Hopf Semimetals

We construct two-band topological semimetals in four dimensions using the unstable homotopy of maps from the three-torus $T^3$ (Brillouin zone of a 3D crystal) to the two-sphere $S^2$. Dubbed ``Hopf semimetals'', these gapless phases generically host nodal lines, with a surface enclosing such a nodal line in the four-dimensional Brillouin zone carrying a Hopf flux. These semimetals show a unique class of surface states: while some three-dimensional surfaces host gapless Fermi-arc states {\em and} drumhead states, other surfaces have gapless Fermi surfaces. Gapless two-dimensional corner states are also present at the intersection of three-dimensional surfaces.Comment: 5 pages, 4 figures + Supplemental Material (4 pages, 2 figures

Obstructed Atomic Insulators and Superfluids of Fermions Coupled to Z2\mathbb{Z}_2 Gauge Fields

We study spin-$\frac{1}{2}$ fermions coupled to $\mathbb{Z}_2$ gauge fields on a lattice. We show how a spatial modulation of the fermion hopping allows for the realization of various obstructed atomic insulators that host higher-order band topology. Studying the effect of quantum dynamics of the gauge fields within a simplified model, we find a rich phase diagram of this system with a number of superfluid phases arising from the attractive interactions meditated by the gauge fields. A key finding of this work is that the evolution from the Bardeen-Cooper-Schrieffer (BCS) superfluid state to a Bose-Einstein condensate (BEC) of tightly bound pairs occurs via the realization of these different superfluid phases separated by first-order transitions.Comment: 7 pages, 4 figures, 1 table, supplemental material (6 pages, 1 figure

