bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloaked microbubbles and acoustic radiation force for ultrasound molecular imaging
Authors: Borden Mark , Sirsi Shashank , Streeter Jason , Dayton Paul
Published: October 2018

In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the biomarker is counterbalanced by the need to minimize interactions with plasma components, and to avoid recognition by the immune system. We have designed a microbubble imaging probe for ultrasound molecular imaging that uses a cloaked surface architecture to minimize unwanted interactions and immunogenicity. Here, we examine the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison to controls. The cloaked microbubbles were then activated for targeted adhesion through the application of the primary acoustic radiation force applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were uncloaked, imaged and silenced. Results showed a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for cloaked microbubbles, while no such increase was found for exposed-ligand microbubbles. We conclude that use of cloaked microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo.
Power-preserving nonlinear modal coupling, feedback frequency/phase modulation, and the stretched allpass filter
Authors: Smyth Tamara , Hsu Jennifer S.
Published: October 2018

Motivated by the sound produced by nonlinear modal coupling in acoustic systems, e.g., changes of sounding frequency in the form of pitch glides/chirps and the generation of harmonics, we model a nonlinear coupling between two modes of oscillation and derive expressions mapping "musical" parameters to the model's "synthesis" parameters. We begin by showing that a unitary power-preserving matrix formulation of the coupled modes leads to a feedback frequency (FM) equation, the instantaneous frequency of which is integrated over time to yield the phase in the corresponding—and preferred—phase modulation (PM) representation. Though the integration is made difficult by the feedback term, an analytic solution is presented by first observing that the real/imaginary parts of the PM equation are equivalent to the real/imaginary parts of the transfer function for a "stretched" allpass filter—one where the delay is not constrained to be a single sample and where the real part produces a periodic comb-like signal, that if made to vary over time (rather than frequency), produces the sounding frequency (a "musical" parameter) resulting from the nonlinear coupling. Ultimately, it is hoped this work may provide computationally efficient models of percussion instruments with rich nonlinear behaviour at little additional computational cost.
Dynamic characterization of grand and upright piano action
Authors: Faraci Philip P. , Case John A. , Farrell Jillian M. , King Eoin A. , Celmer Robert
Published: October 2018

A dynamic characterization was performed on a grand piano and an upright (vertical) piano action assembly. The action assembly consists of a key and a system of levers that transfers a force from the key to the hammer. Measurements of the hammer acceleration profile for a given key force were compared to dynamic simulation results from a computer model constructed in SolidWorks. Single-key action assemblies typically used by piano technicians were used for the dynamic measurements and as a guide for the physical dimensions of the computer model. Measurements of hammer velocity were made using a Laser Doppler Vibrometer, which was differentiated to determine the hammer acceleration. The purpose of the study was to establish a relationship between key force and hammer acceleration for the action assemblies and to construct a computer model whose dynamic behavior closely matches the measured profile. Preliminary results between the measured hammer acceleration and the simulated acceleration will be discussed. [Work supported by a University of Hartford CETA Student Engagement Grant.]
Characterization and modeling of the Erhu
Authors: Waltham Chris , Kim Laura
Published: October 2018

The erhu is a two-string bowed instrument characterized in Chinese organology as a silk instrument (owing to the traditional string material), and by Hornbostel and Sachs as a spike fiddle. The overall length of the instrument is about 80 cm, and the vibrational length of the strings is around half of that. The soundbox is a tube (hexagonal, octagonal, or cylindrical) of about 13 cm length and 9 cm diameter. One end of the tube is covered by a membrane of tensioned python skin and the other is mostly open, usually with a grille. The two strings are stretched over a small bridge positioned centrally on the membrane. In spite of the great difference in soundbox structure between the erhu and a Western violin, the radiated sounds of the two instruments have a lot in common with each other (and with the human voice). Vibrational and acoustic measurements have been made on several erhus: cavity modes, surface velocities and radiated sound. A straightforward coupled-oscillator model has been found to reproduce many of the measurements, and also to allow mechanical characterization of the membrane in situ.
Destructive interferences in resonators created using additive manufacturing
Authors: Berardi Umberto
Published: October 2018

The broad absorption of low-frequency noise typically requires the utilization of large thicknesses of sound absorbing materials. As this creates space issues, there is a demand for thin broad low-frequency absorbers. This research aims to develop an acoustic transparent panel for low-frequency broad sound absorption. Destructive sound resonance tubes were created for this scope using modern tools for generating complex geometries in systems of a few centimeters of thickness. The capability of digital fabrication to enable design freedom and to support the production of complex geometries is explored in this paper. Destructive interference means that two interfering sound waves that are in counter-phase, cancel each other. Digital fabrication is shown to play an important role in developing customized sound absorbing components to absorber below 500 Hz, and especially well below 200 Hz. A parametric script using Grasshopper through Rhinoceros to generate automatically the geometric parameters of the 3d resonators is described. Different materials for 3d printing the resonators are compared. Finally, the challenges of additive manufacturing techniques are finally reported.
Time reversal focusing for nondestructive evaluation of cracks
Authors: Anderson Brian E. , Young Sarah M. , Remillieux Marcel , Le Bas Pierre-yves , Ulrich Timothy J.
Published: October 2018

