APLIKASI E - COMMERCE PADA ANUGERAH BRIDAL

Peran teknologi dalam pemasaran yakni menunjang kegiatan-kegiatan yang saling berhubungan, untuk merencanakan, menentukan harga, serta kaitannya dengan mempromosikan, mendistribusikan barang dan jasa kepada kelompok pembeli. Berkembangnya teknologi kini perlahan mulai mengubah lifestyle masyarakat dalam mencari informasi. Anugerah Bridal adalah usaha yang  menjual perlengkapan pengantin, masalah yang dihadapi Anugerah Bridal adalah pemasaran yang masih minim dengan terbatasnya tempat berjualan dan belum dapat melakukan pemasaran di luar daerah karena terkendala dengan waktu dan tempat. Tujuan  dari penelitian adalah membangun aplikasi berbasis e-commerce yang  dapat membantu Anugerah Bridal dalam menjual,  mempromosikan aksesori dan paket-paket bridal. Metode pengumpulan data yang digunakan adalah wawancara, observasi dan pemodelan menggunakan Unified Modelling Language. Hasil penelitian adalah aplikasi penjualan e-commerce yang diharapkan dengan adanya aplikasi ini dapat membantu Anugerah Bridal dalam menjual dan mempromosikan aksesori dan paket-paket bridal sehingga dapat dikenal lebih luas oleh masyarakat dan juga memperluas jangkauan pemasaran pada Anugerah Bridal.&nbsp

Penerapan Customer Relationship Management (CRM) Pada PT. Media Bumi Animha Berbasis Web

Abstrak. PT. Media Bumi Animha adalah salah satu perusahaan surat kabar berskala kabupaten, yang menerbitkan koran Papua Selatan Pos. Perusahaan  ini beroperasi di wilayah Papua dan berkantor di kabupaten Merauke. Jumlah pelanggan khususnya di kabupaten Merauke 203 pelanggan. Untuk memberikan pelayanan yang baik, tentunya perusahaan perlu mengetahui keluhan dari pelanggan tentang produk yang di jual. Sebagai bahan evaluasi untuk perusahaan guna pelayanan yang lebih baik lagi. Penelitian ini bertujuan membangun Customer Relationship Management (CRM) Pada PT. Media Bumi Animha (Papua Selatan Pos) Berbasis Web agar dapat menampung keluhan pelangan, serta dapat membantu perusahaan dalam mengolah data pelanggan serta pelaporan keluhan pelanggan.  Metode pengembangan sistem ialah waterfall dan pengujian sistem menggunakan BlackBox serta Kuisioner untuk memastikan bahwa sistem relevan dengan tujuan penelitian. Hasil dari pengujian menunjukan bahwa Penerapan Customer Relationship Management (CRM) Pada PT. Media Bumi Animha (Papua Selatan Pos) Berbasis Web dapat menampung keluhan pelanggan dan dapat membantu perusahaan dalam mengolah data pelanggan serta pelaporan keluhan pelanggan.   Kata kunci : Keluhan, pelanggan, Customer Relationship Management

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

Telomerase Inhibition Targets Clonogenic Multiple Myeloma Cells through Telomere Length-Dependent and Independent Mechanisms

Plasma cells constitute the majority of tumor cells in multiple myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time PCR.Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Psychedelic-Inspired Medium-Throughput Assays for the Development of Next-Generation Neurotherapeutics

Major depressive disorder (MDD) affects more than 264 million people worldwide. A wide range of antidepressants are available to treat the disease including, but are not limited to, Prozac™, Elavil™, and Nardil™. Unfortunately, 1 in 3 patients prescribed these traditional antidepressants do not show significant mood improvement in response to the first regimen, and those who do require upwards of 2–4 weeks of treatment before observing any therapeutic effects. This delay of therapeutic onset with currently prescribed medications further highlights the necessity of novel faster-acting antidepressants. Recently, the Food and Drug Administration (FDA) approved esketamine—a ketamine enantiomer with rapid therapeutic effects (hours to days)—for treatment-resistant depression (TRD). It is hypothesized that ketamine produces its therapeutic effects by rectifying the atrophy of neurites, the reduction of the number of dendritic spines, and the loss of synapses in the prefrontal cortex (PFC) observed in postmortem brains of patients who suffered from MDD and rodent models of depression. However, ketamine has serious side effects, including the potential for abuse. Therefore, we are interested in developing, identifying, and optimizing novel chemical scaffolds with unique mechanisms of action that are better tolerated. One series of scaffolds that we are interested in is the classic psychedelics. Recently, the classic psychedelics have undergone a renaissance and have begun to be explored as next-generation therapeutics for the treatment of depression with psilocybin, lysergic acid diethylamide (LSD), and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) leading the way in clinical trials. Thus, we postulate that the scaffolds of the classic psychedelics would prove to be promising targets for next-generation antidepressants. Here, I discuss efforts to develop next-generation therapeutics starting from classic psychedelics. First, I explored the similarities between ketamine and classic psychedelics with respect to their effects on structural neural plasticity. We categorized molecules that promoted plasticity as psychoplastogens, small molecules that can induce structural changes in the brain. Next, I investigated the mechanism of actions of the classic psychedelics and discovered the importance of tropomyosin receptor kinase B (TrkB), brain-derived neurotrophic factor (BDNF), the mammalian target of rapamycin (mTOR), serotonin 2A (5-HT2A), and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors in psychoplastogen-induced plasticity. Furthermore, I examined transient stimulation versus chronic stimulation with the psychoplastogens and observed their effects in promoting long-lasting structural plasticity. Finally, to better facilitate drug discovery of fast-acting antidepressants, I developed two orthogonal assays. First, I established phenotypic assays to examine the efficacy of small molecules in promoting neuritogenesis, spinogenesis, and synaptogenesis. I clustered known fast-acting antidepressants, traditional antidepressants, and non-antidepressant compounds by combining these structural plasticity phenotypes using principal component analysis (PCA). Second, we developed and characterized the first cellular assay to determine the hallucinogenic potential of small molecules using an engineered 5-HT2AR fluorescent biosensor. We identified two novel hallucinogens and several non-hallucinogens through this platform. We then validated their effects in the head-twitch response—a behavioral assay that correlates well with the hallucinogenic potential of small molecules in mice. Lastly, we combined the structural plasticity assays with the 5-HT2AR hallucinogenic potential counter-screen to identify a novel non-hallucinogenic small molecule, AAZ-A-154 (AAZ), with therapeutic potential. We then confirmed these findings using behavioral assays. Overall, this work describes mechanistic studies aimed at understanding the actions of psychedelics, the identification of new potential antidepressants through phenotypic assays, and a novel counter-screen for hallucinogenic potential. These studies will facilitate drug discovery efforts aimed at better-tolerated, fast-acting, next-generation antidepressants

