Representations of Double Affine Lie algebras

We study representations of the double affine Lie algebra associated to a simple Lie algebra. We construct a family of indecomposable integrable representations and identify their irreducible quotients. We also give a condition for the indecomposable modules to be irreducible, this is analogous to a result in the representation theory of quantum affine algebras. Finally, in the last section of the paper, we show, by using the notion of fusion product, that our modules are generically reducible

Review article: the global emergence of Helicobacter pylori antibiotic resistance.

BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance

Akuntansi Pertanggungjawaban sebagai Alat Pengendalian Manajemen terhadap Penilaian Prestasi Kerja

Perkembangan dunia bisnis semakin berkembang pesat di lihat dari teknologi yang semakin canggih, ilmu pengetahuan yang berkembang sangat pesat serta persaingan bisnis yang semakin kuat. Pertumbuhan dan persaingan dunia bisnis dewasa ini mengharuskan Perusahaan untuk memandang jauh ke depan guna mengantisipasi berbagai kemungkinan yang dapat mempengaruhi perkembangan Perusahaannya. Salah satu cara yang ditempuh untuk mengatasi hal tersebut, Perusahaan menerapkan akuntansi pertanggungjawaban. Dengan diterapkannya sistem akuntansi pertanggungjawaban yang baik akan menyebabkan terciptanya suatu pengendalian dan pengukuran prestasi kerja.Penelitian dilakukan pada PT. X yang terletak di Jalan Komplek Ilir Barat Permai Blok D 2 No. 08, Lt. II Palembang. Maksud dari penelitian ini adalah untuk memperoleh bukti empirik peranan sistem akuntansi pertanggungjawaban sebagai alat pengendalian manajemen didalam Perusahaan. Sedangkan tujuan dari penelitian ini adalah untuk mengetahui peranan sistem akuntansi pertanggungjawaban, menganalisis pelaksanaan akuntansi pertanggungjawaban, dan menganalisis sistem akuntansi pertanggungjawaban dapat digunakan untuk menilai prestasi kerja.Metode yang digunakan penulis dalam penelitian ini adalah metode deskriptif analitis, yaitu suatu metode yang dilakukan dengan cara mengumpulkan, menyusun, menganalisis, dan menginterprestasikan data sehingga dapat memberikan gambaran atau keadaan objek peneliti secara nyata untuk kemudian ditarik kesimpulan yang dijadikan dasar untuk mengajukan saran perbaikan bagi objek yang diteliti.Dari hasil penelitian dan pembahasan, dapat ditarik kesimpulan bahwa akuntansi pertanggungjawaban sebagai alat pengendalian manajemen sangat berperan terhadap penilaian prestasi kerja pada PT. X. Hasil hipotesis menunjukkan sebesar 75,07 % bahwa hipotesis diterima (Ho = diterima).Saran penulis bagi PT. X yaitu: (1) secara keseluruhan Perusahaan baik dalam penerapan akuntansi pertanggungjawaban tetapi perlu diperhatikan penilaian prestasi kerja, (2) melihat pentingnya akuntansi pertanggungjawaban, Perusahaan ini seharusnya mempunyai kecenderungan untuk menerapkan semua tahapan kegiatan dalam pusat pertanggungjawaban, (3) Perusahaan ini harus lebih memperhatikan penyusunan anggaran baik penyusunan laporan pertanggungjawaban dimana harus disertakan penyimpangan biaya jika memang terjadi penyimpangan didalam Perusahaan tersebut, dan (4) untuk meningkatkan prestasi kerja, perlu adanya peningkatan kualitas pekerjaan yaitu dengan cara meningkatkan akurasi, ketelitian, penampilan dan output dari pekerjaan

High speed sCMOS-based oblique plane microscopy applied to the study of calcium dynamics in cardiac myocytes

blique plane microscopy (OPM) is a form of light sheet microscopy that uses a single high numerical aperture microscope objective for both fluorescence excitation and collection. In this paper, measurements of the relative collection efficiency of OPM are presented. An OPM system incorporating two sCMOS cameras is then introduced that enables single isolated cardiac myocytes to be studied continuously for 22 seconds in two dimensions at 667 frames per second with 960 × 200 pixels and for 30 seconds with 960 × 200 × 20 voxels at 25 volumes per second. In both cases OPM is able to record in two spectral channels, enabling intracellular calcium to be studied via the probe Fluo-4 AM simultaneously with the sarcolemma and transverse tubule network via the membrane dye Cellmask Orange. The OPM system was then applied to determine the spatial origin of spontaneous calcium waves for the first time and to measure the cell transverse tubule structure at their point of origin. Further results are presented to demonstrate that the OPM system can also be used to study calcium spark parameters depending on their relationship to the transverse tubule structure

Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus.

Usher 1 patients are born profoundly deaf and then develop retinal degeneration. Thus they are readily identified before the onset of retinal degeneration, making gene therapy a viable strategy to prevent their blindness. Here, we have investigated the use of adeno-associated viruses (AAVs) for the delivery of the Usher 1B gene, MYO7A, to retinal cells in cell culture and in Myo7a-null mice. MYO7A cDNA, under control of a smCBA promoter, was packaged in single AAV2 and AAV5 vectors and as two overlapping halves in dual AAV2 vectors. The 7.9-kb smCBA-MYO7A exceeds the capacity of an AAV vector; packaging of such oversized constructs into single AAV vectors may involve fragmentation of the gene. Nevertheless, the AAV2 and AAV5 single vector preparations successfully transduced photoreceptor and retinal pigment epithelium cells, resulting in functional, full-length MYO7A protein and correction of mutant phenotypes, suggesting successful homologous recombination of gene fragments. With discrete, conventional-sized dual AAV2 vectors, full-length MYO7A was detected, but the level of protein expression was variable, and only a minority of cells showed phenotype correction. Our results show that MYO7A therapy with AAV2 or AAV5 single vectors is efficacious; however, the dual AAV2 approach proved to be less effective

