cssi/SciSciGPT-SciSciNet huggingface dataset:
Using repeat lidar to estimate sediment transport in a steep stream

Sediment fluxes in steep mountain streams remain difficult to quantify, despite their importance in geomorphology, ecology, and hazard analysis. In this work, aerial lidar surveys, acquired in 2002, 2008, and 2012, are used to quantify such fluxes in Tahoma Creek, a proglacial stream on Mount Rainier, Washington. As these surveys encompass all coarse sediment sources in the basin, we are able to translate geomorphic change into total bed material transport volumes for the time steps between surveys. By assuming that the relationship between daily sediment transport and daily mean discharge is of the form Qs=a(Q−Qc)b, our two observed total loads and estimates of daily mean discharge allow us to numerically solve for values of a and b to create a bed material sediment rating curve. Comparisons of our transport estimates with sediment deposition in a downstream reservoir indicate that our transport estimates and derived rating curve are reasonable. The method we present thus represents a plausible means of estimating transport rates in energetic settings or during extreme events, applicable whenever at least two cumulative sediment loads and the driving hydrology are known. We use these results to assess the performance of several bed load transport equations. The equations generally overpredict transport at low to moderate flows but significantly underpredict transport rates during an extreme event. Using a critical shear stress value appropriate for steep streams improves agreement at lower flows, whereas a shear-partitioning technique accounting for form drag losses significantly underpredicts transport at all flows.
ZN2+-INDUCED SUBCONDUCTANCE EVENTS IN CARDIAC NA+ CHANNELS PROLONGED BY BATRACHOTOXIN : CURRENT-VOLTAGE BEHAVIOR AND SINGLE-CHANNEL KINETICS

The mechanism of voltage-dependent substate production by external Zn2+ in batrachotoxin-modified Na+ channels from canine heart was investigated by analysis of the current-voltage behavior and single-channel kinetics of substate events. At the single-channel level the addition of external Zn2+ results in an increasing frequency of substate events with a mean duration of approximately 15-25 ms for the substate dwell time observed in the range of -70 to +70 mV. Under conditions of symmetrical 0.2 M NaCl, the open state of cardiac Na+ channels displays ohmic current-voltage behavior in the range of -90 to +100 mV, with a slope conductance of 21 pS. In contrast, the Zn2(+)-induced substate exhibits significant outward rectification with a slope conductance of 3.1 pS in the range of -100 to -50 mV and 5.1 pS in the range of +50 to +100 mV. Analysis of dwell-time histograms of substate events as a function of Zn2+ concentration and voltage led to the consideration of two types of models that may explain this behavior. Using a simple one-site blocking model, the apparent association rate for Zn2+ binding is more strongly voltage dependent (decreasing e-fold per +60 mV) than the Zn2+ dissociation rate (increasing e-fold per +420 mV). However, this simple blocking model cannot account for the dependence of the apparent dissociation rate on Zn2+ concentration. To explain this result, a four-state kinetic scheme involving a Zn2(+)-induced conformational change from a high conductance conformation to a substate conformation is proposed. This model, similar to one introduced by Pietrobon et al. (1989. J. Gen. Physiol. 94:1-24) for H(+)-induced substate behavior in L-type Ca2+ channels, is able to simulate the kinetic and equilibrium behavior of the primary Zn2(+)-induced substate process in heart Na+ channels. This model implies that binding of Zn2+ greatly enhances conversion of the open, ohmic channel to a low conductance conformation with an asymmetric energy profile for Na+ permeation.
A Comparison of Estrogen Effects on Uterine and Pituitary Growth and Prolactin Synthesis in F344 and Holtzman Rats

The pituitary response to chronic estrogen treatment was studied in two strains of rats, the Fischer 344 (F344) and the Holtzman. Silastic tubing implants containing diethylstilbestrol (DES) were placed in weanling animals. Uterine and pituitary growth and protein synthesis were monitored over an 8-week period. The incorporation of [3H]leucine into PRL and GH was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both F344 and Holtzman strains respond to chronic DES with an increase in PRL synthesis. PRL synthesis is 7% of the total protein synthesis in ovariectomized female controls of both strains and increases to 40–50% in 8-week DEStreated F344 rats and to 35–45% in Holtzman rats. The uterine growth responses were similar in both strains and reached a plateau after approximately 2 weeks. Despite their similarity in PRL synthesis and uterine growth, these two strains differ dramatically in their pituitary growth response to DES. In the F344 strain, pituitaries from treated animals a...
Biphasic Culture of Arcobacter spp.