Psychedelic-Inspired Medium-Throughput Assays for the Development of Next-Generation Neurotherapeutics

Major depressive disorder (MDD) affects more than 264 million people worldwide. A wide range of antidepressants are available to treat the disease including, but are not limited to, Prozac™, Elavil™, and Nardil™. Unfortunately, 1 in 3 patients prescribed these traditional antidepressants do not show significant mood improvement in response to the first regimen, and those who do require upwards of 2–4 weeks of treatment before observing any therapeutic effects. This delay of therapeutic onset with currently prescribed medications further highlights the necessity of novel faster-acting antidepressants. Recently, the Food and Drug Administration (FDA) approved esketamine—a ketamine enantiomer with rapid therapeutic effects (hours to days)—for treatment-resistant depression (TRD). It is hypothesized that ketamine produces its therapeutic effects by rectifying the atrophy of neurites, the reduction of the number of dendritic spines, and the loss of synapses in the prefrontal cortex (PFC) observed in postmortem brains of patients who suffered from MDD and rodent models of depression. However, ketamine has serious side effects, including the potential for abuse. Therefore, we are interested in developing, identifying, and optimizing novel chemical scaffolds with unique mechanisms of action that are better tolerated. One series of scaffolds that we are interested in is the classic psychedelics. Recently, the classic psychedelics have undergone a renaissance and have begun to be explored as next-generation therapeutics for the treatment of depression with psilocybin, lysergic acid diethylamide (LSD), and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) leading the way in clinical trials. Thus, we postulate that the scaffolds of the classic psychedelics would prove to be promising targets for next-generation antidepressants. Here, I discuss efforts to develop next-generation therapeutics starting from classic psychedelics. First, I explored the similarities between ketamine and classic psychedelics with respect to their effects on structural neural plasticity. We categorized molecules that promoted plasticity as psychoplastogens, small molecules that can induce structural changes in the brain. Next, I investigated the mechanism of actions of the classic psychedelics and discovered the importance of tropomyosin receptor kinase B (TrkB), brain-derived neurotrophic factor (BDNF), the mammalian target of rapamycin (mTOR), serotonin 2A (5-HT2A), and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors in psychoplastogen-induced plasticity. Furthermore, I examined transient stimulation versus chronic stimulation with the psychoplastogens and observed their effects in promoting long-lasting structural plasticity. Finally, to better facilitate drug discovery of fast-acting antidepressants, I developed two orthogonal assays. First, I established phenotypic assays to examine the efficacy of small molecules in promoting neuritogenesis, spinogenesis, and synaptogenesis. I clustered known fast-acting antidepressants, traditional antidepressants, and non-antidepressant compounds by combining these structural plasticity phenotypes using principal component analysis (PCA). Second, we developed and characterized the first cellular assay to determine the hallucinogenic potential of small molecules using an engineered 5-HT2AR fluorescent biosensor. We identified two novel hallucinogens and several non-hallucinogens through this platform. We then validated their effects in the head-twitch response—a behavioral assay that correlates well with the hallucinogenic potential of small molecules in mice. Lastly, we combined the structural plasticity assays with the 5-HT2AR hallucinogenic potential counter-screen to identify a novel non-hallucinogenic small molecule, AAZ-A-154 (AAZ), with therapeutic potential. We then confirmed these findings using behavioral assays. Overall, this work describes mechanistic studies aimed at understanding the actions of psychedelics, the identification of new potential antidepressants through phenotypic assays, and a novel counter-screen for hallucinogenic potential. These studies will facilitate drug discovery efforts aimed at better-tolerated, fast-acting, next-generation antidepressants