Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Analysis of a Missense Mutation in the Serine Protease Inhibitor SPINT2 Associated with Congenital Sodium Diarrhea

Membrane-bound serine proteases play important roles in different biological processes. Their regulation by endogenous inhibitors is poorly understood. A Y163C mutation in the SPINT2 gene encoding the serine protease inhibitor Hepatocyte Growth Factor Inhibitor HAI-2 is associated with a congenital sodium diarrhea. The functional consequences of this mutation on HAI-2 activity and its physiological targets are unknown. We established a cellular assay in Xenopus laevis oocytes to study functional interactions between HAI-2 and candidate membrane-bound serine proteases expressed in the gastro-intestinal tract. We found that the wild-type form of HAI-2 is a potent inhibitor of nine gastro-intestinal serine proteases. The Y163C mutation in the second Kunitz domain of HAI-2 resulted in a complete loss of inhibitory activity on two intestinal proteases, prostasin and tmprss13. The effect of the mutation of the homologous Y68C in the first Kunitz domain of HAI-2 is consistent with a differential contribution of the two Kunitz domains of HAI-2 in the inhibition of serine proteases. By contrast to the Tyr to Cys, the Tyr to Ser substitution did not change the inhibitory potency of HAI-2, indicating that the thiol-group of the cysteine rather than the Tyr deletion is responsible for the HAI-2 loss of function. Our functional assay allowed us to identify membrane-bound serine proteases as cellular target for inhibition by HAI-2 wild type and mutants, and to better define the role of the Tyr in the second Kunitz domain in the inhibitory activity of HAI-2.
HBV Subgenotype C2 Infection, A1762T/G1764A Mutations May Contribute To Hepatocellular Carcinoma with Cirrhosis in Southeast China

Background: To glean insights into the relationship among hepatitis B virus (HBV) genotype/subgenotypes, A1762T/G1764A mutations and advanced liver disease such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in Southeast China. Methods: A case-control study was performed, consisting of chronic hepatitis B (CHB) patients (n=160), LC patients (n=150), and HCC patients (n=156). Fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect A1762T/G1764A mutations. HBV genotypes/subgenotypes were determined by multiplex PCR. All patients’ clinical data was systematically collected from the hospital records. Results: Our study revealed HBV genotypes C (63.95%) and B (33.69%) were predominant in chronically infected patients, subgenotype B2, C2 and C1 were the major subgenotypes. Both subgenotype C2 infection and A1762T/G1764A mutations were associated with LC and HCC with cirrhosis, subgenotype C2 (OR=2.033, 95%CI=1.246–3.323, P=0.003 for LC vs CHB; OR=3.247, 95%CI=1.742–6.096, P=0.001 for HCC with cirrhosis vs CHB; respectively ), and A1762T/G1764A mutations (OR=1.914, 95%CI=1.188–3.085, P=0.005 for LC vs CHB; OR=2.996, 95%CI=1.683–5.353, P=0.002 for HCC with cirrhosis vs CHB; respectively), but no differences in the frequencies of both variants between LC and HCC with cirrhosis groups were found. Conclusions: HBV subgenotype C2 infection and A1762T/G1764A mutations are both risk factors of LC and HCC with cirrhosis development in the patients with CHB in Southeast China, but all no helpful for predicting HCC development in LC patients.
Survival of patients with Wegener's granulomatosis diagnosed in Finland in 1981–2000

Objective: To determine the survival of and contributing factors in patients diagnosed with Wegener's granulomatosis (WG) between 1981 and 2000 in Finland. Methods: A retrospective cohort study using hospital discharge registers with a review of hospital case records. Analysis of causes of death in Finland up to 30 July 2005. Results: A total of 492 patients received a verified diagnosis of WG between 1981 and 2000. Of these, 203 died before the end of June 2005. The overall 1-year survival rate was 83.3% and the 5-year survival rate was 74.2%. The standardized mortality ratio (SMR) for all WG patients was 3.43 [95% confidence interval (CI) 2.98–3.94], for women 4.38 (95% CI 3.59–5.61) and for men 2.80 (95% CI 2.28–3.41). The most frequent causes of death were WG or another connective tissue disease, cardiovascular events and neoplasms. The prognosis did not change markedly over the 20-year period. Older age and elevated creatinine level at presentation were associated with poorer prognosis, whereas primary ear, nose, and throat (ENT) involvement and prompt treatment with cyclophosphamide predicted longer survival. Conclusions: WG patients had increased mortality compared with the rest of the population. Older age and elevated creatinine level at diagnosis predicted poor prognosis, but ENT involvement initially and cyclophosphamide treatment resulted in a better outcome.
Niche specialization of terrestrial archaeal ammonia oxidizers

