Educating and Training Accelerator Scientists and Technologists for Tomorrow

Accelerator science and technology is inherently an integrative discipline that combines aspects of physics, computational science, electrical and mechanical engineering. As few universities offer full academic programs, the education of accelerator physicists and engineers for the future has primarily relied on a combination of on-the-job training supplemented with intense courses at regional accelerator schools. This paper describes the approaches being used to satisfy the educational interests of a growing number of interested physicists and engineers.Comment: 19 pages, 3 figure

Implementing Information Security and Its Technology: A LineManagement Perspective

Assuring the security and privacy of institutionalinformation assets is a complex task for the line manager responsible forinternational and multi-national transactions. In the face of an unsureand often conflicting international legal framework, the line managermust employ all available tools in an Integrated Security and PrivacyManagement framework that ranges from legal obligations, to policy, toprocedure, to cutting edge technology to counter the rapidly evolvingcyber threat to information assets and the physical systems thatinformation systems control

High Energy & High Luminosity γγ\gamma\gamma Colliders

With the best of modern standard lasers, high-energy $\gamma\gamma$ colliders from electron beams of E larger than 250 GeV are only possible at the expense of photon luminosity, i.e. 10 times lower than for photon colliders at c.m. energies below 0.5 TeV. For existing state-of-the art lasers, an optimistic upper energy limit for x=4.8 is an electron beam of less than 250 GeV. This Snowmass21 Contributed Paper shows how Free Electron Lasers (FEL) pave the way for High Energy & High Luminosity $\gamma\gamma$ colliders. We present and assess a conceptual design study of a FEL with wavelength of 2.4 $\mu$m and an x-factor in the range of 2 to 40, to maximize the luminosity of a $\gamma\gamma$ collider as second interaction region of 0.5 TeV to 10 TeV c.m. $e^+e^-$ colliders.Comment: Contribution to Snowmass 202

Effects of Usnic Acid on Hyperglycemia and Renal Function in Streptozotocin-Induced Diabetic Rats

Background: Diabetic hyperglycemia and glomerular hyper filtration play a causative role in the progression of chronic kidney disease. Renal glucose handling via Sodium-Glucose Cotransporter (SGLT)-2 is a targetable approach and SGLT-2 inhibitors have proven therapeutic benefits in diabetic kidney disease. Usnic Acid (UA) is an active constituent of lichen species and symbiotic organism of algae and fungi, which is variously studied in folk medicine. The objective of this study was to demonstrate the beneficial effects of UA on glucose homeostasis and renal function in streptozotocin-induced diabetic Sprague-Dawley rats and to determine whether UA has an effect on regulation of SGLT that may further aid in glucoregulation and renal function. Methods: Type 1 diabetes was induced in Sprague-Dawley rats with Streptozotocin (STZ, 60mg/kg) by intraperitoneal route on day 0. Diabetic rats were treated with UA (75 mg/kg) from day 15 to 35 via oral gavage. On day 35, urine was collected and Oral Glucose Tolerance Test (OGTT) was performed. After OGTT, blood was collected through cardiac puncture and kidneys were preserved for biochemical analysis. The results are expressed as mean ± standard error of the mean for n=8 rats per study group. The data were subjected to 1-way or 2-way ANOVA with Bonferroni’s multiple comparison post hoc test using Graph Pad Prism 5 and were considered significant at p≤0.05. Results: Diabetic rats chronically treated with UA had improved hyperphagia, hyperglycemia and glucose intolerance, glomerular hyper filtration, and urinary protein excretion (p\u3c0.05). However, UA did not prevent loss of circulating insulin in diabetic rats. UA’s blood glucose lowering effect was associated with enhanced diuretic-glucosuric response and decreased protein expression of renal SGLT-1 (p\u3c0.05). While protein expression of SGLT-2 was partially increased in the diabetic kidney and it was not decreased by UA. Metabolic corrections with UA treatment occurred in parallel with reductions in uremia and improvement of renal function indices. Additionally, in diabetic rat kidney, UA treatment corrected oxidative changes. Conclusions: Based on preliminary findings we conclude that chronic treatment of UA may act in an insulin-independent manner in lowering of diabetic hyperglycemia and improvement of renal function

Future hadron colliders: From physics perspectives to technology R&D

High energy hadron colliders have been instrumental to discoveries in particle physics at the energy frontier and their role as discovery machines will remain unchallenged for the foreseeable future. The full exploitation of the LHC is now the highest priority of the energy frontier collider program. This includes the high luminosity LHC project which is made possible by a successful technology-readiness program for Nb[subscript 3]Sn superconductor and magnet engineering based on long-term high-field magnet R&D programs. These programs open the path towards collisions with luminosity of 5×10[superscript 34] cm[superscript −2] s[superscript −1] and represents the foundation to consider future proton colliders of higher energies. This paper discusses physics requirements, experimental conditions, technological aspects and design challenges for the development towards proton colliders of increasing energy and luminosity

Diuretic, Glucosuric and Natriuretic Effect of Pantoyltaurine in Diabetic Sprague-Dawley Rats

