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PIPETTE TO PALLET: A JOURNEY FROM ACADEMIA TO ENTREPRENEURSHIP
Get PDFPhilosophers, politicians, and scientists alike have long understood that knowledge and technological advancement play a significant, dynamic role in the wealth of nations. Subsequently, a thirst for innovation is at the forefront of many political, societal, and philosophical agendas. Academic research has been identified as a primary source of innovation1–6 and prodigious funding has supported this commonly held belief. One of the most direct methods for translating academic innovation into economic growth is by commercializing academic research. 1–3 This process, known as technology transfer and commercialization, has gained traction over recent years by researchers, institutions, and entrepreneurs due to increased exposure of academic commercialization successes. One study found that over a ten year period, the number of annual executed licenses and number of startups launched has doubled. 1 Despite this growth in research licenses and academic grounded startups, there are still two hurdles that inhibit many would-be scientist-entrepreneurs from making the jump from the lab bench to the board room: a lack of resources, and a lack of knowledge of the process to make the jump. Developing methodologies that support scientist entrepreneurs and demolishing the stigma of technology transfer that still inhabits some pockets of academia is critical for the efficient dissemination of knowledge from the laboratory to society. This paper contributes to existing literature on technology transfer by distilling pertinent information regarding the benefits of technology transfer and highlighting personal experiences to create a framework in which to approach technology commercialization. This framework, presented as roadmap to commercialization could be employed by academics as they embark on their own technology commercialization endeavor. Additionally, the framework could be useful for academic institutions interested in increasing their commercialization output by streamlining their technology commercialization process
How to Save the World in 20 Minutes or Less
Get PDFABSTRACT
When composing a piece with extensive instrument requirements, excessive difficulty or length, or combinations of these factors, obtaining a recording of substantial quality is a challenge for many composers. A composer with a solid understanding of audio production techniques and a network of performers can produce a convincing recording without having to worry about the logistics or cost of assembling and recording a large ensemble.
How to Save the World in 20 Minutes or Less is scored to unconventional media - using footage of a video game being completed in record time. Composed for 23-piece large jazz ensemble, the work utilizes compositional techniques from a number of different musical genres - from funk and swing to fusion and modern jazz styles. A recording of the piece was produced by mixing recordings from 11 different musicians recording independently to simulate a live ensemble
A COMPARISON OF BEHAVIORAL CHARACTERISTICS, CARCASS BY-PRODUCT YIELDS AND CARCASS GRADING PERFORMANCE OF IMPLANTED AND NON-IMPLANTED CROSSBRED STEERS ACROSS VARIOUS MARKETING ENDPOINTS IN A 378-D FEEDING DURATION.
No full textExperiment 1 consisted of the evaluation of behavioral characteristics of growing steers in response to implant, feeding duration, diurnal rhythm and dietary roughage via monitoring of activity and rumination time. Charolais × Angus steers (n = 80) were randomized to harvest (0, 42, 84, 126, 168, 210, 252, 294, 336 or 378 DOF) and implant treatment (REV: Revalor-XS; on d-0 and d-190 or CON: no implant). Activity and rumination were objectively monitored via accelerometers attached to the left ear. Steers consumed 3 rations throughout the study: starter (38.5% roughage), intermediate (23% roughage), and finishing (8.5% roughage). Data was logged in 2-h increments from 77 steers across 361 d and analyzed using mixed models for repeated measures of activity and rumination. Rumination and activity varied (P < 0.01) within 24-h, exhibiting bimodal patterns; rumination peaked at 0600 and 1400 h and troughed at 1000 and 1800 h. Activity peaked at 0800 and 1800 h and troughed at 0400, 1200-1400, and 2200 h. Steers administered REV ruminated less (364 vs 380 min/d; P = 0.04) than CON, however, 24-h activity was similar (P = 0.29) between treatments. Treatment × roughage interactions (P < 0.01) occurred for rumination and activity. Rumination tended to differ (P = 0.06) between CON consuming 38.5% and 23% roughage, however, CON steers ruminated (P < 0.01) more than REV when consuming 8.5% roughage. Implanted and non-implanted steers ruminated less (P < 0.01) as roughage inclusion decreased from 38.5% and 23% to 8.5% (457 and 439 vs 317 min/d) in the finishing ration. Activity was highest for steers consuming 38.5% roughage and was similar (P > 0.05) among treatments, however, activity decreased (P < 0.01) upon transition to 23 and 8.5% roughage. Activity peaks and troughs can be attributed to processing days and weather events. Implanted steers consuming 8.5% roughage were more active (342 vs. 337 and 333 min/d; P < 0.01) than steers of both treatments consuming 23% roughage. In conclusion, rumination and activity are responsive to hour of day, dietary roughage and growth-promoting implants.
