bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening methods: Current status
Authors: Hayes Deborah
Published: May 2003

Two technologies are currently used to screen newborn infants for hearing, auditory brainstem response (ABR), and otoacoustic emissions (OAEs). Each technology is based on detecting the infant's physiologic response to auditory stimulation. ABR is a short‐latency auditory evoked response originating from eighth nerve and brainstem auditory pathway structures and detected by scalp surface electrodes. OAEs are auditory signals generated by cochlear outer hair cells in response to acoustic stimulation and detected by a miniature microphone coupled to the infant's ear. Although each technique requires specific sound generation and response recording technologies, advances in computerized stimulus delivery and response detection algorithms allow these tests to be performed by trained technicians or volunteers under the supervision of an audiologist. Results of test performance, and the advantages and disadvantages of each technique are described. MRDD Research Reviews 2003;9:65–72. © 2003 Wiley‐Liss, Inc.
Quality monitoring for early hearing detection and intervention programs to optimize performance
Authors: Finitzo Terese , Grosse Scott
Published: May 2003

The purpose of this chapter is to review the principles of quality monitoring for newborn screening programs at both a hospital and a public health level. The focus is on quality assurance in Early Hearing Detection and Intervention (EHDI). The chapter addresses the need for a systems approach to quality, beginning with the birth screening, moving to follow‐up re‐screening and on to confirmatory evaluations and life‐long intervention and management for the infants identified with permanent hearing loss. Benchmarks are identified to assist those involved in establishing programs or in improving program performance. As the use of electronic information systems in EHDI becomes widespread, the importance of strict computer‐based logic rules to assure patient privacy is addressed. MRDD Research Reviews 2003;9:73–78. © 2003 Wiley‐Liss, Inc.
The current status of EHDI programs in the United States
Authors: White Karl R.
Published: May 2003

The importance of identifying congenital hearing loss during the first few months of life has been recognized for almost 60 years. Unfortunately, until more effective newborn hearing screening equipment and procedures were developed in the late 1980s, it was not practical to implement programs for identifying hearing loss during the first few months of life. This paper reviews the activities implemented by the federal government in the last 15 years to promote more effective Early Hearing Detection and Intervention (EHDI) programs, and summarizes legislation passed by states related to universal newborn hearing screening. In surveys conducted in 1998 and 2001, State EHDI Coordinators were asked to rate the degree to which various issues were obstacles to implementing effective EHDI programs. The most serious obstacles are the shortage of qualified pediatric audiologists, inadequate reimbursement for screening and diagnosis, and lack of knowledge among primary health care providers about EHDI issues. Opposition to EHDI programs by hospital administrators was rated substantially lower in 2001 than in 1998. State EHDI Coordinators were also surveyed about how well their EHDI program is addressing issues related to screening, diagnosis, early intervention, linkages to medical home providers, tracking and data management, and family support programs. Although substantial progress has been made, many gaps remain with current EHDI programs. MRDD Research Reviews 2003;9:79–88. © 2003 Wiley‐Liss, Inc.
Family perceptions of early hearing, detection, and intervention systems: Listening to and learning from families
Authors: DesGeorges Janet
Published: May 2003

As universal newborn hearing systems (screening, diagnosis, intervention) are being established around the world, the success of children who are identified to be deaf and hard of hearing is critically impacted by parent's reactions, acceptance, and advocacy for their child. It is imperative for professionals who are creating systems for Early Hearing, Detection, and Intervention to understand and learn from families' experiences in order to improve this process. This manuscript will identify the areas in which parents have spoken out about the professionals they have encountered through the system: what parents wish for in a healthy, productive relationship with professionals; and how parents can play a part in advocating for a system in which families needs are met so that infants identified to be deaf or hard of hearing can reach their full potential. MRDD Research Reviews 2003;9:89–93. © 2003 Wiley‐Liss, Inc.
The otolaryngologist's role in management of hearing loss in infancy and childhood
Authors: Doyle Karen Jo , Ray R. Mark
Published: May 2003

This article reviews the role of the otolaryngologist–head and neck surgeon–in the diagnosis and treatment of hearing loss in infants and young children. The otolaryngologist is well‐versed in the anatomy, physiology, and pathophysiology of the auditory system, as well as the craniofacial syndromes that can involve the head and neck in combination with deafness. In this paper, the various causes of congenital hearing loss are described, as well as the steps required for proper diagnosis. Finally, surgeries used by otolaryngologists to treat childhood hearing loss, their indications, and outcomes, are discussed. MRDD Research Reviews 2003;9:94–102. © 2003 Wiley‐Liss, Inc.
Cost‐effectiveness and test‐performance factors in relation to universal newborn hearing screening
Authors: Gorga Michael P. , Neely Stephen T.
Published: May 2003

