Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic Pathways and Barriers for Ligand Binding to Myoglobin*

Myoglobin is a small globular heme protein that increases the aerobic capacity of striated vertebrate muscle cells by taking up oxygen from blood during rest and delivering O2 to mitochondria during muscle contraction when blood flow through capillaries is restricted. The ferrous form of myoglobin can also react with CO and NO, which are produced in vivo as second messengers for regulating various physiological functions including blood pressure, platelet aggregation, and neurotransmission. Its tertiary structure consists of eight tightly packed helices, and the resulting “myoglobin fold” is very similar to that found for the a and b subunits of hemoglobin. Since Gibson’s minireview in 1989, a number of exciting new studies have led to detailed molecular mechanisms of myoglobin function. The rapid progress made in the past 7 years is primarily the result of ultrafast kinetic measurements, mutagenesis experiments, and theoretical molecular dynamics simulations. Significant contributions have been made individually by these approaches, but more progress has occurred when these endeavors have been combined (e.g. Gibson et al., 1992; Braunstein et al., 1993; Schlichting et al., 1994; Teng et al., 1994; Huang and Boxer, 1994; Petrich et al., 1994; Carlson et al., 1994; Quillin et al. 1995). This review focuses on NO, O2, and CO binding to myoglobin mutants under physiological conditions. The objectives are to summarize successes in correlating theoretical, structural, and kinetic results and to identify the major remaining questions in ligand binding dynamics.
Psychiatric Morbidity in Hobart's Dependent Aged

Psychiatric morbidity in the dependent aged was studied in the elderly population of Hobart's nursing homes and long-stay hospitals. Only patients with home addresses in Hobart and who were admitted for the first time aged 70 years or over were included. Three hundred and twelve persons were interviewed with a standard interview, and an informant was interviewed when appropriate. The medical records were searched for diagnoses and drug treatments. Physical disability was rated on an ad hoc scale. Comparisons were made of the prevalence of dementia, depression and anxiety in different types of unit, and between these and two domiciliary samples, one of which received domiciliary nursing services (n = 100) and the other not (n = 100). The differential use of institutions by men and women, and a possible sex difference in the prevalence of dementia is discussed.
Reducing Information Asymmetry in Cloud Marketplaces

Cloud Computing is emerging as a predominant paradigm for obtaining and providing computing functionality in the enterprise. Organizations that are planning to use cloud computing offerings struggle with the question "How do I choose the right offering? " Cloud offerings exhibit a variety of pricing models and different levels of service and functionality. In this article the authors define first Cloud Computing in the context of IT Governance. Then they set criteria to compare different offerings at the level of Software-as-a-Service SaaS. This is an important precondition for the reduction of the verifiable information asymmetry and uncertainty in the cloud market. Besides deficiencies on the supply side, regarding configuration, display and communication of service bundles, the limited knowledge of potential buyers is main reason for the modest adoption. The authors apply strategies derived from information economics to reduce this asymmetry by integrating information substitutes in the service marketplace description, thereby transforming experience and credence qualities into search qualities.
Performance analysis of algorithms for calculation of SRLG disjoint paths of min-sum cost in GMPLS networks