Arcobacter spp. have recently been genetically differentiated as a genus distinct from Campylobacter. Physiologically, Arcobacter spp. are aerotolerant bacteria, while Campylobacter spp. are microaerophilic. However, since Arcobacter spp. have been difficult to grow to high population densities in broth media, alternative culture techniques were investigated. A biphasic culture system was developed in 25 cm2 tissue culture flasks. Biphasic culture, consisting of a solid phase of 10% bovine blood agar and a liquid phase of Brain Heart Infusion broth, was found to increase bacterial population densities by more than 2 log10 cycles for strains of A. butzleri and A. skirrowii. A strain of A. cryaerophilus, which was non-culturable in broth culture, attained population densities of 10(9) cells ml-1 in biphasic culture. Neither the addition of fetal bovine serum to the liquid nor an increase in the surface area from 25 to 75 cm2 resulted in increased cell densities.
Presynaptic NMDA receptor subunit immunoreactivity in GABAergic terminals in rat brain

N-methyl-D-aspartate (NMDA) receptors are commonly found post-synaptically; they mediate fast excitatory neurotransmission in the central nervous system. In this study, we provide immunocytochemical data supporting the existence of presynaptic NMDA receptors in GABAergic terminals using polyclonal antisera raised against the C-terminus of the NMDAR1 subunit. At the light microscope level, rich plexuses of NMDAR1-positive varicose fibers were found in various nuclei in the basal forebrain (bed nucleus of stria terminalis, septum, parastrial nucleus, vascular organ of the lamina terminalis), thalamus (paraventricular nucleus, midline nuclei), and hypothalamus (parvocellular paraventricular nucleus, arcuate nucleus, preoptic nucleus, suprachiasmatic nucleus). In the brainstem, labeled fibers were much less abundant and were confined to the ventral tegmental area, periaqueductal gray, parabrachial nucleus, and locus coeruleus. At the electron microscope level, NMDAR1-immunoreactive terminals examined in the bed nucleus of stria terminalis, parvocellular paraventricular hypothalamic nucleus, and arcuate nucleus formed symmetric synapses, contained darkly stained large dense-core vesicles, and displayed gamma-aminobutyric acid (GABA) immunoreactivity. Terminals with similar ultrastructural features were found in the paraventricular thalamic nucleus. These findings demonstrate the existence of NMDAR1 subunit immunoreactivity in subsets of GABAergic terminals, which raises questions about the potential roles and mechanisms of activation of presynaptic NMDA heteroreceptors in the rat central nervous system. The pattern of distribution and ultrastructural features of these boutons suggest that they may arise from local GABAergic projections interconnecting a group of brain structures mediating stress responses and/or other endocrine, autonomic, and limbic functions.
The Transition to Quasi-Periodicity for Molten Plastics in Large Amplitude Oscillatory Shear

Large amplitude oscillatory shear (LAOS) experiments on three grades of LLDPE including one commercial film blowing resin showed an interesting transition in the shear stress response to LAOS. The shear stress response is initially a nonsinusoidal standing wave which then undergoes a transition to quasi-periodicity. Many line-broadened odd and even harmonics were found in the shear stress amplitude spectra of the quasi-periodic responses. The transition time depends on shear strain amplitude and frequency, but it did not correlate with the weight average molecular weight of the LLDPE’s.
Report on the Symposium on Heavy Ion Inertial Fusion, Darmstadt, Germany, June 1988

Progress on high-current, low-emittance heavy ion beams in both RF linacs and induction linacs was reported at the Symposium on Heavy Ion Inertial Fusion. Significant current amplification in a proof-of-principle multiple-beam induction linac was described. Experimental results from France and Germany show enhanced energy deposition by low-energy heavy ions in hot dense plasmas. The GSI heavy ion synchrotron (SIS) and the experimental storage ring (ESR) are under construction; when completed, the beams will be used for experiments to study hot dense plasma phenomena. >
Remembering Dr Ray W. Gifford, Jr

With the passing of Dr Ray W. Gifford, Jr the medical profession has lost one of its finest. Dr Gifford’s example reflected brilliance, superb clinical judgment, inflexible integrity, uncommon wisdom, total commitment to his patients, and an unparalleled decency of character. Albert Schweitzer said that “example is not the most important thing in influencing others, it is the only thing.” Ray’s example has left an indelible mark on all his friends, colleagues, and those who were fortunate and privileged to know him. Ray was a powerhouse of energy who contributed enormously to the field of hypertension. Whenever …
Focal Adhesion Kinase Versus p53: Apoptosis or Survival?

Focal adhesion kinase (FAK) is a tyrosine kinase that interacts with a multitude of signaling partners and helps cells to survive in the face of various proapoptotic signals. One of the most important interactions for FAK is with the tumor suppressor protein p53. p53 binds not only to the amino-terminal domain of FAK but also to the FAK promoter to inhibit its transcription. A study now reports the biological implications of the kinase-independent interaction of FAK with p53, which opens up future perspectives in cell signaling and cancer research. We focus on FAK and p53 signaling, which link signal transduction pathways from the extracellular matrix and cytoplasm to the nucleus, in human and mouse cells. FAK is proposed to be a critical scaffold protein that sequesters proapoptotic proteins, such as p53, to mediate cell survival.
Prostanoid cascade inhibition prevents cardiovascular and adrenocorticotropic responses to mineral acid infusion