The first portion of this paper reviews current understanding of the cost of universal newborn hearing screening (UNHS), including capital and operating expenses, as well as the costs for follow‐up testing on infants who do not pass the hearing screening test in the perinatal period. Capital expenses include the cost of equipment. Operating expenses include the costs for disposables and personnel. Follow‐up costs relate to the diagnostic testing that must be performed in order to determine hearing status in those infants who do not pass the newborn hearing screening test. This section is followed by a more theoretical approach, in which test performance, prevalence, program costs, and “costs of hearing loss” are combined in a model that includes all costs of hearing loss, including screening, follow‐up testing, and costs (benefits) associated with identifying hearing loss early in life. While some of the model's cost/benefit assumptions may be incorrect, the general approach of taking into account both costs and benefits provides a framework for evaluating the utility of UNHS in a more global manner. Model assumptions (costs, benefits, prevalence, sensitivity, specificity) can be changed to values deemed more appropriate, but the general approach is still informative. With the present assumptions, it is shown that initially, the costs of UNHS exceed its benefits. However, after only four years of operation, UNHS programs will result in a net savings to society. These savings increase rapidly, reaching a maximum annual benefit of seven billion dollars 75 years after initiation of the program, which is also the societal benefit for all years thereafter. MRDD Research Reviews 2003;9:103–108. © 2003 Wiley‐Liss, Inc.
Certification in neurodevelopmental disabilities: The development of a new subspecialty and results of the initial examinations
Authors: Palmer Frederick B. , Percy Alan K. , Tivnan Patricia , Juul Dorthea , Tunnessen Walter W. , Scheiber Stephen C.
Published: May 2003

The American Board of Psychiatry and Neurology, in collaboration with the American Board of Pediatrics, administered the first Subspecialty Certification Examination in Neurodevelopmental Disabilities to 190 candidates on April 3, 2001, and the second to 80 candidates on April 9, 2002. This report describes the history of the certifying examination including the process of its development and the results of the first and second examination administrations. The purpose of the Certification Examination in Neurodevelopmental Disabilities is to assess knowledge of qualified candidates in the subspecialty. A committee comprised of child neurologists and pediatricians developed this examination. Of the 190 pediatricians (n = 169) and child neurologists (n = 21) who completed the examination in 2001, 157 (83%) passed the examination. The second group of examinees included 68 pediatricians and 12 child neurologists, and the pass rate was 70%. The 213 candidates certified to date have received ten‐year time‐limited certificates that may be renewed by recertification process beginning in 2010. After the “grandfathering period,” candidates for the examination must complete ACGME‐approved training programs in the subspecialty. MRDD Research Reviews 2003;9:128–131. © 2003 Wiley‐Liss, Inc.
Capacity and flow assignment issues in MPLS networks
Authors: Liu Xian
Published: June 2003

MPLS technology enables IP networks to accept the challenge raised by emerging communication paradigms. This paper describes a nonlinear model with path capacity as design variables and space priority as constraints. The analysis shows that the close‐form solution exists if traffic flows are allocated by an independent protocol. Copyright © 2003 John Wiley &Sons, Ltd.
Resource allocation in the new fixed and mobile Internet generation
Authors: Pujolle Guy , Körner Ulf , Perros Harry
Published: June 2003

In this paper we study the scalability issue in the design of a centralized policy server controlling resources in the future
IP‐based telecom network generation. The policy servers are in charge of controlling and managing QoS, security and mobility in
a centralized way in future IP‐based telecom networks. Our study demonstrates that the policy servers can be designed in such a
manner that they scale with increase in network capacity. Copyright © 2003 John Wiley &Sons, Ltd.
Design and implementation of WAP‐based LAN segment management system using RMON MIB
Authors: Kim Jong‐Keun , Ahn Seong‐Jin , Chung Jin‐Wook
Published: June 2003

Advances in LAN technology have enabled fast data transmission. However, without effective management of these resources, congestion of networks as well as waste of resources are inevitable. Therefore, it is necessary to supervise, report, and even control, if necessary, the network resource status so that the communication network can be effectively operated without service interruption by monitoring traffic among the hosts. Web‐based network management systems have been developed and applied for remote management without using specific applications. However, such web‐based network management systems have limited manager mobility and poor performance. To overcome such disadvantages, this paper proposes a network management system using wireless communication. Copyright © 2003 John Wiley & Sons, Ltd.
Development of security policies for private networks
Authors: Bakry Saad Haj
Published: June 2003

With the current worldwide emphasis on e‐business, the development of sound network security policies for private networks connected
to the Internet is becoming of increasing importance. This paper identifies a general network security profile upon which current and planned
network security states can be mapped. The paper also provides a process for the development of current security states into target states,
using the network security profile. Copyright © 2003 John Wiley &Sons, Ltd.
Active queue management with flow proportional buffering
Authors: Aweya James , Ouellette Michel , Montuno Delfin Y.
Published: June 2003

Most active queue management schemes maintain an average of the queue length which they use together with a number of queue thresholds to detect congestion. However, the setting of the queue thresholds is problematic because the required buffer size for good sharing among TCP connections is dependent on the number of TCP connections using the buffer. This paper describes an improved active queue management scheme which dynamically changes its threshold settings as the number of connections and system load changes. This technique allows network devices to effectively control packet losses and TCP timeouts while maintaining high link utilization. Copyright © 2003 John Wiley &Sons, Ltd.
Connection set‐up and QoS monitoring in ATM networks
Authors: Tan Sin‐Lam , Tham Chen‐Khong , Ngoh Lek‐Heng
Published: June 2003