Kinasen in der Regulation des epithelialen Transports

Insulin and insulin-like growth factor (IGF-1) regulate renal electrolyte excretion and the signalling includes PI3-kinase, PDK1, PKB and SGK isoforms. Thus SGK isoforms are expected to play a major role in the regulation of renal function which is evident from renal phenotype of sgk1-/- mice. The end effect of PI3-kinase signalling is phosphorylation of GSK3 by PKB/SGK1 which results in inhibition of its activity. Accordingly, similar/parallel renal phenotype can be expected between sgk1-/- mice and gsk3KI mice where GSK3 is resistant to PKB/SGK1 inhibition. The first study was made to elucidate the role of GSK3 in renal electrolyte excretion and hormone release. The plasma aldosterone and corticosterone concentrations were significantly lower while 24-hour urinary aldosterone was significantly higher and urinary corticosterone tended to be higher in gsk3KI mice than in gsk3WT mice. The possibility of reduced salt appetite due to low aldosterone was checked in gsk3KI mice .The gsk3WT mice drank more saline over tap water while gsk3KI mice drank similar amounts of tap and saline water. gsk3KI mice display higher metabolic rate with significantly more food and fluid intake, fecal excretion, GFR, urinary flow rate and urinary Na+, K+ and urea excretion with lower plasma Na+ and urea concentrations and significantly higher blood pressure. Enhanced Na+ excretion may at least partially be due to low aldosterone levels which should however, not increase but decrease the renal K+ excretion. Thus, a renal mechanism involving enhanced ENaC activity presumably causes enhanced renal K+ secretion as Lithium, an inhibitor of GSK3 is shown to downregulate ENaC expression. Higher fluid intake accounts for higher urinary flow rate but does not reflect decreased urine concentrating ability, as urinary osmolarity is increased in gsk3KI mice. Water deprivation did not abrogate the differences in urine output. GSK3 may participate in the regulation of renal tubular water transport. The unrestrained GSK3 could downregulate NO-synthase which induces thirst. The role of GSK3 in eNOS regulation may further contribute to differences in BP. The results thus indicate that the renal phenotype of gsk3KI mice is different from the sgk1-/- mice in several aspects, thereby suggesting a more direct role of GSK3 in renal electrolyte balance. APC fosters degradation of ß-catenin which is known to upregulate a variety of proteins responsible for tumerogenesis. It was suggested and shown that SGK1 is among the proteins that are upregulated. SGK1 expression has also been shown recently to be enhanced in gastric glands of apc Min/+ mice. A similar upregulation was expected in the kidneys of these mice and as SGK1 regulates renal electrolyte homeostasis, a possible renal phenotype for APC mutant mice was expected. The second study was therefore conducted to explore the kidney function in APC mutant mice and thereby elucidate the renal phenotype of those mice. The body weight, food, fluid intake and fecal excretion were not significantly different between the genotypes. Urine flow tended to be lower in apcMin/+ mice than apc+/+ and apcMin/+/sgk1-/- mice. The glomerular filtration rate and Na+ excretion were decreased while fractional excretion of K+ was enhanced in apcMin/+ mice. The antinatriuresis and glomerular filtration tended to be partially reversed by additional lack of SGK1. Fecal sodium and potassium excretion were significantly higher in apcMin/+ mice than in apc+/+ mice. The additional lack of SGK1 could reverse the difference in fecal sodium excretion but not the fecal potassium excretion. The plasma aldosterone and corticosterone concentrations were significantly higher in apcMin/+ mice. While plasma corticosterone concentration was similar in apc+/+ mice and apcMin/+/sgk1-/- mice, plasma aldosterone was even higher in apcMin/+/ sgk1 -/- mice than in apcMin/+ mice. The hyperaldosteronism in apcMin/+ mice was paralleled by elevated plasma volume and blood pressure. The difference in plasma volume and blood pressure were slightly reversed by additional lack of SGK1. The partial reversal of anti-natriuretic, hypervolemic and hypertensive effects in apcMin/+ mice by additional lack of SGK1 implicates its role in