Mineral acid infusion is used to investigate the effects of acidemia on the cardiovascular and respiratory systems. Previous studies have shown that small infusions of HCl increase mean arterial pressure (MAP), adrenocorticotropic hormone (ACTH), and cortisol without producing acidemia. We infused 1 meq/min of 1 N HCl intravenously into chronically catheterized conscious sheep with or without pretreatment with 1.1 mg/kg flunixin-N-methylglucamine, a cyclooxygenase inhibitor (n = 6). Acid infusion resulted in significant increases in heart rate (83 +/- 5 to 94 +/- 7 beats/min), MAP (84 +/- 3 to 104 +/- 6 mmHg), ACTH (97 +/- 23 to 285 +/- 101 pg/ml), cortisol (20 +/- 3 to 37 +/- 16 ng/ml), sodium (149.5 +/- 0.8 to 150.6 +/- 1.3 meq/l), potassium (3.96 +/- 0.09 to 4.31 +/- 0.19 meq/l), and thromboxane (Tx) B2 (stable metabolite of TxA2) (147 +/- 78 to 2,304 +/- 1,213 pg/ml), whereas these changes were prevented by flunixin. Plasma concentrations of 6-ketoprostaglandin F1 alpha (stable metabolite of prostacyclin), prostaglandin E2, interleukin-1 alpha, and hematocrit did not change in either group. Arterial pH decreased, whereas arterial partial pressure of CO2 increased significantly in both groups. Arterial partial pressure of O2 declined in both groups, but the decrease was significantly greater in the group not receiving flunixin. We conclude that a cyclooxygenase metabolite, most likely TxA2, mediates the MAP, heart rate, ACTH, and cortisol responses to mineral acid infusion.
Extensor Tendon Injuries in the Hand.

Until recently, extensor tendon injuries were often discounted as an important hand problem. However, studies have shown that not all extensor lacerations fare well and that loss of flexion can be problematic. Newer postoperative protocols emphasizing tendon gliding have improved results, and better repair techniques and postoperative rehabilitation regimens are under investigation. This article reviews the evaluation of acute open and closed extensor tendon injuries, their conservative and surgical treatment, and postoperative rehabilitation options. J Am Acad Orthop Surg 1997;5:59-66
16 GHz low-power 1:4 prescalar fabricated in 1.0 [micro sign]m BiFET technology

An experimental 16 GHz low-power 1:4 prescalar in 1 /spl mu/m BiFET technology is reported. The prescalar was designed in both heterojunction bipolar (HBT) technology, and BiFET technology. The BiFET version utilised MESFET current sources, thereby reducing the supply voltage from -6.8 to 4.65 V (-6 to -4.15 V at lower frequencies), which results in power savings of approximately 30%.
Three-dimensional, numerical investigation of reactant injection variation in a H2/air rotating detonation engine

Abstract This study characterizes the mixing performance and non-reacting injection flow field within a rotating detonation engine. Initial reactant mixing is accomplished through a counter-rotating vortex pair developing from a jet-in-a-crossflow situation. Radially injected air wraps around the fuel jet, shearing the hydrogen into the vortex structure. The three-dimensional baseline geometry produces poor hydrogen/air mixing in the injection zone due to low fuel penetration into the wide, cross-flowing air stream and low air entrainment into the vortex structure. Injection parameters, including reactant flow rate, injection area, and fuel injection distribution, are varied to assess the impact on mixing. Decreasing air injection area and fuel injection area improve fuel penetration into the air stream and the vortex mixing mechanism, enhancing the level of mixedness within the annulus. For a given air injection area, an optimized number of fuel injection holes exists that provides the greatest level of mixedness. Variations from the optimized geometry reduce the effectiveness of the vortex mixing mechanism. Staggering fuel injection holes produces a decrease in mixedness when compared to collinear fuel injection.
Abstract 4742: Anti-tyrosinase related protein 1 (TRP1) antibody combined with cyclophosphamide induces adaptive immunity against melanoma

Monoclonal antibodies targeting tumor antigens are an effective anti-cancer immunotherapy, with well established benefit against multiple tumor types. They are most potent when given in combination with chemotherapy. The mechanisms underlying the efficacy of combination therapy, however, are poorly understood.1 Tyrosinase-related protein 1 (TRP1) is a protein implicated in pigment formation. TRP1 is found primarily in the melanosome, but surface expression can be detected in vivo. An antibody targeting TRP1 is currently in clinical testing. In mice, anti-TRP1 prophylaxis controls subsequent growth of B16 melanoma, but has minimal activity as a single agent against established disease.2 We have previously shown that anti-TRP1 enhances T cell responses induced by DNA vaccination.3 We now report that anti-TRP1 enhances the cytotoxic effect of cyclophosphamide chemotherapy in the treatment of established cutaneous B16 melanoma. We find considerable efficacy when anti-TRP1 is combined with cyclophosphamide chemotherapy with treatment initiated at timepoints up to day 7 when tumors are palpable with long term disease control observed in some animals. Treatment is ineffective in mice deficient in the Fc receptor common γ chain. Combination therapy is associated with increased infiltration of tumors by CD8+ T lymphocytes visualized by immunofluorescence (IF) and flow cytometry. Mice receiving combination therapy have increased infiltration by CD4+foxp3- T cells, but not by CD4+foxp3+ T cells. Therapeutic efficacy was decreased but not abrogated in animals depleted of CD8+ T cells through injection of anti-CD8 IgG. Surprisingly, although B16 is a non-immunogenic tumor, surviving mice treated with cyclophosphamide and ‘passive’ immunization with anti-TRP1 displayed resistance to repeat inoculation with B16 melanoma. These data strongly implicate a role for adaptive immunity in the therapeutic efficacy of anti-tumor antibodies combined with chemotherapy and has implications for design of future clinical trials using these agents and for the development of novel strategies to induce adaptive anti-tumor immunity. 1. Ferris RL, Jaffee EM, Ferrone S. Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J Clin Oncol 2010;28:4390-9. 2. Hara I, Takechi Y, Houghton AN. Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein. J Exp Med 1995;182:1609-14. 3. Saenger YM, Li Y, Chiou KC, et al. Improved tumor immunity using anti-tyrosinase related protein-1 monoclonal antibody combined with DNA vaccines in murine melanoma. Cancer Res 2008;68:9884-91. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4742. doi:10.1158/1538-7445.AM2011-4742
The Schauder Fixed Point Theorem for Nonexpansive Mappings

