Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost of rNTP/dNTP pool imbalance at the replication fork

The concentration of ribonucleoside triphosphates (rNTPs) in cells is far greater than the concentration of deoxyribonucleoside triphosphates (dNTPs), and this pool imbalance presents a challenge for DNA polymerases (Pols) to select their proper substrate. This report examines the effect of nucleotide pool imbalance on the rate and fidelity of the Escherichia coli replisome. We find that rNTPs decrease replication fork rate by competing with dNTPs at the active site of the C-family Pol III replicase at a step that does not require correct base-pairing. The effect of rNTPs on Pol rate generalizes to B-family eukaryotic replicases, Pols δ and ε. Imbalance of the dNTP pool also slows the replisome and thus is not specific to rNTPs. We observe a measurable frequency of rNMP incorporation that predicts one rNTP incorporated every 2.3 kb during chromosome replication. Given the frequency of rNMP incorporation, the repair of rNMPs is likely rapid. RNase HII nicks DNA at single rNMP residues to initiate replacement with dNMP. Considering that rNMPs will mark the new strand, RNase HII may direct strand-specificity for mismatch repair (MMR). How the newly synthesized strand is recognized for MMR is uncertain in eukaryotes and most bacteria, which lack a methyl-directed nicking system. Here we demonstrate that Bacillus subtilis incorporates rNMPs in vivo, that RNase HII plays a role in their removal, and the RNase HII gene deletion enhances mutagenesis, suggesting a possible role of incorporated rNMPs in MMR.
SPEAKING UNAVOIDABLE TRUTHS: UNDERSTANDING EARLY CHILDHOOD SEXUAL AND PHYSICAL VIOLENCE AMONG WOMEN IN PRISON

Women in prison have often suffered physical and sexual abuse as children which substantively contributes to their substance abuse, violence, and criminal behaviors. To understand women? s offending, and subsequent health issues, it is helpful to understand their own victimization. In this participative action research, women used poetry as both a process and a product to confront the truths of their lives in terms of what was done to them and what they have done to others and themselves. As the women learned to speak their own truths, those same truths became unavoidable to themselves. This rise into consciousness is demonstrated through excerpts from the participants? writings.
Thrombogenic Properties of Vascular Catheter Materials in Vitro

Recent research has stressed the significance of platelets in the development of thrombosis and has underlined that thrombus formation is initiated by the adhesion and aggregation of platelets (MUSTARD et colI. 1962, GLYNN et colI. 1966, HAMPTON 1967, MUSTARD & PACKHAM 1970). Considerable interest thas therefore been focussed on the adhesiveness of the platelets in various diseases, and the degree of such adhesion has also been used as a predictor of thrombosis (EVANS & IRVINE 1966). Thrombus formation in association with vascular catheterization also starts by the adhesion and aggregation of platelets, i.e. to the catheter (JACOBS SON 1969). Since this ready adhesion tends to increase the risk of thromboembolism, the reaction of platelets to catheter materials appears to be an important factor in the evaluation of the thrombogenic properties of the latter. Experiments in vivo have indicated that the reaction of platelets to a catheter varies with the material of which the catheter is made (SCHLOSSMAN 1973). The formation of thrombi on contact between blood and catheters therefore
Histopathological diagnosis and outcome of paediatric nephrotic syndrome.

