Miracle-dz/UniFAR-FTUs huggingface dataset:
State-of-the-Art Automated Patch Clamp Devices: Heat Activation, Action Potentials, and High Throughput in Ion Channel Screening

Ion channels are essential in a wide range of cellular functions and their malfunction underlies many disease states making them important targets in drug discovery. The availability of standardized cell lines expressing ion channels of interest lead to the development of diverse automated patch clamp (APC) systems with high-throughput capabilities. These systems are now available for drug screening, but there are limitations in the application range. However, further development of existing devices and introduction of new systems widen the range of possible experiments and increase throughput. The addition of well controlled and fast solution exchange, temperature control and the availability of the current clamp mode are required to analyze standard cell lines and excitable cells such as stem cell-derived cardiomyocytes in a more physiologically relevant environment. Here we describe two systems with different areas of applications that meet the needs of drug discovery researchers and basic researchers alike. The here utilized medium throughput APC device is a planar patch clamp system capable of recording up to eight cells simultaneously. Features such as temperature control and recordings in the current clamp mode are described here. Standard cell lines and excitable cells such as stem cell-derived cardiomyocytes have been used in the voltage clamp and current clamp modes with the view to finding new drug candidates and safety testing methods in a more physiologically relevant environment. The high-throughput system used here is a planar patch clamp screening platform capable of recording from 96 cells in parallel and offers a throughput of 5000 data points per day. Full dose response curves can be acquired from individual cells reducing the cost per data point. The data provided reveals the suitability and relevance of both APC platforms for drug discovery, ion channel research, and safety testing.
Hsp70 Knockdown by siRNA Decreased Collagen Production in Keloid Fibroblasts

Purpose There are currently no consistently effective treatments for the excessive collagen produced by keloid fibroblasts. Previously, we reported that heat shock protein 70 (Hsp70) is up-regulated in keloid fibroblasts and keloid tissue. We, therefore, investigated whether Hsp70 is related to excessive collagen production in keloid fibroblasts. Materials and Methods We inhibited Hsp70 in keloid fibroblasts by RNA interference and examined the resulting collagen expression. Thus, we selected small interfering RNAs (siRNAs) specific for human Hsp70, transfected them into keloid fibroblasts, and evaluated the resulting phenotypes and protein production using real-time polymerase chain reaction (PCR), Western blot, and a collagen assay. Results The siRNAs dramatically suppressed Hsp70 mRNA expression, resulting in a decrease in collagen production in the keloid fibroblasts compared with controls. The siRNAs did not influence the viability of the keloid fibroblasts. Conclusion Hsp70 overexpression likely plays an important role in the excessive collagen production by keloid fibroblasts. RNA interference has therapeutic potential for the treatment of keloids.
Acetate and Formate Stress: Opposite Responses in the Proteome of Escherichia coli

ABSTRACT Acetate and formate are major fermentation products ofEscherichia coli. Below pH 7, the balance shifts to lactate; an oversupply of acetate or formate retards growth. E. coli W3110 was grown with aeration in potassium-modified Luria broth buffered at pH 6.7 in the presence or absence of added acetate or formate, and the protein profiles were compared by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Acetate increased the steady-state expression levels of 37 proteins, including periplasmic transporters for amino acids and peptides (ArtI, FliY, OppA, and ProX), metabolic enzymes (YfiD and GatY), the RpoS growth phase regulon, and the autoinducer synthesis protein LuxS. Acetate repressed 17 proteins, among them phosphotransferase (Pta). An ackA-pta deletion, which nearly eliminates interconversion between acetate and acetyl-coenzyme A (acetyl-CoA), led to elevated basal levels of 16 of the acetate-inducible proteins, including the RpoS regulon. Consistent with RpoS activation, the ackA-pta strain also showed constitutive extreme-acid resistance. Formate, however, repressed 10 of the acetate-inducible proteins, including the RpoS regulon. Ten of the proteins with elevated basal levels in the ackA-ptastrain were repressed by growth of the mutant with formate; thus, the formate response took precedence over the loss of theackA-pta pathway. The similar effects of exogenous acetate and the ackA-pta deletion, and the opposite effect of formate, could have several causes; one possibility is that the excess buildup of acetyl-CoA upregulates stress proteins but excess formate depletes acetyl-CoA and downregulates these proteins.
The Transformative Nature of Telework: A Review of the Literature