(1977). The Schauder Fixed Point Theorem for Nonexpansive Mappings. The American Mathematical Monthly: Vol. 84, No. 5, pp. 363-364.
Monitoring gastroesophageal reflux in children with ambulatory double gastroesophageal pH

Objective To judge types of Gastroesophageal reflux disease(GERD) in children so as to improve the diagnosis of GERD.Methods Ambulatory 24 hour distal esophageal and gastric pH monitor was conducted in 65 cases of GERD with double pH probe.Results Acid GER was observed in 29 cases (44.6 %).Alkaline GER was observed in 4 cases (6.1 %), totally 33 cases (50.7 %). The parameters were significantly different in two groups than in controls.Conclusions Ambulatory double Gastroesophageal pH monitor can judge the extent and the type of reflux which is helpful in the diagnosis of GERD.
The Research of Cylinder Head Assembly Valve Seal Check

For the sake of meeting the requirement of valve seal,this discourse introduced basic theory of valve seal、valve and seat cooperation、Cylinder head valve seal test,the common reasons for leak and the control measures,also show the validity of measures base on production data.
Implementation of High-Precision Clock Recovery Circuit for HDLC Bit Streams by FPGA

A high-precision clock recovery circuit for HDLC bit streams is presented in the paper.The modular programmable FPGA implementation achieves a high-precision clock recovery through HDLC bit streams by using key techniques such as fractional frequency division,hardware PLL frequency multiplication,data edge sampling and HDLC key words measuring.It is proved by hardware experiment that the implementation has excellent performance.It is practicaly and widely applicable.
Peroxidase-containing microgranules in human neutrophils: physical, morphological, cytochemical, and secretory properties

A microgranule fraction, isolated from human neutrophils by using a novel high-resolution Percoll density gradient system contained granules with the lowest density and diameter when compared with 12 other isopycnic granule fractions. Ultrastructurally, from 34% to 50% of the microgranules showed homogeneous diaminobenzidine (DAB) staining under conditions for localizing peroxidase reactivity. The presence of myeloperoxidase (MPO) was further confirmed by biochemical and spectral analysis and immunodiffusion methods. Periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) intensely stained vicinal glycols in the matrix of greater than 97% microgranules in contrast to the weak or absent staining seen in larger primary granules. Directly sampled segmented neutrophils contained small DAB- and PA-TCH-SP-positive granules, which often appeared in clusters. These DAB-positive microgranules selectively remained within the cells after stimulation of exocytosis with the calcium ionophore A23187. The enriched DAB-positive microgranule fraction recovered from A23187-treated cells also contained lysozyme and beta-glucuronidase but lacked vitamin B12 binding protein activity. A similar small, DAB- and PA-TCH-SP-positive granule type was also identified in normal promyelocytes and was the predominant or only granule type observed in leukemic or preleukemic myeloid cells from four patients. This study demonstrates a unique subpopulation of MPO-containing microgranules in normal and leukemic human myeloid cells that are distinguished from (other) primary granules by their extremely low density, small size, content of complex carbohydrates, and resistance to secretion.
Lymphography in surgically unresectable adenocarcinoma of the exocrine pancreas.

Bipedal lymphograms were performed on 28 consecutive previously untreated patients with biopsy proven and surgically unresectable carcinoma of the pancreas. Four of these patients had findings indicating lymph node metastases. In three of these 4 patients, the lymphogram provided the only evidence of metastatic disease. The information provided by bipedal lymphography may be useful in treatment planning.
Mixed depression and anxiety: serotonin1A receptors as a common pharmacologic link.