This paper describes a system for creating virtual connections based on QoS requirements and providing basic QoS routing
functionality. It effectively bridges the gap between complex protocols like PNNI and tedious manual set‐up of virtual
connections. Copyright © 2003 John Wiley & Sons, Ltd.
Manufacturing tolerances and multiple loading conditions in structural configuration optimization
Authors: Dems K. , Gutkowski W.
Published: June 2003

Most structures, during their service life, are subjected to several loading conditions; moreover, during their assembly, some or all of the assumed design variables are varied due to manufacturing imperfections. In the case of an optimum structure this can be especially dangerous. The problem of imperfections is a random one and its possible solution is not easily applicable due to its complexity. There is thus a need to give designers a tool that will enable them to incorporate the manufacturing tolerances in a relatively simple way. The proposed approach is deterministic, giving approximate minimum weight design with a safety margin. This is because limits of constraints are reduced by products of sensitivities multiplied by given tolerances. This paper is illustrated with two minimum weight designs of truss configurations, under three loading conditions each. Copyright © 2003 John Wiley & Sons, Ltd.
Design sensitivity analysis and optimization for polymer sheet extrusion and mold filling processes
Authors: Smith Douglas E.
Published: June 2003

A polymer processing design methodology is presented which can be used to improve the production of plastic components manufactured via extrusion and injection molding processes. The design method combines polymer process modelling, design sensitivity analysis and numerical optimization. It is applicable to systems with creeping flow of purely viscous non‐Newtonian fluids through thin cavities where the lubrication approximation may be applied. An analysis and an adjoint design sensitivity analysis are presented for the steady‐state coupled system which describes the pressure and residence time distributions in sheeting dies. The resulting methodology is then used to define the optimal die cavity shape and relevant process parameters in a sheeting die design example. A second example considers tooling and process design for the polymer injection molding process. A coupled transient mold filling analysis and design sensitivity analysis based on the direct differentiation method are developed where attention is given to describing the location of the gates in the mold cavity. The latter is illustrated through the process design of a plastic automotive component. Copyright © 2003 John Wiley & Sons, Ltd.
An augmented Newton method in elastic–plastic structural optimization
Authors: Sun Renzhang , Hisada Toshiaki
Published: June 2003

In this paper, an augmented Newton method for the optimization of elastic–plastic structures is proposed. It is shown that the optimization algorithm has to be nested due to the nature of elastic–plastic problems, and in this framework, an efficient and robust algorithm should be developed. For this purpose, the principle of the integrated method is incorporated to enhance the system matrix of the Newton method in the framework of the nested approach. Namely, the system equation is first derived in the extended space, and then it is condensed. After some manipulation, a compact form of the system matrix equation is derived which is similar to that in the conventional Newton method. The augmentation terms can be evaluated based on the design sensitivities, so the computational cost is about the same as that for the conventional method, but it substantially searches for the solution in the extended space. The potential of the proposed method is exemplified in a simple elastic–plastic truss. Copyright © 2003 John Wiley & Sons, Ltd.
FT‐IR Investigation into the miscible interactions in new materials for optical devices
Authors: Sharma Lakshmi , Kimura Tatsumi
Published: June 2003

In this article we determine the miscibility of azobenzene derivative (poly(4‐(N‐(2‐methacryloyloxyethyl)‐N‐ethylamino)‐4′‐nitroazobenzene)90‐co‐(methyl methacrylate)10)/poly(vinyl acetate) (PVAc) and azobenzene derivative/poly(vinyl chloride) (PVC) blends using Fourier Transform infrared (FT‐IR) spectroscopy. With this method we can clearly identify the exact interactions responsible for miscibility. In the azobenzene derivative 50:50PVAc blend new peaks were evident at 2960, 2890, 1237 and 959 cm−1, these peaks depict miscible interactions. These wavenumbers indicate that the miscible interactions occurring are from the CH stretching band, the vinyl acetate CO, conjugated to the ester carbonyl, the cis‐transformation NN stretch frequency and the acetate ester weak doublet. The azobenzene derivative 80:20PVC blend display peaks identical in profile to the blend homopolymers, indicating no miscible interactions. However, this could be due to overlapping of peaks within the same wavenumber region, making resolution difficult.

