Enhancing Manufacturability of SU-8 Piezoelectric Composite Films for Microsystem Applications.

Piezoelectric thin films are extensively used as sensing or actuating layers in various micro-electromechanical systems (MEMS) applications. However, most piezoelectrics are stiff ceramics, and current polymer piezoelectrics are not compatible with microfabrication due to their low Curie Temperature. Recent polymer-composite piezoelectrics have gained interest but can be difficult to pattern. Photodefinable piezoelectric films could resolve these challenges by reducing the manufacturability steps by eliminating the etching process. But they typically have poor resolution and thickness properties. This study explores methods of enhancing the manufacturability of piezoelectric composite films by optimizing the process parameters and synthesis of SU-8 piezo-composite materials. Piezoelectric ceramic powders (barium titanate (BTO) and lead zirconate titanate (PZT)) were integrated into SU-8, a negative epoxy-based photoresist, to produce high-resolution composites in a non-cleanroom environment. I-line (365 nm) light was used to enhance resolution compared to broadband lithography. Two variations of SU-8 were prepared by thinning down SU-8 3050 and SU-8 3005. Different weight percentages of the piezoelectric powders were investigated: 5, 10, 15 and 20 wt.% along with varied photolithography processing parameters. The composites' transmittance properties were characterized using UV-Vis spectroscopy and the films' crystallinity was determined using X-ray diffraction (XRD). The 0-3 SU-8/piezo composites demonstrated resolutions < 2 µm while maintaining bulk piezoelectric coefficients d33 > 5 pm V-1. The films were developed with thicknesses >10 µm. Stacked layers were achieved and demonstrated significantly higher d33 properties.

Are superficial neuromasts proprioceptors underlying fast copulatory behavior?

In male Poeciliid fishes, the modified anal fin (i.e., gonopodium) and its axial and appendicular support are repositioned within the axial skeleton, creating a novel sexually dimorphic ano-urogenital region. During copulation, the relative location of the gonopodium is crucial for successful insemination. Therefore, the repositioning of these structures and organ relied on the reorganization of the efferent circuitry that controls spinal motor neurons innervating appendicular muscles critical for the movement of the gonopodium, including the fast and synchronous torque-trust motion during insemination attempts. Copulation occurs when a male positions himself largely outside a female's field of view, circumducts his gonopodium, and performs a rapid, complex maneuver to properly contact the female urogenital sinus with the distal tip of the gonopodium and transfers sperm. Although understanding of the efferent circuitry has significantly increased in the last 24 years, nothing is known about the cutaneous receptors involved in gonopodium movement, or how the afferent signals are processed to determine the location of this organ during copulation. Using Western mosquitofish, Gambusia affinis, as our model, we attempt to fill this gap in knowledge. Preliminary data showed cutaneous nerves and sensory neurons innervating superficial neuromasts surrounding the base of adult male gonopodium; those cutaneous nerves projected ventrally from the spinal cord through the 14th dorsal root ganglion and its corresponding ventral root towards the base and fin rays of the gonopodium. We asked what role the cutaneous superficial neuromasts play in controlling the positioning and timing of the gonopodium's fast and synchronous movements for effective sperm transfer. First, we found a greater number of superficial neuromasts surrounding the base of the male's gonopodium compared to the base of the female's anal fin. Second, we systemically removed superficial neuromasts surrounding the gonopodium base and observed significant impairment of the positioning and timing of gonopodial movements. Our findings provide a first step to supporting the following hypothesis: during radical reorganization of the Poeciliid body plan, superficial neuromasts have been partially co-opted as proprioceptors that allow the gonopodium to control precise positioning and timing during copulatory attempts.

A porous supramolecular ionic solid.

We report a synthetic strategy to integrate discrete coordination cages into extended porous materials by decorating opposite charges on the singular cage, which offers multidirectional electrostatic forces among cages and leads to a porous supramolecular ionic solid. The resulting material is non-centrosymmetric and affords a piezoelectric coefficient of 8.19 pC N-1, higher than that of the wurtzite ZnO.

Glatiramer acetate persists at the injection site and draining lymph nodes via electrostatically-induced aggregation.

Glatiramer acetate (GA) is widely prescribed for the treatment of relapsing-remitting multiple sclerosis, however, the mechanism of action is still not fully understood. We investigated the structural properties of GA and examined alterations to the drug upon injection into the subcutaneous space. First, a variety of biophysical characterization techniques were employed to characterize GA in solution. GA was found to exist as alpha helices in solution with a hydrodynamic radius of ~3 nm in size. To simulate GA behavior at the site of injection, GA was injected into a solution of 1.5 MDa hyaluronic acid (HA). Visible aggregates were observed immediately upon injection and subsequent testing indicated aggregation was driven by electrostatic interactions between the positively-charged GA and negatively-charged HA. In vivo testing confirmed GA formed spherical particles in the nano- to micrometer size range, suggesting this mechanism contributes to persistence at the injection site and in draining lymph nodes. The aggregates were found to associate with glycosaminoglycans, suggesting an electrostatic mechanism of induced aggregation like the simulated injection. These novel observations may help explain the complex immunomodulatory mechanisms of GA and adverse injection site reactions seen in patients.