Ensuring the resilience of telecommunications networks is an ongoing concern of telecommunications operators. In a Generalized Multiprotocol Label Switching (GMPLS) [4], network information about sets of links that share risks of failure, called Shared Risk Link Groups (SRLG), can be distributed [3]. This information allows Path Computation Elements (PCE) [1] to determine protected routes, i.e. compute a pair (or set) of SRLG-disjoint paths. A PCE must respond quickly to requests without requiring too many resources. This shows the importance of developing efficient algorithms for determining the SRLG disjoint paths. Firstly, a new version of Conflicting SRLG-Exclusion Min Sum (CoSE-MS) heuristic [2, 5] which seeks to determine a pair of SRLG-disjoint paths with minimum additive cost, adequate for dedicated global protection in GMPLS networks, will be described. The new version, designated CoSE-MScd, uses an improved version (designated MSHd) of the Modified Suurballe’s Heurisitc (MSH) proposed in [6] and modifies the process of selection of the conflicting SRLGs used in [2]. The Iterative Modified Suurballes’s Heuristic (IMSH) [6] and the new variant IMSHd, which results from the replacement of MSH by MSHd in IMSH, will also be presented. Secondly, the heuristics kCoSE-MScd and kIMSHd are proposed. To the best of our knowledge these procedures are a first proposal for seeking a set of k (k > 2) node and SRLG disjoint paths of minimal additive cost; these heuristics use a generalization of MSH for obtaining a set of k node and SRLG disjoint paths, which we designate as kMSH. The two heuristics have a similar structure, but the first uses CoSE-MScd to collect a set of node and SRLG disjoint path pairs and the second uses IMSHd for that same purpose. The network used for evaluating the heuristics’ performance was the largest biconnected component of an image of a real network with 231 nodes and 471 edges. Ten different random seeds where used to generate different distributions of SRLGs for that component, resulting in 10 different networks (with the same topology). The accuracy of the solutions obtained by the heuristics was evaluated solving an ILP formulation of the problem, using CPLEX 12.3 on a Desktop. Experimental results in an embedded system (core clock 330MHz, 128 MB RAM), showed that CoSE-MScd is more efficient than CoSE-MS, without compromising its accuracy. IMSHd is more accurate than IMSH (for the same number of iterations) at the cost of more CPU time. The experimental results obtained using kIMSH and kCoSE-MScd show that although both heuristics are quite effective in calculating a set of k = 3, 4 node and SRLG disjoint paths, however only 55%-59% of the sets of size k = 3 have optimal cost, and this value decreases for k = 4. The relative error of the total cost of the sub-optimal paths sets is about 7.5% for k = 3 and close to 15% for k = 4. Nevertheless given the great difficulty in obtaining optimal sets of node and SRLG disjoint paths, these proposals and results seem relevant in this area.
Lateral Subcutaneous Internal Sphincterotomy in Treatment of Anal Fissure

One hundred and three patients with anal fissures have been treated by lateral internal sphincterotomy performed by a subcutaneous myotomy technique, and 99 have been successfully followed up for from 3 to 24 months (mean 11 months). The operation was free from significant complications, apart from slight reactionary bleeding in one case and a perianal abscess in another. The fissure persisted or recurred in three cases, in one of which a further lateral sphincterotomy was performed, with cure. Various minor defects of anal continence were noted in 12 cases. These results have been found to be superior to those obtained previously in the same surgical unit with open posterior internal sphincterotomy and simple sphincter-stretching respectively in the treatment of anal fissure. The most reliable and satisfactory operation at present available for this condition seems, therefore, to be lateral subcutaneous internal sphincterotomy.
Comparison of intrathecal bupivacaine and levobupivacaine combined with opioids for Caesarean section

ABSTRACT Objective: To date, racemic bupivacaine is the most popular local anaesthetic for spinal anaesthesia in parturients undergoing elective Caesarean delivery. However, data suggests that S-enantiomers like levobupivacaine may produce differential sensory and motor blockade. The aim of the present study was to compare fixed doses of intrathecal hypertonic levobupivacaine 0.5% (10 mg) and bupivacaine 0.5% (10 mg) combined with either intrathecal fentanyl (10 and 20 µg), or sufentanil (5 µg) in terms of sensory and motor block characteristics. Research design and methods: 60 parturients with singleton pregnancy and > 34 weeks of gestation who underwent elective Caesarean delivery participated in this randomized, double-blinded clinical trial. They received spinal anaesthesia with either levobupivacaine or bupivacaine and the above mentioned opioids added (n = 10 parturients/group). Sensory block was assessed bilaterally by loss of cold sensation, and the degree of motor block was determined according to the Bromage scale every minute until delivery, subsequently at 5-min intervals until the end of surgery, and at 15-min intervals thereafter until complete resolution of spinal anaesthesia. A visual analogue scale was used postoperatively to measure duration of analgesia at 15-min intervals. Main outcome measures: Levobupivacaine produced a significantly shorter and less pronounced motor blockade than racemic bupivacaine regardless of the kind and dose of opioid added. Duration of motor block Bromage 3 was 53 ± 14 min, 23 ± 18 min and 41 ± 8 min compared to 65 ± 25 min, 70 ± 19 min and 65 ± 22 min in the bupivacaine groups. Also, only n = 5/30 parturients reached Bromage3 in the levobupivacaine groups versus n = 21/30 parturients in the bupivacaine groups. No parturient experienced intraoperative pain. Adding sufentanil 5 µg to either local anaesthetic significantly prolonged duration of effective analgesia compared to supplemental fentanyl 10 or 20 µg. Conclusions: Based on our data, 10 mg of hypertonic levobupivacaine 0.5% combined with sufentanil 5 µg was the most appropriate anaesthetic regimen in parturients undergoing elective Caesarean delivery in spinal anaesthesia.
The practical implications of resistance of malaria vectors to insecticides.