Experiment 2 was conducted to investigate the development of non-carcass components of implanted or non-implanted Charolais × Angus steers across various marketing endpoints. Growth promoting implants containing trenbolone acetate (TBA) and estradiol-17β (E2) are administered to improve rate of gain and feed efficiency of beef cattle. Non-carcass components are by-products of the beef industry that are of metabolic, economic and societal importance. A serial-harvest was conducted to investigate growth of non-carcass components of implanted or non-implanted Charolais × Angus steers. Steers (n = 80) were paired and applied to a 2 x 10 factorial treatment structure in a balanced incomplete block design. Steers were randomly appointed to harvest date (0, 42, 84, 126, 168, 210, 252, 294, 336 or 378 days on feed; DOF) and implant treatment; REV received a Revalor-XS (200mg TBA/40mg E2) on d0 and d190, whereas CON received no implant. Pair was block, steer was experimental unit and data were analyzed using mixed models. Four REV/CON pairs were harvested upon each feeding endpoint. Non-carcass components were removed and weighed; gastrointestinal tracts (GIT) were disassembled, weighed, cleaned, and re-weighed. Empty body weight (EBW), and hot carcass weight (HCW) were 6% greater (P < 0.01) in REV steers vs. CON. No treatment effects (P ≥ 0.12) were observed for fill or dressed carcass yield (DY), however, EBW, HCW and DY increased (P ≤ 0.01) and percentage fill decreased as an effect of DOF. Absolute fill weight did not change across DOF (P ≥ 0.82). Implanted steers had greater (P ≤ 0.05) absolute mass of blood, head, hide, oxtail, liver, spleen, bladder, heart, reticulum, omasum, stomach, small intestine, intestines, GIT, total splanchnic tissue and total offal. Implanted steers also had smaller (P ≤ 0.05) absolute mass of thymus glands and kidney-pelvic-heart fat (KPH) than non-implanted steers. Absolute mass of the spinal cord, small intestine and intestines varied across DOF but did not exhibit linear or quadratic growth, whereas all other tissue weights increased (P ≤ 0.05) or tended to increase (P ≤ 0.06) with DOF. The brain, limbs, thymus, abomasum, KPH and total internal fat (TIF) of REV steers weighed proportionately less (P ≤ 0.03) and the reticulum weighed proportionately more (P = 0.03) than those of CON steers. Proportionate weight of the bladder, gallbladder and spleen was similar for all DOF, whereas all other variables differed (P ≤ 0.04) across DOF. Observed results suggest that TBA + E2 implants increase body and carcass weights and alter many non-carcass components, while reducing excess internal fat accumulation.