Sodium-glucose co-transporter (SGLT) inhibitors offer a novel tool to control hyperglycemia and its complications. We present preliminary findings of pantoyltaurine, N-substituted analog of taurine, as diuretic, glucosuric and natriuretic agent in streptozotocin (60 mg/kg/mL, i.p.)-induced type 1 diabetic Sprague-Dawley rats and whether pantoyltaurine has an effect on regulation of SGLT isoforms that may further help in reducing hyperglycemia and improving renal function. After 14 days of persistent diabetes, phlorizin (0.4 g/kg/day, s.c.) or pantoyltaurine (2.4 mM/kg/day, p.o.) was administered for three weeks, days 15 - 35. As expected, diabetic rats showed persistent hyperglycemia, hyperphagia and weight loss. Pantoyltaurine and phlorizin-treated diabetic rats consumed less diet, showed significant weight loss, reduced persistent hyperglycemia as well as reduced glucose load after oral glucose tolerance test. Diuretic, glucosuric and natriuretic response of diabetic rats was enhanced by pantoyltaurine independent of renal and plasma oxidative stress, plasma insulin and renal expression of SGLT-2. Phlorizin and pantoyltaurine reduced renal expression of SGLT-1, which accounts for ≤ 10% of glucose reabsorption. However, pantoyltaurine, but not phlorizin, normalized elevated fractional excretion of urea nitrogen and clearance of blood urea nitrogen in diabetic rats, suggesting lessening effect of pantoyltaurine on uremic toxicity associated with diabetes. Collectively, our preliminary findings show that chronic treatment with pantoyltaurine may help in an insulin-independent manner to lower diabetic hyperglycemia by producing diuresis, glucosuria and natriuresis that may have translated in improvement of renal function

Bioassay-guided Isolation of the Antidiabetic Active Principle from Salvia miltiorrhiza and its Stimulatory Effects on Glucose Uptake Using 3T3-L1 Adipocytes

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by impaired insulin secretion and insulin sensitivity, which poses an imminent threat to become a worldwide epidemic according to world health organization [1-3]. Type 2 diabetes mellitus is associated with severe complications such as hypertension, dyslipidemia, microvascular and macrovascular cardiovascular diseases [4-6]. Insulin plays a regulatory role in this disease by stimulating the uptake of blood glucose into peripheral tissues through glucose transporters and the promotion of lipid biosynthesis in adipocytes [7]. Insulin resistance causes decrease in peripheral glucose disposal resulting in increased levels of blood glucose [7]. Some of the currently available antidiabetic drugs improve blood glucose levels by increasing the glucose uptake in peripheral tissues. However such drugs are associated with adverse side effects, which limit their use in diabetic patients. Therefore it is highly desirable to discover antidiabetic agents that improve blood glucose levels with minimal side effects. Salviamiltiorrhiza(Labiatae),danshen, is an annual sage mainly found inchinaand neighboring countries. The dried root and its preparations are currently being used inchinato treat patients with cardiovascular and cerebrovascular complications [8]. Many compounds have been isolated from Salviamiltiorrhizaroots, which could be classified as lipid soluble tanshinones and water-soluble phenolic acid compounds [9]. Among phenolic acids, salvianolic acid B is a major component of S.miltiorrhizaand extensive pharmacological studies have been reported for this compound. Salvianolic acid B inhibited the amyloid formation of human islet amyloid polypeptide and protects pancreatic beta cells against cytotoxicity [10]. Many authors have studied the effect of salvianolic acid B on different organ systems in animals as well as in humans. Salvianolic acid B showed beneficial and protective effect to brain from ischemia-reperfusion injury in animal studies [11]. In addition, salvianolic acid B has been shown to inhibit platelet aggregation [12] as well as cause oxidative modification of low-density lipoprotein (LDL) thereby, resulting into decreased uptake of LDL by cultured macrophages [13]. Furthermore, salvianolic acid B has been shown to stimulate the nitric oxide production of the endothelial cell [14] and inhibition of angiotensin IIinduced hyperplasia [15]. It significantly inhibited the activity of stressactivated protein (SAP) kinase [16]. Magnesium salt of salvianolic acid B has been shown to possess potent hepatoprotective activity and shows an improved effect on uremic symptoms [17,18]. An in vitro study also revealed that salvianolic acid B is an excellent scavenger for free radicals, both cation radicals and anion radicals [19]. It has been reported that salvianolic acid B has potent inhibitory effects on lipid or biomembrane peroxidation in a superoxide anion generating system [20,21]

Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients

BACKGROUND: Management of high-grade T1 (HGT1) bladder cancer represents a major challenge. We studied a treatment strategy according to substaging by depth of lamina propria invasion. METHODS: In this prospective observational cohort study, patients received initial transurethral resection (TUR), mitomycin-C, and BCG. Subjects with shallower lamina propria invasion (HGT1a) were followed without further surgery, whereas subjects with HGT1b received a second TUR. Association of clinical and histological features with outcomes (primary: progression; secondary: recurrence and cancer-specific survival) was assessed using Cox regression. RESULTS: Median age was 71 years; 89.5% were males, with 89 (44.5%) cases T1a and 111 (55.5%) T1b. At median follow-up of 71 months, disease progression was observed in 31 (15.5%) and in univariate analysis, substaging, carcinoma in situ, tumour size, and tumour pattern predicted progression. On multivariate analysis only substaging, associated carcinoma in situ, and tumour size remained significant for progression. CONCLUSIONS: In HGT1 bladder cancer, the strategy of performing a second TUR only in T1b cases results in a global low progression rate of 15.5%. Tumours deeply invading the lamina propria (HGT1b) showed a three-fold increase in risk of progression. Substaging should be routinely evaluated, with HGT1b cases being thoroughly evaluated for cystectomy. Inclusion in the TNM system should also be carefully considered

Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma:a paradigm shift to reduce overtreatment of indolent tumors

Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure