Miracle-dz/UniFAR-FTUs huggingface dataset:
ProVal: A protein‐scoring function for the selection of native and near‐native folds

A low‐resolution scoring function for the selection of native and near‐native structures from a set of predicted structures for a given protein sequence has been developed. The scoring function, ProVal (Protein Validate), used several variables that describe an aspect of protein structure for which the proximity to the native structure can be assessed quantitatively. Among the parameters included are a packing estimate, surface areas, and the contact order. A partial least squares for latent variables (PLS) model was built for each candidate set of the 28 decoy sets of structures generated for 22 different proteins using the described parameters as independent variables. The Cα RMS of the candidate structures versus the experimental structure was used as the dependent variable. The final generalized scoring function was an average of all models derived, ensuring that the function was not optimized for specific fold classes or method of structure generation of the candidate folds. The results show that the crystal structure was scored best in 64% of the 28 test sets and was clearly separated from the decoys in many examples. In all the other cases in which the crystal structure did not rank first, it ranked within the top 10%. Thus, although ProVal could not distinguish between predicted structures that were similar overall in fold quality due to its inherently low resolution, it can clearly be used as a primary filter to eliminate ∼90% of fold candidates generated by current prediction methods from all‐atom modeling and further evaluation. The correlation between the predicted and actual Cα RMS values varies considerably between the candidate fold sets. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.
Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

ABSTRACT In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams. Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections. Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state. Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography. The peak concentration of levofloxacin at steady state (Cmax ss)was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of the Cmax ss in CSF to the Cmax ss in plasma being 0.47. The areas under the concentration-time curves during the 12-h dosing interval (AUC0-τs) were 47.69 mg · h/liter for plasma and 33.42 mg · h/liter for CSF, with the ratio of the AUC0-τ for CSF to the AUC0-τ for plasma being 0.71. The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 ± 1.57 and 5.51 ± 1.36 h, respectively; P = 0.034). The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval. In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma. The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults. This cotreatment could be useful both for overcoming Streptococcus pneumoniae resistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.
Nanotribology, nanomechanics and nanomaterials characterization

Nanotribology and nanomechanics studies are needed to develop fundamental understanding of interfacial phenomena on a small scale and to study interfacial phenomena in magnetic storage devices, nanotechnology and other applications. Friction and wear of lightly loaded micro/nanocomponents are highly dependent on the surface interactions (a few atomic layers). These structures are generally coated with molecularly thin films. Nanotribology and nanomechanics studies are also valuable in the fundamental understanding of interfacial phenomena in macrostructures and provide a bridge between science and engineering. An atomic force microscope (AFM) tip is used to simulate a single-asperity contact with a solid or lubricated surface. AFMs are used to study the various tribological phenomena that include surface roughness, adhesion, friction, scratching, wear and boundary lubrication. In situ surface characterization of local deformation of materials and thin coatings can be carried out using a tensile stage inside an AFM. Mechanical properties such as hardness, Young's modulus of elasticity and creep/relaxation behaviour can be determined on micro- to picoscales using a depth-sensing indentation system in an AFM.
Characterization of the proteomes associating with three distinct membrane raft sub‐types in murine sperm

Mammalian sperm are transcriptionally and translationally inactive. To meet changing needs in the epididymis and female tract, they rely heavily on post‐translational modifications and protein acquisition/degradation. Membrane rafts are sterol and sphingolipid‐enriched micro‐domains that organize and regulate various pathways. Rafts have significance in sperm by transducing the stimulus of sterol efflux into changes in intracellular signaling that confer fertilization competence. We recently characterized three biochemically distinct sub‐types of sperm rafts, and now present profiles for proteins targeting to and associating with these sub‐types, along with a fraction largely comprised of “non‐raft” domains. Proteomics analysis using a gel‐based LC‐MS/MS approach identified 190 strictly validated proteins in the raft sub‐types. Interestingly, many of these are known to be expressed in the epididymis, where sperm membrane composition matures. To investigate potential roles for rafts in epididymal protein acquisition, we compared the expression and localization of two different sterol‐interacting proteins, apolipoprotein‐A1 (apoA1) and prominin‐1 (prom1) in sperm from different zones. We found that apoA1 was gradually added to the plasma membrane overlying the acrosome, whereas prom1 was not, suggesting different mechanisms for raft protein acquisition. Our results define raft‐associating proteins, demonstrate functional similarities and differences among raft sub‐types, and provide insights into raft‐mediated epididymal protein acquisition.
Endogenous Formation of Preferences: Choices Systematically Change Willingness-to-Pay for Goods

