Miracle-dz/UniFAR-FTUs huggingface dataset:
Contrasting Groundwater and Streamflow Ages at the Maimai Watershed

Understanding the links between groundwater age, runoff generation processes, and their effects on stream water transit time (TT) is a major research challenge. Here we present new tritium age dating and hydrogeological characterization from 40 bedrock wells drilled at the intensively studied Maimai Experimental Watershed in New Zealand. We investigated the extent, dynamics, and age of the groundwater in a 4.5 ha headwater catchment over a 400 day period. In particular, we explored the controls of bedrock structure on aquifer dynamics, the aquifer flow domain and its influence on time‐varying stream water TT. We show that low permeability hillslope bedrock minimizes deep recharge, thereby regulating groundwater age, stream water MTT, and surface water‐groundwater interaction. Two distinct hydrologic units can represent catchment storage: shallow young soil storage and deep much older bedrock groundwater. Groundwater ages near discharge zones were up to 23 years compared to soil water ages that ranged between 0.1 and 0.5 years. This difference in age for the two main storages resulted in contrasting seasonal stream water TT response. During the 8 month wet season, stream water TT was young and stable while stream water TT in the slightly drier summer season was highly dynamic. These qualitative field observations are a process exemplar that support the Berghuijs and Kirchner (2017) quantitative descriptions of preferential release of young streamflow; and for the Maimai catchment, support the notion that most groundwater is exchanged only slowly with the surface and is therefore relatively old.
Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information.
One-loop quantum corrections to the entropy for an extremal Reissner-Nordström black hole.

The first quantum corrections to the entropy for an eternal 4-dimensional extremal Reissner-Nordstr\"om black hole is investigated at one-loop level, in the large mass limit of the black hole, making use of the conformal techniques related to the optical metric. A leading cubic horizon divergence is found and other divergences appear due to the singular nature of the optical manifold. The area law is shown to be violated.
Optimal Coding for Streaming Authentication and Interactive Communication

We consider the task of communicating a data stream-a long, possibly infinite message not known in advance to the sender-over a channel with adversarial noise. For any given noise rate c <; 1, we show an efficient, constant-rate scheme that correctly decodes a (1 - c) fraction of the stream sent so far with high probability, or aborts if the noise rate exceeds c. In addition, we prove that no constant-rate scheme can recover more than a (1 - c) fraction of the stream sent so far with non-negligible probability, which makes our scheme optimal in that aspect. The parties are assumed to preshare a random string unknown to the channel. Our techniques can also be applied to the task of interactive communication (two-way communication) over a noisy channel. In a recent paper (Braverman and Rao, STOC11), the possibility of two-party interactive communication as long as the noise level is <; 1/4 was shown. By allowing the parties to preshare some private random string, we extend this result and construct a (nonefficient) constant-rate interactive protocol that succeeds with overwhelming probability against noise rates up to 1/2. We complete this result by proving that no constant-rate protocol can withstand noise rates > 1/2.
The generalized Gilbert-Varshamov bound is implied by Turan's theorem [code construction]

The generalization of the Gilbert-Varshamov bound due to Gu and Fuja (1993) is a direct consequence of Turan's theorem on the existence of a clique in a graph with many edges. Turan's theorem allows a slight improvement of Gu and Fuja's result. This improved generalized Gilbert-Varshamov bound is in fact equivalent to Turan's theorem.
Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright.
Combining Clinical, Pathological, and Demographic Factors Refines Prognosis of Lung Cancer: A Population-Based Study