[Comparison of the tests polymerase chain reaction, serology, and blood culture with respect to sensitivity and specificity for detection of Brucella spp in human samples]. / Comparación de las pruebas: reacción en cadena de la polimerasa (PCR), serología y hemocultivo con respecto a sensibilidad y especificidad, para la detección de Brucella spp en muestras humanas.

OBJECTIVE: The aim of this study was to evaluate the sensitivity and specificity of polymerase chain reaction for detection of Brucella spp in human blood samples compared with the serological tests and blood culture. MATERIAL AND METHODS: In 2005, a total of 92 people were sampled from the towns of Anahuac and Sabinas Hidalgo, Nuevo Leon, where an outbreak of human cases had taken place in the same year as this study. The sera collected were analyzed by serological tests according to the NOM 022-SS2-1994. DNA was obtained using CTAB extraction method and it was used to amplify a fragment of 223 bp of the coding sequence for a protein of 31 kDa present in all Brucella species. RESULTS: The polymerase chain reaction test detected 23 positive samples. The sensitivity and specificity compared with RB was 44.68 and 95.56%, respectively. Compared with mouse antibody production, it was 51.61 and 88.52%, and 2-mercaptoethanol was 53.57 and 87.50%. When isolation (positives cultures) was compared with polymerase chain reaction, we obtained 100.0% sensitivity and 80.23% specificity, taking into account people with positive and negative serology. CONCLUSIONS: The polymerase chain reaction test can be an alternative tool to bacterial culture in human brucellosis diagnosis.

Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons.

"Dye-coupling", whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35), and freeze-fracture replica immunogold labeling (FRIL) reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish). To study gap junctions' role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in <20 mS) spermatozeugmata into the female reproductive tract. Dye-coupling in the 14th spinal segment controlling the gonopodium reveals coupling between motor neurons and a commissural primary ascending interneuron (CoPA IN) and shows that the 14th segment has an extensive and elaborate dendritic arbor and more gap junctions than do other segments. Whole-mount immunohistochemistry for Cx35 results confirm dye-coupling and show it occurs via gap junctions. Finally, FRIL shows that gap junctions are at mixed synapses and reveals that >50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment. Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions' role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.

A male poecillid's sexually dimorphic body plan, behavior, and nervous system.

Here we review the literature of a male poecillid's sexually dimorphic body plan, behavior, and nervous system, including work dating from the mid 1800s to the mid 1990s as well as work in press or in preparation for publication. Rosa-Molinar described the remodeling of the sexually dimorphic anal fin appendicular support, confirmed earlier claims about the development of the male and female secondary sex characteristics in the Western Mosquitofish, Gambusia affinis and provided for the first time direct embryonic evidence suggesting that remodeling of the sexually dimorphic anal fin appendicular support is biphasic. The first process begins in embryos and proceeds similarly in immature males and females; the second process occurs only in males and results in the anterior transposition of the anal fin and its appendicular support to the level of vertebra 11 [Rosa-Molinar E, Hendricks SE, Rodriguez-Sierra JF, Fritzsch B. 1994. Development of the anal fin appendicular support in the western mosquitofish, Gambusia affinis (Baird and Girard, 1854): a reinvestigation and reinterpretation. Acta Anat 151:20-35.] and the formation of a gonopodium used for internal fertilization. Studies using high-speed video cameras confirmed and extended Peden's and others' observations of copulatory behavior. The cameras showed that circumduction is a complex movement combining in a very fast sequence abduction, extension and pronation, S-start-type fast-start (defined as torque-thrust), and adduction movements. Recent work on the nervous system demonstrated dye-coupling between motor neurons and interneurons via gap junctions, suggesting an attractive substrate for the rapid motions involved in poecillid copulatory reflexes.

Internal consistency of the Spanish health literacy test (TOFHLA-SPR) for Puerto Rico.

