Artykuły w czasopismach na temat „Bon Shoten”

Raman and infrared measurements of the LiB3O5 (LBO) crystals were completed. The experimental results shown here are more and stronger Raman lines and infrared absorption peaks, which implies that the external vibrations of the trigonal (BO3)3− and tetrahedral (BO4)5− ions, especially the former, in the six-membered boron–oxygen rings at the low wave number are strong and the internal vibrations of the (BO4)5− ions above 200 cm−1 are stronger than those of the (BO3)3− ions if compared with the Raman spectra of BaB2O4 crystals. These are caused due to the slope and distortions of the B3O7 rings and their BO3 and BO4 units in LBO, which change the structural rigidity of the crystals, intensify the long-range electrostatic force and short-range molecular force, and shorten the ultraviolet absorption edge.

One method which is based on model to settle the long development cycle of driver motor control software is adopted for Electric Vehicle (EV). It is to achieve Field Oriented Control algorithm (FOC) designing, model building, and microcontroller driver integration, task scheduling, code generation; Model simulation experiments are completed aiming at three kinds of running conditions such as a constant speed, accelerating, on load; finally, these running conditions are realized in EV and dynamometer platform. Simulation and experimental results show FOC has a well performance on speed regulating by comparing technical parameters with Chang An Ben Ben Mini, adopting the method also shorten the development cycle of motor control software.

Bone marrow necrosis (BMN) is defined as necrosis of the myeloid tissues and stroma without involvement of the cortical bone. We report a case of 66-year-old male with AML-M4 (FAB classification) who was given induction chemotherapy with cytarabine and daunorubicin. Filgrastim at 480 micrograms was administered on days 15–19 to shorten the duration of neutropenia. Consequently patient developed severe pelvic bone pain, leukoerythroblastosis, and severe leukocytosis. Repeat bone marrow aspiration and biopsy on day 21 confirmed bone marrow necrosis. These manifestations responded quickly to discontinuation of filgrastim. Subsequently, he recovered full myelopoiesis. We suggest that there may be more cases of BMN associated with G-CSF that are undiagnosed.

Binarized neural networks (BNNs) and batch normalization (BN) have already become typical techniques in artificial intelligence today. Unfortunately, the massive accumulation and multiplication in BNN models bring challenges to field-programmable gate array (FPGA) implementations, because complex arithmetics in BN consume too much computing resources. To relax FPGA resource limitations and speed up the computing process, we propose a BNN accelerator architecture based on consolidation compressed tree scheme by combining both XNOR and accumulation operation of the low bit into a systematic one. During the compression process, we adopt 0-padding (not ±1) to achieve no-accuracy-loss from software modeling to hardware implementation. Moreover, we introduce shift-addition-BN free binarization technique to shorten the delay path and optimize on-chip storage. To sum up, we drastically cut down the hardware consumption while maintaining great speed performance with the same model complexity as the previous design. We evaluate our accelerator on MNIST and CIFAR-10 dataset and implement the whole system on the ARTIX-7 100T FPGA with speed performance of 2052.65 GOP/s and area efficiency of 70.15 GOPS/KLUT.

Archives have an important role in providing information to users in making decisions. The management of archives in the Early Childhood Islamic Education (PIAUD) study program cannot be separated from the accreditation activities that have been periodically determined by the National Accreditation Board for Higher Education (BAN-PT). Form accreditation documents are often slumped and the archives are irregular which must be arranged, causing the Study Program Management Unit (UPPS) to have difficulty organizing and archiving the required documents. The results of the research on the Early Childhood Islamic Education (PIAUD) study program show that some archive management activities have been carried out well and some have not been carried out properly. Records management for accreditation purposes that has been carried out by the study program plays an important role because it can facilitate, expedite, and shorten the time in recovering archives when needed by either the form filling team or the assessor team.

Abstract The purpose of this study is to develop a strategy for treating pancreatic neuroendocrine tumor (PanNET) through blocking Thymidylate Synthase (TYMS or TS), a DNA metabolic enzyme. Elevated TYMS levels are frequently observed in human PanNET and are associated with worse prognosis and resistance to cytotoxic agents such as 5FU. Elevated TYMS levels directly promote tumorigenesis in vitro and ectopic expression of human TS (hTS) in transgenic mice promotes adenoma development in the endocrine pancreas in vivo. Pancreatic islet tumor formation in hTS transgenic mice occurred with a long latency period, suggesting that additional somatic events are required for PanNET formation and progression. Men1 was shown to be a frequent target for somatic mutation in PanNETs (44% have MEN1 mutations). Therefore, we established a new mouse model designated hTS/Men1-/-, where hTS is overexpressed in pancreatic islet cells carrying conditional Men1 null alleles. We observed that ectopic hTS cooperates with Men1 inactivation to significantly accelerate PanNET progression and shorten survival. Since traditional TYMS inhibitors, such as 5-FU, consistently induce tumor resistance and cannot cure advanced disease, we have now tested the ability of TS-shRNA delivered using adeno-associated viral (AAV) vectors as a pharmacological safe and effective anti-tumor strategy. We packaged TS shRNA under the mouse insulin promoter (mIP) for islet-cell specific expression using capsid optimized Y to F double mutant AAV (AAV8-2M) to generate viral particles of scAAV8-2M-mIP-GFP-hTS-shRNA. We treated hTS/Men1-/- mice with intraperitoneal (IP) injection (1x1011 viral genomes/mice). Treated and control mice were analyzed for PanNET progression, TYMS expression and survival. In addition, we tested a human PanNET tumor cell line (BON) that was isogenic with or without hTS expression for tumor formation in xenograft model. We confirmed sustained reduction of TYMS levels 3 weeks after IP delivery of AA8-2M-mIP-GFP-hTS-shRNA into PanNET tissues of hTS/Men1-/- mice. In addition, AA8-2M-mIP-GFP-hTS-shRNA delivery blocked PanNET tumor progression and enhanced the survival of treated mice as compared to vector controls. We also confirmed that TYMS knock-down in BON cells by hTS-shRNA reduced xenograft tumor growth as compared to non-specific shRNA controls. In conclusion, the ability of AAV-mediated TS shRNA to block PanNET tumor progression directly demonstrates the importance of elevated TYMS in tumorigenesis and offers a novel anti-cancer strategy. Citation Format: Vinod Vijayakurup, Benjamin Meyer, Akbar Nawab, Frederic J. Kaye, Maria V. Guijarro, Maria Zajac-Kaye. TYMS as a novel target for AAV-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2733.