This research demonstrates FT‐IR can deduce favorable interactions for miscibility and therefore numerous miscible blends can successfully be calculated if possessing the same groups responsible for miscibility. This paves the way for a new generation of designer optical materials with the desired properties. Copyright © 2003 John Wiley & Sons, Ltd.
New super‐tough poly(butylene terephthalate) materials based on compatibilized blends with metallocenic poly(ethylene‐octene) copolymer
Authors: Aróstegui A. , Nazábal J.
Published: June 2003

New super‐tough poly(butylene terephthalate) (PBT)/poly(ethylene‐octene) copolymer (PEO) blends containing 2 wt% poly(ethylene‐co‐glycidyl methacrylate) (EGMA) as a compatibilizer were obtained by extrusion and injection molding. The blends comprised of an amorphous PBT‐rich phase with some miscibilized EGMA, a pure PEO amorphous phase, and a crystalline PBT phase that was not influenced by the presence of either PEO or EGMA. The blends showed a fine particle size up to 20 wt% PEO content. Super‐tough blends were obtained with PEO contents equal to or higher than 10%. The maximum toughness was very high (above 710 J/m) and was attained with 20% PEO without chemical modification of the commercial components used. Copyright © 2003 John Wiley & Sons, Ltd.
Surface functionalization of styrene/butyl acrylate latex with a water‐soluble monosaccharide monomer. Synthesis and morphology of the polymer particles
Authors: Deppe O. , Subat M. , Yaacoub E.‐J.
Published: June 2003

New polymer latexes bearing saccharide moieties on the particle surface were synthesized by using a water‐soluble sugar monomer, such as 1‐deoxy‐1‐methacryl‐amido‐D‐glucitol, (MAG). All the latexes were prepared by a two‐stage emulsion polymerization technique. In the first step, the core was prepared with butyl acrylate (BA) and styrene (St). In the second step, the seed latex was polymerized with ethyl acrylate (EA) and MAG. The influence of a bifunctional monomer such as allyl methacrylate (ALMA), introduced at various concentrations, on the final latexes morphologies and properties was investigated. It was found that the latex particles exhibit a core‐shell structure. The mass balance of MAG showed that the main part of the sugar moiety is on the shell layer. The molecular properties, such as structure, composition, and molecular weight, were determined by elemental analysis,
1H‐ and
13C‐NMR spectroscopy. Colloidal (particle size and their distributions), thermal, and rheological properties were also studied. Copyright © 2003 John Wiley & Sons, Ltd.
Properties of low temperature swelling hydrogels prepared with partially saponified PVA and drug release using the hydrogels
Authors: Horiike Satoshi , Yumoto Kyoji , Matsuzawa Shuji , Yamaura Kazuo
Published: June 2003

The hydrogels prepared by the crosslinking of partially saponified poly(vinyl alcohol) (PVA) which has low critical solution temperature (LCST) in water showed characteristics of swelling at low temperature and shrinkage at high temperature. The hydrogels showed repeatable swelling–shrinking behavior. The hydrogels containing release substances such as cyanocobalamin, p‐acetamidophenol, insulin and ovalbumin were prepared by dipping these aqueous solutions and the release substances were studied. Insulin and ovalbumin were not absorbed by the hydrogels when the use of partially PVA with the degrees of polymerization (DPs) of 540 were prepared, but absorbed by the hydrogels with DPs of 1860. The size of the polymer network prepared with a higher DP was suitable for the absorption of insulin and ovalbumin. In accordance with release substances, the release patterns were different. In this way, the polymer network sizes and their swelling behaviors of partially saponified PVAs were estimated. Copyright © 2003 John Wiley & Sons, Ltd.
Preparation of inclusion complex between polyaniline and β‐cyclodextrin in aqueous solution
Authors: Yuan Guo‐Li , Kuramoto Noriyuki , Takeishi Makoto
Published: June 2003

Two routes have been developed inorder to prepare an inclusion complex of polyaniline (PANI) and β‐cyclodextrin (βCyD). The first route was to in situ polymerize N‐phenyl‐1,4‐phenylenediamine (PPD) which was encapsulated in βCyD in advance. The formation of an inclusion complex was confirmed by UV‐vis, circular dichroism (CD), and NMR spectra. It was found that the synthesized complex was readily dissolved in a range of solvents due to the solubility of βCyD. In these solvents, PANI was well encapsulated by βCyD with some conformation change in the chain of PANI, which was proved by the CD spectra of PANI. The second route involved preparing the inclusion complex by post‐encapsulation of PANI emeraldine base (EB) into βCyD in aqueous solution at room temperature. The encapsulation of EB into βCyD was confirmed by FT‐IR and UV‐vis spectra. The band shift in UV‐vis spectra indicated that the inclusion complexation was a gradual process, and the change in the chain conformation of PANI was also observed after it was encapsulated into βCyD. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of molecular weight on gas selectivity of oriented thin polyimide membrane
Authors: Nakajima K. , Nagaoka S. , Kawakami H.
Published: June 2003

In this study, we focused on effect of the molecular weight of polyimide on the gas selectivity of the asymmetric membrane with an oriented surface skin layer prepared at different shear stresses. Asymmetric polyimide membranes, which have a defect‐free surface skin layer supported by a porous substructure, were prepared by a dry/wet phase inversion process. The structures of the asymmetric polyimides consisted of a thin skin layer and a porous substructure characterized by the presence of finger‐voids. The gas selectivities of the asymmetric polyimide membranes increased with an increase in the shear rate or a decrease in the molecular weight, indicating that the oriented polyimide structure in the surface skin layer provided a high size and shape discrimination between the gas molecules. The selectivity values of (O2/N2) and (CO2/CH4) in the asymmetric polyimide membrane prepared from the 7.2 × 104 molecular weight material at 1000 sec−1 shear rate were 12 and 143, respectively. Copyright © 2003 John Wiley & Sons, Ltd.
Data mining crystallization databases: Knowledge‐based approaches to optimize protein crystal screens
Authors: Kimber Matthew S. , Vallee François , Houston Simon , Nečakov Alexander , Skarina Tatiana , Evdokimova Elena , Beasley Steven , Christendat Dinesh , Savchenko Alexei , Arrowsmith Cheryl H. , Vedadi Masoud , Gerstein Mark , Edwards Aled M.
Published: May 2003

