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Biomedical subjects

C L Chien

Publications and source records attributed to C L Chien.

At least 19 recordsLinked to original sources

Enhanced magnetoresistance induced by spin transfer torque in granular films with a magnetic field.

Spin-transfer torques (STT) provide a mechanism to alter the magnetic configurations of magnetic heterostructures, a result previously only achieved by an external magnetic field. In granular solids, we demonstrate a new form of STT effect that can be exploited to induce a large spin disorder when combined with a large magnetic field. We have obtained a very large magnetoresistance effect in excess of 400% at 4.2 K in a large magnetic field, the largest ever reported in any metallic systems. The STT characteristics of granular solids differ significantly from those of multilayers, showing no STT effect at low magnetic fields but prominent STT effects at high fields.

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Magnetic bistability and controllable reversal of asymmetric ferromagnetic nanorings.

Magnetization reversals through the formation of a vortex state and the rotation of an onion state are two processes with comparable probabilities for symmetric magnetic nanorings with a radius of about 50 nanometers. This magnetic bistability is the manifestation of the competition between the exchange energy and the magnetostatic energy in nanomagnets. The relative probability of the two processes in symmetric nanorings is dictated by the ring geometry and cannot be altered after fabrication. In this work, we report a novel type of nanorings--asymmetric nanorings. By tuning the asymmetry, we can control the fraction of the vortex formation process from about 40% to nearly 100% by utilizing the direction of the external magnetic field. The observed results have been accounted for by the dependence of the domain-wall energy on the local cross-section area for which we have provided theoretical calculations.

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Stellate transformation of invasive trophoblast: a distinct phenotype of trophoblast that is involved in decidual vascular remodelling and controlled invasion during pregnancy.

BACKGROUND: Successful implantation relies on the tightly regulated invasion of extravillous trophoblasts (EVTs). However, little is known about their phenotypic differentiation and relevant motile behaviour. Furthermore, the cell-cell interactions between EVTs and decidual arterioles during physiological transformation are also poorly understood. METHODS: A total of 128 decidual specimens from early and late gestations containing components of EVTs and spiral arterioles were investigated using immunohistochemistry and periodic acid-Schiff reaction. RESULTS: Unipolar, tadpole-like EVTs are observed throughout the interstitial area, with a tendency to decrease along the invasive pathway. The stellate differentiation of the EVTs is identified around and inside decidual arterioles or in the third-trimester myometrium. Furthermore, stellate transformation of EVTs precedes its interactions with the decidual arteriole. These specialized stellate trophoblasts invade and infiltrate the tunica media, accompanying lacuna formation inside the vessel wall and perturbation of actin fibre alignment of the tunica media. CONCLUSION: Stellate transformation of trophoblasts may explain controlled invasion of EVTs and probably plays a key role in initiating cell-cell interaction in decidual vascular remodelling.

Arterioles↗

Co1-xFexS2: a tunable source of highly spin-polarized electrons.

In the emerging field of spin-electronics ideal ferromagnetic electron sources would not only possess a high degree of spin polarization, but would also offer control over the magnitude of this polarization. We demonstrate here that a simple scheme can be utilized to control both the magnitude and the sign of the spin polarization of ferromagnetic CoS2, which we probe with a variety of techniques. The position of the Fermi level is fine-tuned by solid solution alloying with the isostructural diamagnetic semiconductor FeS2, leading to tunable spin polarization of up to 85%.

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Antisymmetric magnetoresistance in magnetic multilayers with perpendicular anisotropy.

While magnetoresistance (MR) has generally been found to be symmetric in applied field in nonmagnetic or magnetic metals, we have observed antisymmetric MR in Co/Pt multilayers. Simultaneous domain imaging and transport measurements show that the antisymmetric MR is due to the appearance of domain walls that run perpendicular to both the magnetization and the current, a geometry existing only in materials with perpendicular magnetic anisotropy. As a result, the extraordinary Hall effect gives rise to circulating currents in the vicinity of the domain walls that contributes to the MR. The antisymmetric MR and extraordinary Hall effect have been quantitatively accounted for by a theoretical model.

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Current-driven switching in a single exchange-biased ferromagnetic layer.

We demonstrate spin-transfer torque effects in a single exchange-biased ferromagnetic layer. A current through a point contact to the exchange-biased Co layer reverses the magnetization of a nanodomain in the layer hysteretically for low applied magnetic fields and reversibly for high fields (up to 9 T). These effects are the inverse of the domain wall magnetoresistance, in the same way that similar effects in multilayers are the inverse of giant magnetoresistance.