Maggi was the most popular instant noodles brand in India, which children in particular loved to snack on. The brand had a dominant position until suddenly in mid-2015 it got engulfed in controversy. Several state food regulators found that Maggi contained monosodium glutamate as well as lead well above the prescribed limits. Both these substances were harmful especially for children. When Nestlé India was confronted with lab test results it stuck to its position that they had a world class quality control process in place and that their products were safe for consumption. Finally, the national food regulator FSSAI, ordered a ban on the sale of Maggi including product recall. Consequently, several state governments imposed temporary ban on the sale of Maggi noodles in their respective states. The future of the company suddenly looked very bleak. Nestlé India was slow to respond to this fast unfolding crisis. Further, their responses were very brief and not adequately culture-sensitive. This led to the feeling in several quarters that the company was probably guilty of wrongdoing. To set right things Nestlé's worldwide CEO flew into India to douse the flames of the controversy and draw up an appropriate strategy to bail out the brand. He address the media, put in place a new CEO for Nestlé India and set brand Maggi on the path of recovery. However, Nestlé India was still facing a number of critical issues. What should be done to win over the trust of its customers? How should it recover market share lost to competitors both old rivals and new entrants? What strategy should it develop to succeed with the new products, especially hot heads, launched along with the comeback strategy? Should it change its approach to dealing with government health officials to prevent confrontations in future? How should it shorten the response time and make it effective in the face of a media backed public outcry in future?

The use and effects of studded tires in Oregon are investigated, updating a 1974 report. Studded-tire use was surveyed, rut measurements collected, studded-tire traffic estimated, and pavement wear and damage analyzed. Studded-tire use in Oregon varies geographically. Half of the vehicles equipped with studs use them on all wheels, representing a significant change from 1974 practices. More than 23 percent of vehicles used studded tires in 1994. Studded-tire pavement wear coefficients were calculated and found to be half those reported previously. The coefficients for rigid and flexible pavements are 0.20 mm (0.008 in.) and 0.86 mm (0.034 in.), respectively, per 100,000 studded tire passes. Studded-tire wear will shorten pavement life on high-volume routes in Oregon. Asphalt pavements experiencing average daily traffic (ADT) volumes of 35,000 and 20 percent studded-tire use will reach the threshold rut in 7 years. Portland cement concrete (PCC) pavements experiencing 120,000 ADT and 20 percent studded-tire use will develop the threshold rut depth of 19 mm in 8 years. These estimates substantially reduce Oregon design life expectations for asphalt and PCC pavements. The estimated Oregon studded-tire damage for 1994 is $37 million for the state highway network, with similar damage for municipal and county roads. Alternatives are discussed to reduce the damage caused by studded tires, including a ban on studs, shortened use period, lightweight studs, user fees, and public education initiatives.

Introduction: Pleural cavity drainage is a crucial component of the surgical management of patients with various chest diseases. Digital drainage systems are increasingly used in contemporary thoracic surgical procedure, which is likely a result of their effectiveness in achieving early postoperative ambulation, cutting down on hospital stays and lowering costs. The vast majority of thoracic surgeons worldwide prefer digital drainage systems to traditional ones. The advantages of the former, however, are disputed by some researchers. Aim: The objective of this study was to compare the two types of pleural drainage mechanisms, conventional and digital, in terms of duration of pleural drainage in days, financial cost, and postoperative air leak duration. Materials and methods: The study focused on 80 patients who underwent various thoracic surgical interventions in the Clinic of Thoracic and Abdominal Surgery at St George University Hospital in Plovdiv. They were divided into two groups: group 1 consisted of 42 patients who were postoperatively attached to a conventional non-mobile pleural drainage system, and group 2 consisted of 38 patients in whom a mobile digital pleural drainage system was used. The main analyzed data were duration of pleural drainage, duration of postoperative air leak, hospital stay, and financial costs. Results: The average duration of pleural drainage, regardless of surgery and type of drainage system applied was 4.86±0.8 days. The average duration of pleural drainage in patients attached to the mobile digital drainage system was shorter than that in patients with a conventional pleural non-mobile drainage system, regardless of the type of surgery done. This difference was statistically significant in favor of the digital pleural drainage system. The study also found a statistically significant difference in terms of financial costs in favor of digital draining system. The average cost of a hospital stay for patients attached to a mobile digital drainage system was BGN 119.40±7.15, whereas the average cost of a hospital stay for patients connected to a traditional pleural drainage system (PDS) was BGN 159±10.50. Regarding the duration of postoperative air leak, the difference between the types of pleural drainage mechanism used was not convincing. Conclusions: Digital pleural drainage systems provide clinicians with an opportunity to assess the postoperative air leak more precisely, track its dynamics, shorten hospital stays, reduce postoperative costs, and optimize the time to remove the chest drain. Based on these features, they will undoubtedly continue to enter everyday surgical practice.

Abstract An open question in cloud physics is how rain forms in warm cumulus as rapidly as it is sometimes observed. In particular, the growth of cloud droplets across the size gap from 10 to 50 μm in radius has not been fully explained. In this paper, the authors investigate the growth of cloud droplets by collision–coalescence, taking into account both the gravitational mechanism and several enhancements of the collision–coalescence rate due to air turbulence. The kinetic collection equation (KCE) is solved with an accurate bin integral method and a newly developed parameterization of turbulent collection kernel derived from direct numerical simulation of droplet-laden turbulent flows. Three other formulations of the turbulent collection kernel are also considered so as to assess the dependence of the rain initiation time on the nature of the collection kernel. The results are compared to the base case using the Hall hydrodynamical–gravitational collection kernel. Under liquid water content and eddy dissipation rate values typical of small cumulus clouds, it is found that air turbulence has a significant impact on the collection kernel and thus on the time required to form drizzle drops. With the most realistic turbulent kernel, the air turbulence can shorten the time for the formation of drizzle drops by about 40% relative to the base case, applying measures based on either the radar reflectivity or the mass-weighted drop size. A methodology is also developed to unambiguously identify the three phases of droplet growth, namely, the autoconversion phase, the accretion phase, and the larger hydrometeor self-collection phase. The important observation is that even a moderate enhancement of collection kernel by turbulence can have a significant impact on the autoconversion phase of the growth.