Protein crystallization is a major bottleneck in protein X‐ray crystallography, the workhorse of most structural proteomics projects. Because the principles that govern protein crystallization are too poorly understood to allow them to be used in a strongly predictive sense, the most common crystallization strategy entails screening a wide variety of solution conditions to identify the small subset that will support crystal nucleation and growth. We tested the hypothesis that more efficient crystallization strategies could be formulated by extracting useful patterns and correlations from the large data sets of crystallization trials created in structural proteomics projects. A database of crystallization conditions was constructed for 755 different proteins purified and crystallized under uniform conditions. Forty‐five percent of the proteins formed crystals. Data mining identified the conditions that crystallize the most proteins, revealed that many conditions are highly correlated in their behavior, and showed that the crystallization success rate is markedly dependent on the organism from which proteins derive. Of the proteins that crystallized in a 48‐condition experiment, 60% could be crystallized in as few as 6 conditions and 94% in 24 conditions. Consideration of the full range of information coming from crystal screening trials allows one to design screens that are maximally productive while consuming minimal resources, and also suggests further useful conditions for extending existing screens. Proteins 2003;51:562–568. © 2003 Wiley‐Liss, Inc.
Scaling law in sizes of protein sequence families: From super‐families to orphan genes
Authors: Unger Ron , Uliel Shai , Havlin Shlomo
Published: May 2003

It has been observed that the size of protein sequence families is unevenly distributed, with few super families with a large number of members and many “orphan” proteins that do not belong to any family. Here it is shown that the distribution of sizes of protein families in different databases and classifications (Protomap, Prodom, Cog) follows a power‐law behavior with similar scaling exponents, which is characteristic of self‐organizing systems. Since large databases are used in this study, a more detailed analysis of the data than in previous studies was possible. Hence, it is shown that the size distribution is governed by two exponents, different for the super families and the orphan proteins. A simple model of protein evolution is proposed, in which proteins are dynamically generated and clustered into families. The model yields a scaling behavior very similar to the distribution observed in the actual sequence databases, including the two distinct regimes for the large and small families, and thus suggests that the existence of “super families” of proteins and “orphan” proteins are two manifestations of the same evolutionary process. Proteins 2003;51:569–576. © 2003 Wiley‐Liss, Inc.
Generation of accurate protein loop conformations through low‐barrier molecular dynamics
Authors: Hornak Viktor , Simmerling Carlos
Published: May 2003

Prediction and refinement of protein loop structures are important and challenging tasks for which no general solution has been found. In addition to the accuracy of scoring functions, the main problems reside in (1) insufficient statistical sampling and (2) crossing energy barriers that impede conformational rearrangements of the loop. We approach these two issues by using “low‐barrier molecular dynamics,” a combination of energy smoothing techniques. To address statistical sampling, locally enhanced sampling (LES) is used to produce multiple copies of the loop, thus improving statistics and reducing energy barriers. We introduce a novel extension of LES that can improve local sampling even further through hierarchical subdivision of copies. Even though LES reduces energy barriers, it cannot provide for crossing infinite barriers, which can be problematic when substantial rearrangement of residues is necessary. To permit this kind of loop residue repacking, a “soft‐core” potential energy function is introduced, so that atomic overlaps are temporarily allowed. We tested this new combined methodology to a loop in anti‐influenza antibody Fab 17/9 (7 residues long) and to another loop in the antiprogesterone antibody DB3 (8 residues). In both cases, starting from random conformations, we were able to locate correct loop structures (including sidechain orientations) with heavy‐atom root‐mean‐square deviation (fit to the nonloop region) of ∼1.1 Å in Fab 17/9 and ∼1.8 Å in DB3. We show that the combination of LES and soft‐core potential substantially improves sampling compared to regular molecular dynamics. Moreover, the sampling improvement obtained with this combined approach is significantly better than that provided by either of the two methods alone. Proteins 2003;51:577–590. © 2003 Wiley‐Liss, Inc.
Hidden Markov models that use predicted local structure for fold recognition: Alphabets of backbone geometry
Authors: Karchin Rachel , Cline Melissa , Mandel‐Gutfreund Yael , Karplus Kevin
Published: May 2003