the abnormal elelctrolyte homeostasis in apcMin/+ mice. SGK1 defeciency augments the effect of defective APC on plasma aldosterone indicating a complex interaction of APC and SGK1 or independent regulations of APC and SGK1 in hormone release. The signalling cascade explaining insulin stimulated renal tubular phosphate reabsorption remains elusive. Renal phosphate reabsorption is regulated by membrane abundance of the phosphate transporter, NaPiIIa and PI3-kinase signalling possibly stimulates renal tubular reabsorption by increasing the membrane abundance of NaPiIIa. Again the possible role of SGK isoforms could be expected here and the third study thus focussed on the regulation of renal phosphate handling by SGK3 which is a downstream kinase in insulin signalling. Metabolic studies in sgk3KO mice showed significantly higher phosphate excretion in comparision to wild-type mice supporting this hypothesis. Invitro studies involving coexpression of SGK3 and NaPiIIa in Xenopus oocytes provided additional evidence by showing that phosphate induced current is significantly enhanced in SGK3 and NaPiIIa expressing Xenopus oocytes. Food intake was significantly higher in sgk3 KO mice while the plasma PTH and plasma phosphate concentrations were similar to sgk3WT mice. Plasma vitamin-D concentration and bone mass were significalty lower. Plasma and urinary calcium levels were not different between the genotypes. These observations reveal a direct role of SGK3 in the phosphate transport and the higher phosphate loss and low plasma vit-D in sgk3 KO mice could have contributed to the demineralization of the bones in sgk3KO mice.Insulin und Insulin-like-Growth Factor (Insulinähnlicher Wachstumsfaktor, IGF-1) regulieren die Elektrolytausscheidung in der Niere. An dieser Signalkaskade beteiligen sich die PI3-Kinase, PDK1, PKB und verschiedene Sgk-Isoformen. Demzufolge spielen Sgk-Isoformen erwartungsgemäß eine bedeutende Rolle bei der Regulation der Nierenfunktion, die für den renalen Phänotyp von sgk1-/- Mäusen verantwortlich ist. Am Ende der PI3-Kinase Signalkaskade steht die Phosphorylierung der GSK3 durch PKB/SGK1. Diese Phosphorylierung hat die Inaktivierung der Kinase zur Folge. Demnach ist ein ähnlicher Phänotyp bei sgk1-/- und gsk3KI Mäusen zu erwarten. Der erste Teil der Studie sollte die Funktion der GSK3 in Bezug auf Nierenfunktion und Hormonregulation aufklären. Die Aldosteron- und Kortisolplasmaspiegel waren signifikant erniedrigt. Gleichzeitig konnten signifikant erhöhte Aldosteronkonzentrationen bei den gsk3KI im 24-Stunden-Urin gemessen werden. Die Kortisolausscheidung war bei gsk3KI tendenziell höher als bei gsk3WT Mäusen. Aufgrund der reduzierten Aldosteronplasmaspiegel wurde überprüft, ob gsk3KI Mäuse möglicherweise einen gesteigerten Kochsalzkonsum aufweisen. Im Vergleich tranken gsk3WT Mäuse mehr Kochsalzlösung als normales Trinkwasser, während gsk3KI Mäuse keine Unterschiede im Trinkverhalten zeigten. gsk3KI Mäuse zeichneten sich durch eine gesteigerte von Nahrungs- und Trinkwasseraufnahme, erhöhtes Fekalgewicht, sowie eine erhöhte GFR und Urinvolumen, gesteigerte Elektrolyt- (K+ und Na+) und Harnstoffausscheidung bei niedrigeren Plasmakonzentrationen von Na+ und Kreatinin, sowie signifikant erhöhten Blutdruck aus. Eine gesteigerte Na+-Ausscheidung kann, zumindest teilweise, durch niedrige Aldosteronspiegel erklärt werden. Diese sollten ebenfalls die K+-Ausscheidung vermindern und nicht erhöhen. Vermutlich ist dies ursächlich durch einen renal stimulierten Mechanismus zu erklären, der eine gesteigerte ENaC-Aktivität zur Folge hat. Für Lithium, einen GSK3-Inhibitor, wurde beispielsweise eine Herunterregulation der ENaC-Expression gezeigt. Eine vermehrte Flüssigkeitsaufnahme resultiert in einem größeren Urinvolumen, spiegelt jedoch nicht eine verminderte Konzentrationsfähigkeit des Urins durch die Niere wider. Die Osmolarität des Urins von gsk3KI Mäusen war dementsprechend erhöht. Flüssigkeitsentzug glich den Unterschied in der Ausscheidungsmenge zwischen den Genotypen nicht aus. Möglicherweise spielt die GSK3 beim Wassertransport, der durch die Nierentubuli gewährleistet wird, eine Rolle. Die nicht-inhibierte GSK3 könnte die NO-Synthase, welche Durstgefühl vermittelt, herunterregulieren. Der Einfluss der Kinase auf die NO-Bildung