Miracle-dz/UniFAR-FTUs huggingface dataset:
Metal search: A computer program that helps design tetrahedral metal‐binding sites

We describe a computer program (Metal Search) that helps design tetrahedrally coordinated metal binding sites in proteins of known structure. The program takes as input the backbone coordinates of a protein and outputs lists of four residues that might form tetrahedral sites if wild‐type amino acids were replaced by cysteine or histidine. The program also outputs the side chain dihedral angles of the amino acids and the coordinates of the predicted metal ion. The only function evaluated by Metal Search is the ability of side chains to meet simple geometric criteria for formation of a tetrahedral site, but these criteria are sufficient to produce a manageably small list that can then be evaluated by other means. The program has been used in the introduction of zinc binding sites in the designed four‐helix bundle protein α 4 and in the B1 domain of streptococcal protein G, and in both cases the tetrahedral coordination of a bound metal ion has been confirmed1 (Klemba, M., Gardner, K. H., Marino, S., Clarke, N. D., and Regan, L., Nature: Structural Biology 2:368–373, 1995). © 1995 Wiley‐Liss, Inc.
Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease

Introduction: Cystic fibrosis (CF) is a multisystem genetic disorder, which usually results in significant respiratory dysfunction. At present there is no cure for CF, but advances in pharmacotherapy have gradually increased the life expectancy of CF patients. As many drugs used in the therapy of CF are delivered by inhalation, the demand for effective and convenient inhalational CF drug formulations will grow as CF patients live longer. Knowledge of the current limitations in inhalational CF drug delivery is critical in identifying new opportunities and designing rational delivery strategies. Areas covered: This review discusses current and emerging therapeutic agents for CF therapy, selected physiological challenges to effective inhalational medication delivery, and various approaches to overcoming these challenges. The reader will find an integrated view of the known inhalational drug delivery challenges and the rationales for recent investigational inhalational drug formulations. Expert opinion: An ideal drug/gene delivery system to CF airways should overcome the tenacious sputum, which presents physical, chemical and biological barriers to effective transport of therapeutic agents to the targets and various cellular challenges.
Thymineless death is associated with loss of essential genetic information from the replication origin

Thymine starvation results in a terminal cellular condition known as thymineless death (TLD), which is the basis of action for several common antibiotics and anticancer drugs. We characterized the onset and progression of TLD in Escherichia coli and found that DNA damage is the only salient property that distinguishes cells irreversibly senesced under thymine starvation from cells reversibly arrested by the nucleotide limitation. The damage is manifested as the relative loss of genetic material spreading outward from the replication origin: the extent of TLD correlates with the progression of damage. The reduced lethality in mutants deficient in the RecFOR/JQ repair pathway also correlates with the extent of damage, which explains most of the observed variance in cell killing. We propose that such spatially localized and persistent DNA damage is the consequence of transcription‐dependent initiation of replication in the thymine‐starved cells and may be the underlying cause of TLD.
Silicon substrate ringing in microfabricated ultrasonic transducers

Experimental and theoretical evidence of silicon substrate ringing in microfabricated ultrasonic transducers is presented. This ringing is clearly observed in immersion transducers with a 650 /spl mu/m thick substrate at 7 MHz and harmonics. An analytical model of the ringing is introduced, and simulations based on the model are shown to agree with experimental observation. Experimental results are further compared to simulations carried out in time-domain, large-scale PZFlex models and qualitative agreement is demonstrated. The insights gained from the simulations and experiments are used to design and fabricate a device whose ringing mode is eliminated with a backing layer.
Dense nuclei segmentation based on graph cut and convexity–concavity analysis