An important problem in computational biology is predicting the structure of the large number of putative proteins discovered by genome sequencing projects. Fold‐recognition methods attempt to solve the problem by relating the target proteins to known structures, searching for template proteins homologous to the target. Remote homologs that may have significant structural similarity are often not detectable by sequence similarities alone. To address this, we incorporated predicted local structure, a generalization of secondary structure, into two‐track profile hidden Markov models (HMMs). We did not rely on a simple helix‐strand‐coil definition of secondary structure, but experimented with a variety of local structure descriptions, following a principled protocol to establish which descriptions are most useful for improving fold recognition and alignment quality. On a test set of 1298 nonhomologous proteins, HMMs incorporating a 3‐letter STRIDE alphabet improved fold recognition accuracy by 15% over amino‐acid‐only HMMs and 23% over PSI‐BLAST, measured by ROC‐65 numbers. We compared two‐track HMMs to amino‐acid‐only HMMs on a difficult alignment test set of 200 protein pairs (structurally similar with 3–24% sequence identity). HMMs with a 6‐letter STRIDE secondary track improved alignment quality by 62%, relative to DALI structural alignments, while HMMs with an STR track (an expanded DSSP alphabet that subdivides strands into six states) improved by 40% relative to CE. Proteins 2003;51:504–514. © 2003 Wiley‐Liss, Inc.
Ultraviolet illumination‐induced reduction of α‐lactalbumin disulfide bridges
Authors: Permyakov Eugene A. , Permyakov Serge E. , Deikus Gintaras Y. , Morozova‐Roche Ludmila A. , Grishchenko Valery M. , Kalinichenko Lina P. , Uversky Vladimir N.
Published: May 2003

Prolonged exposure of Ca2+‐loaded or Ca2+‐depleted human α‐lactalbumin to ultraviolet light (270–290 nm, 1 mW/cm2, for 2 to 4 h) results in a 10‐nm red shift of its tryptophan fluorescence spectrum. Gel chromatography of the UV‐illuminated samples reveals two non‐native protein forms: (1) a component with a red‐shifted tryptophan fluorescence spectrum; and (2) a component with kynurenine‐like fluorescent properties. The first component has from 0.6 to 0.9 free DTNB‐reactive SH groups per protein molecule, which are absent in the native protein and is characterized by slightly lowered Ca2+‐affinity (2 × 108 M−1 versus 8 × 108 M−1 for the native protein) and absence of observable thermal transition. The second component corresponds to the protein with photochemically modified tryptophan residues. It is assumed that the UV excitation of tryptophan residue(s) in α‐lactalbumin is followed by a transfer of electrons to the SS bonds, resulting in their reduction. Mass spectrometry data obtained for trypsin‐fragmented UV‐illuminated α‐lactalbumin with acrylodan‐modified free thiol groups reveal the reduction of the 61–77 and 73–91 disulfide bridges. The effect observed has to be taken into account in any UV‐region spectral studies of α‐lactalbumin. Proteins 2003;51:498–503. © 2003 Wiley‐Liss, Inc.
The nature of the turn in omega loops of proteins
Authors: Pal Manoj , Dasgupta Swagata
Published: May 2003

An analysis of Ω loops in a nonredundant set of protein stuctures from the Protein Data Bank has been carried out to determine the nature of the “turn elements” present. Because Ω loops essentially reverse their direction in three‐dimensional space, this analysis was made with respect to four turn elements identified as (1) Gly; (2) Pro; (3) a residue with α‐helical ϕ,ψ angles, termed a helical residue; and (4) a cis peptide. A set of 1079 Ω loops from a set of 680 proteins were used for the analysis. Apart from other criteria that define Ω loops, the selection of an Ω loop from a cluster of loops is based on an exposure index. In this study, analyses have been made with two sets of data: (1) Ω loops arising from a minimum exposure index indicative of a less exposed loop (xmin set) and (2) Ω loops with a maximum exposure index indicative of a relatively exposed loop (xmax set). Overall residue preferences and positional preferences have been examined. Positions of the turn elements for Ω loops of varying length have also been studied. Specific positional preferences are observed for particular turn elements with regard to the length of Ω loops. Analysis in terms of the turn elements can provide guidelines for modeling of loops in proteins. Apart from Pro, which has the natural tendency to form cis peptide bonds, a higher occurrence of non‐Pro cis peptide bonds is observed. Torsion angles in Ω loops also indicate the occurrence of a large number of residues with helical ϕ,ψ angles, necessary for the turn in the loop structures. Proteins 2003;51:591–606. © 2003 Wiley‐Liss, Inc.
Static and dynamic water molecules in Cu,Zn superoxide dismutase
Authors: Falconi M. , Brunelli M. , Pesce A. , Ferrario M. , Bolognesi M. , Desideri A.
Published: May 2003

Understanding protein hydration is a crucial, and often underestimated issue, in unraveling protein function. Molecular dynamics (MD) computer simulation can provide a microscopic description of the water behavior. We have applied such a simulative approach to dimeric Photobacterium leiognathi Cu,Zn superoxide dismutase, comparing the water molecule sites determined using 1.0 ns MD simulation with those detected by X‐ray crystallography. Of the water molecules detected by the two techniques, 20% fall at common sites. These are evenly distributed over the protein surface and located around crevices, which represent the preferred hydration sites. The water mean residence time, estimated by means of a survival probability function on a given protein hydration shell, is relatively short and increases for low accessibility sites constituted by polar atoms. Water molecules trapped in the dimeric protein intersubunit cavity, as identified in the crystal structure, display a trajectory mainly confined within the cavity. The simulation shows that these water molecules are characterized by relatively short residence times, because they continuously change from one site to another within the cavity, thus hinting at the absence of any relationship between spatial and temporal order for solvent molecules in proximity of protein surface. Proteins 2003;51:607–615. © 2003 Wiley‐Liss, Inc.
Analysis of the differences in the folding kinetics of structurally homologous proteins based on predictions of the gross features of residue contacts
Authors: Ichimaru Takehiro , Kikuchi Takeshi
Published: May 2003

