Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization Methods to Determine the HER2/neu Status in Primary Breast Carcinoma using Tissue Microarray

Identification of HER2/neu status is important for predicting response to specific chemotherapy in breast carcinoma. Chromogenic in situ hybridization was performed using tissue microarray technology on 188 primary breast carcinomas. To validate the reliability of novel chromogenic in situ hybridization technology, the results of chromogenic in situ hybridization were correlated with the results of two-color fluorescence in situ hybridization done with the same tumors. On tissue microarray panels containing 188 breast carcinoma tissues, fluorescence in situ hybridization and chromogenic in situ hybridization were conducted simultaneously. HER2/neu amplification was detected in 46 tumors (24.5%) by fluorescence in situ hybridization and in 43 tumors (22.9%) by chromogenic in situ hybridization. Results of each method agreed with each other in 177 tumors (concordance: 94.1%). HER2/neu amplification by fluorescence in situ hybridization was associated with nuclear pleomorphism (P = .021), and HER2/neu amplification by chromogenic in situ hybridization was associated with poor nuclear grade (P = .037). High concordance between fluorescence in situ hybridization and chromogenic in situ hybridization indicated that chromogenic in situ hybridization can be a tempting alternative to fluorescence in situ hybridization for the detection of HER2/neu amplification in breast carcinoma because of its accuracy and relative low cost. HER2/neu appeared to have a prognostic implication because its amplification was associated with aggressive biologic features of the breast carcinoma. Integration of tissue microarray technology enabled high-throughput determination of HER2/neu amplification profile with rapidity and accuracy in large cohorts of the breast carcinoma.
Investment Policies for Defined-Contribution Pension Funds

Dynamic optimal investment policies are derived for a defined-contribution pension plan under expected utility maximization and under minimization of the shortfall probability. It is assumed that the return attributed by the fund on the accrued retirement benefits of employees may depend on the funding ratio and partly on the investment performance of the fund. The resulting investment policies are compared with the reference case where the attributed return is assumed to be constant. Under expected utility maximization the investment strategy becomes more aggressive than in the reference case if the attributed return increases with the funding ratio. Higher net contributions lead to a more aggressive investment strategy. However, participation of employees in the investment performance of the fund has an ambiguous effect on the investment policy. Under expected utility maximization the funding ratio is lognormally distributed and asymptotically well behaved. For the minimization of the shortfall probability a technique developed by Pestien and Sudderth (1985) is used. Formulas for the shortfall probability are derived and discussed.
Stress/Aggressiveness-Induced Immune Changes Are Altered in Adult Rats Submitted to Neonatal Malnutrition

Background/Aims: Neonatal malnutrition induces metabolic and endocrine changes that have beneficial effects on the neonatal in the short term but, in the longer term, these alterations lead to maladaptations. We investigated the effect of neonatal malnutrition on immune responses in adult rats submitted or not to an aggressiveness test. Methods: Male Wistar rats were distributed to one of two groups according to their mothers’ diet during lactation: the well-nourished group (group C, n = 42, receiving 23% of protein) and the malnourished group (group MN, n = 42, receiving 8% of protein). After weaning, all rats received normoproteic diet. Ninety days after birth, each group was subdivided into three subgroups: control rats (n = 14, respectively), aggressive rats (n = 14, respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma corticosterone concentration was measured after FS sessions. Leukocyte counts and humoral immunity were evaluated. Results: In neonatal malnourished animals, FS-induced stress reduced plasma corticosterone concentration. Intraspecific aggressiveness induced alterations in leukocyte counts and antibody titers 7 and 15 days after immunization. Neonatal malnourished animals showed no changes in the immune parameters evaluated. Conclusions: Expression of intraspecific aggressiveness activates the immune system. Neonatal malnutrition seems to have a long-lasting effect on components of both neuroendocrine and immune functions.
The influence of the relative timing of arterial and subarachnoid space pulse waves on spinal perivascular cerebrospinal fluid flow as a possible factor in syrinx development.

