Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

Apicidin, the histone deacetylase inhibitor, suppresses Th1 polarization of murine bone marrow-derived dendritic cells.

Apicidin is a fungal metabolite shown to exhibit anti-proliferative, anti-invasive, and anti-inflammatory properties by the inhibition of histone deacetylase (HDAC). However, the effects of apicidin on the maturation and immunostimulatory function of dendritic cells (DCs) remain unknown. In this study, we investigated whether apicidin modulates surface molecule expression, cytokine production, endocytosis capacity, and underlying signaling pathways in murine bone marrow-derived DCs. We observed that apicidin significantly attenuated surface molecule expression in LPS-stimulated DCs, suppressed production of interleukin (IL)-12 and proinflammatory cytokines (IL-6 and TNF-alpha) by DCs, and reduced IFN-gama production by T cells. The apicidin-treated DCs were found to be highly efficient in antigen capture via mannose receptor-mediated endocytosis. Apicidin also inhibited LPS-induced MAPK activation and NF-kB nuclear translocation in DCs. Moreover, the apicidin-treated DCs were incapable of inducing Th1 responses and normal cell-mediated immune responses. These novel findings not only provide new insights into the immunopharmacological role of apicidin in terms of its effects on DCs, but also broaden current perspectives of the immunopharmacological functions of apicidin, and have implications for the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.

Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice.

BACKGROUND: The ability of apolipoprotein (apo)A-I to induce regression of preexisting atherosclerotic lesions has not been determined, and a mouse model of atherosclerosis regression has not yet been reported. METHODS AND RESULTS: LDL receptor-deficient mice were fed a western-type diet for 5 weeks to induce atherosclerotic lesions. A second-generation recombinant adenovirus encoding human apoA-I or a control adenovirus were injected intravenously in order to express apoA-I in the liver. Three days after injection, total apoA-I levels in mice injected with the apoA-I-expressing adenovirus were 216+/-16.0 mg/dL, compared with 68.0+/-3.0 mg/dL in control virus-injected mice (P<0.001). HDL cholesterol levels in mice injected with the AdhapoA-I vector 7 days after injection were 189+/-21.0 mg/dL, compared with 123+/-8.0 mg/dL in control virus-injected mice (P<0.02). Total and non-HDL cholesterol levels did not differ between the 2 groups. Atherosclerotic lesion area was quantified by en face analysis of the aorta and cross-sectional analysis of the aortic root. Compared with baseline mice, atherosclerosis progressed in mice injected with the control adenovirus. In contrast, in mice expressing apoA-I compared with baseline mice, total en face aortic lesion area was reduced by 70% and aortic root lesion was reduced by 46%. Expression of apoA-I was associated with a significant reduction in the fraction of lesions occupied by macrophages and macrophage-derived foam cells. CONCLUSIONS: Liver-directed gene transfer of human apoA-I resulted in significant regression of preexisting atherosclerotic lesions in LDL receptor-deficient mice as assessed by 2 independent methods.

Long-term efficacy of amiodarone for the maintenance of normal sinus rhythm in patients with refractory atrial fibrillation or flutter.

The purpose of this study was to examine the efficacy and safety of amiodarone to maintain sinus rhythm in patients with refractory atrial fibrillation or flutter. One hundred ten patients with atrial fibrillation or flutter, refractory to > or = 1 class I antiarrhythmic agents (mean +/- SD 2.5 +/- 1.5, median 2), were given low-dose amiodarone (mean maintenance dose 268 +/- 100 mg/day) to determine its efficacy to maintain normal sinus rhythm after chemical or electrical cardioversion. Fifty-three patients had chronic and 57 patients had paroxysmal atrial fibrillation or flutter. Mean age of the study population was 60 +/- 13 years, and the mean follow-up was 36 +/- 38 months (range 31 days to 137 months). Actuarial rates for maintenance of sinus rhythm were 0.87, 0.70, and 0.55 at 1, 3, and 5 years, respectively. Twenty-one patients (19%) with arrhythmia recurrence had an increase in amiodarone dose, and after a mean additional follow-up of 2.5 years, 86% remained in normal sinus rhythm. The only observed predictor of atrial fibrillation or flutter recurrence was paroxysmal arrhythmia (40% recurrence vs 9% in patients with chronic atrial fibrillation or flutter; p < 0.001). Actuarial rates for withdrawal because of adverse effects were 0.08, 0.22, and 0.30 at 1, 3, and 5 years, respectively. The most frequent adverse effects necessitating withdrawal were skin discoloration (4.5%), pulmonary fibrosis (3.6%; none fatal), and thyroid toxicity (2.7%). No deaths occurred during the study period. In conclusion, amiodarone sinus rhythm in patients with atrial fibrillation or flutter, with a relatively low incidence of adverse effects necessitating withdrawal.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 mRNA expression in ectopic and eutopic endometrium in women with endometriosis: a rationale for endometriotic invasiveness.