Standard decision theory assumes that choices result from stable preferences. This position has been challenged by claims that the act of choosing between goods may alter preferences. To test this claim, we investigated in three experiments whether choices between equally valued snack food items can systematically shape preferences. We directly assessed changes in participants’ willingness-to-pay for these items, some of which could be bought at an auction after the experiment, while others could not. We found that chosen items were valued higher, and nonchosen items were valued lower; yet this postdecisional refinement of preferences was only observed for choices and valuations that were relevant, that is, incentive-compatible for items that were available for consumption. Supplementary analyses revealed that incentive-incompatible elicitations of preferences were unreliable and may have masked potential effects of choices on preferences. In conclusion, we propose that preferences can change endogenously, that is, in the absence of external feedback or information, but rather as a function of previous relevant choices.
Effects of intrauterine position on the hepatic microsomal polysubstrate monooxygenase and cytosolic glutathione S-transferase activity, plasma sex steroids and relative organ weights in adult male and female Long-Evans rats.

The intrauterine position of rat fetuses between siblings of the same or opposite sex has been reported to alter sexually dimorphic behavioral and reproductive traits in the adult. The intrauterine fetal position of adult rats is identified by a three letter code as mMm (a male, M, located between two male siblings, m-m) and fFf (a female, F, positioned between two females, f-f). This study sought to determine whether intrauterine location affected the hepatic polysubstrate monooxygenase and glutathione S-transferase activity, plasma sex steroid levels and organ weights in adult Long-Evans rats. The hepatic microsomal cytochrome P-450 content was higher in females located in utero between two male littermates (mFm) than in females positioned between two females (fFf). NADPH cytochrome c reductase activity was higher in mMm males (positioned in utero between two males) than in fMf males (males contiguous to two female littermates) and female rats. Hepatic microsomal testosterone 2 alpha- and 6 beta-hydroxylase activity was undetectable in fFf female but both activities were measurable in mFm female rats. Testosterone 7 alpha-hydroxylase and 5 alpha-reductase activity was higher in females than in males, and higher in fFf than in mFm females. Glutathione S-transferase activity was not altered by fetal contiguity in male and female rats. Adult mMm males had a higher plasma testosterone level and relative gonadal weight, and lower plasma estradiol concentration than fMf males. The plasma progesterone concentration of fFf female was lower than that of mFm female rats. (ABSTRACT TRUNCATED AT 250 WORDS)
Phantom-based experimental validation of computational fluid dynamics simulations on cerebral aneurysms.

PURPOSE Recently, image-based computational fluid dynamics (CFD) simulation has been applied to investigate the hemodynamics inside human cerebral aneurysms. The knowledge of the computed three-dimensional flow fields is used for clinical risk assessment and treatment decision making. However, the reliability of the application specific CFD results has not been thoroughly validated yet. METHODS In this work, by exploiting a phantom aneurysm model, the authors therefore aim to prove the reliability of the CFD results obtained from simulations with sufficiently accurate input boundary conditions. To confirm the correlation between the CFD results and the reality, virtual angiograms are generated by the simulation pipeline and are quantitatively compared to the experimentally acquired angiograms. In addition, a parametric study has been carried out to systematically investigate the influence of the input parameters associated with the current measuring techniques on the flow patterns. RESULTS Qualitative and quantitative evaluations demonstrate good agreement between the simulated and the real flow dynamics. Discrepancies of less than 15% are found for the relative root mean square errors of time intensity curve comparisons from each selected characteristic position. The investigated input parameters show different influences on the simulation results, indicating the desired accuracy in the measurements. CONCLUSIONS This study provides a comprehensive validation method of CFD simulation for reproducing the real flow field in the cerebral aneurysm phantom under well controlled conditions. The reliability of the CFD is well confirmed. Through the parametric study, it is possible to assess the degree of validity of the associated CFD model based on the parameter values and their estimated accuracy range.
Quasi-transform-limited pulse transmission in dispersion managed soliton system

A Gaussian pulse with frequency chirping is transmitted in a dispersion management (DM) soliton system. The existence of an initial chirping makes the pulsewidth and amplitude fluctuate over distance around their initial values, and increases the energy enhancement factor. The quasi-transform-limited pulse generated with spectral windowing is also propagated in the DM soliton system. With proper energy enhancement, the quasi-transform-limited pulse can propagate very stably, and the performance is better than that in a uniform low dispersion soliton system, which suggests that a DM system has more chirping and waveform tolerance in soliton sources than a uniform fiber system.
Transmission Electron Microscopy Studies of Electron-Selective Titanium Oxide Contacts in Silicon Solar Cells

