Miracle-dz/UniFAR-FTUs huggingface dataset:
Space in the brain: how the hippocampal formation supports spatial cognition

Over the past four decades, research has revealed that cells in the hippocampal formation provide an exquisitely detailed representation of an animal's current location and heading. These findings have provided the foundations for a growing understanding of the mechanisms of spatial cognition in mammals, including humans. We describe the key properties of the major categories of spatial cells: place cells, head direction cells, grid cells and boundary cells, each of which has a characteristic firing pattern that encodes spatial parameters relating to the animal's current position and orientation. These properties also include the theta oscillation, which appears to play a functional role in the representation and processing of spatial information. Reviewing recent work, we identify some themes of current research and introduce approaches to computational modelling that have helped to bridge the different levels of description at which these mechanisms have been investigated. These range from the level of molecular biology and genetics to the behaviour and brain activity of entire organisms. We argue that the neuroscience of spatial cognition is emerging as an exceptionally integrative field which provides an ideal test-bed for theories linking neural coding, learning, memory and cognition.
Basal metabolic rate and liver tumors due to azo dyes.

Summary 1.Rats were fed 0.064 per cent of m′ methyl-p-dimethylaminoazobenzene for 4 weeks, followed by 4 weeks during which certain dye-free diets were fed which altered the basal metabolic rate; the dye was then fed for another 4 weeks. Other rats were fed 0.06 per cent of p-dimethylaminoazobenzene (DAB) for 20 weeks in diets which altered the BMR. 2.Hyperthyroid animals receiving DAB usually failed to survive, but the incidence of tumors in the survivors was high.Hyperthyroidism induced in precancerous rats in the absence of azo dye also increased tumor incidence. Thiouracil appeared to increase tumor incidence in rats fed DAB, but the more potent depressant, 6-n-propyl-2-thiouracil, failed to affect a development of tumors when given during the period of interruption. 3.Liver slices from hyperthyroid rats destroyed less than one-fourth as much DAB as slices from normal rats. Slices from rats fed high levels of riboflavin destroyed nearly twice as much dye as slices from control rats, but when the rats which received high riboflavin were made hyperthyroid, the ability to destroy the dye decreased, although liver riboflavin remained high. 4.In media containing inorganic salts and nicotinamide, homogenates from normal livers destroyed the dye at a high rate, while homogenates from hyperthyroid livers failed to destroy much dye. Homogenates from hyperthyroid livers destroyed approximately normal amounts of dye when hexose diphosphate was added to the medium.
The environmental pollutant pyrene induces the production of IL-4.

BACKGROUND Epidemiologic studies and experiments with mouse models suggest that polyaromatic hydrocarbons contained in, among others, diesel exhaust particles can promote the development of allergy. OBJECTIVE Because IL-4 organizes allergic responses in vivo, we have investigated whether pyrene, a major compound of diesel exhaust particles, can affect the production of IL-4. METHODS IL-4 production by primary human T cells was assessed by ELISA and messenger RNA transcription was detected by Northern blotting. Activation of the IL-4 promoter was tested in reporter gene assays with transiently transfected cell lines. RESULTS Pyrene induced transcription of IL-4 messenger RNA and expression of IL-4 protein in primary human T cells. Pyrene, but not related polyaromatic hydrocarbons, enhanced basal transcription of the human and mouse IL-4 promoter. CONCLUSION Our results suggest that pyrene may promote allergic diseases by inducing the production of IL-4.
Measurement of umbilical arterial blood flow to the sheep placenta and fetus in utero. Distribution to cotyledons and the intercotyledonary chorion.