Information and communication technologies (ICT) have had, and continue to have, a profound impact on the way work is organized, undertaken and managed by organizations and their employees. Telework, in particular, allows employees to work anywhere and anytime. These developments are not simply extending earlier temporal and spatial boundaries of work; they are profoundly changing the nature of work itself. To gain a better understanding of the changing nature of work and the implications for organizations and employees, we conducted a literature review that identified in total 24 different advantages and challenges of telework. We also show that there are inherent contradictions among these advantages and challenges, thus outlining interesting questions and opportunities for future research and alerting practitioners to possible dilemmas arising from telework arrangements.
Dietary preferences in early lactation cows as affected by primary tastes and some common feed flavors.

A sequential elimination trial was conducted to test the effects of primary tastes on the preference ranking of TMR diets by six multiparous Holstein cows from 8 to 21 DIM. Four additives and a control were examined; the most preferred (highest total intake) was eliminated after segments of 5, 4, 3, and then 2 d. Diets tasting sweet (sucrose, 1.5% of dietary DM), sour (HCl, 1.25%), bitter (urea, 1%), and salty (NaCl, 4%) were tested. Four of the cows most preferred the sweet diet, and DMI of that diet averaged 12.8% more than for the control, which was next preferred. The probability of a diet being chosen first when all diets were presented together was sucrose, . 59; control, . 36; urea, . 04; NaCl, . 01; and HCl, . 003. Another experiment used the same procedure; however, the additives tested were anise, monosodium glutamate, dehydrated alfalfa meal flavor, and molasses flavor (1.48 g of flavor/kg of DM). Control and monosodium glutamate ranked first equally. The probability of choosing each flavor first in this set was . 5 for the control and monosodium glutamate diets and < . 01 for molasses, alfalfa, and anise. Rankings were not significantly affected by variation among cows in either experiment. Of the additives tested, only sucrose seemed to have the potential to increase intake.
Mutational Analysis of Sclerostin Shows Importance of the Flexible Loop and the Cystine-Knot for Wnt-Signaling Inhibition

The cystine-knot containing protein Sclerostin is an important negative regulator of bone growth and therefore represents a promising therapeutic target. It exerts its biological task by inhibiting the Wnt (wingless and int1) signaling pathway, which participates in bone formation by promoting the differentiation of mesenchymal stem cells to osteoblasts. The core structure of Sclerostin consists of three loops with the first and third loop (Finger 1 and Finger 2) forming a structured β-sheet and the second loop being unstructured and highly flexible. Biochemical data showed that the flexible loop is important for binding of Sclerostin to Wnt co-receptors of the low-density lipoprotein related-protein family (LRP), by interacting with the Wnt co-receptors LRP5 or -6 it inhibits Wnt signaling. To further examine the structural requirements for Wnt inhibition, we performed an extensive mutational study within all three loops of the Sclerostin core domain involving single and multiple mutations as well as truncation of important regions. By this approach we could confirm the importance of the second loop and especially of amino acids Asn92 and Ile94 for binding to LRP6. Based on a Sclerostin variant found in a Turkish family suffering from Sclerosteosis we generated a Sclerostin mutant with cysteines 84 and 142 exchanged thereby removing the third disulfide bond of the cystine-knot. This mutant binds to LRP6 with reduced binding affinity and also exhibits a strongly reduced inhibitory activity against Wnt1 thereby showing that also elements outside the flexible loop are important for inhibition of Wnt by Sclerostin. Additionally, we examined the effect of the mutations on the inhibition of two different Wnt proteins, Wnt3a and Wnt1. We could detect clear differences in the inhibition of these proteins, suggesting that the mechanism by which Sclerostin antagonizes Wnt1 and Wnt3a is fundamentally different.
New Cyclic Cystine Bridged Peptides from the Sponge Suberites waedoensis

Two new peptides, chujamides A (1) and B (2), were isolated from the marine sponge Suberites waedoensis, which was collected from Korean waters. Based upon the results of the combined spectroscopic analyses, the structures of these compounds were determined to be proline-riched and cyclic cystine bridged dodeca- and undecapeptides. The absolute configurations of all amino acid residues were determined to be l by advanced Marfey’s analysis. The new compounds exhibited weak cytotoxicities against A549 and K562 cell-lines, and compound 2 also demonstrated moderate inhibitory activity against Na+/K+-ATPase.
List of contributors.