Time reversal (TR) is a technique that may be used for intentional focusing of wave energy. TR has been developed for crack and defect detection in solid media. Because TR provides a localized focus of elastic energy, it can be used to study the local nonlinear properties at point(s) of interest that are indicative of the presence of cracks and defects. Source transducers may be bonded to the sample under test or to a chaotic cavity that is coupled to a sample under test. A receiver, such as a laser Doppler vibrometer, is placed at a location of interest. Impulse responses are obtained between each source and the receiver and then the impulse responses are reversed in time. The reversed impulse responses are then simultaneously broadcast from the respective source transducers and a focus of energy occurs at the receiver position. Since the largest amplitude is obtained at the receiver position, any amplitude-dependent (nonlinear) vibration that occurs at the receiver position dominates nonlinearities, such as harmonics, that are detected in the signal recorded at the receiver position during focusing. This presentation will review the progress made in the detection of cracks using time reversal and present some recent results.
Study of low-hydrostatic pressure dependent elasticity of porous alumina saturated with various gas media
Authors: Karunarathne Ashoka , Gladden Josh R. , Priyadarshan Gautam
Published: October 2018

Poroelasticity describes how the elasticity of porous materials depend on the material properties: porosity, pore saturation medium and its pressure, nature of pore arrangement, and the skeleton material. The primary goal of this study is to investigate the low-hydrostatic pressure dependent elastic properties of porous alumina saturated with different gas media using resonant ultrasound spectroscopy (RUS). RUS is a precise experimental approach for investigating the elastic properties of solid materials which is capable of measurements at different temperatures and hydrostatic pressures. In RUS, the elastic stiffness tensor of crystalline and polycrystalline solids is determined from the vibrational resonance spectra. In this study, we have used commercially available porous alumina ceramic material which has ~40% of porosity and 2 μm of pore diameter. Here we are reporting the variation of elasticity and acoustic attenuation of porous alumina during the low-hydrostatic pressure cycles from 760 torr (1 atm) to 0.1 torr. An experimentally observed discontinuity of elastic stiffness and acoustic attenuation during the pressure region ~150 torr to 0.1 torr will be described by the transition from viscous to molecular flows, quantified by Knudsen number. The effects of saturated gas medium to the elasticity will also be discussed based on the RUS measurements taken during the air, He, and Ar gas saturation.
Ultrasound elastography unveils the shear wave field: Prospects for medical and geophysical imaging
Authors: Aichele Johannes , Zemzemi Chadi , Catheline Stefan , Roux Philippe
Published: October 2018

Transient elastography is an ultrasonic imaging method primarily applied in medical imaging. Through correlation of echography images it reconstructs the particle velocities and displacements of the transversal wave-field inside a medium of interest. Elastography measurements are therefore not limited to an acquisition surface. We present developments in processing and experimental design that broaden the application horizon for elastography imaging. First, we propose a multiple source-array for shear wave beamforming that adaptively recovers the impulse response of the medium through time-reversal. This allows for targeted shear wave focusing and thus significantly enhances the SNR compared to single source elastography. Due to the time-reversal robustness the focusing holds true for transmission through a rigid barrier as well, which we show by applying the method to a human skull model. Second, we present a geophysical laboratory experiment. Combining a friction test-bed with ultrasound elastography enables us to recover the effect of rupture dynamics on shear wave propagation. Albeit the use of hydro-gels our densely sampled wave-field perfectly illuminates typical rupture phenomena. These include super-shear fronts, sub-Rayleigh ruptures, and stick-slip behavior. In the future, passive elastography, an equivalent to seismic coda correlation, could be used for monitoring local elasticity during the rupture.
Music, speech, and temporal information processing
Authors: Zhao Tian , Kuhl Patricia K.
Published: October 2018

Music and speech share many acoustic characteristics. Both utilize dynamic acoustic cues (e.g., frequency, time, intensity) to convey information and emotion. We focus on temporal information processing at a slower time scale (e.g., musical timing, speech rhythm) to examine connections between music and speech: (1) transfer effects, (2) neural mechanisms and (3) theoretical frameworks. I will focus on early infancy. We observed a transfer effect from music experience to both music and speech processing in 9-month-old infants (Zhao & Kuhl, 2016). Infants were randomly assigned to either a 12-session music intervention that focused on triple meter (waltz) or a 12-session control group (no music) during the “sensitive period” for phonetic learning. The music intervention group exhibited enhanced neural detection of both mistimed musical beats and speech syllables, quantified by the mismatch response (MMR) measured with magnetoencephalography (MEG). The effects were observed in auditory and prefrontal regions of the cortex. Following the "predictive coding" and "dynamic attending" theories, I will discuss a current two-pronged approach that can extend this research to understand the effects of music on infants’ higher-level cognitive skills as well as their early stage sensory encoding of sounds, and implications of these findings for theories of language development.
The flow of language: Respiration and the rhythmic motor control of speech
Authors: MacIntyre Alexis D. , Scott Sophie K.
Published: October 2018