Although depressive and anxious symptoms frequently coexist, most studies tend to dichotomize anxiety disorders from depression. Consequently, pharmacologic agents are designated as antidepressants or anxiolytics. A number of developments are reversing this trend. One is changes in conceptualization of generalized anxiety disorder (GAD) and major depressive disorder to recognize the frequent existence of simultaneous symptoms of anxiety and depression in patients with related affective and anxiety disorders. A second is the increasing recognition that subsyndromal symptoms of anxiety and depression frequently exist that do not reach thresholds for GAD or depression but that may decompensate to overt anxiety disorder or depression. A third is the discovery of partial agonists for serotonin 1A receptor subtypes that have promising efficacy in mixed depression and anxiety.
Hypogonadism and Prostate Cancer: To Treat or Not to Treat

For decades, testosterone replacement therapy has been avoided in men with a history of prostate cancer due to concerns that testosterone may cause prostate cancer progression or recurrence. However, this concern is not well founded by the medical literature. Moreover, during the PSA era, there has been no significant data to show that testosterone causes prostate cancer progression or recurrence. In fact, there have been several studies suggesting that testosterone may be protective against prostate cancer. There are many theories, such as the prostate saturation theory, that may help us understand why testosterone may be safely administered in men with hypogonadism even after surgical treatment of prostate cancer. Because patients with hypogonadism may already be at a significant disadvantage in recovering their erectile function after prostatectomy, they perhaps should receive special consideration as candidates for androgen replacement therapy.
Nonlinear orbital dynamic equations and state-dependent Riccati equation control of formation flying satellites

Precise maneuvers of formation flying satellites require a general orbital dynamic equation and an effective nonlinear control method. In this paper, nonlinear orbital dynamics of relative motion equations are derived for a constant distance separation formation flying problem. This general orbital dynamic equation allows elliptic, noncoplanar, and large separation distances between spacecraft as well as traditional circular, coplanar, and small separation distance cases. Furthermore, for the in-plane formation flying scenario with large constant angle of separation between satellites, we derive the change in position and velocity equations. A nonlinear control method called the state-dependent Riccati equation control method is utilized to solve the formation flying control problem. This novel control method for a nonlinear system allows the intuitive design tradeoff between the control action and the state error similar to the classical linear-quadratic-regulator control method. Two numerical simulations demonstrate the effectiveness of the new state-dependent Riccati equation control method with the newly developed relative motion equations.
Comment on “Evidence of a first-order phase transition to metallic hydrogen”

A recent paper by Zaghoo et al. presents optical data at high-pressure and high-temperature and interprets the data as evidence for a first-order phase transition to metallic hydrogen during heating. Here we argue that the presented data are contradictory with these claims. Elucidating this issue is important for building a coherent picture that is emerging as the results of theoretical calculations of various levels and experimental investigations employing static and dynamic compression techniques. In this context, the use of adequate probes of the electronic and chemical state is crucial. Optical probes that do not address the energy dependent conductivity while making multiple references to the Drude model are highly speculative. Indeed, the available dynamic and static compression data and theoretical modeling show that study of energy dependent conductivity is important for understanding the nature of hot dense hydrogen. Moreover, the most recent investigations suggest that the critical point, which demarcates the regimes of crossover between insulating and plasma state at low densities to the first order liquid-liquid transition, is above 200 GPa. Below we concentrate on inconsistencies in the interpretation of data in Zaghoo et al, which call for careful examination of their claims and further detailed investigations. We analyze their optical data and use finite element calculations and argue that the high-temperature state studied in Zaghoo et al. is not metallic and that the data cannot discriminate between a first-order phase transition and a continuous phase transition, or even a bandgap drop within one phase
Tailoring frequency generation in uniform and concatenated multimode fibers

We demonstrate that frequency generation in multimode parabolic-index fibers can be precisely engineered through appropriate fiber design. This is accomplished by exploiting the onset of a geometric parametric instability that arises from resonant spatiotemporal compression. By launching the output of an amplified Q-switched microchip laser delivering 400 ps pulses at 1064 nm, we observe a series of intense frequency sidebands that strongly depend on the fiber core size. The nonlinear frequency generation is analyzed in three fiber samples with 50 μm, 60 μm, and 80 μm core diameters. We further demonstrate that by cascading fibers of different core sizes, a desired frequency band can be generated from the frequency lines parametrically produced in each section. The observed frequency shifts are in good agreement with analytical predictions and numerical simulations. Our results suggest that core scaling and fiber concatenation can provide a viable avenue in designing optical sources with tailored output frequencies.
Iliac Branch Device Designs

Recent developments of iliac branch devices by several endograft manufacturers have expanded the indications of endovascular repair to patients with aneurysms involving the iliac bifurcation. Endografts are based on polyester or expanded heparin-bonded PTFE coupled with stainless steel or nitinol stents. This chapter describes the specific designs available from different manufacturers.
How an alloreactive T-cell receptor achieves peptide and MHC specificity.

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2− individual received an HLA-A2+ liver allograft. HCV1406 was subsequently shown to recognize the HCV nonstructural protein 3 (NS3):1406–1415 epitope with high specificity when presented by HLA-A2. We show that NS3/HLA-A2 recognition by the HCV1406 TCR is critically dependent on features unique to both the allo-MHC and the NS3 epitope. We also find cooperativity between structural mimicry and a crucial peptide “hot spot” and demonstrate its role, along with the MHC, in directing the specificity of allorecognition. Our results help explain the paradox of specificity in alloreactive TCRs and have implications for their use in immunotherapy and related efforts to manipulate TCR recognition, as well as alloreactivity in general.
Hepatic vein pressure predicts GFR in cirrhotic patients with hemodynamic kidney dysfunction.