OBJECTIVE To determine the histological picture and outcome of treatment in cases of childhood nephrotic syndrome who needed renal biopsy. DESIGN An analytical study. PLACE AND DURATION OF STUDY Department of Paediatrics, King Edward Medical College, and Mayo Hospital, Lahore from 1st June 1996 to 31st December, 2001 over a period of 5-1/2 years. SUBJECTS AND METHODS Children suffering from nephortic syndrome who had atypical features at presentation were initially or late non-responders; frequent relapsers on < 1mg kg/day and were steroid dependent or frequently relapsed on < 1 mg kg/day but developed steroid toxicity were included. Renal biopsy was performed in these patients. Treatment was administered according to the histopathology reports. Prednisolone 60 mg /m2/day followed after response by 40 mg /m2 on alternate days (AD) which was later tapered off. In minimal change nephrotic syndrome (MCNS) with frequent relapses cyclophosphamide, cyclosporine and levimisole were used. For steroid resistant focal segmental glomerulosclerosis (FSGS) intravenous pulses of methyl-prednisolone and cyclosporine were also given. These patients were followed to see the response of the therapy. RESULTS The commonest diagnosis was focal segmental glomerulosclerosis (FSGS) (42%) followed by minimal change disease (MCNS) (22%), membranoproliferative or mesangiocapillary glomerulonephritis (MPGN) (14%) and Mesangioproliferative glomerulonephritis (Mes PGN) (12%). There were 6% cases of membranous nephropathy and 4% of diffuse proliferative glomerulonephritis. On presentation, 40% had hematuria, 20% were found to be hypertensive, 12% patients had renal insufficiency and in 4% C3 level was low. Majority of the patients with MPGN and FSGS had atypical features whereas none of the patients with membranous nephropathy had any of these features. Thirty percent cases each of FSGS and MCNS were responders. Among non-responders there were 4 cases of FSGS and one of MPGN. CONCLUSION FSGS was the commonest histology in cases of childhood nephrotic syndrome that needed renal biopsy. Highest frequency of atypical features was seen in MPGN and FSGS.
Three‐dimensional model of the SHBG‐like region of anticoagulant protein S: New structure–function insights

Protein S (PS) is a vitamin K‐dependent glycoprotein that consists of several modules including a C‐terminal sex hormone‐binding globulin (SHBG)‐like domain that has been subdivided into two laminin LG‐type domains. The SHBG‐like region of PS is known to bind to a complement regulator molecule, C4b‐binding protein (C4BP), coagulation factor Va (FVa) and receptor tyrosine kinases. Inherited PS deficiency has been associated with thromboembolic disease. Yet, study of the mechanisms by which the SHBG‐like region of PS serves its essential functions has so far been hampered because of the lack of structural information. Recently, the three‐dimensional (3D) structure of LG domains from plasma SHBG, laminin and neurexin have been reported and were found related to the pentraxin family. We used these X‐ray structures to build homology models of the SHBG‐like region of human PS. We then analyzed previously reported experimental/clinical data in the light of the predicted structures. A potential calcium‐binding site is found in the first LG domain of PS and D292 could play a role in this process. This region is close to the interface between the two LG domains and is also surrounded by segments that have been suggested by synthetic peptide studies to be important for C4BP or FVa binding. The 39 point mutations linked to PS deficiencies or reported as neutral variants were rationalized in the 3D structure. Proteins 2001;43:203–216. © 2001 Wiley‐Liss, Inc.
Ischaemia-modified albumin in pulmonary hypertension

Background: Pulmonary hypertension (PH) may be associated with subendocardial ischaemia. We investigated whether ischaemia-modified albumin (IMA), an established marker of ischaemia, is elevated in stable patients with PH. Methods: We studied 32 patients with PH and an equal number of age-matched normal volunteers. We assessed serum IMA levels with the albumin cobalt-binding test. Results: Patients’ mean ± SD (range) pulmonary arterial pressure was 56 ± 12 (33–73) mmHg and their exercise capacity was 394 ± 145 (121–688) m in the 6-min walk test. IMA was 92 ± 14 (69–115) U ml−1 in the patient group and 93 ± 9.4 (76–122) U ml−1 in the control group with no significant difference between the two (p = 0.85), although almost one-third of the patients had detectable troponin-I. Conclusions: We conclude that IMA, a marker of ischaemia, does not differ in patients with advanced clinically stable PH compared with normal subjects.
Ganglion Cysts of the Cruciate Ligament : Review of MRI findings , clinical presentations and management options from a series of 31 cases