Improved efficiency associated with TBA + E2 implants has been attributed to a shift in nutrient deposition away from fat deposits often trimmed from the final product, toward the development of lean muscle. Though a decrease in waste fat will improve carcass cutability, a concurrent reduction in intramuscular fat and carcass quality is often observed in implanted animals marketed prior to achieving target composition. A third experiment was designed to evaluate the development of traits contributing to carcass yield and quality in response to implant and days on feed (DOF) in a 2 × 10 factorial study. Charolais × Angus steers (n = 80) were paired for similarity using genetic markers and projected endpoint composition. Pairs were randomized to 1 of 10 harvest dates corresponding to 0, 42, 84, 126, 168, 210, 252, 294, 336 or 378 DOF. Individuals within pair were then randomly assigned to 1 of 2 implant treatments, in which REV steers received a Revalor-XS (200mg trenbolone acetate/40mg estradiol; 4 uncoated and 6 coated pellets) implant on d 0 and d 190, while CON steers represented a non-hormone treated (NHTC) marketing strategy and received no implant throughout the feeding period. Upon each feeding endpoint, 8 steers (4-REV/CON pairs) were harvested and the shrunk body weight (SBW), weight of kidney, pelvic and heart fat (KPH), and hot carcass weight (HCW) were obtained. Carcasses were chilled for 48 h and graded according to USDA quality and yield grade standards. All variables were analyzed using mixed models with implant treatment and DOF as fixed effects and pair as random. While no TRT × DOF interactions (P > 0.05) were observed in yield grade variables, a TRT × DOF interaction occurred (P < 0.01) for skeletal and overall maturity. Implanted steers had a heavier SBW (7%; P < 0.01) and HCW (6%; P < 0.01), and larger (6%; P < 0.01) LM area than non-implanted counterparts. While REV carcasses had 17% less (P < 0.01) KPH than CON carcasses, no treatment effects (P = 0.26) were observed in marbling, suggesting sustained marbling quality throughout the 378-d feeding period. Marbling and 12th rib fat depth increased linearly (P < 0.01) across DOF; SBW, HCW, dressed yield, LM area, KPH, USDA yield grade, and lean maturity increased whereas LM area:HCW decreased quadratically (P < 0.06) with additional DOF. These data support a shift in nutrient deposition from waste-fat accumulation to lean tissue development in response to slow-release TBA + E2 implants compared to NHTC. Additionally, implanted steers exhibited advanced skeletal maturity, however no concurrent compromise in marbling was observed throughout the 378-d feeding period
Strategic Pedagogy: Pursuing Best Practices for Teaching Asychronous Online Health Economics Courses
Get PDFThis chapter provides a summary of my experience, surveying of literature, and usage of relevant statistics in lieu of a traditional data collection approach.This chapter employs eight years of experience and research to develop recommended best practices for choosing a textbook, producing videos, role-playing discussion forums and random block examinations when teaching health economics online asynchronously. Best practice recommendations include picking a textbook that has prebuilt slides, fits the student audience, provides some practice exercises, and has a relatively long shelf life. For video production, I recommend developing a high-quality, short introduction video and producing as many minimal editing videos as possible. I recommend role-playing discussion forum use to improve learning and engagement in discussion forums. I also recommend employing random block examinations with a time constraint and visibility constraint to deter academic dishonesty. I conclude with a final recommendation for other helpful resources such as the Teaching Health Economics Special Interest Group within the International Health Economics Association
EVALUATION OF PERFORMANCE CARCASS CHARACTERISTICS, AND RUMINAL BUFFERING OF FEEDLOT CATTLE CONSUMING DIETS CONTAINING CORN-GRAIN MILLING BYPRODUCTS
Get PDFFeeds such as Sweet Bran™ (SB) and wet distillers grains with solubles (WDGS) contribute high concentrations of dietary energy and low starch while potentially providing buffering qualities that may improve rumen health and performance. Feeding combinations of SB and WDGS is common but research is limited. This study evaluated the effects of SB and WDGS in the diet alone or in combination on performance, carcass characteristics, ruminal pH, and rumination time of finishing beef cattle. The study was a randomized complete block design using pen as the experimental unit. Steers (n = 455; 373 ± 15.5 kg) were randomly allocated to 48 pens (12 blocks, 4 pens/block) and transitioned over 20 d to 1 of 4 steam-flaked corn-based dietary treatments containing: no byproducts (CON), 20% WDGS (WDGS), 20% SB (SB), or 20% SB and 10% WDGS (COMBO). Within each pen, 2 steers were randomly selected to receive an indwelling ruminal pH bolus to quantify pH of the rumen and a 3-axis accelerometer tag to measure rumination for the first 92 d of the study. Diet samples were collected weekly to determine particle size, NDF concentration, and physically effective fiber (peNDF). Cattle performance (BW, DMI, ADG, G:F) was not different (P = 0.96) through the transition period across all treatments. Overall, final BW, DMI, and ADG were greater (P < 0.01) for WDGS, SB, and COMBO than CON. Although overall G:F was not different (P = 0.48), feed cost of gain was greatest (P < 0.01) for CON, intermediate for WDGS