Speech rhythm can be described as the temporal patterning by which sequences of vocalic and gestural actions unfold, within and between interlocutors. Despite efforts to quantify and model speech rhythm across languages, it remains a scientifically enigmatic aspect of prosody. For example, the existence and/or form of a basic speech rhythmic unit is hotly contested. One challenge is that the primary means of speech rhythm research has been the analysis of the acoustic signal. As speech is multimodal and motoric, investigations of speech rhythm will likely benefit from a greater range of complementary measures, including physiological recordings. The current experiment explores respiratory effort as a contributing factor in speech rhythm production. Undergoing simultaneous inductive plethysmography and acoustic recording, participants produce speech by reading novel prosaic texts aloud in single and dyadic conditions. Speech-associated breathing patterns are analysed in conjunction with traditional acoustic-phonological approaches to speech rhythm. It is hypothesized that, like spoken utterances, speech breathing is subject to rhythmic constraints. Preliminary results are therefore interpreted with a focus on the temporal relationship between inhalation events and previously proposed phonological rhythmic units (e.g., inter-stress, p-centre, syllable), underscoring breathing as a necessary, yet often overlooked, component in speech rhythm planning and production.
Vowel content influences relative pitch perception in vocal melodies: A comparison of models based on brightness vs. intrinsic pitch of vowels
Authors: Russo Frank A. , Vuvan Dominique
Published: October 2018

Past research involving real and synthesized instrumental timbres has found that note-to-note changes in brightness can influence perception of interval size. Changes that are congruent with changes in pitch led to an expansion, whereas changes that are incongruent lead to a contraction. In the case of singing, the brightness of individual notes (as measured by the spectral centroid) will vary as a function of vowel content. In a recent study, we investigated whether note-to-note changes in the brightness of sung notes were capable of influencing the perception of interval size. While results were consistent with past work on instrumental timbres, we were not able to completely rule out an alternative explanation concerning a perceptual correction for the intrinsic pitch of vowels (e.g., f0 of /i/ tends to be produced higher than /a/). In the present study, we created 288 unique note pairs that varied with regard to absolute change in f0 as well as vowel content. Vowels were sampled from across the vowel space, which allowed us to generate unique predictors for change in brightness (spectral centroid) and changes in intrinsic pitch (F2). Regression analyses will compare the effectiveness of competing models.
Numerical investigation of non-reciprocal wave propagation in mechanically-modulated elastic metamaterials
Authors: Goldsberry Benjamin M. , Wallen Samuel P. , Haberman Michael R.
Published: October 2018

Acoustic systems that break reciprocity have recently received great attention due to their potential to increase control over wave propagation and to have far-reaching impacts on engineering applications, including more efficient acoustic communication devices and vibration isolation. One means to break reciprocity is by spatiotemporal modulation of material properties, typically via electromagnetic actuation. In the present work, tunable mechanical metamaterials are investigated as a platform to achieve non-reciprocity, where effective dynamic property modulations are induced by an external pre-strain of a two-dimensional cellular material. These elastic metamaterials are studied using a nonlinear finite element model, which is suitable for unit cells having complex geometry and undergoing large deformation caused by the external pre-strain [Goldsberry et al., J. Appl. Phys., 123, 091711 (2018)]. A small-on-large approximation is used to analyze linear elastic, non-reciprocal wave propagation in the presence of a slowly-varying pre-strain. Results on non-reciprocal wave propagation in negative stiffness honeycombs, a structure exhibiting large stiffness modulations due to the presence of a mechanical instability [Correa et al., Rapid Prototyping J., 21(2), 193–200, (2015)], are shown as a case example. [Work supported by NSF.]
Deep learning for ethoacoustical mapping: Application to a single Cachalot long term recording on joint observatories in Vancouver Island
Authors: Glotin Herve , Spong Paul , Symonds Helena , Roger Vincent , Balestriero Randall , Ferrari Maxence , Poupard Marion , Towers Jared , Veirs Scott , Marxer Ricard , Giraudet Pascale , pilkinton james , Veirs Val , Wood Jason , Ford John , Dakin Thomas
Published: October 2018