BACKGROUND: Low functional health literacy has been related to poor viral control, and lower levels of ART adherence in people living with HIV/AIDS. Research in functional health literacy among people living with HIV/AIDS in Puerto Rico (PR) is an unexplored area. The purpose of this paper is to describe how the full-length Spanish Version of the Test of Functional Health Literacy in Adults (TOFHLA-S) scale was adapted to PR. METHODS: Thirty participants (women = 16, men = 14) completed a basic demographic questionnaire, the TOFHLA-S and participated in an interview. Analyses were performed to examine the information provided by participants and the internal consistency of the TOFHLA-S. RESULTS: The mean age was 47.7 years (range 34-77). Thirty-seven percent had less than 12 years of formal schooling and 43% reported having education above high school. Changes suggested by participants included: increasing font size from 14 to 16 points for better readability and changes/simplification of several words in order to make them colloquial and comprehensible for the PR context. The reliability coefficient obtained for this scale was strong (estimated alpha = 0.95) however, differences were observed by subtype: numeracy (estimated alpha(num) = .819 vs. comprehension (estimated alpha =. 953). CONCLUSIONS: Based on this process, we have adapted the original version of the TOFHLA-S and the new version of the full-length TOFHLA-S, PR is now valid for further research and testing levels of functional health literacy in a larger sample in PR.

Long-term AZT exposure alters the metabolic capacity of cultured human lymphoblastoid cells.

The antiretroviral efficacy of 3'-azido-3'-deoxythymidine (AZT) is dependent upon intracellular mono-, di-, and triphosphorylation and incorporation into DNA in place of thymidine. Thymidine kinase 1 (TK-1) catalyzes the first step of this pathway. MOLT-3, human lymphoblastoid cells, were exposed to AZT continuously for 14 passages (P(1)-P(14)) and cultured for an additional 14 passages (P(15)-P(28)) without AZT. Progressive and irreversible depletion of the enzymatically active form of the TK-1 24-kDa monomer with loss of active protein was demonstrated during P(1)-P(5) of AZT exposure. From P(15) to P(28), both the 24- and the 48-kDa forms of TK-1 were undetectable and a tetrameric 96-kDa form was present. AZT-DNA incorporation was observed with values of 150, 133, and 108 molecules of AZT/10(6) nucleotides at the 10 microM plasma-equivalent AZT dose at P(1), P(5), and P(14), respectively. An exposure-related increase in the frequency of micronuclei (MN) was observed in cells exposed to either 10 or 800 microM AZT during P(1)-P(14). Analysis of the cell cycle profile revealed an accumulation of S-phase cells and a decrease in G(1)-phase cells during exposure to 800 microM AZT for 14 passages. When MOLT-3 cells were grown in AZT-free media (P(15)-P(29)), there was a reduction in AZT-DNA incorporation and MN formation; however, TK-1 depletion and the persistence of S-phase delay were unchanged. These data suggest that in addition to known mutagenic mechanisms, cells may become resistant to AZT partially through inactivation of TK-1 and through modulation of cell cycle components.

The western mosquitofish (Gambusia affinis affinis): a new laboratory animal resource for the study of sexual dimorphism in neural circuits.

The western mosquitofish (Gambusia affinis affinis) is a useful model for the study of sexual dimorphism and the neural circuits associated with sexual differentiation. This is largely because of its anal fin, which undergoes radical postnatal transformation in males. Understanding the neural mechanisms involved in this process may also help elucidate basic principles of the nervous system. The authors describe the mosquitofish as a model for research and present guidelines for the care and use of this species.

Correlación entre PCR en exudado nasal y la reacción de tuberculina para la detección de organismos del complejo Mycobacterium tuberculosis en bovinos / Correlation between PCR and tuberculin test for detection of Mycobacterium tuberculosis complex organisms in bovine cattle

En México, la tuberculosis (TB) es motivo de regionalización del país de acuerdo a la prevalencia, por tal motivo, la comercialización y/o exportación de bovinos, así como su movilización, es restringida. El diagnóstico oficial de la TB en bovinos en campo se realiza con la prueba de tuberculina, y posmorten con histopatología y/o por aislamiento del agente etiológico. Aunque la prueba de la tuberculina tiene baja especificidad, es suficiente para enviar animales reactores a sacrificio, lo que no garantiza que el animal esté infectado. Lo anterior, hace patente la necesidad de métodos más sensibles y específicos. En la presente investigación se analizaron muestras de exudado nasal de bovinos, para detectar microorganismos del complejo Mycobacterium tuberculosis mediante la prueba de reacción en cadena de la polimerasa (PCR). Todos los animales positivos a la tuberculina se consideraron como animales infectados y éstos fueron comparados con los positivos a PCR. Se muestrearon 420 animales provenientes de zonas de alta y baja prevalencia. El ADN de los exudados nasales se obtuvo con el método de extracción bromuro de cetiltrimetilamonio, y éste se utilizó en una PCR anidada para amplificar dos fragmentos (583 pb y 200 pb) de la secuencia IS6110 del complejo M. tuberculosis. La prueba de PCR logró detectar un mayor número de muestras positivas en las zonas de alta prevalencia (57 por ciento), comparada con las zonas de baja prevalencia (20 por ciento). La sensibilidad de la prueba de PCR fue del 90,5 por ciento y la especificidad del 58,3 por ciento, comparada con la prueba de tuberculina. Quedó demostrado que la prueba de PCR en secreciones nasales puede utilizarse en situaciones de compra-venta o en exposiciones ganaderas como un análisis de tamizaje para prevenir el contagio y la introducción de la enfermedad a rebaños sanos.