A method of estimating the magnitude and distribution of umbilical blood flow by means of radioactive microspheres in sheep fetuses in utero is described. Simultaneous measurements of total umbilical flow by this method and the steady-state diffusion technique showed agreement within ± 11%. In 11 fetuses of 90 to 150 days gestational age, the distribution of umbilical flow to the intercotyledonary chorion was 6.2 ± 0.8% of the total. This information has been used to estimate the effect of venous admixture of cotyledonary and noncotyledonary blood on the umbilical vein-uterine vein concentration difference of inert molecules with flow-limited transplacental clearance. ADDITIONAL
Charge State Determination of Peptide Tandem Mass Spectra Using Support Vector Machine (SVM)

A single mass spectrometry experiment could produce hundreds of thousands of tandem mass spectra. Several search engines have been developed to interpret tandem mass spectra. All search engines need to determine the masses of peptide ions from their mass/charge ratios. Unfortunately, mass spectrometers do not detect the charges of ions. A current strategy is to search candidate peptides multiple times, once for each possible charge state (typically +2 or +3 ). However, this strategy not only wastes the search time, but also increases the risk of false positive peptide identification. This paper aims at discriminating doubly charged spectra from triply charged ones. Twenty-eight features are introduced to describe the discriminant characteristics of doubly charged and triply charged spectra. The support vector machine (SVM) technique is used to train the classifier on these 28 features. To verify the proposed method, computational experiments are conducted on two types of datasets: ISB dataset generated from the low-resolution ion-trap instrument and TOV dataset generated from the high-resolution quadrupole-time-of-flight instrument. For each type of dataset, the SVM-based classifiers are trained and tested on 20 randomly sampled subdatasets. The results show that the proposed method reaches average correct rates of 95% and 93% to discriminate doubly charged spectra from triply charged ones for the low-resolution ISB dataset and the high-resolution TOV dataset, respectively.
The NUF1 gene encodes an essential coiled-coil related protein that is a potential component of the yeast nucleoskeleton

In an attempt to identify structural components of the yeast nucleus, subcellular fractions of yeast nuclei were prepared and used as immunogens to generate complex polyclonal antibodies. One such serum was used to screen a yeast genomic lambda gt11 expression library. A clone encoding a gene called NUF1 (for nuclear filament-related) was identified and extensively characterized. Antibodies to NUF1 fusion proteins were generated, and affinity-purified antibodies were used for immunoblot analysis and indirect immunofluorescence localization. The NUF1 protein is 110 kD in molecular mass and localizes to the yeast nucleus in small granular patches. Intranuclear staining is present in cells at all stages of the cell cycle. The NUF1 protein of yeast is tightly associated with the nucleus; it was not removed by extraction of nuclei with nonionic detergent or salt, or treatment with RNAse and DNAse. Sequence analysis of the NUF1 gene predicts a protein 945 amino acids in length that contains three domains: a large 627 residue central domain predicted to form a coiled-coil structure flanked by nonhelical amino-terminal and carboxy-terminal regions. Disruption of the NUF1 gene indicates that it is necessary for yeast cell growth. These results indicate that NUF1 encodes an essential coiled-coil protein within the yeast nucleus; we speculate that NUF1 is a component of the yeast nucleoskeleton. In addition, immunofluorescence results indicate that mammalian cells contain a NUF1-related nuclear protein. These data in conjunction with those in the accompanying manuscript (Yang et al., 1992) lead to the hypothesis that an internal coiled-coil filamentous system may be a general structural component of the eukaryotic nucleus.
Interplay between spontaneous and induced brain activity during human non-rapid eye movement sleep

Humans are less responsive to the surrounding environment during sleep. However, the extent to which the human brain responds to external stimuli during sleep is uncertain. We used simultaneous EEG and functional MRI to characterize brain responses to tones during wakefulness and non-rapid eye movement (NREM) sleep. Sounds during wakefulness elicited responses in the thalamus and primary auditory cortex. These responses persisted in NREM sleep, except throughout spindles, during which they became less consistent. When sounds induced a K complex, activity in the auditory cortex was enhanced and responses in distant frontal areas were elicited, similar to the stereotypical pattern associated with slow oscillations. These data show that sound processing during NREM sleep is constrained by fundamental brain oscillatory modes (slow oscillations and spindles), which result in a complex interplay between spontaneous and induced brain activity. The distortion of sensory information at the thalamic level, especially during spindles, functionally isolates the cortex from the environment and might provide unique conditions favorable for off-line memory processing.
Sex Differences in Simple Reaction Tasks