Data expiration is an essential component of data warehousing solutions: whenever large amounts of data are repeatedly collected over a period of time, it is essential to have a clear approach to identifying parts of the data nolonger needed and a policy that allows disposing and/or archiving these parts of the data. Such policies are necessary even if adding storage to accommodate an ever-growing collection of data were possible, since the growing amount of data needs to be examined during querying and in turn leads to deterioration of query performance over time. The approaches to data expiration range from ad-hoc administrative policies or regulations to sophisticated data analysis-based techniques. The approaches have, however, one thing in common: intuitively, they try to identify the parts of the data collection that are not needed in the future. The key to deciding if a piece of information will be needed in the future lies in identifying what queries can be asked over the collection of data and how the collection can evolve from its current state. The various techniques proposed in the literature differ in the way they identify parts of data no longer needed. This chapter formalizes the notion of data expiration in terms of how the data is used to answer queries. We survey existing approaches to the problem in a unified framework and discuss their features and limits, and the limits of data expiration based techniques in general. The particular focus of the chapter is on comparing the space performance of various data expiration methods.
The risks associated with pregnancy in women aged 35 years or older.

The obstetric risks of adverse outcome during pregnancy in women aged > or =35 years were quantified using a retrospective analysis of data from 385 120 singleton pregnancies in the North West Thames Region, UK, between 1988 and 1997. A comparison of pregnancy outcome was made on the basis of maternal age at delivery: 18-34 years (n = 336 462), 35-40 years (n = 41 327) and women aged > 40 years (n = 7331). Women aged <18 years (n = 5246) were excluded from the study. Data are presented as percentages of 18-34 year old women, 35-40 year old and > 40 year old women, with adjusted odds ratios (OR) according to age group. Pregnant women aged 35-40 years were at increased risk of: gestational diabetes, OR = 2.63 [99% confidence interval (CI) 2.40-2.89]; placenta praevia = 1.93 (1.58-2.35); breech presentation = 1.37 (1.28-1.47); operative vaginal delivery = 1.5 (1.43-1.57); elective Caesarean section = 1.77 (1.68-1.87); emergency Caesarean section = 1.59 (1.52-1.67); postpartum haemorrhage = 1.14 (1.09-1.19); delivery before 32 weeks gestation = 1.41 (1.24-1.61); birthweight below the 5th centile = 1.28 (1.20-1. 36); and stillbirth = 1.41 (1.17-1.70). Women aged >40 years had higher OR for the same risks. Pregnant women aged >/=35 years are at increased risk of complications in pregnancy compared with younger women.
Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism.

PURPOSE We sought to determine whether venous thromboembolism in cancer patients is associated with aberrant plasma levels of hemostatic and angiogenic factors. PATIENTS AND METHODS Peripheral blood was collected before anticoagulant therapy from cancer patients with acute deep venous thrombosis (DVT; DVT + cancer group, n = 32), those without DVT (cancer control group, n = 36), and patients with acute DVT but no cancer (DVT control group, n = 58). Plasma assays of activation and inhibition of coagulation and fibrinolysis, as well as angiogenesis activation, were then performed. RESULTS Median levels of thrombin-antithrombin complex, prothrombin fragments 1 + 2, and von Willebrand factor antigen were significantly greater in the DVT + cancer group than in the cancer control and DVT control groups (17.8 ng/mL v 4.6 ng/mL and 9.8 ng/mL, P =.0001 and P =.003, respectively; 3.65 nmol/L v 1.60 nmol/L and 2.71 nmol/L, P <.0001 and P =.011, respectively; and 4.04 U/mL v 2.26 U/mL and 2.06 U/mL, P <.0001, respectively). Median levels of tissue-type plasminogen activator were also significantly higher, while protein C activity was lower in the DVT + cancer group than in the DVT control group (14.6 ng/mL v 9.50 ng/mL, respectively, P =.0005; 0.89 U/mL v 1.11 U/mL, respectively, P =.0008). CONCLUSION These data not only support prior observations of coagulation activation in patients with malignancy, but also provide new evidence for enhanced coagulation activation in the setting of acute venous thromboembolism in cancer. Future prospective studies are warranted to determine whether these and other potential markers of hypercoagulability may help to identify cancer patients at highest risk for venous thromboembolism.
A Cooperative Parallel Search-Based Software Engineering Approach for Code-Smells Detection