OBJECT The mechanisms of syringomyelia have long puzzled neurosurgeons and researchers alike due to difficulties in identifying the driving forces behind fluid flow into a syrinx, apparently against a pressure gradient between the spinal cord and the subarachnoid space (SAS). Recently, the synchronization between CSF flow and the cardiac cycle has been postulated to affect fluid flow in the spinal cord. This study aims to determine the effect of changes in the timing of SAS pressure on perivascular flow into the spinal cord. METHODS This study uses a computational fluid dynamics model to investigate whether the relative timing of a spinal artery cardiovascular pulse wave and fluid pressure in the spinal SAS can influence CSF flow in the perivascular spaces. RESULTS The results show that the mass flow rate of CSF through a model periarterial space is strongly influenced by the relative timing of the arterial pulse wave and the SAS pressure. CONCLUSIONS These findings suggest that factors that might alter the timing of the pulse wave or the fluid flow in the SAS could potentially affect fluid flow into a syrinx.
Estrogen regulation of human osteoblast function is determined by the stage of differentiation and the estrogen receptor isoform

Although osteoblasts have been shown to respond to estrogens and express both isoforms of the estrogen receptor (ERα and ERβ), the role each isoform plays in osteoblast cell function and differentiation is unknown. The two ER isoforms are known to differentially regulate estrogen‐inducible promoter‐reporter gene constructs, but their individual effects on endogenous gene expression in osteoblasts have not been reported. We compared the effects of 17β‐estradiol (E) and tamoxifen (TAM) on gene expression and matrix formation during the differentiation of human osteoblast cell lines stably expressing either ERα (hFOB/ERα9) or ERβ (hFOB/ERβ6). Expression of the appropriate ER isoform in these cells was confirmed by northern and western blotting and the responses to E in the hFOB/ERβ6 line were abolished by an ERβ‐specific inhibitor. The data demonstrate that (1) in both the hFOB/ER cell lines, certain responses to E or TAM (including alkaline phosphatase, IL‐6 and IL‐11 production) are more pronounced at the late mineralization stage of differentiation compared to earlier stages, (2) E exerted a greater regulation of bone nodule formation and matrix protein/cytokine production in the ERα cells than in ERβ cells, and (3) the regulated expression of select genes differed between the ERα and ERβ cells. TAM had no effect on nodule formation in either cell line and was a less potent regulator of gene/protein expression than E. Thus, both the ER isoform and the stage of differentiation appear to influence the response of osteoblast cells to E and TAM. J. Cell. Biochem. 83: 448–462, 2001. © 2001 Wiley‐Liss, Inc.
Behavioral and Psychological Symptoms of Dementia and Bipolar Spectrum Disorders: Review of the Evidence of a Relationship and Treatment Implications

Abstract Dementia is a neuropsychiatric disorder characterized by cognitive impairment and behavioral disturbances. The behavioral and psychological symptoms of dementia (BPSD) are common, contributing to caregiver burden and premature institutionalization. Management of BPSD is complex and often needs recourse to psychotropic drugs. Though widely prescribed, there is a lack of consensus concerning their use, and serious side effects are frequent. This is particularly the case with antidepressant treatment based on the assumption that BPSD is depressive in nature. A better understanding of BPSD etiology could lead to better management strategies. We submit that some BPSD could be the consequence of both dementia and an undiagnosed comorbid bipolar spectrum disorder, or a pre-existing bipolar diathesis pathoplastically altering the clinical expression of dementia. The existence of such a relationship is based on clinical observation, as far as the high frequency of bipolar spectrum disorders in the general population, with a prevalence estimated to be between 5.4% and 8.3%, and the psychopathological similarities between BPSD and mood disorder episodes in bipolar illness. We will review the concept of the bipolar spectrum and explain BPSD before proposing clinical pointers of a possible bipolar spectrum contaminating the phenomenology of dementia, which could lead to the targeted prescription of mood-stabilizing agents in lieu of antidepressant monotherapy. These considerations are of heuristic interest in reconceptualizing the origin of the behavioral manifestations of dementia, with important implications for geriatric practice.
An Innovative Topical Drug Formulation for Wound Healing and Infection Treatment: In vitro and in vivo Investigations of a Povidone-Iodine Liposome Hydrogel