Objective: A case series for ganglion cyst of the cruciate ligament with MRI findings, clinical presentation, and management options is presented. Methods: Of 8663 consecutive patients referred for knee MR imaging, 21 were diagnosed with ganglion cysts of the cruciate ligaments, including 21 men and 10 women of ages 12 to 73 years (mean: 37). A review of charts revealed that knee pain was the chief complaint in all cases. Arthroscopic debridement of ganglion cyst was performed in 11 patients. Results: MRI proved to be a valuable tool in diagnosing and deciding management of these cases. All 11 patients who underwent arthroscopic treatment were symptom-free on follow-up (range: 10 months to 2 years). Conclusions: Cyst formation associated with cruciate ligament of the knee is an infrequent cause of knee pain. MR imaging was important in confirming the cyst lesions and provided useful information prior to arthroscopy. Arthroscopic debridement of ganglion cyst produced excellent outcome without recurrence. This study describes the pertinent MRI and intraoperative findings of ganglion cyst.
Relative short‐term efficacy and acceptability of agomelatine versus vortioxetine in adult patients suffering from major depressive disorder

Agomelatine and vortioxetine are antidepressants with different mechanisms of action compared to other pharmaceutical treatment options. The objective of this present analysis is to determine the relative efficacy and acceptability of agomelatine (25–50 mg) compared to vortioxetine (10–15–20 mg) in adult patients with major depressive disorder. We performed an adjusted indirect comparison using placebo as a common control. The main outcomes were efficacy (response to treatment by Montgomery‐Åsberg depression rating scale/Hamilton Rating Scale for Depression) and acceptability (withdrawal rate for any reason or due to adverse events). 10 agomelatine and 11 vortioxetine studies were included in the analysis. For efficacy, no difference was shown between agomelatine and vortioxetine (E[95% CI] = −0.03 [−0.12;0.05]). For acceptability, no significant difference was found between both antidepressants.
Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease

ABSTRACT Introduction: Inositol and its derivatives comprise a huge field of biology. Myo-inositol is not only a prominent component of membrane-incorporated phosphatidylinositol, but participates in its free form, with its isomers or its phosphate derivatives, to a multitude of cellular processes, including ion channel permeability, metabolic homeostasis, mRNA export and translation, cytoskeleton remodeling, stress response. Areas covered: Bioavailability, safety, uptake and metabolism of inositol is discussed emphasizing the complexity of interconnected pathways leading to phosphoinositides, inositol phosphates and more complex molecules, like glycosyl-phosphatidylinositols. Expert opinion: Besides being a structural element, myo-inositol exerts unexpected functions, mostly unknown. However, several reports indicate that inositol plays a key role during phenotypic transitions and developmental phases. Furthermore, dysfunctions in the regulation of inositol metabolism have been implicated in several chronic diseases. Clinical trials using inositol in pharmacological doses provide amazing results in the management of gynecological diseases, respiratory stress syndrome, Alzheimer’s disease, metabolic syndrome, and cancer, for which conventional treatments are disappointing. However, despite the widespread studies carried out to identify inositol-based effects, no comprehensive understanding of inositol-based mechanisms has been achieved. An integrated metabolomics-genomic study to identify the cellular fate of therapeutically administered myo-inositol and its genomic/enzymatic targets is urgently warranted.
Resting heart rate at hospital admission and its relation to hospital outcome in patients with heart failure.

BACKGROUND Resting heart rate (HR) has been proven to influence long-term prognosis in patients with chronic heart failure (HF). The aim of this study was to assess the relationship between resting HR at hospital admission and hospital outcome in patients with HF. METHODS The study included Polish patients admitted to hospital due to HF who agreed to participate in Heart Failure Pilot Survey of the European Society of Cardiology. RESULTS The final analysis included 598 patients. Median HR at hospital admission was 80 bpm. In univariate analyses, higher HR at admission was associated with more frequent use of inotropic support (p = 0.0462) and diuretics (p = 0.0426), worse clinical (New York Heart Association - NYHA) status at discharge (p = 0.0483), longer hospital stay (p = 0.0303) and higher in-hospital mortality (p = 0.003). Compared to patients who survived, patients who died during hospitalization (n = 21; 3.5%) were older, more often had a history of stroke or transient ischemic attack and were characterized by higher NYHA class, higher HR at admission, lower systolic and diastolic blood pressure at admission, lower ejection fraction, lower glomerular filtration rate, and lower natrium and hemoglobin concentrations at hospital admission. In multivariate analysis, higher HR at admission (OR 1.594 [per 10 bpm]; 95% CI 1.061-2.395; p = 0.0248) and lower natrium concentration at admission (OR 0.767 [per 1 mmol/L]; 95% CI 0.618-0.952; p = 0.0162) were the only independent predictors of in-hospital mortality. CONCLUSIONS In patients with HF, higher resting HR at hospital admission is associated with increased in-hospital mortality.
Long‐term Prevention of Vagal Atrial Arrhythmias by Atrial Pacing at 90/Minute: Experience with 6 Cases