Abstract In this study, the cross-section of electron-selective titanium oxide (TiO2) contacts for n-type crystalline silicon solar cells were investigated by transmission electron microscopy. It was revealed that the excellent cell efficiency of 21.6% obtained on n-type cells, featuring SiO2/TiO2/Al rear contacts and after forming gas annealing (FGA) at 350°C, is due to strong surface passivation of SiO2/TiO2 stack as well as low contact resistivity at the Si/SiO2/TiO2 heterojunction. This can be attributed to the transformation of amorphous TiO2 to a conducting TiO2−x phase. Conversely, the low efficiency (9.8%) obtained on cells featuring an a-Si:H/TiO2/Al rear contact is due to severe degradation of passivation of the a-Si:H upon FGA.
Interaction of 17β-estradiol and dietary fatty acids on energy and glucose homeostasis in female mice

Fatty acid-induced hypothalamic inflammation (HI) is a potential cause of the obesity epidemic. It is unclear whether saturated or n-6 polyunsaturated fat is the primary driver of these effects. Premenopausal women are protected, in part, from obesity and associated comorbidities by circulating 17β-estradiol (E2). It is unknown how HI interacts with E2, because most studies of HI do not examine females despite the involvement of E2 in hypothalamic energy homeostasis. Our objective is to determine the effects of high-fat diets with varying levels of linoleic acid (LA) and saturated fat on the energy and glucose homeostasis in female mice with and without E2. Female C57BL/6J mice were fed either a control diet or a 45% kilocalories from fat diet with varying levels of LA (1, 15, or 22.5% kilocalories from LA) with or without E2 (300 μg/kg/day orally). After 8 weeks, the oil-treated high-fat groups gained more weight than control groups regardless of fat type. E2 reduced body fat accumulation in all high-fat groups. Glucose clearance from glucose challenge was impaired by LA. Nighttime O2 consumption was increased by E2, regardless of diet and independent of activity. Neuropeptides and HI genes were not affected by LA or SFA content. These data show that fatty acid type does not affect body weight, but does affect glucose metabolism in females, and these effects are not associated with an induction in HI gene expression.
Control and path planning method for simultaneous manufacturing with robot and milling machine

For automation of machining centers such as milling machines a common approach is to integrate robots for tasks like (un)loading workpieces. However, the controllers of machine tool and robot are usually not integrated. This limits the possibilities for a close cooperation between machine and robot significantly. This paper describes a milling machine that has been integrated with a robot both mechanically and on the controller level. To allow for robot and milling spindle to machine on the same workpiece at the same time, the control concept is extended and a concept for a path planning method is developed. The path planning module is evaluated for the process combinations of milling and robot based deburring. The paths of robot and machine are first planned sequentially and then fed into the planning module. The planning module splits up the paths and performs collision simulations to find possible combinations of process steps that can be executed simultaneously. The result is a collision matrix that allows selecting collision free path combinations for simultaneous operations.
Prevention of rhinovirus and poliovirus uncoating by WIN 51711, a new antiviral drug

WIN 51711, a potent new antipicornavirus drug, has been shown to inhibit an early event in the replication cycle of human poliovirus type 2 and human rhinovirus type 2. WIN 51711 was not virucidal and had no measurable effect on the adsorption of [3H]uridine-labeled virions to cells. When virion penetration of the plasma membrane was determined through loss of sensitivity to neutralizing antisera, WIN 51711 had no effect on poliovirus penetration, but inhibited rhinovirus penetration by 40%. In the presence of WIN 51711, exposure of neutral red-encapsidated virus-infected cells to light at 3 h postinfection resulted in a 3-log reduction in the number of infectious centers, indicating that WIN 51711 maintained the viral RNA in the encapsidated state after penetrating the cell membrane. The inhibition of uncoating by WIN 51711 in the neutral red assay was found to be concentration dependent, with a concentration of 0.03 micrograms/ml resulting in a 90% inhibition of uncoating. Sucrose gradient sedimentation of lysates from whole cells infected with [3H]uridine-labeled poliovirus showed that poliovirions remained intact in the presence of WIN 51711, but were uncoated in the absence of drug. WIN 51711 also prevented thermal inactivation of poliovirus infectivity, indicating a direct stabilizing effect of this compound on virion capsid conformation.
LE DESIGN ORGANISATIONNEL TERRITORIAL

Acteurs publics et prives s'engagent de plus en plus dans des demarches de design organisationnel territorial (DOT), qui ont pour objet l'utilisation partenariale de ressources communes ou la gestion collective de contraintes. Fonde sur des economies externes liees a la disponibilite locale de biens collectifs, le DOT repose sur des reseaux heterogenes et non hierarchises et s'inscrit dans les procedures de gouvernance territoriale.
The B cell repertoire of patients with rheumatoid arthritis. Frequencies and specificities of peripheral blood B cells reacting with human IgG, human collagens, a mycobacterial heat shock protein and other antigens