The role of “nephrocongestion” in hemodynamic renal disease is understudied. Intra-abdominal hypertension accompanies liver disease and renal disease. Our hypothesis states that in those patients with liver disease, hepatic vein pressure measured during a transjugular intrahepatic portosystemic shunt (TIPS) procedure reflects intra-abdominal pressure and predicts estimated glomerular filtration rate (eGFR). We gathered data from our clinical database and chart review on a cohort of cirrhotic patients who received TIPS at Montefiore as part of their clinical care between 2004 and 2014. We evaluated association of demographic and measured variables with eGFR in those subjects without end-stage renal disease (ESRD). Using multivariate regression, we examined the relationship between eGFR and hepatic vein pressure while adjusting for age, proteinuria, and ultrasound evidence for parenchymal kidney disease. The mean age of the subjects was 57 years old. Two thirds of the patients were male, 23% were White, and 20% were Black. A higher percentage of patients with chronic kidney disease (CKD), as determined by lower than 60 mL/min/1.73 m2, had proteinuria and ultrasound evidence for parenchymal kidney disease. A multivariate linear regression showed a significant and negative association between hepatic vein pressure and eGFR when adjusting for age, race, and proteinuria. Hepatic vein pressure is negatively and significantly associated with eGFR in those patients with liver failure. This finding has major implications for the way we evaluate hemodynamic renal disease.
Neonatal Systemic AAV-Mediated Gene Delivery of GDF11 Inhibits Skeletal Muscle Growth

Growth and differentiation factor 11 (GDF11; BMP11) is a circulating cytokine in the transforming growth factor beta (TGF-β) superfamily. Treatment with recombinant GDF11 (rGDF11) protein has previously been shown to reverse skeletal muscle dysfunction in aged mice. However, the actions of GDF11 in skeletal muscle are still not fully understood. Because GDF11 activates the TGF-β-SMAD2/3 pathway, we hypothesized that GDF11 overexpression would inhibit skeletal muscle growth. To test this hypothesis, we generated recombinant adeno-associated virus serotype 9 (AAV9) vectors harboring the gene for either human GDF11 (AAV9-GDF11) or human IgG1 Fc-fused GDF11 propeptide (AAV9-GDF11Pro-Fc-1) to study the effects of GDF11 overexpression or blockade on skeletal muscle growth and function in vivo. After intravenous administration of AAV9-GDF11 into neonatal C57BL/6J mice, we observed sustained limb muscle growth inhibition along with reductions in forelimb grip strength and treadmill running endurance at 16 weeks. Conversely, treatment with AAV9-GDF11Pro-Fc-1 led to increased limb muscle mass and forelimb grip strength after 28 weeks, although a difference in the total body mass/muscle mass ratio was not observed between treatment and control groups. In sum, our results suggest GDF11 overexpression has an inhibitory effect on skeletal muscle growth.
Vaginal Repair and Concurrent Prolapse and Continence Surgery

The prevalence of pelvic organ prolapse and urinary incontinence is increasing and with it the need for corrective surgery. As the risk factors are similar it is inevitable that women will commonly present with both. The usual offer of conservative treatment should be made. Prior to undertaking concurrent surgery it is important to give patients the option of having a two stage procedure and for those choosing to have surgery for both conditions concurrently to be aware of the implications of this. This has become an increasingly litigious area and is discussed in this chapter.
Endoplasmic Reticulum Stress in Vertebrate Mutant Rhodopsin Models of Retinal Degeneration

Rhodopsin mutations cause many types of heritable retinitis pigmentosa (RP). Biochemical and in vitro studies have demonstrated that many RP-linked mutant rhodopsins produce misfolded rhodopsin proteins, which are prone to aggregation and retention within the endoplasmic reticulum, where they cause endoplasmic reticulum stress and activate the Unfolded Protein Response signaling pathways. Many vertebrate models of retinal degeneration have been created through expression of RP-linked rhodopsins in photoreceptors including, but not limited to, VPP/GHL mice, P23H Rhodopsin frogs, P23H rhodopsin rats, S334ter rhodopsin rats, C185R rhodopsin mice, T17M rhodopsin mice, and P23H rhodopsin mice. These models have provided many opportunities to test therapeutic strategies to prevent retinal degeneration and also enabled in vivo investigation of cellular and molecular mechanisms responsible for photoreceptor cell death. Here, we examine and compare the contribution of endoplasmic reticulum stress to retinal degeneration in several vertebrate models of RP generated through expression of mutant rhodopsins.
All four core histone N-termini contain sequences required for the repression of basal transcription in yeast.

