The detection and segmentation of meaningful figures from their background is one of the primary functions of vision. While work in nonhuman primates has implicated early visual mechanisms in this figure–ground modulation, neuroimaging in humans has instead largely ascribed the processing of figures and objects to higher stages of the visual hierarchy. Here, we used high-field fMRI at 7 Tesla to measure BOLD responses to task-irrelevant orientation-defined figures in human early visual cortex (N = 6, four females). We used a novel population receptive field mapping-based approach to resolve the spatial profiles of two constituent mechanisms of figure–ground modulation: a local boundary response, and a further enhancement spanning the full extent of the figure region that is driven by global differences in features. Reconstructing the distinct spatial profiles of these effects reveals that figure enhancement modulates responses in human early visual cortex in a manner consistent with a mechanism of automatic, contextually driven feedback from higher visual areas.

SIGNIFICANCE STATEMENT A core function of the visual system is to parse complex 2D input into meaningful figures. We do so constantly and seamlessly, both by processing information about visible edges and by analyzing large-scale differences between figure and background. While influential neurophysiology work has characterized an intriguing mechanism that enhances V1 responses to perceptual figures, we have a poor understanding of how the early visual system contributes to figure–ground processing in humans. Here, we use advanced computational analysis methods and high-field human fMRI data to resolve the distinct spatial profiles of local edge and global figure enhancement in the early visual system (V1 and LGN); the latter is distinct and consistent with a mechanism of automatic, stimulus-driven feedback from higher-level visual areas.

Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster, coding for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. β4*nAChRs have been implicated in nicotine withdrawal, aversion, and reinforcement. Here we show that β4*nAChRs also are involved in non-nicotine-mediated responses that may predispose to addiction-related behaviors. β4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and in reward-based Go/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by directly injecting nicotine into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, β4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and β4KO self-administered more than WT mice, whereas β4-overexpressing mice avoided nicotine injections. Viral expression of β4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of β4KO mice revealed dose- and region-dependent differences: β4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas β4*nAChRs in the MHb-IPN pathway, limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional β4*nAChRs result in deficits in reward sensitivity including increased ICSA at high doses of nicotine that is restored by re-expression of β4*nAChRs in the MHb-IPN. These data indicate that β4 is a critical modulator of reward-related behaviors.

SIGNIFICANCE STATEMENT Human genetic studies have provided strong evidence for a relationship between variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and nicotine addiction. Yet, little is known about the role of β4 nicotinic acetylcholine receptor (nAChR) subunit encoded by this cluster. We investigated the implication of β4*nAChRs in anxiety-, food reward- and nicotine reward-related behaviors. Deletion of the β4 subunit gene resulted in an addiction-related phenotype characterized by low anxiety, high novelty-induced response, lack of sensitivity to palatable food rewards and increased intracranial nicotine self-administration at high doses. Lentiviral vector-induced re-expression of the β4 subunit into either the MHb or IPN restored a "stop" signal on nicotine self-administration. These results suggest that β4*nAChRs provide a promising novel drug target for smoking cessation.

SOLIDWORKS Multibody Part Assembly An Exploded View is used to communicate your design or drawings in a more proper and precise way. It really helps to clearly understand the sequential order of the assembly. Moreover, the exploded view is used

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Following the University-wide commencement ceremony on May 9, Penn State Shenango will host a virtual celebration for the Class of 2020.

The UK looks likely to operate under slightly different lockdown rules next week after announcements by the leaders of the Welsh and Scottish Governments suggested deviation between nations.

Infantile colic affects almost 10% of all infants and is characterized by crying and fussing in an otherwise healthy and well-fed infant. Prenatal exposure to tobacco smoking is a risk factor, but it is unclear whether nicotine causes the association.

Infants exposed to nicotine replacement therapy during pregnancy had elevated infantile colic risk of the same magnitude as infants exposed to tobacco smoking. Intrauterine exposure to nicotine may play a causal role in the pathogenesis of infantile colic. (Read the full article)

Children in foster care are at elevated risk for adverse outcomes. Placement instability and failure to achieve timely permanence exacerbate that risk. A handful of studies have found that parent-management training is effective in promoting placement stability and timely permanence.