During February and March, 2018, a lone sperm whale known as Yukusam was recorded first by Orcalab in Johnstone Strait and subsequently on multiple hydrophones within the Salish Sea [1]. We learn and denoise these multichannel clicks trains with AutoEncoders Convolutional Neural Net (CNN). Then, we build a map of the echolocations to elucidate variations in the acoustic behavior of this unique animal over time, in different environments and distinct levels of boat noise. If CNN approximates an optimal kernel decomposition, it requires large amounts of data. Via spline functionals we offer analytics kernels with learnable coefficients do reduce it. We [1-3] identify the analytical mother wavelet to represent the input signal to directly learn the wavelet support from scratch by gradient descend on the parameters of cubic splines [2]. Supplemental material http://sabiod.org/yukusam [1] Balestriero, Roger, Glotin, Baraniuk, Semi-Supervised Learning via New Deep Network Inversion, arXiv preprint arXiv:1711.04313, 2017 [2] Balestriero, Cosentino, Glotin, Baraniuk, WaveletNet : Spline Filters for End-to-End Deep Learning, Int. Conf. on MachineLearning, ICML, Stockholm, http://sabiod.org/bib, 2018 [3] Spong P., Symonds H., et al., Joint Observatories Following a Single male Cachalot during 12 weeks—The Yukusam story, ASA 2018.
Steel pan developments
Authors: Hansen Uwe J. , Rossing Thomas
Published: October 2018

The Caribbean steel pan is likely the single most significant new acoustic musical instrument of the 20th Century. Some major developments incorporated by Felix Rohner of Panart have led to important instrument modifications. Among the differences to be discussed are as follows: using specified steel alloys in the sheet metal to replace commercial 55 Gal drums, sinking the pan in a press rather than by hand, surface hardening the playing surface in a nitride bath, dispensing with chiseled note section boundaries, adding a central dome to each note section, replacing the pan by a Hang (a lap-held instrument played by hand), and finally an additional air volume enclosed, to enhance low frequency resonances (the Gubal).
Deterministic quantum teleportation through fiber channels
Authors: Huo Meiru , Qin Jiliang , Cheng Jialin , Yan Zhihui , Qin Zhongzhong , Su Xiaolong , Jia Xiaojun , Xie Changde , Peng Kunchi
Published: October 2018

The deterministic teleportation of optical modes over a 6.0-km fiber channel is realized with continuous variable entanglement.
A three-dimensional photonic topological insulator using a two-dimensional ring resonator lattice with a synthetic frequency dimension
Authors: Lin Qian , Sun Xiao-Qi , Xiao Meng , Zhang Shou-Cheng , Fan Shanhui
Published: October 2018

Topology traps photons in a one-way channel in the frequency space with the help of ring resonators.
Photonic implementation of Majorana-based Berry phases
Authors: Xu Jin-Shi , Sun Kai , Pachos Jiannis K. , Han Yong-Jian , Li Chuan-Feng , Guo Guang-Can
Published: October 2018

Experimental realization of Berry phases brings us closer to the exotic physics of Majorana fermions.
Full-field imaging of thermal and acoustic dynamics in an individual nanostructure using tabletop high harmonic beams
Authors: Karl Robert M. , Mancini Giulia F. , Knobloch Joshua L. , Frazer Travis D. , Hernandez-Charpak Jorge N. , Abad Begoña , Gardner Dennis F. , Shanblatt Elisabeth R. , Tanksalvala Michael , Porter Christina L. , Bevis Charles S. , Adams Daniel E. , Kapteyn Henry C. , Murnane Margaret M.
Published: October 2018

We built a stroboscopic extreme UV microscope with tabletop high harmonics to make nanoscale movies of thermal and acoustic waves.
Colossal grain growth yields single-crystal metal foils by contact-free annealing
Authors: Jin Sunghwan , Huang Ming , Kwon Youngwoo , Zhang Leining , Li Bao-Wen , Oh Sangjun , Dong Jichen , Luo Da , Biswal Mandakini , Cunning Benjamin V. , Bakharev Pavel V. , Moon Inyong , Yoo Won Jong , Camacho-Mojica Dulce C. , Kim Yong-Jin , Lee Sun Hwa , Wang Bin , Seong Won Kyung , Saxena Manav , Ding Feng , Shin Hyung-Joon , Ruoff Rodney S.
Published: October 2018

Turning many into one

Single-crystal metal foils are valuable for their surface properties that allow for synthesis of materials like graphene. Jinet al.present a strategy for creating colossal single-crystal metal foils called “contact-free annealing” (see the Perspective by Rollett). The method relies on hanging and heating commercially available, inexpensive, cold-rolled metal foils. Almost as if by magic, the polycrystalline grains rotate and anneal into a large single-crystal sheet with a specific crystal orientation. The strategy allows for the creation of much larger and much cheaper single-crystal metal foils.