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Oscillatory exchange bias due to an antiferromagnet with incommensurate spin-density waves.

Oscillatory exchange bias in both magnitude and in sign has been observed in epitaxial (100)Cr/Ni(81)Fe19 bilayers due to the incommensurate spin-density waves in antiferromagnetic (100)Cr layers. Salient effects due to the spin-flip transition between longitudinal and transverse spin-density waves as well as that of expanding wavelength have been observed.

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Current-induced spin-wave excitations in a single ferromagnetic layer.

Evidence for a current-induced spin-transfer torque effect has been investigated in a series of point contacts to single ferromagnetic layers. At specific current densities, abrupt resistance changes, similar to those attributed to current-induced spin-wave excitations in multilayers, have been observed for one current polarity. The critical current for these resistance changes depends linearly on the external field applied perpendicular to the layer. The observed effect is interpreted as a current-driven heterogeneous instability in an otherwise uniform ferromagnetic layer.

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Amorphous structures in the immiscible Ag-Ni system.

Vapor quenching in the phase-separating Ag-Ni system creates alloys that appear homogeneously amorphous under conventional probes. However, an atomic-level structural analysis based on extended x-ray absorption fine structures in combination with reverse Monte Carlo and molecular dynamics simulations demonstrates that these new phases are characterized by nonuniform, spinodal-like structures on an extremely fine scale. This heterogeneous nature of the structure is directly responsible for the unexpectedly low heat (and temperature) of crystallization observed in calorimetric measurements.

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The distribution of PGP9. 5, BDNF and NGF in the vallate papilla of adult and developing mice.

The development and innervation of vallate papillae and taste buds in mice were studied using antibodies against the neuronal marker, protein gene product 9.5 (PGP 9.5), and against nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). PGP 9.5 immunohistochemical studies revealed that the earliest sign of median vallate papilla formation was an epithelial bulge at embryonic day 13 (E13), and at E14, a dense nerve plexus was found within the connective tissue core of the papilla. Thin nerve fibers penetrated the apical and medial trench wall epithelium of the papilla at E16 and a few of these began to invade the lateral trench wall epithelium at E17. At postnatal day 1 (P1), the newly formed taste buds were recognizable and a small number of PGP 9.5-immunoreactive (IR) cells appeared on the medial trench wall epithelium. The number of PGP 9.5-IR taste bud cells then increased gradually and reached the adult level at postnatal week 2. PGP 9.5 immunoreactivity increased systematically with age. NGF and BDNF immunoreactivity was first seen at the boundary between the columnar cells in the apical epithelium of the developing vallate papilla at E13, then in the medial and lateral trench walls at E15 (BDNF) or E18 (NGF). At P1, BDNF immunoreactivity was exclusively present in the newly formed taste buds of the medial trench wall. The number of BDNF-IR taste bud cells then increased gradually, reaching the adult level at P7. Similar degrees of NGF and BDNF immunoreactivity were seen in the developing vallate papilla. In the present study, we found that the vallate papilla was formed prior to its innervation, and we propose that initiation of papilla formation does not require any direct influence from the specific gustatory nerve. We also suggest that neurotrophins in the early developing vallate papillae might act as local tropic factors for the embryonic growth of nerve fibers to induce differentiation of the taste buds.

Animals↗

Effects of zinc deficiency on the vallate papillae and taste buds in rats.