Insecticide resistance is an inherent characteristic dependent on relatively simple genetic mechanisms. This seems to be especially true of dieldrin resistance in anopheline mosquitos, though less obvious in DDT resistance among these species; little is known as yet about the inheritance of organophosphate and carbamate resistance as it occurs in Anopheles albimanus. The speed of selection of resistance depends on the original frequency of the gene or genes involved, the nature of the resistance imparted, and the selection pressure of the insecticide. This in turn depends on the inherent toxicity of the chemical, the efficiency with which it is applied, the proportion of the mosquito population coming under its influence, and the behaviour of the mosquito. In the past, too much reliance has been placed on the determination of the LD(50) in assessing the presence or absence of insecticide resistance. Quite high incidences of resistant individuals can result in such small changes in the LD(50) that resistance may be overlooked. The use of single discriminating dosages is advocated, based on concentrations of insecticides that normally kill all susceptible individuals. The authors discuss such dosages in respect of dieldrin and DDT, and put forward newly-established tentative discriminating dosages for organophosphorus and carbamate insecticides, which await field confirmation.From a practical standpoint, an insecticide should not be abandoned or replaced by another as soon as resistance is confirmed. This may not be necessary where the degree of resistance is not high and the vector is not highly efficient. Certain procedures are proposed in order to assess the epidemiological and entomological implications of resistance before the insecticide concerned is abandoned.
Humoral immune response in human syphilis to polypeptides of Treponema pallidum.

A molecular characterization of the polypeptide antigens of Treponema pallidum reactive with sera from patients with different stages of syphilis is described. Polypeptides of motile, virulent T. pallidum, purified from rabbit testes, were separated on SDS polyacrylamide gels and electrophoretically transferred to nitrocellulose for antigenic analysis ("Western blotting"). Serum IgG from uninfected individuals reacts weakly with three polypeptides of 45,000, 33,000, and 30,000 m.w. In this study patients with primary syphilis have IgM antibody, and all patients with syphilis have IgG antibody to at least four polypeptides of 45,000, 33,000, 30,000, and 15,500 m.w. Antibody to polypeptides of 42,000 and 16,500 m.w. appear to be markers for nonprimary syphilis. These six polypeptides have been termed the major antigenic proteins (MAP) of T. pallidum. Those patients studied with secondary and early latent syphilis acquire antibody to a set of 16 additional polypeptide antigens. Those patients studied with late latent or late syphilis have antibody to a much smaller set of five or four antigens, respectively, in addition to MAP. The results suggest that a correlation exists between acquisition of antibody and the development of "chancre immunity. " Additionally, the loss of antibody that characterizes late latent and late syphilis may be associated with the potential development of destructive late syphilis.
Energy-Efficient Water-Filling with Order Statistics