We propose in this paper to consider code-smells detection as a distributed optimization problem. The idea is that different methods are combined in parallel during the optimization process to find a consensus regarding the detection of code-smells. To this end, we used Parallel Evolutionary algorithms (P-EA) where many evolutionary algorithms with different adaptations (fitness functions, solution representations, and change operators) are executed, in a parallel cooperative manner, to solve a common goal which is the detection of code-smells. An empirical evaluation to compare the implementation of our cooperative P-EA approach with random search, two single population-based approaches and two code-smells detection techniques that are not based on meta-heuristics search. The statistical analysis of the obtained results provides evidence to support the claim that cooperative P-EA is more efficient and effective than state of the art detection approaches based on a benchmark of nine large open source systems where more than 85 percent of precision and recall scores are obtained on a variety of eight different types of code-smells.
Development of a Marine Mammal Marker (MAMMARK) for In-Situ Environmental Monitoring

Current understanding of the behavior of marine mammals (or pinnipeds) is quite limited by the observation technology used. Surface tracking using geolocation and Service Argos tags have shown that these mammals range much farther than previously thought. Relatively simple time/depth recorders (TDR’s) have shown that they dive to depths of over 1000 meters deep and for durations of over one hour. In order to further the understanding of these aquatic creatures, a smaller and more capable tag was developed that can be deployed for longer durations and with more sensing capabilities. The tag, called the MAMMARK, which measures approximately 2.5 x 4 cm. , has a low-power microprocessor, and a set of sensors that can be multiplexed through a high resolution analog-to-digital converter. The sensing suite consists of temperature, depth, speed, salinity, three axes of magnetic field, three axes of acceleration, and GPS. GPS measurements are, of course, only available at the surface, however, the GPS receiver is kept in a hot-start mode such that it can reacquire the satellite signals in less than 10 seconds after returning to the surface. The three-axis magnetometer and three-axis accelerometer are used to construct the attitude of the creature (or three-dimensional orientation). Integrating this attitude with water speed, and an initial estimate of position from GPS, a full underwater trajectory can be reconstructed (using error correction from the return surface position and depth measurement to improve the accuracy and estimate the ocean currents). The tag is equipped with an RF beeper for ease of recovery, and dumps its data to a high capacity external flash card. As currently configured, it can withstand extreme pressures and record data for up to one year.
A multicenter evaluation of the efficacy and duration of action of alcaftadine 0.25% and olopatadine 0.2% in the conjunctival allergen challenge model