With the rapid advancement of 3D confocal imaging technology, more and more 3D cellular images will be available. However, robust and automatic extraction of nuclei shape may be hindered by a highly cluttered environment, as for example, in fly eye tissues. In this paper, we present a novel and efficient nuclei segmentation algorithm based on the combination of graph cut and convex shape assumption. The main characteristic of the algorithm is that it segments nuclei foreground using a graph‐cut algorithm with our proposed new initialization method and splits overlapping or touching cell nuclei by simple convexity and concavity analysis. Experimental results show that the proposed algorithm can segment complicated nuclei clumps effectively in our fluorescent fruit fly eye images. Evaluation on a public hand‐labelled 2D benchmark demonstrates substantial quantitative improvement over other methods. For example, the proposed method achieves a 3.2 Hausdorff distance decrease and a 1.8 decrease in the merged nuclei error per slice.
A Genetic Analysis of the Drosophila mcm5 Gene Defines a Domain Specifically Required for Meiotic Recombination

Members of the minichromosome maintenance (MCM) family have pivotal roles in many biological processes. Although originally studied for their role in DNA replication, it is becoming increasingly apparent that certain members of this family are multifunctional and also play roles in transcription, cohesion, condensation, and recombination. Here we provide a genetic dissection of the mcm5 gene in Drosophila that demonstrates an unexpected function for this protein. First, we show that homozygotes for a null allele of mcm5 die as third instar larvae, apparently as a result of blocking those replication events that lead to mitotic divisions without impairing endo-reduplication. However, we have also recovered a viable and fertile allele of mcm5 (denoted mcm5A7) that specifically impairs the meiotic recombination process. We demonstrate that the decrease in recombination observed in females homozygous for mcm5A7 is not due to a failure to create or repair meiotically induced double strand breaks (DSBs), but rather to a failure to resolve those DSBs into meiotic crossovers. Consistent with their ability to repair meiotically induced DSBs, flies homozygous for mcm5A7 are fully proficient in somatic DNA repair. These results strengthen the observation that members of the prereplicative complex have multiple functions and provide evidence that mcm5 plays a critical role in the meiotic recombination pathway.
Evidence for a Stimulatory Action of Melanin‐Concentrating Hormone on Luteinising Hormone Release Involving MCH1 and Melanocortin‐5 Receptors

The present series of studies aimed to further our understanding of the role of melanin‐concentrating hormone (MCH) neurones in the central regulation of luteinising hormone (LH) release in the female rat. LH release was stimulated when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial preoptic area (mPOA), but not when injected into the zona incerta (ZI), of oestrogen‐primed ovariectomised rats. In rats that were steroid‐primed to generate a surge‐like release of LH, MCH administration into the ZI blocked this rise in LH release: no such effect occurred when MCH was injected into the rPOA or mPOA. In vitro, MCH stimulated gonadotrophin‐releasing hormone (GnRH) release from hypothalamic explants. Double‐label immunohistochemistry showed GnRH‐immunoreactive neurones in the vicinity of and intermingled with immunoreactive MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1‐R). Previously, we have shown a role for melanocortin‐5 receptors (MC5‐R) in the stimulatory action of MCH, so we next investigated the involvement of both MCH1‐R and/or MC5‐R in mediating the actions of MCH on GnRH and hence LH release. The stimulatory action of MCH in the rPOA was inhibited by administration of antagonists for either MCH1‐R or MC5‐R. However, in the mPOA, the action of MCH was blocked only by the MC5‐R antagonist. LH release was stimulated by an agonist for MC5‐R injected into the rPOA or mPOA; this was blocked by the MC5‐R antagonist but not the MCH1‐R antagonist. These results indicate that both MCH1‐R and MC5‐R are involved in the central control of LH release by MCH.
Phonological neighbourhood effects in French spoken-word recognition