Many anatomical and brain mapping studies show a higher bilateral symmetry of female brains and a higher asymmetry of male brains so correlations between simple visual and auditory, left- and right-hand reaction times were examined for such sex differences. 20 healthy women and 20 men were tested in two sessions. For women all six response times correlated with each other significantly in Session A, but in Session B there were only two significant interhemispheric correlations. This represented different changes in visual and auditory reaction times between Sessions A and B. Men showed the same pattern in both sessions: a significant correlation between the interhemispheric visual reaction times and one between auditory reaction times. Women showed a total correlation pattern in Session A and an interhemispheric correlation pattern in Session B. This was interpreted as a transition between a holistic information-processing strategy in Session A and an analytic strategy in Session B. Men showed an analytic strategy in both sessions.
Optimized Cutoff Value and Indication for Washout Thyroglobulin Level According to Ultrasound Findings in Patients with Well-Differentiated Thyroid Cancer

BACKGROUND AND PURPOSE: Washout thyroglobulin provides evidence for metastatic or recurrent lesions, However, the cutoff value is still controversial. We investigated an optimized cutoff value and indication for the use of washout thyroglobulin from fine-needle aspiration in neck lymph nodes from preoperative or postoperative patients with well-differentiated thyroid cancers. MATERIALS AND METHODS: A total of 177 lymph nodes from 161 patients underwent sonographically guided fine-needle aspiration cytology and washout thyroglobulin measurement and then underwent surgery and clinical follow-up. We assessed an optimized cutoff value of washout thyroglobulin for diagnosing metastasis and compared its diagnostic performance with that of washout thyroglobulin > 10 ng/mL, the currently accepted cutoff value. We also analyzed diagnostic performances of fine-needle aspiration cytology alone and of the combination of fine-needle aspiration cytology and washout thyroglobulin on the basis of the presence or absence of suspicious ultrasonographic findings. RESULTS: Of the 177 lymph nodes, 77 were metastases and 100 were benign. An optimized cutoff value for washout thyroglobulin was 1.8 ng/mL. The sensitivity and negative predictive value in diagnosing metastasis improved significantly with a cutoff value of 1.8 ng/mL compared with a cutoff value of 10 ng/mL (P = .0412 for sensitivity, P = .0188 for negative predictive value). In patients with suspicious ultrasonographic findings, applying washout thyroglobulin along with fine-needle aspiration cytology significantly enhanced the sensitivity and negative predictive value of fine-needle aspiration cytology performances to 100% and 100%, respectively (P = .0051, and P = .0088). There was no difference in diagnostic performance between fine-needle aspiration cytology and the combination of the 2 methods in patients without suspicious ultrasonographic findings. CONCLUSIONS: Applying the optimized cutoff value of washout thyroglobulin of 1.8 ng/mL in patients with suspicious ultrasonographic features facilitates the diagnostic evaluation of neck lymph nodes in both preoperative and postoperative patients with well-differentiated thyroid cancer.
Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials.