Unlike parent-management training, youth focused interventions have not been systematically evaluated for their impact on placement and permanency outcomes. A mentoring and skills group intervention for preadolescents in foster care demonstrated better placement and permanency outcomes, especially for high-risk subgroups. (Read the full article)

Smoking has been found to increase the risk of some specific congenital anomalies; however, results remain inconsistent. Nicotine replacement therapy (NRT) is increasingly being used as for smoking cessation in pregnancy although little is known about its association with congenital anomalies.

Being prescribed NRT while pregnant was not associated with major congenital anomalies (MCA), except a small increase in respiratory anomalies (3/1000 births). This must be considered in context of the rarity of MCAs and higher morbidities in the NRT group. (Read the full article)

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

Penn State's virtual commencement ceremony, set for 2 p.m. on May 9, is the first step in recognizing the Class of 2020 at Penn State Berks, which will offer additional celebratory programming for Berks graduates via the campus' website and social media.

Penn State Harrisburg has announced plans for spring 2020 commencement to celebrate the achievements of its more than 800 graduates.

Penn State Harrisburg senior Jessica Sheets and her father, Ethan, have a lot in common, including both having had their commencement ceremonies preempted by historic events — hers by the coronavirus epidemic, and his by Hurricane Agnes in 1972.

AP has managed to dodge the partisan pitfalls that have felled other ambitious curricular efforts—so far, write Chester E. Finn Jr. and Andrew E. Scanlan.

D. Brooks Smith, Chief Judge of the United States Court of Appeals for the Third Circuit, will deliver the Penn State Law in University Park 2020 commencement address on May 16 in Eisenhower Auditorium.

Penn State York graduates will celebrate their achievements on Saturday, May 9 during the University-wide virtual commencement ceremony and with videos honoring them.

Following UN Special Representative for Libya Bernardino León’s announcement of a new Government of National Accord, Joost Hiltermann, Crisis Group’s Middle East and North Africa Program Director, had the following reaction.

Keep up with information about various happenings at Penn State, including study volunteer requests, activities and other opportunities.

To prepare to view the University's virtual commencement ceremony on May 9, graduates and guests may on Thursday and Friday test the livestream and confirm that browser settings are adjusted to view the livestream.

In response to the growing coronavirus pandemic, orders from the state government and recommendations from global public health organizations, Penn State will hold its spring 2020 commencement ceremony via livestream on May 9. The virtual ceremony will recognize all Penn State undergraduate students and all graduate students in the Penn State Graduate School.

At 2 p.m. on Saturday, May 9, Penn State will host its first virtual commencement. The ceremony will be livestreamed, and available internationally, at https://spring2020.commencement.psu.edu/.

Policymakers, Public Join Together for Women’s History Month Celebration and Lecture DOVER, Del. – Governor John Carney, Delaware’s Office for Women’s Advocacy and Advancement, the Delaware Department of Human Resources, the Delaware Commission for Women, and Delaware Women’s Workforce Council, today hosted the first lecture of its kind titled “Redefining Women in the Workplace” in honor […]

CoronaVirus (Covid-19) has been declared as pandemic (“an epidemic occurring worldwide”) by World Health Organisation (“WHO”) on 11.03.2020. While many consider Covid-19 as a message from nature to mankind, in this Article we

"Rupert Grint and Georgia Groome are delighted to confirm the birth of their baby girl," the couple's representative said in a statement

Agency: OMB Closing Date: 7/9/2020

Agency: NCC Closing Date: 5/18/2020

Agency: NCC Closing Date: 5/18/2020

Agency: OMB Closing Date: 6/18/2020

Agency: OMB Closing Date: 6/3/2020

Agency: OMB Closing Date: 6/9/2020

Agency: LEG Closing Date: 6/19/2020

Hartly --

Location: Brittney Lane between Halltown Road and Yoder Road, near Hartly.

Times and Dates: 7:00 a.m. on Monday, March 23, 2020 until 3:00 p.m. on Friday, March 27, 2020, pending weather.

Traffic Information: DelDOT announces to motorists that Brittney Lane will be closed for the removal and replacement of a crossroad pipe for drainage improvements. [More]

Bear --

Location: US 13 Southbound, at Route 71/Red Lion Road, Bear.

Dates and Times: 8:00 p.m. until 4:00 p.m. Sunday through Friday. [More]