According to activation-based models of spoken-word recognition, words with many and high-frequency phonological neighbours are processed more slowly than words with few and low-frequency phonological neighbours. Although considerable empirical support for inhibitory neighbourhood density effects has accumulated, especially in English, little or nothing is known about the effects of neighbourhood frequency and its interaction with neighbourhood density. In this study we examine both effects first separately and then simultaneously in French lexical decision experiments. As in English, we found that words in dense neighbourhoods are recognized more slowly than words in sparse neighbourhoods. Moreover, we showed that words with higher frequency neighbours are processed more slowly than words with no higher frequency neighbours, but only for words occurring in sparse neighbourhoods. Implications of these results for spoken-word recognition models are discussed.
Sleep Duration and Child Well-Being: A Nonlinear Association

Although numerous studies among adults have shown a U-shaped association between sleep duration and health outcomes, fewer studies have investigated the theory that children also have an optimal sleep duration range, with both lower and upper limits. We evaluated whether children’s sleep duration at ages 5 and 9 has a U-shaped association with both behavioral problems and physical health at age 9. We analyzed data from 1,965 participants in a longitudinal birth cohort, the Fragile Families and Child Wellbeing Study. This sample of children was 52% male and approximately 22% non-Hispanic White, 52% non-Hispanic Black, 23% Hispanic, and 3% some other race/ethnicity. The child’s primary caregiver reported the predictor of interest: sleep duration at age 5 and age 9. Both children and primary caregivers reported on outcomes of the child’s behavior problems (internalizing and externalizing) and overall physical health. We found that the association between children’s sleep duration and well-being was typically nonlinear and U-shaped. Adjusting for their sleep duration at age 5, children who sleep either too much or too little at age 9 had higher levels of behavior problems and scored lower on a global measure of physical health. These nonlinear patterns were similar whether children or primary caregivers reported child outcomes, with the exception that there was a linear and increasing association of longer sleep duration and caregiver-rated child health. This study highlights that both short and long sleep duration may be risk factors for adverse behavioral and health outcomes in school-age children.
Mobile Phones Security Using Biometrics

Stealing cell phone has become the eye catching business for culprits. There should be a reliable method of protecting the instrument from burglars. Our paper proposes a new innovative, reliable, fool proof security measure for cell phones using voice recognition and fingerprint recognition. Our proposal demands neither external hardware nor extra cost. The above methods possess no hardship for the user unlike the present security systems. This method can be adopted universally in all models of Cell phones for protection.
Glia Tell Neurons to Build Synapses

Although glia account for 90% of the cells in the adult human brain, they9ve been written off as simple scaffolding that supports neurons, as sources of nutrition, or as a waste-disposal mechanism for sopping up extra ions and neurotransmitter molecules. But a new study on page 657 shows that glia play a more important role in neuron-to-neuron communication: They tell neurons to start talking to one another.
The relationship of laser-Doppler skin blood flow measurements to the cutaneous microvascular anatomy.

The hairless plantar paw surface of the rat shows high skin blood flow with a substantial response to thermal stimulation. This contrasts with hair-covered areas such as the back, where there is much lower basal flow and thermal response. These properties are similar to the differences seen in humans between skin sites which have a high density of arterioles and venules (AV areas) and sites with predominantly nutritive (NUTR) capillary perfusion. However, there has been no previous study of the microvascular anatomy of rodent skin. We used NIH Image, a quantitative imaging program, to count the capillaries, arterioles, and venules in the skin of the plantar paw surface and the back of 14 Wistar-Kyoto rats. We also used laser-Doppler techniques to determine skin blood flow at these sites. We found significantly more vessels per unit area at the paw. There were twice as many capillaries in the paw (19.6 +/- 2.4 per mm2) compared to the back (9 +/- 1.5 per mm2) (P < 0.001). Similarly, there were three times as many venules (11.8 +/- 1.2 per mm2 vs 3. 48 +/- 0.45 per mm2; P < 0.001). The largest difference was in the number of arterioles (7.76 +/- 0.74 per mm2 vs 0.79 +/- 0.13 per mm2 at the back; P < 0.001). The greater microvascular density at the paw was reflected in a threefold higher basal blood flow (6.6 +/- 0. 44 ml/min/100 g) compared to that in the back (1.99 +/- 0.07 ml/min/100 g) (P < 0.001). Microvascular volume at the back was 0.14 +/- 0.01 x 10(6) RBC/ml in the basal state compared to 0.31 +/- 0.01 x 10(6) RBC/ml at the paw. Thus, the increased number of vessels at the paw resulted in a twofold increase in microvascular volume. The plantar paw surface has considerably more vessels than the back. As might be expected, there is a higher proportion of arterioles and venules compared to capillaries at the paw than at the back. Thus, the plantar paw surface is an AV site compared to the back, which is a NUTR site. Although our prior studies have largely assumed that we could use the paw and back as contrast sites comparable to AV and NUTR sites in humans, we have now for the first time conclusively established this fact. The increased microvascular density at the paw results in higher skin blood flow at this site.
Correlations Among Hospital Quality Measures: What “Hospital Compare” Data Tell Us