and SB and least for COMBO. Hot carcass weight was greatest (P = 0.04) for SB and WDGS, intermediate for COMBO, and least for CON. A tendency (P = 0.09) was observed for yield grade; it was greatest for WDGS, intermediate for SB and COMBO, and lowest for CON. Dressing percentage, marbling score, quality grade, 12th-rib fat, ribeye area, and percentage KPH fat did not differ (P ≥ 0.32) among treatments. Abscessed livers were not statistically different (P = 0.27), but CON had a numerically greater percentage of liver abscesses. The percentage of particles > 4.0 mm was greatest (P < 0.01) for CON, intermediate for SB, and least for WDGS and COMBO. However, NDF (P < 0.01) and peNDF (P < 0.01) were greatest for COMBO, intermediate for WDGS and SB, and least for CON. A treatment × day interaction (P < 0.01) was observed for daily rumination minutes per kg of DMI, NDF, and peNDF. A treatment × h interaction (P < 0.01) was observed such that CON cattle spent less time ruminating at 0800 and 1000 h in a 24 h period. Ruminal pH was greatest (P < 0.01) for COMBO, intermediate for SB and WDGS, and least for CON, but SB did not differ from COMBO or WDGS. Ruminal pH was least (P < 0.01) for CON from 0800 to 1800 h. Addition of WDGS and/or SB improved performance and reduced feed cost of gain when incorporated into steam-flaked corn-based finishing diets. Relationships between peNDF, rumination behavior, and ruminal pH suggest that SB and WDGS similarly enhance buffering capacity when steam-flaked corn is replaced in the diet
Inhibition of Sorcin Protein to Improve the Efficacy of Doxorubicin in the Treatment of Metastatic Breast Cancer
Get PDFData Collection Methodology
For the cytotoxicity experiments, all individual preparations of free doxorubicin (Dox), free DMY, and the combination (Dox+DMY) were dissolved in DMSO to create a working 4mM stock solution. These solutions were then sterile filtered and diluted in the respective cell-line dependent maintenance media. Serial dilutions of each stock solution were prepared to the necessary concentrations for this study (0.01 μM 0.1 μM, 1.00 μM, 10 μM, and 100 μM ). Each cell line (MCF-10A or MDA-MB-231) was plated on a 96-well tissue culture treated plate at 10,000 cells/well and incubated for 24 hours. The cells were then treated with the varying concentrations of each aforementioned preparations. Following a 48 hour incubation, an MTT assay was conducted to assess cell viability, which was analyzed by using an Infinite M200 fluorescence plate reader at λ=570nm. The data analyzed was graphed using OriginPro software. For the western blot, lysates of both MDA-MB-231 and MCF-10A cells were prepared and analyzed using an SDS-PAGE method. The nitrocellulose membrane was subsequently blocked in a 5% milk/TBST solution for a minimum of one hour. After a series of washes, the membrane was incubated in the primary anti-sorcin antibody (1:200) and anti-GAPDH (1:5,000) for a minimum of one hour. The membrane was then incubated in the secondary antibody for a minimum of one hour (goat anti-rabbit, goat anti-mouse 1:15,000) followed by several washes with TBST. Finally, 1-Step NBT/BCIP was then applied to the membrane until bands were observed. The results were then analyzed and quantified using ImageJ software.
Expected Findings
The results of this study indicate an overall increase in the efficacy of doxorubicin in the presence of the sorcin inhibitor, DMY, when used to treat metastatic breast cancer, while no observable difference was observed when treating non-cancerous cells with either free doxorubicin or doxorubicin in the presence of the inhibitor. As well, western blot analysis indicates roughly a three-fold increase in sorcin expression in MDA-MB-231 cells versus the non-cancerous MCF-10A cells. These data may support a correlation between decreased sorcin expression and increased cytotoxic capability of doxorubicin. As previously stated, future work will aim to include a targeted-liposomal formulation in which DMY and doxorubicin will be co-encapsulated in a liposome decorated with a unique targeting peptide specifically designed to target the α3β1 integrin known to be overexpressed in metastatic breast cancer.Doxorubicin, and the liposomal formulation Doxil, are among the first-line chemotherapeutic agents used in the treatment of a variety of cancers, including metastatic breast cancer. Although doxorubicin has proven to be an effective cytotoxic agent, one major challenge in current therapy is the development of cancer cell resistance to this drug. One possible mechanism by which this resistance can occur is through overexpression of the calcium-binding protein, sorcin, which has the potential to directly bind doxorubicin, thereby limiting its cytotoxic effects. Therefore, the focus of this research is to utilize the compound dihydromyricetin (DMY), a known inhibitor of sorcin to potentially increase the overall efficacy of doxorubicin. In this study, a series of cytotoxicity assays were conducted to assess cytotoxic effect of doxorubicin against metastatic breast cancer cells (MDA-MB-231) as well as non-cancerous breast cells (MCF-10A), both with and without the inhibitor. A significant increase in cytotoxic capabilities of doxorubicin was observed in the metastatic cell line when coupled with DMY. Furthermore, western blot analysis was used to probe for the overexpression of sorcin in both non-cancerous breast cells as well as the metastatic cell line. Future work will involve the incorporation of doxorubicin and DMY into a unique, targeted-liposomal formulation which will ultimately be tested in cytotoxicity assays