Background In the treatment of lung cancer, an accurate estimation of patient clinical outcome is essential for choosing an appropriate course of therapy. It is important to develop a prognostic stratification model which combines clinical, pathological and demographic factors for individualized clinical decision making. Methodology/Principal Findings A total of 234,412 patients diagnosed with adenocarcinomas or squamous cell carcinomas of the lung or bronchus between 1988 and 2006 were retrieved from the SEER database to construct a prognostic model. A model was developed by estimating a Cox proportional hazards model on 500 bootstrapped samples. Two models, one using stage alone and another comprehensive model using additional covariates, were constructed. The comprehensive model consistently outperformed the model using stage alone in prognostic stratification and on Harrell's C, Nagelkerke's R2, and Brier Scores in the whole patient population as well as in specific treatment modalities. Specifically, the comprehensive model generated different prognostic groups with distinct post-operative survival (log-rank P<0.001) within surgical stage IA and IB patients in Kaplan-Meier analyses. Two additional patient cohorts (n = 1,991) were used as an external validation, with the comprehensive model again outperforming the model using stage alone with regards to prognostic stratification and the three evaluated metrics. Conclusion/Significance These results demonstrate the feasibility of constructing a precise prognostic model combining multiple clinical, pathologic, and demographic factors. The comprehensive model significantly improves individualized prognosis upon AJCC tumor staging and is robust across a range of treatment modalities, the spectrum of patient risk, and in novel patient cohorts.
The Feedback Regulation of Angiotensinogen Production by Components of the Renin‐Angiotensin System

The in vivo generation of angiotensin appears to be dependent on both plasma renin and angiotensinogen concentrations. Much less is known about the control of hepatic angiotensino-gen synthesis and release, as compared to that of renin. In this study, we examined the feedback regulation of angiotensinogen synthesis and release by various components of the renin-angiotensin system, using an in vitro rat liver slice system. Livers were removed for study from rats which were subjected to various systemic infusions or physiological perturbations. Infusion of angiotensin II has been reported to increase angiotensinogen release rate. However, infusion of angiotensin I (with simultaneous suppression of plasma renin by antirenin antibody infusion and angiotensin II production by captopril administration) had no effect on the angiotensinogen release rate. Direct infusion of renin in rats treated with captopril resulted in further suppression of the angiotensinogen release rate, compared with those given captopril alone. We postulate that renin (or des-angiotensin I-angiotensinogen) inhibits the angiotensinogen release rate, whereas angiotensin II stimulates it. Angiotensin I has no effect on angiotensinogen release rate. This hypothesis was evaluated further in rats with various physiological states. Indeed, when conditions were such that the renin-angiotensin system was completely suppressed, such as binephrectomy and antirenin antibody infusion, angiotensinogen release rate was markedly stimulated. When angiotensin II production was prevented by captopril treatment, angiotensinogen release rate declined. This appeared to be the case for all states of sodium balance. Thus, angiotensinogen release rate is subject to a complex feedback control by other components of the renin-angiotensin system.
Mutagen treatment as a means for selecting immunogenic variants from otherwise poorly immunogenic malignant murine tumors.

The selection of nontumorigenic (tum-), highly immunogenic variants from four different tumorigenic but poorly immunogenic murine tumors by mutagen treatment and cloning is described. Several factors were found to determine the successful nature of this selection procedure including: the nature of the tumor used; the nature of the mutagen; the number of mutagen treatments; and the time at which cloning is performed after treatment. In some cases, e.g. , the TA3 adenocarcinoma or the BALB/c SS1 spontaneous mammary adenoacanthoma, a single treatment with ethyl methanesulfonate or N -methyl- N ′-nitro- N -nitrosoguanidine led to a very high frequency of tum- clones, whereas in others, e.g. , the MDAY-D2 tumor line, no stable tum- clones were obtained. The immunogenic clones selected were always immunologically cross-reactive with the parent tumor from which they were derived and were found to protect the murine host against challenge with the parent tumor in vivo . Thus, the cloned immunogenic variants share an antigen with the parent tumor. Additional evidence, however, suggested that each clone also expresses a new private or unique antigen. The frequency of immunogenic variant selection ranged from a low of 6% to a high of 95%. In some cases in which the frequencies were very high, cloning was not required to reveal the tum- phenotype. Finally, we also noted that selection for drug resistance, e.g. , resistance to 6-thioguanine, after mutagenesis could have an enhancing effect on the generation of highly immunogenic tum- clones. The results show that the immunogenicity of poorly immunogenic tumors, including those of spontaneous origin, can be dramatically enhanced by appropriate mutagen treatments but that there is considerable variation in the ease with which highly immunogenic variants can be obtained.
Incorporation of α‐Tocopherol in Liposomes Promotes the Retention of Liposome‐encapsulated Glutathione in the Rat Lung