В статье определена проблема эффективности контроля за ограничением конституционного права отправления и получения почтово-телеграфных отправлений при избрании судом определенных видов мер пресечения. В частности, недостаточно урегулирован в действующем законодательстве, в подзаконных нормативных актах, в том числе приказах контролирующих органов процесс осуществления контроля за соблюдением такого запрета,. При проведении исследования использовались общенаучные и частнонаучные методы. Для разрешения поставленной проблемы исследуется законодательство, регламентирующее правоотношения по отправлению и получению почтово-телеграфных отправлений, особенности организации на практике контроля и мнения по субъекту контроля за ограничением конституционного права. Согласно анализу законодательства предлагается замена субъекта, осуществляющего контроль общения посредством почтовой связи. По результатам исследования автор делает обоснованный вывод по субъекту контроля, что, безусловно, влияет на механизм рассматриваемого правоотношения по организации контроля. А именно о целесообразности следователю, дознавателю либо суду самостоятельно направлять оператору почтовой связи постановление суда об избрании меры пресечения, содержащей запрет отправлять и получать почтово-телеграфные отправления, с указанием извещения следователя либо суда о наличии почтово-телеграфного отправления от имени подозреваемого (обвиняемого) либо на имя подозреваемого (обвиняемого), что сократит время уведомления лица, осуществляющего предварительное расследование или судебное разбирательство. The article defines the problem of the effectiveness of control over the restriction of the constitutional right to send and receive postal and telegraphic items when the court chooses certain types of preventive measures in criminal proceedings. Namely, the process of monitoring compliance with such a ban as sending and receiving postal and telegraphic items is not sufficiently regulated in the current legislation, in subordinate regulations, including orders of regulatory authorities. General scientific and private scientific methods were used in the research. Namely, in order to solve the problem posed, the legislation regulating the legal relations on the dispatch and receipt of postal and telegraphic items, the specifics of the control organization in practice and opinions on the subject of control over the restriction of constitutional law are being investigated. According to the analysis of the legislation, it is proposed to replace the entity that controls communication through postal communication. According to the results of the study, the author makes a reasonable conclusion on the subject of control, which, of course, affects the mechanism of the legal relationship under consideration for the organization of control. Namely, the expediency of the investigator, the inquirer or the court to independently send a court order to the postal operator on the election of a preventive measure containing a ban on sending and receiving postal and telegraphic items, indicating the notification of the investigator or the court about the presence of postal and telegraphic items on behalf of the suspect (accused) or in the name of the suspect (accused), which will shorten the notification time of the person conducting the preliminary investigation or trial.

SIGNIFICANCE This study provides a faster method for objectively measuring accommodative amplitude with an open-field autorefractor in a research setting. PURPOSE Objective measures of accommodative amplitude with an autorefractor take time because of the numerous stimulus demands tested. This study compares protocols using different amounts and types of demands to shorten the process. METHODS One hundred participants were recruited for four age bins (5 to 9, 10 to 14, 15 to 19, and 20 to 24 years) and monocular amplitude measured with an autorefractor using three protocols: proximal, proximal-lens (letter), and proximal-lens (picture). For proximal, measurements were taken as participants viewed a 0.9 mm “E” placed at 13 demands (40 to 3.3 cm = 2.5 to 30 D). The other protocols used a target (either the “E” or a detailed picture) placed at 33 and 12.5 cm followed by 12.5 cm with a series of lenses (−2, −4, and −5.5 D). Adjustments were made for lens effectivity for the three lens conditions, which were thus 9.6, 11.1, and 12.0 D for individuals without additional spectacle lenses. Accommodative amplitude was defined as the greatest response measured with each technique. One-way analysis of variance was used to compare group mean amplitudes across protocols and differences between letter protocols by age bin. RESULTS Amplitudes were significantly different between protocols (p < 0.001), with proximal having higher amplitudes (mean ± standard deviation, 8.04 ± 1.70 D) compared with both proximal-lens protocols (letter, 7.48 ± 1.42 D; picture, 7.43 ± 1.42 D) by post hoc Tukey analysis. Differences in amplitude between the proximal and proximal-lens (letter) protocol were different by age group (p = 0 .003), with the youngest group having larger differences (1.14 ± 1.58 D) than the oldest groups (0.17 ± 0.58 and 0.29 ± 0.48 D, respectively) by post hoc Tukey analysis. CONCLUSIONS The proximal-lens protocols took less time and identified the maximum accommodative amplitude in participants aged 15 to 24 years; however, they may underestimate true amplitude in younger children.

. النظام العربي وآفاق المستقبل. أحمد يوسف وآخرون، عمان: مؤسسة شومان ودار الشروق، 2002. الإسلام، أوربا، الغرب: رهانات المعنى وإرادات الهيمنة، محمد أركون، ترجمة هاشم صالح، لندن وبيروت: دار الساقي،2001، 259ص. الفكر العربي في القرن العشرين (1950-2000)، شاكر النابلسي، بيروت: المؤسسة العربية للدراسات والنشر، 2001، 1614ص. مقاصد الشريعة الخاصة بالتصرفات المالية، عز الدين زغيبة، دبي: مركز جمعية الماجد للثقافة والتراث، 2001، 400 ص. لو لم يظهر الإسلام ما حال العرب الآن؟، شاكر النابلسي، بيروت: دار الآفاق الجديدة، 2002، 384ص. العلمانية الجزئية والعلمانية الشاملة. عبد الوهاب المسيري، بيروت: دار الشروق، 2002، 344ص. . L’Afrique Sans La France. Jean Paul Ngoupande, Paris: Albin Michel, 2002, 393 pp. Netocracy: The New Power Elite and Life After Capitalism. Jonathan B.L. Bard and Jan Soderqvist, New Jersey: Financial Times Prentice Hall, 2002, 288 pp. La Guerre Israélienne de l’information: Désinformation et fausses symetries dans le conflit Israélio-Paletstinien, Joss Dray and Denis Sieffert, Paris: La Decofart, 2002, 127 pp. The Fall of Advertising and the Rise of PR, Al Ries and Laura Ries, New York: HarperCollins Publishers, 2002, 320 pp. Reason before Identity. Amartya Sen, Oxford: Oxford University Press, 2002, 313 pp. The Root Causes of Sudan’s Civil Wars. Douglas S Johnson, Indianapolis: Indiana University Press, 2003, 234 p. The Clash of Orthodoxies: Law, Religion, and Morality in Crisis. Robert P. George, Delaware: ISI Books, 2001, 387 p. The Heart of Islam: Enduring Values for Humanity. Sayyed Hossein Nasr. New York: Harper Collins, 2002, 338 p. Jihad: The Rise of Militant Islam in Central Asia, Ahmed Rashid, New Haven, Cincinnati: Yale University Press, 2002, 272 pp. Forbidden Truth: U.S.-Taliban Secret Oil Diplomacy and the Failed Hunt for Bin Laden, Jean-Charles Brisard and Guillaume Dasquie, California: Avalon Publishing Group, 2002, 249 pp. War Without End: Cultural Conflict and the Struggle for America’s Political Future. Robert Shogan, New York: Westview Press, 2002, 360 pp. Gods in the Sky: Astronomy from the Ancients to the Renaissance. Allan Chapman, London: Channel Four Books, 2002, 342 pp. Islam and Democracy: The failure of Dialoque in Algeria. Frederic Vopi. London, Sterling, VA: Pluto Press, 2003. p. 168. للحصول على كامل المقالة مجانا يرجى النّقر على ملف ال PDF في اعلى يمين الصفحة.