Background: In topical wound treatment, the combination of anti-infectious therapy and a healing-promoting moisturization has not been accomplished yet. Objective: Evaluation of a new topical drug consisting of a povidone-iodine (PVP-I) liposome hydrogel allowing for both antiseptic and moist treatment. Methods: Pharmaceutical formulation of a complex of PVP-I (3%) and phosphatidylcholine in a hydrogel. In vitro, interaction of the complex with relevant micro-organisms was analysed by electron microscopy. Antimicrobial activity was investigated using Staphylococcus aureus in a suspension test. Tissue toxicity was examined by an explantation test in a rodent model. A randomized clinical study on efficacy and tolerability in wound healing was carried out on 35 patients with mesh grafts in parallel groups (PVP-I liposome hydrogel vs. Bactigras) for proof of concept in humans. Results: A direct interaction of the PVP-I liposomes with micro-organisms by attachment to the cell surface was documented. A significantly better microbicidal activity and tissue tolerability of the PVP-I liposome hydrogel compared to conventional PVP-I formulations was shown. The results of the clinical study, especially measurements of neo-epithelization per time and transplant loss, demonstrate significant differences in favour of the PVP-I liposome hydrogel. Conclusion: The novel PVP-I liposome hydrogel combines microbicidal and wound healing activities resulting in enhanced epithelization.
Endocrine pancreatic cells from Xenopus laevis: light and electron microscopic studies.

Insulin, glucagon, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), somatostatin (SST)-28 (1-12), salmon (s) SST-25, and SST-14 immunoreactivities were demonstrated in the pancreatic endocrine cells of Xenopus laevis using light and electron microscopic immunocytochemistry. Insulin-, SST-28 (1-12)/SST-14-, and PYY-immunoreactive (ir) cells were found throughout the pancreas either isolated in small clusters of a single cell type or, except in the case of PYY-ir cells, forming islets consisting of various cell types. Anti-sSST-25 serum detected the invariant SST-14 form. Cells that were only immunoreactive to glucagon were isolated or clustered in the duodenal lobe, while in the splenic lobe cells immunoreactive to both glucagon and PP were observed in isolation, clustered, or in the periphery of the islets. There were no cells that were immunoreactive only to PP or to NPY. Ultrastructurally, the endocrine cells were characterized by their secretory granules, which were immunogold labeled with the corresponding antisera. Insulin cells had large round secretory granules with a round, irregular, or crystalline-like dense core. Glucagon-ir cells had round secretory granules with a dense core and a clear halo. Glucagon/PP- and PYY-ir cells showed round, ovoid, or pear-shaped secretory granules, which were larger and less electron dense in the latter cell type. The secretory granules of SST-ir cells were ovoid or bacillary with a medium electron-dense content. A sixth cell type with very small secretory granules could only be characterized by conventional electron microscopy, since it did not immunoreact with any of the antisera applied in this study.
Differences between lactating and non-lactating dairy cows in concentration and secretion rate of insulin.

1. Four parameters of insulin metabolism were compared in catheterized lactating and non-lactating Friesian x Ayrshire dairy cows. 2. The four parameters, i.e. arterial and portal-venous concentrations of insulin, and pancreatic output and hepatic uptake of insulin, were approx. 2-, 3-, 3- and 5-fold higher respectively in the non-lactating cows than in the lactating cows in the normal fed state. Statistical significance was not achieved for the differences in magnitude in the case of the latter two parameters, however. 3. All four parameters increased significantly about 4-fold when non-lactating cows were infused intravenously with glucose for 48 h at a rate of 4.2 mmol/min. The parameters also increased in the lactating cows during glucose infusion, but the values reached were substantially lower than in the non-lactating cows and the increases were not statistically significant. 4. Arterial insulin concentrations doubled in the non-lactating cows during a 3 h infusion of propionate into a mesenteric vein, but remained unaltered in the lactating cows. 5. Differences in insulin concentration and output between the lactating and non-lactating cows were not consistently related to differences in either glucose concentration or glucose-entry rate. Arterial propionate concentrations were similar in both groups of cows at all times. 6. It is concluded that in the dairy cow, insulin secretion in response to an insulinotropic agent is diminished during lactation.
Near-atomic resolution structural model of the yeast 26S proteasome