Abstract— The present study was undertaken to investigate whether α‐tocopherol incorporated in liposomes could improve the retention of entrapped glutathione (GSH) in the lung following intratracheal instillation in rats. Rats were treated with a single dose of [3H]GSH entrapped in liposomes with or without 30 mol% α‐tocopherol and killed 0, 24 or 48 h later. The retention of GSH in the lung was assessed by measuring the recovery of either 3H‐label or GSH in the lung. Animals instilled with free [3H]GSH were found to retain only 2% of the administered dose at 24 h after treatment and no detectable radioactivity at 48 h. Liposome encapsulation altered the pulmonary retention of GSH with 18 and 10% of radioactivity remaining in the lung at 24 and 48 h post‐treatment, respectively. The instillation of GSH encapsulated in α‐tocopherol‐containing liposomes resulted in the highest level of GSH retention in the lung, namely 37 and 30% of the administered GSH dose at 24 and 48 h, respectively. Results from Sepharose 4B column chromatography revealed that lung homogenates, obtained from rats instilled with GSH entrapped in α‐tocopherol‐containing liposomes, 24 and 48 h earlier, contained 2 eluted GSH‐related components—one associated with the liposomal lipid marker in the void volume and the other as free GSH tripeptide, suggesting a slow sustained release effect mediated by the liposomal formulation. The same liposome preparation containing both α‐tocopherol and GSH also conferred better protection against FeADP‐induced lipid peroxidation than liposomes containing either α‐tocopherol or GSH alone, indicative of a potentially effective antioxidant formulation for treating oxidative lung injury.
Relative Contributions of Axonal and Somatic Na Channels to Action Potential Initiation in Cerebellar Purkinje Neurons

Neuronal excitability is likely to be regulated by the site of action potential initiation, the location on a neuron that crosses threshold first. Although initiation is axonal in many neurons, in Purkinje cells, somatic conductances can generate spontaneous action potentials, suggesting that the perisomatic region (soma and/or initial segment) contributes to spike initiation and may regulate firing. To identify directly the cellular regions at which Na channel modulation significantly influences firing, we measured spontaneous and evoked action potentials in Purkinje cells in cerebellar slices from postnatal day 14–28 mice while applying drugs locally to either the soma/initial segment or the first node of Ranvier. Na currents were decreased by tetrodotoxin (TTX) or increased by β-pompilidotoxin (β-PMTX). Dual somatic and axonal recordings indicated that spike thresholds and input–output curves were sensitive to TTX or β-PMTX at the perisomatic region but were unchanged by either drug at the first node. When perisomatic Na channel availability was reduced with subsaturating TTX, however, the input–output curve became shallower during additional TTX block of nodal channels, revealing a latent role for nodal Na channels in facilitating firing. In perisomatic TTX, axons failed to generate spontaneous or evoked spike trains. In contrast, choline block of the initial segment alone altered normal input–output curves. The data suggest that, although the first node reliably follows action potentials, spike initiation in Purkinje neurons occurs in the initial segment. Moreover, Purkinje cell output depends on the density, availability, and kinetics of perisomatic Na channels, a characteristic that may distinguish spontaneously firing from quiescent neurons.
Impact of MYH6 variants in hypoplastic left heart syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P < 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P < 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P < 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P < 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications.
Adaptive neural network control for a class of low-triangular-structured nonlinear systems

In this paper, a class of unknown perturbed nonlinear systems is theoretically stabilized by using adaptive neural network control. The systems, with disturbances and nonaffine unknown functions, have low triangular structure, which generalizes both strict-feedback uncertain systems and pure-feedback ones. There do not exist any effective methods to stabilize this kind of systems. With some new conclusions for Nussbaum-Gain functions (NGF) and the idea of backstepping, semiglobal, uniformal, and ultimate boundedness of all the signals in the closed-loop is proved at equilibrium point. The two problems, control directions and control singularity, are well dealt with. The effectiveness of proposed scheme is shown by simulation on a proper nonlinear system.
Cardiac output in four-, five-, and six-week-old broilers, and hemodynamic responses to intravenous injections of epinephrine.