Science, this issue p.1021; see also p.996
Programmed DNA destruction by miniature CRISPR-Cas14 enzymes
Authors: Harrington Lucas B. , Burstein David , Chen Janice S. , Paez-Espino David , Ma Enbo , Witte Isaac P. , Cofsky Joshua C. , Kyrpides Nikos C. , Banfield Jillian F. , Doudna Jennifer A.
Published: October 2018

A programmable type of CRISPR system

CRISPR-Cas9 systems have been causing a revolution in biology. Harrington
et al.
describe the discovery and technological implementation of an additional type of CRISPR system based on an extracompact effector protein, Cas14. Metagenomics data, particularly from uncultivated samples, uncovered the CRISPR-Cas14 systems containing all the components necessary for adaptive immunity in prokaryotes. At half the size of class 2 CRISPR effectors, Cas14 appears to target single-stranded DNA without class 2 sequence restrictions. By leveraging this activity, a fast and high-fidelity nucleic acid detection system enabled detection of single-nucleotide polymorphisms.

Science
, this issue p.
839
PCR in laboratory diagnosis of human Borrelia burgdorferi infections
Authors: Schmidt B L
Published: October 2018

The laboratory diagnosis of Lyme borreliosis, the most prevalent vector-borne disease in the United States and endemic in parts of Europe and Asia, is currently based on serology with known limitations. Direct demonstration of Borrelia burgdorferi by culture may require weeks, while enzyme-linked immunosorbent assays for antigen detection often lack sensitivity. The development of the PCR has offered a new dimension in the diagnosis. Capable of amplifying minute amounts of DNA into billions of copies in just a few hours, PCR facilitates the sensitive and specific detection of DNA or RNA of pathogenic organisms. This review is restricted to applications of PCR methods in the diagnosis of human B. burgdorferi infections. In the first section, methodological aspects, e.g., sample preparation, target selection, primers and PCR methods, and detection and control of inhibition and contamination, are highlighted. In the second part, emphasis is placed on diagnostic aspects, where PCR results in patients with dermatological, neurological, joint, and ocular manifestations of the disease are discussed. Here, special attention is given to monitoring treatment efficacy by PCR tests. Last, specific guidelines on how to interpret PCR results, together with the advantages and limitations of these new techniques, are presented.
Waterborne protozoan pathogens
Authors: Marshall M M , Naumovitz D , Ortega Y , Sterling C R
Published: October 2018

Protozoan parasites were the most frequently identified etiologic agents in waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli, and the microsporidia are reviewed. For each parasite, the review includes history, life cycle, incidence, symptoms, and therapy. Clinical detection methods are compared, and emerging technologies are discussed. Information on the association of these parasites with waterborne outbreaks is reviewed. Current information on protozoan parasites identified as etiological agents in waterborne outbreaks is discussed. Water industry issues related to recent disease outbreaks are examined in the context of water quality testing regulations for G. lamblia and those proposed for C. parvum. The review identifies the limitations of the American Society of Testing and Materials water-testing method for these parasites. An overview of federal regulations affecting the water industry and laboratories that test for water quality is also provided. The article highlights the importance of the clinical laboratory as a frontline defense for the detection of infectious organisms. The review points to the need for clinical laboratories, physicians, and public health personnel to cooperatively plan and assess the challenge of meeting this potential public health threat.
Yersinia enterocolitica: the charisma continues
Authors: Bottone E J
Published: October 2018

Yersinia enterocolitica, a gram-negative coccobacillus, comprises a heterogeneous group of bacterial strains recovered from animal and environmental reservoirs. The majority of human pathogenic strains are found among distinct serogroups (e.g. O:3, O:5,27, O:8, O:9) and contain both chromosome- and plasmid (60 to 75 kb)-mediated virulence factors that are absent in "avirulent" strains. While Y. enterocolitica is primarily a gastrointestinal tract pathogen, it may produce extraintestinal infections in hosts with underlying predisposing factors. Postinfection sequelae include arthritis and erythema nodosum, which are seen mainly in Europe among patients with serogroups O:3 and O:9 infection and HLA-B27 antigen. Y. enterocolitica is acquired through the oral route and is epidemiologically linked to porcine sources. Bacteremia is prominent in the setting of immunosuppression or in patients with iron overload or those being treated with desferrioxamine. metastatic foci following bacteremia are common and often involve the liver and spleen. Of particular concern is blood transfusion-related bacteremia. Evidence has accumulated substantiating the role of Y. enterocolitica as a food-borne pathogen that has caused six major outbreaks in the United States. The diagnosis of Y. enterocolitica gastroenteritis is best achieved through isolation of the bacterium on routine or selective bacteriologic media. When necessary, serogrouping, biogrouping, and assessment for plasmid-encoded virulence traits may aid in distinguishing virulent from "avirulent" strains. Epidemiologically, outside of identified food-borne outbreaks, the source (reservoir) of Y. enterocolitica in sporadic cases is speculative. Therefore, prevention and control measures are difficult to institute.
Infection in the bone marrow transplant recipient and role of the microbiology laboratory in clinical transplantation
Authors: LaRocco M T , Burgert S J
Published: October 2018