ErbB- and MUC1-targetted CAR-T cell immunotherapy of oral squamous cell carcinoma

Chimeric antigen receptor T (CAR-T) cell therapy has shown great success in treating B cell malignancies however, there are many challenges which limit their therapeutic efficacy in solid tumours. Immunotherapy of head and neck squamous cell carcinoma (HNSCC), and in particular, oral squamous cell carcinoma (OSCC), presents a unique set of challenges including lack of consistently expressed tumour associated antigens (TAAs) and the immunosuppressive tumour microenvironment (TME). Currently, there are few clinical trials investigating the use of CAR-T cells in HNSCC/OSCC however results from trials investigating similar solid tumours, such as breast cancer, can be adopted to help evaluate the use of CAR-T in this cancer. In this review, the process of CAR-T cell engineering, and different generations of these cells will be summarised, highlighting their potential use in treating HNSCC through targeting ErbB and MUC1; TAAs highly expressed by this solid tumour. Potential strategies including combination therapy, utilising both TAA-targeting CAR-Ts and immune checkpoint inhibitors, such as PD-L1, has been discussed, in an attempt to develop synergistic anti-tumour responses. In addition to this, the use of dual-targeting CAR-T cells, synthetic NOTCH (synNOTCH) receptors and alternative non-tumour targets of the TME have been reviewed. Such combination therapies have been shown to help limit solid tumour progression and enhance both the safety and efficacy of CAR-T cell immunotherapy, which may be adopted for the treatment and management of OSCC

Modifying the Response of Male Broiler Chickens to Heat Stress Through Early Age Feed Restriction and Thermal Conditioning

Two experiments were conducted to investigate the effects of early age feed restriction and heat conditioning on tolerance to acute and chronic heat stress in male broiler chickens. In both experiments, equal numbers of chickens were subjected to (i) 60% feed restriction on day 4, 5, and 6 (FR), (ii) exposure to 36±IoC and 50-60% relative humidity for 1 hour from day 1 to 21 (HT), (iii) 60% feed restriction on day 4, 5, and 6 and exposure to 36± l oC and 50-60% relative humidity for 1 hour from day 1 to 21 (FRHT). (iv) ad libitum feeding and no heat treatment (control). In experiment I, on day 35, all birds were exposed to 39± l oC for 6 hours and 50% relative humidity. Subjecting chicks to FR, HT and FRHT reduced HLR response to the heat challenge. Following heat exposure, the FR and FRHT chick had greater heat shock protein (hsp) 70 density than those of controls. The hsp 70 response of HT birds was not significantly different from the other three groups. The FRHT birds were more hyperthermic than controls during heat challenge. In experiment II, from day 36- 50, all birds were exposed to 38± l oC and 80 % relative humidity for 2 hours/day. One day following heat exposure (day 37), all birds were administrated intranasally with infectious bursal disease (IBD) vaccine virus. The dosage used was l Ox of the recommended level. Subjecting chicks to FRHT improved relative weight gain and resistance to IBD infection and reduced HLR in response to the heat treatment as compared with the control birds. Although there is evidence that FR and HT can improve heat tolerance, the FRHT combination may further enhance the ability of birds to withstand chronic heat stress. The acquired improved heat tolerance resulting from FRHT, FR, and HT could be attributed to enhanced hsp 70 response. The trend of hsp 70 response correlated well with IBD lesion scores, suggesting hsp 70 may play a role in resistance against viral infection. Based on experiment I and II, it can be concluded that the present findings confirmed earlier studies that FR is effective in alleviating the adverse effects of heat stress. Subjecting birds to FRHT can further improve tolerance to chronic but not acute heat stress

Electrophysiological and morphological changes in colonic myenteric neurons from chemotherapy-treated patients: A pilot study

BACKGROUND: Patients receiving anticancer chemotherapy experience a multitude of gastrointestinal side‐effects. However, the causes of these symptoms are uncertain and whether these therapeutics directly affect the enteric nervous system is unknown. Our aim was to determine whether the function and morphology of myenteric neurons are altered in specimens of the colon from chemotherapy‐treated patients. METHODS: Colon specimens were compared from chemotherapy‐treated and non‐treated patients following colorectal resections for removal of carcinoma. Intracellular electrophysiological recordings from myenteric neurons and immunohistochemistry were performed in whole mount preparations. KEY RESULTS: Myenteric S neurons from chemotherapy‐treated patients were hyperexcitable; more action potentials (11.4 ± 9.4, p < 0.05) were fired in response to depolarising current pulses than in non‐treated patients (1.4 ± 0.5). The rheobase and the threshold to evoke action potentials were significantly lower for neurons from chemotherapy‐treated patients compared to neurons from non‐treated patients (p < 0.01). Fast excitatory postsynaptic potential reversal potential was more positive in neurons from chemotherapy‐treated patients (p < 0.05). An increase in the number of neurons with translocation of Hu protein from the cytoplasm to the nucleus was observed in specimens from chemotherapy‐treated patients (103 ± 25 neurons/mm(2), 37.2 ± 7.0%, n = 8) compared to non‐treated (26 ± 5 neurons/mm(2), 11.9 ± 2.7%, n = 12, p < 0.01). An increase in the soma size of neuronal nitric oxide synthase‐immunoreactive neurons was also observed in these specimens. CONCLUSIONS & INFERENCES: This is the first study suggesting functional and structural changes in human myenteric neurons in specimens of colon from patients receiving anticancer chemotherapy. These changes may contribute to the causation of gastrointestinal symptoms experienced by chemotherapy‐treated patients