Female broilers were evaluated at 4, 5, and 6 wk of age (1.2, 1.8, and 2.3 kg BW, respectively) to assess changes in cardiac output and related hemodynamics associated with BW gain, and to evaluate cardiopulmonary hemodynamic adjustments occurring secondary to i.v. injections of epinephrine (0.1 mg/ kg BW). Cardiac output increased with BW (253, 348, and 434 mL/min at 4, 5, and 6 wk, respectively) due to increases in stroke volume (0.70, 1.03, and 1.33 mL/beat) that more than compensated for reductions in heart rate (362, 337, and 328 bpm). Normalization for BW eliminated the differences in cardiac output and stroke volume. Increases in cardiac output were not associated with age- or BW-related increases in mean systemic arterial pressure (101.5, 108.6, and 108.0 mm Hg) due to corresponding reductions in total peripheral resistance (0.41, 0.32, and 0.26 relative resistance units). Epinephrine initially triggered immediate (within 90 s) threefold increases in total peripheral resistance and pulmonary vascular resistance, which, in turn, increased the systemic arterial pressure and pulmonary arterial pressure in spite of concurrent reductions in cardiac output that were associated with diminished venous return and dependent reductions in stroke volume and heart rate. Within 150 s after epinephrine injection, the systemic and pulmonary vascular resistances returned to preinjection control levels. By 300 s postinjection, stroke volume and heart rate increased, causing cardiac output to rise above preinjection control levels, which, in turn, elicited variable pulmonary arterial pressure responses apparently reflecting individual variability in the capacity for flow-dependent pulmonary vasodilation. These studies demonstrate that chronic (age- and BW-related) and acute (epinephrine-induced) changes in cardiac output in broilers reflect complex interactions among hemodynamic variables that include stroke volume, heart rate, and systemic and pulmonary vascular resistances.
New treatments for type 2 diabetes mellitus: combined therapy with sitagliptin

Background: Sitagliptin is a highly selective oral dipeptidyl peptidase-4 inhibitor. This drug increases the plasma concentration of active glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide. These two hormones then simulate the secretion of insulin in a glucose-dependent manner and inhibit glucagon secretion, thus reducing circulating glucose levels. In animal models, GLP-1 increases β-cell mass. Objective: To review the efficacy and safety of sitagliptin in combined therapies (as add on or initial combination treatment) in type 2 diabetes. Methods: A Medline search on published clinical trials involving sitagliptin in combined therapies was performed; additional information from published papers and abstracts to congresses on preclinical and basic science issues was also included to support the mechanistic rationale of combinations. Results/conclusion: In humans sitagliptin administration reduces fasting and postprandial glucose and A1c levels. Sitagliptin is as effective as glipizide (close to 0.7% mean A1c reduction), but has fewer hypoglycemic events than other oral insulin secretagogues. Since metformin reduces hepatic glucose production and increases GLP-1 release, combined therapy with sitagliptin becomes complementary and has been shown to have important additive effects. Sitagliptin combined with pioglitazone resulted in improved metabolic control when compared with pioglitazone plus placebo. Combined administration with insulin requires further studies. The weight neutral effect of sitagliptin, its glucose-dependent action (lower risk of hypoglycemia), the beneficial effects on β-cell function and its eventual protective action on β-cell mass makes it an excellent option for monotherapy or combined with metformin, glitazones or even sulfonylurea.