The 26S proteasome operates at the executive end of the ubiquitin-proteasome pathway. Here, we present a cryo-EM structure of the Saccharomyces cerevisiae 26S proteasome at a resolution of 7.4 Å or 6.7 Å (Fourier-Shell Correlation of 0.5 or 0.3, respectively). We used this map in conjunction with molecular dynamics-based flexible fitting to build a near-atomic resolution model of the holocomplex. The quality of the map allowed us to assign α-helices, the predominant secondary structure element of the regulatory particle subunits, throughout the entire map. We were able to determine the architecture of the Rpn8/Rpn11 heterodimer, which had hitherto remained elusive. The MPN domain of Rpn11 is positioned directly above the AAA-ATPase N-ring suggesting that Rpn11 deubiquitylates substrates immediately following commitment and prior to their unfolding by the AAA-ATPase module. The MPN domain of Rpn11 dimerizes with that of Rpn8 and the C-termini of both subunits form long helices, which are integral parts of a coiled-coil module. Together with the C-terminal helices of the six PCI-domain subunits they form a very large coiled-coil bundle, which appears to serve as a flexible anchoring device for all the lid subunits.
A 14 mW 2.5 MS/s 14 bit  $\Sigma\Delta$ Modulator Using Split-Path Pseudo-Differential Amplifiers

This paper presents the design and experimental results of a 1.25 MHz signal bandwidth 14 bit CMOS SigmaDelta modulator. With our proposed switched-capacitor split-path pseudo-differential amplifiers, this modulator achieves high power efficiency, high sampling frequency, and small die area. A new signal and reference front-end sampling network eliminates the input common-mode voltage and reduces power consumption and linearity requirement of the opamp. A prototype chip has been designed and fabricated in a 0.25 mum CMOS technology with a core area of 0.27 mm2. Experimental results show that an 84 dB dynamic range is achieved over a 1.25 MHz signal bandwidth when clocked at 125 MHz. The power dissipation is 14 mW at 2.4 V including on-chip voltage reference buffers.
Proximity of excitatory and inhibitory axon terminals adjacent to pyramidal cell bodies provides a putative basis for nonsynaptic interactions

Although pyramidal cells are the main excitatory neurons in the cerebral cortex, it has recently been reported that they can evoke inhibitory postsynaptic currents in neighboring pyramidal neurons. These inhibitory effects were proposed to be mediated by putative axo-axonic excitatory synapses between the axon terminals of pyramidal cells and perisomatic inhibitory axon terminals [Ren M, Yoshimura Y, Takada N, Horibe S, Komatsu Y (2007) Science 316:758–761]. However, the existence of this type of axo-axonic synapse was not found using serial section electron microscopy. Instead, we observed that inhibitory axon terminals synapsing on pyramidal cell bodies were frequently apposed by terminals that established excitatory synapses with neighbouring dendrites. We propose that a spillover of glutamate from these excitatory synapses can activate the adjacent inhibitory axo-somatic terminals.
Relative Age Effect in Japanese Male Athletes

The present study investigated the relative age effect, a biased distribution of elite athletes' birthdates, in Japanese male athletes. Japan applies a unique annual-age grouping for sport and education, which is from April 1 to March 31 of the following year. A total of 4,318 male athletes was evaluated from 12 sports: baseball, soccer, basketball, volleyball, handball, golf, horse racing, rugby, American football, sumo, Ekiden (track and field in long distance), and badminton. They played in the top level of Japanese leagues for each sport in 2010. The distribution of the birth dates was examined in each sport and showed significant relative age effect in baseball, soccer, volleyball, Ekiden, basketball, sumo, and horse racing, but not in all sports. The findings suggest that although the school year in Japan starts on April 1, significant relative age effects are observed in some sporting events.
Prenatal development of the rodent rostral migratory stream