Six patients (5 men, 1 woman) with a history ranging from 3–16 years of resistant vagal atrial arrhythmias were treated by atrial pacing at a rate of 90Jmin. These patients have been followed up for an average of 5.5 years (range 2–11 years) with favorable resutls. The arrhythmias were charactemed by daily or weekly attacks of rypical alrial flutter and atrial fibrillalion occurring mainly or exclusively at night, at rest, or in the digestive periods in otherwise normal hearts of middle‐aged palients (first attack between 25 and 54, mean 40). The arrhythmias werc resistant to quinidinc, and were usually aggravated by digitalis, beta‐blockers and verapamil. Amiodaroneisusually the only effective drug in this syndrome, but was not used before pacing in the 2 first cases, and was in effective in the other 4 cases. Electrophysiologic studies confirmed the absence of sick sinus syndrome, and the close relationship betwecn a relative bradycardia and the onset of the arrhythmia. Atrial pacing alone totally controiled the arrhythmia in 1 palient; amiodarone was used in conjunction with pacing in 3 palients. In 1 patient the improvement was clear but incomplete, and in 1 patient permanent alrial fibrillation occurred shortly afler pacemaker implantalion.
Combining visual recognition and computational linguistics : linguistic knowledge for visual recognition and natural language descriptions of visual content

Extensive efforts are being made to improve visual recognition and semantic understanding of language. However, surprisingly little has been done to exploit the mutual benefits of combining both fields. In this thesis we show how the different fields of research can profit from each other. First, we scale recognition to 200 unseen object classes and show how to extract robust semantic relatedness from linguistic resources. Our novel approach extends zero-shot to few shot recognition and exploits unlabeled data by adopting label propagation for transfer learning. Second, we capture the high variability but low availability of composite activity videos by extracting the essential information from text descriptions. For this we recorded and annotated a corpus for fine-grained activity recognition. We show improvements in a supervised case but we are also able to recognize unseen composite activities. Third, we present a corpus of videos and aligned descriptions. We use it for grounding activity descriptions and for learning how to automatically generate natural language descriptions for a video. We show that our proposed approach is also applicable to image description and that it outperforms baselines and related work. In summary, this thesis presents a novel approach for automatic video description and shows the benefits of extracting linguistic knowledge for object and activity recognition as well as the advantage of visual recognition for understanding activity descriptions.
A Review of Classic Edge Detectors

In this paper some of the classic alternatives for edge detection in digital images are studied. The main idea of edge detection algorithms is to find where abrupt changes in the intensity of an image have occurred. The first family of algorithms reviewed in this work uses the first derivative to find the changes of intensity, such as Sobel, Prewitt and Roberts. In the second reviewed family, second derivatives are used, for example in algorithms like Marr-Hildreth and Haralick. The obtained results are analyzed from a qualitative point of view (perceptual) and from a quantitative point of view (number of operations, execution time), considering different ways to convolve an image with a kernel (step required in some of the algorithms). Source Code For all the reviewed algorithms, an open source C implementation is provided which can be downloaded from the IPOL web page of this article 1 . An online demonstration is also available,
The Clock Gene period Plays an Essential Role in Photoperiodic Control of Nymphal Development in the Cricket Modicogryllus siamensis