The article highlights the results of studies of the effectiveness of index selection in herds of Simmental cattle in organic and conventional milk production using the selection index of R. Teinber, indicating the feasibility of its use, because the indicators of dairy productivity of animals of different groups are significantly different. The improvement of the quantitative indicators of milk productivity of cows in the herd of the Simmental breed, both in conventional and organic dairy production, largely depends on the value of the selection index. The strength of the influence of the selection index in the herd of Miroslavel-Agro on milk yield for 305 days of lactation of cows was 67%, milk fat – 88, milk protein – 77, total production of fat and protein – 86%, in the herd of "Galeks-Agro", respectively: 71, 87, 74 and 84% (P < 0.001). The first-calf cows of the Simmental breed under the conditions of organic milk production were somewhat dominated by animals of the conventional herd in terms of milk productivity - in terms of milk yield per 305 days of lactation per 114 kg, with an insignificant difference. First-calf cows under conditions of organic milk production had worse reproduction parameters (service period – 136 days, reproductive rate – 0.89), compared to conventional milk production (127 days and 0.91), which is associated with the prohibition of the use of artificial vitamins, hormonal veterinary drugs to stimulate hunting, and shorten the duration of biological periods. The lowest milk productivity among the experimental groups were characterized by animals of the fifth group of both herds – their yield for 305 days of the first lactation amounted to 5042 and 4912 kg of milk, fat milk 4.08 and 4.11%, protein milk 3.37 and 3.46%. With a decrease in the selection index in animals has been established a decrease in dairy yield from 6767 (first group) to 5452 kg (fifth group), milk fat – from 290.7 to 204.8, milk protein – from 244.4 to 177.8 kg in the herd "Myroslavel-Agro" and from 7170 (first group) to 4912 kg (fifth group), milk fat – from 303.5 to 201.3, milk protein – from 252.8 to 169.5 kg in stage of "Halex-Agro". We recommend to use for repair of a herd of cows whose referred to the first two groups with the value of the selection index not lower than +23.0 (for "Myroslavel-Agro") and +26.3 (for "Galex-Agro"). The worst in terms of milk productivity, with the lowest value of the selection index (respectively: -44.9 and -51.7), it is desirable to sell to subsidiaries or other farms. It was found that when selecting animals according to the Tainber`s index, animals in organic and conventional herds are characterized by a lack of harmonious interaction with their habitat - cows are characterized by high dairy yields with simultaneous deterioration of their reproductive capacity, which confirms the well-known inverse relationship between these traits. The first-calf cows of the Simmental breed in the conditions of organic milk production slightly outnumber the animals of the conventional herd in terms of dairy productivity - in terms of milk yield for 305 days of lactation by 114 kg (P > 0.05). The first-calf cows in the conditions of organic milk production had worse reproduction parameters (service period – 136 days, reproductive rate – 0.89), compared to conventional milk production (127 days and 0.91). In our opinion, this is due to the peculiarities of the dairy industry in organic milk production and the ban on the use of artificial vitamins, hormonal veterinary drugs to stimulate hunting and reduce the duration of biological periods of reproduction.