BACKGROUND AND PURPOSE: Zinc deficiency is associated with multiple clinical complications, including taste disturbance, anorexia, growth retardation, skin changes, and hypogonadism. We investigated the zinc-deficiency-induced morphologic changes in the vallate taste buds of weanling and young adult male Wistar rats. METHODS: A total of 24 weanling and 30 young adult rats were used. Each age group was further divided into a control group fed a zinc-adequate (50 ppm) diet, a zinc-deficient (< 1 ppm) diet group, and a zinc-adequate pair-fed group who were fed the same amount of food as that taken by the zinc-deficient group. Weanling rats were fed for 4 weeks and young adult rats were fed for 6 weeks. The morphometry and morphologic changes of vallate taste buds were analyzed using light and transmission electron microscopy. RESULTS: Light microscopy revealed no significant difference in papilla size and morphology among the various groups. In both weanling and young adult rats in the zinc-deficient diet and pair-fed groups, the number of taste buds per papilla (per animal) and the average profile area of the taste bud were significantly smaller than those of the corresponding controls (p < 0.05). Ultrastructural changes were seen only in the taste buds of weanling rats fed the zinc-deficient diet, with derangement of the architecture of the taste bud and widening of the intercellular space between taste bud cells. The proportion of type I taste bud cells in the taste buds of weanling rats fed the zinc-deficient diet decreased from 59% to 39%, and that of type II taste bud cells decreased from 25% to 12%. No obvious changes in the ultrastructure of type III taste bud cells were observed. CONCLUSIONS: The main effects of zinc deficiency in weanling and young adult rats and in adequate diet pair-fed rats were changes in the number and size of taste buds, and fine structure changes in the taste bud cells, especially during the accelerated growth stage after weaning.

Aging↗

Asymmetry in elementary events of magnetization reversal in a ferromagnetic/antiferromagnetic bilayer.

Real-time magneto-optical indicator film images reveal distinct asymmetry in the motion of a single domain wall in a wedged-NiFe/uniform-FeMn bilayer due to the nucleation and behavior of an exchange spring in the antiferromagnetic layer. Magnetization reversal from the ground state begins at the thick end of the wedge where the exchange anisotropy field (HE) is minimal and the magnetostatic field (HMS) is maximal, whereas reversal into the ground state begins from the thin end where HE is maximal and HMS is minimal.

Journal Article↗

Overexpression of alpha-internexin causes abnormal neurofilamentous accumulations and motor coordination deficits in transgenic mice.

alpha-Internexin is the first neuronal intermediate filament (IF) protein expressed in postmitotic neurons of the developing nervous system. In the adult, its expression is restricted to mature neurons in the CNS. To study the potential role of alpha-internexin in neurodegeneration, we have generated transgenic mice that overexpress rat alpha-internexin. The total levels of alpha-internexin expressed in the hemizygous and homozygous transgenic mice were approximately 2 and approximately 3 times the normal level, respectively. Overexpression of alpha-internexin resulted in the formation of cerebellar torpedoes as early as 1 month of age. These torpedoes are abnormal swellings of Purkinje cell axons that are usually seen in neurodegenerative diseases involving the cerebellum. EM studies showed accumulations of high levels of IFs and abnormal organelles in the torpedoes and soma of Purkinje cells, as well as in the large pyramidal neurons of the neocortex and in the ventral anterior and posteromedial nuclei of the thalamus. Behavioral tests demonstrate that these mice have a deficit in motor coordination as early as 3 months of age, consistent with the morphological neuronal changes. Our data further demonstrate that the neurofilamentous inclusions also lead to progressive loss of neurons in the aged transgenic mice. The motor coordination deficit and the loss of neurons are transgene dosage-dependent. These data yield direct evidence that high levels of misaccumulated neuronal IFs lead to neuronal dysfunction, progressive neurodegeneration, and ultimate loss of neurons. Moreover, the degrees of neuronal dysfunction and degeneration are proportional to the levels of misaccumulated neuronal IFs.

Animals↗

Immunohistochemical studies of transforming growth factor-beta and its receptors in the gastric mucosa of patients with refractory gastric ulcer.

Transforming growth factor (TGF)-beta regulates cell growth and differentiation, and is known to play regulatory roles in the process of tissue repair and remodeling. However, the functional role of TGF-beta in gastric ulcer healing has not been addressed. In this study, we assayed the expression of TGF-beta and its receptors in the gastric mucosa of patients with healed or refractory gastric ulcers. Antibodies against TGF-beta and its receptors (both type I and type II) were employed to examine expression levels. Sixteen gastric ulcer patients, including four with completely healed ulcers and 12 with ulcers refractory to treatment were included in this study. All four patients with healed ulcers showed remarkable expression levels of both TGF-beta and its receptors. On the other hand, two of the 12 patients with refractory ulcers had weak or deficient TGF-beta expression in the gastric mucosa, and seven lacked expression of at least one of the TGF-beta receptors. The remaining three patients had normal (moderate to weak) expression levels of TGF-beta and its two receptors. These results suggest that both TGF-beta and its receptors are essential for gastric ulcer healing.

Adult↗

Distribution of neuronal intermediate filament proteins in the developing mouse olfactory system.