This paper proposes a methodology based on order statistics to study the energy-efficient (EE) power allocation for wireless communication transmitters. Water-filling power allocation maximizes the EE when transmitting and processing power consumption is considered. Solutions are typically presented in an iterative form, which complicates analysis and adaptive implementation. Time-consuming simulations are rather required to assess their performance. Order statistics allows analyzing the solution without knowledge of the channel realization. We analytically show how the EE depends on the system parameters. The computing efficiency of our proposal, which is executing one or two orders of magnitude faster than the state-of-the-art algorithms with a performance loss of less than 1 dB, facilitates its applicability in vehicular environments.
Inattention/hyperactivity and aggression from early childhood to adolescence: Heterogeneity of trajectories and differential influence of family environment characteristics

Inattention/hyperactivity and aggressive behavior problems were measured in 335 children from school entry throughout adolescence, at 3-year intervals. Children were participants in a high-risk prospective study of substance use disorders and comorbid problems. A parallel process latent growth model found aggressive behavior decreasing throughout childhood and adolescence, whereas inattentive/hyperactive behavior levels were constant. Growth mixture modeling, in which developmental trajectories are statistically classified, found two classes for inattention/hyperactivity and two for aggressive behavior, resulting in a total of four trajectory classes. Different influences of the family environment predicted development of the two types of behavior problems when the other behavior problem was held constant. Lower emotional support and lower intellectual stimulation by the parents in early childhood predicted membership in the high problem class of inattention/hyperactivity when the trajectory of aggression was held constant. Conversely, conflict and lack of cohesiveness in the family environment predicted membership in a worse developmental trajectory of aggressive behavior when the inattention/hyperactivity trajectories were held constant. The implications of these findings for the development of inattention/hyperactivity and for the development of risk for the emergence of substance use disorders are discussed.This work was supported by National Institute on Alcohol Abuse and Alcoholism grants (RO1 AA12217 to R.A.Z. and J.T.N. and R37 AA07065 to R.A.Z. and H.E.F.). We are indebted to Bengt Muthén for his advice on the statistical analyses for this study.
Power electronics technology: present trends and future developments

The history of special issues of the P ROCEEDINGS OF THE IEEE on subjects concerning power electronics started in August 1967 with the Special Issue on “High Power Semiconductor Devices” (Guest Editors F. E. Gentry and R. A. York) with 26 papers, including one on a power integrated circuit. This was followed in April 1988 with the Special Issue on “Power Electronics” (Guest Editors R. G. Hoft and H. A. Owen) with 17 papers, highlighting many new and exciting applications throughout the whole power range. The Special Issue on “Power Electronics and Motion Control” of August 1994 (Guest Editor B. K. Bose), with 12 papers, reflected very much the topics of the time with the accent on the role of power electronics in drives and their control. We now proudly present you with the new special issue in this field for June 2001. With the appearance of this fourth special issue, composed of 16 papers, we have a chance to look back on a century of power electronics—some retrospection and evaluation may be in order. From its humble beginnings at the start of the 20th century, tied to the technology of mastering the conduction processes in gases and in vacuum, the electronic processing of electrical energy—or power electronics—has come a long way through several generations of technologies. In this process of continuous growth, it has for a long time been clear that the limiting aspect of all these technologies was the electronic switching components. The frequencies of operation and the switch transition times were in such a range that the rest of the circuit elements—capacitors, inductors, transformers—had near ideal behavior, especially during initial system conception. The focus was on getting better and better power switches. Every increase in switch performance led to a corresponding improvement in power electronics technology. In response to every major power semiconductor technology development, power electronics really took off. In particular, bipolar power transistors, thyristors, power MOSFETs, GTOs, IGBTs, and IGCTs really delivered their promises. Power electronics stretched from microwatts to approaching the gigawatt range, while frequencies now cover from power frequencies to the megahertz range. The
Muscarinic, adenosine A(2) and histamine H(3) receptor modulation of haloperidol-induced c-fos expression in the striatum and nucleus accumbens.