AGE DISTRIBUTION AND SURVIVAL OF COYOTES AND GRAY FOXES IN WESTERN TEXAS
No full textThe coyote (Canis latrans) is one of the top predators in the state of Texas. They have been able to adapt to urbanization and continue to thrive in the wild. The coyote is also considered a top down keystone species. As such, coyote management can influence how other species are managed. Female coyotes can become sexually mature once they experience their first estrus cycle in the first year of life. Gray foxes (Urocyon cinereoargenteus) occur throughout Texas. Both male and female gray foxes can attain sexual maturity at an early age. Females on average breed for the first time at about 9-10 months of age. A better understanding of the age structure and survival rate of both species, we can better understand how many possible individuals we have that will be in prime breeding age, and how exploitation of the species may be effecting structure of the population. Given that both species are harvested in predator hunts and nuisance animal situations, I wanted to explore age structure and survival of coyotes and gray foxes in western Texas. I collected the lower canine tooth from 378 coyotes from the Panhandle and southwest areas of Texas. I also collected 288 lower canine teeth of gray fox samples from the Edwards Plateau and the Trans Pecos ecoregion. The teeth were processed for cementum annuli to access age for each individual. I then developed age distributions and used these distributions to calculate annual survival rates using a-structured regression. The overall survival of coyotes in Texas was 0.659. For females in total, annual survival was 0.709. Males annual survival was 0.686. The annual survival of all the gray foxes together is 0.650. Females annual survival was 0.647. Male’s annual survival was 0.643. The coyote and gray fox are adaptive species and can survive in different habitats and situations. The age structure in both species does suggest that exploitation is changing the age structure towards a younger dominant composition. However, these age structures also suggest that all of the populations I examined have not been over-harvested. Shifting populations to younger age classes can reduce age at maturity and increases litter sizes. Thus, the demographic strategy of these species apparently allows them to be resilient to current exploitation levels in this region
Understanding the 2020 GOP Primary in Texas' 13th Congressional District - Includes the July 2020 Runoff Election (Revised and Updated)
No full textThis paper expands the earlier Applied Politics Research Brief by including another variable to measure voter participation in the July 2020 runoff election. The addition of the new variable did not significantly improve the explanatory power of the model
Framing Multilevel Marketing on Corporate Websites and Consultants' Instagram Posts
Get PDFThe focus of this study is on the visual and textual framing of MLM opportunities or
products on corporate websites and in public Instagram posts made by presumed consultants for
FRAMING MULTI-LEVEL MARKETING 3
those MLMs, based on hashtags contained in the posts. Ten MLM companies were identified for
inclusion in this study: Amway, Thirty-One Gifts, Stella and Dot, Paparazzi, Youngliving,
Scentsy, Mary and Martha, Norwex, Isagenix, and Pampered Chef.
For each company’s website, analysis focused on visuals and text on the home page,
“about us” and “join us” pages. Additionally, two popular Instagram hashtags, one productrelated and one seller-related, for each MLM in the study were identified and 10 recent public
posts for each of the hashtags collected, for a total of 200 Instagram posts (20 per company). A
random number generator was used to select which 10 specific posts from among the 100 most
recent public posts for each hashtag to collect. Screen capture was used to save the post image
and caption for analysis. Collection of the Instagram posts was spread across five different days
in September 2019, with all 20 posts for two different companies collected each day. Therefore,
these posts represent the work of anywhere from 10 (1 per company) to 200 (20 per company)
unique MLM consultants, depending on each consultant’s level of posting activity on the day the
posts were collected for their company.The rise of smartphone applications and related internet-based technologies has been
accompanied by an increased interest in the so-called “gig economy” in which workers labor in
one-off arrangements with no guarantee of continued employment. Some workers seek these
arrangements for their flexibility or as a “side hustle,” while others may struggle to find other
types of work (Abraham, Haltiwanger, Sandusky & Spletzer, 2018). At the same time, these and
similar forms of creative labor via social media are valorized as being entrepreneurial (Duffy &
Wissinger, 2017). Such digital entrepreneurship is often positioned as a way for women to “have
it all” and balance work with traditional family life (Duffy & Hund, 2015).
