Ranked prediction of p53 targets using hidden variable dynamic modeling

Full exploitation of microarray data requires hidden information that cannot be extracted using current analysis methodologies. We present a new approach, hidden variable dynamic modeling (HVDM), which derives the hidden profile of a transcription factor from time series microarray data, and generates a ranked list of predicted targets. We applied HVDM to the p53 network, validating predictions experimentally using small interfering RNA. HVDM can be applied in many systems biology contexts to predict regulation of gene activity quantitatively

Do Irrelevant Sounds Impair the Maintenance of All Characteristics of Speech in Memory?

Several studies have shown that maintaining in memory some attributes of speech, such as the content or pitch of an interlocutor's message, is markedly reduced in the presence of background sounds made of spectrotemporal variations. However, experimental paradigms showing this interference have only focused on one attribute of speech at a time, and thus differ from real-life situations in which several attributes have to be memorized and maintained simultaneously. It is possible that the interference is even greater in such a case and can occur for a broader range of background sounds. We developed a paradigm in which participants had to maintain the content, pitch and speaker size of auditorily presented speech information and used various auditory distractors to generate interference. We found that only distractors with spectrotemporal variations impaired the detection, which shows that similar interference mechanisms occur whether there are one or more speech attributes to maintain in memory. A high percentage of false alarms was observed with these distractors, suggesting that spectrotemporal variations not only weaken but also modify the information maintained in memory. Lastly, we found that participants were unaware of the interference. These results are similar to those observed in the visual modalit

RNA Polymerase Pausing during Initial Transcription

In bacteria, RNA polymerase (RNAP) initiates transcription by synthesizing short transcripts that are either released or extended to allow RNAP to escape from the promoter. The mechanism of initial transcription is unclear due to the presence of transient intermediates and molecular heterogeneity. Here, we studied initial transcription on a lac promoter using single-molecule fluorescence observations of DNA scrunching on immobilized transcription complexes. Our work revealed a long pause (‘‘initiation pause,’’ �20 s) after synthesis of a 6-mer RNA; such pauses can serve as regulatory checkpoints. Region sigma 3.2, which contains a loop blocking the RNA exit channel, was a major pausing determinant. We also obtained evidence for RNA backtracking during abortive initial transcription and for additional pausing prior to escape. We summarized our work in a model for initial transcription, in which pausing is controlled by a complex set of determinants that modulate the transition from a 6- to a 7-nt RNA

Randomly Broken Nuclei and Disordered Systems

Similarities between models of fragmenting nuclei and disordered systems in condensed matter suggest corresponding methods. Several theoretical models of fragmentation investigated in this fashion show marked differences, indicating possible new methods for distinguishing models using yield data. Applying nuclear methods to disordered systems also yields interesting results.Comment: 10 pages, 4 figure

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Управління комплексною вентиляційною мережею соляної шахти Trotus

The attestation of salt extraction in these areas was located in the Geto-Dacian period at Oituz and Târgu Ocna. The oldest written testimony dates from 1380. The mining works that serve the Trotuş mine within the Tg. Ocna Salt Mine, are located in the Feţele Târgului salt massif located near the town of Tg. Ocna, on the left side of the Trotuş river. The exploitation of the salt was carried out until 1870 at the Ocnița Mine with a bell-shaped chamber and continued in the Moldova Veche and Moldova Nouă mines with trapezoidal chambers. Since 1967, the salt has been exploited with "small rooms and abandoned square pillars". The exploitation is carried out descending, on the horizons. Currently, the Trotuș Salt Mine has 14 horizons: 2 at the Pilot mine and 12 at the Trotuș mine. The specialized 3D CANVENT program was used to establish the optimal distribution of air flows. A number of 492 junctions and 697 branches were used to solve the ventilation network related to the Trotuș Salt Mine.Атестація видобутку солі в цих районах проходила в гето-дакійський період в Ойтузі та Тиргу-Очна. Найдавніші письмові свідчення датуються 1380 роком. Гірничі роботи, що обслуговують шахту Тротуш у межах Тг. Соляна шахта Окна, розташована в соляному масиві Фецеле-Тиргулуй, що знаходиться недалеко від міста Тг. Очна, з лівого боку річки Тротуш. Експлуатація солі велася до 1870 р. На шахті Окниця з дзвоноподібною камерою і продовжувалась у шахтах Молдова Вече та Молдова Ноуа з трапецієподібними камерами. З 1967 р. Сіль експлуатується в "маленьких кімнатах і занедбаних квадратних стовпах". Експлуатація здійснюється низхідно, по горизонтах. В даний час соляна шахта Тротуш має 14 горизонтів: 2 на пілотній шахті та 12 на шахті Тротуш. Для встановлення оптимального розподілу повітряних потоків була використана спеціалізована програма 3D CANVENT. Для вирішення вентиляційної мережі, що стосується соляної шахти Тротуш, було використано 492 перехрестя та 697 гілок