Photoperiodic regulation of development is a common strategy for insects in the temperate zone to adapt to the seasonally changing environment. Although the circadian clock is generally thought to be involved, the underlying time measurement mechanism is still elusive. Here, we demonstrate that the circadian clock gene period (per) plays an essential role in the photoperiodic regulation of nymphal development in the cricket Modicogryllus siamensis. Nymphal development of this cricket depends on photoperiods, being accelerated by long days and slowed down by short days. We examined the role of per in the nymphal photoperiodic response as well as circadian rhythm generation using parental RNA interference (pRNAi). per mRNA levels in nymphal heads showed a rhythmic expression with the pattern dependent on photoperiods, and pRNAi significantly suppressed the per mRNA level with no significant rhythmicity in the early nymphal stage. Irrespective of photoperiods, nymphs treated with per pRNAi showed adult emergence patterns neither of intact nymphs nor of DsRed2 pRNAi nymphs kept under long days or under short days but similar to those kept under constant dark conditions. Most per pRNAi adults showed arrhythmic or aberrant circadian locomotor activity. These results suggest that the photoperiodic time measurement requires the normal circadian clock that is controlled by the per gene.
The productivity effects of multiple pay incentives

Drawing on recent incentive theory and the growing use of multiple incentives by firms, this article examines the effects of combining incentives on workplace labour productivity. Utilizing data from the British Workplace Employment Relations Survey, the article explores whether multiple incentives are more effective than single incentives. It is found that the productivity effects of individualized incentives are enhanced by profit sharing though not by collective payment by result schemes (PBR). Profit sharing also enhances the effect of collective PBR, and it is found that two group incentives are more effective than a single individual incentive. However there are limits on the number of incentive schemes that can be combined effectively. The effects of mixed incentives tend to be greater in workplaces with worker discretion and task variety, thereby providing support for a contingency perspective.
Net community production in the North Atlantic Ocean derived from Volunteer Observing Ship data

The magnitude of marine plankton net community production (NCP) is indicative of both the biologically driven exchange of carbon dioxide between the atmosphere and the surface ocean and the export of organic carbon from the surface ocean to the ocean interior. In this study the seasonal variability in the NCP of five biogeochemical regions in the North Atlantic was determined from measurements of surface water dissolved oxygen and dissolved inorganic carbon (DIC) sampled from a Volunteer Observing Ship (VOS). The magnitude of NCP derived from dissolved oxygen measurements (NCP O2 ) was consistent with previous geochemical estimates of NCP in the North Atlantic, with an average annual NCP O2 of 9.5 ± 6.5 mmol O2 m−2 d−1. Annual NCP O2 did not vary significantly over 35° of latitude and was not significantly different from NCP derived from DIC measurements (NCPDIC). The relatively simple method described here is applicable to any VOS route on which surface water dissolved oxygen concentrations can be accurately measured, thus providing estimates of NCP at higher spatial and temporal resolution than currently achieved.
REAL men: a group-randomized trial of an HIV prevention intervention for adolescent boys.

OBJECTIVES We tested the efficacy of an intervention among 11- to 14-year-old adolescent boys to promote delay of sexual intercourse, condom use among those who were sexually active, and communication on sexuality between fathers (or father figures) and sons. METHODS Sites were randomly assigned to the intervention and control groups. Assessments were conducted prior to the intervention and at 3-, 6-, and 12-month follow-up interviews. RESULTS A total of 277 fathers and their sons completed baseline assessments. Most participants were African American, and most fathers lived with their sons. Significantly higher rates of sexual abstinence and condom use and of intent to delay initiation of sexual intercourse were observed among adolescent boys whose fathers participated in the intervention. Fathers in the intervention group reported significantly more discussions about sexuality and greater intentions to discuss sexuality than did control-group fathers. CONCLUSIONS The study demonstrates that fathers can serve as an important educator on HIV prevention and sexuality for their sons.
Subject-specific geometrical detail rather than cost function formulation affects hip loading calculation*

Abstract This study assessed the relative importance of introducing an increasing level of medical image-based subject-specific detail in bone and muscle geometry in the musculoskeletal model, on calculated hip contact forces during gait. These forces were compared to introducing minimization of hip contact forces in the optimization criterion. With an increasing level of subject-specific detail, specifically MRI-based geometry and wrapping surfaces representing the hip capsule, hip contact forces decreased and were more comparable to contact forces measured using instrumented prostheses (average difference of 0.69 BW at the first peak compared to 1.04 BW for the generic model). Inclusion of subject-specific wrapping surfaces in the model had a greater effect than altering the cost function definition.