In recent years the networked aspects of social media have intersected with societal
trends toward a gig economy to produce a rise in multilevel marketing companies (MLMs) that
rely heavily on the internet to recruit and sell. Multilevel marketing is a subset of direct selling or
network marketing approaches to doing business that relies on recruiting new participants in a
complex system of uplines and downlines to move product. MLMs have existed for decades, and
like current discourse around creative work on social media, have often used a rhetoric of
entrepreneurship to attract participants and project legitimacy (Carl, 2004). Many of the most
well-known MLMs, such as Avon and Mary Kay cosmetics, are targeted toward women and are
sometimes framed as home-based businesses (Amundson, 2008). MLMs and related direct
selling schemes are big business, generating over $35 billion in retail sales in 2018, with 6.2
million people acting as direct sellers, 75% of whom were women (Direct Selling Association,
2019).
To date, there is limited research on the intersection of multilevel marketing, social
media, and digital entrepreneurship. Given existing research that demonstrates the centrality of
entrepreneurialism to MLMs’ framing of their legitimacy in order to attract potential independent
consultants or sellers (Carl, 2004), the present study examines the websites of 10 active MLM
companies to qualitatively identify and assess themes that emerge regarding how participation in
the MLM is framed for potential sellers. Additionally, the study examines 200 public Instagram
posts made by MLM consultants (sellers) in order to assess how these sellers frame their
participation in the MLM for others, including whether and how these posts reflect similar or
different themes, or frames, from those presented by the MLMs themselves. Doing so will help
us to better understand the role of MLMs within the current media and economic environment.
This study may also provide insight into gendered aspects of such digital entrepreneurialism.
The following research questions are posed:
RQ1: What themes emerge in how MLM companies use their websites to frame
participation in the MLM for potential sellers as entrepreneurialism?
RQ2: What themes emerge in how MLM consultants use their Instagram posts to frame
their participation in the MLM as a form of entrepreneurialism
Preparation and Characterization of Crop-Waste Biochars
Get PDFWe expect to determine the important surface and material distinctions between biochars made from different feedstock and production methods. These distinctions will inform the use of biochar in environmental and agricultural applications.Biochar is a carbon-rich and porous material; it is produced through the pyrolysis of waste biomass. This material is capable of adsorbing chemical constituents from water, air, or other media. This capability has allowed it to become an alternative water filtration option potentially comparable to activated carbon. Raw biomass crop waste including cotton hull, pecan shell, and rice husk were converted to biochar through Top-Lifted Updraft (TLUD) and Muffle Furnace (MF) pyrolysis processes. The material properties of these biochars have been characterized through the use of XRD, FTIR, TGA, DSC, SEM, and BET surface area analytical tools. The analyses reveal the physical and chemical characteristics of the raw materials and biochar. XRD analysis of the raw materials and biochars shows that these materials are noncrystalline (amorphous). FTIR analysis shows the presence of O-H, C-H, C-C, CH2, C-H, and C-O-C functional groups in the cellulose structure of the raw material; this ensures that an oxidizer is present in the cellulose structure of these raw materials. The crop waste biochar predominantly contain the C-O-C functional groups. TGA and DSC analyses show that raw materials and biochars undergo pyrolysis at around 260°C and 340°C, respectively. This indicates a higher thermal stability of biochar and a greater availability of oxidizer in the raw materials. The raw crop wastes undergoes pyrolysis at lower temperatures than biochar. SEM images show the porous structure in biochar while the BET surface analysis reveals the pore size distribution. The presence of a porous structure and active functional groups in biochar makes them an excellent candidate as a filter and membrane for the removal of pollutants from water. The fact that a quality biochar sorbent, as shown in this can study, can be made from commonly found crop waste by inexpensive, simple pyrolysis techniques demonstrates its usefulness in many environmental and chemical process applications