It is a general notion that proteins with very similar three‐dimensional structures would show very similar folding kinetics. However, recent studies reveal that the folding kinetic properties of some proteins contradict this thought (i.e., the members in a same protein family fold through different pathways). For example, it has been reported that some β‐proteins in the intracellular lipid‐binding protein family fold through quite different pathways (Burns et al., Proteins 1998;33:107–118). Similar differences in folding kinetics are also observed in the members of the globin family (Nishimura et al., Nat Struct Biol 2000;7:679–686). In our study, we examine the possibility of predicting qualitative differences in folding kinetics of the intracellular lipid‐binding proteins and two globin proteins (i.e., myoglobin and leghemoglobin). The problem is tackled by means of a contact map based on the average distance statistics between residues, the Average Distance Map (ADM), as constructed from sequence. The ADMs for the three proteins show overall similarity, but some local differences among maps are also observed. Our results demonstrate that some properties of the protein folding kinetics are consistent with local differences in the ADMs. We also discuss the general possibility of predicting folding kinetics from sequence information. Proteins 2003;51:515–530. © 2003 Wiley‐Liss, Inc.
Guided docking: First step to locate potential binding sites
Authors: Fitzjohn Paul W. , Bates Paul A.
Published: May 2003

The long‐range electrostatic forces of the targets in round 2 of the Critical Assessment of PRediction of Interactions (CAPRI) experiment were examined and a simple guided docking method, based on these forces, was applied. The method described consists of calculating an initial rigid body trajectory and an optional final, fully flexible refinement stage. Although only limited success was found in predicting the final complexes, some interesting information was discovered. In particular, the long‐range forces seem to give some insight into the unusual binding mode of target 4 while raising some questions about target 7, which warrant further investigation. Proteins 2003;52:28–32. © 2003 Wiley‐Liss, Inc.
CAPRI: A Critical Assessment of PRedicted Interactions
Authors: Janin Joël , Henrick Kim , Moult John , Eyck Lynn Ten , Sternberg Michael J. E. , Vajda Sandor , Vakser Ilya , Wodak Shoshana J.
Published: May 2003

CAPRI is a communitywide experiment to assess the capacity of protein‐docking methods to predict protein–protein interactions. Nineteen groups participated in rounds 1 and 2 of CAPRI and submitted blind structure predictions for seven protein–protein complexes based on the known structure of the component proteins. The predictions were compared to the unpublished X‐ray structures of the complexes. We describe here the motivations for launching CAPRI, the rules that we applied to select targets and run the experiment, and some conclusions that can already be drawn. The results stress the need for new scoring functions and for methods handling the conformation changes that were observed in some of the target systems. CAPRI has already been a powerful drive for the community of computational biologists who development docking algorithms. We hope that this issue of Proteins will also be of interest to the community of structural biologists, which we call upon to provide new targets for future rounds of CAPRI, and to all molecular biologists who view protein–protein recognition as an essential process. Proteins 2003;52:2–9. © 2003 Wiley‐Liss, Inc.
ICM‐DISCO docking by global energy optimization with fully flexible side‐chains
Authors: Fernández‐Recio Juan , Totrov Maxim , Abagyan Ruben
Published: May 2003

The ICM‐DISCO (Docking and Interface Side‐Chain Optimization) protein–protein‐docking method is a direct stochastic global energy optimization from multiple starting positions of the ligand. The first step is performed by docking of a rigid all‐atom ligand molecule to a set of soft receptor potentials precalculated on a 0.5 Å grid from realistic solvent‐corrected force‐field energies. This step finds the correct solution as the lowest energy conformation in almost 100% of the cases in which interfaces do not change on binding. The second step is needed to deal with the induced changes and includes the global optimization of the interface side‐chains of up to 400 best solutions. The CAPRI predictions were performed fully automatically with this method. Available experimental information was included as a filtering step to favor expected docking surfaces. In three of the seven proposed targets, the ICM‐DISCO method found a good solution (>50% of correct contacts) within the five submitted models. The procedure is global and fully automated. We demonstrate that the algorithm handles the induced changes of surface side‐chains but is less successful if the backbone undergoes large‐scale rearrangements. Proteins 2003;52:113–117. © 2003 Wiley‐Liss, Inc.
Evaluation of the third solvent clusters fitting procedure for the prediction of protein–protein interactions based on the results at the CAPRI blind docking study
Authors: Komatsu Katsuichiro , Kurihara Youji , Iwadate Mitsuo , Takeda‐Shitaka Mayuko , Umeyama Hideaki
Published: May 2003