BackgroundRecently, TIGIT+PD1 blockade was shown to confer additive survival benefits in orthotopic glioblastoma and colon cancer mouse models1 2—notably, this included experiments3 that used the 1G9 TIGIT monoclonal antibody (mAb) that has potentially agonistic effects.1 Herein we investigated the TIGIT/CD226/CD155 axis and effects of combining clinically analogous PD-1/PD-L1 mAbs with TIGIT-targeting 1G9 mAb in murine glioblastoma models.MethodsThe overall survival (OS) associated with TIGIT (non-depleting IG9; 200μg every 3days for 4 doses),1 PD-1 (8H3; initial 500μg followed by 250μg every 3days for 7 doses), PD-L1 (6A2; initial 500μg followed by 250μg every 3days for 7 doses), and/or IgG mAbs was assessed in immunocompetent C57BL/6 albino mice intracranially implanted with syngeneic GL261-luc2 or CT2A-luc.4 5 The roles of T cells and NK cells were examined using depletion with CD8a, CD4, or NK1.1 mAbs. Expression of TIGIT/CD226/CD155 and PD-1/PD-L1/PD-L2 by tumor and tumor-infiltrating immune cells was evaluated using flow cytometry and RT-qPCR.ResultsIn vitro, GL261-luc2 and CT2A-luc tumor cells moderately expressed PD-L1, PD-1, and TIGIT; but strongly expressed TIGIT’s inhibitory ligand CD155.(Figure1A-B) Ex vivo, >83% of CD8+ and CD4+TILs in GL261-luc2 co-expressed TIGIT+/CD226+: ≥2x the proportions in CT2A-luc.(Figure 2A) CD155 and PD-L1 were highly co-expressed on tumor-infiltrating macrophages: greater in GL261-luc2 than CT2A-luc tumors.(Figure 2B)In GL261-luc2 mice, anti-TIGIT monotherapy displayed minimal OS improvement; whereas anti-PD-1 and anti-PD-L1 monotherapies demonstrated robust OS responses.(Figure 3A) Adding anti-TIGIT to PD-1/PD-L1 blockade demonstrated synergism with anti-PD-1. Anti-TIGIT plus anti-PD-1 displayed nominally improved OS in CT2A-luc compared to anti-PD-1 monotherapy (p=0.11).(Figure 3B).Given robust T-cell expression of TIGIT and PD-1, we examined how CD4+ or CD8+ depletion affected responses in GL261-luc2 mice: depletion completely abrogated anti-PD-1’s benefits.(Figure 4) Although CD4/CD8 depletion also reduced anti-TIGIT+anti-PD1’s efficacy, the resulting OS matched that of non-depleted anti-PD-1 monotherapy. Additionally, NK cell depletion had no effect on anti-TIGIT+anti-PD1’s efficacy.Abstract 256 Figure 1TIGIT/CD155 axis and PD-1/PD-L1/PD-L2 axis expression in murine glioblastoma model tumor cells. Protein and RNA expression of the TIGIT and PD-1 immune checkpoints — and their ligands CD155 and PDL-1/PD-L2 respectively — on GL261-luc2 and CT2A-luc tumor cells using (A) flow cytometry (blue=samples, red=unstained controls) and (B) RT-qPCR (grey=GL261-luc2, black=CT2A-luc). Pdcd1 encodes PD-1, Cd274 encodes PD-L1, Pvr encodes CD155Abstract 256 Figure 2TIGIT/CD155 axis and PD-1/PD-L1/PD-L2 axis expression in murine glioblastoma model tumor-infiltrating immune cells. (A) Flow cytometry analysis of protein expression for TIGIT (y-axis) and CD226 (x-axis; a competitor of TIGIT) on CD8+, CD4+/FOXP3+ Treg, and CD4+/FOXP3- Teff tumor-infiltrating lymphocytes (TILs) from GL261-luc2 and CT2A-luc tumor-bearing mice. (B) Flow cytometry analysis of protein expression for CD155 (TIGIT’s ligand; bottom) and PD-L1 (PD-1’s ligand; top) on tumor-infiltrating myeloid populations from GL261-luc2 and CT2A-luc tumor-bearing mice. Mean fluorescent intensity (MFI) was compared between cell lines, *indicates statistical significance. Myeloid populations included CD45+/CD11b+/CD11c+/F4-80+ macrophages, CD11b+/CD11c+ and CD11b-/CD11c+ dendritic cells (DCs), CD11b+/CD11c-/Ly6C+/Ly6G- monocytes, CD11b+/CD11c-/Ly6Cmid/Ly6G+ granulocytes, and CD45dim/CX3CR1+ microglia. Tumors were dissociated and leukocytes were enriched for using Percoll gradient. n=5 mice per group.Abstract 256 Figure 3The survival associated with TIGIT-targeting mAb therapy with/without clinically-analogous PD-1/PD-L1 blockade. (A) Kaplan-Meier estimated overall survival (measured from day of intracranial tumor implantation) of GL261-luc2 mice treated with TIGIT (1G9), PD-1 (8H3), PD-L1 (6A2), TIGIT + PD-1, TIGIT + PD-L1 mAbs, or IgG control. (B) A) Kaplan-Meier estimated overall survival (measured from day of intracranial tumor implantation) of CT2A-luc mice treated with TIGIT (1G9), PD-1 (8H3), TIGIT + PD-1 mAbs, or IgG control. For both experiments, all treatments were started on day 6 following implantation, with the following dosing: anti-TIGIT was given as 200μg every 3days for 4 doses. Both anti-PD-1 and anti-PD-L1 were given as an initial 500μg dose followed by 250μg every 3days for 7 doses.4 The n per group and number at risk table is included underneath each graph, along with the corresponding Cox regression analysis. Treatment groups with significantly different OS from the combination TIGIT + PD-1 combination-treated reference group were highlighted in yellow. HR = hazard ratio, CI = confidence interval.Abstract 256 Figure 4How depletion of CD8+ T cells, CD4+ T cells, or NK cells affects survival associated with TIGIT-targeting mAb therapy with/without clinically-analogous PD-1 blockade. Kaplan-Meier estimated overall survival (measured from day of intracranial tumor implantation) of GL261-luc2 mice treated with TIGIT (1G9), PD-1 (8H3), TIGIT + PD-1 mAbs, or IgG control; and compared to groups that additional had CD8+, CD4+, or NK1.1+ antibody-based depletion. The treatment and dosing characteristics were the same as Figure 3. The n per group and number at risk table is included underneath the graph, along with the corresponding Cox regression analysis. Treatment groups with significantly different OS from the combination TIGIT + PD-1 combination-treated reference group were highlighted in yellow. HR = hazard ratio, CI = confidence interval.ConclusionsOur results recapitulate published findings regarding the synergistic benefits of combining TIGIT 1G9 mAb with anti-PD-1 using the clinically-relevant 8H3 mAb in syngeneic mouse glioblastoma, and extend those findings to anti-TIGIT+anti-PDL1 combinations. TIGIT/CD226 was highly co-expressed by immuno-responsive GL261-luc2’s tumor-infiltrating lymphocytes (TILs); wheres CD155/PD-L1 expression predominated in tumor-infiltrating myeloid cells. Depletion of CD8+ or CD4+ TILs modestly reduced anti-TIGIT+anti-PD1’s efficacy—suggesting a mechanism that is at least partially independent of T (and NK) cells. Our preliminary results suggest a complex interplay between TIGIT/CD226/CD155 and PD-1/PD-L1/PD-L2 axes in tumors and their microenvironmental constituents that warrants further investigation; plus, careful consideration of antibody clones’ functionality is necessary for designing immunotherapy combinations.AcknowledgementsWe gratefully acknowledge the support of the The Jennifer Oppenheimer Cancer Research Initiative; The Ben and Catherine Ivy Foundation; Hope It’s A Beach Thing; and the Pan Mass Challenge (Erica’s Entourage and CRUS11TOUR), and the NCI (P01CA236749; K12CA090354).ReferencesDixon KO, Schorer M, Nevin J, Etminan Y, Amoozgar Z, Kondo T, Kurtulus S, Kassam N, Sobel RA, Fukumura D, Jain RK, Anderson AC, Kuchroo VK, Joller N. Functional anti-TIGIT antibodies regulate development of autoimmunity and antitumor immunity. J Immunol 2018 April 15;200(8):3000–3007.Hung AL, Maxwell R, Theodros D, Belcaid Z, Mathios D, Luksik AS, Kim E, Wu A, Xia Y, Garzon-Muvdi T, Jackson C, Ye X, Tyler B, Selby M, Korman A, Barnhart B, Park SM, Youn JI, Chowdhury T, Park CK, Brem H, Pardoll DM, Lim M. TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM. Oncoimmunology 2018 May 24;7(8):e1466769.Raphael I, Kumar R, McCarl LH, Shoger K, Wang L, Sandlesh P, Sneiderman CT, Allen J, Zhai S, Campagna ML, Foster A, Bruno TC, Agnihotri S, Hu B, Castro BA, Lieberman FS, Broniscer A, Diaz AA, Amankulor NM, Rajasundaram D, Pollack IF, Kohanbash G. TIGIT and PD-1 immune checkpoint pathways are associated with patient outcome and anti-tumor immunity in glioblastoma. Front Immunol 2021 May 7;12:637146.Reardon DA, Gokhale PC, Klein SR, Ligon KL, Rodig SJ, Ramkissoon SH, Jones KL, Conway AS, Liao X, Zhou J, Wen PY, Van Den Abbeele AD, Hodi FS, Qin L, Kohl NE, Sharpe AH, Dranoff G, Freeman GJ. Glioblastoma eradication following immune checkpoint blockade in an orthotopic, immunocompetent model. Cancer Immunol Res 2016 February;4(2):124–35. Iorgulescu JB, Gokhale PC, Speranza MC, Eschle BK, Poitras MJ, Wilkens MK, Soroko KM, Chhoeu C, Knott A, Gao Y, Lim-Fat MJ, Baker GJ, Bonal DM, Nguyen QD, Grant GRL, Ligon KL, Sorger PK, Chiocca EA, Anderson AC, Kirschmeier PT, Sharpe AH, Freeman GJ, Reardon DA. Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma. Clin Cancer Res 2021 January 1;27(1):276–287.

