Better Late than Never: Publication of the Decisions from the 1845 Term of the Republic of Texas Supreme Court

Two years ago, this column featured the rediscovery of a full year\u27s worth of decisions issued by the Supreme Court of the Republic of Texas that had never been printed. Paulsen & Hambleton, Whatever Happened to 7845? The Missing Decisions of the Texas Supreme Court, 48 Tex. B.J. 830 (1985). Those decisions now have been collected and will appear in the December 1986 issue of the Texas Law Review (The Missing Cases of the Republic, 65 Texas L. Rev. 377 (1986)). Although none of the missing cases are likely to have any direct bearing on the outcome of the Texaco-Pennzoil appeal or any other great legal issue of our day, the opinions nevertheless should be of considerable interest to attorneys, law librarians, and historians

Better Late than Never: Publication of the Decisions from the 1845 Term of the Republic of Texas Supreme Court

Two years ago, this column featured the rediscovery of a full year\u27s worth of decisions issued by the Supreme Court of the Republic of Texas that had never been printed. Paulsen & Hambleton, Whatever Happened to 7845? The Missing Decisions of the Texas Supreme Court, 48 Tex. B.J. 830 (1985). Those decisions now have been collected and will appear in the December 1986 issue of the Texas Law Review (The Missing Cases of the Republic, 65 Texas L. Rev. 377 (1986)). Although none of the missing cases are likely to have any direct bearing on the outcome of the Texaco-Pennzoil appeal or any other great legal issue of our day, the opinions nevertheless should be of considerable interest to attorneys, law librarians, and historians

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

A semiparametric modeling framework for potential biomarker discovery and the development of metabonomic profiles

<p>Abstract</p> <p>Background</p> <p>The discovery of biomarkers is an important step towards the development of criteria for early diagnosis of disease status. Recently electrospray ionization (ESI) and matrix assisted laser desorption (MALDI) time-of-flight (TOF) mass spectrometry have been used to identify biomarkers both in proteomics and metabonomics studies. Data sets generated from such studies are generally very large in size and thus require the use of sophisticated statistical techniques to glean useful information. Most recent attempts to process these types of data model each compound's intensity either discretely by positional (mass to charge ratio) clustering or through each compounds' own intensity distribution. Traditionally data processing steps such as noise removal, background elimination and m/z alignment, are generally carried out separately resulting in unsatisfactory propagation of signals in the final model.</p> <p>Results</p> <p>In the present study a novel semi-parametric approach has been developed to distinguish urinary metabolic profiles in a group of traumatic patients from those of a control group consisting of normal individuals. Data sets obtained from the replicates of a single subject were used to develop a functional profile through Dirichlet mixture of beta distribution. This functional profile is flexible enough to accommodate variability of the instrument and the inherent variability of each individual, thus simultaneously addressing different sources of systematic error. To address instrument variability, all data sets were analyzed in replicate, an important issue ignored by most studies in the past. Different model comparisons were performed to select the best model for each subject. The m/z values in the window of the irregular pattern are then further recommended for possible biomarker discovery.</p> <p>Conclusion</p> <p>To the best of our knowledge this is the very first attempt to model the physical process behind the time-of flight mass spectrometry. Most of the state of the art techniques does not take these physical principles in consideration while modeling such data. The proposed modeling process will apply as long as the basic physical principle presented in this paper is valid. Notably we have confined our present work mostly within the modeling aspect. Nevertheless clinical validation of our recommended list of potential biomarkers will be required. Hence, we have termed our modeling approach as a "framework" for further work.</p