Soil pH is a major determinant of microbial ecosystem processes and potentially a major driver of evolution, adaptation, and diversity of ammonia oxidizers, which control soil nitrification. Archaea are major components of soil microbial communities and contribute significantly to ammonia oxidation in some soils. To determine whether pH drives evolutionary adaptation and community structure of soil archaeal ammonia oxidizers, sequences of amoA, a key functional gene of ammonia oxidation, were examined in soils at global, regional, and local scales. Globally distributed database sequences clustered into 18 well-supported phylogenetic lineages that dominated specific soil pH ranges classified as acidic (pH <5), acido-neutral (5≤ pH <7), or alkalinophilic (pH ≥7). To determine whether patterns were reproduced at regional and local scales, amoA gene fragments were amplified from DNA extracted from 47 soils in the United Kingdom (pH 3.5–8.7), including a pH-gradient formed by seven soils at a single site (pH 4.5–7.5). High-throughput sequencing and analysis of amoA gene fragments identified an additional, previously undiscovered phylogenetic lineage and revealed similar pH-associated distribution patterns at global, regional, and local scales, which were most evident for the five most abundant clusters. Archaeal amoA abundance and diversity increased with soil pH, which was the only physicochemical characteristic measured that significantly influenced community structure. These results suggest evolution based on specific adaptations to soil pH and niche specialization, resulting in a global distribution of archaeal lineages that have important consequences for soil ecosystem function and nitrogen cycling.
College Women’s Experiences of Sexual Coercion

The literature on college women’s experiences with sexual coercion is reviewed, with an emphasis on work published since 1990. Sexual coercion is defined as any situation in which one person uses verbal or physical means (including the administration of drugs or alcohol, with or without the other person’s consent) to obtain sexual activity against consent. We argue that coercive sexual behavior among college students can best be understood within the context of other sexual behaviors and values on college campuses. Significant definitional and methodological problems are identified and discussed. Important victim, perpetrator, and situational variables are identified and discussed. These include attitudes toward women, beliefs about sexual behavior (including rape-supporting beliefs and values), communication problems, coercion-supporting peer groups (including fraternities and athletics), concepts of masculinity and femininity, sexual promiscuity, and alcohol.
Carbon dioxide exchange of larch (Larix gmelinii) cones during development.

Larch (Larix gmelinii (Rupr.) Rupr. ) cone scales are green, but little is known of their photosynthetic role in cone development or about how they differ in gas exchange characteristics from needle leaves. In contrast to leaf photosynthesis (Pleaf), we found that stomatal regulation of cone photosynthetic rate (Pcone) was marginal because the photosynthetic carbon came from internal recycling of respiratory carbon dioxide (CO2). Photosynthetic recycling of respired CO2 was confirmed by the finding that the intercellular CO2 concentration (Ci) in cone scales was much higher than ambient [CO2]; also, there was a positive correlation between Pcone and Ci, whereas Pleaf was almost constant as Ci varied. Low chlorophyll (Chl) concentration was a limiting factor for Pcone, but not for Pleaf, as indicated by the correlation between Pcone and chlorophyll concentration. Moreover, chlorophyll utilization efficiency (Psat/Chl a+b) for cone scales was lower than that for leaves. In both cones and leaves, nitrogen (N) was positively correlated with photosynthetic capacity (P), but the P/N value was much lower for cones than for leaves. For both organs, the ratio of respiration to N was broadly similar. Although mature cones have no photosynthetic capacity, Pcone of young cones was as high as 5.3 micromol m(-2) s(-1), about 1.26 times the value of Pleaf, and accounted for the refixation of 30-40% of the respiratory CO2 produced by cones, equivalent to the photosynthetic capacity of a bundle of short shoots near each cone. Thus, Pcone may be an important additional source of photosynthate for cones, given the weak assimilating capacity of leaves that are not fully expanded during cone development.
Feeding difficulties in disabled children leads to malnutrition: experience in an Indian slum