Background The purpose of this study was to evaluate the efficacy and duration of action of once-daily dosing with alcaftadine 0.25% ophthalmic solution and olopatadine 0.2% ophthalmic solution as compared with placebo in the prevention of ocular itching, and to directly compare the efficacy of alcaftadine 0.25% with olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis using the conjunctival allergen challenge model. Methods Subjects with allergic conjunctivitis (n = 127) were enrolled in a multicenter, double-masked, randomized, active-controlled and placebo-controlled clinical trial. Using the conjunctival allergen challenge model, this study was conducted over the course of approximately 5 weeks. Subjects were randomized into one of three treatment arms: alcaftadine 0.25% ophthalmic solution, olopatadine 0.2% ophthalmic solution, or placebo. Study medications were administered twice over the course of the trial. The primary efficacy measure for the study was ocular itching evaluated by the subject at 3, 5, and 7 minutes post challenge. Secondary endpoints, measured at 7, 15, and 20 minutes post challenge, included conjunctival, ciliary, and episcleral redness, lid swelling, chemosis, and tearing. Duration of action was measured at 16 and 24 hours post-instillation of the study medication at visits 3 and 4, respectively. Results For the primary measure of ocular itching, both actives, alcaftadine 0.25% and olopatadine 0.2%, were statistically superior to placebo at all three measured time points for both the 16-hour and 24-hour measures (P < 0.0001). Eyes treated with alcaftadine 0.25% had numerically lower mean ocular itching scores than eyes treated with olopatadine 0.2% at every time point, and this difference was statistically significant at the 3-minute time point 16 hours post instillation (P = 0.026). Eyes treated with alcaftadine 0.25% and with olopatadine 0.2% displayed significantly less lid swelling relative to placebo at every time point for the 16-hour and 24-hour post-instillation visits (P < 0.005). Alcaftadine 0.25% was the only active treatment that provided statistically significant relief of chemosis at every time point of the 24-hour post-instillation visit. Conclusion Both the alcaftadine 0.25% and olopatadine 0.2% ophthalmic solutions provided highly effective relief of ocular itching at both 16 and 24 hours post-instillation. Treatment differences between the actives were most pronounced at the earliest time point (3 minutes post-challenge) following conjunctival allergen challenge (16 hours), when alcaftadine 0.25% ophthalmic solution was statistically superior to olopatadine 0.2% ophthalmic solution. Alcaftadine 0.25% was the only treatment to provide significant relief from chemosis at both 16 and 24 hours post-instillation. Both active treatments and placebo were generally safe and well tolerated.
Network Coding with a Cost Criterion

We consider applying network coding in settings where there is a cost associated with network use. We show that, while minimum-cost multicast problems without network coding are very difficult except in the special cases of unicast and broadcast, finding minimum-cost subgraphs for single multicast connections with network coding can be posed as a linear optimization problem. In particular, we apply our approach to the problem of minimum-energy multicast in wireless networks with omnidirectional antennas and show that it can be handled by a linear optimization problem when network coding is used. For the case of multiple multicast connections, we give a partial solution: We specify a linear optimization problem that yields a solution of no greater cost than any solution without network coding and that we suspect can potentially be substantially better.
Covarying collexemes

Abstract Adopting the perspective of construction grammar and related frameworks, this paper introduces a corpus-based method for investigating correlations between lexical items occurring in two different slots of a grammatical construction. On the basis of three case studies dealing with the into -causative, English possessive constructions, and the way-construction, we show that such correlations are determined by semantic coherence. We identify three kinds of coherence: one based on frame-semantic knowledge, one based on semantic prototypes, and one based on image schemas. We conclude by proposing a method that can potentially enhance the precision of our results and that allows us to identify ever-finer contrasts by adopting a multidimensional perspective towards co-occurrence patterns.
A Novel Type of Chloroplast Stromal Hexokinase Is the Major Glucose-phosphorylating Enzyme in the Moss Physcomitrella patens*

Hexokinase catalyzes the first step in the metabolism of glucose but has also been proposed to be involved in sugar sensing and signaling both in yeast and in plants. We have cloned a hexokinase gene, PpHXK1, in the moss Physcomitrella patens where gene function can be studied directly by gene targeting. PpHxk1 is a novel type of chloroplast stromal hexokinase that differs from previously studied membrane-bound plant hexokinases. Enzyme assays on a knock-out mutant revealed that PpHxk1 is the major glucose-phosphorylating enzyme in Physcomitrella, accounting for 80% of the total activity in protonemal tissue. The mutant is deficient in the response to glucose, which in wild type moss induces the formation of caulonemal filaments that protrude from the edge of the colony. Growth on glucose in the dark is strongly reduced in the mutant. Sequence data suggest that most plants including Physcomitrella and Arabidopsis have both chloroplast-imported hexokinases similar to PpHxk1 and traditional membrane-bound hexokinases. We propose that the two types of plant hexokinases have distinct physiological roles.