Over the past quarter century, tremendous technological advances have been made in bone marrow and solid organ transplantation. Despite these advances, an enduring problem for the transplant recipient is infection. As immunosuppressive regimens have become more systematic, it is apparent that different pathogens affect the transplant recipient at different time points in the posttransplantation course, since they are influenced by multiple intrinsic and extrinsic factors. An understanding of this evolving risk for infection is essential to the management of the patient following transplantation and is a key to the early diagnosis and treatment of infection. Likewise, diagnosis of infection is dependent upon the quality of laboratory support, and services provided by the clinical microbiology laboratory play an important role in all phases of clinical transplantation. These include the prescreening of donors and recipients for evidence of active or latent infection, the timely and accurate microbiologic evaluation of the transplant patient with suspected infection, and the surveillance of asymptomatic allograft recipients for infection. Expert services in bacteriology, mycology, parasitology, virology, and serology are needed and communication between the laboratory and the transplantation team is paramount for providing clinically relevant, cost-effective diagnostic testing.
Bacterial persistence and expression of disease
Authors: Domingue G J , Woody H B
Published: October 2018

A considerable body of experimental and clinical evidence supports the concept that difficult-to-culture and dormant bacteria are involved in latency of infection and that these persistent bacteria may be pathogenic. This review includes details on the diverse forms and functions of individual bacteria and attempts to make this information relevant to the care of patients. A series of experimental studies involving host-bacterium interactions illustrates the probability that most bacteria exposed to a deleterious host environment can assume a form quite different from that of a free-living bacterium. A hypothesis is offered for a kind of reproductive cycle of morphologically aberrant bacteria as a means to relate their diverse tissue forms to each other. Data on the basic biology of persistent bacteria are correlated with expression of disease and particularly the mechanisms of both latency and chronicity that typify certain infections. For example, in certain streptococcal and nocardial infections, it has been clearly established that wall-defective forms can be induced in a suitable host. These organisms can survive and persist in a latent state within the host, and they can cause pathologic responses compatible with disease. A series of cases illustrating idiopathic conditions in which cryptic bacteria have been implicated in the expression of disease is presented. These conditions include nephritis, rheumatic fever, aphthous stomatitis, idiopathic hematuria, Crohn's disease, and mycobacterial infections. By utilizing PCR, previously nonculturable bacilli have been identified in patients with Whipple's disease and bacillary angiomatosis. Koch's postulates may have to be redefined in terms of molecular data when dormant and nonculturable bacteria are implicated as causative agents of mysterious diseases.
Yeast killer systems
Authors: Magliani W , Conti S , Gerloni M , Bertolotti D , Polonelli L
Published: October 2018

The killer phenomenon in yeasts has been revealed to be a multicentric model for molecular biologists, virologists, phytopathologists, epidemiologists, industrial and medical microbiologists, mycologists, and pharmacologists. The surprisingly widespread occurrence of the killer phenomenon among taxonomically unrelated microorganisms, including prokaryotic and eukaryotic pathogens, has engendered a new interest in its biological significance as well as its theoretical and practical applications. The search for therapeutic opportunities by using yeast killer systems has conceptually opened new avenues for the prevention and control of life-threatening fungal diseases through the idiotypic network that is apparently exploited by the immune system in the course of natural infections. In this review, the biology, ecology, epidemiology, therapeutics, serology, and idiotypy of yeast killer systems are discussed.
In search of a selective antiviral chemotherapy
Authors: De Clercq E
Published: October 2018

This article describes several approaches to a selective therapy of virus infections: (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU [brivudin]) for the therapy of herpes simplex virus type 1 and varicella-zoster virus infections: (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC [cidofovir]) for the therapy of various DNA virus (i.e., herpesvirus, adenovirus, papillomavirus, polyomavirus, and poxvirus) infections; 9-(2-phosphonylmethoxyethyl)adenine (PMEA [adefovir]) for the therapy of retrovirus, hepadnavirus, and herpesvirus infections; (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for the therapy and prophylaxis of retrovirus and hepadnavirus infections; and nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(IH)-one and -thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), alpha-anilinophenylacetamide (alpha-APA), and 2',5'bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxat hiole- 2",2"-dioxide)pyrimidine (TSAO) derivatives, and thiocarboxanilides for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. For the clinical use of NNRTIs, some guidelines have been elaborated, such as starting treatment with combinations of different compounds at sufficiently high concentrations to effect a pronounced and sustained suppression of the virus. Despite the diversity of the compounds described here and the different viruses at which they are targeted, they have a number of characteristics in common. As they interact with specific viral proteins, the compounds achieve a selective inhibition of the replication of the virus, which, in turn, should be able to develop resistance to the compounds. However, as has been established for the NNRTIs, the problem of viral resistance may be overcome if the compounds are used from the start at sufficiently high doses, which could be reduced if different compounds are combined. For HIV infections, drug treatment regimens should be aimed at reducing the viral load to such an extent that the risk for progression to AIDS will be minimized, if not avoided entirely. This may result in a real "cure" of the disease but not necessarily of the virus infection, and in this sense, HIV disease may be reduced to a dormant infection, reminiscent of the latent herpesvirus infections. Should virus replication resume after a certain time, the armamentarium of effective anti-HIV and anti-herpesvirus compounds now available, if applied at the appropriate dosage regimens, should make the virus return to its dormant state before it has any chance to damage the host. It is unlikely that this strategy would eradicate the virus and thus "cure" the viral infection, but it definitely qualifies as a cure of the disease.
A primer on cytokines: sources, receptors, effects, and inducers
Authors: Curfs J H , Meis J F , Hoogkamp-Korstanje J A
Published: October 2018