könnte darüber hinaus eine Ursache für den erhöhten Blutdruck der gsk3KI Mäuse sein. Der Konsens dieser Ergebnisse deutet auf einen nachweisbaren Unterschied des Nierenphänotyps zwischen gsk3KI und sgk1-/- Mäusen hin und lässt die Rolle der GSK3 bezüglich des Elektolythaushaltes als bedeutender erscheinen. APC fördert den Abbau von Beta-Catenin, welches für die Hochregulation einer großen Anzahl an Proteinen, die für die Tumorgenese von Bedeutung sind, wichtig ist. SGK1 befindet sich nachweislich unter diesen hochregulierten Proteinen. Ebenso konnte bewiesen werden, dass die Expression der SGK1 in den Magendrüsen von apcMin/+ Mäusen erhöht ist. Ähnliche Regulationsmechansimen hätte man in der Expression der Nieren dieser Mäuse erwartet, und, da bekannt ist, dass SGK1 die renale Elektrolytausscheidung reguliert, auch einen möglicher relevanter Nierenphänotyp. Der zweite Teil dieser Studie wurde daher der Exploration der Nierenfunktion von APC-defekten Mäusen gewidmet. Köpergewicht, Nahrungs- und Trinkverhalten und Fekalvolumen war nicht unterschiedlich. Das Urinvolumen erschien bei den apcMin/+ Mäusen niedriger als bei den apcMin/+ und apcMin/+/sgk1-/- Mäusen. Die glomeruläre Filtrationsrate und Na+-Ausscheidung waren erniedrigt während die fraktionelle K+-Ausscheidung bei den apcMin/+ erhöht war. Die verminderte GFR und Exkretion von Na+ wurde teilweise durch die Abwesenheit der SGK1 (apcMin/+/sgk1-/-) aufgehoben. Der Na+ und K+-Gehalt in den Feces waren bei den apcMin/+ im Vergleich zu den apcMin/+ Mäusen signifikant erhöht. Die verminderte Na+-Ausscheidung wurde durch den zusätzlichen Mangel an SGK1 egalisiert während die K+-Ausscheidung im Stuhl unverändert blieb. Die Konzentrationen an gemessenen Aldosteron- und Kortisolspiegeln im Plasma waren bei den apcMin/+ signifikant erhöht. Die Kortisolplasmakonzentrationen der apcMin/+ und apcMin/+/sgk1-/- Mäusen waren gleich, die Aldosteronkonzentration war bei den apcMin/+/sgk1-/- sogar höher als bei den apcMin/+ Mäusen. Der Hyperaldosteronismus der apcMin/+ Mäuse ging einher mit einem gesteigerten Plasmavolumen sowie einem erhöhtem Blutdruck, beides wurde durch einen zusätzlichen Mangel an SGK1l zu einem gewissen Grad normalisiert. Die partielle Aufhebung der antinatriuretischen, hypervolämischen und hypertensiven Effekte bei den apcMin/+/sgk1-/- Mäusen lässt einen Zusammenhang zwischen einem SGK1-knock-out und dem veränderten Elektrolythaushalt der apcMin/+ Mäuse vermuten. Das Fehlen von SGK1 erhöht die Auswirkung von nicht-funktionellem APC auf die Plasmaaldosteronkonzentration und deutet auf eine komplexe Interaktion zwischen APC und SGK1 hin. Eine unabhängige Hormonregulation durch APC und SGK1 ist ebenfalls denkbar und daher in Betracht zu ziehen. Die Signalkaskade, welche die Insulin stimulierte renal-tubuläre Phosphatrückresorption erklären könnte, bleibt unklar. Die Phosphatrückresorption in der Niere wird durch die Anwesenheit von Phosphattransportern (NaPiIIa) in der Membran reguliert. Die PI3-Kinasekaskade stimuliert möglicherweise diese Rückresorption, indem die Menge des NaPiIIa in der Membran hochreguliert wird. Auch hier wäre ein möglicher Einfluss der SGK-Isoformen denkbar, daher fokussierte der dritte Teil der Studie die Wirkung der SGK3, eine Kinase innerhalb der Insulinsignalkaskade, auf den renalen Phosphattransport. Untersuchungen an SGK3-defizienten (sgk3-/-) Mäusen zeigten eine signifikant erhöhte Phosphatausscheidung. Dieser Befund unterstützte die These einer möglichen Beteiligung der Insulinsignalkaskade an der renalen Phosphatregulation. Voltage clamp Untersuchungen, die in vitro Experimente an Oozyten beinhalteten, zeigten, dass die Koexpression von SGK3 und NaPiIIa in den Oozyten den Phosphatausstrom aus den Zellen signifikant erhöhte. Die Nahrungsaufnahme war bei sgk3-/- Mäusen signifikant erhöht. Die Konzentrationen von Parathormon und Phosphat im Plasma ähnlich deren von sgk3+/+ Mäusen. Die Plasmakonzentration von Vitamin D und die Knochenmasse waren bei den sgk3+/+ Mäusen signifikant vermindert. Die Calciumkonzentration im Plasma und Urin unterschieden sich nicht. Diese Befunde decken einen direkten Einfluss der SGK3 auf den Phosphathaushalt und dessen Regulationsmechansimen, der den Vitamin D-Haushalt und die Knochenmineralisierung beeinträchtigt, auf