Recently, corporate bond has been becoming a controversial debate topic in Vietnam. During 2022 Vietnamese economy experienced several devastating scandals relating to corporate bond that leading to the issuance of several legal regulations by the Government. Realistically, given the strong encouragement of Vietnamese Government, the size of corporate bond market has reached approximately 21% of national GDP (VCCI, 2022) illustrating a considerable attention of potential investors and local businesses on this typical capital raising instruments. However, from both academic and society perspectives, there has been a research gap in the extant literature review on the underlying reasons for corporate bond demand in an emerging country. Hence, the study aims to comprehensively examine the determinants of investor demand for corporate bond in the context of Vietnam. The research objectives are achieved by applying both qualitative and quantitative approaches. While the qualitative method which based on VCCI (2022) questionnaires to identify and document the corporate bond demand, the quantitative method provides statistical evidences on determinants of corporate bond demand. The research result show that the credit risk and bond market presence are significant attributes for investor demand. These indicators are more pronounced during the crisis period which is explained by information asymmetry theory and the benefit of diversifications. The research findings are consistent with prior studies of Hotchkiss and Ronen (2002), Hale and Santos (2008) stating that high investor demand shorten the time for subsequent bond issuance events and potentially reduces the corporate’s cost of capital. Therefore, the research is beneficial to the Government, corporate bond issuers and researchers.

Recent stitch-based simulation methods permit effective and realistic simulation for the planar structure of warp-knitted fabrics. However, simulating the warp-knitted fully formed jacquard fabric with a specific shape remains a challenge. Characteristics of diversity and complexity of this kind of fabric greatly raise the simulation difficulty. We propose a new modeling and simulation method based on the mesh model with complex shapes. We start from the analysis of the double needle bed warp-knitting technique, and establish a three-dimensional fabric mesh model, producing a finer stitch placement on a double needle bed knitted structure. Due to the deformation date derived from the jacquard pattern, stitches are placed at the actual locations. The used stitches forming the fully formed products are rendered according to the jacquard pattern. Using the two-dimensional plates and corresponding three-dimensional objects as input models to define the shape of the warp-knitted products, stitches are transferred from two to three-dimensional model objects by spatial mapping. The interface of our modeling system allows for designing complex jacquard patterns and selecting specific models for warp-knitted products. The method we propose leads to a visible design process with results visualization, which is convenient for designers to modify the knitting parameters covering knitting information and jacquard pattern before the product is knitted. The simulation method can be applied to the rapid design of the warp-knitted boa, which can reduce duplicate sampling, shorten the design process, and save raw material costs. Further research will be carried out in the future to improve this simulation method.

Abstract Recent studies have demonstrated that the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) could be used to detect superbugs, such as methicillin-resistant Staphylococcus aureus (MRSA). Due to an increasingly clinical need to classify between MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) efficiently and effectively, we were motivated to develop a systematic pipeline based on a large-scale dataset of MS spectra. However, the shifting problem of peaks in MS spectra induced a low effectiveness in the classification between MRSA and MSSA isolates. Unlike previous works emphasizing on specific peaks, this study employs a binning method to cluster MS shifting ions into several representative peaks. A variety of bin sizes were evaluated to coalesce drifted or shifted MS peaks to a well-defined structured data. Then, various machine learning methods were performed to carry out the classification between MRSA and MSSA samples. Totally 4858 MS spectra of unique S. aureus isolates, including 2500 MRSA and 2358 MSSA instances, were collected by Chang Gung Memorial Hospitals, at Linkou and Kaohsiung branches, Taiwan. Based on the evaluation of Pearson correlation coefficients and the strategy of forward feature selection, a total of 200 peaks (with the bin size of 10 Da) were identified as the marker attributes for the construction of predictive models. These selected peaks, such as bins 2410–2419, 2450–2459 and 6590–6599 Da, have indicated remarkable differences between MRSA and MSSA, which were effective in the prediction of MRSA. The independent testing has revealed that the random forest model can provide a promising prediction with the area under the receiver operating characteristic curve (AUC) at 0.8450. When comparing to previous works conducted with hundreds of MS spectra, the proposed scheme demonstrates that incorporating machine learning method with a large-scale dataset of clinical MS spectra may be a feasible means for clinical physicians on the administration of correct antibiotics in shorter turn-around-time, which could reduce mortality, avoid drug resistance and shorten length of stay in hospital in the future.

Abstract In shipbuilding industry, to reduce the staying time of the ship in a dock, floating crane and floating dock are used to handle the mega-blocks, thus it increased the turnover of the dock. Therefore, spatial scheduling for mega-block in an assembly yard becomes important in shipbuilding industry. However, spatial scheduling of mega-blocks has some unique characteristics compared with the well-known classic bin-packing problem, and not many studies can be found on this issue. This research proposes an enhanced mathematical formulation and a heuristic algorithm for spatial scheduling of mega-block arrangement problem. The formulation provides tight bound compared with the existing formulation, and the proposed heuristic can obtain good quality of the solution in a reasonable amount of time even when the size of the instance became large. Introduction Shipbuilding industry involves constructing ships and other floating vessels. Block is a base element of the shipbuilding process, and the blocks are assembled and welded in the block assembly shop, and finally erected to a ship in a dry dock. A size of a block is around 15~30 meters with a weight of around 30~300 tons (Zheng et al. 2011), and a large ship consists of around 150 blocks (Koh et al. 2011b). Some blocks are outsourced and timely delivery and quality of blocks have an absolute impact on the ship’s quality. Also, it is possible to shorten the dock duration by receiving blocks from several companies at the same time.