It is generally believed that haloperidol exerts its motor side effects and therapeutic effects mainly by antagonizing dopamine D(2) receptors in the striatum and the nucleus accumbens, respectively. Several neurotransmitters/modulators, including glutamate, acetylcholine, adenosine and histamine, affect dopaminergic activity in these centers. We have recently shown that N-methyl-D-aspartate receptor-mediated modulation of haloperidol-induced c-fos expression differs in functionally specific regions of the striatum and the nucleus accumbens. In the present study, the entire striatum and the nucleus accumbens were comprehensively examined for the pattern of modulation of haloperidol-induced c-fos expression by adenosine A(2), histamine H(3) and muscarinic receptor antagonists. Blockade of muscarinic and H(3) receptors resulted in a profound suppression of haloperidol-induced c-fos expression in the dorsolateral part of the striatum. In addition, the H(3) receptor antagonist suppressed the effects of haloperidol in the ventrolateral aspect of the striatum and the rostral parts of the medial striatum. Muscarinic receptor antagonists suppressed haloperidol-induced c-fos expression throughout the shell and in the mid-level of the core of the nucleus accumbens while A(2) and H(3) receptor antagonists did not.We found that the muscarinic and H(3) receptor antagonists suppress the induction of c-fos by haloperidol in the dorsolateral aspect of the striatum, an area implicated in the development of extrapyramidal motor symptoms following chronic haloperidol treatment. By contrast, haloperidol-induced c-fos expression in the nucleus accumbens, an area implicated in the therapeutic effects of haloperidol, was suppressed by the muscarinic receptor antagonist, but not by the H(3) receptor antagonist. Therefore we conclude that H(3) receptor modulation may provide a useful therapeutic target in future efforts to minimize neuroleptic-induced motor side effects.
Identification and Characterization of New Chemical Entities Targeting Apurinic/Apyrimidinic Endonuclease 1 for the Prevention of Chemotherapy-Induced Peripheral Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially debilitating side effect of a number of chemotherapeutic agents. There are currently no U.S. Food and Drug Administration–approved interventions or prevention strategies for CIPN. Although the cellular mechanisms mediating CIPN remain to be determined, several lines of evidence support the notion that DNA damage caused by anticancer therapies could contribute to the neuropathy. DNA damage in sensory neurons after chemotherapy correlates with symptoms of CIPN. Augmenting apurinic/apyrimidinic endonuclease (APE)-1 function in the base excision repair pathway reverses this damage and the neurotoxicity caused by anticancer therapies. This neuronal protection is accomplished by either overexpressing APE1 or by using a first-generation targeted APE1 small molecule, E3330 [(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-undecanoic acid; also called APX3330]. Although E3330 has been approved for phase 1 clinical trials (Investigational New Drug application number IND125360), we synthesized novel, second-generation APE1-targeted molecules and determined whether they would be protective against neurotoxicity induced by cisplatin or oxaliplatin while not diminishing the platins’ antitumor effect. We measured various endpoints of neurotoxicity using our ex vivo model of sensory neurons in culture, and we determined that APX2009 [(2E)-2-[(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-N,N-diethylpentanamide] is an effective small molecule that is neuroprotective against cisplatin and oxaliplatin-induced toxicity. APX2009 also demonstrated a strong tumor cell killing effect in tumor cells and the enhanced tumor cell killing was further substantiated in a more robust three-dimensional pancreatic tumor model. Together, these data suggest that the second-generation compound APX2009 is effective in preventing or reversing platinum-induced CIPN while not affecting the anticancer activity of platins.
Compact quasi planar silicon bandpass filters based on metallic periodic structure for Q and V band applications

Small size filters are presented here, they are based on a periodic lattice of metallic holes that form coupled silicon resonators. The first structure is a filter at 45 GHz with 8% bandwidth at -3 db, realized on 430 /spl mu/m thick high resistivity silicon wafer using a wet etching process. I/O CPW feeds are printed on the top of the substrate. The second structure is a filter at 58.5 GHz with 2% bandwidth at -3 db. The via holes lattice is realized with deep RIE process and the filter is bonded to a PCB with a flip chip technique. Based on the same principle, a CPW to waveguide transition is finally presented.