Protection against pathogens is a prerequisite for survival of most organisms. To cope with this continuous challenge, complex defense mechanisms have evolved. The construction, adaptation, and maintenance of these mechanisms are under control of an extensive network of regulatory proteins called cytokines. A great number of cytokines have been described over the last 2 decades. This review consists of an overview of cytokines that are involved in immune responses and describes some historical and general aspects as well as prospective clinical applications. Major biological effects together with information on cytokine receptors, producers, inducers, and biochemical and molecular characteristics are listed in tables. In addition, some basic information is given on cytokine receptor signal transduction. Finally, the recent discoveries of cytokine receptors functioning as coreceptors in the pathogenesis of human immunodeficiency virus are summarized.
Use of Licensed Vaccines for Active Immunization of the Immunocompromised Host
Authors: Pirofski Liise-anne , Casadevall Arturo
Published: October 2018

The latter part of the 20th century has witnessed an unprecedented rise in the number of individuals with impaired immunity. This is primarily attributable to the increased development and use of antineoplastic therapy for malignancies, organ and bone marrow transplantation, and the AIDS epidemic. Individuals with impaired immunity are often at increased risk for infections, and they can experience more severe and complicated courses of infection. The lack of therapy for a variety of viruses and the rise in antimicrobial resistance of many pathogens have focused attention on vaccination to prevent infectious diseases. The efficacy of most licensed vaccines has been established in immunocompetent hosts. However, there is also considerable experience with most vaccines in those with impaired immunity. We reviewed the use of licensed live, inactivated, and polysaccharide vaccines in this group, and several themes emerged: (i) most vaccines are less immunogenic in those with impaired immunity than in normal individuals; (ii) live vaccines are generally contraindicated in this group; and (iii) the efficacy of many commonly used vaccines has not been established in people with impaired immunity. This review suggests that for most vaccines there are little or no efficacy data in those with impaired immunity but their use in this patient group is generally safe.
DiarrheagenicEscherichia coli
Authors: Nataro James P. , Kaper James B.
Published: October 2018

Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli strains, however, have developed the ability to cause disease of the gastrointestinal, urinary, or central nervous system in even the most robust human hosts. Diarrheagenic strains of E. coli can be divided into at least six different categories with corresponding distinct pathogenic schemes. Taken together, these organisms probably represent the most common cause of pediatric diarrhea worldwide. Several distinct clinical syndromes accompany infection with diarrheagenic E. coli categories, including traveler’s diarrhea (enterotoxigenic E. coli), hemorrhagic colitis and hemolytic-uremic syndrome (enterohemorrhagic E. coli), persistent diarrhea (enteroaggregative E. coli), and watery diarrhea of infants (enteropathogenic E. coli). This review discusses the current level of understanding of the pathogenesis of the diarrheagenic E. coli strains and describes how their pathogenic schemes underlie the clinical manifestations, diagnostic approach, and epidemiologic investigation of these important pathogens.
The Lipids of
Pneumocystis carinii
Authors: Kaneshiro Edna S.
Published: October 2018

Information about a number of Pneumocystis carinii lipids obtained by the analyses of organisms isolated and purified from infected lungs of corticosteroid-immunosuppressed rats has been reported in recent years. Of the common opportunistic protists associated with AIDS (Cryptosporidium, Toxoplasma, and the microsporidia), more is currently known about the lipids of P. carinii than the others. Lipids that are synthesized by the organism but not by humans are attractive targets for drug development. Thus, the elucidation of Δ
7
C-24-alykylated sterol and cis-9,10-epoxystearic acid biosyntheses in P. carinii is currently being examined in detail, since these have been identified as P. carinii-specific lipids. The development of low-toxicity drugs that prevent sterol C-24 alkylation and the specific inhibition of the lipoxygenase that forms cis-9,10-epoxystearic acid might prove fruitful. Although humans can synthesize coenzyme Q
10
, the anti-P. carinii activity and low toxicity of ubiquinone analogs such as atovaquone suggest that the electron transport chain in the pathogen may differ importantly from that in the host. Although resistance to atovaquone has been observed, development of other naphthoquinone drugs would provide a broader armamentarium of drugs to treat patients with P. carinii pneumonia. Studies of bronchoalveolar lavage fluid and of infected lungs have demonstrated that the infection causes a number of chemical abnormalities. Bronchoalveolar lavage fluid obtained after the removal of lung cellular material and the organisms has been shown to contain larger amounts of surfactant proteins and smaller amounts of phospholipids than do comparable samples from P. carinii-free lungs. Increased phospholipase activity, inhibition of surfactant secretion by type II cells, and uptake and catabolism of lipids by the pathogen may explain this phenomenon related to P. carinii pneumonia. Although not yet thoroughly examined, initial studies on the uptake and metabolism of lipids by P. carinii suggest that the organism relies heavily on exogenous lipid nutrients.
Microbiological and Clinical Aspects of Infection Associated with
Stenotrophomonas maltophilia
Authors: Denton Miles , Kerr Kevin G.
Published: October 2018

