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In vivo dynamics of clathrin and its adaptor-dependent recruitment to the actin-based endocytic machinery in yeast.
No full textClathrin-mediated transport is a major pathway for endocytosis. However, in yeast, where cortical actin patches are essential for endocytosis, plasma membrane-associated clathrin has never been observed. Using live cell imaging, we demonstrate cortical clathrin in association with the actin-based endocytic machinery in yeast. Fluorescently tagged clathrin is found in highly mobile internal trans-Golgi/endosomal structures and in smaller cortical patches. Total internal reflection fluorescence microscopy showed that cortical patches are likely endocytic sites, as clathrin is recruited prior to a burst of intensity of the actin patch/endocytic marker, Abp1. Clathrin also accumulates at the cortex with internalizing alpha factor receptor, Ste2p. Cortical clathrin localizes with epsins Ent1/2p and AP180s, and its recruitment to the surface is dependent upon these adaptors. In contrast, Sla2p, End3p, Pan1p, and a dynamic actin cytoskeleton are not required for clathrin assembly or exchange but are required for the mobility, maturation, and/or turnover of clathrin-containing endocytic structures
US Patent 8858922 - Broad Spectrum UVA Stable, Non-Toxic, Zinc Oxide Based Complex
No full textDisclosed is a new composition of matter that is a compound which also is presented as a dispersion with broad UVA and UVB spectral absorption stability, heat absorption, and insulation properties, anti-microbial, water resistance, and high SPF properties. The composition of matter is a zinc oxide complex that is provided with distilled water buffered to a pH of greater than 10 using ammonium hydroxide, L-arginine, or other buffering agents, and zinc oxide particles. The zinc oxide complex may be dried and rinsed to increase stability. An emollient, such as glycerine, and/or an emulsifier such as a combination of cetearyl alcohol and cetearyl glucoside and/or sodium stearoyl glutamate and/or cetearyl glucoside may also be added to the zinc oxide complex. The zinc oxide complex is made from natural-based, earth-derived, Ecocert® certified ingredients is non-toxic, and may be used or combined with any compound in which UVA/UVB stability is desired. The applications for the zinc oxide complex are numerous and include; roofing materials, composite building materials, automobile and aircraft parts, textiles, wire and cable insulation, use in conductor and semi-conductor technologies, as well as for sunscreens and cosmetics
Exile to the Equator: Chinese Anti-Colonialism and Nationalism in Southeast Asia, 1939–1946
No full textThis paper discusses and compares the ideas of Chinese leftists in exile, as expressed in their publications and journals and in their anti-colonial activism in collaboration with the overseas Chinese in Southeast Asia from 1939 to 1946. Describing Chinese anti-colonialism and nationalism through a transnational conceptualization and an ethnographic approach, stories that occur “behind the scenes” enhance our ability to decode key words and reveal the complexities of concrete economic and political conflicts from multiple sources that involve migration, ethnicities, and capitalism. The class nature of Chinese anti-colonial internationalism that was forged during and after the Second World War was deeply embedded in the “liberal” discourses of freedom, democracy, equality, liberty, and women’s emancipation. It was also rooted in the mass politics of anti-capitalism, which was global in scope and fine-grained, local, and rooted in everyday life. The Chinese leftist geopolitical configuration of the “nations below the wind” and “the equator” enabled the perception of a proto-global South—South alliance as a world-historical force, with the dual goals of overturning unequal development and achieving an integrated path of anti-colonialism and national independence
A Geospatial Approach to Understanding Poaching Behavior of ESA-listed and Endemic Dudleya on Santa Cruz Island within Channel Islands National Park
No full textThe Covid 19 pandemic has catalyzed the increase in plant poaching incidents, particularly with species of Dudleya in California. As people were confined to their homes, houseplant collecting popularity rose worldwide. For Santa Cruz Island, the threat is great with large areas of land and few on-ground managers to monitor for such risks. These managers face the challenge of how best to predict poaching before it occurs in an area to maximize the efficiency of their smaller staff. Using geospatial data, I model three distinct poaching behaviors to gain a better understanding on how to proactively monitor for poaching events. I also use the models to identify areas where certain poaching behaviors are not represented, presenting an opportunity for model tuning through site visits. Through proactive behavioral modeling, land managers have an increased understanding of where to focus their attention to minimize poaching risk