A number of quality rating systems to rank health care providers have been developed over the years with the intention of helping consumers make informed health care purchasing decisions. Many use sets of individual quality measures to calculate a global rating. The utility of a global rating for consumer choice hinges on the relationships among included measures and the extent to which they jointly reflect an underlying dimension of quality. Publicly reported data on 4 quality domains—complication, mortality, readmission, and patient safety—from Centers for Medicare & Medicaid Services’ Hospital Compare website were used to examine correlations among individual measures within each measure group (within-group correlations) and correlations between pairs of measures across different measure groups (between-group correlations). Modest within-group correlations were found in only 2 domains (mortality and readmission), and there were no meaningful between-group associations. These findings raise questions about whether consumers can reliably depend on global quality ratings to make informed decisions.
Physical activity and prevalence and incidence of mental disorders in adolescents and young adults

ABSTRACT Background Although positive effects of physical activity on mental health indicators have been reported, the relationship between physical activity and the development of specific mental disorders is unclear. Method A cross-sectional (12-month) and prospective-longitudinal epidemiological study over 4 years in a community cohort of 2548 individuals, aged 14–24 years at outset of the study. Physical activity and mental disorders were assessed by the DSM-IV Composite International Diagnostic Interview (CIDI) with an embedded physical activity module. Multiple logistic regression analyses controlling for age, gender and educational status were used to determine the cross-sectional and prospective associations of mental disorders and physical activity. Results Cross-sectionally, regular physical activity was associated with a decreased prevalence of any and co-morbid mental disorder, due to lower rates of substance use disorders, anxiety disorders and dysthymia. Prospectively, subjects with regular physical activity had a substantially lower overall incidence of any and co-morbid mental disorder, and also a lower incidence of anxiety, somatoform and dysthymic disorder. By contrast, the incidence of bipolar disorder was increased among those with regular physical activity at baseline. In terms of the population attributable fraction (PAF), the potential for preventive effects of physical activity was considerably higher for men than for women. Conclusions Regular physical activity is associated with a substantially reduced risk for some, but not all, mental disorders and also seems to reduce the degree of co-morbidity. Further examination of the evidently complex mechanisms and pathways underlying these associations might reveal promising new research targets and procedures for targeted prevention.
Nanoparticles and microparticles as vaccine-delivery systems

Vaccine-delivery systems are generally particulate (e.g., emulsions, microparticles and liposomes) and have comparable dimensions to the pathogens, which the immune system evolved to combat. Increasingly more sophisticated delivery systems are being developed in which immunostimulatory adjuvants may be incorporated with the antigen. The rationale for this approach is to ensure that both the antigen and adjuvant are delivered into the same population of antigen-presenting cells. Enhancement of adjuvant activity through the use of micro- and nanoparticulate delivery systems is particularly exciting, as synergistic effects are often seen resulting in immune responses stronger than those elicited by the adjuvant or delivery system alone. Micro- and nanoparticles also offer the possibility of enhancement of their uptake by appropriate cells through manipulation of their surface properties. The next important step in the development of many of the experimental microparticle- and nanoparticle-based technologies will be evaluation of effectiveness in human trials.
Relational Risk Mitigation: The Relationship Approach to Mitigating Risks  in Business Process Outsourcing