To calculate the effect of changes in carbohydrate and fatty acid intake on serum lipid and lipoprotein levels, we reviewed 27 controlled trials published between 1970 and 1991 that met specific inclusion criteria. These studies yielded 65 data points, which were analyzed by multiple regression analysis using isocaloric exchanges of saturated (sat), monounsaturated (mono), and polyunsaturated (poly) fatty acids versus carbohydrates (carb) as the independent variables. For high density lipoprotein (HDL) we found the following equation: delta HDL cholesterol (mmol/l) = 0.012 x (carb----sat) + 0.009 x (carb----mono) + 0.007 x (carb---- poly) or, in milligrams per deciliter, 0.47 x (carb----sat) + 0.34 x (carb----mono) + 0.28 x (carb----poly). Expressions in parentheses denote the percentage of daily energy intake from carbohydrates that is replaced by saturated, cis-monounsaturated, or polyunsaturated fatty acids. All fatty acids elevated HDL cholesterol when substituted for carbohydrates, but the effect diminished with increasing unsaturation of the fatty acids. For low density lipoprotein (LDL) the equation was delta LDL cholesterol (mmol/l) = 0.033 x (carb----sat) - 0.006 x (carb----mono) - 0.014 x (carb----poly) or, in milligrams per deciliter, 1.28 x (carb----sat) - 0.24 x (carb----mono) - 0.55 x (carb---- poly). The coefficient for polyunsaturates was significantly different from zero, but that for monounsaturates was not. For triglycerides the equation was delta triglycerides (mmol/l) = -0.025 x (carb----sat) - 0.022 x (carb----mono) - 0.028 x (carb---- poly) or, in milligrams per deciliter, -2.22 x (carb----sat) - 1.99 x (carb----mono) - 2.47 x (carb----poly). (ABSTRACT TRUNCATED AT 250 WORDS)
School of Chemical Technology Degree Programme of Chemical Technology Iiro Kiiski DEVELOPMENT OF IMMOBILIZED ENZYME MICROREACTORS FOR CYTOCHROME P450 MEDIATED DRUG METABOLISM Master’s thesis for the degree of Master of Science in Technology

The cytochrome P450 (CYP) enzyme family is responsible for eliminating exogenous chemicals from the human body. As most drugs are metabolized by the same small number of CYP isoenzymes, the risk of drug-drug interactions grows as the use of drugs increases. Consequently, it is important to study the metabolic pathways of a new drug candidate as early in the development pipeline as possible to be able to either modify the molecule or abandon the candidate before continuing to the cost-intensive clinical stage. The general aim of this thesis was to develop new immobilization methods for cytochrome P450 enzymes with a view to implementation of immobilized enzyme microreactors for pharmaceutical applications. Two main approaches for immobilizing CYP-containing human liver microsomes (HLM) were studied: the immobilization of HLM on commercial streptavidin-coated magnetic particles and the immobilization of HLM on in-house fabricated thiol-ene based microfluidic chips. On the basis of literature search, a novel immobilization method utilizing biotin-labelled fusogenic liposomes (FL) was developed. When immobilizing HLM on magnetic particles, the use of FL conferred a 3-fold increase in enzyme activity compared to a previously published method based on physical adsorption on the bead surface. The Km value of the immobilized HLM was determined, and was comparable to the Km of the soluble HLM (2.5 ± 0.49 μM and 0.5-2 μM, respectively), which is essential for the prospective applications in metabolic studies. Enzyme stability remains an issue, as the activity of the immobilized enzyme quickly decreased with consecutive incubations, probably due to both thermal inactivation and leaching. Three different methods for HLM immobilization on thiol-ene micropillar chips were studied. HLM were solubilized on a chip surface functionalized with lipid bilayers and HLM labeled with biotin using FL was bound on streptavidin-functionalized chip surface. For comparison, HLM was also immobilized on chip surface by physical adsorption. The highest initial activities could be achieved by adsorption, but the activity also decreased very rapidly. With the other two methods, initial reactor activities were lower, but the decline of enzyme activity could be slowed down. However, the enzyme activity of all reactors faded within 2 hours. In the future, practical applications based on the developed immobilization approaches could be developed for in vitro studies of human drug metabolism. Another valid application for these reactors is the in situ preparation of analytical standards of CYP metabolites.
Intermediate filament-like proteins in bacteria and a cytoskeletal function in Streptomyces