Computer software for business and specific purposes in wood industry

V 211 slovenskih mikro in majhnih lesnih podjetjih, katerih osnovna dejavnost (po SKD) zajema proizvodnjo pohištva za poslovne prostore, proizvodnjo kuhinjskega pohištva in proizvodnjo drugega pohištva, smo preučili razširjenost ter uporabo poslovnih in namenskih računalniških programov. Raziskava je temeljila na primerjalni analizi in oceni stanja programske opreme. Oceno stanja smo izvedli s pomočjo ankete, ki smo jo distribuirali prek različnih medijev. Odziv na anketo je bil v povprečju 23,7 %. Ocenimo lahko, da so računalniški programi v mikro in majhnih lesnih podjetjih na nekaterih področjih intenzivneje uporabljani kot na drugih. Ugotovili smo, da podjetja v večini uporabljajo pri poslovanju pisarniške programe, predvsem tiste podjetja Microsoft. Uporaba specializirane programske opreme je še precej omejena, saj jo pri poslovanju uporablja le 40 % preučevanih podjetij. Nekoliko bolj uporabljajo programsko opremo namenjeno konstruiranju (60 %).The range and usage of computer software for business and specific purposes were researched in 211 micro and minor wood firms, encompasing the production of office furniture, kitchen furniture and some other furniture as the basic activity, according to Statistical Classification Activities (SCA). The research was based on comparative analysis and software condition evaluation. Evaluation of the current situation was carried out by means of a questionnaire, distributed with the help of media. The response was as high as 23.7 %. It can be estimated that the computer software in these micro and minor wood firms is used more often in some areas than in others. It was found out that the firms use mainly office software- especially Microsoft ones. The usage of specialized software equipment is still quite limited in these firms. Only 40 % of the tested firms use is software for their business, meanwhile the equipment designed for construction is more frequently used (60 %)

Comparison of the structure and activity of glycosylated and asglycosylated human carboxylesterase 1

Human Carboxylesterase 1 (hCES1) is the key liver microsomal enzyme responsible for detoxification and metabolism of a variety of clinical drugs. To analyse the role of the single N-linked glycan on the structure and activity of the enzyme, authentically glycosylated and aglycosylated hCES1, generated by mutating asparagine 79 to glutamine, were produced in human embryonic kidney cells. Purified enzymes were shown to be predominantly trimeric in solution by analytical ultracentrifugation. The purified aglycosylated enzyme was found to be more active than glycosylated hCES1 and analysis of enzyme kinetics revealed that both enzymes exhibit positive cooperativity. Crystal structures of hCES1 a catalytically inactive mutant (S221A) and the aglycosylated enzyme were determined in the absence of any ligand or substrate to high resolutions (1.86 Å, 1.48 Å and 2.01 Å, respectively). Superposition of all three structures showed only minor conformational differences with a root mean square deviations of around 0.5 Å over all Cα positions. Comparison of the active sites of these un-liganded enzymes with the structures of hCES1-ligand complexes showed that side-chains of the catalytic triad were pre-disposed for substrate binding. Overall the results indicate that preventing N-glycosylation of hCES1 does not significantly affect the structure or activity of the enzyme

Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Background: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results: The $AUC_{0-10 hr}$ and $C_{max}$ values increased nonlinearly between 100 mg and 1500 mg. The slope of the $AUC_{0-10 hr}$ vs dose, as well as the $C_{max}$ vs dose, plots are steepest at the lowest thiamine doses. Conclusion: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process

COVID-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity

Dynamics of Inflammatory Responses After SARS-CoV-2 Infection by Vaccination Status in the USA: A Prospective Cohort Study

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation

Selective Loss of Cysteine Residues and Disulphide Bonds in a Potato Proteinase Inhibitor II Family

Disulphide bonds between cysteine residues in proteins play a key role in protein folding, stability, and function. Loss of a disulphide bond is often associated with functional differentiation of the protein. The evolution of disulphide bonds is still actively debated; analysis of naturally occurring variants can promote understanding of the protein evolutionary process. One of the disulphide bond-containing protein families is the potato proteinase inhibitor II (PI-II, or Pin2, for short) superfamily, which is found in most solanaceous plants and participates in plant development, stress response, and defence. Each PI-II domain contains eight cysteine residues (8C), and two similar PI-II domains form a functional protein that has eight disulphide bonds and two non-identical reaction centres. It is still unclear which patterns and processes affect cysteine residue loss in PI-II. Through cDNA sequencing and data mining, we found six natural variants missing cysteine residues involved in one or two disulphide bonds at the first reaction centre. We named these variants Pi7C and Pi6C for the proteins missing one or two pairs of cysteine residues, respectively. This PI-II-7C/6C family was found exclusively in potato. The missing cysteine residues were in bonding pairs but distant from one another at the nucleotide/protein sequence level. The non-synonymous/synonymous substitution (Ka/Ks) ratio analysis suggested a positive evolutionary gene selection for Pi6C and various Pi7C. The selective deletion of the first reaction centre cysteine residues that are structure-level-paired but sequence-level-distant in PI-II illustrates the flexibility of PI-II domains and suggests the functionality of their transient gene versions during evolution