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome

Liver retransplantation as a therapeutic method in graft dysfunctions in the immediate postoperative period

Departament Chirurgie Generală, I.C. Fundeni, București, România, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaCu toate că în ultimii ani au apărut progrese importante în domeniul hepatic, problema prevenirii apariției disfuncției și eșecului post-transplant nu a prezentat progrese semnificative. Intrucât disfuncția hepatică primară influențează dramatic evoluția grefei și a pacientului transplantat hepatic, prevenirea acestui fenomen devine obligatoriu. Creșterea penuriei de organe și a numărului persoanelor aflate pe lista de așteptare a dus la folosirea unor grefe ce depășesc criteriile normale de selecție pentru recoltare precum și transplantarea unor donatori considerați marginali. Aceste circumstanțe au adus în prim plan importanța diagnosticării și tratamentului disfuncției hepatice primare. Conceptul de disfuncție hepatică primară nu este clar definit. Există un spectru de evenimente ce definesc disfuncția hepatică postoperatorie precoce: non funcția primară (PNF), nonfuncția întârziată, funcția slabă/săracă inițială (initial poor function – IPF), non funcția inițială, insuficiența hepatică primară și disfuncția primară. Distincția între aceste entități ia în considerare gradul disfuncției hepatice, necesitatea retransplantării urgente, precum și apariția și durata acestor evenimente după transplantul hepatic.Although important progress has been made over the last few years, the problem of preventing dysfunction and post-transplant liver failure has not shown significant progress. Since primary liver dysfunction dramatically influences the progress of the graft and the liver transplant patient, prevention of this phenomenon becomes obligatory. The increase in organ shortage and the number of people on the waiting list led to the use of grafts that exceeded the normal selection criteria for harvesting as well as the transplantation of marginal donors. These circumstances have highlighted the importance of diagnosis and treatment of primary hepatic dysfunction. The concept of primary liver dysfunction is not clearly defined. There is a spectrum of events that defines early postoperative liver dysfunction: primary non-function (PNF), delayed dysfunction, initial poor function (IPF), primary hepatic failure, and primary dysfunction. The distinction between these entities takes into account the degree of hepatic dysfunction, the need for urgent retransplantation, and the occurrence and duration of these events after liver transplantation

A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain

Progranulin-deficient frontotemporal dementia (GRN-FTD) is a major cause of familial FTD with TAR DNA-binding protein 43 (TDP-43) pathology, which is linked to exon dysregulation. However, little is known about this dysregulation in glial and neuronal cells. Here, using splice-junction-covering enrichment probes, we introduce single-nuclei long-read RNA sequencing 2 (SnISOr-Seq2), targeting 3,630 high-interest genes without loss of precision, and complete the first single-cell, long-read-resolved case-control study for neurodegeneration. Exons affected by FTD-associated skipping are shorter than those whose inclusion is increased. Up to 30% of cell-(sub)type-specific splicing dysregulation is masked by other cell types or cortical layers. Surprisingly, strong splicing dysregulation events can occur in select but not all cell types. In some cases, a cell type switches in FTD to the splicing pattern of a different cell type. In addition, in separate GRN-FTD samples, the more FTD-prone frontal cortex exhibits more FTD-associated splicing patterns than the occipital cortex. Our methodologies are widely applicable to brain and other diseases.</p