Quantifying Biomarkers for Brain Disease State Monitoring and Intervention
No full textThe burden of neurological diseases in the country is growing and the need for improved therapies is critical. One approach to understanding and managing neurological diseases is through the electrical signals of the brain. Local field potentials (LFPs) are electrical signals recorded from the brain that represent the activity of populations of neurons surrounding the recording site. During injury and disease, the normal electrophysiological behavior of neurons is replaced by aberrant activity. Disease biomarkers are pathophysiological LFPs that are present during disease. Investigating neural biomarkers can shed light on disease progression as well as inform treatment options. In this dissertation, we improve current technology to allow for superior biomarker quantification in two applications: monitoring disease state and informing therapeutic intervention. In the first part of this dissertation, we developed new technology to enhance brain monitoring for ischemic stroke. After initial injury, there is a critical period of days and weeks during which the brain is at risk of further damage. Spreading depolarizations (SDs) are disease biomarkers that are implicated in worsened outcomes (i.e. larger volumes of dead tissues). However, the exact contribution of SDs to disease progression remains unclear: SDs might be detrimental or beneficial depending on the phase of the progression. Therefore, the ability to concurrently track SDs and brain disease state (i.e. tissue viability) is critical for advancing our knowledge of disease progression and ultimately drive therapy development. We have addressed technological challenges that, until now, prevented the simultaneous monitoring of SDs and stroke boundaries. We validated our novel recording technique using in vivo electrophysiology in rodents. Our findings show that high density micro-electrocorticography (µECoG) arrays are able to record reliably both sub-hertz activity (the frequency range of SDs) and underlying spontaneous brain activity (that reflects tissue health and viability). These advances will enable long-term tracking of SD contribution to stroke boundaries.
In the second part of this dissertation, we developed novel paradigms to guide delivery of deep brain stimulation (DBS) in Parkinson’s disease (PD). DBS is a well-established treatment option for people with PD that manages motor symptoms. Current research efforts are focused on optimizing DBS by only delivering therapy as needed, based on a patient’s current clinical state. This approach is called closed-loop DBS and holds promise for providing optimal symptom relief while avoiding stimulation-induced side effects and reducing battery consumption. Even though biomarkers have already been extracted from the LFP of the basal ganglia during DBS for PD, clinical translation of these biomarkers as guides for closed-loop DBS faces other challenges. Most notably, the window between two stimulation pulses during which biomarkers local to the stimulation site are recorded is rather short ( 100 Hz). Stimulation artifacts often persist after the pulse is over (for up to multiple milliseconds) and obscure underlying biomarkers. Through intra-operative studies, we demonstrated that temporally non-regular patterns of DBS can provide longer windows for biomarker recording (~ 50 ms) while maintaining clinical efficacy. We also quantified the effect of mismatched source impedances on the stimulation artifact and proposed a novel pre-amplification circuit to minimize the stimulation artifact during DBS recordings. These advances will facilitate biomarker quantification during DBS therapy, ultimately aiding clinical translation of closed-loop paradigms. </p
Intermediate curvature, spacetime harmonic functions and the monotonicity of the Hawking energy
No full textThis dissertation is based on the manuscripts \cite{BHJ, Hirsch, HKK, HirschZhang}.The paper \cite{BHJ} is joint with Simon Brendle and Florian Johne, \cite{HKK} is joint with Demetre Kazaras and Marcus Khuri, \cite{HirschZhang} is joint with Yiyue Zhang, and \cite{Hirsch} is a solo-authored.First, we introduce \emph{-intermediate curvature } which interpolates between Ricci () and scalar curvature () and prove in this context a generalized Geroch conjecture \cite{BHJ}.In particular, we show that , , does not admit a metric with .Next we study initial data sets which are used in General Relativity to describe isolated gravitational systems.We introduce \emph{spacetime harmonic functions}, i.e. functions solving the PDE \Delta u=-\tr_gk|\nabla u|, to give a new lower bound for the mass of .
This lower bound in particular implies the spacetime positive mass theorem \cite{HKK} including the case of equality \cite{HirschZhang}.Finally, we discuss recent progress towards the spacetime Penrose conjecture \cite{Hirsch}.We demonstrate how the famous monotonicity formula for the Hawking energy under inverse mean curvature flow can be generalized to initial data sets.