Exclusion and Inclusion -- A model agnostic approach to feature importance in DNNs

Deep Neural Networks in NLP have enabled systems to learn complex non-linear relationships. One of the major bottlenecks towards being able to use DNNs for real world applications is their characterization as black boxes. To solve this problem, we introduce a model agnostic algorithm which calculates phrase-wise importance of input features. We contend that our method is generalizable to a diverse set of tasks, by carrying out experiments for both Regression and Classification. We also observe that our approach is robust to outliers, implying that it only captures the essential aspects of the input.Comment: 8 pages, 4 figure

An Interpretable Deep Learning System for Automatically Scoring Request for Proposals

The Managed Care system within Medicaid (US Healthcare) uses Request For Proposals (RFP) to award contracts for various healthcare and related services. RFP responses are very detailed documents (hundreds of pages) submitted by competing organisations to win contracts. Subject matter expertise and domain knowledge play an important role in preparing RFP responses along with analysis of historical submissions. Automated analysis of these responses through Natural Language Processing (NLP) systems can reduce time and effort needed to explore historical responses, and assisting in writing better responses. Our work draws parallels between scoring RFPs and essay scoring models, while highlighting new challenges and the need for interpretability. Typical scoring models focus on word level impacts to grade essays and other short write-ups. We propose a novel Bi-LSTM based regression model, and provide deeper insight into phrases which latently impact scoring of responses. We contend the merits of our proposed methodology using extensive quantitative experiments. We also qualitatively asses the impact of important phrases using human evaluators. Finally, we introduce a novel problem statement that can be used to further improve the state of the art in NLP based automatic scoring systems.Comment: 8 pages, 4 figure

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation

Undermining Whiteness: Hannah Arendt's Participatory Freedom and the Political Ethics of Antiracism

Thesis (Ph.D.)--University of Washington, 2013This dissertation seeks to develop a political ethics of antiracism through the work of 20th century political theorist Hannah Arendt. Although Arendt's political theory does not take up the particular question of antiracism, I posit that Arendt's theorization of freedom, which emphasizes the participatory and transformative dimensions of freedom, can help us articulate a destabilizing politics, one that privileges practices that might undermine the norm of whiteness. An Arendtian approach to antiracism might challenge the Left orthothodox approach to racism in post-Civil Rights America, which, through the ideals of social justice and equality, relies on the State to prosecute acts of racism and increase non-whites' access to valuable resources. Although the Left's State-centered approach may have been necessary during an era when white violence was blatant and forthcoming, an over-reliance on the State and its repressive apparatus has curbed prospects for conversations that might lead to greater public understanding of how race has structured and continues to structure American life. This dissertation explains how Arendt's concept of participatory freedom might reenergize antiracist politics in the 21st century. Participatory freedom highlights the experience of freedom as opposed to the protections that freedom may offer, which might be better conceptualized as liberty or rights; or the psychological state of freedom, which might be better conceptualized as autonomy. By highlighting the experiential dimension of freedom, participatory freedom emboldens us to encounter potentially radical difference, which we can do only in political life. Although participatory freedom need not replace justice-, equality-, or rights- based approaches to antiracism, these approaches do not automatically foster encounters across difference. It is these encounters that yield the potential to undermine deeply entrenched norms, such as whiteness

Total synthesis of (+)-cephalostatin 1 and dihydrocephalostatin 1

Reported herein are the first total syntheses of (+)-Cephalostatin 1 and Dihydrocephalostatin 1. Pertinent highlights of the above stated syntheses include (1) the proximal functionalization of the C-18 methyl group in alcohol 2.19 via Meystre\u27s hypoiodite method (2) the regioselective rhodium-carbenoid mediated O-H insertion reaction of ethyldiazophosphonate 2.50 into the primary neopentiyl hydroxyl group of triol 2.18 (3) the regiospecific intramolecular Wadsworth-Emmons reaction in the diketophosphonate ester 2.47 to exclusively afford the six-membered dihydropyran ester 2.49 (4) establishment of the stereochemistry of spiroketals 3.11, 3.12$\alpha$ and 3.12$\beta$, obtained from the acid-catalyzed spirocyclization reaction of 3.10, using state-of-the-art two-dimensional NMR methods and subsequent confirmation of the NMR assigned configurations via X-ray crystallography (5) conversion of the South spiroketal 3.20, of Dihydrocephalostatin 1 (1.33) into the South spiroketal 3.34, of Cephalostatin 1 (1.1) and (6) unsymmetrical coupling of the South $\alpha$-azidoketones 2.11 and 2.12 with the North $\alpha$-aminomethoxime 2.13 to complete the syntheses of Dihydrocephalostatin 1 (1.33) and (+)-Cephalostatin 1 (1.1), respectively