OBJECTIVE: To investigate mRNA expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in ectopic endometriosis tissue and uterine endometrium from women with and without endometriosis throughout the menstrual cycle. DESIGN: Molecular studies in human tissue. SETTING: Department of Gynecology and Obstetrics, Reproductive Immunology Laboratory, Stanford University Medical Center. PATIENT(S): Fifty-three premenopausal woman (23 women with endometriosis and 30 women without endometriosis undergoing laparoscopic surgery). Endometrium and ectopic endometriosis tissue were obtained at the time of surgery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): mRNA expression from eutopic and ectopic endometrium was analyzed by quantitative, competitive PCR. RESULT(S): Both uterine endometrium and ectopic endometriotic tissue from women with endometriosis expressed significantly (P<.05) lower levels of TIMP-3 than endometrium from normal women. Also, ectopic endometrium expressed higher levels of MMP-9 and a higher ratio of MMP-9/TIMP-3 than eutopic endometrium from normal and endometriosis patients. CONCLUSION(S): These results suggest that ectopic and eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater MMP and less TIMP-3 mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometrium, resulting in the development of endometriosis.

Eating frequency is inversely associated with blood pressure and hypertension in Korean adults: analysis of the Third Korean National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVES: A lower eating frequency (EF) has been suggested to be important in the development of cardiovascular risk factors such as obesity and hyperlipidemia. However, the association between EF and blood pressure (BP) remains unclear. SUBJECTS/METHODS: The aim of this study was to explore the association of EF with BP and hypertension after adjusting for confounding variables, including body mass index (BMI) and waist circumference (WC). This cross-sectional study used data from the Third Korean National Health and Nutrition Examination Survey. A total of 4625 subjects aged ≥ 19 years were included. To explore the association of EF with BP and hypertension, we performed multiple linear regression analyses and multiple logistic regression analyses for survey design, respectively. RESULTS: EF was inversely associated with systolic BP (SBP) and diastolic BP (DBP). As EF increased from ≤ 2 to 3, 4 and ≥ 5 times per day, estimated adjusted means of both SBP and DBP decreased, showing a significant linear trend independent of obesity (SBP: 120.66, 120.23, 119.18 and 117.92 mm Hg, respectively; P<0.001; DBP: 78.36, 77.78, 77.25 and 76.50 mm Hg, respectively; P=0.004). The inverse association between EF and hypertension was gradually attenuated and significant after adjustment for confounding variables including BMI and WC (P=0.040). CONCLUSIONS: This study suggests that lower EF is significantly associated with higher BP, which may be partially mediated by the effect of central obesity. Further prospective studies are needed to verify this causal relationship.

14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death.

14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.

Roles of 14-3-3η in mitotic progression and its potential use as a therapeutic target for cancers.

14-3-3 proteins are involved in several cellular processes, including the G1/S and G2/M cell cycle transitions. However, their roles during mitosis are not well understood. Here, we showed that depletion of 14-3-3η, a 14-3-3 protein isoform, enhanced mitotic cell death, resulting in sensitization to microtubule inhibitors and inhibition of aneuploidy formation. The enhanced mitotic cell death by depletion of 14-3-3η appeared to be both caspase-dependent and independent. Furthermore, enhanced mitotic cell death and a reduction in aneuploidy following 14-3-3η depletion were independent of the mitotic checkpoint, which is thought to be the primary signaling event in the regulation of the cell death induced by microtubule inhibitors. When 14-3-3η depletion was combined with microtubule inhibitors in HCT116 and U87MG cells, it sensitized both cancer cell lines to microtubule inhibitors. These results collectively suggest that 14-3-3η may be required for mitotic progression and may be considered as a novel anti-cancer strategy in combination with microtubule inhibitors.

Interplay between carrier and impurity concentrations in annealed Ga1-xMnxAs: intrinsic anomalous hall effect.

Investigating the scaling behavior of annealed Ga1-xMnxAs anomalous Hall coefficients, we note a universal crossover regime where the scaling behavior changes from quadratic to linear. Furthermore, measured anomalous Hall conductivities in the quadratic regime when properly scaled by carrier concentration remain constant, spanning nearly a decade in conductivity as well as over 100 K in T_[C] and comparing favorably to theoretically predicated values for the intrinsic origins of the anomalous Hall effect. Both qualitative and quantitative agreements strongly point to the validity of new equations of motion including the Berry phase contributions as well as the tunability of the anomalous Hall effect.