The aim of the present study was to explore the nature, extent and probable causes of nutritional deficiencies among children with disabilities living in Dharavi, a slum in Mumbai, India. A cross-sectional study was conducted to investigate whether the nutritional status of children with disabilities, aged 2–6 years (n 141), was worse than that of non-disabled sibling controls (n 122) and neighbour controls (n 162). Data on food patterns, anthropometry, micronutrient status and feeding difficulties reported by parents were collected. The mean weight for age of the children with disabilities (−2·44 (sd 1·39) Z scores; n 120) was significantly lower (P<0·05) compared with the sibling (−1·70 (sd 1·20) Z scores; n 109) and neighbour (−1·83 (sd 1·290) Z scores; n 162) control groups. The children with disabilities had significantly lower (P<0·05) mean haemoglobin levels (92 (sd 23) g/l; n 134) compared with siblings (102 (sd 18) g/l; n 103) and neighbours (99 (sd 18) g/l; n 153). Relative risk (RR) analysis indicated that the disabled children with feeding difficulties were significantly more likely (P<0·05) to be malnourished, by the indicator of weight for age (RR 1·1; 95 % CI 1·08, 1·20) compared with the disabled children without a feeding difficulty. They were also significantly more likely to be malnourished using the indicators of height for age (RR 1·3; 95 % CI 1·19, 1·43) and weight for height (RR 2·4; 95 % CI 1·78, 3·23) compared with the disabled children without a feeding difficulty. Feeding difficulties were identified as a risk factor for vulnerability to inadequate nutritional status among children with disabilities.
Apparent Interfacial Tension Effects in Protein Stabilized Emulsions Prepared with Microstructured Systems

Proteins are mostly used to stabilize food emulsions; however, production of protein containing emulsions is notoriously difficult to capture in scaling relations due to the complex behavior of proteins in interfaces, in combination with the dynamic nature of the emulsification process. Here, we investigate premix membrane emulsification and use the Ohnesorge number to derive a scaling relation for emulsions prepared with whey protein, bovine serum albumin (BSA), and a standard emulsifier Tween 20, at various concentrations (0.1%, 0.5%, 1.25% and 2%). In the Ohnesorge number, viscous, inertia, and interfacial tension forces are captured, and most of the parameters can be measured with great accuracy, with the exception of the interfacial tension. We used microfluidic Y-junctions to estimate the apparent interfacial tension at throughputs comparable to those in premix emulsification, and found a unifying relation. We next used this relation to plot the Ohnesorge number versus P-ratio defined as the applied pressure over the Laplace pressure of the premix droplet. The measured values all showed a decreasing Ohnesorge number at increasing P-ratio; the differences between regular surfactants and proteins being systematic. The surfactants were more efficient in droplet size reduction, and it is expected that the differences were caused by the complex behavior of proteins in the interface (visco-elastic film formation). The differences between BSA and whey protein were relatively small, and their behavior coincided with that of low Tween concentration (0.1%), which deviated from the behavior at higher concentrations.
Prolactin Levels and Erectile Function in Patients Treated With Risperidone

Abstract: Treatment with risperidone is associated with prolactin (PRL) elevation, and PRL elevations are associated with erectile dysfunction (ED). We evaluated whether the PRL elevations caused by risperidone treatment of subjects with schizophrenia are associated with objective measures of erectile function. Subjects were hospitalized for 2 nights, and serum measurements of PRL, total testosterone, and free and weakly bound testosterone were performed in the morning and afternoon of each day. Risperidone levels, parent compound, and 9-hydroxy metabolite levels were drawn on the first day. Erectile function assessments, using the RigiScan, an instrument that measures nocturnal penile tumescence and rigidity, were performed on both nights. Consistent with previous reports, the correlation between total risperidone level and PRL was very high (r = 0.92, df = 12, P < 0.0001), but risperidone did not appear to affect either testosterone (r = 0.29, df = 5, P = 0.51) or free and weakly bound testosterone (r = −0.11, df = 10, P = 0.72). Contrary to expectations, PRL levels from the second night were positively correlated with erectile function (r = 0.68, df = 9, P = 0.022). Using objective measures, we were unable to confirm a detrimental association between PRL levels and male erectile function. These results are tentative given the small sample.
Regulation of N-myc gene expression: use of an adenovirus vector to demonstrate posttranscriptional control

We present evidence that differences in the levels of N-myc mRNA among different cell types are the result of posttranscriptional control. First, we noted that while steady-state mouse N-myc mRNA could be detected only in fetal mouse brain, it was transcribed at an equivalent rate in adult brain, liver, spleen, and placenta and in fetal brain. Similarly, the human N-myc gene was transcribed at an equivalent rate in HeLa cells, which do not accumulate this RNA in the cytoplasm, and cell lines G401 (a Wilms tumor-derived cell line) and SKNMc (established from a primitive neuroepithelioma), which do express N-myc RNA. As expected, the N-myc promoter functioned at equivalent rates, as demonstrated by the level of a reporter gene, when introduced into these cell types by using a recombinant adenovirus vector. The suggestion that posttranscriptional mechanisms control the level of this RNA was supported by the observation that sequences in the N-myc third exon specifically decreased the level of E1A mRNA when these sequences were placed downstream of the E1A promoter in a recombinant adenovirus. Finally, we further localized these sequences to a 600-bp fragment of the third exon by introducing various subclones of this sequence downstream of the E1A promoter in both viral and plasmid vectors.
Why the Rich May Favor Poor Protection of Property Rights