Abstract Nucleosomes prevent the recognition of TATA promoter elements by the basal transcriptional machinery in the absence of induction. However, while Saccharomyces cerevisiae histones H3 and H4 contain N-terminal regions involved in the activation and repression of GAL1 and in the expression of heterochromatin-like regions, the sequences involved in repressing basal transcription have not yet been identified. Here, we describe the mapping of new N-terminal domains, in all four core histones (H2A, H2B, H3 and H4), required for the repression of basal, uninduced transcription. Basal transcription was monitored by the use of a GAL1 promoter-URA3 reporter construct whose uninduced activity can be detected through cellular sensitivity to the drug, 5-fluoroorotic acid. We have found for each histone that the N-terminal sequences repressing basal activity are in a short region adjacent to the structured alpha-helical core. Analysis of minichromosome DNA topology demonstrates that the basal domains are required for the proper folding of DNA around the chromosomal particle. Deletion of the basal domain at each histone significantly decreases plasmid superhelical density, which probably reflects a release of DNA from the constraints of the nucleosome into the linker region. This provides a means by which basal factors may recognize otherwise repressed regulatory elements.
Dynamic hypoxic hypoxemia in brain tissue: experimental and theoretical methodologies.

An experimental system was assembled to study feline cerebral cortex cellular and extracellular pO2 response to rapid changes in carotid artery oxygen levels. The system has been described in prior articles in this series and elsewhere (Bogue and Dorson, 1973; Dorson and Bogue, 1973; Dorson and Bogue, 1976; Bogue, 1974). Changes in carotid artery oxygen level could be accomplished either by varying the ventilatory gas composition or by a carotid-jugular computer controlled exchange method. The latter technique involved cannulation of both internal carotid arteries and jugular veins. All other perfusion routes were supressed by compression. Relatively open flow was allowed in both directions with exchange between venous and arterial blood on an equal volume flow basis. This system resulted in the most rapid possible input change while maintaining close to normal physiological function. Many different types of changes were investigated, and this report will concentrate on oscillatory inputs caused by both the ventilation gas and blood exchange methods. No difference in response was noted up to the upper frequency limit of the ventilation method of 0.1 Hz while the exchange method was capable of 1.0 Hz oscillations.
Transmission Factor, Filters, and Transients (Küpfmüller’s Theory)

The response of mechanical and electrical systems usually differs considerably from the time pattern of the exciting force or voltage, particularly if this time pattern is nonsinusoidal. Mechanical systems do not act like generators that are switched on and off; their steady-state vibrations are attained gradually, and they die out gradually when the excitation stops. The variation of the response of the system from that of the driving force or voltage is usually described as its transient response. As a consequence of their transients, mechanical and electrical systems are not just reproducers, they exhibit their own idiosyncracies.
Catalyzed non-isocyanate polyurethane (NIPU) coatings from bio-based poly(cyclic carbonates)

Formulations of bio-based poly(cyclic carbonates) and amines using cooperative catalysis were studied to produce non-isocyanate polyurethanes (NIPUs). Concerns on the use of isocyanates as starting materials for polyurethanes (PUs) have risen due to their effects on human health after exposure and also because their synthesis involves the use of phosgene. Polyurethanes are highly versatile materials used in widespread industries such as automotive, building, construction, and packaging. They have also been used as flexible and rigid foams, adhesives, coatings, thermoplastic, or thermoset materials. Traditionally, PUs are synthesized from polyols and polyisocyanates. In order to circumvent the concerns, much research has been devoted to exploring alternative approaches to the synthesis of PUs. NIPU synthesis using cyclic carbonates and amines has gained popularity as one of the new approaches. In this study, novel bio-based resins were synthesized by converting epoxidized sucrose soyate into carbonated sucrose soyate (CSS) under supercritical conditions. Initial studies have shown promise in systems where CSS is crosslinked with multifunctional amines generating coatings with good solvent resistance. This work focused on studying the effect of catalysts and developing formulations of bio-based non-isocyanate polyurethane coatings.
The pyrimidine biosynthetic pathway and its regulation in Pseudomonas jessenii

The control of the pyrimidine biosynthetic pathway by pyrimidine bases was examined in Pseudomonas jessenii ATCC 700870. The pyrimidine biosynthetic enzymes aspartate transcarbamoylase, dihydroorotase, dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5′-monophosphate (OMP) decarboxylase activities were found to be higher in the succinate-grown ATCC 700870 cells than the glucose-grown cells. All the enzyme activities were depressed in uracil-supplemented ATCC 700870 glucose-grown cells relative to the unsupplemented cells which was indicative of possible repression of enzyme synthesis by uracil. In the succinate-grown, ATCC 700870 cells, transcarbamoylase, dihydroorotase and dehydrogenase activities were decreased by uracil and orotate supplementation while decarboxylase activity was decreased following uracil addition. A pyrimidine auxotroph was isolated by conventional chemical mutagenesis and resistance to 5-fluoroorotic acid whose pyrimidine requirement was met by uracil or cytosine. The mutant strain was deficient for orotate phosphoribosyltransferase activity. Pyrimidine limitation of the mutant strain cells for 1 or 2 h caused about a two-fold increase in aspartate transcarbamoylase or dihydroorotase activity independent of carbon source relative to excess uracil growth conditions. At the level of enzyme activity, aspartate transcarbamoylase activity in P. jessenii ATCC 700870 was inhibited strongly by pyrophosphate, ATP, UTP, GTP and UMP under saturating substrate concentrations.
Impact force to a rigid obstruction from a granular mass sliding down a smooth incline