This leads to new notion of \emph{spacetime inverse mean curvature flow} which is based on double null foliations.Further papers I wrote during my time in graduate school \cite{BHHWZ, BHKKZ, BHKKZ2, HKKZ, HKKZ2, HirschLesourd, HirschLi, HirschMiao, HMT2, HMT, HirschZhu} will not be discussed.</p
Heralded Bell State of Dissipative Qubits Using Classical Light in a Waveguide.
No full textMaximally entangled two-qubit states (Bell states) are of central importance in quantum technologies. We show that heralded generation of a maximally entangled state of two intrinsically open qubits can be realized in a one-dimensional (1D) system through strong coherent driving and continuous monitoring. In contrast to the natural idea that dissipation leads to decoherence and so destroys quantum effects, continuous measurement and strong interference in our 1D system generate a pure state with perfect quantum correlation between the two open qubits. Though the steady state is a trivial product state that has zero coherence or concurrence, we show that, with carefully tuned parameters, a Bell state can be generated in the system's quantum jump trajectories, heralded by a reflected photon. Surprisingly, this maximally entangled state survives the strong coherent state input-a classical state that overwhelms the system. This simple method to generate maximally entangled states using classical coherent light and photon detection may, since our qubits are in a 1D continuum, find application as a building block of quantum networks
Effect of Obesity on Radiographic Alignment and Short-Term Complications After Surgical Treatment of Adult Cervical Deformity.
No full textObjectiveWe investigated the 30-day complication incidence and 1-year radiographic correction in obese patients undergoing surgical treatment of cervical deformity.MethodsThe patients were stratified according to World Health Organization's definition for obesity: obese, patients with a body mass index of ≥30 kg/m2; and nonobese, patients with a body mass index of 2. The patients had undergone surgery for the treatment of cervical deformity. The patient baseline demographic, comorbidity, and radiographic data were compared between the 2 groups at baseline and 1 year postoperatively. The 30-day complication incidence was stratified according to complication severity (any, major, or minor), and type (cardiopulmonary, dysphagia, infection, neurological, and operative). Binary logistic regression models were used to assess the effect of obesity on developing those complications, with adjustment for patient age and levels fused.ResultsA total of 124 patients were included, 53 obese and 71 nonobese patients. The 2 groups had a similar T1 slope minus cervical lordosis (obese, 37.2° vs. nonobese, 36.9°; P = 0.932) and a similar C2-C7 (-5.9° vs. -7.3°; P = 0.718) and C2-C7 (50.1 mm vs. 44.1 mm; P = 0.184) sagittal vertical axis. At the 1-year follow-up examination, the T1 pelvic angle (1.0° vs. -3.1°; P = 0.021) and C2-S1 sagittal vertical axis (-5.9 mm vs. -35.0 mm; P = 0.036) were different, and the T1 spinopelvic inclination (-1.0° vs. -2.9°; P = 0.123) was similar. The obese patients had a greater risk of overall short-term complications (odds ratio, 2.5; 95% confidence interval, 1.1-6.1) and infectious complications (odds ratio, 5.0; 95% confidence interval, 1.0-25.6).ConclusionsObese patients had a 5 times greater odds of developing infections after surgery for adult cervical deformity. Obese patients also showed significantly greater pelvic anteversion after cervical correction
Return to work after adult spinal deformity surgery.
No full textPurposeTo determine the proportions of patients returning to work at various points after adult spinal deformity (ASD) surgery and the associations between surgical invasiveness and time to return to work.MethodsUsing a multicenter database of patients treated surgically for ASD from 2008 to 2015, we identified 188 patients (mean age 51 ± 15 years) who self-reported as employed preoperatively and had 2-year follow-up. Per the ASD-Surgical and Radiographical Invasiveness Index (ASD-SR), 118 patients (63%) underwent high-invasiveness (HI) surgery (ASD-SR ≥ 100) and 70 (37%) had low-invasiveness (LI) surgery (ASD-SR ResultsPreoperatively, 69% of employed patients worked full time. Postoperatively, 15% of employed patients were full time at 6 weeks, 70% at 6 months, 83% at 1 year, and 84% at 2 years. Percentage of employed patients working full time at 2 years was greater than preoperatively (p ConclusionsMost adults returned to full-time work after ASD surgery. A smaller percentage of patients in the HI group than in the LI group returned to full-time work at 6 weeks. Patients employed full time preoperatively will likely return to full-time employment after ASD surgery.Level of evidenceIII