Discussions of the economic theory of planned obsolescence—the purposeful embedding of redundancy into the functionality or other aspect of a product—in the 1980s and 1990s often focused on the impact of such a design strategy on manufacturers, consumers, the market, and, ultimately, profits (see, for example, Bulow; Lee and Lee; Waldman). More recently, assessments of such shortened product life cycles have included calculations of the environmental and other costs of such waste (Claudio; Kondoh; Unruh). Commonly utilised examples are consumer products such as cars, whitegoods and small appliances, fashion clothing and accessories, and, more recently, new technologies and their constituent components. This discourse has been adopted by those who configure workers as human resources, and who speak both of skills (Janßen and Backes-Gellner) and human capital itself (Chauhan and Chauhan) being made obsolete by market forces in both predictable and unplanned ways. This includes debate over whether formal education can assist in developing the skills that make their possessors less liable to become obsolete in the workforce (Dubin; Holtmann; Borghans and de Grip; Gould, Moav and Weinberg). However, aside from periodic expressions of disciplinary angst (as in questions such as whether the Liberal Arts and other disciplines are becoming obsolete) are rarely found in discussions regarding higher education. Yet, higher education has been subsumed into a culture of commercial service provision as driven by markets and profit as the industries that design and deliver consumer goods. McKelvey and Holmén characterise this as a shift “from social institution to knowledge business” in the subtitle of their 2009 volume on European universities, and the recent decade has seen many higher educational institutions openly striving to be entrepreneurial. Despite some debate over the functioning of market or market-like mechanisms in higher education (see, for instance, Texeira et al), the corporatisation of higher education has led inevitably to market segmentation in the products the sector delivers. Such market segmentation results in what are called over-differentiated products, seemingly endless variations in the same product to attempt to increase consumption and attendant sales. Milk is a commonly cited example, with supermarkets today stocking full cream, semi-skimmed, skimmed, lactose-free, soy, rice, goat, GM-free and ‘smart’ (enriched with various vitamins, minerals and proteins) varieties; and many of these available in fresh, UHT, dehydrated and/or organic versions. In the education market, this practice has resulted in a large number of often minutely differentiated, but differently named, degrees and other programs. Where there were once a small number of undergraduate degrees with discipline variety within them (including the Bachelor of Arts and Bachelor of Science awards), students can now graduate with a named qualification in a myriad of discipline and professional areas. The attempt to secure a larger percentage of the potential client pool (who are themselves often seeking to update their own skills and knowledges to avoid workforce obsolescence) has also resulted in a significant increase in the number of postgraduate coursework certificates, diplomas and other qualifications across the sector. The Masters degree has fractured from a research program into a range of coursework, coursework plus research, and research only programs. Such proliferation has also affected one of the foundations of the quality and integrity of the higher education system, and one of the last bastions of conventional practice, the doctoral degree. The PhD as ‘Gold-Standard’ Market Leader? The Doctor of Philosophy (PhD) is usually understood as a largely independent discipline-based research project that results in a substantial piece of reporting, the thesis, that makes a “substantial original contribution to knowledge in the form of new knowledge or significant and original adaptation, application and interpretation of existing knowledge” (AQF). As the highest level of degree conferred by most universities, the PhD is commonly understood as indicating the height of formal educational attainment, and has, until relatively recently, been above reproach and alteration. Yet, whereas universities internationally once offered a single doctorate named the PhD, many now offer a number of doctoral level degrees. In Australia, for example, candidates can also complete PhDs by Publication and by Project, as well as practice-led doctorates in, and named Doctorates of/in, Creative Arts, Creative Industries, Laws, Performance and other ‘new’ discipline areas. The Professional Doctorate, introduced into Australia in the early 1990s, has achieved such longevity that it now has it’s own “first generation” incarnations in (and about) disciplines such as Education, Business, Psychology and Journalism, as well as a contemporary “second generation” version which features professionally-practice-led Mode 2 knowledge production (Maxwell; also discussed in Lee, Brennan and Green 281). The uniquely Australian PhD by Project in the disciplines of architecture, design, business, engineering and education also includes coursework, and is practice and particularly workplace (or community) focused, but unlike the above, does not have to include a research element—although this is not precluded (Usher). A significant number of Australian universities also currently offer a PhD by Publication, known also as the PhD by Published Papers and PhD by Published Works. Introduced in the 1960s in the UK, the PhD by Publication there is today almost exclusively undertaken by academic staff at their own institutions, and usually consists of published work(s), a critical appraisal of that work within the research context, and an oral examination. The named degree is rare in the USA, although the practice of granting PhDs on the basis of prior publications is not unknown. In Australia, an examination of a number of universities that offer the degree reveals no consistency in terms of the framing policies except for the generic Australian Qualifications Framework accreditation statement (AQF), entry requirements and conditions of candidature, or resulting form and examination guidelines. Some Australian universities, for instance, require all externally peer-refereed publications, while others will count works that are self-published. Some require actual publications or works in press, but others count works that are still at submission stage. The UK PhD by Publication shows similar variation, with no consensus on purpose, length or format of this degree (Draper). Across Australia and the UK, some institutions accept previously published work and require little or no campus participation, while others have a significant minimum enrolment period and count only work generated during candidature (see Brien for more detail). Despite the plethora of named degrees at doctoral level, many academics continue to support the PhD’s claim to rigor and intellectual attainment. Most often, however, these arguments cite tradition rather than any real assessment of quality. The archaic trappings of conferral—the caps, gowns and various other instruments of distinction—emphasise a narrative in which it is often noted that doctorates were first conferred by the University of Paris in the 12th century and then elsewhere in medieval Europe. However, challenges to this account note that today’s largely independently researched thesis is a relatively recent arrival to educational history, being only introduced into Germany in the early nineteenth century (Bourner, Bowden and Laing; Park 4), the USA in a modified form in the mid-nineteenth century and the UK in 1917 (Jolley 227). The Australian PhD is even more recent, with the first only awarded in 1948 and still relatively rare until the 1970s (Nelson 3; Valadkhani and Ville). Additionally, PhDs in the USA, Canada and Denmark today almost always incorporate a significant taught coursework element (Noble). This is unlike the ‘traditional’ PhD in the UK and Australia, although the UK also currently offers a number of what are known there as ‘taught doctorates’. Somewhat confusingly, while these do incorporate coursework, they still include a significant research component (UKCGE). However, the UK is also adopting what has been identified as an American-inflected model which consists mostly, or largely, of coursework, and which is becoming known as the ‘New Route British PhD’ (Jolley 228). It could be posited that, within such a competitive market environment, which appears to be driven by both a drive for novelty and a desire to meet consumer demand, obsolescence therefore, and necessarily, threatens the very existence of the ‘traditional’ PhD. This obsolescence could be seen as especially