In unequal societies, the rich may benefit from shaping economic institutions in their favor. This paper analyzes the dynamics of institutional subversion by focusing on the public protection of property rights. If this institution functions imperfectly, agents have incentives to invest in private protection of property rights. The ability to maintain private protection systems makes the rich natural opponents of public property rights and precludes grass-roots demand to drive the development of the market-friendly institution. The economy becomes stuck in a bad equilibrium with low growth rates, high inequality of income, and wide-spread rent-seeking. The Russian oligarchs of 1990s, who controlled large stakes of newly privatized property, provide motivation for this paper.
Anticipation in familial leukemia.

Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22.
Optimal Noise Adding Mechanisms for Approximate Differential Privacy

We study the (nearly) optimal mechanisms in (ϵ, δ)-differential privacy for integer-valued query functions and vector-valued (histogram-like) query functions under a utility-maximization/cost-minimization framework. Within the classes of mechanisms oblivious of the database and the queries beyond the global sensitivity, we characterize the tradeoff between ϵ and δ in utility and privacy analysis for histogram-like query functions, and show that the (ϵ, δ)-differential privacy is a framework not much more general than the (ϵ, 0)-differential privacy and (ϵ, δ)-differential privacy in the context of ℓ<sup>1</sup> and ℓ<sup>2</sup> cost functions, i.e., minimum expected noise magnitude and noise power. In the same context of ℓ<sup>1</sup> and ℓ<sup>2</sup> cost functions, we show the near-optimality of uniform noise mechanism and discrete Laplacian mechanism in the high privacy regime (as (ϵ, δ) → (0, 0)). We conclude that in (ϵ, δ)-differential privacy, the optimal noise magnitude and the noise power are Θ(min((1/ϵ), (1/δ))) and Θ(min((1/ϵ<sup>2</sup>), (1/δ<sup>2</sup>))), respectively, in the high privacy regime.
Performance availability for networks of workstations

Software systems for large-scale distributed and parallel machines are difficult to build. When run in dynamic, production environments, not only must such systems perform correctly, but they must also operate with high performance. Much of the previous work in distributed computing has addressed the design of large-scale systems that function correctly, in spite of correctness faults of individual components [17, 48, 81, 85]. However, there has been little development of techniques to tolerate performance faults—unexpected performance fluctuations from the components that comprise the system. Due to this shortcoming, many systems are overly sensitive to performance variations, in that global performance is high if and only if all system components perform exactly as expected. In this dissertation, we address this deficiency by formalizing the concept of performance availability. Our hypothesis is that modern software systems must provide mechanisms to enable performance availability. Without such mechanisms, global system performance is likely to be unpredictable and substantially less than ideal. By furnishing application writers with the proper tools to cope with common performance faults, robust system performance can be achieved. To test our hypothesis, we present the design and implementation of River. River provides a generic data-flow environment as a substrate for the construction of performance-robust applications. Two novel, distributed algorithms form the heart of performance availability in River: a distributed queue allows producers to flexibly move data to variable rate consumers, thus avoiding consumer-side performance faults, and graduated declustering carefully allocates producer bandwidth across consumers, similarly avoiding producer-side performance faults. In tandem, with no centralized components or global information, these two constructs can be used to implement performance-robust applications. We demonstrate the utility and efficiency of the River environment and its core primitives through a series of simulation and implementation experiments. First, we rigorously explore the performance properties of both the distributed queue and graduated declustering, establishing that they perform as desired under a broad range of performance faults. Then, we apply the mechanisms to the construction of several data-intensive query-processing primitives, transforming them into programs that are robust to disk performance faults.
Direction-of-arrival estimation and array calibration for partly-calibrated arrays

In this paper, a new direction-of-arrival (DOA) estimation technique applicable to partly-calibrated arrays (PCAs) composed of arbitrary subarrays with unknown subarray displacements is developed. The new method is not restricted to any specific array geometry and allows joint estimation of the DOAs and calibration of the entire sensor array. Computer simulations show that the proposed approach substantially outperforms the known DOA estimation methods applicable to such PCAs.