The development of child care programs for urban low-income areas.

PIP: Korea has realized remarkable economic growth in the past 3 decades, consequently the rate of female employment increased from 39.6% in 1975 to 45.0% in 1980. It is estimated that 1,500,000 children need child care but only 200,000 can afford it. Although 200 voluntary small-scale community child care centers in low-income areas meet the need of some double-income married couples, they do not suffice. The research objectives were to assess actual conditions of family and community child-care, to devise standards for founding child-care centers; to develop educational courses for caregivers in small-scale child-care, and to develop child-care programs for children under age 3. The sample consisted of 60 childcare agencies. 30 family child-care practitioners were selected from among the trainees of 7 child-care education centers Seoul and 30 community child-care centers were chosen from the metropolitan area from among the members of the Community Child-Care Association and the Catholic Child-Care Association. 5 researchers were employed and trained. Caregivers in family and community child-care centers were interviewed from August 28, 1989 to September 24, 1989, by means of a questionnaire. 59 (98.3%) of 60 subjects answered the questionnaire. 96.7% of the programs had full-day child-care, and 94.9% had mixed-age children. 66.1% of the programs were open from 8:00 AM to 9:00 PM, and 49 programs (85.9%) were open more than 10 hours a day. All the caregivers were women with education above the high school level. 93.2% had completed child-care education programs and 79.7% had graduated from in-service programs. 76.3% were using a general educational plan. 11.9% had no outdoor playground, although 76.3% included picnics in their program. Based on the findings, it is recommended that the standard should be a full-day, mixed-age child-care system with more systematic program planning, parental education, and links to nearby hospitals for emergency treatment.^ieng

Colossal magnetoresistance is a Griffiths singularity.

It is now widely accepted that the magnetic transition in doped manganites that show large magnetoresistance is a type of percolation effect. This paper demonstrates that the transition should be viewed in the context of the Griffiths phase that arises when disorder suppresses a magnetic transition. This approach explains unusual aspects of susceptibility and heat capacity data from a single crystal of La0.7Ca0.3MnO3.

Direct measurement of the spin polarization of the magnetic semiconductor (Ga,Mn)As.

We have carried out a direct measurement of the degree of spin polarization (P) of the magnetic semiconductor Ga1-xMnxAs using Andreev reflection spectroscopy. Analyses of the conductance spectra of high transparency Ga(0.95)Mn(0.05)As/Ga junctions consistently yield an intrinsic value for P greater than 85%. Our experiments also revealed an extreme sensitivity of the measured spin polarization to the nature and quality of the interface for this material.

Rapid regression of atherosclerosis induced by liver-directed gene transfer of ApoE in ApoE-deficient mice.

Apolipoprotein E (apoE) is a multifunctional protein synthesized by the liver and tissue macrophages. ApoE-deficient mice have severe hyperlipidemia and develop accelerated atherosclerosis on a chow diet. Both liver-derived and macrophage-derived apoEs have been shown to reduce plasma lipoprotein levels and slow the progression of atherosclerosis in apoE-deficient mice, but regression of atherosclerosis has not been demonstrated in this model. We utilized second-generation adenoviruses to achieve hepatic expression of human apoE in chow-fed, apoE-deficient mice with established atherosclerotic lesions of different stages. As expected, hepatic expression of human apoE3 significantly reduced plasma cholesterol levels. Liver-derived apoE also accumulated substantially within preexisting atherosclerotic lesions, indicating that plasma apoE gained access to the arterial intima. Hepatic expression of human apoE3 for 6 weeks resulted in significant quantitative regression of both early fatty streak lesions as well as advanced, complex lesions in both the aortic root and the aortic arch. In addition, hepatic expression of apoE induced substantial morphological changes in lesions, including decreased foam cells and increased smooth muscle cells and extracellular matrix content. In parallel, human apoE4 and apoE2 were also expressed in the liver by using recombinant adenoviruses. ApoE4 reduced cholesterol levels to the same extent as did apoE3 and also prevented progression but did not induce significant regression of preexisting lesions. ApoE2 reduced cholesterol levels to a lesser degree than did apoE3 and apoE4 and lesion progression was reduced, but regression was not induced. In summary, (1) regression of preexisting atherosclerotic lesions in apoE-deficient mice can be rapidly induced by hepatic expression of apoE, despite the absence of macrophage-derived apoE; (2) the morphological changes seen in this model of regression resemble those in other animal models, induced over longer periods of time; (3) liver-derived apoE gained access to and was retained by intimal atherosclerotic lesions; and (4) apoE4 was less effective in inducing regression, despite its effects on plasma lipoproteins that were similar to those of apoE3. The rapid regression of preexisiting atherosclerotic lesions induced by apoE gene transfer in apoE-deficient mice could provide a convenient murine model for investigation of the molecular events associated with atherosclerosis regression.