likely as, alongside the existence of the above mentioned ‘new’ degrees, the ‘traditional’ research-based PhD at some universities in Australia and the UK in particular is, itself, also in the process of becoming ‘professionalised’, with some (still traditionally-framed) programs nevertheless incorporating workplace-oriented frameworks and/or experiences (Jolley 229; Kroll and Brien) to meet professionally-focused objectives that it is acknowledged cannot be met by producing a research thesis alone. While this emphasis can be seen as operating at the expense of specific disciplinary knowledge (Pole 107; Ball; Laing and Brabazon 265), and criticised for that, this workplace focus has arisen, internationally, as an institutional response to requests from both governments and industry for training in generic skills in university programs at all levels (Manathunga and Wissler). At the same time, the acknowledged unpredictability of the future workplace is driving a cognate move from discipline specific knowledge to what have been described as “problem solving and knowledge management approaches” across all disciplines (Gilbert; Valadkhani and Ville 2). While few query a link between university-level learning and the needs of the workplace, or the motivating belief that the overarching role of higher education is the provision of professional training for its client-students (see Laing and Brabazon for an exception), it also should be noted that a lack of relevance is one of the contributors to dysfunction, and thence to obsolescence. The PhD as Dysfunctional Degree? Perhaps, however, it is not competition that threatens the traditional PhD but, rather, its own design flaws. A report in The New York Times in 2007 alerted readers to what many supervisors, candidates, and researchers internationally have recognised for some time: that the PhD may be dysfunctional (Berger). In Australia and elsewhere, attention has focused on the uneven quality of doctoral-level degrees across institutions, especially in relation to their content, rigor, entry and assessment standards, and this has not precluded questions regarding the PhD (AVCC; Carey, Webb, Brien; Neumann; Jolley; McWilliam et al., "Silly"). It should be noted that this important examination of standards has, however, been accompanied by an increase in the awarding of Honorary Doctorates. This practice ranges from the most reputable universities’ recognising individuals’ significant contributions to knowledge, culture and/or society, to wholly disreputable institutions offering such qualifications in return for payment (Starrs). While generally contested in terms of their status, Honorary Doctorates granted to sports, show business and political figures are the most controversial and include an award conferred on puppet Kermit the Frog in 1996 (Jeffries), and some leading institutions including MIT, Cornell University and the London School of Economics and Political Science are distinctive in not awarding Honorary Doctorates. However, while distracting, the Honorary Doctorate itself does not answer all the questions regarding the quality of doctoral programs in general, or the Doctor of Philosophy in particular. The PhD also has high attrition rates: 50 per cent or more across Australia, the USA and Canada (Halse 322; Lovitts and Nelson). For those who remain in the programs, lengthy completion times (known internationally as ‘time-to-degree’) are common in many countries, with averages of 10.5 years to completion in Canada, and from 8.2 to more than 13 years (depending on discipline) in the USA (Berger). The current government performance-based funding model for Australian research higher degrees focuses attention on timely completion, and there is no doubt that, under this system—where universities only receive funding for a minimum period of candidature when those candidates have completed their degrees—more candidates are completing within the required time periods (Cuthbert). Yet, such a focus has distracted from assessment of the quality and outcomes of such programs of study. A detailed survey, based on the theses lodged in Australian libraries, has estimated that at least 51,000 PhD theses were completed in Australia to 2003 (Evans et al. 7). However, little attention has been paid to the consequences of this work, that is, the effects that the generation of these theses has had on either candidates or the nation. There has been no assessment, for instance, of the impact on candidates of undertaking and completing a doctorate on such facets of their lives as their employment opportunities, professional choices and salary levels, nor any effect on their personal happiness or levels of creativity. Nor has there been any real evaluation of the effect of these degrees on GDP, rates of the commercialisation of research, the generation of intellectual property, meeting national agendas in areas such as innovation, productivity or creativity, and/or the quality of the Australian creative and performing arts. Government-funded and other Australian studies have, however, noted for at least a decade both that the high numbers of graduates are mismatched to a lack of market demand for doctoral qualifications outside of academia (Kemp), and that an oversupply of doctorally qualified job seekers is driving wages down in some sectors (Jones 26). Even academia is demanding more than a PhD. Within the USA, doctoral graduates of some disciplines (English is an often-cited example) are undertaking second PhDs in their quest to secure an academic position. In Australia, entry-level academic positions increasingly require a scholarly publishing history alongside a doctoral-level qualification and, in common with other quantitative exercises in the UK and in New Zealand, the current Excellence in Research for Australia research evaluation exercise values scholarly publications more than higher degree qualifications. Concluding Remarks: The PhD as Obsolete or Retro-Chic? Disciplines and fields are reacting to this situation in various ways, but the trend appears to be towards increased market segmentation. Despite these charges of PhD dysfunction, there are also dangers in the over-differentiation of higher degrees as a practice. If universities do not adequately resource the professional development and other support for supervisors and all those involved in the delivery of all these degrees, those institutions may find that they have spread the existing skills, knowledge and other institutional assets too thinly to sustain some or even any of these degrees. This could lead to the diminishing quality (and an attendant diminishing perception of the value) of all the higher degrees available in those institutions as well as the reputation of the hosting country’s entire higher education system. As works in progress, the various ‘new’ doctoral degrees can also promote a sense of working on unstable ground for both candidates and supervisors (McWilliam et al., Research Training), and higher degree examiners will necessarily be unfamiliar with expected standards. Candidates are attempting to discern the advantages and disadvantages of each form in order to choose the degree that they believe is right for them (see, for example, Robins and Kanowski), but such assessment is difficult without the benefit of hindsight. Furthermore, not every form may fit the unpredictable future aspirations of candidates or the volatile future needs of the workplace. The rate with which everything once new descends from stylish popularity through stages of unfashionableness to become outdated and, eventually, discarded is increasing. This escalation may result in the discipline-based research PhD becoming seen as archaic and, eventually, obsolete. Perhaps, alternatively, it will lead to newer and more fashionable forms of doctoral study being discarded instead. Laing and Brabazon go further to find that all doctoral level study’s inability to “contribute in a measurable and quantifiable way to social, economic or political change” problematises the very existence of all these degrees (265). Yet, we all know that some objects, styles, practices and technologies that become obsolete are later recovered and reassessed as once again interesting. They rise once again to be judged as fashionable and valuable. Perhaps even if made obsolete, this will be the fate of the PhD or other doctoral degrees?References Australian Qualifications Framework (AQF). “Doctoral Degree”. AQF Qualifications. 4 May 2009 ‹http://www.aqf.edu.au/doctor.htm›. Australian Vice-Chancellors’ Committee (AVCC). Universities and Their Students: Principles for the Provision of Education by Australian Universities. Canberra: AVCC, 2002. 4 May 2009 ‹http://www.universitiesaustralia.edu.au/documents/publications/Principles_final_Dec02.pdf›. 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