In Mexico, the bovine tuberculosis (TB) is associated with both regionalization of the country, considering the levels of prevalence of the disease and restrictions in commercialization and/or exportation of cattle. In Mexico, the diagnosis of the bovine tuberculosis is conducted by using the tuberculin test in live animals, bacteriologic isolation and histopathological analysis in postmortem. Although the low sensibility of tuberculin test, is used to sent the animal reactors to slaughter and maybe the animal is not infected. Considering that some diagnosis methods are not sufficiently reliable and specific to detect the presence of the casual agent of this disease, the use of the polymerase chain reaction (PCR) test was evaluated from bovine nasal mucus. For the detection of the Mycobacterium tuberculosis complex, PCR of nasal mucus was better than Caudal-fold Tuberculin Test (CTT). The sensibility of PCR compared with CTT was 90.5% and specifity was 58.3%. The PCR of nasal mucus can use in buy and sell operations and cattle expositions to prevent the contagious and the introduction the pathogens in health cattle.

Human inter-individual variability in metabolism and genotoxic response to zidovudine.

A mainstay of the antiretroviral drugs used for therapy of HIV-1, zidovudine (AZT) is genotoxic and becomes incorporated into DNA. Here we explored host inter-individual variability in AZT-DNA incorporation, by AZT radioimmunoassay (RIA), using 19 different strains of normal human mammary epithelial cells (NHMECs) exposed for 24 h to 200 microM AZT. Twelve of the 19 NHMEC strains showed detectable AZT-DNA incorporation levels (16 to 259 molecules of AZT/10(6) nucleotides), while 7 NHMEC strains did not show detectable AZT-DNA incorporation. In order to explore the basis for this variability, we compared the 2 NHMEC strains that showed the highest levels of AZT-DNA incorporation (H1 and H2) with 2 strains showing no detectable AZT-DNA incorporation (L1 and L2). All 4 strains had similar (> or =80%) cell survival, low levels of accumulation of cells in S-phase, and no relevant differences in response to the direct-acting mutagen bleomycin (BLM). Finally, when levels of thymidine kinase 1 (TK1), the first enzyme in the pathway for incorporation of AZT into DNA, were determined by Western blot analysis in all 19 NHMEC strains at 24 h of AZT exposure, higher TK1 protein levels were found in the 12 strains showing AZT-DNA incorporation, compared to the 7 showing no incorporation (p=0.0005, Mann-Whitney test). Furthermore, strains L1 and L2, which did not show AZT-DNA incorporation at 24 h, did have measurable incorporation by 48 and 72 h. These data suggest that variability in AZT-DNA incorporation may be modulated by inter-individual differences in the rate of induction of TK1 in response to AZT exposure.

[Response to the treatment of brucellosis among children. Evaluation with Huddleson reaction and PCR]. / Respuesta al tratamiento de brucelosis en niños. Evaluación con reqcción de Huddleson y PCR.

INTRODUCTION: Brucellosis poses a significant public health problem and requires meticulous diagnosis; the outcome has frequent relapses even when the treatment is appropriate. OBJECTIVE: To evaluate the response to the treatment in children with brucellosis by means of Huddleson seroaglutination test and PCR. METHODS: Using a prospective design, a cohort of children with brucellosis was followed up by carrying out Huddleson seroaglutination test of and PCR for Brucella at 6, 12 and 24 weeks. Most of children were treated with trimetoprim + sulfametoxazole and rifampicine. The progress towards therapeutic failure or relapse was evaluated. RESULTS: Twenty-three children fulfilled the inclusion criteria. The median age was 4.7 years; 61 % had consumed potentially infected milk or dairy products. The duration of symptoms ranged from 7 days to 1 year. Brucella sp. was isolated in blood culture in two of 21 children and Brucella melitensis in myeloculture in one of four children. 69 % had positive Huddleson serological test from 1:160 to >1:12000. PCR tested positive in 100% of children when entering to the study. Six weeks after beginning treatment 17% of children had therapeutic failure. At 12 weeks, three children (13 %) persisted with positive PCR and their antimicrobial treatment was modified. At 24 weeks, five children (21.7 %) presented relapse. A child persisted positive in spite of modifying the antimicrobial scheme. The agreement between the two tests was low in the three follow-up periods (k = 0.08, k = 0.12 and k = 0.28 respectively). CONCLUSIONS: A 6-week treatment cannot be enough to eliminate Brucella. PCR test can be used to early identify relapses.