Magnetotransport in manganites and the role of quantal phases: theory and experiment.

While low-temperature Hall resisitivity rhoxy of La2/3(Ca,Pb)1/3MnO3 single crystals can be separated into ordinary (OHE) and anomalous (AHE) contributions, no such decomposition is possible near the Curie temperature Tc. Rather, the rhoxy data collapse to a single function of the reduced magnetization m=M/Msat, with an extremum at approximately 0.4 m. A new mechanism for the AHE in the inelastic hopping regime is identified that reproduces the scaling curve. An extension of Holstein's model for the hopping OHE, the mechanism arises from the combined effects of the double-exchange-induced quantal phase in triads of Mn ions and spin-orbit interactions.

Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia.

During human placental development, cytotrophoblast stem cells differentiate and invade the uterus. Simultaneously, the cells modulate their expression of several classes of stage-specific antigens that mark transitions in the differentiation process and play a role in either uterine invasion (integrin cell-extracellular matrix receptors and matrix metalloproteinase-9) or immune interactions (HLA-G). The pregnancy disease pre-eclampsia is associated with shallow cytotrophoblast invasion. Previously we showed, by immunofluorescence localization on placental tissue, that in pre-eclampsia invasive cytotrophoblasts fail to properly modulate their integrin repertoire. This finding suggests possible abnormalities in the differentiation pathway that leads to uterine invasion. Here we used a culture system that supports this differentiation process to compare the differentiative and invasive potential of cytotrophoblasts obtained from control (n = 8, 22 to 38 weeks) and pre-eclamptic (n = 9, 24 to 38 weeks) placentas. In culture, the cells from pre-eclamptic placentas failed to properly modulate alpha1 integrin and matrix metalloproteinase-9 expression at the protein and mRNA levels. Their invasive potential was also greatly reduced. Likewise, the cells failed to up-regulate HLA-G protein and mRNA expression. These results suggest that defective cytotrophoblast differentiation/invasion can have significant consequences to the outcome of human pregnancy (ie, development of pre-eclampsia) and that, by the time delivery becomes necessary, the defect is not reversed by removing the cells from the maternal environment.

Germline mutations of the APC gene in Korean familial adenomatous polyposis patients.

We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated Korean patients with familial adenomatous polyposis (FAP) for identification of germline adenomatous polyposis coli (APC) gene mutations. We adopted both single-strand conformation polymorphism (SSCP) analysis and a method of analysis involving the reverse transcription-polymerase chain reaction (RT-PCR) followed by a protein truncation test (PTT). DNA sequencing confirmed all alterations represented by aberrant bands. Germline mutations were identified in 38 patients (61%). Nineteen of the detected mutations were presumed to be novel, thus emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients. In the initial 48 patients, SSCP analysis was followed by PTT for those patients for whom no detectable mutations were found by SSCP. Using this combined approach, we identified germline APC gene mutations in 29 of the 48 FAP patients (60%), including 6 patients in whom SSCP analysis failed to distinguish the mutant allele. In the 14 later patients, we identified truncating mutations in 9 patients (64%) using PTT only. Our results confirm that the mutation detection rate with PTT was superior to that with SSCP, and suggest that PTT would be a more practical screening method to detect germline mutations of the APC gene in FAP patients.

Mullerian adenosarcoma with sarcomatous overgrowth of the cervix presenting as cervical polyp: a case report and review of the literature.

An aggressive variant of adenosarcoma, mullerian adenosarcoma with sarcomatous overgrowth (MASO) in the cervix is extremely rare. This variant contains obvious, high-grade sarcoma in addition to a low-grade form. In this report, we describe a case of MASO of the uterine cervix and review the clinical and pathological features of these tumors. The patient was a 37-year-old woman with a cervical polypoid mass, which was morphologically considered as a benign endocervical polyp. Microscopically, polypoid cervical mass showed diffuse and dense malignant spindle cell proliferation around the benign endocervical glands and also an area of markedly anaplastic and pleomorphic spindle cell proliferation, so called, sarcomatous overgrowth. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection were performed. The patient has been followed-up and neither chemotherapy nor other adjuvant therapies have been administered. At present, she has been clinically free of disease for 9 months since she received surgery. It is extremely rare that MASO of the uterine cervix is presented in premenopausal woman. Gynecologists and pathologists should be aware of the difficulties associated with a delay in the diagnosis of MASO when the tumor is present as a benign looking cervical polyp.