The aim of this study was to elucidate the embryological origins of the unique neuronal progenitor cells that form the rostral migratory stream (RMS), the path traversed by cells from the anterior part of the forebrain subventricular zone (SVZa) en route to the olfactory bulb. To determine when and where cells constituting the RMS initially exhibit their characteristic neuronal phenotype and high mitotic capacity, we analyzed the cells of the rat forebrain between embryonic day 14 (E14) and postnatal day 2 (P2). At E14, cells with a neuronal phenotype were observed within the ventricular zone in close proximity to the mantle layer of the future olfactory bulb. By E15, cells expressing neuronal markers are also PSA‐NCAM immunoreactive and become aligned in chains of similarly oriented cells, a hallmark of the postnatal RMS. The cells that form chains organize into a patch that enlarges in the anterior‐posterior and medial‐lateral dimensions from E16 to E22 (birth). In comparing the forebrain cytoarchitecture to the pattern of cell type‐specific staining, the patch constitutes only the central part of the proximal RMS. Early during development, the region of the RMS surrounding the patch expresses low levels of PSA‐NCAM and neuron‐specific markers. The proliferative activity of cells forming the patch vs. nonpatch regions of the RMS was analyzed following a short bromodeoxyuridine (BrdU) exposure. Between E15 and E22, the patch can be recognized by the mitotic activity of its cells; the cells of the patch incorporate less BrdU than the nonpatch portion of the RMS. The time course of appearance of cells forming the RMS indicates that the RMS arises in advance and independently of the cortical SVZ. Although the patch and the nonpatch regions of the embryonic RMS appear to merge postnatally, the two regions may originate separately under the influence of distinct intrinsic and extrinsic factors. J. Comp. Neurol. 463:402–418, 2003. © 2003 Wiley‐Liss, Inc.
The role of early mechanisms in motion transparency and coherence.

Perceptual dissociation of moving plaid patterns into independently moving bar gratings occurs most readily when the grating signals are combined as if the bars were semi-transparent objects (Ramachandran, V. S. (1990) in: AI and the Eye. Wiley, Chichester, pp. 21-77. Stoner, G. R. , Albright, T. D. and Ramachandran, V. S. (1990) Nature 344, 153-155). These and other examples of motion transparency are exploited to constrain the set of viable models for human motion processing. For example, one may exclude any fixed recombination of local motion signals into a plaid motion signal. Broad classes of linear and non-linear mechanisms for tracking blobs, corners, and other unambiguous plaid motion cues can also be ruled out because they fail to reproduce the experimental results even qualitatively. The shifting balance between the 'coherent plaid' and 'sliding gratings' percepts are attributed to processing stages before any integration or combination of local motion signals. The first essential stage is a roughly logarithmic nonlinearity before orientation filtering. In general, the resulting cross-products (at the intersections) code unambiguously for the true plaid motion vector, but these signals will be nulled for multiplicatively combined plaid components. Supporting evidence for this idea is obtained in our measurements of detection thresholds for the 'plaid' and 'sliding' percepts. The essential element of the second stage consists of 'end-stop' cells which detect the nullable intersection signal, and so produce a plaid-motion signal with the required characteristics. Finally, it is argued that the ecological role of the proposed mechanism lies in the ability to handle movement of patterned objects in lighting conditions dominated by complicated cast shadows.
Effects of lameness, subclinical mastitis and loss of body condition on the reproductive performance of dairy cows

A total of 318 cows were monitored in the pre-breeding postpartum period for the presence of three production stressors: lameness, subclinical mastitis and body condition score (BCS) loss. For each stressor, cows were given a classification of severely, moderately or non-affected based on mobility scores, somatic cell counts and BCS change. The number of days from calving to onset of the first luteal phase was greater in cows that had one severe production stressor (median 44 days) or two moderate production stressors (41 days) compared with cows that had no stressors (31 days) (P=0.02 and P=0.04, respectively). More than one severe stressor increased the interval further. There was no difference between cows with one moderate stressor (median 38 days) and those with none (P=0.13). The delay to the first luteal phase was significantly longer in cows with two moderate stressors if the onset of one stressor occurred at the time when resumption of ovarian activity was expected. The presence of these production stressors in early lactation had no effect on the interval from calving to establishment of the next pregnancy or the number of inseminations required despite the negative effect on the onset of the luteal phase.