The gram-negative bacterium Stenotrophomonas maltophilia is increasingly recognized as an important cause of nosocomial infection. Infection occurs principally, but not exclusively, in debilitated and immunosuppressed individuals. Management of S. maltophilia-associated infection is problematic because many strains of the bacterium manifest resistance to multiple antibiotics. These difficulties are compounded by methodological problems in in vitro susceptibility testing for which there are, as yet, no formal guidelines. Despite its acknowledged importance as a nosocomial pathogen, little is known of the epidemiology of S. maltophilia, and although it is considered an environmental bacterium, its sources and reservoirs are often not readily apparent. Molecular typing systems may contribute to our knowledge of the epidemiology of S. maltophilia infection, thus allowing the development of strategies to interrupt the transmission of the bacterium in the hospital setting. Even less is known of pathogenic mechanisms and putative virulence factors involved in the natural history of S. maltophilia infection and this, coupled with difficulties in distinguishing colonization from true infection, has fostered the view that the bacterium is essentially nonpathogenic. This article aims to review the current taxonomic status of S. maltophilia, and it discusses the laboratory identification of the bacterium. The epidemiology of the organism is considered with particular reference to nosocomial outbreaks, several of which have been investigated by molecular typing techniques. Risk factors for acquisition of the bacterium are also reviewed, and the ever-expanding spectrum of clinical syndromes associated with S. maltophilia is surveyed. Antimicrobial resistance mechanisms, pitfalls in in vitro susceptibility testing, and therapy of S. maltophilia infections are also discussed.
Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research
Authors: Baker David G.
Published: October 2018

Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Frequently, these organisms cause no overt signs of disease. However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. While the number and prevalence of these pathogens have declined considerably, many still turn up in laboratory animals and represent unwanted variables in research. Investigators using mice, rats, and rabbits in biomedical experimentation should be aware of the profound effects that many of these agents can have on research.
Structures ofToxoplasma gondiiTachyzoites, Bradyzoites, and Sporozoites and Biology and Development of Tissue Cysts
Authors: Dubey J. P. , Lindsay D. S. , Speer C. A.
Published: October 2018

Infections by the protozoan parasite Toxoplasma gondii are widely prevalent worldwide in animals and humans. This paper reviews the life cycle; the structure of tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites and enteroepithelial stages of T. gondii; and the mode of penetration of T. gondii. The review provides a detailed account of the biology of tissue cysts and bradyzoites including in vivo and in vitro development, methods of separation from host tissue, tissue cyst rupture, and relapse. The mechanism of in vivo and in vitro stage conversion from sporozoites to tachyzoites to bradyzoites and from bradyzoites to tachyzoites to bradyzoites is also discussed.
Onychomycosis: Pathogenesis, Diagnosis, and Management
Authors: Elewski Boni E.
Published: October 2018

Although not life-threatening, onychomycosis (a fungal infection of the nail, usually caused by a dermatophyte) constitutes an important public health problem because of its high prevalence (about 10% of the U.S. population) and associated morbidity. The disease can have certain negative consequences for patients, such as pain, and can potentially undermine work and social lives. This review discusses the etiology, classification, diagnosis, and treatment of onychomycosis. Four types of onychomycosis are recognized based on the site and pattern of fungal invasion. Dermatophyte fungi are the predominant pathogens, but yeasts (especially Candida albicans) and nondermatophyte molds may also be implicated. Accurate diagnosis requires direct microscopy and fungal culture. The differential diagnosis includes psoriasis, lichen planus, onychogryphosis, and nail trauma. Onychomycosis is more difficult to treat than most dermatophytoses because of the inherent slow growth of the nail. Older antifungal agents (ketoconazole and griseofulvin) are unsuitable for onychomycosis because of their relatively poor efficacy and potential adverse effects. Three recently developed antimycotic agents (fluconazole, itraconazole, and terbinafine) offer high cure rates and good safety profiles. In addition, the short treatment times (<3 months) and intermittent dosing schedules are likely to enhance compliance and reduce the costs of therapy.