Managing risks in outsourcing has been widely researched but is still not fully understood by either academics or practitioners. Recent research on IS outsourcing relationships has addressed the relationship between formal and relational governance, but has not revealed how individual relational factors affect outsourcing risk. Surveying 335 business process outsourcing initiatives, our data supports the separation of an operational, performance-driven approach and an embedded, financial-driven one in order to mitigate risks through relational factors. Our findings show that relationship processes, particularly conflict resolution, are the most important for controlling performance risk, while inherent relationship attributes, such as trust, are the most suitable and promising for managing financial risk. Overall, our findings recommend a more integrated, specific study of contractual and relational governance mechanisms on individual risk and benefit measures.
LinoSPAD: a time-resolved 256×1 CMOS SPAD line sensor system featuring 64 FPGA-based TDC channels running at up to 8.5 giga-events per second

LinoSPAD is a reconfigurable camera sensor with a 256×1 CMOS SPAD (single-photon avalanche diode) pixel array connected to a low cost Xilinx Spartan 6 FPGA. The LinoSPAD sensor’s line of pixels has a pitch of 24 μm and 40% fill factor. The FPGA implements an array of 64 TDCs and histogram engines capable of processing up to 8.5 giga-photons per second. The LinoSPAD sensor measures 1.68 mm×6.8 mm and each pixel has a direct digital output to connect to the FPGA. The chip is bonded on a carrier PCB to connect to the FPGA motherboard. 64 carry chain based TDCs sampled at 400 MHz can generate a timestamp every 7.5 ns with a mean time resolution below 25 ps per code. The 64 histogram engines provide time-of-arrival histograms covering up to 50 ns. An alternative mode allows the readout of 28 bit timestamps which have a range of up to 4.5 ms. Since the FPGA TDCs have considerable non-linearity we implemented a correction module capable of increasing histogram linearity at real-time. The TDC array is interfaced to a computer using a super-speed USB3 link to transfer over 150k histograms per second for the 12.5 ns reference period used in our characterization. After characterization and subsequent programming of the post-processing we measure an instrument response histogram shorter than 100 ps FWHM using a strong laser pulse with 50 ps FWHM. A timing resolution that when combined with the high fill factor makes the sensor well suited for a wide variety of applications from fluorescence lifetime microscopy over Raman spectroscopy to 3D time-of-flight.
Role of proP and proU in Betaine Uptake by Yersinia enterocolitica under Cold and Osmotic Stress Conditions

ABSTRACT Yersinia enterocolitica is a food-borne pathogen with the ability to grow at cold temperatures and tolerate high osmolarity. The bacterium tolerates osmotic stress by intracellular accumulation of osmolytes, such as betaine. The proP gene and proU operon of Y. enterocolitica were sequenced, and single (ProP− ProU+ and ProP+ ProU−) and double (ProP− ProU−) mutants were generated. Upon exposure to osmotic or chill stress, the single and double mutants demonstrated a reduction in betaine uptake compared to that in the wild type, suggesting that proP and proU play a role in betaine uptake during osmotic and chill stress responses of Y. enterocolitica.
Modeling bone fixation implants with absorbable polymers using 3-D printing

The purpose of this project is to fabricate a material, using a novel combination of biocompatible and biodegradable materials that is 3-D printed into an internal fixation screw model. In vitro degradation testing, as well as various mechanical testing specified by ASTM Standards, were used to ensure that the material has excellent mechanical properties that can withstand heavy load-bearing, and chemical properties that allow the material to degrade at a rate paralleled to the rate at which the surrounding bone and tissue heals.