35%) patients were malnourished with weight less than 80% of the expected weight for age and only 9% were overweight. Yearly distribution of cases showed a steady increase in number of cases from 2005. Rickets and metabolic disorders constituted 56.4% of patients; Diabetes mellitus was diagnosed in 12.8%, adrenal disoders in 10.6%, pubertal disorders in 5.3% and growth disorders in 4.3% of the patients. Thyroid disorders were present in 6.4%, obesity in 3.2% while the least common disorder was Diabetes insipidus (1%). About 58% of the children had parents in the low socioeconomic status and the management of the cases were severely hampered by lack of funds. About 60.6% of these patients were lost to follow up, during the period. Conclusions: Paediatric endocrine disorders are associated with a high incidence of malnutrition. Most patients presented with rickets which is a preventable condition.
High performance RF filters via bandwidth scaling with Kerr micro-combs

We demonstrate high-resolution photonic RF filters using an RF bandwidth scaling approach based on integrated Kerr optical micro-combs. By employing both an active nonlinear micro-ring resonator (MRR) as a high-quality micro-comb source and a passive high-Q MRR to slice the RF spectra modulated on the shaped comb, a large RF instantaneous bandwidth of 4.64 GHz and a high resolution of 117 MHz are achieved, together with a broad RF operation band covering 3.28-19.4 GHz (L to Ku bands) using thermal tuning. We achieve programmable RF transfer functions including binary-coded notch filters and RF equalizing filters with reconfigurable slopes. Our approach is an attractive solution for RF spectral shaping with high performance and flexibility.
Myocardial recovery: a focus on the impact of left ventricular assist devices

Heart failure remains one of the most prevalent diseases worldwide and in recent decades, left ventricular assist devices (LVADs) have become an important treatment option. With increasing device experience, there is particular interest in the use of LVADs as a bridge to recovery that allows the patient’s heart to undergo reverse remodeling, whereby the device can be explanted and the heart can function at an improved state. There are many considerations that play a role in this process, including the ability of the device to unload the heart, the innate physiology of the heart to recover and the use of concomitant therapies. This review provides an overview of the most current literature as it pertains to these processes and gives a view into the future directions of LVADs as a tool for achieving myocardial recovery.
Optimal Sensor and Actuator Placement in Complex Dynamical Networks

Abstract Controllability and observability have long been recognized as fundamental structural properties of dynamical systems, but have recently seen renewed interest in the context of large, complex networks of dynamical systems. A basic problem is sensor and actuator placement: choose a subset from a finite set of possible placements to optimize some real-valued controllability and observability metrics of the network. Surprisingly little is known about the structure of such combinatorial optimization problems. In this paper, we show that an important class of metrics based on the controllability and observability Gramians has a strong structural property that allows efficient global optimization: the mapping from possible placements to the trace of the associated Gramian is a modular set function. We illustrate the results via placement of power electronic actuators in a model of the European power grid.