Actin and tubulin cytoskeletons are conserved and widespread in bacteria. A strikingly intermediate filament (IF)‐like cytoskeleton, composed of crescentin, is also present in Caulobacter crescentus and determines its specific cell shape. However, the broader significance of this finding remained obscure, because crescentin appeared to be unique to Caulobacter. Here we demonstrate that IF‐like function is probably a more widespread phenomenon in bacteria. First, we show that 21 genomes of 26 phylogenetically diverse species encoded uncharacterized proteins with a central segmented coiled coil rod domain, which we regarded as a key structural feature of IF proteins and crescentin. Experimental studies of three in silico predicted candidates from Mycobacterium and other actinomycetes revealed a common IF‐like property to spontaneously assemble into filaments in vitro. Furthermore, the IF‐like protein FilP formed cytoskeletal structures in the model actinomycete Streptomyces coelicolor and was needed for normal growth and morphogenesis. Atomic force microscopy of living cells revealed that the FilP cytoskeleton contributed to mechanical fitness of the hyphae, thus closely resembling the function of metazoan IF. Together, the bioinformatic and experimental data suggest that an IF‐like protein architecture is a versatile design that is generally present in bacteria and utilized to perform diverse cytoskeletal tasks.
What Can An Intermediate Care Unit Do For You?

In a competitive healthcare environment with inflationary pressure on healthcare costs twice that of the national consumer price index, creative cost containment solutions are essential. Likewise, an aging nursing workforce with the average age of a registered nurse (RN) being 46.8 years and with 51% of the workforce older than 50 years mandates strategies to replace experienced professionals leaving the workforce. One strategy used in my institution to address these issues was the initiation of the progressive care unit, which is called an intermediate care unit (IMCU). The IMCU also presented new opportunities and experiences for educating highly skilled critical care nurses. The IMCU is now referred to as the ‘‘farm league’’ or training ground for future intensive care unit (ICU) RNs. The realized economic advantages to using the IMCU for part of the patients’ hospital stay is that it decreased patients’ ICU length of stay (LOS) and decreased throughput from the emergency department by reducing time on ICU diversion.
Engineering bone tissue from human embryonic stem cells

In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the implantation of engineered bone in immunodeficient mice for 8 wk resulted in the maintenance and maturation of bone matrix, without the formation of teratomas that is consistently observed when undifferentiated hESCs are implanted, alone or in bone scaffolds. Our study provides a proof of principle that tissue-engineering protocols can be successfully applied to hESC progenitors to grow bone grafts for use in basic and translational studies.
Effect of Gravity Waves From Small Islands in the Southern Ocean on the Southern Hemisphere Atmospheric Circulation

The effect of small islands in the Southern Ocean on the atmospheric circulation in the Southern Hemisphere is considered with a series of simulations using the NASA Goddard Earth Observing System Chemistry‐Climate Model in which the gravity wave stress generated by these islands is increased to resemble observed values. The enhanced gravity wave drag leads to a 2 K warming of the springtime polar stratosphere, partially ameliorating biases in this region. Resolved wave drag declines in the stratospheric region in which the added orographic gravity waves deposit their momentum, such that changes in gravity waves are partially compensated by changes in resolved waves, though resolved wave drag increases further poleward. The orographic drag from these islands has impacts for surface climate, as biases in tropospheric jet position are also partially ameliorated. These results suggest that these small islands are likely contributing to the missing drag near 60°S in the upper stratosphere evident in many data assimilation products.
Geometric structures for three-dimensional shape representation

Different geometric structures are investigated in the context of discrete surface representation. It is shown that minimal representations (i.e., polyhedra) can be provided by a surface-based method using nearest neighbors structures or by a volume-based method using the Delaunay triangulation. Both approaches are compared with respect to various criteria, such as space requirements, computation time, constraints on the distribution of the points, facilities for further calculations, and agreement with the actual shape of the object.
Toward robot-assisted stapes fenestration with a handheld micromanipulator

Stapedectomy is a delicate surgical procedure of the middle ear to improve hearing. In the middle ear there are anatomical structures that can be damaged during the surgery. Suppression of tremor during the procedure may reduce the likelihood of damage. This paper reports on a study of the feasibility of using Micron, a fully handheld micromanipulator, in stapedectomy. An ergonomic handle, a special tip, and a brace attachment were designed for this purpose and tested in a perforation task through a fixed speculum. Fenestration area and time in forbidden zones were analyzed in a penetration task under two conditions: unaided, and aided by tremor compensation. Preliminary results show a statistically significant improvement in cross-sectional area of fenestration and in time spent in forbidden zones.