The impact force to a rigid obstruction from a granular mass sliding down a smooth incline provides insights into the solid-like and fluid-like behaviors of granular avalanches and useful information for risk assessment and engineering design against landslides. In this study, a series of 2-D flume tests were performed to systematically investigate the effects of inclination angle, sliding distance, and initial relative density on the flow front velocity and impact force on a rigid obstruction. The experimental results show that for inclination angles smaller than the critical state friction angle of sand, an increase in the sliding distance and/or initial relative density results in smaller impact forces; for higher inclination angles, the trend is reversed. Based on the experimental results, an analytical equation is proposed to estimate the flow front velocity and an empirical approach is presented to estimate the maximum impact force based on elastic solid and hydrodynamic methods. The proposed equations are found to provide more accurate predictions for the maximum impact force than similar equations in the literature.
Three-dimensional soft tissue analysis of the face following micro-implant-supported maxillary skeletal expansion

Skeletal maxillary expander (MSE) is one of the more recent expander designs being utilized for skeletal expansion by splitting the midpalatal sutures applying forces through palatal micro-implants. Its effects on the soft tissue remain a question asked by both patients and clinicians. The aim of this study was to analyze and quantify soft tissue facial changes induced by MSE. 3D facial images (3dMD) were used to capture face scans of 25 patients generating 3D soft tissue meshes before expansion (T0), right after expansion (T1), and 1 year in retention (T2). MATLAB was then used, utilizing non-rigid iterative closest point algorithm, to align all samples in vertex correspondence and generate averages. Surface mapping of each average, along with its variance, allows for quantification of changes between the three pools of samples in 3D space. The generated 3D p-maps between T0 and T1 demonstrate that statistically significant changes (p < 0.05 and p < 0.01) are localized in the circummaxillary area (paranasal, lips, and both cheeks). Vector map shows a mean displacement of 1.5 mm in the paranasal area. The right cheek showing a mean displacement magnitude of 2.5 mm while the left cheek has a mean of 2.9 mm. Direction of vectors are latero-anterior with more dominant anterior direction. There are significant changes in paranasal, upper lip, and at both cheeks following expansion using MSE with greater magnitude at the cheeks area. Those changes do not relapse after 1 year (p < 0.05).
Differential Impacts of Subsistence on Developmental Stress in Prehistoric Ohio Valley Children

Bioarchaeologists often assume that the intensification of agriculture results in an increase in physiological stress, but it is necessary to also consider duration and age of occurrence of stress events. Linear enamel hypoplasias (LEH) are indicators of such events. By analyzing LEH on the permanent anterior teeth of 40 children from prehistoric Ohio Valley, this project compares the timing and duration of stress events of foragers (4000-3000 B.P.) with those of agriculturalists (A.D. 1000-1500). A scanning electron microscope was used to create 50X photomontages of the tooth surfaces. LEH from systemic stress were recorded from these photomontages as those that concurrently match among other teeth from the same individual. Ages were calculated at which stress events occurred. The total number of perikymata within each defect furrow were used to reflect the duration of the stress events. Variables were compared between samples using Fisher’s exact tests and pairwise ANOVA. Agriculturalist children endured the most stress events, although foraging children suffered the longest stress events. Variation can be attributable to cultural or nutritional change in the Ohio Valley, resulting in agriculturalist children being more frail. Results are similar to previous studies exploring transitions in physiological stress with the rise of agriculture.
Stable Spondylolisthesis: Should Management Change Based on Presence of Facet Cysts?

Study design This is a retrospective cohort review. Objective To determine whether a correlation exists between facet cysts and lumbar instability. Summary of background data Lumbar facet cysts are common degenerative entities observed in patients with low-grade spondylolisthesis at a rate of 10%-50%. Surgical management with partial facetectomy with or without fusion remains controversial. Methods Review of 86 patients with lumbar degenerative spondylolisthesis is performed. Preoperative magnetic resonance imagings were reviewed for the presence of lumbar facet cysts and Facet Fluid Indices (FFI)-calculated as the ratio of facet fluid width to facet width. Instability was defined as a difference of >3 mm in vertebral displacement between flexion and extension radiographs. T tests and the Pearson correlation analyses were used to determine statistical significance. Results In total, 26 patients had unstable and 60 had stable spondylolisthesis. Facet cysts were present at an overall prevalence of 30.1%-in 10/26 patients in the unstable group and in 18/60 patients in the stable group (P>0.05). The average FFIs for the unstable and stable groups were 0.13 and 0.09, respectively (P>0.05). FFI in patients with facet cysts was significantly higher than those without (P 3 mm. Conclusions Lack of correlation with instability hints that the presence of facet cysts may not indicate instability in lumbar degenerative spondylolisthesis. Therefore, presence of facet cysts in static magnetic resonance imaging revealing spondylolisthesis should not preclude the physician from performing dynamic films to evaluate for instability. Significantly higher FFI in patients with facet cysts reaffirms the degenerative pathophysiology involved in their formation. Although this is not an outcomes study, it does spark interest into whether patients with stable spondylolisthesis and concurrent facet cysts are suitable for partial facetectomy alone with fusion.