Using a potent in vitro limiting dilution culture system, we have activated human peripheral blood B cells to proliferate and to differentiate into antibody‐secreting cells (ASC). Under these conditions 25–100 % of B cells are clonally expanded and produce IgM, IgG or IgA. Culture supernatants were tested for antibodies binding to human IgG‐Fc fragments (RF), the 65‐kD heat shock protein of Mycobacterium bavis (hsp60), human collagens type I, II, IV, V, transferrin, lactoferrin, albumins, and gelatine. All blood samples contained precursors of ASC (p‐ASC) able to produce IgM binding to these antigens in frequencies above 003% of B cells. Most interestingly, a significant difference exists between rheumatoid arthritis (RA) patients and controls, concerning the relative frequencies of p‐ASC able to produce monospecific or multircactive RF. Whereas most p‐ASC(RF) in RA patients are monospecific (mean ratio 3.7), most p‐ASC(RF) in healthy control persons are cross‐reactive with at least one of five other antigens tested (mean ratio 0.2). The data suggest a disease‐specific expansion of p‐ASC committed to the production of monospecific rheumatoid factors.
The Fibronectin-binding MSCRAMM FnbpA ofStaphylococcus aureus Is a Bifunctional Protein That Also Binds to Fibrinogen*

Staphylococcus aureus is an important pathogen capable of causing a wide spectrum of diseases in humans and animals. This bacterium expresses a variety of virulence factors that participate in the process of infection. These include MSCRAMMs (microbial surface componentsrecognizing adhesive matrixmolecules) that mediate the adherence of the bacteria to host extracellular matrix components, such as collagen, fibronectin (Fn), and fibrinogen (Fg). Two Fn-binding MSCRAMMs, FnbpA and FnbpB, have been previously identified. The Fn binding activity has been localized to the ∼40-amino acid residue D repeats in the C-terminal part of these proteins. However, no biological activity has yet been attributed to the N-terminal A regions of these proteins. These regions exhibit substantial amino acid sequence identity to the A regions of other staphylococcal MSCRAMMs, including ClfA, ClfB, and SdrG (Fbe), all of which bind Fg. This raises the question of whether the Fn-binding MSCRAMMs can also bind specifically to Fg. In this report, we show that a recombinant form of the A region of FnbpA does specifically recognize Fg. We localize the binding site in Fg for recombinant FnbpA to the γ-chain, in particular to the C-terminal residues of this polypeptide, the site also recognized by ClfA. In addition, we demonstrate that recombinant FnbpA can compete with ClfA for binding to both immobilized and soluble Fg. By the use of surface plasmon resonance spectroscopy and fluorescence polarization, we determine the dissociation equilibrium constant for the interaction of recombinant FnbpA with intact immobilized Fg and with a synthetic C-terminal γ-chain peptide, respectively. Finally, by overexpressing FnbpA in a mutant strain of S. aureus that lacks the expression of both ClfA and ClfB, we show that native FnbpA can mediate the interaction of S. aureus with soluble Fg.
History of endoscopic skull base surgery: its evolution and current reality.

The history of the endoscope exemplifies the manner in which technological advances influence medicine and surgery. Endoscopic systems have evolved and improved, and they currently provide detailed visualization of a variety of deep organ structures. Otorhinolaryngological surgeons have used the endoscope for more than 30 years. In the 1990s, a number of influential neurosurgeons and otorhinolaryngological surgeons began performing purely endoscopic pituitary surgery. Endoscopic transsphenoidal operations are now extending beyond the sella. The collaboration between otorhinolaryngologists and neurosurgeons has produced a new subspecialty of "endoscopic skull base surgery. " There is a great deal of progress still to be made in developing skills, instruments, and improving skull base repair. The extended skull base approaches allow surgical exposures from the olfactory groove to C-2 and to the infratemporal region and jugular fossa laterally. This article discusses the history of the endoscope, the pivotal technological advances, and the key figures in the burgeoning field of endoneurosurgery.
Herbivore exclusion drives the evolution of plant competitiveness via increased allelopathy.

The 'Evolution of Increased Competitive Ability (EICA)' hypothesis predicts the evolution of plant invasiveness in introduced ranges when plants escape from their natural enemies. So far, the EICA hypothesis has been tested by comparing plant vigor from native and invasive populations, but these studies are confounded by among-population differences in additional environmental factors and/or founder effects. We tested the major prediction of EICA by comparing the competitive ability (CA) of Solidago altissima plants originating from artificial selection plots in which we manipulated directly the exposure to above-ground herbivores. In a common garden experiment, we found an increase in inter-specific, but not intra-specific, CA in clones from herbivore exclusion plots relative to control plots. The evolutionary increase in inter-specific CA coincided with the increased production of polyacetylenes, whose major constituent was allelopathic against a heterospecific competitor, Poa pratensis, but not against conspecifics. Our results provide direct evidence that release from herbivory alone can lead to an evolutionary increase in inter-specific CA, which is likely to be mediated by the increased production of allelopathic compounds in S. altissima.