The distribution of neuronal intermediate filament proteins in the developing mouse olfactory bulb and olfactory epithelium was characterized by immunocytochemical approach. Antibodies against alpha-internexin, neurofilament triplet proteins (NFTPs; NF-L, NF-M, and NF-H) and peripherin were used to determine their expression at different developmental stages. Alpha-internexin and peripherin were first found to be co-localized in the olfactory neuroepithelium during early development. At the perinatal stage, expression patterns of alpha-internexin and peripherin are distinguishable by spatial and temporal manner: peripherin is predominantly expressed in the olfactory nerves; whereas alpha-internexin is expressed in both olfactory nerves and olfactory bulb. Our observation suggests that peripherin as well as alpha-internexin may play some roles in the process formation of olfactory nerves during development. In the developing olfactory periglomerulus, alpha-internexin was found around postnatal Day 3, whereas NFTPs were not observed until postnatal Day 7. Our data showed that the expression of alpha-internexin preceded those of the NFTPs in most neurons of the developing olfactory bulb. Some small neurons in the adult olfactory bulb were uniquely labeled with antibody to alpha-internexin. Our results suggest that alpha-internexin may play a functional role in the neuronal cytoarchitecture of developing olfactory system, and can be a neuronal marker for detecting postmitotic migrating neurons in the adult olfactory bulb.

Animals↗

GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with neurons and exhibit a reduced amount of intermediate filaments and an increased cell saturation density.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein predominantly expressed in cells of astroglial origin. To allow for the study of the biological functions of GFAP we have previously generated GFAP-negative mice by gene targeting [Pekny et al. (1995) EMBO J. 14, 1590-1598]. Astrocytes in culture, similar to reactive astrocytes in vivo, express three intermediate filament proteins: GFAP, vimentin, and nestin. Using primary astrocyte-enriched cultures from GFAP-negative mice, we now report on the effect of GFAP absence on (i) the synthesis of other intermediate filament proteins in astrocytes, (ii) intermediate filament formation, (iii) astrocyte process formation (stellation) in response to neurons in mixed cerebellar astrocyte/neuron cultures, and (iv) saturation cell density in vitro. GFAP-/- astrocytes were found to produce both nestin and vimentin. At the ultrastructural level, the amount of intermediate filaments as revealed by transmission electron microscopy was reduced in GFAP-/- astrocytes compared to that in GFAP+/+ astrocytes. GFAP-/- astrocytes retained the ability to form processes in response to neurons in mixed astrocyte/neuron cultures from the cerebellum. GFAP-/- astrocyte-enriched primary cultures exhibited an increased final cell saturation density. The latter leads us to speculate that the loss of GFAP expression observed focally in a proportion of human malignant gliomas may reflect tumor progression toward a more rapidly growing and malignant phenotype.

Animals↗

Ultrastructural studies of carboxyl-terminal truncation mutants of the neuronal intermediate filament protein peripherin.

We have prepared carboxyl-terminal truncation mutants of the neuronal intermediate filament (IF) protein peripherin and examined the assembly characteristics of these mutant proteins in SW13 cells in the presence and absence of vimentin. In the absence of vimentin, tailless peripherin protein (Per-C424) self-assembles into bundles and clumps as observed by immunofluorescence, whereas a peripherin mutant that is missing the tail as well as a small portion of the rod (Per-C356) appears as spherical aggregates. Similar phenotypes are observed when vimentin-positive cells are transfected with Per-C424 or Per-C356. In these cells, the entire IF network is disrupted, and vimentin colocalizes with the mutant peripherin proteins. To examine the morphology of the bundles and clumps formed by Per-C424 at the electron microscopic level, we prepared stable cell lines expressing different levels of this mutant protein. By immunofluorescence, Per-C424 appears as either clumps or bundles of filaments depending on the expression level of the mutant protein. However, under electron microscopy, it is apparent that both clumps and bundles are composed of tightly packed IFs. We were unable to obtain stable cell lines expressing Per-C356, indicating that this mutant may prevent cell proliferation. Using a vector containing an internal ribosomal entry site, we prepared a construct that expresses Per-C356 and green fluorescent protein as a single mRNA, and we were able to isolate cells that expressed Per-C356 by fluorescence-activated cell sorting. Electron microscopic analysis of these cells showed that these aggregates are solid and contain no obvious filamentous structures.

Cell Line↗