To predict protein–protein interactions, rough or coarse handling for the induced fit problem is proposed. Our method involves the overlap of two hydrophobic interactions as “third solvent clusters fitting.” Predictions for binding sites and geometric centers were acceptable, but those of the binding axes were poor. In this study, only the largest benzene cluster was used for the third solvent clusters fitting. For the next CAPRI targets, we must perform protein–protein interaction analyses, which include other smaller benzene clusters. Proteins 2003;52:15–18. © 2003 Wiley‐Liss, Inc.
Modeling protein complexes with BiGGER
Authors: Krippahl Ludwig , Moura José J. , Palma P. Nuno
Published: May 2003

This article describes the method and results of our participation in the Critical Assessment of PRediction of Interactions (CAPRI) experiment, using the protein docking program BiGGER (Bimolecular complex Generation with Global Evaluation and Ranking) (Palma et al., Proteins 2000;39:372–384). Of five target complexes (CAPRI targets 2, 4, 5, 6, and 7), only one was successfully predicted (target 6), but BiGGER generated reasonable models for targets 4, 5, and 7, which could have been identified if additional biochemical information had been available. Proteins 2003;52:19–23. © 2003 Wiley‐Liss, Inc.
ZDOCK predictions for the CAPRI challenge
Authors: Chen Rong , Tong Weiwei , Mintseris Julian , Li Li , Weng Zhiping
Published: May 2003

The CAPRI Challenge is a blind test of protein–protein‐docking algorithms that predict the complex structure from the crystal structures of the interacting proteins. We participated in both rounds of this blind test and submitted predictions for all seven targets, relying mainly on our Fast Fourier Transform based algorithm ZDOCK that combines shape complementarity, desolvation, and electrostatics. Our group made good predictions for three targets and had at least some success with three others. Implications of the treatment of prior biological information as well as contributions of manual inspection to docking predictions are also discussed. Proteins 2003;52:68–73. © 2003 Wiley‐Liss, Inc.
A protein–protein docking benchmark
Authors: Chen Rong , Mintseris Julian , Janin Joël , Weng Zhiping
Published: May 2003

We have developed a nonredundant benchmark for testing protein–protein docking algorithms. Currently it contains 59 test cases: 22 enzyme‐inhibitor complexes, 19 antibody‐antigen complexes, 11 other complexes, and 7 difficult test cases. Thirty‐one of the test cases, for which the unbound structures of both the receptor and ligand are available, are classified as follows: 16 enzyme‐inhibitor, 5 antibody‐antigen, 5 others, and 5 difficult. Such a centralized resource should benefit the docking community not only as a large curated test set but also as a common ground for comparing different algorithms. The benchmark is available at (http://zlab.bu.edu/∼rong/dock/benchmark.shtml). Proteins 2003;52:88–91. © 2003 Wiley‐Liss, Inc.
Weighted geometric docking: Incorporating external information in the rotation‐translation scan
Authors: Ben‐Zeev Efrat , Eisenstein Miriam
Published: May 2003

Weighted geometric docking is a prediction algorithm that matches weighted molecular surfaces. Each molecule is represented by a grid of complex numbers, storing information about the shape of the molecule in the real part and weight information in the imaginary part. The weights are based on experimental biochemical and biophysical data or on theoretical analyses of amino acid conservation or correlation patterns in multiple‐sequence alignments of homologous proteins. Only a few surface residues on either one or both molecules are weighted. In contrast to methods that use postscan filtering based on biochemical information, our method incorporates the external data in the rotation‐translation search, producing a different set of docking solutions biased toward solutions in which the up‐weighted residues are at the interface. Similarly, interactions involving specified residues can be impeded. The weighted geometric algorithm was applied to five systems for which regular geometric docking of the unbound molecules gave poor results. We obtained much better ranking of the nearly correct prediction and higher statistical significance when weighted geometric docking was used. The method was successful even when the weighted portion of the surface corresponded only partially and approximately to the binding site. Proteins 2003;52:24–27. © 2003 Wiley‐Liss, Inc.
Prediction of the unknown: Inspiring experience with the CAPRI experiment
Authors: Ben‐Zeev Efrat , Berchanski Alexander , Heifetz Alexander , Shapira Boaz , Eisenstein Miriam
Published: May 2003

We submitted predictions for all seven targets in the CAPRI experiment. For four targets, our submitted models included acceptable, medium accuracy predictions of the structures of the complexes, and for a fifth target we identified the location of the binding site of one of the molecules. We used a weighted‐geometric docking algorithm in which contacts involving specified parts of the surfaces of either one or both molecules were up‐weighted or down‐weighted. The weights were based on available structural and biochemical data or on sequence analyses. The weighted‐geometric docking proved very useful for five targets, improving the complementarity scores and the ranks of the nearly correct solutions, as well as their statistical significance. In addition, the weighted‐geometric docking promoted formation of clusters of similar solutions, which include more accurate predictions. Proteins 2003;52:41–46. © 2003 Wiley‐Liss, Inc.